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Archive for the ‘Renal Denervation’ Category


AGENDA – ICI Conference – Innovation in Cardiovascular Interventions – December 14-16, at the David InterContinental Hotel, Tel Aviv, Israel

Reporter: Aviva Lev-Ari, PhD, RN

 

1. ICI Scientific Program

ICI2014 speakers are some of the leading figures in the field. The preliminary list can be viewed at the ICI website.

ICI2014 will hold for the second time the “Wall to Wall Session – From the Great Wall of China to the Jerusalem Wall”. Click here for a glance at the 2013 program endorsed by Yanping Gao, the Chinese Ambassador in Israel.

Attendees will:

 Be exposed to promising research and new therapies in various phases of development.

 Learn from live case presentations on the impact of emerging technologies on current and future therapies.

 Gain insights from international experts speaking on important clinical topics—with an emphasis on future perspectives.

2. ICI Exhibition

The heart of the ICI Meeting is the strong International collaboration between Medicine and Industry. With an emphasis on technological developments, novel knowledge-rich technologies, and the diligent pursuit of solutions to yet unsolved problems in heart, brain and cardiovascular medicine, the ICI meeting features a State-of-the-Art Exhibition and Innovative Technology Parade.

Since 1995, the ICI exhibition is rapidly growing with more than 90 international exhibitors and sponsors, including the strongest players in the market alongside cutting edge innovative startups. ICI Exhibition is the perfect opportunity to connect and interact with the people that can affect the future of this field.

3. ICI Technology Parade

Focused on innovation, ICI provides an extensive platform for startup companies presenting their latest technologies. The Technology Parade can be a springboard for new companies with bright and creative new ideas. This is the perfect opportunity to help your business move “from idea to reality”. The Technology Parade Sessions enjoy a tremendous success in every meeting, attracting a wide variety of leading clinicians, scientists and corporate representatives. The wide spectrum of investors who will be in attendance will find the ICI Meeting a valuable forum for exposure to the development and advancement of innovative ideas in cardiology.

The ICI meeting is a tremendous opportunity to review the most innovative startups in the field of medical devices and meet in person at the B2B area. This event can be your chance to look into the latest most prominent investments opportunity. 

SOURCE

http://2014.icimeeting.com/

Conference PROGRAM

http://2014.icimeeting.com/ici-2014-program/

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SACHS FLYER 2014 CVD Title

Please see Further Titles at

https://pharmaceuticalintelligence.com/biomed-e-books/

Please see Further Information on the Sachs Associates 14th Annual Biotech in Europe Forum for Global Investing & Partnering at:

https://pharmaceuticalintelligence.com/2014/03/25/14th-annual-biotech-in-europe-forum-for-global-partnering-investment-930-1012014-%E2%80%A2-congress-center-basel-sachs-associates-london/

AND

http://www.sachsforum.com/basel14/index.html

why-is-twitter-s-logo-named-after-larry-bird--b8d70319daON TWITTER Follow at

@SachsAssociates

#Sachs14thBEF

@pharma_BI

@AVIVA1950 

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Cardiovascular Research Foundation (CRF) Events – tctmd – The Source for Interventional Cardiovascular

 

Reporter: Aviva Lev-Ari, PhD, RN

SOURCE

http://www.tctmd.com/news.aspx

JOURNAL NEWS

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Monday, July 28, 2014 | Source: EuroIntervention

Proximal May Be Preferred Form of Embolic Protection in Carotid Stenting

By Kim Dalton
A proximal protection device can be successfully and safely used as the first choice for embolic protection during most carotid artery stenting…

Friday, July 25, 2014 | Source: The American Heart Journal

Meta-analysis: Patient Sex Affects Response to Routine Invasive Approach for NSTE-ACS

By Todd Neale
A routine invasive strategy—relative to a more selective approach—appears beneficial over the long term for men but not women with non-ST-segment elevation…

Thursday, July 24, 2014 | Source: American Journal of Cardiology

PCI for Stable CAD Drives Overall Decline in Use of Procedure Since 2009

By Yael L. Maxwell
National use of percutaneous coronary intervention (PCI) has decreased steadily since 2009, mostly driven by a reduction in procedures for patients…

Thursday, July 24, 2014 | Source: European Heart Journal

Pre-AMI Ischemia May Reduce Early Mortality

By Kim Dalton
Patients who report angina symptoms or are diagnosed with ischemia shortly before an acute myocardial infarction (AMI) are less likely to die within…

Wednesday, July 23, 2014 | Source: EuroIntervention

Bioresorbable Scaffold Performs Well, But Thrombosis Raises Concerns

By Todd Neale
Percutaneous coronary intervention (PCI) with an everolimus-eluting bioresorbable vascular scaffold (BVS) results in an “acceptable” rate of target…

Tuesday, July 22, 2014 | Source: Journal of the American College of Cardiology

New CMR-Identified Myocardial Injury Post-TAVR Linked With Decreased LV Function

By Yael L. Maxwell
New ischemic myocardial injury, presumably of embolic origin, is common after transcatheter aortic valve replacement (TAVR) and is associated with…

Tuesday, July 22, 2014 | Source: JAMA Internal Medicine

Catheter-Directed Thrombolysis for DVT Increases Bleeding Compared With Standard Anticoagulation

By L.A. McKeown
While catheter-directed thrombolysis and anticoagulation for deep vein thrombosis (DVT) does not appear to increase mortality over standard anticoagulation…

Monday, July 21, 2014 | Updated With New Commentary | Source: Lancet

HEAT-PPCI Published: Discrepant Finding of Heparin’s Superiority over Bivalirudin in Primary PCI Still Puzzles

By Yael L. Maxwell
The HEAT-PPCI trial, published July 5, 2014, ahead of print in the Lancet , reports better efficacy and comparable safety with bivalirudin than…

Monday, July 21, 2014 | Source: Journal of the American College of Cardiology

One-Time Platelet Testing Appears Insufficient to Guide Clopidogrel Therapy

By Kim Dalton
In many patients with stable coronary artery disease (CAD), platelet reactivity varies markedly over time despite an unchanged dose of clopidogrel,…

Friday, July 18, 2014 | Source: American Heart Journal

Hybrid Revascularization a Promising Option for Diabetic Patients

By L.A. McKeown
A hybrid procedure combining percutaneous revascularization with minimally invasive coronary artery grafting results in similar short-term and…

CONFERENCE NEWS

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Wednesday, May 28, 2014 | Source: EuroPCR 2014

EuroPCR 2014: Clinical Challenges, Novel Innovations Share the Limelight

By Caitlin E. Cox
PARIS, France—Research presented at EuroPCR 2014, held May 20 23, offered both new ways to improve on current therapies and fresh approaches to treating…

Friday, May 23, 2014 | Source: EuroPCR 2014

Studies Document Initial Steps Toward Percutaneous Mitral Valve Replacement

By Caitlin E. Cox
PARIS, France—Early data on 2 different catheter-based mitral valve therapies were presented in the same Hot Line session at EuroPCR on May 21, 2014.…

Friday, May 23, 2014 | Source: EuroPCR 2014

PERFUSE Registry: Diagnostic Accuracy Achieved with CT-Derived FFR Plus CT Perfusion Imaging

By Yael L. Maxwell
PARIS, France—A strategy combining fractional flow reserve (FFR) derived from computed tomography (CT) with CT perfusion imaging has demonstrated high…

Friday, May 23, 2014 | Source: EuroPCR 2014

Benefit of LAA Closure Becomes Most Evident After 1 Year

By Caitlin E. Cox
PARIS, France—Most of the stroke protection derived from percutaneous left atrial appendage (LAA) closure does not become apparent until 1 year after…

Friday, May 23, 2014 | Source: EuroPCR 2014

Nobori BES Demonstrates Good Long-term Outcomes with No Stent Thrombosis Beyond 3 Years

By Yael L. Maxwell
PARIS, France—A novel biolimus A9-eluting, biodegradable-polymer stent (BES) shows favorable long-term clinical outcomes and very low rates of device-related…

Friday, May 23, 2014 | Source: EuroPCR 2014

New Iteration of Sapien Device Associated with Low Rates of Early Mortality, Stroke

By L.A. McKeown
A new lower-profile valve and delivery system for transcatheter aortic valve replacement (TAVR) appears promising, with low mortality and stroke rates,…

Thursday, May 22, 2014 | Source: EuroPCR 2014

SYMPLICITY HTN-3: Predictors of Response Still Relevant After Trial’s Negative Findings

By Yael L. Maxwell
PARIS, France—Even though 6 month findings of the long awaited SYMPLICITY HTN 3 randomized trial demonstrated little effect of renal denervation on…

Thursday, May 22, 2014 | Source: EuroPCR 2014

UK Registry Finds Long-Term Survival After TAVR Depends on Patient Characteristics

By Caitlin E. Cox
PARIS, France—Nearly half of high-risk patients who undergo transcatheter aortic valve replacement (TAVR) for severe aortic stenosis live at least…

Thursday, May 22, 2014 | Source: EuroPCR 2014

Global SYMPLICITY Substudy Teases out Reasons for Non-response in Real-World Patients

By Yael L. Maxwell
PARIS, France—Renal denervation has spurred much controversy in recent months, with the sham-controlled SYMPLICITY HTN-3 trial demonstrating little…

Thursday, May 22, 2014 | Source: EuroPCR 2014

Early Data Show Novel Catheter-Implanted Device Benefits Patients with Left Heart Failure

By Caitlin E. Cox
PARIS, France—A first-in-man study presented Tuesday, May 20, at EuroPCR 2014 introduced a new percutaneous treatment for heart failure. Josep Rodés-Cabau,…

 

ACC NEWS

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Monday, June 24, 2013 | Source: ACC News Releases

Study Shows Heart Failure Survivors at Greater Risk for Cancer Trend toward more cancers and more deaths among heart failure patients

By ACC News Releases
WASHINGTON (June 25, 2013) – Heart failure patients are surviving more often with the heart condition but they are increasingly more likely to be diagnosed…

Tuesday, June 04, 2013 | Source: ACC News Releases

New Program to Help Heart Patients Navigate Care, Reduce Readmissions AstraZeneca sponsorship to help support patient-centered programs in 35 hospitals

By ACC News Releases
WASHINGTON (June 5, 2013) – The American College of Cardiology is developing a program with support from founding sponsor AstraZeneca to provide personalized…

Tuesday, June 04, 2013 | Source: ACC News Releases

ACC/AHA Update Guideline for Management of Heart Failure Update increases emphasis on quality of life, care coordination, palliative care

By ACC News Releases
WASHINGTON (June 5, 2013) – The American College of Cardiology and the American Heart Association today released an expanded clinical practice guideline…

Sunday, March 10, 2013 | Source: ACC News Releases

Study Shows On-Pump Bypass Comparable to Off-Pump at Year Mark

By ACC News Releases
30-day neurocognitive differences disappeared by one-year follow up Read More

Sunday, March 10, 2013 | Source: ACC News Releases

Screenings, Targeted Care Reduce Heart Failure in At-Risk Patients

By ACC News Releases
Study shows simple blood test may help patients with risks for heart disease Read More

Sunday, March 10, 2013 | Source: ACC News Releases

Digoxin Reduces Hospital Admissions in Older Patients with Chronic Heart Failure

By ACC News Releases
If replicated in heart failure patients discharged from hospital, drug may help hospitals avoid readmission penalties Read…

Monday, March 26, 2012 | Source: Clinical Trials

Rule Out Myocardial Ischemia/Infarction Using Computer Assisted Tomography

By Clinical Trials
The goal of the trial was to evaluate a strategy of cardiac computed tomography (CT) angiography compared with standard emergency department (ED)…

Monday, March 26, 2012 | Source: ACC News Releases

STUDY SUGGESTS BETTER SURVIVAL IN PATIENTS UNDERGOING BYPASS SURGERY COMPARED TO CORONARY ANGIOPLASTY

By ACC News Releases
Patients with coronary heart disease and their doctors have long been challenged by the decision of whether to pursue bypass surgery or opt for the…

Monday, March 26, 2012 | Source: ACC News Releases

CARDIAC CT IS FASTER, MORE EFFECTIVE FOR EVALUATING PATIENTS WITH SUSPECTED HEART ATTACK

By ACC News Releases
Cardiac computed tomography angiography scans (CT scans that look at the heart) can provide a virtually instant verdict on whether chest pain is…

Monday, March 26, 2012 | Source: Clinical Trials

EINSTEIN–Pulmonary Embolism (PE) Study

By Clinical Trials
The goal of the trial was to evaluate treatment of the oral direct factor Xa inhibitor, rivaroxaban, compared with standard therapy among patients…

 

 

 

Upcoming Meetings:
 CRF Podium Icon LAA Closure 
A Technique-Oriented Course
July 17-19, 2014
Chicago, IL
 CRF Podium Icon NYC Cineangiogram Case Review Dinner Series for Fellows
July 17, 2014
Opia Restaurant
(inside the Renaissance 57 Hotel)
130 East 57th St
New York, NY
 CRF Podium Icon BRS 
Bioresorbable Vascular Scaffolds: Transformational Technology for PCI
July 25-26, 2014
The Fairmont Copley Plaza
Boston, MA
 TCT Icon Transcatheter Cardiovascular Therapeutics (TCT) 2014
Sept. 13-17, 2014
Walter E. Washington Convention Center
Washington, DC
 CRF Podium Icon NYC Cineangiogram Case Review Dinner Series for Fellows
Sep 25, 2014
Opia Restaurant
(inside the Renaissance 57 Hotel)
130 East 57th St
New York, NY
 CRF Podium Icon The VEINS 
Venous Endovascular Interventional Strategies
Oct 9-11, 2014
The Swissotel Hotel
Chicago, IL
 CRF Podium Icon NYC Cineangiogram Case Review Dinner Series for Fellows
Nov 6, 2014
Opia Restaurant
(inside the Renaissance 57 Hotel)
130 East 57th St
New York, NY
 CRF Podium Icon Transradial Symposium 2014
November 8, 2014
W New York Union Square
New York, NY
 CRF Global Partner Events 
 CRF Podium Icon TCT India 
Advanced CardioVascular Solutions (ACVS) India 2014 with TCT
Aug 1-4, 2014
Hyderabad, India
 CRF Podium Icon TCT 2014 Highlights at GISE 
Oct 14-17, 2014
Genoa, Italy
 CRF Podium Icon ICI 
Innovations in Cardiovascular Interventional Cardiology
Dec 14-16, 2014
Tel-Aviv, Israel

SOURCE

http://www.tctmd.com/show.aspx?id=43158

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MedTech (Cardiac Imaging) and Medical Devices for Cardiovascular Repair – Curations, Co-Curations and Reporting by Aviva Lev-Ari, PhD, RN


MedTech (Cardiac Imaging) and Medical Devices for Cardiovascular Repair – Curations, Co-Curations and Reporting by Aviva Lev-Ari, PhD, RN

Cardiac Imaging and Cardiovascular Medical Devices in use for

Cardiac Surgery, Cardiothoracic Surgical Procedures and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty

List of Publications updated on 8/13/2018

 

Single-Author Curation by Aviva Lev-Ari, PhD, RN

 

42c       Experimental Therapy (Left inter-atrial shunt implant device) for Heart Failure: Expert Opinion on a Preliminary Study on Heart Failure with preserved Ejection Fraction

Article Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/05/09/experimental-therapy-left-inter-atrial-shunt-implant-device-for-heart-failure-expert-opinion-on-a-preliminary-study-on-heart-failure-with-preserved-ejection-fraction/

 

41c       Spectranetics, a Technology Leader in Medical Devices for Coronary Intervention, Peripheral Intervention, Lead Management to be acquired by Philips for 1.9 Billion Euros

Reporter and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/06/28/spectranetics-a-technology-leader-in-medical-devices-for-coronary-intervention-peripheral-intervention-lead-management-to-be-acquired-by-philips-for-1-9-billion-euros/

 

40c       Moderate Ischemic Mitral Regurgitation: Outcomes of Surgical Treatment during CABG vs CABG without Mitral Valve Repair

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/04/04/moderate-ischemic-mitral-regurgitation-outcomes-of-surgical-treatment-during-cabg-vs-cabg-without-mitral-valve-repair/

 

39c       Patients with Heart Failure & Left Ventricular Dysfunction: Life Expectancy Increased by coronary artery bypass graft (CABG) surgery: Medical Therapy alone and had Poor Outcomes

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/04/04/patients-with-heart-failure-left-ventricular-dysfunction-life-expectancy-increased-by-coronary-artery-bypass-graft-cabg-surgery/

 

38c       Mapping the Universe of Pharmaceutical Business Intelligence: The Model developed by LPBI and the Model of Best Practices LLC

Author and Curator of Model A: Aviva Lev-Ari, PhD, RN and Reporter on Model B: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/13/mapping-the-universe-of-pharmaceutical-business-intelligence-the-model-developed-by-lpbi-and-the-model-of-best-practices-llc/

 

37c     MedTech & Medical Devices for Cardiovascular Repair – Curations by

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/17/medtech-medical-devices-for-cardiovascular-repair-curation-by-aviva-lev-ari-phd-rn/

 

36c     Stem Cells and Cardiac Repair: Scientific Reporting by: Aviva Lev-Ari, PhD, RN

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/17/stem-cells-and-cardiac-repair-content-curation-scientific-reporting-aviva-lev-ari-phd-rn/

 

35c       CVD Prevention and Evaluation of Cardiovascular Imaging Modalities: Coronary Calcium Score by CT Scan Screening to justify or not the Use of Statin

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/03/03/cvd-prevention-and-evaluation-of-cardiovascular-imaging-modalities-coronary-calcium-score-by-ct-scan-screening-to-justify-or-not-the-use-of-statin/

 

34c       “Sudden Cardiac Death,” SudD is in Ferrer inCode’s Suite of Cardiovascular Genetic Tests to be Commercialized in the US

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/10/sudden-cardiac-death-sudd-is-in-ferrer-incodes-suite-of-cardiovascular-genetic-tests-to-be-commercialized-in-the-us/

 

33c       Transcatheter Valve Competition in the United States: Medtronic CoreValve infringes on Edwards Lifesciences Corp. Transcatheter Device Patents

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/26/transcatheter-valve-competition-in-the-united-states-medtronic-corevalve-infringes-on-edwards-lifesciences-corp-transcatheter-device-patents/

 

32c       Developments on the Frontier of Transcatheter Aortic Valve Replacement (TAVR) Devices

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/26/developments-on-the-frontier-of-transcatheter-aortic-valve-replacement-tavr-devices/

 

31c       Market Impact on Global Suppliers of Renal Denervation Systems by Pivotal US Trial: Metronics’ Symplicity Renal Denervation System FAILURE at Efficacy Endpoint

Curator and Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/09/market-impact-on-global-suppliers-of-renal-denervation-systems-by-pivotal-us-trial-metronics-symplicity-renal-denervation-system-failure-at-efficacy-endpoint/

 

30c     Stenting for Proximal LAD Lesions

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/18/stenting-for-proximal-lad-lesions/

 

29c       Stent Design and Thrombosis:  Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

 

28c       Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/01/calcium-molecule-in-cardiac-gene-therapy-inhalable-gene-therapy-for-pulmonary-arterial-hypertension-and-percutaneous-intra-coronary-artery-infusion-for-heart-failure-contributions-by-roger-j-hajjar/

 

27c       Call for the abandonment of the Off-pump CABG surgery (OPCAB) in the On-pump / Off-pump Debate, +100 Research Studies

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/31/call-for-the-abandonment-of-the-off-pump-cabg-surgery-opcab-in-the-on-pump-off-pump-debate-100-research-studies/

 

26c       3D Cardiovascular Theater – Hybrid Cath Lab/OR Suite, Hybrid Surgery, Complications Post PCI and Repeat Sternotomy

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/19/3d-cardiovascular-theater-hybrid-cath-labor-suite-hybrid-surgery-complications-post-pci-and-repeat-sternotomy/

 

25c       Vascular Surgery: International, Multispecialty Position Statement on Carotid Stenting, 2013 and Contributions of a Vascular Surgeon at Peak Career – Richard Paul Cambria, MD

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/14/vascular-surgery-position-statement-in-2013-and-contributions-of-a-vascular-surgeon-at-peak-career-richard-paul-cambria-md-chief-division-of-vascular-and-endovascular-surgery-co-director-thoracic/

 

24c       Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/09/research-programs-george-m-linda-h-kaufman-center-for-heart-failure-cleveland-clinic/

 

23c       Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications 

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/08/becoming-a-cardiothoracic-surgeon-an-emerging-profile-in-the-surgery-theater-and-through-scientific-publications/

 

22c       Fractional Flow Reserve (FFR) & Instantaneous wave-free ratio (iFR): An Evaluation of Catheterization Lab Tools (Software Validation) for Endovascular Lower-extremity Revascularization Effectiveness: Vascular Surgeons (VSs), Interventional Cardiologists (ICs) and Interventional Radiologists (IRs)

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/01/endovascular-lower-extremity-revascularization-effectiveness-vascular-surgeons-vss-interventional-cardiologists-ics-and-interventional-radiologists-irs/

 

21c       No Early Symptoms – An Aortic Aneurysm Before It Ruptures – Is There A Way To Know If I Have it?

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/10/no-early-symptoms-an-aortic-aneurysm-before-it-ruptures-is-there-a-way-to-know-if-i-have-it/

 

20c       Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/17/synthetic-biology-on-advanced-genome-interpretation-for-gene-variants-and-pathways-what-is-the-genetic-base-of-atherosclerosis-and-loss-of-arterial-elasticity-with-aging/

 

19c       Revascularization: PCI, Prior History of PCI vs CABG

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/04/25/revascularization-pci-prior-history-of-pci-vs-cabg/

 

18c       Minimally Invasive Structural CVD Repairs: FDA grants 510(k) Clearance to Philips’ EchoNavigator – X-ray and 3-D Ultrasound Image Fused.

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/03/21/minimally-invasive-structural-cvd-repairs-fda-grants-510k-to-philips-echonavigator-x-ray-and-3-d-ultrasound-image-fused/

 

17c       Acute Chest Pain/ER Admission: Three Emerging Alternatives to Angiography and PCI

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/03/10/acute-chest-painer-admission-three-emerging-alternatives-to-angiography-and-pci/

 

16c       Clinical Trials on Transcatheter Aortic Valve Replacement (TAVR) to be conducted by American College of Cardiology and the Society of Thoracic Surgeons

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/02/12/american-college-of-cardiologys-and-the-society-of-thoracic-surgeons-entrance-into-clinical-trials-is-noteworthy-read-more-two-medical-societies-jump-into-clinical-trial-effort-for-tavr-tech-f/

 

15c       FDA Pending 510(k) for The Latest Cardiovascular Imaging Technology

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/01/28/fda-pending-510k-for-the-latest-cardiovascular-imaging-technology/

 

14c       The ACUITY-PCI score: Will it Replace Four Established Risk Scores — TIMI, GRACE, SYNTAX, and Clinical SYNTAX

Curator: Aviva Lev-Ari, PhD, RN   https://pharmaceuticalintelligence.com/2013/01/03/the-acuity-pci-score-will-it-replace-four-established-risk-scores-timi-grace-syntax-and-clinical-syntax/

13c       Renal Sympathetic Denervation: Updates on the State of Medicine

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/12/31/renal-sympathetic-denervation-updates-on-the-state-of-medicine/

 

12c       Coronary artery disease in symptomatic patients referred for coronary angiography: Predicted by Serum Protein Profiles

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/12/29/coronary-artery-disease-in-symptomatic-patients-referred-for-coronary-angiography-predicted-by-serum-protein-profiles/

 

11c       CABG or PCI: Patients with Diabetes – CABG Rein Supreme

Curator: Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2012/11/05/cabg-or-pci-patients-with-diabetes-cabg-rein-supreme/

 

10c       Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/10/19/clinical-trials-results-for-endothelin-system-pathophysiological-role-in-chronic-heart-failure-acute-coronary-syndromes-and-mi-marker-of-disease-severity-or-genetic-determination/

 

9c         Imbalance of Autonomic Tone: The Promise of Intravascular Stimulation of Autonomics

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/09/02/imbalance-of-autonomic-tone-the-promise-of-intravascular-stimulation-of-autonomics/

 

8c         New Drug-Eluting Stent Works Well in STEMI

Curator: Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2012/08/22/new-drug-eluting-stent-works-well-in-stemi/

 

7c         Coronary Artery Disease – Medical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/13/coronary-artery-disease-medical-devices-solutions-from-first-in-man-stent-implantation-via-medical-ethical-dilemmas-to-drug-eluting-stents/

 

6c         DELETED, identical to 7r

 

5c         Percutaneous Endocardial Ablation of Scar-Related Ventricular Tachycardia

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/07/18/percutaneous-endocardial-ablation-of-scar-related-ventricular-tachycardia/

 

4c         Global Supplier Strategy for Market Penetration & Partnership Options (Niche Suppliers vs. National Leaders) in the Massachusetts Cardiology & Vascular Surgery Tools and Devices Market for Cardiac Operating Rooms and Angioplasty Suites

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/06/22/global-supplier-strategy-for-market-penetration-partnership-options-niche-suppliers-vs-national-leaders-in-the-massachusetts-cardiology-vascular-surgery-tools-and-devices-market-for-car/

 

3c         Competition in the Ecosystem of Medical Devices in Cardiac and Vascular Repair: Heart Valves, Stents, Catheterization Tools and Kits for Open Heart and Minimally Invasive Surgery (MIS)

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/06/22/competition-in-the-ecosystem-of-medical-devices-in-cardiac-and-vascular-repair-heart-valves-stents-catheterization-tools-and-kits-for-open-heart-and-minimally-invasive-surgery-mis/

 

2c         Executive Compensation and Comparator Group Definition in the Cardiac and Vascular Medical Devices Sector: A Bright Future for Edwards Lifesciences Corporation in the Transcatheter Heart Valve Replacement Market

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/06/19/executive-compensation-and-comparator-group-definition-in-the-cardiac-and-vascular-medical-devices-sector-a-bright-future-for-edwards-lifesciences-corporation-in-the-transcatheter-heart-valve-replace/

 

1c         Treatment of Refractory Hypertension via Percutaneous Renal Denervation

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/06/13/treatment-of-refractory-hypertension-via-percutaneous-renal-denervation/

 

Lev-Ari, A. (2006b). First-In-Man Stent Implantation Clinical Trials & Medical Ethical Dilemmas.

Bouve College of Health Sciences, Northeastern University, Boston, MA 02115

 

Co-Curation Articles on MedTech and Cardiac Medical Devices by LPBI Group’s Team Members and Aviva Lev-Ari, PhD, RN

67co     ATP – the universal energy carrier in the living cell: Reflections on the discoveries and applications in Medicine

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/27/atp-the-universal-energy-carrier-in-the-living-cell-reflections-on-the-discoveries-and-applications-in-medicine/

66co     Eric Topol, M.D.

Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/09/22/eric-topol-m-d/

 

65co     Summary of Translational Medicine – e-Series A: Cardiovascular Diseases, Volume Four – Part 1

Author and Curator: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/28/summary-of-translational-medicine-cardiovascular-diseases-part-1/

 

64co     Introduction to e-Series A: Cardiovascular Diseases, Volume Four Part 2: Regenerative Medicine

Author and Curator: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/27/larryhbernintroduction_to_cardiovascular_diseases-translational_medicine-part_2/

 

63co     Epilogue: Volume 4 – Translational, Post-Translational and Regenerative Medicine in Cardiology

Larry H Bernstein, MD, FCAP, Author and Curator, Consultant for Series B,C,D,E

Justin Pearlman, MD, PhD, FACC, Content Consultant for Series A: Cardiovascular Diseases

Aviva Lev-Ari, PhD, RN, Co-Editor and Editor-in-Chief, BioMed e-Series

https://pharmaceuticalintelligence.com/2014/05/12/epilogue-volume-4-post-translational-and-transformative-cardiology/

 

62co     Introduction to Translational Medicine (TM) – Part 1: Translational Medicine

Author and Curator: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/25/introduction-to-translational-medicine-tm-part-1/

 

61co     Acute Myocardial Infarction: Curations of Cardiovascular Original Research A Bibliography

Curators: Aviva Lev-Ari, PhD, RN and Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2014/01/22/acute-myocardial-infarction-curations-of-cardiovascular-original-research-a-bibliography/

60co     Mitral Valve Repair: Who is a Patient Candidate for a Non-Ablative Fully Non-Invasive Procedure?

Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC and Article Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/11/04/mitral-valve-repair-who-is-a-candidate-for-a-non-ablative-fully-non-invasive-procedure/

 

59co     Coronary Circulation Combined Assessment: Optical Coherence Tomography (OCT), Near-Infrared Spectroscopy (NIRS) and Intravascular Ultrasound (IVUS) – Detection of Lipid-Rich Plaque and Prevention of Acute Coronary Syndrome (ACS)

Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC and Article Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/25/coronary-circulation-combined-assessment-optical-coherence-tomography-oct-near-infrared-spectroscopy-nirs-and-intravascular-ultrasound-ivus-detection-of-lipid-rich-plaque-and-prevention-of-a/

 

58co     Normal and Anomalous Coronary Arteries: Dual Source CT in Cardiothoracic Imaging

Reporters: Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/18/normal-and-anomalous-coronary-arteries-dual-source-ct-in-cardiothoracic-imaging/

 

57co     Alternative Designs for the Human Artificial Heart: Patients in Heart Failure –  Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community

Authors and Curators: Larry H Bernstein, MD, FCAP and Justin D Pearlman, MD, PhD, FACC and Article Curator and Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/05/alternative-designs-for-the-human-artificial-heart-the-patients-in-heart-failure-outcomes-of-transplant-donorimplantation-artificial-and-monitoring-technologies-for-the-transplantimplant-pat/

 

56co     Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

Author, Introduction and Summary: Justin D Pearlman, MD, PhD, FACC, and Article Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/23/cardiovascular-complications-of-multiple-etiologies-repeat-sternotomy-post-cabg-or-avr-post-pci-pad-endoscopy-andor-resultant-of-systemic-sepsis/

 

55co     The Cardiorenal Syndrome in Heart Failure: Cardiac? Renal? syndrome?

Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/30/the-cardiorenal-syndrome-in-heart-failure/

 

54co     Mechanical Circulatory Assist Devices as a Bridge to Heart Transplantation or as “Destination Therapy“: Options for Patients in Advanced Heart Failure

Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/30/advanced-heart-failure/

 

53co     Heart Transplantation: NHLBI’s Ten year Strategic Research Plan to Achieving Evidence-based Outcomes

Author and Curator: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/30/heart-transplantation-research-in-the-next-decade-a-goal-to-achieving-evidence-based-outcomes/

 

52co     After Cardiac Transplantation: Sirolimus acts as immunosuppressant Attenuates Allograft Vasculopathy

Author and Curator: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/30/sirolimus-as-primary-immunosuppression-attenuates-allograft-vasculopathy/

51co     Orthotropic Heart Transplant (OHT): Effects of Autonomic Innervation / Denervation on Atrial Fibrillation (AF) Genesis and Maintenance

Author and Curator: Larry H. Bernstein, MD, FCAP and

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/30/decreased-postoperative-atrial-fibrillation-following-cardiac-transplantation/

 

50co     CABG Survival in Multivessel Disease Patients: Comparison of Arterial Bypass Grafts vs Saphenous Venous Grafts

Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/30/multiple-arterial-grafts-improve-late-survival-of-patients-with-multivessel-disease/

49co     Coronary Reperfusion Therapies: CABG vs PCI – Mayo Clinic preprocedure Risk Score (MCRS) for Prediction of in-Hospital Mortality after CABG or PCI

Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/30/mayo-risk-score-for-percutaneous-coronary-intervention/

 

48co     Pre-operative Risk Factors and Clinical Outcomes Associated with Vasoplegia in Recipients of Orthotopic Heart Transplantation in the Contemporary Era

Writer and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/30/vasoplegia-in-orthotopic-heart-transplants/

 

47co     Carotid Endarterectomy (CEA) vs. Carotid Artery Stenting (CAS): Comparison of CMMS high-risk criteria on the Outcomes after Surgery:  Analysis of the Society for Vascular Surgery (SVS) Vascular Registry Data

Writer and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/28/effect-on-endovascular-carotid-artery-repair-outcomes-of-the-cmms-high-risk-criteria/

 

46co     Improved Results for Treatment of Persistent type 2 Endoleak after Endovascular Aneurysm Repair: Onyx Glue Embolization

Author and Curator: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/28/onyx-glue-for-the-treatment-of-persistent-type-2-endoleak/

 

45co     DELETED, was identical to 47co

 

44co     Open Abdominal Aortic Aneurysm (AAA) repair (OAR) vs. Endovascular AAA Repair (EVAR) in Chronic Kidney Disease (CKD) Patients – Comparison of Surgery Outcomes

Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/28/the-effect-of-chronic-kidney-disease-on-outcomes-after-abdominal-aortic-aneurysm-repair/

 

43co     Effect of Hospital Characteristics on Outcomes of Endovascular Repair of Descending Aortic Aneurysms in US Medicare Population

Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/27/effect-of-hospital-characteristics-on-outcomes-of-endovascular-repair-of-descending-aortic-aneurysms-in-us-medicare-population/

 

42co     First case in the US: Valve-in-Valve (Aortic and  Mitral) Replacements with Transapical Transcatheter Implants – The Use of Transfemoral Devices

Author: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/23/valve-in-valve-replacements-with-transapical-transcatheter-implants/

 

41co     Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty

Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/23/comparison-of-cardiothoracic-bypass-and-percutaneous-interventional-catheterization-survivals/

 

40co     Ventricular Assist Device (VAD): A Recommended Approach to the Treatment of Intractable Cardiogenic Shock

Author: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/18/a-recommended-approach-to-the-treatmnt-of-intractable-cardiogenic-shock/

39co     Trans-apical Transcatheter Aortic Valve Replacement in a Patient with Severe and Complex Left Main Coronary Artery Disease (LMCAD)

Author: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/17/management-of-difficult-trans-apical-transcatheter-aortic-valve-replacement-in-a-patient-with-severe-and-complex-arterial-disease/

 

38co     Transcatheter Aortic Valve Replacement (TAVR): Postdilatation to Reduce Paravalvular Regurgitation During TAVR with a Balloon-expandable Valve

Curator: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/17/postdilatation-to-reduce-paravalvular-regurgitation-during-transcatheter-aortic-valve-replacement/

 

37co     Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone

Justin Pearlman, MD, PhD and Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2013/05/22/acute-and-chronic-myocardial-infarction-quantification-of-myocardial-viability-fdg-petmri-vs-mri-or-pet-alone/

 

36co     On Devices and On Algorithms: Arrhythmia after Cardiac SurgeryPrediction and ECG Prediction of Paroxysmal Atrial Fibrillation Onset

Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC and Article Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/07/on-devices-and-on-algorithms-arrhythmia-after-cardiac-surgery-prediction-and-ecg-prediction-of-paroxysmal-atrial-fibrillation-onset/

 

35co     Vascular Repair: Stents and Biologically Active Implants

Author and Curator: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/04/stents-biologically-active-implants-and-vascular-repair/

 

34co     Drug Eluting Stents: On MIT‘s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES

Author: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/04/25/contributions-to-vascular-biology/

 

33co     Mitral Valve Repair: Who is a Patient Candidate for a Non-Ablative Fully Non-Invasive Procedure?

Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC and Article Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/11/04/mitral-valve-repair-who-is-a-candidate-for-a-non-ablative-fully-non-invasive-procedure/

 

32co     Source of Stem Cells to Ameliorate Damaged Myocardium (Part 2)

Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/10/29/source-of-stem-cells-to-ameliorate-damaged-myocardium/

 

31co     State of Cardiology on Wall Stress, Ventricular Workload and Myocardial Contractile Reserve: Aspects of Translational Medicine (TM)

Curators: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/09/30/state-of-cardiology-on-wall-stress-ventricular-workload-and-myocardial-contractile-reserve-aspects-of-translational-medicine/

 

30co  DELETED identical to 58co

 

29co  DELETED identical to 58co

 

28co  DELETED identical to 57co

 

27co  DELETED identical to 47co

 

26co     Cardiac Resynchronization Therapy (CRT) to Arrhythmias: Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion

Curators: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/22/cardiac-resynchronization-therapy-crt-to-arrhythmias-pacemakerimplantable-cardioverter-defibrillator-icd-insertion/

 

25co     Emerging Clinical Applications for Cardiac CT: Plaque Characterization, SPECT Functionality, Angiogram’s and Non-Invasive FFR

Curators: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/17/emerging-clinical-applications-for-cardiac-ct-plaque-characterization-spect-functionality-angiograms-and-non-invasive-ffr/

 

24co     Fractional Flow Reserve (FFR) & Instantaneous wave-free ratio (iFR): An Evaluation of Catheterization Lab Tools (Software Validation) for Ischemic Assessment (Diagnostics) – Change in Paradigm: The RIGHT vessel not ALL vessels

Reporters: Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/04/fractional-flow-reserve-ffr-instantaneous-wave-free-rario-ifr-an-evaluation-of-catheterization-lab-tools-for-ischemic-assessment/

 

23co  DELETED identical to 24co

 

22co  DELETED identical to 49co

 

21co  DELETED identical to 52co

 

20co  DELETED identical to 50co

 

19co  DELETED identical to 57co

 

18co     Open Abdominal Aortic Aneurysm (AAA) repair (OAR) vs. Endovascular AAA Repair (EVAR) in Chronic Kidney Disease (CKD) Patients – Comparison of Surgery Outcomes

Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/28/the-effect-of-chronic-kidney-disease-on-outcomes-after-abdominal-aortic-aneurysm-repair/

 

17co     Improved Results for Treatment of Persistent type 2 Endoleak after Endovascular Aneurysm Repair: Onyx Glue Embolization

Author & Curator: Larry H Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/28/onyx-glue-for-the-treatment-of-persistent-type-2-endoleak/

16co     Effect of Hospital Characteristics on Outcomes of Endovascular Repair of Descending Aortic Aneurysms in US Medicare Population

Author and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/27/effect-of-hospital-characteristics-on-outcomes-of-endovascular-repair-of-descending-aortic-aneurysms-in-us-medicare-population/

 

15co     Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) / Coronary Angioplasty

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/23/comparison-of-cardiothoracic-bypass-and-percutaneous-interventional-catheterization-survivals/

 

14co     First case in the US: Valve-in-Valve (Aortic and Mitral) Replacements with Transapical Transcatheter Implants – The Use of Transfemoral Devices.

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/23/valve-in-valve-replacements-with-transapical-transcatheter-implants/

 

13co     Phrenic Nerve Stimulation in Patients with Cheyne-Stokes Respiration and Congestive Heart Failure

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/20/phrenic-nerve-stimulation-in-patients-with-cheyne-stokes-respiration-and-congestive-heart-failure/

 

12co  DELETED identical to 40co

11co  DELETED identical to 38co

10co  DELETED identical to 39co

 

9co       Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

Curators: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/24/imaging-biomarker-for-arterial-stiffness-pathways-in-pharmacotherapy-for-hypertension-and-hypercholesterolemia-management/

 

8co       DELETED identical to 37co

 

7co       Treatment, Prevention and Cost of Cardiovascular Disease: Current & Predicted Cost of Care and the Potential for Improved Individualized Care Using Clinical Decision Support Systems

Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC, Author and Curator: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems-2/

 

6co       Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus

Curators: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/11/arterial-elasticity-in-quest-for-a-drug-stabilizer-isolated-systolic-hypertension-caused-by-arterial-stiffening-ineffectively-treated-by-vasodilatation-antihypertensives/

 

5co       DELETED identical to 36co

 

4co       Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization

Author and Curator: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/05/bioengineering-of-vascular-and-tissue-models/

 

3co       Cardiovascular Diseases: Decision Support Systems for Disease Management Decision Making

Curators: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/04/cardiovascular-diseases-decision-support-systems-for-disease-management-decision-making/

 

2co    DELETED identical to 35co

 

1co    DELETED identical to 34co

 

Single-Author Reporting on MedTech and Cardiac Medical Devices by

Aviva Lev-Ari, PhD, RN

 

162r Rhythm Management Device Hardware (Dual-chamber Pacemaker) coupled with BackBeat’s Cardiac Neuromodulation Therapy (CNT) bioelectronic therapy for Lowering Systolic Blood Pressure for patients with Pacemakers

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/10/03/rhythm-management-device-hardware-dual-chamber-pacemaker-coupled-with-backbeats-cardiac-neuromodulation-therapy-cnt-bioelectronic-therapy-for-lowering-systolic-blood-pressure-for-patients-w/

 

161r Pulmonary Valve Replacement and Repair: Valvuloplasty Device – Tissue (bioprosthetic) or mechanical valve;  Surgery type – Transcatheter Pulmonary Valve Replacement (TPVR) vs Open Heart, Valve Repair – Commissurotomy, Valve-ring Annuloplasty

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/09/30/pulmonary-valve-replacement-and-repair-valvuloplasty-device-tissue-bioprosthetic-or-mechanical-valve-surgery-type-transcatheter-pulmonary-valve-replacement-tpvr-vs-open-heart-valve-re/

 

160r Are TAVR volume requirements limiting rural and minority access to this life-saving procedure, or are they still necessary for patient safety?

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/09/20/are-tavr-volume-requirements-limiting-rural-and-minority-access-to-this-life-saving-procedure-or-are-they-still-necessary-for-patient-safety/

159r Top 100 of 415 articles published on PubMed in 2018 on TAVR

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/08/14/top-100-of-415-articles-published-on-pubmed-in-2018-on-tavr/

158r Aortic Stenosis (AS): Managed Surgically by Transcatheter Aortic Valve Replacement (TAVR) – Search Results for “TAVR” on NIH.GOV website, Top 16 pages

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/08/14/aortic-stenosis-as-managed-surgically-by-transcatheter-aortic-valve-replacement-tavr-search-results-for-tavr-on-nih-gov-website-top-16-pages/

 

157r Comparison of four methods in diagnosing acute myocarditis: The diagnostic performance of native T1, T2, ECV to LLC

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/08/08/comparison-of-four-methods-in-diagnosing-acute-myocarditis-the-diagnostic-performance-of-native-t1-t2-ecv-to-llc/

 

156r   Left ventricular outflow tract (LVOT) obstruction (LVOTO): The Role of CT in TAVR and in TMVR

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/07/25/left-ventricular-outflow-tract-lvot-obstruction-lvoto-the-role-of-ct-in-tavr-and-in-tmvr/

 

155r   CABG: a Superior Revascularization Modality to PCI in Patients with poor LVF, Multivessel disease and Diabetes, Similar Risk of Stroke between 31 days and 5 years, post intervention

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/07/25/cabg-a-superior-revascularization-modality-to-pci-in-patients-with-poor-lvf-multivessel-disease-and-diabetes-similar-risk-of-stroke-between-31-days-and-5-years-post-intervention/

 

154r   Stanford University researchers have developed a scanner that unites optical, radioluminescence, and photoacoustic imaging to evaluate for Thin-Cap Fibro Atheroma (TCFA)

Reporter: Aviva Lev-Ari, RN

https://pharmaceuticalintelligence.com/2018/07/23/stanford-university-researchers-have-developed-a-scanner-that-unites-optical-radioluminescence-and-photoacoustic-imaging-to-evaluate-for-thin-cap-fibro-atheroma-tcfa/

 

153r   An Overview of the Heart Surgery Specialty: heart transplant, lung transplant, heart-lung transplantation, aortic valve surgery, bypass surgery, minimally invasive cardiac surgery, heart valve surgery, removal of cardiac tumors, reoperation valve surgery

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/07/11/the-heart-surgery-specialty-heart-transplant-lung-transplant-heart-lung-transplantation-aortic-valve-surgery-bypass-surgery-minimally-invasive-cardiac-surgery-heart-valve-surgery-removal-of-ca/

 

152r   PCI, CABG, CHF, AMI – Two Payment Methods: Bundled payments (hospitalization costs, up to 90 days of post-acute care, nursing home care, complications, and rehospitalizations) vs Diagnosis-related groupings cover only what happens in the hospital.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/07/10/pci-cabg-chf-ami-two-payment-methods-bundled-payments-hospitalization-costs-up-to-90-days-of-post-acute-care-nursing-home-care-complications-and-rehospitalizations-vs-diagnosis-related-gro/

 

151r   Expanded Stroke Thrombectomy Guidelines: FDA expands treatment window for use (Up to 24 Hours Post-Stroke) of clot retrieval devices (Stryker’s Trevo Stent) in certain stroke patients

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/02/27/expanded-stroke-thrombectomy-guidelines-fda-expands-treatment-window-for-use-up-to-24-hours-post-stroke-of-clot-retrieval-devices-strykers-trevo-stent-in-certain-stroke-patients/

 

150r   What is the Role of Noninvasive Diagnostic Fractional Flow Reserve (FFR) CT vs Invasive FFR for PCI?

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/02/27/what-is-the-role-of-noninvasive-diagnostic-fractional-flow-reserve-ffr-ct-vs-invasive-ffr-for-pci/

 

149r   Renowned Electrophysiologist Dr. Arthur Moss Died on February 14, 2018 at 86

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/02/27/renowned-electrophysiologist-dr-arthur-moss-died-on-february-14-2018-at-86/

 

148r   Mitral Valve Repair Global Leader: Edwards LifeSciences acquired Harpoon Medical for $250 in 12/2017 followed by $690 million buyout of Valtech Cardio 1/2017 and $400 million acquisition of CardiAQ Valve Technologies in 8/2017

Reporter: Aviva Lev-Ari, PhD

https://pharmaceuticalintelligence.com/2017/12/08/mitral-valve-repair-global-leader-edwards-lifesciences-acquired-harpoon-medical-for-250-in-12-2017-followed-by-690-million-buyout-of-valtech-cardio-1-2017-and-400-million-acquisitio/

 

147r   2017 American Heart Association Annual Meeting: Sunday’s Science at #AHA17 – Presidential Address

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/11/13/2017-american-heart-association-annual-meeting-sundays-science-at-aha17-presidential-address/

 

146r   Medical Devices Early Feasibility FDA’s Pathway – Accelerated Recruitment for Randomized Clinical Trials: Replacement and Repair of Mitral Valves

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/11/13/medical-devices-early-feasibility-fdas-pathway-accelerated-recruitment-for-randomized-clinical-trials-replacement-and-repair-of-mitral-valves/

 

145r   Arrhythmias Detection: Speeding Diagnosis and Treatment – New deep learning algorithm can diagnose 14 types of heart rhythm defects by sifting through hours of ECG data generated by some REMOTELY iRhythm’s wearable monitors

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/07/10/arrhythmias-detection-speeding-diagnosis-and-treatment-new-deep-learning-algorithm-can-diagnose-14-types-of-heart-rhythm-defects-by-sifting-through-hours-of-ecg-data-generated-by-some-remotely-irhy/

 

144r   Cleveland Clinic: Change at the Top, Tomislav “Tom” Mihaljevic, M.D., as its next CEO and President to succeed Toby Cosgrove, M.D., effective Jan. 1, 2018

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/09/01/cleveland-clinic-change-at-the-top-tomislay-tom-mihaljevic-m-d-as-its-next-ceo-and-president-to-succeed-toby-cosgrove-m-d-effective-jan-1-2018/

 

143r   Off-Label TAVR Procedures: 1 in 10 associated with higher in-hospital 30-day mortality, 1-year mortality was similar in the Off-Label and the On-Label groups

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/06/22/off-label-tavr-procedures-1-in-10-associated-with-higher-in-hospital-30-day-mortality-1-year-mortality-was-similar-in-the-off-lavel-and-the-on-label-groups/

 

142r   Right Internal Carotid Artery Clot Aspiration: 4.5 Minute Thrombectomy Using the ADAPT-FAST Technique and the ACE68 Catheter

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/05/17/right-internal-carotid-artery-clot-aspiration-4-5-minute-thrombectomy-using-the-adapt-fast-technique-and-the-ace68-catheter/

 

141r   Less is More: Minimalist Mitral Valve Repair: Expert Opinion of Prem S. Shekar, MD, Chief, Division of Cardiac Surgery, BWH – #7, 2017 Disruptive Dozen at #WMIF17

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/05/17/less-is-more-minimalist-mitral-valve-repair-expert-opinion-of-prem-s-shekar-md-chief-division-of-cardiac-surgery-bwh-7-2017-disruptive-dozen-at-wmif17/

140r   What is the history of STEMI? What is the current treatment for Cardiogenic Shock? The Case Study of Detroit Cardiogenic Shock Initiative

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/05/07/what-is-the-history-of-stemi-what-is-the-current-treatment-for-cardiogenic-shock-the-case-study-of-detroit-cardiogenic-shock-initiative/

 

139r   ACC 2017, 3/30/2017 – Poor Outcomes for Bioresorbable Stents in Small Coronary Arteries

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/04/02/acc-2017-3302017-poor-outcomes-for-bioresorbable-stents-in-small-coronary-arteries/

 

138r   Edwards Lifesciences closes $690m a buy of Valtech Cardio and most of the heart valve repair technologies it’s developing

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/01/25/edwards-lifesciences-closes-690m-a-buy-of-valtech-cardio-and-most-of-the-heart-valve-repair-technologies-its-developing/

 

137r   First U.S. TAVR Patients Treated With Temporary Pacing Lead (Tempo Lead)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/21/first-u-s-tavr-patients-treated-with-temporary-pacing-lead-tempo-lead/

 

136r   2017 World Medical Innovation Forum: Cardiovascular, May 1-3, 2017, Partners HealthCare, Boston, at the Westin Hotel, Boston

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/14/2017-world-medical-innovation-forum-cardiovascular-may-1-3-2017-partners-healthcare-boston-at-the-westin-hotel-boston/

 

135r   Advanced Peripheral Artery Disease (PAD): Axillary Artery PCI for Insertion and Removal of Impella Device

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/13/advanced-peripheral-artery-disease-pad-axillary-pci-for-insertion-and-removal-of-impella-device/

 

134r   CorPath robotic system for bifurcation lesions with placement of the Absorb GT1 Bioresorbable Vascular Scaffold (BVS) (Abbott Vascular)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/07/corpath-robotic-system-for-bifurcation-lesions-with-placement-of-the-absorb-gt1-bioresorbable-vascular-scaffold-bvs-abbott-vascular/

 

133r   Hadassah Opens Israel’s First Heart Valve Disease Clinic

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/06/hadassah-opens-israels-first-heart-valve-disease-clinic/

 

132r   Left Main Coronary Artery Disease (LMCAD): Stents vs CABG – The less-invasive option is Equally Safe and Effective

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/06/left-main-coronary-artery-disease-lmcad-stents-vs-cabg-the-less-invasive-option-is-equally-safe-and-effective/

 

131r   Advances and Future Directions for Transcatheter Valves – Mitral and tricuspid valve repair technologies now in development

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/06/advances-and-future-directions-for-transcatheter-valves-mitral-and-tricuspid-valve-repair-technologies-now-in-development/

 

130r   New method for performing Aortic Valve Replacement: Transmural catheter procedure developed at NIH, Minimally-invasive tissue-crossing – Transcaval access, abdominal aorta and the inferior vena cava

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/10/31/new-method-for-performing-aortic-valve-replacement-transmural-catheter-procedure-developed-at-nih-minimally-invasive-tissue-crossing-transcaval-access-abdominal-aorta-and-the-inferior-vena-cava/

 

129r   Robot-assisted coronary intervention program @MGH – The first CorPath Vascular Robotic System, lets Interventional Cardiologists position the right stent in the right place at reduces radiation exposure by 95%

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/10/17/robot-assisted-coronary-intervention-program-mgh-the-first-corpath-vascular-robotic-system-lets-interventional-cardiologists-position-the-right-stent-in-the-right-place-at-reduces-radiation-exposu/

 

128r   Second in the United States to implant Edwards Newly FDA-Approved Aortic Valve “Intuity Elite” Sutureless Valve at Northwestern Medicine

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/10/13/second-in-the-united-states-to-implant-edwards-newly-fda-approved-aortic-valve-intuity-elite-sutureless-valve-at-northwestern-medicine/

 

127r   First-in-Man Mitral Valve Repairs Device used for Tricuspid Valve Repair: Cardioband used by University Hospital Zurich Heart Team

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/10/13/first-in-man-mitral-valve-repairs-device-used-for-tricuspid-valve-repair-cardioband-used-by-university-hospital-zurich-heart-team/

 

126r   Inferior Vena Cava Filters: Device for Prevention of Pulmonary Embolism and Thrombosis

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/10/04/vena-caval-filters-device-for-prevention-of-pulmonary-embolism-and-thrombosis/

 

125r   Chest Radiation Therapy causes Collateral Damage to the Human Heart

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/08/28/chest-radiation-therapy-causes-collateral-damage-to-the-human-heart/

 

124r   Clinical Trials for Transcatheter Mitral Valves Annulus Repairs and TAVR: CT Structural Software for Procedural Planning and Anatomical Assessments

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/08/15/clinical-trials-for-transcatheter-mitral-valves-annulus-repairs-and-tavr-ct-structural-software-for-procedural-planning-and-anatomical-assessments/

 

123r   Lysyl Oxidase (LOX) gene missense mutation causes Thoracic Aortic Aneurysm and Dissection (TAAD) in Humans because of inadequate cross-linking of collagen and elastin in the aortic wall

Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/19/lysyl-oxidase-lox-gene-missense-mutation-causes-thoracic-aortic-aneurysm-and-dissection-taad-in-humans-because-of-inadequate-cross-linking-of-collagen-and-elastin-in-the-aortic-wall/

 

122r   SAPIEN 3 Transcatheter Aortic Valve Replacement in High-Risk and Inoperable Patients with Severe Aortic Stenosis: One-Year Clinical Outcomes

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/14/sapien-3-transcatheter-aortic-valve-replacement-in-high-risk-and-inoperable-patients-with-severe-aortic-stenosis-one-year-clinical-outcomes/

 

121r   Entire Family of Impella Abiomed Impella® Therapy Left Side Heart Pumps: FDA Approved To Enable Heart Recovery

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/06/entire-family-of-impella-abiomed-impella-therapy-left-side-heart-pumps-fda-approved-to-enable-heart-recovery/

 

120r   DELETED identical to 121r

 

119r   FDA approved Absorb GT1 Bioresorbable Vascular Scaffold System (BVS), Everolimus releasing and Absorbed by the body in 3 years

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/07/05/fda-approved-absorb-gt1-bioresorbable-vascular-scaffold-system-bvs-everolimus-releasing-and-absorbed-by-the-body-in-3-years/

 

118r   TAVR with Sapien 3: combined all-cause death & disabling stroke rate was 8.4% and 16.6% for the surgery arm

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/04/05/tavr-with-sapien-3-combined-all-cause-death-disabling-stroke-rate-was-8-4-and-16-6-for-the-surgery-arm/

 

117r   Boston Scientific implant designed to occlude the heart’s left atrial appendage implicated with embolization – Device Sales in Europe halts

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/04/05/boston-scientific-implant-designed-to-occlude-the-hearts-left-atrial-appendage-implicated-with-embolization-device-sales-in-europe-halts/

 

116r   Issue with Delivery System Deployment Process: MitraClip Clip Recalled by Abbott Vascular

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/03/21/issue-with-delivery-system-deployment-process-mitraclip-clip-recalled-by-abbott-vascular/

 

115r   Prospects for First-in-man Implantation of Transcatheter Mitral Valve by Direct Flow Medical

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/03/03/prospects-for-first-in-man-implantation-of-transcatheter-mitral-valve-by-direct-flow-medical/

 

114r   Steps to minimise replacement of cardiac implantable electronic devices

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/02/04/steps-to-minimise-replacement-of-cardiac-implantable-electronic-devices/

 

113r Atrial Fibrillation Surgery Market worth $1.73 Billion by 2020

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/12/15/atrial-fibrillation-surgery-market-worth-1-73-billion-by-2020/

 

112r   Abbott’s Bioabsorbable Stent met its Primary Endpoint in a U.S. Clinical Trial, applications for FDA Approval follows

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/10/13/abbotts-bioabsorbable-stent-met-its-primary-endpoint-in-a-u-s-clinical-trial-applications-for-fda-approval-follows/

 

111r   Low-dose and High-resolution Cardiac Imaging with Revolution™ CT

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/08/23/low-dose-and-high-resolution-cardiac-imaging-with-revolution-ct/

 

110r   Hybrid Imaging 3D Model of a Human Heart by Cardiac Imaging Techniques: CT and Echocardiography

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/08/03/hybrid-imaging-3d-model-of-a-human-heart-by-cardiac-imaging-techniques-ct-and-echocardiography/

 

109r   Premature Ventricular Contraction percentage predicts new Systolic Dysfunction and clinically diagnosed CHF and overall Mortality

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/07/14/premature-ventricular-contraction-percentage-predicts-new-systolic-dysfunction-and-clinically-diagnosed-chf-and-overall-mortality/

 

108r   ‘Mammogram for the heart’ can predict heart attack by Dr. James Min, Director of the Dalio Institute of Cardiovascular Imaging at New York-Presbyterian Hospital and Weill Cornell Medical College

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/07/07/mammogram-for-the-heart-can-predict-heart-attack-by-dr-james-min-director-of-the-dalio-institute-of-cardiovascular-imaging-at-new-york-presbyterian-hospital-and-weill-cornell-medic/

 

107r   Abbott’s percutaneous MitraClip mitral valve repair device SUPERIOR to Pacemaker or Implantable Cardioverter Defibrillator (ICD) for reduction of Ventricular Tachyarrhythmia (VT) episodes

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/05/19/abbotts-percutaneous-mitraclip-mitral-valve-repair-device-superior-to-pacemaker-or-implantable-cardioverter-defibrillator-for-reduction-of-ventricular-tachyarrhythmia-vt-episodes/

 

106r   No evidence to change current transfusion practices for adults undergoing complex cardiac surgery: RECESS evaluated 1,098 cardiac surgery patients received red blood cell units stored for short or long periods

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/04/08/no-evidence-to-change-current-transfusion-practices-for-adults-undergoing-complex-cardiac-surgery-recess-evaluated-1098-cardiac-surgery-patients-received-red-blood-cell-units-stored-for-short-or-lon/

 

105r   3-D BioPrinting in use to create Cardiac Living Tissue: Print Your Heart Out

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/03/16/3-d-bioprinting-in-use-to-create-cardiac-living-tissue-print-your-heart-out/

 

104r   Fractional Flow Reserve vs. Angiography in Non-ST-segment Elevation Myocardial Infarction

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/02/24/fractional-flow-reserve-vs-angiography-in-non-st-segment-elevation-myocardial-infarction/

 

103r   Transradial PCI Bests Transfemoral PCI in UK Analysis, regardless of Patient’s Age

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/02/24/transradial-pci-bests-transfemoral-pci-in-uk-analysis-regardless-of-patients-age/

 

102r   DELETED, identical to 101r

 

101r   Protein Clue to Sudden Cardiac Death: Research @Oxford University

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/02/19/protein-clue-to-sudden-cardiac-death-research-oxford-university/

 

100r   Culprit-Lesion Over Multivessel PCI in STEMI Patients

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/11/07/culprit-lesion-over-multivessel-pci-in-stemi-patients/

 

99r     Convergent Procedure addresses the progressive nature of A-Fib

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/29/convergent-procedure-addresses-the-progressive-nature-of-a-fib/

 

98r     Paul Zoll, MD: Originator of Modern Electrocardiac Therapy – A Biography by Stafford Cohen, MD, BIDMC

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/16/paul-zoll-md-originator-of-modern-electrocardiac-therapy-a-biography-by-stafford-cohen-md-bidmc/

 

 

97r     Surgical Options for Left Atrial Appendage (LAA) Removal for A-Fib Patients without Indication for Anticoagulant Therapy

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/15/surgical-options-for-left-atrial-appendage-laa-removal-for-a-fib-patients-without-indication-for-anticoagulant-therapy/

 

96r     Intracranial Vascular Stenosis: Comparison of Clinical Trials: Percutaneous Transluminal Angioplasty and Stenting (PTAS) vs. Clot-inhibiting Drugs: Aspirin and Clopidogrel (dual antiplatelet therapy) – more Strokes if Stenting

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/15/intracranial-vascular-stenosis-comparison-of-clinical-trials-percutaneous-transluminal-angioplasty-and-stenting-ptas-vs-clot-inhibiting-drugs-aspirin-and-clopidogrel-dual-antiplatelet-therapy/

95r     New Era for PAD as FDA approval in the US of 1st Drug-coated Balloon (DCB) for PDA – CAD Indication for DCB will follow

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/15/new-era-for-pad-as-fda-approval-in-the-us-of-1st-drug-coated-balloon-dcb-for-pda-cad-indication-for-dcb-will-follow/

 

94r     Tethered–Liquid Perfluorocarbon surface (TLP): Biocoating Prevents Blood from Clotting on Implantables

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/10/13/tethered-liquid-perfluorocarbon-surface-tlp-biocoating-prevents-blood-from-clotting-on-implantables/

 

93r     Medtronic’s CoreValve System Sustains Positive Outcomes Through Two Years in Extreme Risk Patients

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/09/15/medtronics-corevalve-system-sustains-positive-outcomes-through-two-years-in-extreme-risk-patients/

 

92r     Thrombus Aspiration for Myocardial Infarction: What are the Outcomes One Year After

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/09/04/thrombus-aspiration-for-myocardial-infarction-what-are-the-outcomes-one-year-after/

 

91r     Fractional Flow Reserve–Guided PCI vs Drug Therapy for Stable Coronary Artery Disease

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/09/04/fractional-flow-reserve-guided-pci-vs-drug-therapy-for-stable-coronary-artery-disease/

90r     Capillaries: A Mapping Geometrical Method using Organ 3D Printing

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/08/22/capillaries-a-mapping-geometrical-method-using-organ-3d-printing/

 

89r     One year Post-Intervention Mortality Rate: TAVR and AVR – Aortic Valve Procedures 6.7% in AVR, 11.0% in AVR with CABG, 20.7 in Transvascular (TV-TAVT) and 28.0% in Transapical (TA-TAVR) Patients

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/08/04/one-year-post-intervention-mortality-rate-tavr-and-avr-aortic-valve-procedures-6-7-in-avr-11-0-in-avr-with-cabg-20-7-in-transvascular-tv-tavt-and-28-0-in-transapical-ta-tavr-patients/

 

88r     CEO of PolyNova: The Paradigm Shift in Heart Valve

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/06/16/ceo-of-polynova-the-paradigm-shift-in-heart-valve/

 

87r     An FDA advisory committee unanimously recommended approval of the Lutonix drug-coated balloon PTA catheter for the treatment of patients with femoropopliteal occlusive disease.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/06/16/an-fda-advisory-committee-unanimously-recommended-approval-of-the-lutonix-drug-coated-balloon-pta-catheter-for-the-treatment-of-patients-with-femoropopliteal-occlusive-disease/

 

86r     Patent Dispute over Heart Defect Repair Technology: Appeals court Upholds Gore win over St. Jude Medical – Helex septal occluder competes with the Amplatzer device made by AGA/St. Jude

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/06/12/patent-dispute-over-heart-defect-repair-technology-appeals-court-upholds-gore-win-over-st-jude-medical-helex-septal-occluder-competes-with-the-amplatzer-device-made-by-agast-jude/

85r     Chest Pain: Cardiac MRI provides the Picture of MI

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/06/03/chest-pain-cardiac-mri-provides-the-picture-of-mi/

 

84r     CardioMEMS sold to St. Jude Medical: Boston Millennia Partners announced that St. Jude Medical (NYSE: STJ) is acquiring the remaining 81 percent of CardioMEMS, Inc. it does not own for $375 million

Reporter: Aviva Lev-Ari,  PhD, RN

https://pharmaceuticalintelligence.com/2014/06/02/implantable-device-cardiomems-hf-system-for-heart-failure-patients-fda-approved/

 

83r     Cardiovascular Biology  – A Bibliography of Research @Technion

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/05/27/cardiovascular-biology-a-bibliography-of-research-technion/

 

82r     Asymptomatic Patients After Percutaneous Coronary Intervention: Low Yield of Stress Imaging – Population-Based Study

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/05/27/asymptomatic-patients-after-percutaneous-coronary-intervention-low-yield-of-stress-imaging-population-based-study/

 

 

81r     Transcatheter Mitral Valve (TMV) Procedures: Centers for Medicare & Medicaid Services (CMS) proposes to cover Transcatheter Mitral Valve Repair (TMVR)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/05/19/transcatheter-mitral-valve-tmv-procedures-centers-for-medicare-medicaid-services-cms-proposes-to-cover-transcatheter-mitral-valve-repair-tmvr/

 

80r     Minimally Invasive Valve Therapy Programs: Recommendations by SCAI, AATS, ACC, STS

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/05/19/minimally-invasive-valve-therapy-programs-recommendations-by-scai-aats-acc-sts/

 

79r     Among those 26 exams deemed low-value, 12 involve medical imaging, in tests that range from preoperative chest radiography to carotid artery screening for asymptomatic patients, imaging for back pain, and CT for headache and rhinosinusitis (JAMA Internal Medicine, May 12, 2014)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/05/13/among-26-exams-deemed-low-value-12-involve-medical-imaging-preoperative-chest-radiography-carotid-artery-screening-imaging-for-back-pain-and-ct-for-headache-and-rhinosinusitis-jama-im-may-12-2/

 

78r     FDA on Medical Devices: Part 1 – User Fee Act (MDUFA) III and Part 2 – Expedited Access Program for Medical Devices that Address Unmet Medical Needs

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/28/fda-on-medical-devices-part-1-user-fee-act-mdufa-iii-and-part-2-expedited-access-program-for-medical-devices-that-address-unmet-medical-needs/

 

77r     Settled Heart Valve Lawsuit: Medtronic to Pay Edwards: Edwards Lifesciences’ Sapien XT beat out Medtronic’s CoreValve

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/16/first-head-to-head-trial-finds-edwards-tavr-superior-to-medtronics/

 

76r     Replacement of the Mitral Valve: Using the Edwards’ Sapien Aortic Valve Device

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/10/replacement-of-the-mitral-valve-using-the-edwards-sapien-aortic-valve-device/

 

75r     Stem-Cell Therapy for Ischemic Heart Failure: Clinical Trial MSC Demonstrates Efficacy

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/04/08/stem-cell-therapy-for-ischemic-heart-failure-clinical-trial-msc-demonstrates-efficacy/

 

 

74r     ATVB (Arteriosclerosis, Thrombosis and Vascular Biology) 2014 Conference  5/1 – 5/3/2014, Sheraton Centre Toronto – Toronto, Ontario

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/03/05/atvb-arteriosclerosis-thrombosis-and-vascular-biology-2014-conference-51-532014-sheraton-centre-toronto-toronto-ontario/

 

73r     Endovascular Aortic Repair: A New Tool for Procedure Planning

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/25/endovascular-aortic-repair-a-new-tool-for-procedure-planning/

 

72r     Females and Non-Atherosclerotic Plaque: Spontaneous Coronary Artery Dissection – New Insights from Research and DNA Ongoing Study

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/12/female-and-non-atherosclerotic-plaque-spontaneous-coronary-artery-dissection-new-insights-from-research-and-dna-ongoing-study/

71r     Of the Cardiac-specific Deaths, Deaths from Heart Attack and Sudden Heart Rhythm Disturbances declined steeply, no decline in Deaths from Heart Failure in a 20,000 PCI patients Study @ Mayo Clinic

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/12/of-the-cardiac-specific-deaths-deaths-from-heart-attack-and-sudden-heart-rhythm-disturbances-declined-steeply-but-there-was-no-decline-in-deaths-from-heart-failure-in-a-20000-pci-patients-study/

 

70r     Cardiac Perfusion Exam, Rapid Heart Scanner, CT, MRI and PET imaging – Innovations in Radiology @ Beth Israel Deaconess Medical Center

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/12/cardiac-perfusion-exam-rapid-heart-scanner-ct-mri-and-pet-imaging-innovations-in-radiology-beth-israel-deaconess-medical-center/

 

69r     Maladaptive Vascular Remodeling found by four-dimensional (4D) flow MRI: Outflow Patterns, Wall Shear Stress, and Expression of Aortopathy are caused by Congenital bicuspid aortic valve (BAV) Cusp Fusion

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/12/maladaptive-vascular-remodeling-found-by-four-dimensional-4d-flow-mri-outflow-patterns-wall-shear-stress-and-expression-of-aortopathy-are-caused-by-congenital-bicuspid-aortic-valve-bav-cusp-fus/

 

68r     “Medicine Meets Virtual Reality” – NextMed-MMVR21 Conference 2/19 – 2/22/2014, Manhattan Beach Marriott, Manhattan Beach, CA

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/09/medicine-meets-virtual-reality-nextmed-mmvr21-conference-219-2222014-manhattan-beach-marriott-manhattan-beach-ca/

 

67r     Preserved vs Reduced Ejection Fraction: Available and Needed Therapies

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/02/03/preserved-vs-reduced-ejection-fraction-available-and-needed-therapies/

 

66r     Developments on the Frontier of Transcatheter Aortic Valve Replacement (TAVR) Devices

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/26/developments-on-the-frontier-of-transcatheter-aortic-valve-replacement-tavr-devices/

 

65r     On-Hours vs Off-Hours: Presentation to ER with Acute Myocardial Infarction – Lower Survival Rate if Off-Hours

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/01/22/on-hours-vs-off-hours-presentation-to-er-with-acute-myocardial-infarction-lower-survival-rate-if-off-hours/

 

64r     Elastin Arteriopathy: The Genetics of Supravalvular Aortic Stenosis

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/30/elastin-arteriopathy-the-genetics-of-supravalvular-aortic-stenosis/

 

63r     Abdominal Aortic Aneurysm: Matrix Metalloproteinase-9 Genotype as a Potential Genetic Marker

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/30/abdominal-aortic-aneurysm-matrix-metalloproteinase-9-genotype-as-a-potential-genetic-marker/

 

62r     Genetics of Aortic and Carotid Calcification: The Role of Serum Lipids

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/12/genetics-of-aortic-and-carotid-calcification-the-role-of-serum-lipids/

 

61r     St. Jude’s CEO is still betting on EnligHTN IV Study Renal Denervation System, despite Medtronic’s setback related to SYMPLICITY Phase IV

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/10/renal-denervation-enlightn-iv-study-called-off-and-potential-novel-indications-diastolic-heart-failure/

 

60r     Ischemic Stable CAD: Medical Therapy and PCI no difference in End Point: Meta-Analysis of Contemporary Randomized Clinical Trials

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/03/ischemic-stable-cad-ffr-in-5000-patients-medical-therapy-and-pci-no-difference-in-end-point-meta-analysis-of-contemporary-randomized-clinical-trials/

 

59r     Resistance Hypertension: Renal Artery Intervention using Stenting

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/02/pad-and-resistance-hypertension-renal-artery-intervention-using-stenting/

 

58r   For Accomplishments in Cardiology and Cardiovascular Diseases: 2015 The Arrigo Recordati International Prize for Scientific Research

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/11/22/for-accomplishments-in-cardiology-and-cardiovascular-diseases-the-arrigo-recordati-international-prize-for-scientific-research/

 

57r   Dalio Institute of Cardiovascular Imaging @ NewYork-Presbyterian Hospital and Weill Cornell Medical College

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/11/12/dalio-institute-of-cardiovascular-imaging-newyork-presbyterian-hospital-and-weill-cornell-medical-college/

 

56r   ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/11/05/accaha-guidelines-for-coronary-artery-bypass-graft-surgery/

 

55r     Risks for Patients’ and Physician’s Health in the Cath Lab

Reporter and Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/10/17/risks-for-patients-contrast-induced-nephropathy-and-physicians-health-radiation-exposure-in-the-cath-lab/

 

54r     Myocardial Infarction: The New Definition After Revascularization

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/10/15/myocardial-infarction-the-new-definition-after-revascularization/

53r     Echocardiogram Quantification: Quest for Reproducibility and Dependability

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/10/12/echocardiogram-quantification-quest-for-reproducibility-and-dependability/

52r     Myocardial Strain and Segmental Synchrony: Age and Gender in Speckle-tracking-based Echocardiographic Study

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/08/05/myocardial-strain-and-segmental-synchrony-age-and-gender-in-speckle-tracking-based-echocardiographic-study/

51r   Hybrid Cath Lab/OR Suite’s da Vinci Surgical Robot of Intuitive Surgical gets FDA Warning Letter on Robot Track Record

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/19/hybrid-cath-labor-suites-da-vinci-surgical-robot-of-intuitive-surgical-gets-fda-warning-letter-on-robot-track-record/

 

50r     Abdominal Aortic Aneurysms (AAA): Albert Einstein’s Operation by Dr. Nissen

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/06/11/abdominal-aortic-aneurysms-aaa-albert-einsteins-operation-by-dr-nissen/

49r     Transposon-mediated Gene Therapy improves Pulmonary Hemodynamics and attenuates Right Ventricular Hypertrophy: eNOS gene therapy reduces Pulmonary vascular remodeling and Arterial wall hyperplasia

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/31/transposon-mediated-gene-therapy-improves-pulmonary-hemodynamics-and-attenuates-right-ventricular-hypertrophy-enos-gene-therapy-reduces-pulmonary-vascular-remodeling-and-arterial-wall-hyperplasia/

 

48r   First-of-Its-Kind FDA Approval for ‘AUI’ Device with Endurant II AAA Stent Graft: Medtronic Expands in Endovascular Aortic Repair in the United States

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/30/first-of-its-kind-fda-approval-for-aui-device-with-endurant-ii-aaa-stent-graft-medtronic-expands-in-endovascular-aortic-repair-in-the-united-states/

 

47r     Bioabsorbable Drug Coating Scaffolds, Stents and Dual Antiplatelet Therapy

Reporter: Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2013/05/29/bioabsorbable-drug-coating-scaffolds-stents-and-dual-antiplatelet-therapy/

 

46r     Svelte Medical Systems’ Drug-Eluting Stent: 0% Clinically-Driven Events Through 12-Months in First-In-Man Study

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/28/svelte-medical-systems-drug-eluting-stent-0-clinically-driven-events-through-12-months-in-first-in-man-study/

 

45r   Echo vs Cardiac Magnetic Resonance Imaging (CMRI): CMRI may be a useful adjunct in Hypertrophic Cardiomyopathy (HCM) family screening in higher risk

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/20/echo-vs-cardiac-magnetic-resonance-imaging-cmri-cmri-may-be-a-useful-adjunct-in-hypertrophic-cardiomyopathy-hcm-family-screening-in-higher-risk/

 

44r   iElastance: Calculates Ventricular Elastance, Arterial Elastance and Ventricular-Arterial Coupling using Echocardiographic derived values in a single beat determination

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/19/ielastance-calculates-ventricular-elastance-arterial-elastance-and-ventricular-arterial-coupling-using-echocardiographic-derived-values-in-a-single-beat-determination/

 

43r   CT Angiography (CCTA) Reduced Medical Resource Utilization compared to Standard Care reported in JACC

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/16/ct-angiography-ccta-reduced-medical-resource-utilization-compared-to-standard-care-reported-in-jacc/

 

42r   Texas Heart Institute: 50 Years of Accomplishments

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/05/04/texas-heart-institute-50-years-of-accomplishments/

 

41r   Economic Toll of Heart Failure in the US: Forecasting the Impact of Heart Failure in the United States – A Policy Statement From the American Heart Association

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/04/25/economic-toll-of-heart-failure-in-the-us-forecasting-the-impact-of-heart-failure-in-the-united-states-a-policy-statement-from-the-american-heart-association/

 

40r   Sudden Cardiac Death invisible at Autopsy: Forensic Power of Postmortem MRI

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/04/18/sudden-cardiac-death-invisible-at-autopsy-forensic-power-of-postmortem-mri/

 

39r   Advanced CT Reconstruction: Plaque Estimation Algorithm for Fewer Errors and Semiautomation

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/04/18/advanced-ct-reconstruction-plaque-estimation-algorithm-for-fewer-errors-and-semiautomation/

 

38r     Dilated Cardiomyopathy: Decisions on implantable cardioverter-defibrillators (ICDs) using left ventricular ejection fraction (LVEF) and Midwall Fibrosis: Decisions on Replacement using late gadolinium enhancement cardiovascular MR (LGE-CMR)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/03/10/dilated-cardiomyopathy-decisions-on-implantable-cardioverter-defibrillators-icds-using-left-ventricular-ejection-fraction-lvef-and-midwall-fibrosis-decisions-on-replacement-using-late-gadolinium/

 

37r     Clinical Trials on transcatheter aortic valve replacement (TAVR) to be conducted by American College of Cardiology and the Society of Thoracic Surgeons

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/02/12/american-college-of-cardiologys-and-the-society-of-thoracic-surgeons-entrance-into-clinical-trials-is-noteworthy-read-more-two-medical-societies-jump-into-clinical-trial-effort-for-tavr-tech-f/

 

36r     Direct Flow Medical Wins European Clearance for Catheter Delivered Aortic Valve

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/01/29/direct-flow-medical-wins-european-clearance-for-catheter-delivered-aortic-valve/

 

35r     DELETED, identical to 15c

 

34r     PCI Outcomes, Increased Ischemic Risk associated with Elevated Plasma Fibrinogen not Platelet Reactivity

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/01/10/pci-outcomes-increased-ischemic-risk-associated-with-elevated-plasma-fibrinogen-not-platelet-reactivity/

 

33r     Cardiac Surgery Theatre in China vs. in the US: Cardiac Repair Procedures, Medical Devices in Use, Technology in Hospitals, Surgeons’ Training and Cardiac Disease Severity

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/01/08/cardiac-surgery-theatre-in-china-vs-in-the-us-cardiac-repair-procedures-medical-devices-in-use-technology-in-hospitals-surgeons-training-and-cardiac-disease-severity/

 

32r     DELETED, identical to 14c

31r     DELETED, identical to 12c

 

30r     Heart Renewal by pre-existing Cardiomyocytes: Source of New Heart Cell Growth Discovered

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/12/23/heart-renewal-by-pre-existing-cardiomyocytes-source-of-new-heart-cell-growth-discovered/

 

29r     Ablation Devices Market to 2016 – Global Market Forecast and Trends Analysis by Technology, Devices & Applications

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/12/23/ablation-devices-market-to-2016-global-market-forecast-and-trends-analysis-by-technology-devices-applications/

 

28r     Abdominal Aortic Aneurysm: Endovascular repair and open repair resulted in similar long-term survival

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/12/03/abdominal-aortic-aneurysm-endovascular-repair-and-open-repair-resulted-in-similar-long-term-survival/

 

27r     Renal Denervation Technology of Vessix Vascular, Inc. been acquired by Boston Scientific Corporation (BSX) to pay up to $425 Million

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/11/08/renal-denervation-technology-of-vessix-vascular-inc-been-acquired-by-boston-scientific-corporation-bsx-to-pay-up-to-425-million/

 

26r     DELETED, identical to 11c

 

25r     To Stent or Not? A Critical Decision

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/10/23/to-stent-or-not-a-critical-decision/

 

24r     FDA Approval for Under-Skin Defibrillator goes to Boston Scientific Corporation

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/10/01/fda-approval-for-under-skin-defibrillator-goes-to-boston-scientific-corporation/

 

23r     Absorb™ Bioresorbable Vascular Scaffold: An International Launch by Abbott Laboratories

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/09/29/absorb-bioresorbable-vascular-scaffold-an-international-launch-by-abbott-laboratories/

 

22r     Carotid Stenting: Vascular surgeons have pointed to more minor strokes in the stenting group and cardiologists to more myocardial infarctions in the CEA cohort.

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/09/21/carotid-stenting-vascular-surgeons-have-pointed-to-more-minor-strokes-in-the-stenting-group-and-cardiologists-to-more-myocardial-infarctions-in-the-cea-cohort/

 

21r     FDA: Strengthening Our National System for Medical Device Post-market Surveillance

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/09/07/fda-strengthening-our-national-system-for-medical-device-post-market-surveillance/

 

20r     Transcatheter Aortic-Valve Replacement for Inoperable Severe Aortic Stenosis

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/09/03/transcatheter-aortic-valve-replacement-for-inoperable-severe-aortic-stenosis/

 

19r     Evidence for Overturning the Guidelines in Cardiogenic Shock

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/09/03/evidence-for-overturning-the-guidelines-in-cardiogenic-shock/

 

18r     Imbalance of Autonomic Tone: The Promise of Intravascular Stimulation of Autonomics

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/09/02/imbalance-of-autonomic-tone-the-promise-of-intravascular-stimulation-of-autonomics/

17r     Intravascular Stimulation of Autonomics: A Letter from Dr. Michael Scherlag

Letter received by Aviva Lev-Ari, PhD, RN on September 1, 2012

https://pharmaceuticalintelligence.com/2012/09/02/intravascular-stimulation-of-autonomics-a-letter-from-dr-michael-scherlag/

 

16r     New Definition of MI Unveiled, Fractional Flow Reserve (FFR)CT for Tagging Ischemia

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/27/new-definition-of-mi-unveiled-fractional-flow-reserve-ffrct-for-tagging-ischemia/

 

15r     DELETED, identical to 8c

 

14r     Expected New Trends in Cardiology and Cardiovascular Medical Devices

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/17/expected-new-trends-in-cardiology-and-cardiovascular-medical-devices/

 

13r     Patient Access to Medical Devices — A Comparison of U.S. and European Review Processes

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/09/patient-access-to-medical-devices-a-comparison-of-u-s-and-european-review-processes/

 

12r   Coronary CT Angiography versus Standard Evaluation in Acute Chest Pain

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/09/coronary-ct-angiography-versus-standard-evaluation-in-acute-chest-pain/

 

11r     Updated Transcatheter Aortic Valve Implantation (TAVI): risk for stroke and suitability for surgery

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/07/transcatheter-aortic-valve-implantation-tavi-risky-and-costly-2/

 

10r     Transcatheter Aortic Valve Implantation (TAVI): FDA approves expanded indication for two transcatheter heart valves for patients at intermediate risk for death or complications associated with open-heart surgery

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/08/02/transcatheter-aortic-valve-implantation-tavi-risky-and-costly/

 

9r      Early Surgery May Benefit Some With Heart Infection

Reporter: Aviva Lev-Ari, RN

https://pharmaceuticalintelligence.com/2012/08/02/early-surgery-may-benefit-some-with-heart-infection/

 

8r      Gaps, Tensions, and Conflicts in the FDA Approval Process: Implications for Clinical Practice

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/07/31/gaps-tensions-and-conflicts-in-the-fda-approval-process-implications-for-clinical-practice/

 

7r      Heart Remodeling by Design – Implantable Synchronized Cardiac Assist Device: Abiomed’s Symphony

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/07/23/heart-remodeling-by-design-implantable-synchronized-cardiac-assist-device-abiomeds-symphony/

 

6r      Percutaneous Endocardial Ablation of Scar-Related Ventricular Tachycardia

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/07/18/percutaneous-endocardial-ablation-of-scar-related-ventricular-tachycardia/

 

5r      Implantable Synchronized Cardiac Assist Device Designed for Heart Remodeling: Abiomed’s Symphony

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/07/11/implantable-synchronized-cardiac-assist-device-designed-for-heart-remodeling-abiomeds-symphony/

 

4r      Percutaneous Transluminal Angioplasty and Stenting (PTAS) – Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/07/05/percutaneous-transluminal-angioplasty-and-stenting-ptas-stenting-versus-aggressive-medical-therapy-for-intracranial-arterial-stenosis/

 

3r      The Centers for Medicare & Medicaid Services (CMS) covers transcatheter aortic valve replacement (TAVR) under Coverage with Evidence Development (CED)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/06/19/the-centers-for-medicare-medicaid-services-cms-covers-transcatheter-aortic-valve-replacement-tavr-under-coverage-with-evidence-development-ced/

 

2r     Investigational Devices: Edwards Sapien Transcatheter Aortic Heart Valve Replacement Transfemoral Deployment

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/06/10/investigational-devices-edwards-sapien-transcatheter-aortic-heart-valve-replacement-transfemoral-deployment/

 

1r     Investigational Devices: Edwards Sapien Transcatheter Aortic Valve Transapical Deployment

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/06/04/investigational-devices-edwards-sapien-transcatheter-heart-valve/

 

 

 

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UPDATED on 1/14/2016

Renal Denervation: This Is Why Device Trials Need Sham Controls

Subtle biases are unavoidable in open-label studies, study suggests

http://www.medpagetoday.com/Cardiology/CardioBrief/55634

 

Potential Explanation to Lack of Efficacy Results of SYMPLICITY HTN-3 Study that Contradict Most Published Data on Renal Denervation

UPDATED on 5/27/2014

PARIS, FRANCE – No one could accuse EuroPCR 2014 of giving up on renal denervation following the negative results of the only large, randomized, sham-controlled trial of this cutting-edge technology.

In its plumpest program to date, this year’s EuroPCR meeting once again had a dedicated track focused on catheter-based interventions for hypertension (and heart failure), featuring more than 60 renal-denervation sessions. These included live cases, new data, how-to sessions, plus additional poster and oral abstract sessions. The two frontrunner companies in this space, Medtronic and St Jude Medical, even had conference rooms named for them, hosting training and information sessions for the duration of the meeting, funded by unrestricted grants.

And the sessions were packed. Without question, the sexiest technology of last year’s conference remained the hottest topic of 2014, with everyone seeking answers to the question: Why wasSYMPLICITY HTN-3 negative when so many preclinical studies, phase 1 and 2 studies, and mushrooming registry data point to beneficial effects of sympathetic modulation via denervation of the renal artery?

Dr David Kandzari (Piedmont Heart Institute, Atlanta, GA), one of the steering committee members for SYMPLICITY HTN-3, acknowledged the unabated enthusiasm in Paris.

“At first glance I was surprised to see there was so much [renal denervation] in the 2014 program,” he admitted. But only by examining the randomized control trial data and other studies addressing procedural techniques and patient appropriateness will researchers learn more about why the SYMPLICITY HTN-3 results were so strikingly at odds with smaller, nonrandomized studies, he said. “So I think the organizers intentionally directed the program toward focusing more on the science of renal denervation and what the next steps are.”

More Insights From SYMPLICITY HTN-3

Kandzari presented a new analysis from SYMPLICITY HTN-3 focused on three variables that may have influenced efficacy in the trial: drug changes/drug adherence, patient population, and procedure-related factors.

For the first, he noted, patients in the study were required to be “stable” on their antihypertensive drug regimen for at least six weeks prior to trial enrollment. Yet during the trial, roughly two out of five participants required medication changes during the study, including 69% that were deemed “medically necessary.”

“This challenges the notion that patients were on their maximum tolerated drugs and that they can be maintained on stable drug regimens,” Kandzari said. Not only that, “it also highlights how different these trials are from clinical practice.” For example, in SYMPLICITY HTN-3, patients in both the intervention and sham arms had, on average, eight points of contact where blood pressure and medication were being closely scrutinized, he said—a factor that would have helped boost BP control in both arms.

Another important factor to emerge in these exploratory analyses was race, he said. Just under one-third of patients enrolled in SYMPLICTY HTN-3, by design, were African American (this was, after all, the pivotal trial designed in consultation with the FDA required for regulatory approval in the US). And, when non–African Americans were analyzed separately, renal-denervation–treated patients experienced drops in office systolic BP that were significantly greater than the sham-control group, something not seen in African American patients.

This finding was part of a larger discussion at EuroPCR circling around the fact that the pivotal phase 3 trial, which enrolled 535 patients in the US, was designed according to findings from SYMPLICITY  1and 2 . Those earlier trials were conducted in non-US patients whose distribution of risk factors and ethnic makeup is very different.

“I’ve been doing renal denervation since 2009, and I have never once seen an African American patient, or a black patient for that matter,” Dr Thomas Zeller (Universitäts-Herzzentrum Freiburg, Bad Krozingen, Germany) said in a Friday session.

Dr. Kulwant Raj|  Internal Medicine37 minutes ago

Amazing new technology for the benefit of treating surgeons, hospitals and for hardware manufacturing/ supplying companies. What is in it for the patient? Is there EVER meant to be anything for the patient? We, the “service providers” are the Gods for whom the patient sacrifices not only all his money but his life too. Hey, did I hear someone say “Gods or demons?” You are out of synch with the times my dear! These days Gods and demons are synonymous, as are “Healthcare” and “Sick-Care”

 

SOURCE

 

 

 UPDATED on 4/22/2014

Hopes Dashed by SYMPLICITY HTN-3

WATCH VIDEO

http://www.medscape.com/viewarticle/823774?nlid=55503_2562&src=wnl_edit_medp_card&uac=93761AJ&spon=2#1

Hi. This is Seth Bilazarian from theheart.org on Medscape, reporting from the American College of Cardiology (ACC) meeting in Washington, DC.

I want to make a few comments on the SYMPLICITY HTN-3 trial.[1,2] Briefly, SYMPLICITY is the name of a series of trials sponsored by the Medtronic company that are evaluating the efficacy and safety of therapy with a renal denervation catheter for a variety of problems, but most importantly for hypertension.

In the area of disclosure, I was a SYMPLICITY investigator. I was not compensated for my work and I am not an employee of the hospital where I performed the procedures, but for purposes of disclosure, I was quite an enthusiast about the potential for this technology, and I was quite disappointed [with the results].

The SYMPLICITY HTN-3 trial had 535 patients, with 2:1 randomization. Patients were blinded to the therapy. They were brought into the catheterization laboratory wearing blindfolds, and headphones with music playing. After having a sheath placed in the groin and an angiogram of the renal artery, patients were randomized to undergo either an actual procedure or a sham procedure in which we would pretend to do something, and then they would leave the room.

Patients were blinded for 6 months afterward, and at the end of 6 months they were unblinded, so the blinding was very effective during the study. The 2:1 randomization was designed to show effective blood pressure lowering. Previous studies in which there wasn’t randomization or sham procedures with blinding showed as much as a 30-mm Hg blood pressure reduction over the course of 12 years, which persisted for many years.

That was the great hope going into this, but the results of the SYMPLICITY HTN-3 trial[1] presented at the ACC Scientific Session showed only about a 2.4-mm Hg greater reduction in office blood pressure at 6 months compared with the sham arm. There was actually a 14-mm Hg blood pressure reduction from baseline to 6 months in the treatment group, but there was also a 12-mm Hg reduction in the sham arm.

These patients, just to be clear, had very significant hypertension. To be in the trial, patients had to have a systolic blood pressure higher than 160 mm Hg and had to be on 3 drugs, all at maximal doses, and 1 of them had to be a diuretic. They could be on more drugs, and many of my patients were on more than 3 drugs. These patients went through this procedure, and the average blood pressure at the end of the trial for all 535 patients in both arms was still higher than 160 mm Hg, so this is a very serious group of patients who are not yet well treated.

Renal Denervation in the Real World

Today, a second trial in the SYMPLICITY family of studies was presented: the Global SYMPLICITY Registry (GSR).[3] This included the first 1000 patients treated commercially outside of the United States where this device is available.

The GSR showed that for a variety of patients, renal denervation lowered blood pressure, as previously shown in nonrandomized trials. In the subset of patients with systolic blood pressures of 160 mm Hg (matching up with what was seen in the SYMPLICITY HTN-3 trial), they showed a 20-mm Hg blood pressure reduction in the registry vs 14 mm Hg in the randomized trial, which is not very different.

Why was this the case? There has been a lot of discussion about it, and many potential explanations have been offered. One is that patients seem to have a very robust decline in their blood pressure in the medical treatment group that is stable and not expected to change. This is a concern for me.

As an investigator, what actually happened to patients’ drug therapy over time is not reported, either in the manuscript or anywhere else that I can find. What happens from a practical standpoint for a community-based physician is that patients walking around with blood pressures of 170-180 mm Hg go to emergency rooms or see their primary care physicians, and their blood pressure medications are altered. That was said not to be the case, but it is not specifically reported, so was there a change?

For anyone who participates in clinical trials, the oversight of a clinical trial is such that the patients are very rigorously followed, and there is pill-counting and recommendations for strict compliance, all of which is very different from what happens with “optimal medical therapy” in real-world practice.

Furthermore, this was a renal denervation strategy with a particular device, so it could be that this particular device isn’t the best device for renal denervation.

A third practical question, which is unanswered, is whether we really achieved renal denervation. The animal and preclinical trials looked at how much energy was needed to create an injury that went from the renal artery lumen down to the renal nerves. Perhaps in this middle-aged group of patients with hypertension on a western diet, there is greater thickening of the renal vessel, which could actually cause problems in delivering the energy required to achieve effective renal denervation.

Uncontrolled Hypertension in the Balance

Those are some of the questions that have come up that may explain why we didn’t see the robust results we were hoping for. Although I don’t have to make the decision, if I were a senior executive at one of the companies involved, a decision to go forward would be very difficult in terms of investing corporate resources on the development of these devices.

As a clinician, however, we really need help, because there are 535 patients still walking around with systolic blood pressures higher than 160 mm Hg despite this therapy and being on 3 maximal-dose drugs. Many patients in our practices aren’t optimally controlled. Many patients can’t take optimal medical therapy because of adherence or intolerance of therapy issues, so a variety of patients would greatly benefit from another strategy.

There is no question that there will be great enthusiasm for a therapy that could deliver the promise of a 30-mm Hg blood pressure reduction that was safe, effective, and durable. Another question is whether it is even correct to compare such a strategy with optimal medical therapy. Wouldn’t it be valuable to show that this technique alone is equally good in terms of long-term clinical results compared with multiple drug therapy?

These questions are yet to be answered, and we may never get the answers because industry may choose not to invest in these programs going forward. Other questions, such as the potential for renal denervation as a therapy for such problems as left ventricular hypertrophy, congestive heart failure, or obstructive sleep apnea, have gone by the wayside at this point.

From my standpoint, I would enthusiastically want to participate as an investigator and talk to my patients, candidly disclosing the results of this trial, about enrolling in a new trial of renal denervation. There is great need for therapies that are effective for this patient population. The risks associated with blood pressure in this range (over 160 mm Hg) are well known, and strategies to treat these patients are greatly needed.

So, there are a lot of unanswered questions, as well as a great disappointment, both for the clinical practicing community as well as for patients. There has been a deflation in the device community about this innovation that has at least stalled progress and presents a hurdle going forward.

That is my quick update on renal denervation. Until next time, thank you, from the ACC in Washington.

SOURCE

 

 

Reporter & Curator: Aviva Lev-Ari, PhD, RN

On March 29, 2014 in NEJM Franz H. Messerli, M.D., and Sripal Bangalore, M.D. wrote:

  • the most likely explanation for the findings of the SYMPLICITY HTN-3 study is the inclusion of a sham-control group.
  • In clinical trials testing interventional procedures and medical devices, sham procedures are seminal, analogous to the use of a placebo in pharmaceutical trials. However, for ethical reasons sham procedures are frowned upon9;
  • neither the SYMPLICITY HTN-1 study nor the HTN-2 study had a sham-control cohort.
  • For this reason, placebo effects may well explain all or most of the blood-pressure differences noted in the first two trials.
  • Lack of efficacy could also be caused by incomplete or ineffective denervation.
  • No reliable markers of renal denervation are available, and questions remain as to
  • what exactly the procedure accomplishes. Nevertheless,
  • the ablation catheter used in the SYMPLICITY HTN-3 study was no different from that used in the SYMPLICITY HTN-1 and HTN-2 studies.
  • A decrease in systolic blood pressure was observed in both the renal-denervation group and the control group, a finding that is in marked contrast to the findings in previous trials.
  • At 6 months, the decrease in office systolic blood pressure from baseline in the renal-denervation group in the SYMPLICITY HTN-3 study was about half that observed in the corresponding group in the SYMPLICITY HTN-2 study, despite the fact that baseline blood pressures were similar in the two studies. This is puzzling, because
  • the degree of reduction in blood pressure is related to pretreatment blood-pressure levels (unpublished data). In addition,
  • there was a larger decrease in blood pressure in the control group of the SYMPLICITY HTN-3 study, as compared with the meager decrease in the SYMPLICITY HTN-2 study.
  • Is it conceivable that greater exposure to spironolactone in the SYMPLICITY HTN-3 study facilitated this decrease (and possibly contributed to a neutral outcome)?

Could we have predicted the outcome of the SYMPLICITY HTN-3 study?

  • The standard deviations of the change in office systolic blood pressure from baseline in both study groups in both trials were remarkably similar, indicating a wide variation in response.
  • In fact, in the SYMPLICITY HTN-2 study, the change in blood pressure from baseline in 95% of patients was between −78 mm Hg and 14 mm Hg in the renal-denervation group and
  • between −43 mm Hg and 41 mm Hg in the control group.
  • The mean blood-pressure reduction in the SYMPLICITY HTN-3 study is well within this range for both study groups.

Conclusion #1

The wide variability in response to renal denervation begs the question of whether this procedure could be more efficacious in selected patients with increased sympathetic drive only, such as those with heart failure. Regardless of this conjecture, the SYMPLICITY HTN-3 study certainly has raised the bar.

  • To be enrolled in a study, patients need to fulfill predefined blood-pressure criteria on a particular day. Patients whose blood pressure is above their usual average will preferentially be enrolled. Thus,
  • subsequent blood-pressure measurements are prone to be lower regardless of whether there was an intervention.
  • This phenomenon, although unlikely to fully explain the differences in blood-pressure decrease among various studies, occurs only when inclusion criteria require a certain blood-pressure level.
  • It should not be confused with regression to the mean or a placebo effect, both of which could also have contributed to the uneven blood-pressure response in the SYMPLICITY trials. Indeed,

Conclusion #2

  • regression to the mean was probably responsible for a less extreme decrease in office systolic blood pressure in the renal-denervation group and a more impressive decrease in the control group, as compared with changes observed in prior studies.

Conclusion #3

  • Exuberance about renal denervation has been widespread, as is illustrated by these statements: “The potential of renal denervation is enormous” and it “may be used not only to treat hypertension, but also . . . diseases that are characterized by high sympathetic activity such as diabetes and hyperinsulinemia, heart failure, arrhythmias, and chronic kidney disease.”10
  • These words, thoroughly referenced, tout the benefits of renal denervation in these metabolic or cardiovascular disorders.
  • In contrast, the conclusions of the SYMPLICITY HTN-3 study by one of the same authors now 6 months later soberingly state that “a significant effect on systolic blood pressure was not observed.

Conclusion #4

  • Further evaluation in rigorously designed clinical trials will be necessary . . . to confirm previously reported benefits of renal denervation in patients with resistant hypertension.
  • ” Should this statement indeed hold true, we will have to come to grips with two facts: the SYMPLICITY studies merely document the natural history of resistant hypertension in clinical trials, and the time has come to turn the page on renal denervation for hypertension but by all means, let’s not close the book.

 

SOURCE

Renal Denervation for Resistant Hypertension?  

Franz H. Messerli, M.D., and Sripal Bangalore, M.D.

March 29, 2014DOI: 10.1056/NEJMe1402388

 

RESULTS of Clinical Trials:

Trials such as the SYMPLICITY HTN-14 and HTN-25 studies

  • showed impressive decreases in blood pressure, seemingly attesting to the efficacy and safety of renal denervation.
  • Three-year follow-up of the SYMPLICITY HTN-1 study revealed a decrease in blood pressure of 32/14 mm Hg.6
  • These unprecedented results seemed to surpass what was achievable with drug therapy and continued to fan the flames of renal denervation.

The SYMPLICITY HTN-3 study, a blinded, sham-controlled study now reported in the Journal by Bhatt et al.,7 brings the renal-denervation train to a grinding halt.

  • After 6 months, office systolic blood pressure decreased from baseline to a similar extent in the renal-denervation and sham-procedure groups (P<0.001 for both comparisons of the change from baseline);
  • the difference in the change in blood pressure between the two groups was a paltry −2.39 mm Hg (Table 1TABLE 1: Selected Findings of the SYMPLICITY HTN-2 and HTN-3 Studies.

In addition, a prespecified difference in 24-hour ambulatory systolic pressure of only 2 mm Hg was not met.

  • Thus, in the SYMPLICITY HTN-3 study, renal denervation had no significant effect on office or 24-hour ambulatory systolic blood pressure,
  • findings that contradict most published data on renal denervation, although a recent trial even suggested inferiority of renal denervation, as compared with adjusted drug treatment.8

http://www.nejm.org/doi/full/10.1056/NEJMe1402388#t=article

 

For additional information of the subject and analysis of the Market impact, go to 

Market Impact on Global Suppliers of Renal Denervation Systems by Pivotal US Trial: Metronics’ Symplicity Renal Denervation System FAILURE at Efficacy Endpoint

https://pharmaceuticalintelligence.com/2014/01/09/market-impact-on-global-suppliers-of-renal-denervation-systems-by-pivotal-us-trial-metronics-symplicity-renal-denervation-system-failure-at-efficacy-endpoint/

Renal Denervation Safe in Real-World Setting: Preliminary results from the Global SYMPLICITY registry, 5/2013

UPDATED 5/29/2014

https://pharmaceuticalintelligence.com/2013/01/14/positive-effects-of-renal-denervation-ablation-for-hypertension-in-controlled-randomized-symplicity-htn-2-trial/

 

REFERENCES
1 Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD. Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med 2009;361:932-934
Free Full Text | Web of Science | Medline

2 Messerli FH, Bangalore S. Treatment-resistant hypertension: another Cinderella story. Eur Heart J 2013;34:1175-1177
CrossRef | Web of Science | Medline

3 Radio waves to kidneys lower persistent high blood pressure. Press release of the American Heart Association, Dallas, December 17, 2012.

4 Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 2009;373:1275-1281
CrossRef | Web of Science | Medline

5 Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (the SYMPLICITY HTN-2 Trial): a randomised controlled trial. Lancet 2010;376:1903-1909
CrossRef | Web of Science | Medline

6 Krum H, Schlaich MP, Sobotka PA, et al. Percutaneous renal denervation in patients with treatment-resistant hypertension: final 3-year report of the SYMPLICITY HTN-1 study. Lancet 2014;383:622-629[Erratum, Lancet 2014;383:602.]
CrossRef | Web of Science | Medline

7 Bhatt DL, Kandzari DE, O’Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. DOI: 10.1056/NEJMoa1402670.

8 Elmula F, Hoffmann P, Larstorp AC, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension 2014 March 3 (Epub ahead of print).

9 Gottlieb S. The FDA wants you for sham surgery: there are better ways to test medical devices than by having patients be placebos who get fake operations. Wall Street Journal. February 18, 2014.

10 Mahfoud F, Bhatt DL. Catheter-based renal denervation: the black box procedure. JACC Cardiovasc Interv 2013;6:1092-1094
CrossRef

 

Other Related Articles Published on this Open access Scientific Journal, include the following:

Renal Sympathetic Denervation: Updates on the State of Medicine

Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/12/31/renal-sympathetic-denervation-updates-on-the-state-of-medicine/

Imbalance of Autonomic Tone: The Promise of Intravascular Stimulation of Autonomics

Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/09/02/imbalance-of-autonomic-tone-the-promise-of-intravascular-stimulation-of-autonomics/

Treatment of Refractory Hypertension via Percutaneous Renal Denervation

Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/06/13/treatment-of-refractory-hypertension-via-percutaneous-renal-denervation/

Read Full Post »


Market Impact on Global Suppliers of Renal Denervation Systems by Pivotal US Trial: Metronics’ Symplicity Renal Denervation System FAILURE at Efficacy Endpoint

Curator and Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 12/8/2015

New Approaches to Denervation Therapy — TCT 2015

http://www.dicardiology.com/videos/new-approaches-denervation-therapy-%E2%80%94-tct-2015/4592515437001

UPDATED on 2/22/2014

Cordis Corporation Receives CE Mark for RENLANE Renal Denervation System to Treat Resistant Hypertension

February 21, 2014 09:59 AM Eastern Standard Time

FREMONT, Calif.–(BUSINESS WIRE)–Cordis Corporation announced today that it has received European CE Mark for its RENLANE™ Renal Denervation System for the treatment of patients with resistant hypertension and has completed the first successful cases in Europe. The RENLANE™ System consists of a unique, helical shaped, irrigated, multi-electrode ablation catheter with a multi-channel radiofrequency (RF) ablation system.

“The design of the catheter also makes handling the device very easy.”

The first successful cases were performed by Hannes Reuter, M.D., at the University of Cologne Hospital in Germany. The treated patients were diagnosed with resistant hypertension and had systolic blood pressures greater than or equal to 160 mm Hg, despite undergoing traditional drug therapy with three or more anti-hypertensive medications. All procedures were performed successfully and patients were discharged after one day.

“The novel technological design of the RENLANE™ Renal Denervation Catheter with its configuration of five electrodes and irrigated technology, allows for shorter procedure duration, sparing of contrasting dye and likely more protection of the endothelium,” said Hannes Reuter, M.D., University of Cologne, Germany. “The design of the catheter also makes handling the device very easy.”

Nearly one billion people worldwide live with hypertension, or high blood pressure, and the World Health Organization estimates that it is the cause of one in every eight deaths, making hypertension the third leading cause of death worldwide.1 Chronic high blood pressure is a serious condition that can lead to increased risk of stroke, kidney disease, heart attack and heart failure. It is estimated that between 15 and 30 percent of treated hypertensive patients are resistant to traditional drug therapy, defined as failure to respond to three or more drugs.2 Uncontrolled hypertension is a major risk factor for mortality so alternative therapies such as renal denervation for treatment-resistant patients have emerged to help address this patient population. Additionally, the economic burden of the condition is significant. The International Society of Hypertension estimates the annual cost of healthcare expenditure directly related to elevated blood pressure to be almost $500 billion.3

“Chronic hypertension poses a significant health risk to patients and also places a huge burden on global health care systems,” said Celine Martin, Worldwide President, Cordis Corporation. “We are pleased to make our RENLANE™ Renal Denervation System available to European clinicians in need of solutions for patients who do not respond to traditional drug therapy. And we are looking forward to gaining more experience with this therapy and making it available to more patients in need of treatment around the world.”4

The RENLANE™ Renal Denervation Catheter features five irrigated electrodes located at the tip of the ablation catheter and is used in conjunction with the RENLANE™ Multi-Channel RF generator for energy delivery. It is indicated for use in adult patients (> 18 years) with drug resistant hypertension to denervate the renal arteries to reduce blood pressure.

The RENLANE™ Renal Denervation System is another addition to Cordis’ broad and growing portfolio of minimally invasive therapies for patients that suffer from cardiovascular disease worldwide. The company is committed to working with leading clinicians to address the significant and growing burden of cardiovascular disease with innovative endovascular solutions that address the clinical needs of our customers and the patients they treat.

About Renal Denervation

Renal denervation is a minimally invasive, catheter-based treatment for resistant hypertension, or high blood pressure that does not respond to traditional drug therapy (three or more drugs). During the procedure, a thin flexible tube called a catheter is inserted through a small incision in the groin and it is then weaved up to the renal arteries through a blood vessel in the leg. Once the catheter tip is placed inside of a renal artery, radiofrequency (RF) energy is delivered to reduce hyperactivity of the surrounding nerves, which causes the kidneys to produce less of the hormones that are responsible for chronic high blood pressure. Both of the renal arteries are treated during the procedure.

About Cordis Corporation

Cordis Corporation, part of the Johnson & Johnson Family of Companies, is a worldwide leader in the development and manufacture of interventional vascular technology. Through the company’s innovation, research and development, Cordis partners with clinicians to treat millions of patients who suffer from cardiovascular disease worldwide. More information about Cordis Corporation can be found at http://www.cordis.com.
1.     The World Health Report 2012. World Health Organization; 2012:58
2.   Pimenta E, Calhoun DA. Resistant hypertension: incidence, prevalence, and prognosis. Circulation. 2012;125:1594-6.
3.   Lawes CM, Vander Hoorn S, Rodgers A; International Society of Hypertension. Global burden of blood-pressure related disease, 2001. Lancet. 2008;371:1513-1518.
4.   The RENLANE™ Renal Denervation System is not available for sale or use in the United States.

Read more: Cordis Corporation Receives CE Mark for RENLANE Renal Denervation System to Treat Resistant Hypertension – FierceMedicalDevices http://www.fiercemedicaldevices.com/press-releases/cordis-corporation-receives-ce-mark-renlane-renal-denervation-system-treat-0#ixzz2u64hQ548

SOURCE

From: FierceMedicalDevices <editors@fiercemedicaldevices.com>
Reply-To: <editors@fiercemedicaldevices.com>
Date: Fri, 21 Feb 2014 18:00:51 +0000 (GMT)
To: <avivalev-ari@alum.berkeley.edu>
Subject: | 02.21.14 | J&J’s Cordis scores renal denervation CE mark

 

UPDATED on 2/7/2014

Renal Denervation Before the Fall. Guest: Deepak Bhatt

Samuel Z. Goldhaber, MD, Deepak L. Bhatt, MD, MPH

January 24, 2014

EDITORS’ RECOMMENDATIONS

VIEW VIDEO

http://www.medscape.com/viewarticle/819665?nlid=47583_1984&src=wnl_edit_medn_card&uac=93761AJ&spon=2

UPDATED on 1/23/2014

Covidien bails on renal denervation

January 21, 2014 by Brad Perriello

Covidien said it’s pulling the plug on its OneShot renal denervation device, citing the slow development of the hypertension market.

Covidien bails on renal denervation

Covidien (NYSE:COV) said it plans to wind down its OneShot renal denervation program, largely due to “slower than expected development of the renal denervation market,” meaning the end for a U.S. clinical trial of the high blood pressure device.

“This decision resulted from Covidien’s regular review of strategic programs and growth potential for various aspects of its product portfolio,” according to a press release. “Over the next several weeks, the company will collaborate with physicians and the renal denervation community to ensure existing OneShot patients are informed and the currently enrolling clinical trials are transitioned appropriately.”

The OneShot device already had CE Mark approval in the European Union for treating resistant hypertension in April 2012, when Covidien paid $60 million in cash and put another $170 million on the table in milestones.

The move means the closure of Covidien’s Rapid II trial, which was projected to enroll 253 patients, comparing treatment with the OneShot device with standard drug treatment in patients with resistant hypertension, according to the release.

SOURCE

http://www.massdevice.com/news/covidien-bails-renal-denervation

UPDATED on 1/21/2014

It’s not that Symple! The Rise (and Fall?) of Renal Denervation by Amy Siegel, http://s2nhealth.com

http://s2nhealth.com/2014/01/17/the-rise-and-fall-of-renal-denervation.html#.Ut7Mmxw8JaE

Clinical Trial Results will impact negatively the following players in the Global Supplier Ecosystem for Renal Denervation Systems:

US Campbell, CA Kona Medical is attempting to address these limitations. The system delivers energy from outside the patient to the renal nerves. Ultimately, the procedure will be a “no puncture,” noninvasive technique, compatible with technologies that will allow for temperature and lesion mapping. A noninvasive procedure will allow titration of the therapy— that is, the application of patient-specific dose fractions while monitoring therapeutic effect in between fractions. The basis of the technology is focused ultrasound, not high intensity (HIFU) as one might see and expect in the treatment of tumors, but low-intensity focused ultrasound (LIFU). The biologic underpinnings of this treatment are described in past literature for treating nerves using ultrasound. Kona noninvasive system. The system is depicted in a custom chair; another version of the system is compatible with a standard fluoroscopy or MRI table. Both ultrasound (through elastography and the evolution of temperature mapping and MRI) allow further imaging and analysis of the treatment area. The dose distribution surrounding the artery is that of an annular ring around the wall of the artery. Kona has shown in animal studies that a heat/vibratory cloud at one plane along the artery is highly effective at long-term inhibition of renal nerves with no visible effect on any portion of the artery at any time point.

US, Ronkonkoma, NY & Germany – Paradise  by ReCor Medical 6-F compatible catheter with a cylindrical transducer that emits ultrasound energy circumferentially, allowing for a more efficient renal denervation procedure First-in-human (15 patients at 3 months) BP drop, mm Hg -32/-16 at 3 mo. The ultrasound transducer lies within a low-pressure balloon that allows for self-centering of the transducer and gentle contact with the artery wall for uniform circumferential denervation. This means that nerves below the surface of the artery wall are damaged in 360° with a single emission. The balloon also enables cooled fluid to circulate during the energy delivery process, thereby cooling the endothelial wall and protecting it from any excessive heating that could be caused by other energy sources or designs. Preliminary F-I-M clinical data for PARADISE were reported previously at the “TRenD 2012” transcatheter renal denervation scientific meeting by cardiologist Thomas A. Mabin, M.D., Vergelegen Medi-Clinic, South Africa. The updated PARADISE data show that systolic blood pressure was reduced by a statistically significant average of 36 mm Hg in 8 patients at 90-days follow-up. The scientific literature demonstrates that only a 5 mm Hg reduction in BP results in a 14% decrease in stroke, a 9% decrease in heart disease, and a 7% decrease in mortality.

US, San Leandro, CA The Mercator Bullfrog by Mercator MedSystems, Inc. is a catheter-guided system designed to inject therapeutic agents directly, nonsystemically, and safely through blood vessel walls into adventitial tissues and has received US Food and Drug Administration 510(k) clearance. The Bullfrog catheter is tipped with a balloon-sheathed microneedle and is guided and inflated in a manner similar to an angioplasty catheter but with far lower expansion pressures (2 atm vs 6–20 atm) in vessels of 3 to 6 mm in diameter. It is compatible with 0.014-inch guidewires and 6-F introducer sheaths. When the desired injection site is reached, the balloon is inflated with saline and radiopaque contrast, securing the system for injection and sliding the microneedle through the vessel wall. Nonclinical studies have shown that the Bullfrog catheter is able to deliver up to 5 mL per injection into the renal artery adventitia with no apparent safety concerns. Guanethidine Ismelin) is delivered to the renal artery adventitia to accomplish sympathetic denervation. Given locally, guanethidine is known to induce an autonomic denervation directly and through an immune-mediated pathway. Mercator’s preclinical experiments have shown that guanethidine, injected at appropriate concentrations into the adventitial space around renal arteries, selectively ablates the nerves in the adventitia around the renal artery after a single, 20-minute procedure

J Neurosci. 1983;3:714-724

US – Laguna Hills, CA – V2 Radiofrequency Baloon by Vessix Vascular, Inc.Bipolar RF balloon catheter REDUCE-HTN pilot (10 patients)

Renal Denervation Technology of Vessix Vascular, Inc. been acquired by Boston Scientific Corporation (BSX) to pay up to $425 Million

https://pharmaceuticalintelligence.com/2012/11/08/renal-denervation-technology-of-vessix-vascular-inc-been-acquired-by-boston-scientific-corporation-bsx-to-pay-up-to-425-million/

BP drop, mm Hg -30/-11 at 1 mo V 2 catheter, a patented noncompliant balloon catheter with RF electrodes and thermistors mounted on the exterior of the balloon, and the proprietary V 2 bipolar RF generator. Once inserted into the renal artery, a 30-second inflation/treatment per renal artery delivers simultaneous RF therapy with independent temperature control to all electrode pairs. V 2 catheter is available in balloon diameters ranging from 4 to 7 mm, with a balloon length of 25 mm. Larger-diameter balloons have eight electrode pairs, and smaller-diameter balloons have four to six electrode pairs made of solid gold, which are biocompatible and facilitate good electrode contact with the renal arterial wall. In addition, the electrodes are radiopaque, allowing the V 2 catheter to be easily visualized under fluoroscopy. Beginning in the first quarter of 2012, the V 2 renal denervation system will be utilized in the company’s first international, multicenter clinical study: REDUCEHTN.

Israel, Tel Aviv – Tivus by Cardiosonic  A6-F transducer-tipped catheter, ultrasound energy (Animal data only) The solution for renal denervation is a high-intensity, nonfocused ultrasonic (US) catheter system named TIVUS (Therapeutic IntraVascular UltraSound) (Figure 3). By applying ultrasonic energy, the TIVUS technology enables remote, localized, controlled, and repeatable thermal modulation of the renal vessel wall tissue, resulting in safe renal nerve ablation. The remote thermal effect is located in the adventitia and perivascular region, with no thermal damage to the endothelium and media, therefore, preventing the development of vessel injury processes. Swine kidney tissue NE concentrations at 30- and 90-day follow-up have demonstrated successful renal denervation as witnessed by a 50% or more decline in tissue NE. Localized tissue thermal modulation/ablation, without damage to the blood vessel wall.

US, MN – SYMPLICITY HTN 2 by Medtronic   average office-based BP drops ofBP drop, mm Hg 32/12 mm Hg at six months in the SYMPLICITY HTN 2 trial, as reported by heartwire, with 84% of patients having had a >10-mm-Hg drop in systolic blood pressure from baseline. 14 points in 30 days and 27 points after 1 year. Available in Europe. Medtronic is the furthest ahead in its development process, predicting it will get Symplicity on the American market by 2015. catheter in the renal artery near each kidney to deliver radiofrequency energy to ablate the nerves. A single electrode in contrast to St. Jude’s mutli-electrode approach, is already on the road to FDA review with clinical trials approved last summer in the U.S. Symplicity system has been safely used in nearly 5,000 patients since commercialization

1/9/2014 – Pivotal US trial of Metronics’ Symplicity Renal Denervation System for Refractory Hypertension FAILED its Efficacy Endpoint

US, MN – EnligHTN 1 by  St Jude radiofrequency (RF) energy to create lesions (tiny scars) along the renal sympathetic nerves Mean office BP changes at one month in BP drop, mm Hg 28 systolic and -10 diastolic after 1 month (p<0.0001 from baseline), with 78% of patients having systolic BP drops of >10 mm Hg. St. Jude Medical’s (St. Paul, MN) announcement in late 2011 of the first patient to be enrolled in their first-in-man ARSENAL trial 15 at the University of Adelaide

Renal Denervation: EnligHTN IV Study Called Off and Potential Novel Indications – Diastolic Heart Failure

https://pharmaceuticalintelligence.com/2013/12/10/renal-denervation-enlightn-iv-study-called-off-and-potential-novel-indications-diastolic-heart-failure/

Ireland, Dublin – OneShot™ by Covidien acquisition of Maya Medical, Saratoga, CA New Irrigated RF Balloon Catheter secure first human use for the device in the third quarter of this year, followed by a CE mark for the drug-resistant hypertension treatment in 2013. Presumably, a filing with the FDA would follow that. the OneShot renal denervation system, was born out of the company’s extensive expertise in radiofrequency (RF) ablation and percutaneous coronary interventions (PCI), drawing upon the benefits and best practice standards of each distinct yet complementary clinical discipline. The result is a unique product platform that could further accelerate the paradigm shift in the management of resistant hypertension. consistent with Maya’s balloon-based approach is the ability to deliver predictable apposition of the RF electrode to the vessel wall for more controlled targeted delivery of the RF energy. By offering a more reliable single-treatment approach coupled with enhanced ease of use and reduced procedure times, Maya Medical believes its OneShot renal denervation system has the potential to significantly expand clinical adoption

http://bmctoday.net/evtoday/2012/02/article.asp?f=renal-artery-denervation-a-brave-new-frontier

1/21/2014

Covidien said it’s pulling the plug on its OneShot renal denervation device, citing the slow development of the hypertension market.

Covidien bails on renal denervation

Covidien (NYSE:COV) said it plans to wind down its OneShot renal denervation program, largely due to “slower than expected development of the renal denervation market,” meaning the end for a U.S. clinical trial of the high blood pressure device.

“This decision resulted from Covidien’s regular review of strategic programs and growth potential for various aspects of its product portfolio,” according to a press release. “Over the next several weeks, the company will collaborate with physicians and the renal denervation community to ensure existing OneShot patients are informed and the currently enrolling clinical trials are transitioned appropriately.”

The OneShot device already had CE Mark approval in the European Union for treating resistant hypertension in April 2012, when Covidien paid $60 million in cash and put another $170 million on the table in milestones.

http://www.massdevice.com/news/covidien-bails-renal-denervation

US, Natick, MA Boston Scientific lags behind in the race to cash in on hypertension-treating devices, incoming CEO Michael Mahoney said at a Monday conference that it has a plan for its RDN renal denervation system. As MassDevice reports, Mahoney said Boston Sci expects to secure first human use for the device in the third quarter of this year, followed by a CE mark for the drug-resistant hypertension treatment in 2013.

Renal Denervation Technology of Vessix Vascular, Inc. been acquired by Boston Scientific Corporation (BSX) to pay up to $425 Million

https://pharmaceuticalintelligence.com/2012/11/08/renal-denervation-technology-of-vessix-vascular-inc-been-acquired-by-boston-scientific-corporation-bsx-to-pay-up-to-425-million/

Heartwire Reported on December 09, 2013

On 1/9/2014 we post that

Pivotal US trial of Metronics’ Symplicity Renal Denervation System for Refractory Hypertension FAILED its Efficacy Endpoint

In the Press

Medtronic to weigh future of Symplicity renal denervation system after US trial failure

(Ref: Yahoo!News, The Wall Street Journal, StreetInsider, Medtronic)

January 9th, 2014
By: Katie Bell

Medtronic said Thursday that a pivotal US trial of its Symplicity renal denervation system for treatment-resistant hypertension failed to meet its main efficacy endpoint. The company noted that based on the results of the SYMPLICITY HTN-3 study, it will form an independent panel “to make recommendations about the future of the global hypertension clinical trial programme, as well as provide advice on continued…access to the Symplicity technology in countries with regulatory approvals.”

Depending on the panel review, the company said that it plans to suspend enrollment in the three countries where renal denervation hypertension studies are under way, including, the SYMPLICITY HTN-4 trial in the US, the HTN-Japan study in Japan and the HTN-India trial in India. Chief medical officer Rick Kuntz remarked that “we believe this course of action…will help us thoroughly evaluate these findings and determine the appropriate next steps for renal denervation therapy.”

The Symplicity system received CE mark approval in 2008, with Medtronicannouncing last month that regulators in Europe and Australia cleared the Symplicity Spyral catheter and Symplicity G3 radio frequency generator. The device maker said Thursday that it is evaluating the value of its renal denervation assets and believes “a one-time impairment charge in the future will be likely,” but reiterated its revenue outlook and diluted earnings per share guidance for fiscal 2014.

The SYMPLICITY HTN-3 trial randomised 535 patients with treatment-resistant hypertension and systolic blood pressure higher than 160 mmHg to a treatment or a control group, with all participants continuing to take blood pressure medications. The primary endpoints of the study were the change in office blood pressure from baseline to six months and incidence of major adverse events. Co-principal investigator Deepak L. Bhatt noted that the study “met its primary safety endpoint related to the incidence of major adverse events one month following randomisation and renal artery stenosis to six months.”

This Open Access Scientific Journal has covered all the major developments reported on Renal Denervation since its inception

The Archive for Renal denervation

https://pharmaceuticalintelligence.com/category/cardiac-and-cardiovascular-surgical-procedures/renal-denervation/

Search Results for Renal Denervation

https://pharmaceuticalintelligence.com/?s=Renal+denervation

For the ORIGINAL work on 

Renal Sympathetic Denervation: Updates on the State of Medicine

the Readers is called to go to the ORIGINAL SOURCES listed below:

Intravascular Stimulation of Autonomics: A Letter from Dr. Michael Scherlag

https://pharmaceuticalintelligence.com/2012/09/02/intravascular-stimulation-of-autonomics-a-letter-from-dr-michael-scherlag/

Imbalance of Autonomic Tone: The Promise of Intravascular Stimulation of Autonomics

https://pharmaceuticalintelligence.com/2012/09/02/imbalance-of-autonomic-tone-the-promise-of-intravascular-stimulation-of-autonomics/

Interaction of Nitric Oxide and Prostacyclin in Vascular Endothelium

https://pharmaceuticalintelligence.com/2012/09/14/interaction-of-nitric-oxide-and-prostacyclin-in-vascular-endothelium/

Absorb™ Bioresorbable Vascular Scaffold: An International Launch by Abbott Laboratories

https://pharmaceuticalintelligence.com/2012/09/29/absorb-bioresorbable-vascular-scaffold-an-international-launch-by-abbott-laboratories/

The Molecular Biology of Renal Disorders: Nitric Oxide – Part III

https://pharmaceuticalintelligence.com/2012/11/26/the-molecular-biology-of-renal-disorders/

Treatment of Refractory Hypertension via Percutaneous Renal Denervation

https://pharmaceuticalintelligence.com/2012/06/13/treatment-of-refractory-hypertension-via-percutaneous-renal-denervation/

Renal Denervation Technology of Vessix Vascular, Inc. been acquired by Boston Scientific Corporation (BSX) to pay up to $425 Million

https://pharmaceuticalintelligence.com/2012/11/08/renal-denervation-technology-of-vessix-vascular-inc-been-acquired-by-boston-scientific-corporation-bsx-to-pay-up-to-425-million/

Read Full Post »


St. Jude’s CEO is still betting on EnligHTN IV Study Renal Denervation System, despite Medtronic’s setback related to SYMPLICITY Phase IV

 

UPDATED on 1/14/2014

This is in continuation to our 1/9/2014 article:

Market Impact on Global Suppliers of Renal Denervation Systems by Pivotal US Trial: Metronics’ Symplicity Renal Denervation System FAILURE at Efficacy Endpoint

https://pharmaceuticalintelligence.com/2014/01/09/market-impact-on-global-suppliers-of-renal-denervation-systems-by-pivotal-us-trial-metronics-symplicity-renal-denervation-system-failure-at-efficacy-endpoint/

In the short term, the company, St. Jude suspended enrollment in three other related trials and announced plans to gather an independent panel of experts to plot a future course. 

St. Jude Medical won a CE mark for its next-gen EnligHTN IV renal denervation system over the summer, but halted its own U.S. trial in December. Minnesota-based St. Jude said it had struggled to recruit viable candidates for the 590-patient trial, and was concerned that Medtronic’s Symplicity might siphon off viable patients needed for its own study. At the time, St. Jude said it would work to develop a new protocol to address trial enrollment challenges.

According to Mark Hollmer:

Symplicity’s setbacks may make that job much easier for St. Jude. They also create new opportunities for other rivals focused on developing similar technology, such as Boston Scientific ($BSX) and Covidien ($COV).

Curator of this article has expressed a different view in 

https://pharmaceuticalintelligence.com/2014/01/09/market-impact-on-global-suppliers-of-renal-denervation-systems-by-pivotal-us-trial-metronics-symplicity-renal-denervation-system-failure-at-efficacy-endpoint/

St. Jude’s CEO is still betting on renal denervation, despite Medtronic’s setback

By Mark Hollmer

Medtronic’s Symplicity renal denervation device

If Medtronic’s ($MDT) recent U.S. clinical trial failure for its Symplicity renal denervation device throws the door wide open for its competitors, St. Jude Medical ($STJ) will likely waste no time walking through.

As MassDevice reported, St. Jude CEO Daniel Starks told an audience at the JPMorgan Healthcare conference in San Francisco that the company plans to keep plowing ahead with the development of its own technology.

“The fact that we had and that there have been favorable early clinical results in numerous other experiences is still valid,” MassDevice quoted Starks as saying. “There is open surgical data dating back several decades that was favorable to the impact of surgical renal denervation to treat hypertension.

That said, he also expressed genuine surprise about Medtronic’s trial setback.

“This was unexpected for us, to have a negative result from Medtronic’s trial, and it’s too soon for us to know what to make of that,” Starks said in the story.

Medtronic’s Symplicity device, which has a CE mark and is a market leader, had done well in previous trials in patients with different forms of hypertension and was on track to win FDA approval in 2015–potentially the first renal denervation device to reach that point.

The Minnesota device giant announced a few days ago that Symplicity proved safe in a 535-patient trial but failed to significantly lower blood pressure for drug-resistant hypertension.

This was a trial that mattered, designed to help fuel FDA approval.

Related Articles:

Medtronic’s flunked trial throws its hypertension program into doubt

St. Jude Medical will try again another day for a U.S. renal denervation study

St. Jude bags EU approval for next-gen renal denervation

 SOURCE

From: FierceMedicalDevices <editors@fiercemedicaldevices.com>
Date: Tue, 14 Jan 2014 18:14:06 +0000 (GMT)
To: <avivalev-ari@alum.berkeley.edu>

Renal Denervation: EnligHTN IV Study Called Off and Potential Novel Indications – Diastolic Heart Failure

Reporter: Aviva Lev-Ari, PhD, RN

This Open Access Scientific Journal has covered all the major developments reported on Renal Denervation since its inception

The Archive for Renal denervation

https://pharmaceuticalintelligence.com/category/cardiac-and-cardiovascular-surgical-procedures/renal-denervation/

Search Results for Renal Denervation

https://pharmaceuticalintelligence.com/?s=Renal+denervation

Heartwire Reported on December 09, 2013

EnligHTN IV Renal Denervation Study Called Off

ST PAUL, MN – The EnligHTN IV study (St Jude Medical, St Paul, MN), testing the multielectrode renal-denervation system in patients with resistant hypertension, has been stopped almost before it even began. The trial, which was announced in June and began enrolling a small number of patients this fall, was canceled because of concerns about slow enrollment.

To heartwire ,

Denise Perkins-Landry, a spokesperson for St Jude Medical, said the decision to discontinue the study was based on “anticipated recruitment challenges” and is not the result of any safety or efficacy issues with the device. “A US clinical trial for EnligHTN remains a very high priority for St Jude Medical, and we will be working with the FDA to develop a new protocol that will address anticipated enrollment challenges,” she stated in an email.

The full results of the SYMPLICITY HTN-3 trial, a study similar to the EnligHTN IV study, which is sponsored by Medtronic (Minneapolis, MN), are expected in early 2014. While neither device is approved for clinical use in the US, it is expected that the Medtronic renal-denervation system will be first. As a result, it might be difficult to enroll patients to a sham procedure if there is another commercially available system for treating resistant hypertension, according to St Jude.

EnligHTN IV was to be a randomized, single-blind, controlled study with patients randomized from as many as 80 clinical centers in the US and Canada. It was intended to show the safety and effectiveness of the renal-denervation system in the reduction of systolic blood pressure in 590 patients with an office blood pressure >160 mm Hg despite taking three or more antihypertensive medications, including a diuretic.

Abrupt Decision to Stop the Study

Dr William White (University of Connecticut Medical Center, Farmington), one of the cochairs of the EnligHTN IV steering committee, told heartwire the decision to cancel the study was made just last week. In fact, there were clinical centers already up and running in terms of enrollment, although these were pilot centers where any “bugs could be worked out.” The meeting for training investigators participating in the trial was scheduled for Saturday in Chicago, IL, although that is now off.

“In the grander scheme of things, I can tell you that the decision was not made because of any problem with the catheter or any safety issues,” said White. “Outside the US, the development is continuing as planned, but the biggest concern is that it might be very difficult, if not impossible, to continue doing a sham-controlled study a year from now if there were a commercially available renal-denervation catheter in the US, which there very well could be with Medtronic.”

Still, White said that it’s not even known if the SYMPLICITY HTN-3 study is positive or if the FDA will be satisfied with the trial and its outcomes. He said a lot of assumptions are being made by St Jude Medical in stopping the trial, and it could turn out to be a bad decision. In addition, reimbursement remains an open question.

“Commercially available doesn’t mean there’s going to be a payer,” White told heartwire . “If that happens, it will be doubly unfortunate for the patients that are out there because they might be willing and able to go into a clinical trial but they won’t have that opportunity.”

As a scientist, White said that he would have preferred the trial be pursued, regardless of what happens with Medtronic. He believes the EnligHTN catheter is “outstanding,” as it has multiple electrodes to enable physicians to thoroughly ablate the renal arteries within a couple of minutes. “The clinical scientist in me would have preferred that we go ahead as planned,” he said. “I think we would have gained a great deal of knowledge. And just because one study shows a p value of 0.05 doesn’t mean a second study will.”

The Medtronic SYMPLICITY renal-denervation system was launched in 2010 and is available in parts of Europe, Asia, Africa, and South America. The first-generation EnligHTN device has had CE Mark approval in Europe since 2012 while the updated second-generation system with multiple electrodes received European approval this past summer.

News of the halting of EnligHTN IV was first reported by Wells Fargo analyst Larry Biegelsen.

SOURCE

http://www.medscape.com/viewarticle/817482?nlid=41903_2105&src=wnl_edit_medp_card&uac=93761AJ&spon=2

On December 06, 2013 Marlene Busko reported to Heartwire on

Renal Denervation’s Structural, Functional Heart Benefits May Be Independent of BP

HAMBURG, GERMANY — In a small study of patients undergoing renal denervation for resistant hypertension, left-ventricular hypertrophy and diastolic function improved independently of changes in blood pressure and heart rate [1].

“The novelty of our findings is the independence of morphologic improvements [regression of LV hypertrophy] from hemodynamic changes (reduction of blood pressure and heart rate),” Dr Stephan H Schirmer (University of Saarland, Hamburg, Germany) told heartwire in an email. “If this is confirmed in larger trials, it might open up novel indications for the use of renal denervation, for example, in [diastolic] heart-failure patients, independent of blood pressure.”

Dr Deepak L Bhatt (Harvard Medical School, Boston, MA) told heartwire that the study observations are “provocative” and “exciting” but stressed that they need to be confirmed in a blinded, larger, multicenter study before they could be accepted into clinical practice. Bhatt and Dr George Bakris (University of Chicago, IL) are co–principal investigators for the ongoing SYMPLICITY HTN-3 trial of bilateral renal denervation in patients with uncontrolled hypertension.

The study was published online December 4, 2013 in the Journal of the American College of Cardiology.

Are Renal Denervation Effects Always Tied to BP Change?

Renal denervation reduces heart rate and blood pressure in patients with resistant hypertension, and as reported by heartwire , a recent small study suggested that the procedure also reduces left-ventricular mass and improves diastolic function in such patients, Schirmer and colleagues write.

They hypothesized that renal denervation might affect cardiac structure and function, independent of the effect on blood pressure.

They enrolled 66 consecutive patients who underwent renal denervation using the Flex catheter system (Medtronic) at their center during 2010 and 2011 for treatment of resistant hypertension (office systolic blood pressure >140 mm Hg). Patients had a mean age of 64 years, and 55% were men. They were on a mean of 4.3 antihypertensive drugs. All were taking a diuretic, 89% were taking a beta-blocker, and 55% were taking an angiotensin-receptor blocker.

Six months after renal denervation,

  • Mean blood pressure decreased from 172.9/92.5 to 151.3/85.5 mm Hg, confirmed by 24-hour ambulatory monitoring, if available (n=50).
  • Mean heart rate decreased from 67.7 to 60.5 bpm.
  • Mean left-ventricular mass index decreased from 61.5 to 53.4 g/m2.
  • Measures of diastolic function also improved.

The changes in cardiac function and ventricular size were not tied to the magnitude of the blood-pressure reduction, which “suggest[s] a direct effect of the sympathetic nervous system on myocardial morphology and function,” Schirmer and colleagues write. They call for further research to investigate functional cardiovascular benefits of renal denervation beyond blood-pressure reduction.

Promising Early Benefit, Needs Confirmation

In an accompanying editorial [2], Bakris and Dr Sandeep Nathan (University of Chicago) commend Schirmer and colleagues “for providing promising early benefit of catheter-based renal denervation and for highlighting a possible blood-pressure–independent facet of this technique.” However, they caution that although the findings are “intriguing,” the study’s limitations include that it was

  • relatively small,
  • conducted at a single center,
  • lacked a sham control, and
  • relied on echocardiography rather than magnetic resonance imaging.

Therefore, “these observations need confirmation before acceptance in clinical practice . . . and can only be applied to those with inclusion criteria used in their study,” the editorialists conclude.

“It’s an exciting, provocative result, and there’s a good chance that it will stand the test of time, but I still think in general, it’s best to be cautious about new technologies and relatively small studies, because time typically shows that they provide an overestimate of what the true effects will be,” Bhatt commented when interviewed.

“Whether the reduction in left-ventricular mass is beyond what would be anticipated with blood-pressure and heart-rate reduction—certainly this analysis suggests that is a possibility—needs to be confirmed in larger studies,” he added, echoing the authors and editorialists.

Potentially referring physicians, in the United States where the procedure is investigational, and even in Europe where it’s approved, appear to be waiting for the results of SYMPLICITY HTN-3, Bhatt said. This blinded, randomized, multicenter trial will provide a clearer picture of what sort of blood-pressure reductions are achievable in patients with resistant hypertension who undergo renal denervation. Results are expected by mid-2014.

References

  1. Schirmer SH, Sayed M, Reil J-C, et al. Improvements of left-ventricular hypertrophy and diastolic function following renal denervation – Effects beyond blood pressure and heart rate reduction. J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2013.10.073. Abstract
  2. Bakris G, Nathan S. Renal denervation and left ventricular mass regression: A benefit beyond blood pressure reduction? J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2013.11.015. Editorial

SOURCE

This Open Access Scientific Journal has covered all the major developments reported on Renal Denervation since its inception

The Archive for Renal denervation

https://pharmaceuticalintelligence.com/category/cardiac-and-cardiovascular-surgical-procedures/renal-denervation/

Search Results for Renal Denervation

https://pharmaceuticalintelligence.com/?s=Renal+denervation

For the ORIGINAL work on 

Renal Sympathetic Denervation: Updates on the State of Medicine

the Readers is called to go to the ORIGINAL SOURCES listed below:

Intravascular Stimulation of Autonomics: A Letter from Dr. Michael Scherlag

https://pharmaceuticalintelligence.com/2012/09/02/intravascular-stimulation-of-autonomics-a-letter-from-dr-michael-scherlag/

Imbalance of Autonomic Tone: The Promise of Intravascular Stimulation of Autonomics

https://pharmaceuticalintelligence.com/2012/09/02/imbalance-of-autonomic-tone-the-promise-of-intravascular-stimulation-of-autonomics/

Interaction of Nitric Oxide and Prostacyclin in Vascular Endothelium

https://pharmaceuticalintelligence.com/2012/09/14/interaction-of-nitric-oxide-and-prostacyclin-in-vascular-endothelium/

Absorb™ Bioresorbable Vascular Scaffold: An International Launch by Abbott Laboratories

https://pharmaceuticalintelligence.com/2012/09/29/absorb-bioresorbable-vascular-scaffold-an-international-launch-by-abbott-laboratories/

The Molecular Biology of Renal Disorders: Nitric Oxide – Part III

https://pharmaceuticalintelligence.com/2012/11/26/the-molecular-biology-of-renal-disorders/

Treatment of Refractory Hypertension via Percutaneous Renal Denervation

https://pharmaceuticalintelligence.com/2012/06/13/treatment-of-refractory-hypertension-via-percutaneous-renal-denervation/

Renal Denervation Technology of Vessix Vascular, Inc. been acquired by Boston Scientific Corporation (BSX) to pay up to $425 Million

https://pharmaceuticalintelligence.com/2012/11/08/renal-denervation-technology-of-vessix-vascular-inc-been-acquired-by-boston-scientific-corporation-bsx-to-pay-up-to-425-million/

Read Full Post »


Advanced Topics in Sepsis and the Cardiovascular System at its End Stage

Author: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-Sepsis-and-the-Cardiovascular-System-at-its-End-Stage/

This article was written in continuation to and it is addressing additional scientific matters to the content presented on this subject in the third Section titled

III. Incidence of Sepsis (circulation infection with serious consequences)

of the 7/23/2013 article on:

Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/23/cardiovascular-complications-of-multiple-etiologies-repeat-sternotomy-post-cabg-or-avr-post-pci-pad-endoscopy-andor-resultant-of-systemic-sepsis/

The Cardiac Dysfunction Attributable to Sepsis, Hemodynamic Collapse, and the Search for Therapeutic Options

Sepsis and the Heart – Cardiovascular Involvement in General Medical Conditions
M.W. Merx, MD; C. Weber, MD
University Hospital (C.W.), RWTH Aachen University, Aachen, Germany.
Circulation.2007; 116: 793-802doi: 10.1161/​CIRCULATIONAHA.106.678359
http://circ.ahajournals.org/content/116/7/793.full

Sepsis is generally viewed as a disease aggravated by an inappropriate immune response encountered in the afflicted individual. As an important organ system frequently compromised by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear to date. There is currently no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis.  A circulating myocardial depressant factor in septic shock has long been proposed, and potential candidates for a myocardial depressant factor include cytokines, prostanoids, and nitric oxide, among others.  Endothelial activation and induction of the coagulatory system also contribute to the pathophysiology in sepsis.

Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory.  We delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches.

Sepsis, defined by consensus conference as “the systemic inflammatory response syndrome (SIRS) that occurs during infection,” is generally viewed as a disease aggravated by the inappropriate immune response encountered in the affected individual.  Morbidity and mortality are high, resulting in sepsis and septic shock being the 10th most common cause of death in the United States.  The total national hospital cost invoked by severe sepsis in the United States was estimated at approximately $16.7 billion with 215 000 associated deaths annually. A study from Britain documented a 46% in-hospital mortality rate for patients presenting with severe sepsis on admission to the intensive care unit.

Current Criteria for Establishment of the Diagnosis of SIRS, Sepsis, and Septic Shock

The cardiovascular system is an important organ system frequently affected by sepsis and always affected by septic shock.  Waisbren was the first to describe cardiovascular .dysfunction due to sepsis in 1951.  He recognized a hyperdynamic state with full bounding pulses, flushing, fever, oliguria, and hypotension.  He also described a second, smaller patient group who presented clammy, pale, and hypotensive with low volume pulses and who appeared more severely ill. The latter group might well have been volume underresuscitated, and indeed, timely and adequate volume therapy has been demonstrated to be one of the most effective supportive measures in sepsis therapy.

Under conditions of adequate volume resuscitation, the profoundly reduced systemic vascular resistance typically encountered in sepsis leads to a concomitant elevation in cardiac index that obscures the myocardial dysfunction that also occurs. As early as the mid-1980s, significant reductions in both stroke volume and ejection fraction in septic patients were observed with normal total cardiac output. The presence of cardiovascular dysfunction in sepsis is associated with a significantly increased mortality rate of 70% to 90% compared with 20% in septic patients without cardiovascular impairment.

Characteristics of Myocardial Dysfunction in Sepsis

Using portable radionuclide cineangiography, Calvin et al. were the first to demonstrate myocardial dysfunction in adequately volume-resuscitated septic patients who had decreased ejection fraction and increased end-diastolic volume index. Adding pulmonary artery catheters to serial radionuclide cineangiography, Parker and colleagues extended these observations with the 2 major findings that

(1) survivors of septic shock were characterized by increased end-diastolic volume index and decreased ejection fraction, whereas nonsurvivors typically maintained normal cardiac volumes, and

(2) these acute changes in end-diastolic volume index and ejection fraction, although sustained for several days, were reversible.

More recently, echocardiographic studies have demonstrated impaired left ventricular systolic and diastolic function in septic patients. These human studies, in conjunction with experimental studies have clearly established decreased contractility and impaired myocardial compliance as major factors that cause myocardial dysfunction in sepsis. Similar functional alterations, as discussed above, have been observed for the right ventricle.

Myocardial dysfunction in sepsis has also been analyzed with respect to its prognostic value. Parker et al. reviewing septic patients on initial presentation and at 24 hours to determine prognostic indicators, found a heart rate of <106 bpm to be the only cardiac parameter on presentation that predicted a favorable outcome.  At 24 hours after presentation, a systemic vascular resistance index > 1529 dyne · s−1 · cm−5 · m−2, a heart rate < 95 bpm or a reduction in heart rate >18 bpm, and a cardiac index > 0.5 L · min−1 · m−2 suggested survival.  In a prospective study, Rhodes et al. demonstrated the feasibility of a dobutamine stress test for outcome stratification, with nonsurvivors being characterized by an attenuated inotropic response.

The well-established biomarkers in myocardial ischemia and heart failure, cardiac troponin I and T, as well as B-type natriuretic peptide, have also been evaluated with regard to sepsis-associated myocardial dysfunction. B-type natriuretic peptide studies have delivered conflicting results in septic patients, confounded by pre-existing heart failure early in the course. Several small studies have reported a relationship between elevated cardiac troponin T and I and left ventricular dysfunction in sepsis, as assessed by echocardiographic ejection fraction or pulmonary artery catheter–derived left ventricular stroke work index.  Cardiac troponin levels also correlated with the duration of hypotension and the intensity of vasopressor therapy. In addition, increased sepsis severity, measured by global scores such as the Simplified Acute Physiology Score II (SAPS II) or the Acute Physiology And Chronic Health Evaluation II score (APACHE II), was associated with increased cardiac troponin levels, as was poor short-term prognosis.

Despite the heterogeneity of study populations and type of troponin studied, the mentioned studies were unequivocal in concluding that elevated troponin levels in septic patients reflect higher disease severity, myocardial dysfunction, and worse prognosis. In a recent meta-analysis of 23 observational studies, Lim et al. found cardiac troponin levels to be increased in a large percentage of critically ill patients. Furthermore, in a subset of studies that permitted adjusted analysis and comprised 1706 patients, this troponin elevation was associated with an increased risk of death (odds ratio, 2.5; 95% CI, 1.9 to 3.4, P<0.001). Thus, it appears reasonable to recommend inclusion of cardiac troponins in the monitoring of patients with severe sepsis and septic shock to facilitate prognostic stratification and to increase alertness to the presence of cardiac dysfunction in individual patients.

Mechanisms Underlying Myocardial Dysfunction in Sepsis

Cardiac depression during sepsis is probably multifactorial. Nevertheless, it is important to identify individual contributing factors and mechanisms to generate worthwhile therapeutic targets. As a consequence, a vast array of mechanisms, pathways, and disruptions in cellular homeostasis have been examined in septic myocardium.

An early theory of myocardial depression in sepsis based on the hypothesis of global myocardial ischemia has no support. Septic patients have been shown to have high coronary blood flow and diminished coronary artery–coronary sinus oxygen difference.  Coronary sinus blood studies in patients with septic shock have demonstrated complex metabolic alterations in septic myocardium, including increased lactate extraction, decreased free fatty acid extraction, and decreased glucose uptake.  Several magnetic resonance studies in animal models of sepsis have demonstrated the presence of normal high-energy phosphate levels in the myocardium.  CAD-aggravating factors encountered in sepsis encompass generalized inflammation and the activated coagulatory system. The endothelium plays a prominent role in sepsis, but little is known of the impact of preexisting, CAD-associated endothelial dysfunction in this context. In a postmortem study of 21 fatal cases of septic shock, previously undiagnosed myocardial ischemia at least contributed to death in 7 of the 21 cases (all 21 patients were males, with a mean age of 60.4 years

Myocardial Depressant Substance

Parrillo et al. first proposed  a circulating myocardial depressant factor in septic shock  more than 50 years ago. They quantitatively linked the clinical degree of septic myocardial dysfunction with the effect that serum, taken from respective patients, had on rat cardiac myocytes, with clinical severity correlating well with the decrease in extent and velocity of myocyte shortening. These effects were not seen when serum from convalescent patients whose cardiac function had returned to normal was applied or when serum was obtained from other critically ill, nonseptic patients. These findings were extended when ultrafiltrates from patients with severe sepsis and simultaneously reduced left ventricular stroke work index (< 30 g · m−1 · m−2) displayed cardiotoxic effects and contained significantly increased concentrations of interleukin (IL)-1, IL-8, and C3a. Recently, Mink et al. demonstrated that lysozyme c, a bacteriolytic agent believed to originate mainly from disintegrating neutrophilic granulocytes and monocytes, mediates cardiodepressive effects during Escherichia coli sepsis and, importantly, that competitive inhibition of lysozyme c can prevent myocardial depression in the respective experimental sepsis model. Additional potential candidates for myocardial depressant substance include other cytokines, prostanoids, and nitric oxide (NO).

Cytokines

Infusion of lipopolysaccharide (LPS, an obligatory component of Gram-negative bacterial cell walls) into both animals and humans partially mimics the hemodynamic effects of septic shock. Only a minority of patients with septic shock have detectable LPS levels, and the prolonged time course of septic myocardial dysfunction make the role of LPS inconsistent with LPS representing the sole myocardial depressant substance. Tumor necrosis factor-α (TNF-α) is an important early mediator of endotoxin-induced shock. TNF-α is mainly derived from activated macrophages. Studies using monoclonal antibodies directed against TNF-α or soluble TNF-α receptors failed to improve survival in septic patients. IL-1 is synthesized by monocytes, macrophages, and neutrophils in response to TNF-α and plays a crucial role in the systemic immune response. IL-1 depresses cardiac contractility by stimulating NO synthase (NOS). Transcription of IL-1 is followed by delayed transcription of IL-1 receptor antagonist (IL-1-ra), which functions as an endogenous inhibitor of IL-1. Recombinant IL-1-ra was evaluated in phase III clinical trials, which showed a tendency toward improved survival and increased survival time in a retrospective analysis of the patient subgroup with the most severe sepsis; but this initially promising therapy failed to deliver a survival benefit. IL-6, another proinflammatory cytokine, has also been implicated in the pathogenesis of sepsis and is considered a more consistent predictor of sepsis than TNF-α because of its prolonged elevation in the circulation. Although cytokines may very well play a key role in the early decrease in contractility, they cannot explain the prolonged duration of myocardial dysfunction in sepsis, unless they result in the induction or release of additional factors that in turn alter myocardial function, such as prostanoids or NO.

Prostanoids

Prostanoids are produced by the cyclooxygenase enzyme from arachidonic acid (an omega-6 derivative). The expression of cyclooxygenase enzyme-2 is induced, among other stimuli, by LPS and cytokines (cyclooxygenase enzyme-1 is expressed constitutively). Elevated levels of prostanoids such as thromboxane and prostacyclin that alter coronary autoregulation, coronary endothelial function, and intracoronary leukocyte activation, have been demonstrated in septic patients. Early animal studies with cyclooxygenase inhibitors such as indomethacin yielded very promising results. Along with other positive results, these led to an important clinical study involving 455 septic patients who were randomized to receive intravenous ibuprofen or placebo, but that study did not demonstrate improved survival for the treatment arm. Similarly, a smaller study on the effects of lornoxicam failed to provide evidence for a survival benefit through cyclooxygenase inhibition in sepsis.

Endothelin-1

Endothelin-1 upregulation has been demonstrated within 6 hours of LPS-induced septic shock. Cardiac overexpression of ET-1 triggers an increase in inflammatory cytokines (among others, TNF-α, IL-1, and IL-6), interstitial inflammatory infiltration, and an inflammatory cardiomyopathy that results in heart failure and death. The involvement of ET-1 in septic myocardial dysfunction is supported by the observation that tezosentan, a dual endothelin-A and endothelin-B receptor antagonist, improved cardiac index, stroke volume index, and left ventricular stroke work index in endotoxemic shock. However, higher doses of tezosentan exhibited cardiotoxic effects and led to increased mortality. Although ET-1 has been demonstrated to be of pathophysiological importance in a wide array of cardiac diseases through autocrine, endocrine, or paracrine effects, its biosynthesis, receptor-mediated signaling, and functional consequences in septic myocardial dysfunction warrant further investigation to assess the therapeutic potential of ET-1 receptor antagonists.

Free Radicals and Antioxidants: an Overview

The presence of free radicals in biological materials was discovered about 50 years ago. Today, there is a large body of evidence indicating that patients in hospital intensive care units (ICUs) are exposed to excessive free radicals from drugs and other substances that alter cellular reduction -oxidation (redox) balance, and disrupt normal biological functions. However, low levels of free radicals are also vital for many cell signaling events and are essential for proper cell function.

Normal cellular metabolism involves the production of ROS, and in humans, superoxide (O2 -) is the most commonly produced free radical. Phagocytic cells such as macrophages and neutrophils are prominent sources of O2 -. During an inflammatory response, these cells generate free radicals that attack invading pathogens such as bacteria and, because of this, the production of O2- by activated phagocytic cells in response to inflammation is one of the most studied free radical producing systems.

Excess free radicals can result from a variety of conditions such as tissue damage and hypoxia (limiting oxygen levels), overexposure to environmental factors (tobacco smoke, ultraviolet radiation, and pollutants), a lack of antioxidants, or destruction of free radical scavengers. When the production of damaging free radicals exceeds the capacity of the body’s antioxidant defenses to detoxify them, a condition known as oxidative stress occurs.

The hydroxyl radical (.OH) is the most reactive of the free radical molecules. OH- damages cell membranes and lipoproteins by a process termed lipid peroxidation. In fact, lipid peroxidation can be defined as the process whereby free radicals “steal” electrons from the lipids in our cell membranes, resulting in cell damage and increased production of ROS.

Catalase and glutathione peroxidase both work to detoxify O2-reactive radicals by catalyzing the formation of H2O2 derived from O2 -. The liver, kidney, and red blood cells possess high levels of catalase, which helps to detoxify chemicals in the body. The water-soluble tripeptide-thiol glutathione also plays an important role in a variety of detoxification processes. Glutathione is found in millimolar concentrations in the cell cytosol and other aqueous phases, and readily interacts with free radicals, especially the hydroxyl radical, by donating a hydrogen atom.

Adhesion Molecules

Surface-expression upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 has been demonstrated in murine coronary endothelium and cardiomyocytes after LPS and TNF-α stimulation. After cecal ligation and double puncture, myocardial intercellular adhesion molecule-1 expression increases in rats. Vascular cell adhesion molecule-1 blockade with antibodies has been shown to prevent myocardial dysfunction and decrease myocardial neutrophil accumulation, whereas both knockout and antibody blockade of intercellular adhesion molecule-1 ameliorate myocardial dysfunction in endotoxemia without affecting neutrophil accumulation. But neutrophil depletion does not protect against septic cardiomyopathy, which suggests that the cardiotoxic potential of neutrophils infiltrating the myocardium is of lesser importance in this context.

Cells and signaling pathways

It is believed that sepsis and therefore septic shock are due to the inappropriate increase in the innate immune response via circulating and tissue inflammatory cells, such as monocytes/macrophages and neutrophils. These cells normally exist in a nonactivated state but are rapidly activated in response to bacteria. Sepsis induces a dysfunction in immune cells that contributes to the development of injuries by producing mediators such as cytokines and ROS.

LPS of Gram-negative organisms induces macrophages to secrete cytokines, which in turn activate T, and B cells to upregulate the adaptive immune responses. Toll-like receptor 4 (TLR4) is the LPS receptor and its stimulation induces nuclear factor kB (NF-kB) activation. The activation of NF-kB involves phosphorylation and degradation of IkB, an inhibitor of NF-kB. The NF-kB/IkB system exerts transcriptional regulation on proinflammatory genes encoded for various adhesion molecules and cytokines. Activation of NF-kB leads to the induction of NF-kB binding elements in their promoter regions and also leads to the induction of NF-kB dependent effector genes, which produce modifications in blood flow, and aggregation of neutrophils, and platelets. This results in damaged endothelium and also coagulation abnormalities often seen in patients with sepsis and septic shock. Therefore, NF-kB is reported to be an O2 sensor in LPS-induced endotoxemia.

The sources of ROS during sepsis are:

  • the mitochondrial respiratory chain.
  • the metabolic cascade of arachidonic acid.
  • the protease-mediated enzyme xanthine oxidase.
  • granulocytes and other phagocytes activated by complement, bacteria, endotoxin, lysosomal enzymes, etc.
  • Other oxidases mainly NADPH oxidase.

Activated immune cells produce O2 – as a cytotoxic agent as part of the respiratory burst via the action of membrane-bound NADPH oxidase on O2.

The increase of ROS after LPS challenge has been demonstrated in different models of septic shock in peritoneal macrophages and lymphocytes. This disturbance in the balance between pro-oxidants (ROS) and antioxidants in favor of the former is characteristic of oxidative stress in immune cells in response to endotoxin. In this context,

a typical behavior of these cells under an oxidative stress situation implies changes in different immune functions such as an increase in adherence and phagocytosis and a decrease in chemotaxis.  Neutrophils play a crucial role in the primary immune defense against infectious agents,which includes phagocytosis and the production of ROS. In addition, endogenous antioxidant defenses exist in a number of locations, namely intracellularly, on the cell membrane and extracellularly. The immune system is highly reliant on accurate cell-cell communication for optimal function, and any damage to the signaling systems involved will result in an impaired immune responsiveness.

Oxidative stress and modulation on GSH/GSSG (GSSG=oxidized GSH) levels also up-regulate gene expression of several other antioxidant proteins, such as manganese SOD, glutathione peroxidase, thioredoxin (Trx) and metallothionein.

Nitric Oxide

The current understanding of sepsis is a cascade of events that involves the microcirculation unevenly because of a differential effect on the large and contiguous intestinal epithelium, secondary effects on cardiopulmonary blood flows and cardiac output. This leads to a substantial body of work on therapeutic targets, either aimed at total inhibition or selective inhibition of NO synthase, and the special role of iNOS.

NO is synthesized from L-arginine by different isoenzymes of (NOS), and is implicated in a wide range of disease processes, exerting both detrimental and beneficial effects at the cellular and vascular levels. To date, three main isoforms of NOS are known:

  • neuronal NOS (NOS-1 or nNOS),
  • inducible NOS (NOS-2 or iNOS), and
  • endothelial NOS (NOS-3 or eNOS).

NO has been shown to play a key role in the pathogenesis of septic shock

Hyperproduction of NO induces

  • excessive vasodilation,
  • changes in vascular permeability, and
  • inhibition of noradrenergic nerve transmission,
  • all characteristics of human septic shock.

The recogniton of NO production by activated macrophages as part of the inflammatory process was an important milestone for assesing both the biological production of NO and the phenomenon of induction of NOS activity. The observation has been extended to neutrophils, lymphocytes, and other cell types. The role of NO in the pathophysiology of endotoxic shock was advanced by Thiemermann and Vane, who observed that administration of the specific NOS inhibitor N-methyl-L-arginine (L-NMMA) decreased the severe hypotension produced by administration of LPS. Other groups simultaneously reported similar results indicating that endotoxin increases NO production and prompted the idea that pharmacological inhibition of NOS may be useful in the treatment of inflammation and septic shock. However, clinical trials using L-NMMA failed to show a beneficial effect in septic shock patient. The major limitation for the use of NOS inhibitors in clinical studies is the development of pulmonary hypertension as a side effect of NOS blockade, which can be alleviated by the use of inhaled NO.

However, several compounds which modulate NO synthesis have been patented in recent years, such as various inflammatory mediators that have been implicated in the induction and activation of iNOS, particularly IFNg, TNFa, IL-1b, and platelet-activating factor (PAF) alone or synergistically. In addition to the activation of iNOS, cytokines and endotoxin may increase NO release by increasing arginine availability through the opening of the specific y+ channels and the expression of the cationic amino acid transporter (CAT), or by increasing tetrahydrobiopterin levels, a key cofactor in NO synthesis. Several experimental studies have demonstrated a decrease in NOS activity resulting in an impairment in endothelial-dependent relaxation during endotoxemia and experimental sepsis, possibly as the result of a cytokine-or hypoxia-induced shortened half-life of NOS mRNA, or of altered calcium mobilization.

Advanced Topics in Sepsis and the Cardiovascular System –  Augmentation for the third Section titled:

III. Incidence of Sepsis (circulation infection with serious consequences)

of the 7/23/2013 article on: Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

NO exerts in vitro toxic effects including nuclear damage, protein and membrane phospholipid alterations, and the inhibition of mitochondrial respiration in several cell types. Mitochondrial impairment could also be considered as an adaptive phenomenon, decreasing cellular metabolism when the energy supply is limited. The toxicity of NO itself may be enhanced by the formation of ONOO- from the reaction of NO with O-2. Therefore, the multiple organ failure syndrome (MOFS) that often accompanies severe sepsis may be related to the cellular effects of excess NO or ONOO-.

Involvement of Nitrogen Species

NO reacts rapidly with ferrous iron, and at physiological concentrations, NO also binds to soluble guanylate cyclase and to another hemoprotein, cytochrome c oxidase (Complex IV), the terminal enzyme of the mitochondrial respiratory chain. NO can therefore control cellular functions via the reversible inhibition of respiration. There are a number of reactive NO species, such as

N2O3 and
ONOO-
that can also alter critical cellular components.

During the first hours after injury, iNOS-mediated NO production is upregulated, producing a burst of NO that far exceeds basal levels. This overabundance of NO produces significant cellular injury via several mechanisms.

NO may directly promote overwhelming peripheral vasodilation, resulting in vascular decomposition;

NO may upregulate the transcription NF-kB initiating an inflammatory signaling pathway that, in turn, triggers numerous inflammatory cytokines.

NO also interacts with the O-2 to yield ONOO-, a highly reactive compound that exacerbates the injury produced by either O-2 alone or NO alone.

The ONOO- generation which occurs during fluid resuscitation in the injured subject produces cellular death by enhancing DNA single strand breakage, activates the nuclear enzyme polyADP ribose synthetase (PARS), leading to cellular energy depletion and cellular necrosis. The detrimental effects of ONOO- in shock and resuscitation have been attributed to oxidation of sulfhydryl groups, the nitration of tyrosine, tryptophane, and guanine, as well as inhibition of the membrane sodium-potassium adenosine triphosphatase. PARS activation depletes NAD and thus alters electron transport, ATP synthesis, and glycolysis; and leads to DNA fragmentation and cellular apoptosis.

The activation of monocytes, macrophages and endothelial cells by LPS results in the expression of iNOS, and consequently increases the transformation of L-arginine to NO, which can combine with O2- to form ONOO-, causing tissue injury during shock, inflammation and ischemia reperfusion. NO stimulates H2O2 and O-2 production by mitochondria, increasing leakage of electrons from the respiratory chain. H2O2, in turn, participates in the upregulation of iNOS expression via NFkB activation. ONOO- has been shown to stimulate H2O2 production by isolated mitochondria. On the other hand, NO can decrease ROS-produced damage that occurs at physiological levels of NO. The high reactivity of NO with radicals might be beneficial in vivo by scavenging peroxyl radicals and inhibiting peroxidation. ONOO- may also be a signal transmitter and can mediate vasorelaxation, similarly to NO.

In sepsis, NO may exert direct and indirect effects on cardiac function. Sustained generation of NO occurs in systemic inflammatory reactions, such as septic shock with involvement in circulatory failure. In fact, myocardial iNOS activity has been reported in response to endotoxin and cytokines and inversely correlated with myocardial performance. Low-to-moderate doses of iNOS inhibitors restore myocardial contractility in hearts exposed to proinflammatory cytokines, whereas at higher doses, the effects are reversed. This finding may indicate that small amounts of NO produced by iNOS may be necessary to maintain contractility and can be cardio-protective in experimental sepsis.

A list of effects of NO in sepsis is as follows:

  • Inhibition of nitric oxide synthesis causes myocardial ischemia in endotoxemic rats
  • Nitric oxide causes dysfunction of coronary autoregulation in endotoxemic rats
  • Prolonged inhibition of nitric oxide synthesis in severe septic shock

Effect of L-NAME, an inhibitor of nitric oxide synthesis, on cardiopulmonary function in human septic shock:  Pulmonary hypertension and reduced cardiac output during inhibition of nitric oxide synthesis in human septic shock

Effect of L-NAME, an inhibitor of nitric oxide synthesis, on plasma levels of IL-6, IL-8, TNF-a and nitrite/nitrate in human septic shock

Endothelin-1 and blood pressure after inhibition of nitric oxide synthesis in human septic shock

Distribution and metabolism of NO-nitro-L-arginine methyl ester in patients with septic shock

Pulmonary hypertension and reduced cardiac output can be major side effects of continuous NO synthase inhibition. Pulmonary vasoconstriction is undesirable because it may compromise pulmonary gas exchange and because it increases the workload on the right ventricle.

Blood pressure and systemic vascular resistance increased during infusion of the NO synthase inhibitor L-NAME, and the dosage of catecholamines was reduced. The vasoconstrictive response to L-NAME most likely was the result of blocking the NO system . In addition to the systemic effects of L-NAME, severe pulmonary vasoconstriction was observed with L-NAME.

S-Methylisothiourea sulfate (SMT) is at least 10- to 30-fold more potent as an inhibitor of inducible NOS (iNOS) in immuno-stimulated cultured macrophages (EC50, 6 ,AM) and vascular smooth muscle cells (EC50, 2 ,uM) than NG-methyl-L-arginine (MeArg) or any other NOS inhibitor yet known. The effect of SMT on iNOS activity can be reversed by excess L-arginine in a concentration-dependent manner.  SMT, a potent and selective inhibitor of iNOS, may have considerable value in the therapy of circulatory shock of various etiologies and other pathophysiological conditions associated with induction of iNOS. SMT, or other iNOS-selective inhibitors, are likely to have fewer side effects which are related to the inhibition of eNOS, such as excessive vasoconstriction and organ ischemia), increased platelet and neutrophil adhesion and accumulation, and microvascular leakage.

Administration of the iron (III) complex of diethylenetriamine pentaacetic acid (DTPA iron (III), prevented death in Corynebacterium parvum 1 LPS-treated mice. Using electrochemistry, the binding of NO to DTPA iron (II) is confirmed.  Treatment with DTPA iron (III) resulted in a significant decrease in mortality compared to the untreated controls. The efficacy of DTPA iron (III) increased when given to mice 2 h or more after infection. The best results were observed when DTPA iron (III) was given 5 h after infection.  The iron (III) complex of diethylenetriamine pentaacetic acid (DTPA iron [III]) protected mice and baboons from the lethal effects of an infusion with live LD 100 Escherichia coli. In mice, optimal results were obtained when DTPA iron (III) was administered two or more hours after infection.

PJ34, a novel, potent PARP-1 inhibitor was found to protect against LPS induced tissue damage. PARP inhibitors protected Langendorff-perfused hearts against ischemia-reperfusion induced damages by activating the PI3-kinase–Akt pathway. The importance of the PI3-kinase–Akt pathway in LPS induced inflammatory mechanisms has gained support, raising the question whether this pathway was involved in the effect of PJ34 on LPS-induced septic shock.
Activation of the PI3-kinase–Akt/protein kinase B cytoprotective pathway is likely to contribute to the protective effects of PARP inhibitors in shock and inflammation.

Asymmetrical dimethyl arginine (ADMA) is an endogenous non-selective inhibitor of nitric oxide synthase that may influence the severity of organ failure and the occurrence of shock secondary to an infectious insult. Levels may be genetically determined by a promoter polymorphism in a regulatory gene encoding dimethylarginine dimethylaminohydrolase II (DDAH II).

ADMA levels and Sequential Organ Failure Assessment scores were directly associated on day one (p = 0.0001) and day seven (p = 0.002). The degree of acidaemia and lactaemia was directly correlated with ADMA levels at both time points (p < 0.01). On day seven, IL-6 was directly correlated with ADMA levels (p = 0.006). The variant allele with G at position -449 in the DDAH II gene was associated with increased ADMA concentrations at both time points (p < 0.05).
https://pharmaceuticalintelligence.com/2012/10/20/nitric-oxide-and-sepsis-hemodynamic-collapse-and-the-search-for-therapeutic-options/  larryhbern

Sepsis, Multi-organ Dysfunction Syndrome, and Septic Shock: A Conundrum of Signaling Pathways Cascading Out of Control   larryhbern
https://pharmaceuticalintelligence.com/2012/10/13/sepsis-multi-organ-dysfunction-syndrome-and-septic-shock-a-conundrum-of-signaling-pathways-cascading-out-of-control/

During sepsis, the inflammation triggers widespread coagulation in the bloodstream. A severe form of acute lung injury features pulmonary inflammation and increased capillary leak, is associated with a high mortality rate, and accounts for 100,000 deaths annually in the United States, especially associated with  sepsis. Neutrophils are major effector cells at the frontier of innate immune responses, and they play a critical role in host defense against invading .microorganisms. The tissue injury appears to be related to proteases and toxic reactive oxygen radicals released from activated neutrophils. Excessive procoagulant activity is of pathophysiological significance in these disease settings. This is consistent with a pneumonia or lung injury preceding sepsis. Indeed, it is not surprising that abdominal, cardiac bypass, and post cardiac revascularization may also lead to events resembling sepsis and/or cardiovascular collapse.

The activation of the coagulation cascade is one of the earliest events initiated following tissue injury. The prime function of this complex and highly regulated proteolytic system is to generate insoluble, crosslinked fibrin strands, which bind and stabilize weak platelet hemostatic plugs, formed at sites of tissue injury. The tissue factor-dependent extrinsic pathway is the predominant mechanism by which the coagulation cascade is locally activated. The cellular effects mediated via activation of proteinase-activated receptors (PARs) may be of particular importance. In this regard, studies in PAR1 knockout mice have shown that this receptor plays a major role in orchestrating the interplay between coagulation, inflammation and lung fibrosis.  The systemic inflammatory response syndrome (SIRS) is the massive inflammatory reaction resulting from systemic mediator release that may lead to multiple organ dysfunction.

For signal transduction, 01TREM-1 couples to the ITAM-containing adapter DNAX activation protein of 12 kDa (23DAP12 ). MARV and EBOV activate TREM-1 on human neutrophils, resulting in 12DAP12 phosphorylation, TREM-1 shedding, mobilization of intracellular calcium, secretion of proinflammatory cytokines, and phenotypic changes. TREM-1 is the best-characterized member of a growing family of 12DAP12-associated receptors that regulate the function of myeloid cells in innate and adaptive responses. TREM-1 (triggering receptor expressed on myeloid cells), a recently discovered receptor of the immunoglobulin superfamily, activates neutrophils and monocytes/macrophages by signaling through the adapter protein 12DAP12.

Circulating and organ-specific cell populations are activated to produce proinflammatory mediators during sepsis. Neutrophils and PBMCs bear TLR2 and TLR4, as well as other receptors, such as protein —coupled receptor, that induce increased generation of cytokines and other immunoregulatory proteins, as well as enhance release of proinflammatory mediators, including reactive oxygen species.

The expression of cytokines such as TNF-α and IL-1β is increased in sepsis, and engagement of TNF-α with type I(p55) and type II(p75) TNF receptors or IL-1β with IL-1 receptors belonging to the TLR/IL-1 receptor family produces activation of kinases (including Src, p38, extracellular signal—regulated kinase, and phosphoinositide 3–kinase) and transcriptional factors (such as nuclear factor [NF]–κB) important for further up-regulation of inflammatory proteins.

Identification of patients with cellular phenotypes characterized by increased activation of NF-κB, Akt, and protein 38, as well as discrete patterns of gene activation, may permit identification of patients with sepsis who are likely to have a worse clinical outcome In support of the hypothesis, greater nuclear accumulation of NF-κB is accompanied by higher mortality and worse clinical course in patients with sepsis. Persistent activation of NF-κB was found in nonsurvivors, with surviving patients having lower nuclear concentrations of NF-κB at early time points in their septic course than did nonsurvivors as well as more rapid return of nuclear accumulation of NF-κB. A study of surgical patients without sepsis supports the hypothesis that neutrophil phenotypes defined by NF-κB activation patterns predict clinical outcome. In that clinical series of patients undergoing repair of aortic aneurysms, higher preoperative levels of NF-κB in peripheral neutrophils were associated with death and with the development of postoperative organ dysfunction.

Insulin alleviates degradation of skeletal muscle protein by inhibiting the ubiquitin-proteasome system in septic rats

Qiyi Chen, Ning Li, Weiming Zhu, Weiqin Li, Shaoqiu Tang, et al. Chen et al. Journal of Inflammation 2011, 8:13

http://www.journal-inflammation.com/content/8/1/13

Hypercatabolism is common under septic conditions. Skeletal muscle is the main target organ for hypercatabolism, and this phenomenon is a vital factor in the deterioration of recovery in septic patients. In skeletal muscle, activation of the ubiquitin-proteasome system plays an important role in hypercatabolism under septic status. Insulin is a vital anticatabolic hormone and previous evidence suggests that insulin administration inhibits various steps in the ubiquitin-proteasome system. However, whether insulin can alleviate the degradation of skeletal muscle protein by inhibiting the ubiquitin-proteasome system under septic condition is unclear. This paper confirmed that mRNA and protein levels of the ubiquitin-proteasome system were upregulated and molecular markers of skeletal muscle proteolysis (tyrosine and 3-methylhistidine) simultaneously increased in the skeletal muscle of septic rats. We concluded that the ubiquitin-proteasome system is important skeletal muscle hypercatabolism in septic rats. Infusion of insulin can reverse the detrimental metabolism of skeletal muscle by inhibiting the ubiquitin-proteasome system, and the effect is proportional to the insulin infusion dose.

The International Sepsis Forum’s frontiers in sepsis: high cardiac output should be maintained in severe sepsis

Jean-Louis Vincent
Erasme Hospital, University of Brussels, Brussels, Belgium
Critical Care 2003; 7:276-278 (DOI 10.1186/cc2349)

Despite a usually normal or high cardiac output, severe sepsis is associated with inadequate tissue oxygenation, leading to organ failure and death. Some authors have suggested that raising cardiac output and oxygen delivery to predetermined supranormal values may be associated with improved

survival. While this may be of benefit in certain patients, bringing all patients to similar, supranormal values, is simplistic. It is much preferable to titrate therapy according to the needs of each individual patient. A combination of variables should be used for this purpose, in addition to a careful clinical evaluation, including not only cardiac  output but also the mixed venous oxygen saturation and the blood lactate concentrations. The concept is to assess the adequacy of the cardiac output in patients with severe sepsis, enabling management strategies aimed at optimizing cardiac output to be tailored to the individual patient.

The State of US Health, 1990-2010:  Burden of Diseases, Injuries, and Risk Factors

JAMA Aug 14, 2013, Vol 310, No. 6
US Burden of Disease Collaborators

We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages.  From 1990 to 2010, US life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations. http://jama.jamanetwork.com/article.aspx?articleid=1710486HYPERLINK “http://jama.jamanetwork.com/article.aspx?articleid=1710486&goback=.gde_3267353_member_265629812#%21″&HYPERLINK “http://jama.jamanetwork.com/article.aspx?articleid=1710486&goback=.gde_3267353_member_265629812#%21″goback=%2Egde_3267353_member_265629812#%21

The Evolution of an Inflammatory Response.

Stephen F Lowry
Surgical Infections 09/2009; 10(5):419-25. · 1.80 Impact Factor

An understanding of patient-specific variation and adaptability could direct individualized biologic and management interventions for severe injury and infection. Despite more detailed appreciation of the molecular mechanisms of danger and pathogen recognition and response biology, we have much to learn about the complexity of severe injury and infection. There is a great need to extend our investigation of these mechanisms to experimental and stress-modified clinical scenarios.

Frailty and Heart Disease.

Stephan von Haehling, Stefan D Anker, Wolfram Doehner, John E Morley, Bruno Vellas
Department of Cardiology, Campus Virchow-Klinikum, Berlin, Germany.
Int j cardiol (impact factor: 7.08). 08/2013; DOI:10.1016/j.ijcard.2013.07.068

Frailty is emerging as a syndrome of pre-disability that can identify persons at risk for negative outcomes. Its presence places the individual at risk for rapid deterioration when a major event such as myocardial infarction or hospitalization occurs. In patients with cardiovascular disease, frailty is about three times more prevalent than among elderly persons without.

Pro-atrial natriuretic peptide is a prognostic marker in sepsis, similar to the APACHE II score: an observational study

Nils G Morgenthaler1, Joachim Struck1, Mirjam Christ-Crain2, Andreas Bergmann1 and Beat Müller2

1Research Department, BRAHMS AG, Biotechnology Center, Hennigsdorf/Berlin, Germany

2Department of Internal Medicine, University Hospital, Basel, Switzerland
Critical Care 2005, 9:R37-R45 (DOI 10.1186/cc3015)

This article is online at: http://ccforum.com/content/9/1/R37

Additional biomarkers in sepsis are needed to tackle the challenges of determining prognosis and optimizing selection of high-risk patients for application of therapy. In the present study, conducted in a cohort of medical intensive care unit patients, our aim was to compare the prognostic

value of mid-regional pro-atrial natriuretic peptide (ANP) levels with those of other biomarkers and physiological scores.  Blood samples obtained in a prospective observational study conducted in 101 consecutive critically ill patients admitted to the intensive care unit were analyzed. The prognostic value of pro-ANP levels was compared with that of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and with those of various biomarkers (i.e. C-reactive protein, IL-6 and procalcitonin). Mid-regional pro-ANP was detected in EDTA plasma from all patients using a new sandwich immunoassay.  The median pro-ANP value in the survivors was 194 pmol/l (range 20–2000 pmol/l), which was significantly lower than in the nonsurvivors (median 853.0 pmol/l, range 100–2000 pmol/l; P < 0.001). On the day of admission, pro-ANP levels, but not levels of other biomarkers, were significantly higher in surviving than in nonsurviving sepsis patients (P = 0.001). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the area under the curve (AUC) for pro-ANP was 0.88, which was significantly greater than the AUCs for procalcitonin and C-reactive protein, and similar to the AUC for the APACHE II score.

Bench-to-Bedside Review: Significance and Interpretation of Elevated Troponin in Septic Patients

Raphael Favory1,2 and Remi Neviere1
1Physiology Department, School of Medicine, EA2689 University of Lille, France

2Medical Intensive Care Unit, Universitary Hospital of Lille, France

Critical Care 2006, 10:224 (doi:10.1186/cc4991)  http://ccforum.com/content/10/4/224

Because no bedside method is currently available to evaluate myocardial contractility independent of loading conditions, a biological marker that could detect myocardial dysfunction in the early stage of severe sepsis would be a helpful tool in the management of septic patients. Clinical and experimental studies have reported that plasma cardiac troponin levels are increased in

sepsis and could indicate myocardial dysfunction and poor outcome. The high prevalence of elevated levels of cardiac troponins in sepsis raises the question of what mechanism results in their release into the circulation.
(Note: This study is prior to the hs-troponins)
The presence of microvascular failure and regional wall motion abnormalities, which are frequently observed in positive-troponin patients, also suggest ventricular wall strain and cardiac cell necrosis. Altogether, the available studies

support the contention that cardiac troponin release is a valuable marker of myocardial injury in patients with septic shock.

Myocardial Protection in Sepsis

Simon Shakar and Brian D Lowes
University of Colorado Denver, Aurora, CO 80045, USA
Critical Care 2008, 12:177 (doi:10.1186/cc6978)  http://ccforum.com/content/12/5/177

Sepsis with myocardial dysfunction is seen commonly. Beta-blockers have been used successfully to treat chronic heart failure based on the premise that chronically elevated adrenergic drive is detrimental to the myocardium. However, recent reports on the acute use of beta-blockers in situations with potential hemodynamic compromise have shown the risks associated with this approach.

Myocardial injury and depression are common during sepsis and are likely multi-factorial in etiology. The adrenergic nervous system is activated in sepsis and pharmacological doses of agonists are commonly utilized during goal directed therapy to support oxygen delivery and maintain perfusion pressure. There is a large body of evidence suggesting that excessive adrenergic levels can cause myocardial damage.

Recent large prospective trials would mandate caution when using beta-blockers in acute settings of hemodynamic compromise. The COMMIT trial in acute myocardial infarction showed that metoprolol’s benefit in reducing reinfarction and arrhythmia (10 per 1,000) was offset by an increase in cardiogenic shock (11 per 1,000). This was most prominent in the first day of therapy in elderly patients with tachycardia and low blood pressure, a population reminiscent

of the one discussed in the current series. The POISE trial showed that metoprolol, started 2 to 4 hours before surgery in high risk cardiac patients, led to increased rates of death and stroke. The rates of myocardial infarction were

reduced. Hypotension was very instrumental in causing the adverse events. Interestingly, sepsis and infection were also clearly more common on metoprolol.

Myocardial depression with beta-blockers could explain the need to escalate therapy with vasoactive drugs in the current series. Gore and colleagues showed that esmolol acutely reduced cardiac output by 20% in septic patients. There was also a reduction in blood pressure and oxygen delivery. Kukin

and colleagues studied low dose beta-blockers in chronic heart failure patients. They found that even 6.25 mg of metoprolol, given orally, acutely decreased cardiac output, stroke volume and stroke work index. After 3 months and uptitration to 50 mg bid, the administration of the drug continued to cause a decrease in cardiac output and stroke work index.

Bench-to-Bedside Review: Beta-Adrenergic Modulation in Sepsis

Etienne de Montmollin, Jerome Aboab, Arnaud Mansart and Djillali Annane
Service de Réanimation Polyvalente de l’hôpital Raymond Poincaré,  Garches, France
Critical Care 2009, 13:230 (doi:10.1186/cc8026  http://ccforum.com/content/13/5/230
Sepsis, despite recent therapeutic progress, still carries unacceptably high mortality rates. The adrenergic system, a key modulator of organ function and cardiovascular homeostasis, could be an interesting new therapeutic target for septic shock. beta-adrenergic regulation of the immune function in sepsis is complex and is time dependent. However, beta-2 activation as well as beta-1 blockade seems to downregulate proinflammatory response by modulating the

cytokine production profile. beta-1 blockade improves cardiovascular homeostasis in septic animals, by lowering myocardial oxygen consumption without altering organ perfusion, and perhaps by restoring normal cardiovascular variability. Beta-Blockers could also be of interest in the systemic catabolic response to sepsis, as they oppose epinephrine which is known to promote hyperglycemia, lipid and protein catabolism. Beta-1 blockade may reduce platelet aggregation and normalize the depressed fibrinolytic status induced by adrenergic stimulation. Therefore, beta-2 blockade as well as beta-2 activation improves sepsis-induced immune, cardiovascular and coagulation

dysfunctions. Beta-2 blocking, however, seems beneficial in the metabolic field. Enough evidence has been accumulated in the literature to propose beta-2 adrenergic modulation, beta-1 blockade and beta-2 activation in particular, as new promising therapeutic targets for septic dyshomeostasis, modulating favorably immune, cardiovascular, metabolic and coagulation systems.

Brain Natriuretic Peptide for Prediction of Mortality in Patients with Sepsis: a Systematic Review and Meta-Analysis

Fei Wang1†, Youping Wu1†, Lu Tang2,3†, Weimin Zhu1, Feng Chen1, et al.
Critical Care 2012, 16:R74    http://ccforum.com/content/16/3/R74

The prognostic role of brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) in septic patients remains controversial. The purpose of this systematic review and meta-analysis was to investigate the value of elevated BNP or NT-proBNP in predicting mortality in septic patients.
PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched (up to February 18, 2011). Studies were included if they had prospectively collected data on all-cause mortality in adult septic patients with either plasma BNP or NT-proBNP measurement. 12 studies with a total of 1,865 patients were included.
Elevated natriuretic peptides were significantly associated with increased risk of mortality (odds ratio (OR) 8.65, 95% confidence interval (CI) 4.94 to 15.13, P < 0.00001). The association was consistent for BNP (OR 10.44, 95% CI 4.99 to 21.58, P < 0.00001) and NT-proBNP (OR 6.62, 95% CI 2.68 to 16.34, P < 0.0001). The pooled sensitivity, specificity, positive likelihood ratio, and negative

likelihood ratio were 79% (95% CI 75 to 83), 60% (95% CI 57 to 62), 2.27 (95% CI 1.83 to 2.81) and 0.32 (95% CI 0.22 to 0.46), respectively.

Genetic Variation in Vitamin D Biosynthesis is associated with Increased Risk of Heart Failure

Genetic variation in CYP27B1 is associated with congestive heart failure in patients with hypertension.
RA Wilke, RU Simpson, BN Mukesh, SV Bhupathi, et al.
Pharmacogenomics 2009; 10(11): 1789-1797. http://dx.doi.org/10.2217/pgs.09.101

Genetic variation in vitamin D-dependent signaling is associated with congestive heart failure in human subjects with hypertension. Functional polymorphisms were selected from five candidate genes:

CYP27B1, CYP24A1, VDR, REN and ACE.

Using the Marshfield Clinic Personalized Medicine Research Project,
205 subjects with hypertension and congestive heart failure,
206 subjects with hypertension alone and
206 controls (frequency matched by age and gender) were genotyped.

In the context of hypertension, a SNP in CYP27B1 was associated with congestive heart failure (odds ratio: 2.14 for subjects homozygous for the C allele; 95% CI: 1.05–4.39).

Novel Mechanism for Disease Etiology for the Cardiac Phenotype: Modulation of Nuclear and Cytoskeletal Actin Polymerization.
Lamin A/C and emerin regulate MKL1–SRF activity by modulating actin dynamics

Chin Yee Ho, Diana E. Jaalouk, Maria K. Vartiainen & Jan Lammerding
Nature (2013) doi:10.1038/nature12105  http://www.nature.com/nature/journal/vaop/ncurrent/full/nature121

Laminopathies, caused by mutations in the LMNA gene encoding the nuclear envelope proteins lamins A and C, represent a diverse group of diseases that include Emery–Dreifuss muscular dystrophy (EDMD), dilated cardiomyopathy (DCM), limb-girdle muscular dystrophy, and Hutchison–Gilford progeria syndrome1. Most LMNA mutations affect skeletal and cardiac muscle by mechanisms that remain incompletely understood. Loss of structural function and altered interaction of mutant lamins with (tissue-specific) transcription factors have been proposed to explain the tissue-specific phenotypes.

Altered nucleo-cytoplasmic shuttling of MKL1 was caused by altered actin dynamics in Lmna−/− and Lmna N195K/N195K mutant cells. Ectopic expression of the nuclear envelope protein emerin, which is mislocalized in Lmna mutant cells and also linked to EDMD and DCM, restored MKL1 nuclear translocation and rescued actin dynamics in mutant cells.

These findings present a novel mechanism that could provide insight into the disease aetiology for the cardiac phenotype in many laminopathies, whereby lamin A/C and emerin regulate gene expression through modulation of nuclear and cytoskeletal actin polymerization.

Heart Disease and Stroke Statistics—2011 Update

A Report From the American Heart Association
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Circulation. 2011;123:e18-e209DOI: 10.1161/CIR.0b013e3182009701


● On the basis of 2007 mortality rate data, more than 2200 Americans die of CVD each day, an average of 1 death every 39 seconds. More than 150 000 Americans killed by CVD (I00 –I99) in 2007 were  65 years of age. In 2007,

nearly 33% of deaths due to CVD occurred before the age of 75 years, which is well before the average life expectancy of 77.9 years.

● Coronary heart disease caused  1 of every 6 deaths in the United States in 2007. Coronary heart disease mortality in 2007 was 406 351. Each year, an estimated 785 000 Americans will have a new coronary attack, and  470 000 will have a recurrent attack. It is estimated that an additional 195 000 silent first myocardial infarctions occur each year. Approximately every 25 seconds, an American will have a coronary event, and approximately every minute, someone will die of one.

Prevalence and Control of Traditional Risk Factors Remains an Issue for Many Americans

● Data from the National Health and Nutrition Examination Survey (NHANES) 2005–2008 indicate that 33.5% of US adults 20 years of age have hypertension (Table 7-1). This amounts to an estimated 76 400 000 US adults with hypertension. The prevalence of hypertension is nearly equal between men and women. African American adults have among the highest rates of hypertension in the world, at 44%. Among hypertensive adults, ~ 80% are aware of their condition, 71% are using antihypertensive medication, and only 48% of those aware that they have hypertension have their condition controlled.

● Despite 4 decades of progress, in 2008, among Americans ­­>18 years of age, 23.1% of men and 18.3% of women continued to be cigarette smokers. In 2009, 19.5% of students in grades 9 through 12 reported current tobacco use. The percentage of the nonsmoking population with detectable serum cotinine (indicating exposure to secondhand smoke) was 46.4% in 1999 to 2004, with declines occurring, and was highest for those 4 to 11 years of age (60.5%) and those 12 to 19 years of age (55.4%).

● An estimated 33 600 000 adults > 20 years of age have total serum cholesterol levels > 240 mg/dL, with a prevalence of 15.0% (Table 13-1).

● In 2008, an estimated 18 300 000 Americans had diagnosed diabetes mellitus, representing 8.0% of the adult population. An additional 7 100 000 had undiagnosed diabetes mellitus, and 36.8% had prediabetes, with abnormal

fasting glucose levels. African Americans, Mexican Americans, Hispanic/Latino individuals, and other ethnic minorities bear a strikingly disproportionate burden of diabetes mellitus in the United States (Table 16-1).

Commentary on Other Related Articles on this topic published on this Open Access Online Scientific Journal:

Automated Inferential Diagnosis of SIRS, sepsis, septic shock
https://pharmaceuticalintelligence.com/2012/08/01/automated-inferential-diagnosis-of-sirs-sepsis-septic-shock/  larryhbern

The role of biomarkers in the diagnosis of sepsis and patient management
https://pharmaceuticalintelligence.com/2012/07/28/the-role-of-biomarkers-in-the-diagnosis-of-sepsis-and-patient-management/   larryhbern

The SIRS reaction involves hormonally driven changes in liver glycogen reserves, triggering of  lipolysis, lean body proteolysis, and reprioritization of hepatic protein synthesis. The SIRS reaction unabated leads to a recurring cycle with hemodynamic collapse from septic shock, indistinguishable from cardiogenic shock, and death.
Alternative Designs for the Human Artificial Heart: Patients in Heart Failure –  Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community
https://pharmaceuticalintelligence.com/2013/08/05/alternative-designs-for-the-human-artificial-heart-the-patients-in-heart-failure-outcomes-of-transplant-donorimplantation-artificial-and-monitoring-technologies-for-the-transplantimplant-pat/

LH Bernstein, J Pearlman, A Lev-Ari

Postoperative Results

No injury (2324) Injury (231) P
PRCs 4.5 7.2 6.5 8.9 0.046
ICU stay (h) 102.3 228.6 146.3 346.9 < 0.001
Reoperation 127 5.5% 21 9.1% 0.024
sepsis 86 3.7% 16 6.9% 0.017
stroke 56 2.4% 11 4.8% 0.033
Prolonged
ventilation
505 21.7% 97 42.0% <0.001
Pneumonia 123 5.3% 25 10.8% <0.001
ARDS 32 1.4% 8 3.5% 0.015
Postop RenalFailure 237 10.2% 51 22.1% <0.001
MODS 45 1.9% 13 5.6% <0.001
Hosp Death 151 6.5% 43 18.6 <0.001

Confined Indolamine 2, 3 dioxygenase (IDO) Controls the Hemostasis of Immune Responses for Good and Bad
https://pharmaceuticalintelligence.com/2013/07/31/confined-indolamine-2-3-dehydrogenase-controls-the-hemostasis-of-immune-responses-for-good-and-bad/ Demet Sag

The immune response mechanism is the holy grail of the human defense system for health.   IDO, indolamine 2, 3-dioxygenase, is a key gene for homeostasis of immune responses and producing an enzyme catabolizing the first rate-limiting step in tryptophan degradation metabolism. The hemostasis of immune system is complicated.  IDO belongs to globin gene family to carry oxygen and heme.

The main function and genesis of IDO comes from the immune responses during host-microbial invasion and choice between tolerance and immunogenicity. In addition IDO has a role in vascular tone as well.  In human there are three kinds of IDOs, which are IDO1, IDO2, and TDO, with distinguished mechanisms and expression profiles. , IDO mechanism includes three distinguished pathways: enzymatic acts through IFNgamma, non-enzymatic acts through TGFbeta-IFNalpha/IFNbeta and moonlighting acts through AhR/Kyn.

IDO is a key homeostatic regulator and confined in immune system mechanism for the balance between tolerance and immunity.  This gene encodes indoleamine 2, 3-dioxygenase (IDO) – a heme enzyme (EC=1.13.11.52) that catalyzes the first rate-limiting step in tryptophan catabolism to N-formyl-kynurenine and acts on multiple tryptophan substrates including D-tryptophan, L-tryptophan, 5-hydroxy-tryptophan, tryptamine, and serotonin (1; 2; 3; 4).

Expression of IDO is common in antigen presenting cells (APCs), monocytes (MO), macrophages (MQs), DCs, T-cells, and some B-cells. IDO presentation in APCs is related to its role in the hierarchy and level of DC expression, but includes MOs in three DC cell subsets, CD14+CD25+, CD14++CD25+ and CD14+CD25++.

There are three types of IDO, pro-IDO like, IDO1, and IDO2.  In addition, another enzyme called TDO, tryptophan 2, 3, dehydrogenase solely degrades L-Trp by a rate-limiting mechanism in liver and brain.

The IDO1 mechanism is the target for immunotherapy applications. The initial discovery of IDO in human physiology is protection of pregnancy since lack of IDO results in premature recurrent abortion.   The initial rate-limiting step of tryptophan metabolism is catalyzed by either IDO or tryptophan 2, 3-dioxygenase (TDO), but the two are regulated with different mechanisms due to a His55 in TDO and a Ser167b in IDO.

IDO binds to only immune response cells, and TDO relates to NAD biosynthesis and is expressed solely in liver and brain.  It has been shown that knowledge on NADH/NAD, Kyn/Trp or Trp/Kyn ratios as well as Th1/Th2, CD4/CD8 or Th17/Th_reg are equally important for assessing the metabolic state.

DCs are the orchestrator of the immune response  with list of functions in uptake, processing, and presentation of antigens; activation of effector cells, such as T-cells and NK-cells; and secretion of cytokines and other immune-modulating molecules to direct the immune response.

Systemic inflammation (pneumonia, sepsis, malaria) creates hypotension and IDO expression has the effect of decreased vascular tone.  Moreover, inflammation activates the endothelial coagulation activation system causing coagulopathies on patients.  This reaction is namely endothelial cell activation of IDO by IFNgamma inducing Trp to Kyn conversion. Inflammation induces IDO expression in endothelial cells producing Kyn causing decrease of trp, arterial relaxation, and hypotension.

IDO for Commitment of a Life Time: The Origins and Mechanisms of IDO, indolamine 2, 3-dioxygenase
https://pharmaceuticalintelligence.com/2013/08/04/ido-for-commitment-of-a-life-time-the-origins-and-mechanisms-of-ido-indolamine-2-3-dioxygenase/

IDO, indolamine 2, 3-dioxygenase, is a key gene for homeostasis of immune responses and producing an enzyme catabolizing the first rate-limiting step in tryptophan degradation metabolism.

The mechanism of microbial response and origination of IDO is based on duplication of microbial IDO .  During microbial responses, Toll-like receptors (TLRs) play a role to differentiate and determine the microbial structures as a ligand to initiate production of cytokines and pro-inflammatory agents to activate specific T helper cells. Uniqueness of TLR comes from four major characteristics of each individual TLR by ligand specificity, signal transduction pathways, expression profiles and cellular localization . Thus, TLRs are important part of the immune response signaling mechanism to initiate and design adoptive responses from innate (naïve) immune system to defend the host.

The modification of IDO+ monocytes manage towards a specific subset of T cell activation with specific TLRs are significantly important.  The type of cell with correct TLR and stimuli improves or decreases the effectiveness of stimuli. .

3D Cardiovascular Theater – Hybrid Cath Lab/OR Suite, Hybrid Surgery, Complications Post PCI and Repeat Sternotomy/  A Lev-Ari
https://pharmaceuticalintelligence.com/2013/07/19/3d-cardiovascular-theater-hybrid-cath-labor-suite-hybrid-surgery-complications-post-pci-and-repeat-sternotomy/

Treatment options for LV failure, temporary circulatory support, IABP, impella recover.
https://pharmaceuticalintelligence.com/2013/07/17/treatment-options-for-left-ventricular-failure-temporary-circulatory-support-intra-aortic-balloon-pump-iabp-impella-recover-ldlp-5-0-and-2-5-pump-catheters-non-surgical-vs-bridge-therapy/  larryhbern

Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care/ A Lev-Ari
https://pharmaceuticalintelligence.com/2013/06/03/clinical-indications-for-use-of-inhaled-nitric-oxide-ino-in-the-adult-patient-market-clinical-outcomes-after-use-therapy-demand-and-cost-of-care/

Inhaled nitric oxide is a selective pulmonary vasodilator that improves ventilation–perfusion matching at low doses in patients with acute respiratory failure, potentially improving oxygenation and lowering pulmonary vascular resistance.

Treatment Goals for Inhaled Nitric Oxide

  • Improved oxygenation
  • Decreased pulmonary vascular resistance
  • Decreased pulmonary edema
  • Reduction or prevention of inflammation
  • Protection against infection

Dose-Response for Respiratory Failure in the Adult Patient – a response is defined as a 20 percent increase in oxygenation.
Dose-Response for Pulmonary Hypertension in the Adult Patient – a 30 percent decrease in pulmonary vascular resistance during the inhalation of nitric oxide (10 ppm for 10 minutes) has been used to identify an association with vascular responsiveness to agents that can be helpful in the long term.

Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems
https://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems-2/  JPearlman, LH Bernstein, A lev-Ari

among older Americans, more are hospitalized for HF than for any other medical condition.

Prevalence estimates for HF were determined from 1999–2008 National Health and Nutrition Examination Survey (NHANES) and US Census Bureau projected population counts for years 2012 to 2030. HF is a clinical syndrome that results from a variety of cardiac disorders.

In the Western world the top 3 causes of HF are:

  • coronary artery disease
  • valvular disease
  • hypertension

Stages C and D represent the symptomatic phases of HF, with stage C manageable and stage D failing medical management, resulting in marked symptoms at rest or with minimal activity despite optimal medical therapy.

Classic demographic risk factors for the development of HF include:

  • older age,
  • male gender,
  • ethnicity, and
  • low socioeconomic status.
  • comorbid disease states contribute to the development of HF
  • Ischemic heart disease
  • Hypertension

Diabetes mellitus, insulin resistance, and obesity are also linked to HF development,
with diabetes mellitus increasing the risk of HF by +2-fold in men and up to 5-fold in women.
Smoking remains the single largest preventable cause of disease and premature death in the United States.

Hypertension caused by Arterial Stiffening is Ineffectively Treated by Diuretics and Vasodilatation Antihypertensives
Dr Reuven Zimlichman (Tel Aviv University, Israel)
http://www.theheart.org/article/1502067.do
the definitions of hypertension, as well as the risk-factor tables used to guide treatment, are no longer appropriate for a growing number of patients. New ambulatory blood-pressure-monitoring devices also measure arterial elasticity. “Unquestionably, these will improve our ability to diagnose both the status of the arteries and the changes of the arteries with time as a result of our treatment. So if we treat the patient and we see no improvement in arterial elasticity, something is not working—either the patient is not taking the medication, or our choice of medication is not appropriate, or the dose is insufficient, etc.”

Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus
https://pharmaceuticalintelligence.com/2013/05/11/arterial-elasticity-in-quest-for-a-drug-stabilizer-isolated-systolic-hypertension-caused-by-arterial-stiffening-ineffectively-treated-by-vasodilatation-antihypertensives/   J Pearlman & A Lev-Ari

Conceptual development of the subject is presented in the following nine parts:
1.            Physiology of Circulation and Role of Arterial Elasticity
2.            Isolated Systolic Hypertension caused by Arterial Stiffening may be inadequately treated by Diuretics or Vasodilatation Antihypertensive Medications
3.            Physiology of Circulation and Compensatory Mechanism of Arterial Elasticity
4.            Vascular Compliance – The Potential for Novel Therapies Novel Mechanism for Disease Etiology: Modulation of Nuclear and Cytoskeletal Actin Polymerization. Genetic Therapy targeting Vascular Conductivity, Regenerative Medicine for Vasculature Protection
5.            In addition to curtailing high pressures, stabilizing BP variability is a potential target for management of hypertension
6.            Mathematical Modeling: Arterial stiffening explains much of primary hypertension
7.            Classification of Blood Pressure and Hypertensive Treatment Best Practice of Care in US
8.            Genetic Risk for High Blood Pressure
9.            Is it Hypertension or Physical Inactivity: Cardiovascular Risk and Mortality – New results in 3/2013.

Elastance in a cyclic pressure system of systole-diastole (contraction-dilation) presents impedance as a pulsatile load on the heart. Chronic exposure to elevated vascular impedance leads to impairment of lusiotropy (diastolic failure, stiff heart) and inotropy (systolic failure, weak heart).

Stiff or “lead pipe” blood vessels drop pressure precipitously to dangerously low levels in response to diuretics.
Stiff walls due to fibrosis or scar tissue have limited ability to dilate

Physiology of Circulation and Compensatory Mechanism of Arterial Elasticity

Arguably, HMG-CoA reductase inhibitors,  statin therapy is a second example of a medication that helps protect vascular elasticity, both by its lipid effects and its anti-inflammatory effects.

https://pharmaceuticalintelligence.com/2012/11/28/special-considerations-in-blood-lipoproteins-viscosity-assessment-and-treatment/

https://pharmaceuticalintelligence.com/2012/11/28/what-is-the-role-of-plasma-viscosity-in-hemostasis-and-vascular-disease-risk/

While among other reasons for Hypertension increasing prevalence with aging, arterial stiffening is one.

Yet, stiffer vessels are more efficient at transmitting pressure to distal targets. With aging, muscle mass diminishes markedly and the contribution to circulation from skeletal muscle tissue compressions combined with competent venous valves fades.

https://pharmaceuticalintelligence.com/2012/08/27/endothelial-dysfunction-diminished-availability-of-cepcs-increasing-cvd-risk-for-macrovascular-disease-therapeutic-potential-of-cepcs/

https://pharmaceuticalintelligence.com/2012/10/19/clinical-trials-results-for-endothelin-system-pathophysiological-role-in-chronic-heart-failure-acute-coronary-syndromes-and-mi-marker-of-disease-severity-or-genetic-determination/

https://pharmaceuticalintelligence.com/2012/11/13/peroxisome-proliferator-activated-receptor-ppar-gamma-receptors-activation-pparγ-transrepression-for-angiogenesis-in-cardiovascular-disease-and-pparγ-transactivation-for-treatment-of-dia/

With aging heart contractility diminishes. These issues can cause under perfusion of tissues, inadequate nutrient blood delivery (ischemia), lactic acidosis, tissue dysfunction and multi-organ failure. Hardened arteries may compensate. Thus, pharmacotherapy to increase Arterial Elasticity may be counter-indicated for patients with mild to progressive CHF.

https://pharmaceuticalintelligence.com/2013/05/05/bioengineering-of-vascular-and-tissue-models/

https://pharmaceuticalintelligence.com/2012/10/20/nitric-oxide-and-sepsis-hemodynamic-collapse-and-the-search-for-therapeutic-options/

https://pharmaceuticalintelligence.com/2012/10/17/chronic-heart-failure-personalized-medicine-two-gene-test-predicts-response-to-beta-blocker-bucindolol/

https://pharmaceuticalintelligence.com/2013/04/28/genetics-of-conduction-disease-atrioventricular-av-conduction-disease-block-gene-mutations-transcription-excitability-and-energy-homeostasis/

https://pharmaceuticalintelligence.com/2013/04/14/mitochondrial-metabolism-and-cardiac-function/

https://pharmaceuticalintelligence.com/2012/10/28/mitochondrial-damage-and-repair-under-oxidative-stress/

The hypothesis that we should focus on cellular therapies to increase vascular compliance may decrease the circulation efficiency and result in worsening of cardiac right ventricular morphology and development of Dilated cardiomyopathy and hypertrophic cardiomyopathy (muscle thickening and diastolic failure), an undesirable outcome resulting from an attempt to treat the hypertension.

https://pharmaceuticalintelligence.com/2012/10/01/ngs-cardiovascular-diagnostics-long-qt-genes-sequenced-a-potential-replacement-for-molecular-pathology/

https://pharmaceuticalintelligence.com/2012/08/29/positioning-a-therapeutic-concept-for-endogenous-augmentation-of-cepcs-therapeutic-indications-for-macrovascular-disease-coronary-cerebrovascular-and-peripheral/

https://pharmaceuticalintelligence.com/2012/08/28/cardiovascular-outcomes-function-of-circulating-endothelial-progenitor-cells-cepcs-exploring-pharmaco-therapy-targeted-at-endogenous-augmentation-of-cepcs/

https://pharmaceuticalintelligence.com/2013/02/28/the-heart-vasculature-protection-a-concept-based-pharmacological-therapy-including-thymosin/

Mitochondrial Dysfunction and Cardiac Disorders   larryhbern
https://pharmaceuticalintelligence.com/2013/04/14/mitochondrial-dysfunction-and-cardiac-disorders/

Mitochondria and Cardiovascular Disease: A Tribute to Richard Bing, Larry H Bernstein, MD, FACP https://pharmaceuticalintelligence.com/2013/04/14/chapter-5-mitochondria-and-cardiovascular-disease/

Mitochondrial Metabolism and Cardiac Function, Larry H Bernstein, MD, FACP https://pharmaceuticalintelligence.com/2013/04/14/mitochondrial-metabolism-and-cardiac-function/

Reversal of Cardiac mitochondrial dysfunction, Larry H Bernstein, MD, FACP https://pharmaceuticalintelligence.com/2013/04/14/reversal-of-cardiac-mitochondrial-dysfunction/

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Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

Author, Introduction and Summary: Justin D Pearlman, MD, PhD, FACC

and

Article Curator: Aviva Lev-Ari, PhD, RN

The Curator recommends the e-Reader to read the following book on Surgical Complications:

Complications
“Essential Reading For Anyone Involved In Medicine”–Amazon.com –  2002

Cardiovascular Complications:

I. Reoperative Sternotomy after prior CABG, MVR, AVR, or radiation therapy

IIa. PCI, and

IIb. PAD Endovascular Interventions: Carotid Artery Endarterectomy

III. Incidence of Sepsis (circulation infection with serious consequences)

UPDATED 11/2/2013

As minimally interventional techniques improve, patients are offered a choice of invasive surgical remedies or less invasive procedures (video assisted, robotic, or percutaneous). The decision should not rest on the size of the scar or even the up front risk and discomfort, but rather should weigh all aspects of the risks and benefits. In addition to the risks and benefits for the current problem, one should also consider why the problem occurred and its likelihood of recurrence. Open chest surgery has a clear disadvantage when it comes to recurrences, as the scars from first surgery interfere with second surgery. Opening the chest (sternotomy) for a second or third time poses elevated risks analyzed herein. This article reviews data from major centers addressing the risks from repeat sternotomy and from minimally invasive cardiovascular surgeries. Any invasion of the body elevates risk of infection, which can lead to sepsis and possible death, so that risk is also addressed.

I. Risk of Injury During Repeat Sternotomy for CABG or Aortic Valve Replacement, Open Heart Surgery

II. Complications After Percutaneous Coronary intervention (PCI) and endovascular surgery for Peripheral Artery Disease (PAD)

  • (a) Post PCIand 
  • (b) PAD Endovascular Interventions: Carotid Artery Endarterectomy

III. Cardiac Failure During Systemic Sepsis

This article addresses specific reports of complications but does not cover numerous other complications that may occur, such as lung collapse, cardiogenic shock, blood loss, local infection, emboli, thrombus, stroke.

I. Risk of Injury During Open Heart Surgery after prior Coronary Artery Bypass Grafting (CABG), Aortic Valve Replacement, Mitral Valve Replacement, or Radiation Therapy 

Conclusions of a Study conducted @Mayo Clinic on Reoperative (Repeat) Sternotomy (opening of the chest through the sternum):

Chan B. Park, MD,a,b Rakesh M. Suri, MD,a Harold M. Burkhart, MD,a Kevin L. Greason, MD,a

Joseph A. Dearani, MD,a Hartzell V. Schaff, MD,a and Thoralf M. Sundt III, MDa

Identifying patients at particular risk of injury during repeat sternotomy: Analysis of 2555 cardiac reoperations

Authors Affiliations: From the Division of Cardiovascular Surgery,

a Mayo Clinic, Rochester, Minn; and the Department of Thoracic and Cardiovascular Surgery,

b St. Paul’s Hospital, The Catholic University of Korea, Seoul, Korea.

Disclosures: None.

Read at the 90th Annual Meeting of The American Association for Thoracic Surgery, Toronto, Ontario, Canada, May 1–5, 2010. Received for publication April 6, 2010; revisions received July 19, 2010; accepted for publication July 30, 2010.

doi:10.1016/j.jtcvs.2010.07.086

Particular attention to protective strategies should be considered during reoperative sternotomy among patients with multiple previous sternotomies, previous mediastinal radiotherapy, and those with patent internal thoracic artery grafts. (J Thorac Cardiovasc Surg 2010;140:1028-35)

Of the 2555 patients,

  • 1537 (60%) had undergone previous coronary artery bypass grafting,
  • 700 (27%) previous mitral valve surgery, and
  • 643 (25%) previous aortic valve replacement (AVR).
  • 61 (2%) had prior mediastinal radiotherapy, and
  • 424 (17%) had more than one previous sternotomy.

 Injury Analysis – 9% events in 231 Patient in the study

In 231 patients, 267 injuries (9.0%) occurred.

Injury occurred

  • during sternotomy in 87 patients (33%) and
  • during prepump dissection in 135 (51%).

Hospital mortality rate was

6.5% among those without injury and

18.5% among those with injury (P < .001);

25% when injury occurred during sternal division

Injuries were more common

1. after previous coronary artery bypass grafting

  • 11% with previous coronary artery bypass grafting vs
  • 7% without, (P = .0012)

but not

  • previous aortic valve surgery,
  • previous mitral valve surgery, or
  • previous aorta surgery.

2.  Injury was also more common when the current operation was aortic valve replacement (AVR)

  • 10% with AVR vs
  • 8% without, (P = .04) or

3.  aorta surgery

  • 14% vs
  • 8% (P = .004).

Predicted injury by multivariate analysis –

Injury was an independent risk factor of hospital death (odds ratio, 2.6).

4.   previous radiotherapy (odds ratio, 4.9)

5.  a greater number of previous sternotomies (odds ratio 1.7), and

6.  a patent internal thoracic artery (odds ratio, 1.8)

J Thorac Cardiovasc Surg. 2010 Nov;140(5):1028-35. doi: 10.1016/j.jtcvs.2010.07.086.

Identifying patients at particular risk of injury during repeat sternotomy: analysis of 2555 cardiac reoperations.

Source

Division of Cardiovascular Surgery, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

OBJECTIVES:

A variety of protective strategies during repeat sternotomy been proposed; however, it remains unclear for which patients they are warranted.

METHODS:

We identified adults undergoing repeat median sternotomy for routine cardiac surgery at our institution between January 1, 1996, and December 31, 2007. The operative notes and perioperative outcomes were reviewed.

RESULTS:

Of the 2555 patients, 1537 (60%) had undergone previous coronary artery bypass grafting, 700 (27%) previous mitral valve surgery, and 643 (25%) previous aortic valve replacement (AVR). Sixty-one patients (2%) had prior mediastinal radiotherapy, and 424 (17%) had more than one previous sternotomy. In 231 patients, 267 injuries (9.0%) occurred. Injury occurred during sternotomy in 87 patients (33%) and during prepump dissection in 135 (51%). The hospital mortality rate was 6.5% among those without injury and 18.5% among those with injury (P < .001); when injury occurred during sternal division, the mortality rate was 25%. Injuries were more common after previous coronary artery bypass grafting (11% with previous coronary artery bypass grafting vs 7% without, P = .0012) but not previous AVR, mitral valve surgery, or aortic surgery. Injury was also more common when the current operation was AVR (10% with AVR vs 8% without, P = .04) or aortic surgery (14% vs 8%, P = .004). On multivariate analysis, previous radiotherapy (odds ratio, 4.9), a greater number of previous sternotomies (odds ratio 1.7), and a patent internal thoracic artery (odds ratio, 1.8) predicted injury. Injury was an independent risk factor of hospital death (odds ratio, 2.6).

CONCLUSIONS:

Particular attention to protective strategies should be considered during reoperative sternotomy among patients with multiple previous sternotomies, previous mediastinal radiotherapy, and those with patent internal thoracic artery grafts.

Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Comment in

TABLE 2. Hospital mortality according to Timing of Injury

Timing Mortality rate with injury P value

  • Re-entry 19/76 (25.0%) <.001
  • Prepump 20/121 (16.5%) <.001
  • Cardiopulmonary bypass (CPB)  3/14 (21.4%) .05
  • Aortic CrossClamp (ACC 1/11) (9.1%) .85
  • Closing 5/17 (29.4%) <.001

TABLE 1. Preoperative patient characteristics

Characteristic No injury (n 1/4 2324) Injury (n 1/4 231) P value

Age (y) 66.9  12.4 67.7  11.5 .509

Men 1583 (68.1%) 167 (72.3%) .192

Diabetes mellitus 499 (21.5%) 61 (26.4%) .084

Hypertension 1536 (66.2%) 158 (68.4%) .490

Hypercholesterolemia 1656 (71.4%) 171 (74.0%) .395

Myocardial infarction 633 (27.3%) 68 (29.4%) .480

Congestive heart failure 758 (32.6%) 89 (38.5%) .069

NYHA .064

I-II 492 (21.2%) 37 (16.0%)

III-IV 1830 (78.8%) 184 (84.0%)

Previous operation No injury (n 1/4 2324) Injury (n 1/4 231) P value

CABG 1375 (59.2%) 162 (70.1%) .001

Aortic valve surgery 586 (25.2%) 57 (24.7%) .857

Mitral valve surgery 645 (27.8%) 55 (23.8%) .200

Tricuspid valve surgery 64 (2.8%) 9 (3.9%) .320

Aorta surgery 167 (7.2%) 20 (8.7%) .413

Current operation No injury (n 1/4 2324) Injury (n 1/4 231) P value

CABG 897 (38.6%) 104 (45.0%) .056

Aortic valve surgery 1020 (43.9%) 118 (51.1%) .036

Mitral valve surgery 821 (35.3%) 80 (34.6%) .833

Tricuspid valve surgery 414 (17.8%) 52 (22.5%) .078

Aortic surgery 232 (10.0%) 37 (16.0%) .004

DISCUSSION

The results of the present study have confirmed the significant risk of cardiovascular injury during reoperative cardiac surgery. The death rate from such injury can be 10-30%, particularly  when occurring during division of the sternum. These risks are greatest among patients with multiple previous sternotomies or prior chest radiotherapy.

Current PROTOCOL at Virginia University, now suggested to be considered for adoption @Mayo Clinic:

The Mayo Clinic’s Authors write: Our findings are more consistent with those reported by Roselli and colleagues.2 The explanation of these institutional differences is unclear, although a number of practice differences are likely present between these institutions in terms of both patient substrate and surgical practice. Compared with the series from the University of Virginia, the Mayo series we have reported represents a greater percentage of total cases performed at the institution (13.5% vs 7.8%), with a somewhat greater percentage of those reoperations being for CABG (41% vs 60%). In the Mayo series, a lower percentage were first-time repeat sternotomies (83% vs 90%) and a greater percentage were the fourth time or more (2.7% vs 1.1%).

The incidence of previous radiotherapy in the University of Virginia series was not reported.

It is also unclear to what degree the differences in surgical practice, including the role of the assistant surgeons in performing the repeat sternotomy, could account for these differences. In the present retrospective study, we were unable to demonstrate an effect of experience or expertise in either the occurrence of injury or the outcome. However, it is clear to all practicing surgeons that, when injury occurs, the judgment and expertise of the operating surgeon is critical to expeditious institution of CPB or other ‘‘rescue’’ maneuvers.

Perhaps of more practical value and broad applicability, however, is the standardized approach to repeat sternotomy advocated by the group at the University of Virginia, including routine preoperative CT scanning if the procedure is the third or fourth sternotomy and insertion of a femoral arterial line by which emergent percutaneous arterial inflow cannulation can be accomplished, if necessary. In their series, emergent institution of CPB using the femoral route was instituted in 1.8% of reoperative patients, constituting 19% of the patients with injury. Most notably, in their series, no deaths occurred among these patients. Serious consideration should be given to adopting such protocols.

Our high mortality rate associated with SVG injury during sternotomy, however, supports the  recommendation by others to carefully assess the course of bypass grafts by preoperative angiography. Routine preoperative CT imaging of all patients with more than one previous sternotomy has been advocated by Morishita and colleagues,3 with a demonstrable reduction in operative complications. Roselli and colleagues2 identified a lack of preparative imaging as the most common ‘‘lapse’’ in the preventive strategy among patients with injury. Our data suggest that CT scanning might be particularly helpful in the subset of patients with multiple previous sternotomies or radiotherapy and would support the institution of a policy of routine scanning for these patients.

FIGURE 1. Hospital mortality according to emergent cardiopulmonary bypass (CPB) in The Journal of Thoracic and Cardiovascular Surgery c November 2010, pp. 1032

TABLE 5. Postoperative results

No injury (n 1/4 2324) —  Injury (n 1/4 231) — P value

Postoperative transfusion (U)

PRCs 4.5  7.2 6.5  8.9 .046

ICU stay (h) 102.3  228.6 146.3 +/- 346.9 <.001

Reoperation for bleeding 127 (5.5%) 21 (9.1%) .024

Sepsis 86 (3.7%) 16 (6.9%) .017

Stroke 56 (2.4%) 11 (4.8%) .033

Prolonged ventilation 505 (21.7%) 97 (42.0%) <.001

Pneumonia 123 (5.3%) 25 (10.8%) <.001

ARDS 32 (1.4%) 8 (3.5%) .015

Postoperative renal failure 237 (10.2%) 51 (22.1%) <.001

Multisystem failure 45 (1.9%) 13 (5.6%) <.001

Perioperative MI 9 (0.4%) 2 (0.9%) .289

Hospital death 151 (6.5%) 43 (18.6%) <.001

Abbreviations:

IABP, intra-aortic balloon pump; ICU, intensive care unit; ARDS, acute respiratory

distress syndrome; MI, myocardial infarction.

SOURCE
The Journal of Thoracic and Cardiovascular Surgery c November 2010, pp. 1032

Independent predictors for injury during repeat median sternotomy

The structures injured and the timing of injury in our study were similar to those reported by Roselli and colleagues.2  Bypass grafts were the most commonly injured and, perhaps in contrast to expectations, most injuries occurred during dissection, not during sternal division. Unlike their study, however, we found injury during sternal division to carry a greater mortality risk. We observed a remarkably high mortality rate associated with injury to the right ventricle, as did Roselli and colleagues.2  This may be particularly true in the presence of pulmonary hypertension, when attempts to repair the injury are hampered by inadequate access, progressive tearing of the ventricle secondary to traction injury, and what can be a relatively thin and friable free wall. The incidence of injury to the Internal thoracic artery (ITA) in our series (4.9%) was comparable to the 4.4%–5.3% reported by other investigators.11-14 Because the ITA was damaged more often during prepump dissection (20.7%) than during re-entry (11.5%), these data support the trend to avoid dissecting and isolating the ITA during AVR after previous CABG.12,13

FOUR CONCLUSIONS

1. On the basis of these data, we would advocate preoperative axial CT imaging to define the proximity of cardiovascular structures to the sternum of patients who have undergone more than one previous sternotomy and those who have undergone radiotherapy because these patients statistically have the greatest risk of injury.

2. We would also advocate considering percutaneous or open access of the femoral vessels, if not the institution of CPB, before sternotomy in these same patients, as well as those with significant pulmonary hypertension.

3. Because injury is common during prepump dissection, we support a philosophy of leaving patent ITA grafts undisturbed by attempts to gain control during AVR after previous CABG.

4. Finally, given the mortality rate associated with graft injury, patients with previous CABG should be considered for graft angiography or high-resolution CT.

Summary 

This is a very important study  on the Outcomes and the Complications involved in Cardiac Surgery @Mayo Clinic.

Study’s Objectives: A variety of protective strategies during repeat sternotomy been proposed; however, it remains unclear for which patients they are warranted.

Authors @Mayo Clinic reported:

We were unable to definitively assess the effect of any specific protective strategies on the incidence of injury. Because we do not have standardized or uniform prospective institutional policies in this regard, it was not possible to account for the confounding factor of the clinician’s judgment in the decision to use these strategies in particularly highrisk patients.

Our high mortality rate associated with saphenous vein graft (SVG) injury during sternotomy, however, supports the  recommendation by others to carefully assess the course of bypass grafts by preoperative angiography. Routine preoperative CT imaging of all patients with more than one previous sternotomy has been advocated by Morishita and colleagues,3 with a demonstrable reduction in operative complications.

The reader is advised to review another article Co-Curated by us on the following related study by Mayo Clinic researches, This article examines 10-year to 15-year survivals from arterial bypass grafts using arterial vs saphenous venous grafts.

CABG Survival in Multivessel Disease Patients: Comparison of Arterial Bypass Grafts vs Saphenous Venous Grafts

The conclusions in this article are:

In patients undergoing isolated coronary artery bypass graft surgery with LIMA to left anterior descending artery,

  • arterial grafting of the non-left anterior descending vessels conferred a survival advantage at 15 years compared with Saphenous Venous grafting (SVG).

It is still unproven whether these results apply to higher-risk subgroups of patients.

Related study

Coronary Artery Disease – Medical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents,

REFERENCES

1. Sabik JF III, Blackstone EH, Houghtaling PL,Walts PA, LytleBW. Is reoperation

still a risk factor in coronary artery bypass surgery? Ann Thorac Surg. 2005;80:

1719-27.

2. Roselli EE, Pettersson GB, Blackstone EH, Brizzio ME, Houghtaling PL,

Lauck R, et al. Adverse events during reoperative cardiac surgery: Frequency,

characterization, and rescue. J Thorac Cardiovasc Surg. 2008;135:316-23.

3. Morishita K, Kawaharada N, Fukada J, Yamada A, Masaru T, Kuwaki K, et al.

Three or more median sternotomies for patients with valve disease: Role of computed

tomography. Ann Thorac Surg. 2003;75:1476-81.

4. Luciani N, Anselmi A, De Geest R, Martinelli L, Perisano M, Possati G. Extracorporeal

circulation by peripheral cannulation before redo sternotomy: Indications

and results. J Thorac Cardiovasc Surg. 2008;136:572-7.

5. Potter DD, Sundt TM III, Zehr KJ, Dearani JA, Daly RC, Mullany CJ, et al. Risk

of repeat mitral valve replacement for failed mitral valve prostheses. Ann Thorac

Surg. 2004;78:67-72.

6. Potter DD, Sundt TM III, Zehr KJ, Dearani JA, Daly RC, Mullany CJ, et al. Operative

risk of reoperative aortic valve replacement. J Thorac Cardiovasc Surg.

2005;129:94-103.

7. Sundt TM III, Murphy SF, Barzilai B, Schuessler RB, Mendeloff EN,

Huddleston CB, et al. Previous coronary artery bypass grafting is not a risk factor

for aortic valve replacement. Ann Thorac Surg. 1997;64:651-7.

8. Ellman PI, Smith RL, Girotti ME, Thompson PW, Peeler BB, Kern JA, et al. Cardiac

injury during resternotomy does not affect perioperative mortality. JAm Coll

Surg. 2008;206:993-9.

9. Chang ASY, Smedira NG, Chang CL, Benavides MM, Myhre U, Feng J, et al.

Cardiac surgery after mediastinal radiation: Extent of exposure influences outcome.

J Thorac Cardiovasc Surg. 2007;133:404-13.

10. Schmuziger M, Christenson JT, Maurice J, Mosimann E, Simonet F, Velebit V.

Reoperative myocardial revascularization: An analysis of 458 reoperations and

2645 single operations. Cardiovasc Surg. 1994;2:623-9.

11. Gillinov AM, Casselman FP, Lytle BW, Blackstone EH, Parsons EM, Loop FD,

et al. Injury to a patent left internal thoracic artery graft at coronary reoperation.

Ann Thorac Surg. 1999;67:382-6.

12. Byrne JG, Karavas AN, Filsoufi F, Mihaljevic T, Aklog L, Adams DH, et al. Aortic

valve surgery after previous coronary artery bypass grafting with functioning

internal mammary artery grafts. Ann Thorac Surg. 2002;73:779-84.

13. Smith RL, Ellman PI, Thompson PW, Girotti ME, Mettler BA, Ailawadi G, et al.

Do you need to clamp a patent left internal thoracic artery—Left anterior descending

graft in reoperative cardiac surgery? Ann Thorac Surg. 2009;87:742-7.

14. Coltharp WH, Decker MD, Lea JWIV, Petracek MR, Glassford DM,

Thormas CS, et al. Internal mammary artery graft at reoperation: Risks, benefits,

and methods of preservation. Ann Thorac Surg. 1991;52:225-9.

15. O’Brien MF, Harrocks S, Clarke A, Garlick B, Barnett AG. How to do safe sternal

reentry and the risk factors of redo cardiac surgery: A 21-year review with

zero major cardiac injury. J Cardiac Surg. 2002;17:4-13.

16. Klein G. Naturalistic decision making. Human Factors. 2008;50:456-60.

II. Complications After Percutaneous Coronary intervention (PCI) and endovascular surgery for Peripheral Artery Disease (PAD)

(a) after prior PCI, and

(b) after prior PAD Endovascular Interventions: Carotid Artery Endarterectomy

II(a)  PCI  After Prior PCI – Major occurring Complications include the following:

 

  • Hematoma (a firm collection of blood greater than 2 cm around or in the proximity of the access site).
  • Pseudoaneurysm / dissection,
  • A-V fistula and ischemic leg were also considered along with
  • Retroperitoneal bleed. Retroperitoneal bleeding was defined by any amount of bleeding in the retroperitoneum diagnosed by computer tomography.
  • Inflammation of the Lower extremity on the side of the access site to the femoral artery

UPDATED 11/2/2013

VIEW VIDEO

Impact of Intra-procedural Stent Thrombosis during Percutaneous Coronary Intervention: Insights from the CHAMPION PHOENIX Trial ONLINE FIRST

Philippe Généreux, MD1; Gregg W. Stone, MD1; Robert A. Harrington, MD4; C. Michael Gibson, MD5; Ph. Gabriel Steg, MD6; Sorin J. Brener, MD10; Dominick J. Angiolillo, MD, PhD11; Matthew J. Price, MD12; Jayne Prats, PhD13; Laura LaSalle, MPH2; Tiepu Liu, MD, PhD12; Meredith Todd, B.Sc12; Simona Skerjanec, Pharm.D12; Christian W. Hamm, MD14; Kenneth W. Mahaffey, MD4; Harvey D. White, DSc15; Deepak L. Bhatt, MD, MPH16
J Am Coll Cardiol. 2013;():. doi:10.1016/j.jacc.2013.10.022

Abstract

Objective  We sought to evaluate the clinical impact of intra-procedural stent thrombosis (IPST), a relatively new endpoint.

Background  In the prospective, double-blind, active-controlled CHAMPION PHOENIX trial, cangrelor significantly reduced periprocedural and 30-day ischemic events in patients undergoing percutaneous coronary intervention (PCI), including IPST.

Methods  An independent core laboratory blinded to treatment assignment performed a frame-by-frame angiographic analysis in 10,939 patients for the development of IPST, defined as new or worsening thrombus related to stent deployment anytime during the procedure. Adverse events were adjudicated by an independent, blinded clinical events committee.

Results  IPST developed in 89 patients (0.8%), including 35/5470 (0.6%) and 54/5469 (1.0%) in the cangrelor and clopidogrel arms, respectively (OR [95%CI] = 0.65 [0.42,0.99], p=0.04). Compared to patients without IPST, IPST was associated with a marked increase in composite ischemia (death, myocardial infarction [MI], ischemia-driven revascularization, or new onset out-of-lab stent thrombosis [ARC]) at 48 hours and at 30 days (29.2% vs. 4.5% and 31.5% vs. 5.7%, P<0.0001 for both). After controlling for potential confounders, IPST remained a strong predictor of all adverse ischemic events at both time points.

Conclusion  In the large-scale CHAMPION PHOENIX trial, the occurrence of IPST was strongly predictive of subsequent adverse cardiovascular events. The potent intravenous ADP antagonist cangrelor substantially reduced IPST, contributing to its beneficial effects at 48 hours and 30 days.

Clinical trial info  CHAMPION PHOENIX; NCT01156571

Bleeding and Vascular Complications at the Femoral Access Site Following Percutaneous Coronary Intervention (PCI): An Evaluation of Hemostasis Strategies

Author(s):

Dale R. Tavris, MD, MPH1, Yongfei Wang, MS2, Samantha Jacobs, BS1, Beverly Gallauresi, MPH, RN1, Jeptha Curtis, MD2, John Messenger, MD3, Frederic S. Resnic, MD, MSc4, Susan Fitzgerald, MS, RN5

Authors Affiliation

From the 1US Food and Drug Administration (FDA), Silver Spring, Maryland, 2Yale University, New Haven, Connecticut, 3University of Colorado, Boulder, Colorado, 4Brigham and Women’s Hospital, Boston, Massachusetts, and 5the American College of Cardiology, Bethesda, Maryland.

Abstract: Background. Previous research found at least one vascular closure device (VCD) to be associated with excess vascular complications, compared to manual compression (MC) controls, following cardiac catheterization. Since that time, several more VCDs have been approved by the Food and Drug Administration (FDA). This research evaluates the safety profiles of current frequently used VCDs and other hemostasis strategies. Methods. Of 1089 sites that submitted data to the CathPCI Registry from 2005 through the second quarter of 2009, a total of 1,819,611 percutaneous coronary intervention (PCI) procedures performed via femoral access site were analyzed. Assessed outcomes included bleeding, femoral artery occlusion, embolization, artery dissection, pseudoaneurysm, and arteriovenous fistula. Seven types of hemostasis strategy were evaluated for rate of “any bleeding or vascular complication” compared to MC controls, using hierarchical multiple logistic regression analysis, controlling for demographic factors, type of hemostasis, several indices of co-morbidity, and other potential confounding variables. Rates for different types of hemostasis strategy were plotted over time, using linear regression analysis.Results. Four of the VCDs and hemostasis patches demonstrated significantly lower bleeding or vascular complication rates than MC controls: Angio-Seal (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.65-0.70); Perclose (OR, 0.54; CI, 0.51-0.57); StarClose (OR, 0.77; CI, 0.72-0.82); Boomerang Closure Wire (OR, 0.63; CI, 0.53-0.75); and hemostasis patches (OR, 0.70; CI, 0.67-0.74). All types of hemostasis strategy, including MC, exhibited reduced complication rates over time. All trends were statistically significant except one. Conclusions. This large, nationally representative observational study demonstrated better safety profiles for most of the frequently used VCDs, compared to MC controls.

J INVASIVE CARDIOL 2012;24(7):328-334

Key words: hemostasis patch, mechanical compression, vascular closure device

Problems and Complications of the Transradial Approach for Coronary Interventions: A Review

The Journal of invasive Cardiology

Elizabeth Bazemore, BS and J. Tift Mann, III, MD

The benefits of the transradial approach have clearly been documented in numerous studies in the past ten years.1–9 Access site bleeding complication rates are lower and early ambulation results in a significant reduction in patient morbidity and a lower total procedure cost.3,4 Both patients undergoing the procedure and staff caring for these patients overwhelmingly prefer the transradial approach.10
As a result of these benefits, there has been an increase in the use of the radial artery for interventional procedures worldwide in the past several years. This experience has led to an understanding of the problems and complications that can result from the transradial approach. The purpose of the present manuscript is to review these issues.
Radial artery occlusion. Although this complication is a major concern, the consequences of radial artery occlusion are usually benign. The dual blood supply to the hand is an extremely protective mechanism (Figure 1). Hand ischemia with necrosis has occurred following prolonged cannulation of the radial artery for hemodynamic monitoring in critically ill patients; however, this complication has not been reported thus far after transradial coronary procedures.
The absence of ischemic complications is largely the result of the original recommendation by Kiemeneij that the transradial procedure be performed only in patients with a documented patent ulnar artery and palmar arch.1 This has traditionally been evaluated using the Allen’s test, but ultrasound, Doppler, and plethysmography prior to the procedure are more accurate methods.11
Plethysmography is probably the simplest and most effective method. A pulse oximetry test is performed with the probe placed on the patient’s thumb (Figure 2). The persistence of waveform and high oximetry readings after digital occlusion of the radial artery is very strong evidence that the patient will have sufficient collateral flow to prevent hand ischemia if the radial artery should become occluded as a result of the procedure. Barbeau has demonstrated the reappearance of the waveform and a high oximetry reading two minutes after initial negative results.11 This delayed recruitment of collaterals may be an additional explanation for the absence of hand ischemia with radial occlusion.
Several variables influence the incidence of radial artery occlusion. Adequate anticoagulation is extremely important. This is usually not an issue in patients undergoing interventional procedures, but the incidence of radial occlusion was as high as 30% in patients receiving only 1,000 units of heparin during diagnostic catheterization.12 The incidence of radial occlusion is reduced significantly by administering at least 5,000 units of heparin during the procedure.12,13 Due to this risk of radial occlusion, we tend to reserve the use of the radial artery for interventional procedures and “look-see” diagnostic catheterization. Elective diagnostic catheterizations are performed transradially only when there is an increased risk of femoral complications.
Catheter size has been shown to be an important predictor of post-procedure radial artery occlusion. Saito has studied the ratio of the radial artery internal diameter to the external diameter of the arterial sheath.14 The incidence of occlusion was 4% in patients with a ratio of greater than 1, as compared to 13% in those with a ratio of less than 1. Radial procedures have traditionally been performed using 6 Fr catheters, and most patients have an internal radial artery diameter larger than the 2.52 mm external 6 Fr sheath diameter.14 The incidence of radial occlusion following 6 Fr procedures is less than 5%, but the rate increases with larger sheath sizes.4,13 Virtually all interventional procedures can now be performed through large-bore, 6 Fr guide catheters, and larger-sized catheters are rarely necessary. For straightforward procedures, 5 Fr guide catheters may be utilized and are particularly useful in smaller women.
When the radial artery is utilized for hemodynamic monitoring in critically ill patients, the incidence of radial occlusion is significantly higher in patients with cannulation times greater than 24 hours, as compared to those under 20 hours.15 Since catheters are virtually always removed at the conclusion of a catheterization or interventional procedure, the time of cannulation may not be a factor. However, prolonged post-procedure compression times, particularly with high pressure using a mechanical device, may be a factor. We use sufficient pressure only to achieve hemostasis and try to remove the device as quickly as possible. Even in patients with intensive anticoagulation, it is rarely necessary to maintain mechanical compression for longer than one to two hours. A compression dressing using non-occlusive pressures can then be applied.
In summary, post-procedure radial occlusion occurs only in a small percentage of patients and is virtually always asymptomatic because of the dual blood supply to the hand. Patients with generalized vascular disease, diabetes mellitus, and those undergoing repeat procedures are more susceptible. The incidence can be minimized with appropriate anticoagulation, proper sheath selection, and avoiding prolonged high-pressure compression following the procedure.
Non-occlusive radial artery injury. Recent studies have demonstrated that permanent radial artery injury without occlusion may occur following transradial intervention in some patients. Mean radial artery internal diameter as measured by ultrasound was smaller in patients undergoing repeat transradial interventional procedures as compared to the initial procedure.16 This smaller diameter was not present on the day following the procedure, but developed during a mean follow up of 4.5 months. Wakeyama et al. demonstrated with intravascular ultrasound that this progressive narrowing is due to intimal hyperplasia, presumably induced by trauma from the cannulation sheath or catheter.17 The studies in our laboratory show that this hyperplasia is usually segmental rather than diffuse and is not present in all patients with a previous transradial procedure (Figure 3). The incidence of subsequent intimal hyperplasia in patients undergoing radial procedures is yet to be determined.
The ramifications of this injury are important not only in patients undergoing repeat interventional procedures, but also in patients in whom the radial artery may be used as a conduit for coronary artery bypass surgery. At our center, this is not an issue as most procedures are performed from the right radial artery and surgeons use the left radial artery for bypass graft purposes. At present, it would seem prudent not to use a radial artery that previously has been used for a catheterization as a bypass graft.
Radial artery spasm. Much of the morbidity of the transradial procedure is related to vasospasm induced by the introduction of a sheath or catheter into the radial artery. The vessel has a prominent medial layer that is largely dominated by alpha-1 adenoreceptor function.18 Thus, increased levels of circulating catecholamines are a cause of radial artery spasm. Local anesthesia and adequate sedation to control anxiety during catheter insertion are important preventative measures.
It has been demonstrated in isolated radial artery ring segments that nitroglycerin and verapamil are effective agents in preventing arterial spasm.19 Indeed, a vasodilator cocktail consisting of 3–6 mg of verapamil injected intra-arterially prior to sheath insertion is extremely effective in preventing radial artery spasm. The effect of the drug is immediate and significant arterial dilatation can be seen within minutes of its administration (Figure 4).
Intra-arterial verapamil and nitroglycerin have virtually eliminated vasospasm as a cause of significant morbidity of the procedure. It is now possible to perform transradial procedures using short sheaths and arm discomfort generally occurs only in patients with very small or tortuous radial arteries, particularly if guide catheter manipulation is excessive.
Spasm distal to the access site may be a cause of access failure. Occasionally, guide wire or guide catheter induced focal spasm may occur in a tortuous segment. Angiographic visualization of these areas is important as they generally respond to repeat verapamil administration and can be traversed with an angled hydrophilic coated guide wire. A soft-tipped coronary guide wire may also be used to cross these areas (Figure 5).
Sheath-induced spasm is also minimized by the use of sheaths with hydrophilic coating. Kiemeneij has documented that both patient discomfort and the force required to remove a sheath as measured by an automatic pull-back device was significantly less with hydrophilic coated sheaths as opposed to non-coated sheaths.20
Local access bleeding. The most important benefit of transradial procedures is the elimination of access site bleeding complications.1–4 The radial artery puncture site is located over bone and can easily be compressed with minimal pressure. Thus, bleeding from the radial access site can virtually always be prevented. Although manual pressure from an experienced operator is the ideal method to obtain hemostasis, several compression devices have been developed in an attempt to maximize operator and staff efficiency. Local hematomas may occur as a result of improper device application or device failure. It is important to emphasize that compression of the radial artery both proximally and distally to the puncture site must be performed because of retrograde flow from the palmar arch collaterals.
Forearm hematoma. Bleeding may occur from a site in the radial artery remote from the access site. The most common cause is perforation of a small side branch by the guide wire in patients receiving a platelet glycoprotein IIb/IIIa inhibitor (Figure 6). Avulsion of a small radial recurrent artery arising from a radial loop is another important cause of this syndrome.21,22 Hydrophilic guidewires preferentially select this small arterial remnant in patients with a radial loop and forceful advancement of the guide catheter can result in avulsion of the vessel. Radial artery perforation has been described in 1% of patients although in our experience the incidence is substantially lower. A low threshold to perform a radial artery arteriogram when any resistance to guide wire or catheter insertion is encountered will help prevent this complication.
Recognition of this bleeding remote from the access site is important as hemostatic pressure must be applied to an area other than the access site. Hemostasis is usually easily accomplished by the application of an Ace bandage to the forearm. A blood pressure sphygmomanometer may also be utilized. The latter is inflated to systolic pressure and then gradually released over a period of one to two hours. Sealing of a perforation with a long sheath is also an option, but this is rarely necessary.22
Compartment syndrome is the most dreaded complication of radial artery hemorrhage. A large hematoma causes hand ischemia due to pressure-induced occlusion of both the radial and ulnar arteries. Fasciotomy with hematoma evacuation must be performed as an emergency procedure to prevent chronic ischemic injury. This complication is rare, occurring only once in our early experience; it should always be preventable.

Access failure. Failure to cannulate the radial artery using a 20 gauge needle and a 0.025 mm straight Terumo guide wire occurs in less than 5% of patients with an experienced operator. The importance of adequate patient sedation and local anesthesia in the prevention of radial artery spasm has previously been emphasized. In addition, meticulous attention to detail is important as the probability of failure increases as the number of unsuccessful attempts to puncture the artery increases. It should be emphasized that the puncture site is proximal to the styloid process of the radius bone. The radial artery distally usually bifurcates and becomes less superficial and attempting to puncture the vessel too distally is a common cause of access failure (Figure 7).
The radial loop is the most common congenital anomaly of the radial artery and may be a cause of access failure. It occurs in 1–2% of patients and may be unilateral or bilateral.21 Wide loops can occasionally be traversed with hydrophilic guidewires and 5 Fr catheters without excessive patient discomfort.23 However, in most cases, it is preferable to consider an alternative access site.
Radial arteries that are smaller than 2 mm in diameter are difficult to access. These are generally seen in smaller women and patients with previous radial procedures. The use of a 5 Fr guide in this situation may be an option. However, complex or difficult procedures cannot be performed through a 5 Fr guide catheter.
Miscellaneous complications. Pseudoaneurysm formation may rarely occur at the radial artery access site. This is usually easily managed with thrombin injection and/or mechanical compression. However, surgery may be required. Radial artery avulsion due to intense spasm has been described but this complication should virtually never occur using contemporary techniques. Sterile abscesses rarely occur with the use of hydrophilic coated sheaths.24
Conclusion. The radial artery is an excellent access site for coronary interventions. Although technically more challenging with a definite learning curve, there are significant advantages to this approach. Complications are infrequent and many are preventable with careful technique.

 http://www.invasivecardiology.com/article/3821

J Invasive Cardiol. 2010 Apr;22(4):175-8.

Vascular complications after percutaneous coronary intervention following hemostasis with the Mynx vascular closure device versus the AngioSeal vascular closure device.

Source

Department Cardiology, New York Medical College, Macy Pavilion, Valhalla, NY 10595, USA.

Abstract

We investigated the prevalence of vascular complications after PCI following hemostasis in 190 patients (67% men and 33% women, mean age 64 years) treated with the AngioSeal vascular closure device (St. Jude Medical, Austin, Texas) versus 238 patients (67% men and 33% women, mean age 64 years) treated with the Mynx vascular closure device (AccessClosure, Mountain View, California).

RESULTS:

Death, myocardial infarction or stroke occurred in none of the 190 patients (0%) treated with the AngioSeal versus none of 238 patients (0%) treated with the Mynx. Major vascular complications occurred in 4 of 190 patients (2.1%) treated with the AngioSeal versus 5 of 238 patients (2.1%) treated with the Mynx (p not significant). Major vascular complications in patients treated with the AngioSeal included removal of a malfunctioning device (1.1%), hemorrhage requiring intervention (0.5%) and hemorrhage with a loss of > 3g Hgb (0.5%). The major vascular complications in patients treated with the Mynx included retroperitoneal bleeding requiring surgical intervention (0.8%), pseudoaneurysm with surgical repair (0.8%) and hemorrhage with a loss of > 3g Hgb (0.4%). These complications were not significantly different between the two vascular closure devices (p = 0.77). Minor complications included hematoma > 5 cm (0.5%, n = 1) within the AngioSeal group, as well as procedure failure requiring > 30 minutes of manual compression after device deployment, which occurred in 7 out of 190 patients (3.7%) treated with the AngioSeal versus 22 of 238 patients with the Mynx (9.2%) (p = 0.033).

CONCLUSIONS:

Major vascular complications after PCI following hemostasis with vascular closure devices occurred in 2.1% of 190 patients treated with the AngioSeal vascular closure device versus 2.1% of 238 patients treated with the Mynx vascular closure device (p not significant). The Mynx vascular closure device appears to have a higher rate of device failure.

Comment in

http://www.ncbi.nlm.nih.gov/pubmed/20351388

Z Kardiol. 2005 Jun;94(6):392-8.

Incications and complications of invasive diagnostic procedures and percutaneous coronary interventions in the year 2003. Results of the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).

Source

Herzzentrum Ludwigshafen, Bremserstrasse 79, 67063 Ludwigshafen, Germany. Uwe.Zeymer@t-online.de

Abstract

BACKGROUND:

The ALKK registry contains about 20% of the invasive and interventional cardiological procedures performed in Germany.

METHODS:

In 2003 a total of 82,282 consecutive diagnostic invasive and 30,689 interventional procedures from 75 hospitals were centrally collected and analyzed.

RESULTS:

The main indication for an invasive diagnostic procedure was coronary artery disease in 92.5% of cases, myocardial disease in 1.6%, impaired left ventricular function in 4.0%, valve disease in 4% and other indications in 1.9%. An acute coronary syndrome was present in 25% of the patients. The rate of severe complications in patients with a lone diagnostic invasive procedure was low (<0.5%). The indication for percutaneous coronary intervention (n=30,689) was stable angina in 44.1%, ST elevation myocardial infarction in 22.3%, non ST elevation myocardial infarction in 14.8%, unstable angina in 10.0%, silent ischemia in 2.2%, prognostic in 5.2% of patients. The majority of interventions were performed directly after the diagnostic procedure (n=23,887=78.6%). The intervention was successful in 94.6% of cases. Stent implantation was performed in 77.2%, with 1 stent in 88.4%, two stents in 7.6% and 3 or more stents in 3.3%. A drug-eluting stent was implanted in 3.6% of the cases. The complication rate after PCI was influenced by the indication for the intervention. The in-hospital mortality in patients with cardiogenic shock was 33%, while in patients with stable angina, silent ischemia and prognostic indication only 0.2% died.

CONCLUSION:

There is an increase of invasive diagnostic and interventional procedures in patients with acute coronary syndromes, with 47% of PCIs performed in these patient. PCIs were performed in 75% of the cases directly after the diagnostic procedure. The rate of stent implantation seems to have reached a plateau at around 80%, while drug-eluting stents were implanted only in a minority of cases. The complication rate is mainly dependent on the clinical presentation of the patients and the indication for PCI.

http://www.ncbi.nlm.nih.gov/pubmed/15940439

Coronary arterial complications after percutaneous coronary intervention in Behçet’s disease

Authors: Kinoshita T, Fujimoto S, Ishikawa Y, Yuzawa H, Fukunaga S, Toda M, Wagatsuma K, Akasaka Y, Ishii T, Ikeda T

Published Date February 2013 Volume 2013:4 Pages 9 – 12

DOI: http://dx.doi.org/10.2147/RRCC.S41240,

Published: 05 February 2013
Toshio Kinoshita,1 Shinichiro Fujimoto,Yukio Ishikawa,2 Hitomi Yuzawa,1 Shunji Fukunaga,1Mikihito Toda,3 Kenji Wagatsuma,3 Yoshikiyo Akasaka,2 Toshiharu Ishii,2 Takanori Ikeda1
1Department of Cardiovascular Medicine, 2Department of Pathology, 3Division of Interventional Cardiology, Toho University Faculty of Medicine, Ohta City, Tokyo, Japan

Abstract: Behçet’s disease is a multisystemic vascular inflammatory disease, but concurrent cardiac diseases, such as acute myocardial infarction, are rare. Several complications may arise after coronary intervention for coronary lesions that interfere with treatment, and the incidence of coronary arterial complications due to invasive therapy remains unclear. Further, the long-term outcomes in patients with Behçet’s disease after stenting for acute myocardial infarction have not been described. The present report describes a 35-year-old Japanese man with Behçet’s disease who developed acute myocardial infarction. A coronary aneurysm developed at the stenting site of the left anterior descending coronary artery, along with stenosis in the left anterior descending segment proximal to the site. Although invasive therapy was considered, medication including immunosuppressants was selected because of the high risk of vascular complications after invasive therapy. The coronary artery disease has remained asymptomatic for the 4 years since the patient started medication. This case underscores the importance of considering the incidence of coronary arterial complications and of conservative treatment when possible.

Keywords: Behçet’s disease, myocardial infarction, coronary arterial complications, percutaneous coronary intervention, immunosuppressants

http://www.dovepress.com/coronary-arterial-complications-after-percutaneous-coronary-interventi-peer-reviewed-article-RRCC-recommendation1

REFERENCES

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  2. Heart Disease and Stroke Statistics — 2011 Update. American Heart Association, 2011.
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  6. An initiative of the American College of Cardiology Foundation, the NCDR, National Cardiovascular Data Registry, is a comprehensive, outcomes-based suite of registries focused on quality improvement. www.ncdr.com. 
  7. Applegate RJ, Sacrinty MT, Kutcher MA, et al. Propensity score analysis of vascular complications after diagnostic cardiac catheterization and percutaneous coronary intervention 1998-2003. Catheter Cardiovasc Interv. 2006;67(4):556-562.
  8. Applegate RJ, Sacrinty M, Kutcher MA, et al. Vascular complications with newer generations of Angio-Seal vascular closure devices. J Interv Cardiol. 2006;19(1):67-74.
  9. Applegate RJ, Sacrinty MT, Kutcher MA, et al. Propensity score analysis of vascular complications after diagnostic cardiac catheterization and percutaneous coronary intervention using thrombin hemostatic patch-facilitated manual compression. J Invasive Cardiol. 2007;19(4):164-170.
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Frequency and Costs of Ischemic and Bleeding Complications After Percutaneous Coronary Interventions: Rationale for New Antithrombotic Therapy

Journal of Invasive Cardiology

http://www.invasivecardiology.com/article/2489

Author(s):

Mauro Moscucci, MD

Recent advances in catheter technology and antithrombotic therapy have led to a continuous improvement in outcomes of percutaneous coronary intervention (PCI). These improved outcomes have been associated with broadening of the indications for PCI, with an exponential growth in number of procedures performed, but they have also been paralleled by incremental procedure costs. The estimated costs of PCI currently range from $8,000–$13,000.1 With over 800,000 cases performed each year in the United States (US) alone, this represents over $10 billion annually for the US Healthcare System.2 Roughly half of these costs are incurred by the Center for Medicare and Medicaid Services (CMS, formerly known as the Health Care Financing Administration).3 Total costs of PCI include disposable equipment used during the procedure (balloons, catheters, stents, etc.), cardiac catheterization laboratory overhead and depreciation, nursing and pharmacy costs, laboratory costs and physician services. In addition, factors that have been found to be associated with increased PCI costs include the use of special devices such as atherectomy or vascular closure devices, the use of multiple stents, the use of platelet glycoprotein (GP) IIb/IIIa inhibitors, and the presence of certain patient demographic characteristics including advanced age, gender and other comorbidities.1,4,5 Finally, complications related to the procedure have been identified in several studies as the single most significant contributor to increased costs of PC.5–7

Methods to reduce the cost of PCI include re-use of balloon catheters,8 percutaneous revascularization performed at the same time as diagnostic catheterization,9 reduced anticoagulation, the use of new devices or pharmacological interventions to reduce restenosis and complications, and the use of competitive bidding for cardiac cath lab supplies.10 For example, the evolution of anticoagulation therapy in stented patients from a regime of post-procedural heparin and warfarin to one of thienopyridines and aspirin,11 and the subsequent reduction of length of stay from 4 days in 1995 to 2 days in 2000, have helped keep total procedure costs down.12 In addition, a reduction in complication rates appears to be a key target for cost reduction efforts. In support of this statement, in the economic assessment of the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) trial in high-risk patients, Mark et al. identified bleeding complications, urgent and non-urgent coronary artery bypass graft surgery (CABG), and urgent and non-urgent percutaneous transluminal coronary angioplasty (PTCA) as important correlates of incremental costs.7 Unfortunately, standard aggressive antithrombotic therapy aimed toward a reduction of ischemic complications is often associated with an increase in bleeding complications. In the analysis of the EPIC trial, the benefits of abciximab in decreasing procedure costs through a reduction of ischemic complications were offset by drug acquisition costs and by an increase in bleeding complications.7 Thus, with ischemic complications becoming more rare as a result of improvement in PCI technology and more aggressive antithrombotic therapy, bleeding has become a rather common and costly complication of PCI, with a blood transfusion estimated to add up to $8,000 to the cost of care for the PCI patient.13

Based on these premises, it appears that the next challenge in the care of PCI patients will be to determine how to continue to prevent ischemic complications without increasing the risk of bleeding. This paper examines the frequency of PCI complications in both recent clinical trials and actual practice, discusses the costs of complications, and explores improvements in patient management and particularly changes in anticoagulation therapy that might impact total costs of PCI.

Complication rates in clinical trials

Ischemic complications in clinical trials. Despite advances in PCI technology and adjunctive pharmacotherapy, data from clinical trials indicate that ischemic complications still occur in 5–15% of patients.14–19 Typically, clinical trials define ischemic complications as a combination of death, myocardial infarction (MI; both Q-wave and non-Q wave) and either urgent or any target vessel revascularization (TVR). Different definitions of MI or revascularization can make comparisons across trials difficult. However, comparisons may still be possible through the application of strict meta-analysis methodology. A recent meta-analysis combined data from 6 double-blind PCI trials conducted predominantly in North America between 1993 and 1998.20 A total of 16,546 patients were enrolled in these trials (Table 1). Protocols and case report forms for trials included in the analysis were compared to ensure reasonable consistency of study methods, patient management, data reporting and data structure. Integration of the databases from the trials enabled a direct comparison of key event rates at 7 days, using standard classifications and criteria for severity. The meta-analysis showed that the use of high-dose heparin (175 U/kg) was associated with significantly less frequent clinical ischemic events (8.1%) than lower doses of heparin (100 U/kg; 10.3%). In this same meta-analysis, event rates in patients treated with low-dose heparin (70 U/kg) plus a GP IIb/IIIa inhibitor was 6.5%.20 Although not included in this meta-analysis, it is worth noting that the incidence of death, MI and revascularization in the ESPRIT trial was 9.3% in patients treated with low-dose heparin alone (60 U/kg).21

Bleeding complications in clinical trials. In clinical trials of antiplatelet and anti-thrombotic therapy in PCI, bleeding complications are generally defined using either thrombolysis in myocardial infarction (TIMI)22 or global utilization of streptokinase or tPA outcomes (GUSTO)23 criteria (Table 2). Rates of major bleeding in clinical trials using these criteria are generally less than 2% (Table 3).14–19,21,24,25 However, these restrictive definitions may not capture all clinically significant bleeding. For example, neither the TIMI nor the GUSTO major bleeding definition includes the need for a blood transfusion as part of the criteria. Thus, a broader measure of bleeding using a combination of both major and minor bleeding defined by TIMI or GUSTO criteria appears more likely to be representative of bleeding rates in clinical practice.

In the meta-analysis of contemporary PCI trials, TIMI criteria were used to classify hemorrhagic events, permitting direct comparisons between trials. In the high-dose heparin group, the combination of TIMI major and minor bleeding occurred in 10.5% of patients compared with a rate of 10.7% in the low-dose heparin group, while the bleeding rate was 14.3% in patients receiving a combination of GP IIb/IIIa inhibitors and low-dose heparin.

As shown in Table 3, when both TIMI major and minor bleeding are combined in contemporary PCI trials, bleeding complications average 4–14%, depending on patient characteristics and the drug regime used. In addition, when transfusions are included in the definition, the frequency of bleeding complications increases substantially. For example, in NICE-3, bleeding complications were 10.5% when transfusions were included in the criteria, but only 2% of the patients experienced TIMI major bleeding.26

Notably, the only adjunctive anti-thrombotic agent shown to reduce both ischemic and bleeding complications in PCI is bivalirudin. In the Bivalirudin Angioplasty Trial,27 the risk of bleeding was decreased 62% in the bivalirudin group compared with high-dose heparin. The combined rate of TIMI major and TIMI minor bleeding in bivalirudin patients (n = 2,161) was found to be 4.3% in the meta-analysis of contemporary PCI trials with a corresponding ischemic event rate of 6.6%.20

Complications in practice

Ischemic complications in practice. Rates of ischemic complications in clinical practice are difficult to determine. Although several investigators have published data from multicenter databases, these data tend to be 3–5 years old by the time manuscripts are in print. Since trends in the published literature do show continued reduction in PCI complications over time, the frequency of complications noted in these publications may overestimate the actual rate of complications in clinical practice today. In addition, rates of complications can vary widely across institutions due to differences in practice patterns, definitions, operator skills and resource utilization. For example, in the Society for Cardiac Angiography and Interventions (SCA&I) registry, stent use among laboratories varied from 29–95%.28 Others have found lower complication rates in patients whose procedure was performed by a high-volume operator or in a high-volume institution.29 We identified 6 published reports of PCI complications in clinical practice reporting a variety of ischemic outcomes.1,28–31

Saucedo et al. prospectively collected data on 900 patients undergoing successful elective stent placement in native coronary arteries between January 1994 and December 1995.30 The purpose of this study was to evaluate the incidence and long-term clinical consequences of patients with creatine kinase (CK) myocardial isoenzyme band (CK-MB) elevations after stenting. By design, all patients in this observational study had a successful procedure defined as an increase of > 20% in luminal diameter with final percent diameter stenosis of < 50%, without the occurrence of any major complications (death, Q-wave MI and CABG). Nevertheless, 26.4% of patients had CK-MB elevations 1–5 times the upper limit of normal (ULN) and 8.5% had CK-MB elevations > 5 times ULN. In total, 3.9% of patients required a repeat diagnostic catheterization for recurrent ischemia and 1.2% required urgent target vessel revascularization. In this study, patients requiring the use of GP IIb/IIIa inhibitors were excluded.

The Northern New England group (NNE) collected data on 14,498 patients undergoing PCI between 1994 and 1996.29 In this study, outcomes included the in-hospital occurrence of death; emergency CABG (eCABG) or non-eCABG; or new MI (defined as chest pain, diaphoresis, dyspnea or hypotension associated with the development of new Q-waves or ST-T wave changes and a rise in CK to at least twice normal with a positive CK-MB). Overall, death occurred in 1.2% of patients, CABG in 2.6% (0.8% eCABG and 1.8% non-eCABG), and MI in 2%. Stents were used in 22% of patients enrolled in this registry.

In the National Cardiovascular Network database (NCN), Batchelor et al. reported complications of PCI in 109,708 patients who underwent PCI between 1994 and 1997.31 In this observational study, in-hospital mortality was defined as the occurrence of death after the procedure, MI was defined as the appearance of new Q-waves in 2 contiguous leads on a 12-lead electrocardiogram (ECG) for up to 30 days post-PCI, and repeat revascularization was defined as the need for CABG or additional PCI prior to discharge. In this study, death occurred in 1.3% of patients, Q-wave MI in 1.4% and repeat revascularization in 4.5%. Half of the patients underwent stenting in this study. Notably, this database did not record myocardial enzymes or the use of GP IIb/IIIa inhibitors.

Aronow and colleagues observed outcomes in a cohort of consecutive registry patients undergoing coronary stent placement between 1995 and 1997.32 A total of 373 patients underwent PCI during this time period, with death occurring in 9 patients (2.4%), CABG in 3 (0.8%) and MI in 19 (5.1%, including both QWMI and NQWMI). Repeat diagnostic catheterization was performed in 3.2% of patients and repeat PCI in 0.8%.

The SCA&I registry evaluated outcomes in 16,811 patients undergoing either balloon angioplasty (n = 6,121) or stenting (n = 10,690) between July 1996 and December 1998.28 In this observational analysis, 12.9% of patients received a GP IIb/IIIa inhibitor, 87% of patients enrolled in the database underwent PCI between 1997 and 1998, and 60% of the stent patients were enrolled in 1998. Outcomes reported included in-hospital death (occurring at any time during the hospitalization) and eCABG, defined as CABG occurring immediately after PCI. Death occurred in 0.4% of patients and eCABG in 0.5%.

Finally, Cohen and others recorded in-laboratory complications in 26,421 patients at 70 different centers undergoing PCI in 1998.1 In-laboratory complications were rare, with death occurring in 0.17%, cardiac arrest in 0.32%, stroke in 0.03%, ventricular fibrillation or tachycardia in 0.94%, abrupt closure in 0.71%, and eCABG in 0.53%. Overall, 72% of patients received stents and 20% received GP IIb/IIIa inhibitors.

In addition to published reports of PCI complications, data from unpublished sources can be used to determine outcomes in a more contemporary cohort of patients undergoing PCI.33 The MQ-Profile (MQ-Pro) Database [Cardinal Information Corporation (CIC), Marlborough, Massachusetts] is maintained by CIC, which sells and distributes software to US acute-care hospitals for the collection of detailed clinical and administrative data. Data from 5,373 PCI procedures performed between July 1, 1998 and June 30, 1999 were obtained from the database using International Classification of Diseases 9th Edition (ICD-9) procedure codes for PCI (36.01, 36.02, 36.05). Demographic, clinical and economic data were collected on each patient using a combination of database retrieval and chart review. In this analysis, death was defined as discharge disposition of “deceased”, MI as the presence of ECG changes consistent with MI (new Q-waves or ST-segment changes) or an increase in CK-MB of at least 2 times the testing facility’s ULN. CABG was identified by the presence of ICD-9 procedure code 36.1 and repeat PCI by either code 36.01, 36.02, or 36.05. Failed PCI was defined by the term “failed PTCA” in chart notes (for patients without a previous history of PCI) and recurrent ischemia documented by ECG changes. Death occurred in 2.0% of patients, MI in 3.1%, CABG in 1.3% and repeat PCI in 5.5%. Translated into a combined endpoint similar to those used in clinical trials, the rate of death/MI/revascularization was 11.9%.

Data from these published and unpublished observations of contemporary PCI practice indicate that while in-laboratory ischemic complications are exceedingly rare, in-hospital ischemic complications still occur in a substantial number of patients. Using an approximation of outcomes from these published and unpublished reports, mortality averages 1%, Q-wave MI occurs in 2% of patients, NQWMI in 6%, CABG in 2% and repeat PCI occurs in 3–5% of patients. It is important to underscore that although most deaths following PCI are due to underlying comorbidities (i.e., acute MI, cardiogenic shock, etc.) rather than to the procedure itself, few deaths still occur as a complication of the procedure.34,35 Extrapolated to the estimated PCI population of 800,000 cases per year, then 8,000 people will die and 64,000 will experience an MI. In addition, approximately 16,000 will require CABG and as many as 40,000 will need a repeat PCI before hospital discharge.

II(b) PAD Endovascular Interventions: Carotid Artery Endarterectomy

  • Original Contributions

Medical Complications Associated With Carotid Endarterectomy

Stroke.1999; 30: 1759-1763  doi: 10.1161/​01.STR.30.9.1759

  1. Maurizio Paciaroni, MD;
  2. Michael Eliasziw, PhD;
  3. L. Jaap Kappelle, MD;
  4. Jane W. Finan, BScN;
  5. Gary G. Ferguson, MD;
  6. Henry J. M. Barnett, MD;
  7. for the North American Symptomatic Carotid Endarterectomy Trial (NASCET) Collaborators

+Author Affiliations


  1. From the John P. Robarts Research Institute (M.P., M.E., L.J.K., J.W.F., H.J.M.B) and the Departments of Epidemiology and Biostatistics (M.E.) and Clinical Neurological Sciences (M.E., G.G.F., H.J.M.B.), University of Western Ontario, London, Ontario, Canada.
  1. Correspondence to Dr H.J.M. Barnett, John P. Robarts Research Institute, PO Box 5015, 100 Perth Dr, London, ON N6A 5K8, Canada. E-mail barnett@rri.on.ca

Abstract

Background and Purpose—Carotid endarterectomy (CE) has been shown to be beneficial in patients with symptomatic high-grade (70% to 99%) internal carotid artery stenosis. To achieve this benefit, complications must be kept to a minimum. Complications not associated with the procedure itself, but related to medical conditions, have received little attention.

Methods—Medical complications that occurred within 30 days after CE were recorded in 1415 patients with symptomatic stenosis (30% to 99%) of the internal carotid artery. They were compared with 1433 patients who received medical care alone. All patients were in the North American Symptomatic Carotid Endarterectomy Trial (NASCET).

Results—One hundred fifteen patients (8.1%) had 142 medical complications: 14 (1%) myocardial infarctions, 101 (7.1%) other cardiovascular disorders, 11 (0.8%) respiratory complications, 6 (0.4%) transient confusions, and 10 (0.7%) other complications. Of the 142 complications, 69.7% were of short duration, and only 26.8% prolonged hospitalization. Five patients died: 3 from myocardial infarction and 2 suddenly. Medically treated patients experienced similar complications with one third the frequency. Endarterectomy was ≈1.5 times more likely to trigger medical complications in patients with a history of myocardial infarction, angina, or hypertension (P<0.05).

Conclusions—Perioperative medical complications were observed in slightly fewer than 1 of every 10 patients who underwent CE. The majority of these complications completely resolved. Most complications were cardiovascular and occurred in patients with 1 or more cardiovascular risk factors. In this selected population, the occurrence of perioperative myocardial infarction was uncommon.

Key Words:

The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Endarterectomy Trial showed unequivocal benefit of carotid endarterectomy (CE) in symptomatic patients with high-grade internal carotid artery (ICA) stenosis (70% to 99%).1 2 The parallel study dealing with symptomatic patients with moderate-grade stenosis (30% to 69%) showed benefits of CE only in a carefully selected group of patients.3 Currently, CE is the most common elective peripheral vascular procedure, which in 1997 was performed in ≈130 000 patients in the United States.4

Despite benefit in the long term, CE may cause complications either by the operation itself or by concomitant medical conditions. The challenge for the future is to reduce the perioperative risk as much as possible. The incidence and type of complications that are directly related to the surgical procedure have been the subject of many reports,5 6 7 8 910 whereas medical complications that are not directly caused by the procedure have received less attention. The aim of the present study is to describe the incidence and type of medical complications that occurred in patients randomized into NASCET and to determine their association with baseline risk factors.

Subjects and Methods

The methods of the NASCET have been described in detail elsewhere.1 11 Briefly, NASCET was a randomized clinical trial designed to compare the benefit of best medical therapy alone with best medical therapy plus CE in patients with recent transient or nondisabling neurological deficit caused by cerebral or retinal ischemia in the territory of the ICA. Among the exclusions were patients with recent history (6 months) of myocardial infarction, unstable angina pectoris, atrial fibrillation, recent congestive heart failure, and valvular heart disease. For inclusion, the ICA had to have a 30% to 99% stenosis as assessed by selective carotid angiography and to be technically suitable for CE. Baseline evaluations included a detailed medical history and complete physical and neurological examination.

Surgeons were invited to join NASCET if the center had a documented CE stroke and death rate of ≤6% in a minimum of 50 consecutive cases over a 2-year period. Surgery was completed at the earliest opportunity after randomization, and patients underwent a second complete physical and neurological examination 30 days after surgery. All medical and surgical complications that caused transient or permanent disability within the 30-day period were recorded.

Medical complications consisted of myocardial infarction (based on ECG and cardiac enzyme changes), arrhythmia (requiring antiarrhythmic medication), congestive heart failure, angina pectoris, hypertension (diastolic blood pressure >100 mm Hg requiring intravenous medication), hypotension (systolic pressure <90 mm Hg requiring administration of vasopressor agent), sudden death, respiratory problems (pneumonia, atelectasis, pulmonary edema, or exacerbation of chronic obstructive pulmonary disease), renal failure (doubling of preoperative urea and/or creatinine), depression, and confusion (requiring restraint). Complications were considered mild if they were transient and did not prolong hospital stay, moderate if they were transient but caused delay in hospital discharge, and severe if they were associated with permanent disability or death.

In the present study, patients were excluded from the analyses if they had serious complications that were directly attributable to the surgical procedure, such as those due to anesthesia, thrombosis at the operative site, wound hematomas requiring surgical intervention, or deficits from a vagus nerve injury interfering with swallowing. These surgical complications are described in detail elsewhere.12 For comparative purposes, a list of complications that occurred in the medically treated arm of NASCET was compiled for the 32-day period after randomization (ie, the 30-day period plus the average 2 days that lapsed from randomization to CE in the surgical arm). In both the surgical and medical arms, patients were censored at the time of a stroke, since the subsequent medical complications are commonly the result of the stroke.

Cox proportional hazards regression modeling was used to identify baseline factors that increased the risk of perioperative medical complications. Adjusted hazard rates and adjusted hazard ratios were used to summarize the results. The estimated hazard ratio (or relative hazard) is a measure of association that can be interpreted as a relative risk. Hazard ratios with corresponding probability value of <0.05 were considered statistically significant. Adjusted hazard rates were obtained from the regression model by using the mean value for a factor being adjusted.

The modeling strategy consisted of initially fitting a “full” model, which included all factors. A “final” model was determined by eliminating all factors that were not significantly predictive of the medical complications, using a backward selection approach. The “change-in-estimate” strategy was used to determine whether the remaining factors in the final model were independent risk factors. A factor was considered an independent risk factor if the change in hazard ratios between the full and final models was <10%.

Results

A total of 1436 eligible patients were randomized to the surgical arm and 1449 to the medical arm of the NASCET. In the surgical arm, 21 patients were not operated on for various reasons.12 In the medical arm 16 patients crossed over to surgical therapy within 30 days, leaving 1433 patients for analysis. CE was performed in 1415 patients (328 patients with severe stenosis and 1087 with moderate stenosis). Of the 1415, 59 (4.2%) patients had serious surgical complications that excluded them from further analyses, and 115 (8.1%) had medical complications (Table 1). Of the 142 complications, 69.7% were mild, 26.8% were moderate, and 3.5% were severe. Twenty patients had ≥2 complications. No patient had pulmonary embolus, renal failure, or depression requiring medication. Cardiovascular disorders were >4 times as common as all other conditions combined. All 5 severe complications were fatal and were caused by cardiovascular disorders: 3 patients had fatal myocardial infarction, and 2 patients died suddenly. Of the patients with fatal myocardial infarction, 2 patients had massive myocardial infarctions on the day of surgery. In the other patient, CE was prolonged (7 hours) because of intraoperative occlusion of the ICA. Twenty-four hours after CE, the patient had a myocardial infarction followed by cardiac arrest, leaving the patient in a vegetative state. The patient died 2 months later. Two patients died suddenly on days 3 and 6 after CE, and both had a history of previous myocardial infarction. All patients with fatal medical complications were male, and all had multiple cardiovascular risk factors.

http://stroke.ahajournals.org/content/30/9/1759.full

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  18. Adams HP Jr, Brott TG, Crowell RM, Furlan AJ, Gomez CR, Grotta J, Helgason CM, Marler JR, Woolson RF, Zivin JA, Feinberg W, Mayberg M. Guidelines for the management of patients with acute ischemic stroke: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 1994;25:1901–1914.
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  30. Chambers BR, Smidt U, Koh O. Hyperperfusion post-endarterectomy.Cerebrovasc Dis. 1994;4:32–37.
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  32. Baptista MV, Maeder P, Dewarrat A, Bogousslavsky J. Conflicting images.Lancet. 1998;351:414.

Intraoperative use of dextran is associated with cardiac complications after carotid endarterectomy.

J Vasc Surg. 2013 Mar;57(3):635-41. doi: 10.1016/j.jvs.2012.09.017. Epub 2013 Jan 18.

Source

Section of Vascular and Endovascular Surgery, Boston University Medical Center, Boston, MA, USA. Alik.Farber@bmc.org

Abstract

OBJECTIVE:

Although dextran has been theorized to diminish the risk of stroke associated with carotid endarterectomy (CEA), variation exists in its use. We evaluated outcomes of dextran use in patients undergoing CEA to clarify its utility.

METHODS:

We studied all primary CEAs performed by 89 surgeons within the Vascular Study Group of New England database (2003-2010). Patients were stratified by intraoperative dextran use. Outcomes included perioperative death, stroke, myocardial infarction (MI), and congestive heart failure (CHF). Group and propensity score matching was performed for risk-adjusted comparisons, and multivariable logistic and gamma regressions were used to examine associations between dextran use and outcomes.

RESULTS:

There were 6641 CEAs performed, with dextran used in 334 procedures (5%). Dextran-treated and untreated patients were similar in age (70 years) and symptomatic status (25%). Clinical differences between the cohorts were eliminated by statistical adjustment. In crude, group-matched, and propensity-matched analyses, the stroke/death rate was similar for the two cohorts (1.2%). Dextran-treated patients were more likely to suffer postoperative MI (crude: 2.4% vs 1.0%; P = .03; group-matched: 2.4% vs 0.6%; P = .01; propensity-matched: 2.4% vs 0.5%; P = .003) and CHF (2.1% vs 0.6%; P = .01; 2.1% vs 0.5%; P = .01; 2.1% vs 0.2%; P < .001). In multivariable analysis of the crude sample, dextran was associated with a higher risk of postoperative MI (odds ratio, 3.52; 95% confidence interval, 1.62-7.64) and CHF (odds ratio, 5.71; 95% confidence interval, 2.35-13.89).

CONCLUSIONS:

Dextran use was not associated with lower perioperative stroke but was associated with higher rates of MI and CHF. Taken together, our findings suggest limited clinical utility for routine use of intraoperative dextran during CEA.

J Vasc Surg. 2008 Nov;48(5):1139-45. doi: 10.1016/j.jvs.2008.05.013. Epub 2008 Jun 30.

Factors associated with stroke or death after carotid endarterectomy in Northern New England.

Source

Section of Vascular Surgery Dartmouth-Hitchcock Medical Center, Lebanon, NH 03765, USA. philip.goodney@hitchcock.org

Abstract

OBJECTIVE:

This study investigated risk factors for stroke or death after carotid endarterectomy (CEA) among hospitals of varying type and size participating in a regional quality improvement effort.

METHODS:

We reviewed 2714 patients undergoing 3092 primary CEAs (excluding combined procedures or redo CEA) at 11 hospitals in Northern New England from January 2003 through December 2007. Hospitals varied in size (25 to 615 beds) and comprised community and teaching hospitals. Fifty surgeons reported results to the database. Trained research personnel prospectively collected >70 demographic and clinical variables for each patient. Multivariate logistic regression models were used to generate odds ratios (ORs) and prediction models for the 30-day postoperative stroke or death rate.

RESULTS:

Across 3092 CEAs, there were 38 minor strokes, 14 major strokes, and eight deaths (5 stroke-related) < or =30 days of the index procedure (30-day stroke or death rate, 1.8%). In multivariate analyses, emergency CEA (OR, 7.0; 95% confidence interval [CI], 1.8-26.9; P = .004), contralateral internal carotid artery occlusion (OR, 2.8; 95% CI, 1.3-6.2; P = .009), preoperative ipsilateral cortical stroke (OR, 2.4; 95% CI, 1.1-5.1; P = .02), congestive heart failure (OR, 1.6; 95% CI, 1.1-2.4, P = .03), and age >70 (OR, 1.3; 95% CI, 0.8-2.3; P = .315) were associated with postoperative stroke or death. Preoperative antiplatelet therapy was protective (OR, 0.4; 95% CI, 0.2-0.9; P = .02). Risk of stroke or death varied from <1% in patients with no risk factors to nearly 5% with patients with > or =3 risk factors. Our risk prediction model had excellent correlation with observed results (r = 0.96) and reasonable discriminative ability (area under receiver operating characteristic curve, 0.71). Risks varied from <1% in asymptomatic patients with no risk factors to nearly 4% in patients with contralateral internal carotid artery occlusion (OR, 3.2; 95% CI, 1.3-8.1; P = .01) and age >70 (OR, 2.9; 95% CI, 1.0-4.9, P = .05). Two hospitals performed significantly better than expected. These differences were not attributable to surgeon or hospital volume.

CONCLUSION:

Surgeons can “risk-stratify” preoperative patients by considering the variables (emergency procedure, contralateral internal carotid artery occlusion, preoperative ipsilateral cortical stroke, congestive heart failure, and age), reducing risk with antiplatelet agents, and informing patients more precisely about their risk of stroke or death after CEA. Risk prediction models can also be used to compare risk-adjusted outcomes between centers, identify best practices, and hopefully, improve overall results.

III. Cardiac Failure During Systemic Sepsis

CHANGES IN HEART FUNCTION DURING SEPSIS

The patient with sepsis has severely altered physiology in a number of ways, which can influence cardiac function. Firstly, there is a

  • Loss of intravascular volume due to excessive third space loss that results in a decrease in preload. Systemic vascular resistance is decreased which results in a fall in afterload. In addition,
  • end diastolic volumes often increase and
  • ejection fraction falls. However, many of these changes are overcome by an
  • increase in heart rate that may result in an increase in cardiac output. However, it should be remembered that even in the presence of high cardiac outputs it is usually always possible to demonstrate
  • ventricular dysfunction in patients with sepsis. Echocardiographic studies consistently confirm that there is decreased left ventricular systolic function in humans with sepsis.

In addition, there have been many studies in animals and a few in humans which have confirmed the presence of

  • diastolic dysfunction – particularly in those patients that go on to die from sepsis.

In the presence of adequate fluid resuscitation there is an increase in end diastolic volume and this is probably a normal response to a decrease in contractility. However, in the non-survivors of sepsis there is a normal or low end diastolic volume that is the result of a decrease in ventricular diastolic compliance. Thus, there is a decreased end diastolic volume at the same filling pressure.

During sepsis, a

  • decrease in contractility results in a shift to the right of the end-systolic pressure / volume curve and if this is not compensated for results in a
  • decrease in stroke volume and cardiac output.

When patients with sepsis are appropriately fluid resuscitated there is an

  • increase in end diastolic pressure that increases stroke volume. In addition, the
  • decrease in afterload will also increase stroke volume and will prevent a decrease in ejection fraction.

Alas, because there is a decrease in systolic contractility it would be expected that there would also be a decrease in diastolic stiffness which would allow cardiac output to be maintained despite the relatively low filling pressures. However, if this diastolic compliance change does not occur (as in the nonsurvivors of sepsis) then it is apparent  that the ability of the ventricle to generate a stroke volume is impaired at both ends of the curve.

The cause of the altered cardiac function in sepsis remains unknown although there are many theoretical explanations. Clearly, one of the most important mechanisms which can be readily corrected is hypovolaemia.

  • Myocardial oedema may contribute to a decrease in contractility.
  • Increased circulating catecholamines can result in a decrease in diastolic compliance, particularly important since these agents are often used to improve myocardial contractility.
  • Increased intrathoracic pressure caused by positive pressure ventilation can also result in decreased diastolic compliance. In addition, many of the
  • mediators of the inflammatory response, including products of activated endothelial cells and polymorphonuclear leucocytes (e.g. nitric oxide, tumour necrosis factor and interleukins 1 and 2) have all been postulated as negative inotropes and negative lusitropes.

Another, as yet, unidentified agent which is believed to be released from the splanchnic bed –

  • myocardial depressant factor – is postulated to play a role.

Treatments aimed at correcting the effects of these various inflammatory mediators may be eventually found but until these approaches have been proven to be beneficial the septic patient will continue to be managed according to the physiological principles outlined by Starling.

http://www.rcsed.ac.uk/RCSEDBackIssues/journal/vol46_1/4610005.htm

Sepsis and the Heart – Cardiovascular Involvement in General Medical Conditions

  1. M.W. Merx, MD;
  2. C. Weber, MD

+Author Affiliations


  1. From the Department of Medicine (M.W.M.), Division of Cardiology, Pulmonary Diseases and Vascular Medicine and the Institute of Molecular Cardiovascular Research (IMCAR) at the University Hospital (C.W.), RWTH Aachen University, Aachen, Germany.
  1. Correspondence to Marc W. Merx, MD, Medizinische Klinik I, Universitätsklinikum der RWTH Aachen, Pauwelstraße 30, 52057 Aachen, Germany (e-mailmmerx@ukaachen.de), or Christian Weber, MD, Institut für Kardiovaskuläre Molekularbiologie, Universitätsklinikum der RWTH Aachen, Pauwelstraße 30, 52057 Aachen, Germany (e-mail cweber@ukaachen.de).
Circulation.2007; 116: 793-802doi: 10.1161/​CIRCULATIONAHA.106.678359

Abstract

Sepsis is generally viewed as a disease aggravated by an inappropriate immune response encountered in the afflicted individual. As an important organ system frequently compromised by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear to date. There is currently no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis; however, in septic patients with coexistent and possibly undiagnosed coronary artery disease, regional myocardial ischemia or infarction secondary to coronary artery disease may certainly occur.

A circulating myocardial depressant factor in septic shock has long been proposed, and potential candidates for a myocardial depressant factor include

  • cytokines,
  • prostanoids, and
  • nitric oxide, among others.
  • Endothelial activation and
  • induction of the coagulatory system also contribute to the pathophysiology in sepsis.

Prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory. The purpose of this review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches.

Key Words:

Sepsis, defined by consensus conference as “the systemic inflammatory response syndrome (SIRS) that occurs during infection,”1 is generally viewed as a disease aggravated by the inappropriate immune response encountered in the affected individual (for review, see Hotchkiss and Karl2 and Riedemann et al,3). The Table gives the current criteria for the establishment of the diagnosis of systemic inflammatory response syndrome, sepsis, and septic shock.1,4 Morbidity and mortality are high, resulting in sepsis and septic shock being the 10th most common cause of death in the United States.5 The incidence of sepsis and sepsis-related deaths appears to be increasing by 1.5% per year.6 In a recent study,6 the total national hospital cost invoked by severe sepsis in the United States was estimated at approximately $16.7 billion on the basis of an estimated severe sepsis rate of 751 000 cases per year with 215 000 associated deaths annually. A recent study from Britain documented a 46% in-hospital mortality rate for patients presenting with severe sepsis on admission to the intensive care unit.7

Current Criteria for Establishment of the Diagnosis of SIRS, Sepsis, and Septic Shock1,4

As an important organ system frequently affected by sepsis and always affected by septic shock, the cardiovascular system and its dysfunction during sepsis have been studied in clinical and basic research for more than 5 decades. In 1951, Waisbren was the first to describe cardiovascular dysfunction due to sepsis.8 He recognized a hyperdynamic state with full bounding pulses, flushing, fever, oliguria, and hypotension. In addition, he described a second, smaller patient group who presented clammy, pale, and hypotensive with low volume pulses and who appeared more severely ill. With hindsight, the latter group might well have been volume underresuscitated, and indeed, timely and adequate volume therapy has been demonstrated to be one of the most effective supportive measures in sepsis therapy.9

Under conditions of adequate volume resuscitation, the profoundly reduced systemic vascular resistance typically encountered in sepsis10 leads to a concomitant elevation in cardiac index that obscures the myocardial dysfunction that also occurs. However, as early as the mid-1980s, significant reductions in both stroke volume and ejection fraction in septic patients were observed despite normal total cardiac output.11 Importantly, the presence of cardiovascular dysfunction in sepsis is associated with a significantly increased mortality rate of 70% to 90% compared with 20% in septic patients without cardiovascular impairment.12 Thus, myocardial dysfunction in sepsis has been the focus of intense research activity. Although a number of mediators and pathways have been shown to be associated with myocardial depression in sepsis, the precise cause remains unclear.

The purpose of the present review is to delineate some characteristics of septic myocardial dysfunction, to assess the most commonly cited and reported underlying mechanisms of cardiac dysfunction in sepsis, and to briefly outline current therapeutic strategies and possible future approaches. This review is not intended to be all inclusive.

Characteristics of Myocardial Dysfunction in Sepsis

Using portable radionuclide cineangiography, Calvin et al13 were the first to demonstrate myocardial dysfunction in adequately volume-resuscitated septic patients with decreased ejection fraction and increased end-diastolic volume index. Adding pulmonary artery catheters to serial radionuclide cineangiography, Parker and colleagues11 extended these observations with the 2 major findings that (1) survivors of septic shock were characterized by increased end-diastolic volume index and decreased ejection fraction, whereas nonsurvivors typically maintained normal cardiac volumes, and (2) these acute changes in end-diastolic volume index and ejection fraction, although sustained for several days, were reversible. More recently, echocardiographic studies have demonstrated impaired left ventricular systolic and diastolic function in septic patients.14–16 These human studies, in conjunction with experimental studies ranging from the cellular level17 to isolated heart studies18,19 and to in vivo animal models,20–22 have clearly established decreased contractility and impaired myocardial compliance as major factors that cause myocardial dysfunction in sepsis.

Notwithstanding the functional and structural differences between the left and right ventricle, similar functional alterations, as discussed above, have been observed for the right ventricle, which suggests that right ventricular dysfunction in sepsis closely parallels left ventricular dysfunction.23–26 However, the relative contribution of the right ventricle to septic cardiomyopathy remains unknown.

Myocardial dysfunction in sepsis has also been analyzed with respect to its prognostic value. Parker et al,27 reviewing septic patients on initial presentation and at 24 hours to determine prognostic indicators, found a heart rate of <106 bpm to be the only cardiac parameter on presentation that predicted a favorable outcome. At 24 hours after presentation, a systemic vascular resistance index >1529 dyne · s−1 · cm−5 · m−2, a heart rate <95 bpm or a reduction in heart rate >18 bpm, and a cardiac index >0.5 L · min−1 · m−2 suggested survival.27 In a prospective study, Rhodes et al28 demonstrated the feasibility of a dobutamine stress test for outcome stratification, with nonsurvivors being characterized by an attenuated inotropic response. The well-established biomarkers in myocardial ischemia and heart failure, cardiac troponin I and T, as well as B-type natriuretic peptide, have also been evaluated with regard to sepsis-associated myocardial dysfunction. Although B-type natriuretic peptide studies have delivered conflicting results in septic patients (for review, see Maeder et al29), several small studies have reported a relationship between elevated cardiac troponin T and I and left ventricular dysfunction in sepsis, as assessed by echocardiographic ejection fraction30–33 or pulmonary artery catheter–derived left ventricular stroke work index.34 Cardiac troponin levels also correlated with the duration of hypotension35 and the intensity of vasopressor therapy.34In addition, increased sepsis severity, measured by global scores such as the Simplified Acute Physiology Score II (SAPS II) or the Acute Physiology And Chronic Health Evaluation II score (APACHE II), was associated with increased cardiac troponin levels,31,33 as was poor short-term prognosis.32,33,35,36 Despite the heterogeneity of study populations and type of troponin studied, the mentioned studies were univocal in concluding that elevated troponin levels in septic patients reflect higher disease severity, myocardial dysfunction, and worse prognosis. In a recent meta-analysis of 23 observational studies, Lim et al37 found cardiac troponin levels to be increased in a large percentage of critically ill patients. Furthermore, in a subset of studies that permitted adjusted analysis and comprised 1706 patients, this troponin elevation was associated with an increased risk of death (odds ratio, 2.5; 95% CI, 1.9 to 3.4, P<0.001)37; however, the underlying mechanisms clearly require further research.

Thus, it appears reasonable to recommend inclusion of cardiac troponins in the monitoring of patients with severe sepsis and septic shock to facilitate prognostic stratification and to increase alertness to the presence of cardiac dysfunction in individual patients. However, it remains to be shown whether risk stratification based on cardiac troponins can identify patients in whom aggressive therapeutic regimens might reap the greatest benefit and so translate into a survival benefit.

Mechanisms Underlying Myocardial Dysfunction in Sepsis

Cardiac depression during sepsis is probably multifactorial (Figure). Nevertheless, it is important to identify individual contributing factors and mechanisms to generate worthwhile therapeutic targets. As a consequence, a vast array of mechanisms, pathways, and disruptions in cellular homeostasis have been examined in septic myocardium.

Figure

View larger version:

Synopsis of potential underlying mechanisms in septic myocardial dysfunction. MDS indicates myocardial depressant substance.

Global Ischemia

An early theory of myocardial depression in sepsis was based on the hypothesis of global myocardial ischemia; however, septic patients have been shown to have high coronary blood flow and diminished coronary artery–coronary sinus oxygen difference.38 As in the peripheral circulation, these alterations can be attributed to disturbed flow autoregulation or disturbed oxygen utilization.39,40 Coronary sinus blood studies in patients with septic shock have also demonstrated complex metabolic alterations in septic myocardium, including increased lactate extraction, decreased free fatty acid extraction, and decreased glucose uptake.41 Furthermore, several magnetic resonance studies in animal models of sepsis have demonstrated the presence of normal high-energy phosphate levels in the myocardium.42,43 It has also been proposed that myocardial dysfunction in sepsis may reflect hibernating myocardium.44 To reach this conclusion, Levy et al44 studied a murine cecal ligation and double-puncture model and observed diminished cardiac performance, increased myocardial glucose uptake, and deposits of glycogen in a setting of preserved arterial oxygen tension and myocardial perfusion. Although all of the above-mentioned findings reflect important alterations in coronary flow and myocardial metabolism, mirroring effects observed in peripheral circulation during sepsis, there is no evidence supporting global ischemia as an underlying cause of myocardial dysfunction in sepsis. However, in septic patients with coexistent and possibly undiagnosed coronary artery disease (CAD), regional myocardial ischemia or infarction secondary to CAD may certainly occur. The manifestation of myocardial ischemia due to CAD might even be facilitated by the volatile hemodynamics in sepsis, as well as by the generalized microvascular dysfunction so frequently observed in sepsis.45 Additional CAD-aggravating factors encountered in sepsis encompass generalized inflammation and the activated coagulatory system. Furthermore, the endothelium plays a prominent role in sepsis (see below), but little is known of the impact of preexisting, CAD-associated endothelial dysfunction in this context. In a postmortem study of 21 fatal cases of septic shock, previously undiagnosed myocardial ischemia at least contributed to death in 7 of the 21 cases (all 21 patients were males, with a mean age of 60.4 years).46 It certainly appears prudent to remain wary of CAD complications while treating sepsis, especially in patients with identifiable risk factors and in view of the ever-increasing mean age of intensive care unit patients and including septic patients.

Myocardial Depressant Substance

A circulating myocardial depressant factor in septic shock was first proposed more than 50 years ago.47 Parrillo et al48 quantitatively linked the clinical degree of septic myocardial dysfunction with the effect the serum, taken from respective patients, had on rat cardiac myocytes, with clinical severity correlating well with the decrease in extent and velocity of myocyte shortening. These effects were not seen when serum from convalescent patients whose cardiac function had returned to normal was applied or when serum was obtained from other critically ill, nonseptic patients.48 In extension of these findings, ultrafiltrates from patients with severe sepsis and simultaneously reduced left ventricular stroke work index (<30 g · m−1 · m−2) displayed cardiotoxic effects and contained significantly increased concentrations of interleukin (IL)-1, IL-8, and C3a.49Recently, Mink et al50 demonstrated that lysozyme c, a bacteriolytic agent believed to originate mainly from disintegrating neutrophilic granulocytes and monocytes, mediates cardiodepressive effects during Escherichia coli sepsis and, importantly, that competitive inhibition of lysozyme c can prevent myocardial depression in the respective experimental sepsis model. Additional potential candidates for myocardial depressant substance include other cytokines, prostanoids, and nitric oxide (NO). Some of these will be discussed below.

Cytokines

Infusion of lipopolysaccharide (LPS, an obligatory component of Gram-negative bacterial cell walls) into both animals and humans51 partially mimics the hemodynamic effects of septic shock.51,52 However, only a minority of patients with septic shock have detectable LPS levels, and the prolonged time course of septic myocardial dysfunction and the chemical characteristics of LPS are not consistent with LPS representing the sole myocardial depressant substance.48,53 Tumor necrosis factor-α (TNF-α) is an important early mediator of endotoxin-induced shock.54 TNF-α is derived from activated macrophages, but recent studies have shown that TNF-α is also secreted by cardiac myocytes in response to sepsis.55 Although application of anti-TNF-α antibodies improved left ventricular function in patients with septic shock,56 subsequent studies using monoclonal antibodies directed against TNF-α or soluble TNF-α receptors failed to improve survival in septic patients.57–59 IL-1 is synthesized by monocytes, macrophages, and neutrophils in response to TNF-α and plays a crucial role in the systemic immune response. IL-1 depresses cardiac contractility by stimulating NO synthase (NOS).60 Transcription of IL-1 is followed by delayed transcription of IL-1 receptor antagonist (IL-1-ra), which functions as an endogenous inhibitor of IL-1. Recombinant IL-1-ra was evaluated in phase III clinical trials, which showed a tendency toward improved survival61 and increased survival time in a retrospective analysis of the patient subgroup with the most severe sepsis62; however, to date, this initially promising therapy has failed to deliver a statistically significant survival benefit. IL-6, another proinflammatory cytokine, has also been implicated in the pathogenesis of sepsis and is considered a more consistent predictor of sepsis than TNF-α because of its prolonged elevation in the circulation.63 Although cytokines may very well play a key role in the early decrease in contractility, they cannot explain the prolonged duration of myocardial dysfunction in sepsis, unless they result in the induction or release of additional factors that in turn alter myocardial function, such as prostanoids or NO.64,65

Prostanoids

Prostanoids are produced by the cyclooxygenase enzyme from arachidonic acid. The expression of cyclooxygenase enzyme-2 is induced, among other stimuli, by LPS and cytokines (cyclooxygenase enzyme-1 is expressed constitutively).66 Elevated levels of prostanoids such as thromboxane and prostacyclin, which have the potential to alter coronary autoregulation, coronary endothelial function, and intracoronary leukocyte activation, have been demonstrated in septic patients.67 Early animal studies with cyclooxygenase inhibitors such as indomethacin yielded very promising results.68,69Along with other positive results, these led to an important clinical study involving 455 septic patients who were randomized to receive intravenous ibuprofen or placebo.70Unfortunately, that study did not demonstrate improved survival for the treatment arm. Similarly, a more recent, smaller study on the effects of lornoxicam failed to provide evidence for a survival benefit through cyclooxygenase inhibition in sepsis.71 Animal studies aimed at elucidating possible benefits of isotype-selective cyclooxygenase inhibition have so far produced conflicting results.72,73

Endothelin-1

Endothelin-1 (ET-1; for an in-depth review of endothelin in sepsis, see Gupta et al74) upregulation has been demonstrated within 6 hours of LPS-induced septic shock.75Cardiac overexpression of ET-1 triggers an increase in inflammatory cytokines (among others, TNF-α, IL-1, and IL-6), interstitial inflammatory infiltration, and an inflammatory cardiomyopathy that results in heart failure and death.76 The involvement of ET-1 in septic myocardial dysfunction is supported by the observation that tezosentan, a dual endothelin-A and endothelin-B receptor antagonist, improved cardiac index, stroke volume index, and left ventricular stroke work index in endotoxemic shock.77 However, higher doses of tezosentan exhibited cardiotoxic effects and led to increased mortality.77Although ET-1 has been demonstrated to be of pathophysiological importance in a wide array of cardiac diseases through autocrine, endocrine, or paracrine effects, its biosynthesis, receptor-mediated signaling, and functional consequences in septic myocardial dysfunction warrant further investigation to assess the therapeutic potential of ET-1 receptor antagonists.

Nitric Oxide

NO exerts a plethora of biological effects in the cardiovascular system.78 It has been shown to modulate cardiac function under physiological and a multitude of pathophysiological conditions. In healthy volunteers, low-dose NO increases LV function, whereas inhibition of endogenous NO release by intravenous infusion of the NO synthase (NOS) inhibitor NG-monomethyl-L-arginine reduced the stroke volume index.79 Higher doses of NO have been shown to induce contractile dysfunction by depressing myocardial energy generation.80 The absence of the important NO scavenger myoglobin (Mb) in Mb knockout mice results in impaired cardiac function that is partially reversible by NOS inhibition.81 Endogenous NO contributes to hibernation in response to myocardial ischemia by reducing oxygen consumption and preserving calcium sensitivity and contractile function.82 NO also represents a potent modulator of myocardial ischemia/reperfusion injury. However, as in sepsis-related NO research, the reported effects of NO on ischemia/reperfusion injury are inconsistent owing to a multitude of confounding experimental factors.83

Sepsis leads to the expression of inducible NOS (iNOS) in the myocardium,84,85 followed by high-level NO production, which in turn importantly contributes to myocardial dysfunction, in part through the generation of cytotoxic peroxynitrite, a product of NO and superoxide (for an excellent review, see Pacher et al86). In iNOS-deficient mice, cardiac function is preserved after endotoxin challenge.87 Nonspecific NOS inhibition restores cardiac output and stroke volume after LPS injection.88 Strikingly, in septic patients, infusion of methylene blue, a nonspecific NOS inhibitor, improves mean arterial pressure, stroke volume, and left ventricular stroke work and decreases the requirement for inotropic support but, unfortunately, does not alter outcome.89 An interesting study comparing the inhibition of NO superoxide and peroxynitrite in cytokine-induced myocardial contractile failure found peroxynitrite to indeed be the most promising therapeutic target.90 It has also been proposed that the constitutively expressed mitochondrial isoform of NOS (mtNOS), the expression of which can be augmented by induction, controls rates of oxidative phosphorylation by inhibiting various steps of the respiratory chain.91 Although this hypothesis would provide a plausible explanation for the reduced coronary oxygen extraction observed during sepsis (see above), the effects of sepsis on expression of mtNOS and NO generation remain to be explored. Furthermore, the constitutively expressed endothelial NOS (eNOS), previously neglected in the context of sepsis, has been shown to be an important regulator of iNOS expression, resulting in a more stable hemodynamic status in eNOS-deficient mice after endotoxemia.92 Very recently, a functional NOS in red blood cells (rbcNOS) was identified that regulates deformability of erythrocyte membranes and inhibits activation of platelets.93 With both effect targets thus far demonstrated for rbcNOS lying at the core of microvascular dysfunction in sepsis, this discovery opens a whole new window to NO-related sepsis research. Given the existence of different NOS isoforms and their various modulating interactions, dose-dependent NO effects, and the precise balance of NO, superoxide, and thus peroxynitrite generated in subcellular compartments, further advances in our understanding of the complex NO biology and its derived reactive nitrogen species hold the promise of revealing new, more specific and effective therapeutic targets.

Adhesion Molecules

Surface-expression upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 has been demonstrated in murine coronary endothelium and cardiomyocytes after LPS and TNF-α stimulation.94 After cecal ligation and double puncture, myocardial intercellular adhesion molecule-1 expression increases in rats.95Vascular cell adhesion molecule-1 blockade with antibodies has been shown to prevent myocardial dysfunction and decrease myocardial neutrophil accumulation,94,96 whereas both knockout and antibody blockade of intercellular adhesion molecule-1 ameliorate myocardial dysfunction in endotoxemia without affecting neutrophil accumulation.94 In addition, neutrophil depletion does not protect against septic cardiomyopathy, which suggests that the cardiotoxic potential of neutrophils infiltrating the myocardium is of lesser importance in this context.94 Other aspects of adhesion molecules are discussed in conjunction with possible statin effects below.

The e-Reader is advised to consider the following expansion on the subject matter carrying the discussion to additional related clinical issues:

Advanced Topics in Sepsis and the Cardiovascular System at its End Stage

Author: Larry H Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-sepsis-and-the-cardiovascular-system-at-its-end-stage/

Therapeutic Approaches: The Present and the Future

A detailed discussion of therapeutic options in septic patients would clearly be beyond the scope of this review, and readers are kindly referred to the multiple excellent reviews published on the subject (eg, Hotchkiss and Karl,2 Annane et al,4 and Dellinger et al97). Although a number of preventive measures, such as prophylactic antibiotics, maintenance of normoglycemia, selective digestive tract decontamination, vaccines, and intravenous immunoglobulin, have shown benefit in distinct patient populations, preventive strategies with a broader aim remain elusive. Once sepsis is manifest (see the Table for criteria), prompt and adequate antibiotic therapy accompanied by surgical removal of the infectious focus, if indicated and feasible, is the mainstay and also the only strictly causal line of therapy. In the presence of severe sepsis and septic shock, supportive treatment in addition to causal therapy is mandatory. Supportive therapy encompasses early and goal-directed fluid resuscitation,9 vasopressor and inotropic therapy, red blood cell transfusion, mechanical ventilation, and renal support when indicated. It is very likely beneficial to monitor cardiac performance in these patients. A wide array of techniques are available for this purpose, ranging from echocardiography to pulmonary catheters, thermodilution techniques, and pulse pressure analysis.98 Because none of these techniques have demonstrated superiority, physicians should use the method with which they are most familiar. Whichever method is chosen, it should be applied frequently to tailor supportive therapy to the individual patient and to achieve the “gold standard” of early goal-directed therapy. In recent years, several attempts have been made to therapeutically address myocardial dysfunction in sepsis. Although the combination of norepinephrine as vasopressor and dobutamine as inotropic agent is probably the most frequently applied in septic shock, there is currently no evidence to recommend one catecholamine over the other.97 In human endotoxemia, epinephrine has been demonstrated to inhibit proinflammatory pathways and coagulation activation, as well as to augment antiinflammatory pathways,99,100 whereas no immunomodulatory or coagulant effects could be demonstrated for dobutamine in a similar setting.101 Isoproterenol has recently been applied successfully in a small group of patients with septic shock, no known history of CAD, and inappropriate mixed venous oxygen concentration despite correction of hypoxemia and anemia.102 In a cecal ligation and double-puncture model of sepsis, the β-blocker esmolol given continuously after sepsis induction improved myocardial oxygen utilization and attenuated myocardial dysfunction,103 which suggests that therapeutic strategies proven in ischemic heart failure might also hold promise in septic cardiomyopathy. However, the optimal mode of β-receptor stimulation (or indeed inhibition) to limit myocardial dysfunction remains a wide-open field for inspired investigation.

Given the generally accepted view of sepsis as a disease largely propelled by an inappropriate immune response, numerous basic research and clinical trials have been undertaken to curb the lethal toll of sepsis through modulation of this uncontrolled immune response.2,3 To date, activated protein C104 and low-dose hydrocortisone105 have emerged as the only inflammation-modulating substances that have been confirmed to be of benefit in patients with severe sepsis and septic shock. Over the past years, increasing evidence has accumulated that suggests that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, or statins, have therapeutic benefits independent of cholesterol lowering, termed “pleiotropic” effects. These have added a wide scope of potential targets for statin therapy that range from decreasing renal function loss106 and lowering mortality in patients with diastolic heart failure107 to prevention and treatment of stroke,108 to name just a few. These pleiotropic effects include antiinflammatory and antioxidative properties, improvement of endothelial function, and increased NO bioavailability and thus might contribute to the benefit observed with statin therapy. Notably, these important immunomodulatory effects of statins have been demonstrated to be independent of lipid lowering109 and appear to be mediated via interference with the synthesis of mevalonate metabolites (nonsteroidal isoprenoid products). Blockade of the mevalonate pathway has been shown to suppress T-cell responses,110 reduce expression of class II major histocompatibility complexes on antigen presenting cells,109 and inhibit chemokine synthesis in peripheral blood mononuclear cells.111 Furthermore, CD11b integrin expression and CD11b-dependent adhesion of monocytes have been found to be attenuated by the initiation of statin treatment in hypercholesterolemic patients.112 In this context, Yoshida et al113 have reported that statins reduce the expression of both monocytic and endothelial adhesion molecules, eg, the integrin leukocyte function-associated antigen-1 (LFA-1), via an inhibition of Rho GTPases, in particular their membrane anchoring by geranylation. In addition, mechanisms for antiinflammatory actions of statins have been revealed that are not related to the isoprenoid metabolism. For instance, Weitz-Schmidt et al114 have identified that some statins act as direct antagonists of LFA-1 owing to their capacity to bind to the regulatory site in the LFA-1 i-domain. In addition to these multifaceted antiinflammatory effects, statins may interfere with activation of the coagulation cascade, as illustrated by the suppression of LPS-induced monocyte tissue factor in vitro.115 Beyond their immunomodulatory functions, statins have been shown to exert direct antichlamydial effects during pulmonary infection with Chlamydia pneumoniae in mice,116 and a recent report suggests the benefit of statins may also extend to viral pathogens.117

Given the strong impact of statins on inflammation, statins might represent a welcome enforcement in the battle against severe infectious diseases such as sepsis. Consequently, several investigators have evaluated the role of statins in the prevention and treatment of sepsis. In a retrospective analysis, Liappis et al118 demonstrated a reduced overall and attributable mortality in patients with bacteremia who were treated concomitantly with statins. Pretreatment with simvastatin has been shown to profoundly improve survival in a polymicrobial murine model of sepsis by preservation of cardiovascular function and inhibition of inflammatory alterations.19 Encouraged by these findings, the same model was used to successfully treat sepsis in a clinically feasible fashion, ie, treatment was initiated several hours after the onset of sepsis. With different statins (atorvastatin, pravastatin, and simvastatin) being effective, the therapeutic potential of statins in sepsis appears to be a class effect.22 Recently, Steiner et al119observed that pretreatment with simvastatin can suppress the inflammatory response induced by LPS in healthy human volunteers. Furthermore, in a prospective observational cohort study in patients with acute bacterial infections performed by Almog et al,120previous treatment with statins was associated with a considerably reduced rate of severe sepsis and intensive care unit admissions. A total of 361 patients were enrolled in that study, and 82 of these patients had been treated with statins for at least 4 weeks before their admission. Severe sepsis developed in 19% of patients in the no-statin group compared with only 2.4% in patients who were taking statins. The intensive care unit admission rates were 12.2% for the no-statin group and 3.7% for the statin group. Because of the number of patients enrolled, the study was not powered to detect differences in mortality, although the large effect on sepsis rate and intensive care unit admission were at least suggestive. As the most recent development in this field, Hackam et al121 have produced an impressive observational study by initial evaluation of 141 487 cardiovascular patients, which resulted in a well-paired and homogenous study cohort of 69 168 patients after propensity-based matching. Drawing from this solid base, Hackam and coauthors were able to support the conclusion that statin therapy is associated with a considerably decreased rate of sepsis (hazard ratio, 0.81; 95% CI, 0.72 to 0.90), severe sepsis (hazard ratio, 0.83; 95% CI, 0.70 to 0.97), and fatal sepsis (hazard ratio, 0.75; 95% CI, 0.61 to 0.93). This protective effect prevailed at both high and low statin doses and for several clinically important subpopulations, such as diabetic and heart failure patients.

As has been suggested previously,122 statins might provide cumulative benefit by reducing mortality from cardiovascular and infectious diseases such as sepsis. However, statins may have detrimental effects in distinct subsets of patients. Therefore, caution should prevail, and the use of statins in patients with sepsis must be accompanied by meticulous monitoring of unexpected side effects and well-designed randomized, controlled clinical trials.

Beyond an apparent rationale for randomized trials on statins in sepsis, it is notable that the results with other immunomodulatory approaches in sepsis have yielded rather limited success. For instance, use of the anti-TNF antibody F(ab′)2 fragment afelimomab led to a significant but rather modest reduction in risk of death and to improved organ-failure scores in patients with severe sepsis and elevated IL-6 levels.123 Moreover, a selective inhibitor of group IIA secretory phospholipase A2 failed to improve clinical outcome for patients with severe sepsis, with a negative trend most pronounced among patients with cardiovascular failure.124 Hence, because none of the available strategies proven to be effective in sepsis are designed specifically to target myocardial dysfunction, one might conclude that strategies that preferentially address cardiac morbidity in sepsis may be a promising area for investigation. For instance, lipoteichoic acid, a major virulence factor in Gram-positive sepsis, causes cardiac depression by activating myocardial TNF-α synthesis via CD14 and induces coronary vascular disturbances by activating thromboxane 2 synthesis. It thus contributes to cardiac depression and may therefore be a worthwhile and cardiac-specific target.125 The implications of intensified efforts in the search for successful novel approaches to the treatment of myocardial dysfunction in sepsis may be considerable with regard to improved patient care that results in reduced mortality. This is of major significance in view of the substantial economic consequences of increasing sepsis morbidity in an aging population.

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Circulation.2007; 116: 793-802doi: 10.1161/​CIRCULATIONAHA.106.678359

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https://pharmaceuticalintelligence.com/2013/07/08/becoming-a-cardiothoracic-surgeon-an-emerging-profile-in-the-surgery-theater-and-through-scientific-publications/

Pearlman, JD and A. Lev-Ari  7/4/2013 Fractional Flow Reserve (FFR) & Instantaneous wave-free ratio (iFR): An Evaluation of Catheterization Lab Tools (Software Validation) for Ischemic Assessment (Diagnostics) – Change in Paradigm: The RIGHT vessel not ALL vessels

https://pharmaceuticalintelligence.com/2013/07/04/fractional-flow-reserve-ffr-instantaneous-wave-free-rario-ifr-an-evaluation-of-catheterization-lab-tools-for-ischemic-assessment/

Lev-Ari, A. 7/1/22013 Endovascular Lower-extremity Revascularization Effectiveness: Vascular Surgeons (VSs), Interventional Cardiologists (ICs) and Interventional Radiologists (IRs)

https://pharmaceuticalintelligence.com/2013/07/01/endovascular-lower-extremity-revascularization-effectiveness-vascular-surgeons-vss-interventional-cardiologists-ics-and-interventional-radiologists-irs/

Lev-Ari, A. 6/10/2013 No Early Symptoms – An Aortic Aneurysm Before It Ruptures – Is There A Way To Know If I Have it?

https://pharmaceuticalintelligence.com/2013/06/10/no-early-symptoms-an-aortic-aneurysm-before-it-ruptures-is-there-a-way-to-know-if-i-have-it/

Lev-Ari, A. 6/9/2013 Congenital Heart Disease (CHD) at Birth and into Adulthood: The Role of Spontaneous Mutations

https://pharmaceuticalintelligence.com/2013/06/09/congenital-heart-disease-at-birth-and-into-adulthood-the-role-of-spontaneous-mutations-the-genes-and-the-pathways/

Lev-Ari, A. 6/3/2013 Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care

https://pharmaceuticalintelligence.com/2013/06/03/clinical-indications-for-use-of-inhaled-nitric-oxide-ino-in-the-adult-patient-market-clinical-outcomes-after-use-therapy-demand-and-cost-of-care/

Lev-Ari, A. 6/2/2013 Inhaled Nitric Oxide in Adults: Clinical Trials and Meta Analysis Studies – Recent Findings

https://pharmaceuticalintelligence.com/2013/06/02/inhaled-nitric-oxide-in-adults-with-acute-respiratory-distress-syndrome/

Pearlman, JD and A. Lev-Ari 5/24/2013 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

https://pharmaceuticalintelligence.com/2013/05/24/imaging-biomarker-for-arterial-stiffness-pathways-in-pharmacotherapy-for-hypertension-and-hypercholesterolemia-management/

Pearlman, JD and A. Lev-Ari 5/22/2013 Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone

https://pharmaceuticalintelligence.com/2013/05/22/acute-and-chronic-myocardial-infarction-quantification-of-myocardial-viability-fdg-petmri-vs-mri-or-pet-alone/

Lev-Ari, A. 5/17/2013 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

https://pharmaceuticalintelligence.com/2013/05/17/synthetic-biology-on-advanced-genome-interpretation-for-gene-variants-and-pathways-what-is-the-genetic-base-of-atherosclerosis-and-loss-of-arterial-elasticity-with-aging/

Justin D Pearlman, HL Bernstein and A. Lev-Ari 5/15/2013 Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems

https://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems-2/

Pearlman, JD and A. Lev-Ari 5/11/2013 Hypertension and Vascular Compliance: 2013 Thought Frontier – An Arterial Elasticity Focus

https://pharmaceuticalintelligence.com/2013/05/11/arterial-elasticity-in-quest-for-a-drug-stabilizer-isolated-systolic-hypertension-caused-by-arterial-stiffening-ineffectively-treated-by-vasodilatation-antihypertensives/

Pearlman, JD and A. Lev-Ari 5/7/2013 On Devices and On Algorithms: Arrhythmia after Cardiac Surgery Prediction and ECG Prediction of Paroxysmal Atrial Fibrillation Onset

https://pharmaceuticalintelligence.com/2013/05/07/on-devices-and-on-algorithms-arrhythmia-after-cardiac-surgery-prediction-and-ecg-prediction-of-paroxysmal-atrial-fibrillation-onset/

Pearlman, JD and A. Lev-Ari 5/4/2013 Cardiovascular Diseases: Decision Support Systems for Disease Management Decision Making

https://pharmaceuticalintelligence.com/2013/05/04/cardiovascular-diseases-decision-support-systems-for-disease-management-decision-making/

Lev-Ari, A. 5/3/2013 Gene, Meis1, Regulates the Heart’s Ability to Regenerate after Injuries.

https://pharmaceuticalintelligence.com/2013/05/03/gene-meis1-regulates-the-hearts-ability-to-regenerate-after-injuries/

Lev-Ari, A. 4/30/2013 Prostacyclin and Nitric Oxide: Adventures in Vascular Biology – A Tale of Two Mediators

https://pharmaceuticalintelligence.com/2013/04/30/prostacyclin-and-nitric-oxide-adventures-in-vascular-biology-a-tale-of-two-mediators/

Lev-Ari, A. 4/28/2013 Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

https://pharmaceuticalintelligence.com/2013/04/28/genetics-of-conduction-disease-atrioventricular-av-conduction-disease-block-gene-mutations-transcription-excitability-and-energy-homeostasis/

Lev-Ari, A. 4/25/2013 Economic Toll of Heart Failure in the US: Forecasting the Impact of Heart Failure in the United States – A Policy Statement From the American Heart Association

https://pharmaceuticalintelligence.com/2013/04/25/economic-toll-of-heart-failure-in-the-us-forecasting-the-impact-of-heart-failure-in-the-united-states-a-policy-statement-from-the-american-heart-association/

Lev-Ari, A. 4/24/2013 Harnessing New Players in Atherosclerosis to Treat Heart Disease

https://pharmaceuticalintelligence.com/2013/04/25/harnessing-new-players-in-atherosclerosis-to-treat-heart-disease/

Lev-Ari, A. 4/25/2013 Revascularization: PCI, Prior History of PCI vs CABG

https://pharmaceuticalintelligence.com/2013/04/25/revascularization-pci-prior-history-of-pci-vs-cabg/

Lev-Ari, A. 4/7/2013 Cholesteryl Ester Transfer Protein (CETP) Inhibitor: Potential of Anacetrapib to treat Atherosclerosis and CAD

https://pharmaceuticalintelligence.com/2013/04/07/cholesteryl-ester-transfer-protein-cetp-inhibitor-potential-of-anacetrapib-to-treat-atherosclerosis-and-cad/

Lev-Ari, A. 4/4/2013 Hypertriglyceridemia concurrent Hyperlipidemia: Vertical Density Gradient Ultracentrifugation a Better Test to Prevent Undertreatment of High-Risk Cardiac Patients

https://pharmaceuticalintelligence.com/2013/04/04/hypertriglyceridemia-concurrent-hyperlipidemia-vertical-density-gradient-ultracentrifugation-a-better-test-to-prevent-undertreatment-of-high-risk-cardiac-patients/

Lev-Ari, A. 4/3/2013 Fight against Atherosclerotic Cardiovascular Disease: A Biologics not a Small Molecule – Recombinant Human lecithin-cholesterol acyltransferase (rhLCAT) attracted AstraZeneca to acquire AlphaCore

https://pharmaceuticalintelligence.com/2013/04/03/fight-against-atherosclerotic-cardiovascular-disease-a-biologics-not-a-small-molecule-recombinant-human-lecithin-cholesterol-acyltransferase-rhlcat-attracted-astrazeneca-to-acquire-alphacore/

Lev-Ari, A. 3/31/2013 High-Density Lipoprotein (HDL): An Independent Predictor of Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker for Cardiovascular Risk

https://pharmaceuticalintelligence.com/2013/03/31/high-density-lipoprotein-hdl-an-independent-predictor-of-endothelial-function-artherosclerosis-a-modulator-an-agonist-a-biomarker-for-cardiovascular-risk/

Lev-Ari, A. 3/10/2013 Acute Chest Pain/ER Admission: Three Emerging Alternatives to Angiography and PCI

https://pharmaceuticalintelligence.com/2013/03/10/acute-chest-painer-admission-three-emerging-alternatives-to-angiography-and-pci/

Lev-Ari, A. and L H Bernstein 3/7/2013 Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013

https://pharmaceuticalintelligence.com/2013/03/07/genomics-genetics-of-cardiovascular-disease-diagnoses-a-literature-survey-of-ahas-circulation-cardiovascular-genetics-32010-32013/

Lev-Ari, A. 2/28/2013 The Heart: Vasculature Protection – A Concept-based Pharmacological Therapy including THYMOSIN

https://pharmaceuticalintelligence.com/2013/02/28/the-heart-vasculature-protection-a-concept-based-pharmacological-therapy-including-thymosin/

Lev-Ari, A. 2/27/2013 Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel

https://pharmaceuticalintelligence.com/2013/02/27/arteriogenesis-and-cardiac-repair-two-biomaterials-injectable-thymosin-beta4-and-myocardial-matrix-hydrogel/

Lev-Ari, A. 12/29/2012. Coronary artery disease in symptomatic patients referred for coronary angiography: Predicted by Serum Protein Profiles

https://pharmaceuticalintelligence.com/2012/12/29/coronary-artery-disease-in-symptomatic-patients-referred-for-coronary-angiography-predicted-by-serum-protein-profiles/

Bernstein, HL and Lev-Ari, A. 11/28/2012. Special Considerations in Blood Lipoproteins, Viscosity, Assessment and Treatment

https://pharmaceuticalintelligence.com/2012/11/28/special-considerations-in-blood-lipoproteins-viscosity-assessment-and-treatment/

Lev-Ari, A. 11/13/2012 Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes

https://pharmaceuticalintelligence.com/2012/11/13/peroxisome-proliferator-activated-receptor-ppar-gamma-receptors-activation-pparγ-transrepression-for-angiogenesis-in-cardiovascular-disease-and-pparγ-transactivation-for-treatment-of-dia/

Lev-Ari, A. 10/19/2012 Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?

https://pharmaceuticalintelligence.com/2012/10/19/clinical-trials-results-for-endothelin-system-pathophysiological-role-in-chronic-heart-failure-acute-coronary-syndromes-and-mi-marker-of-disease-severity-or-genetic-determination/

Lev-Ari, A. 10/4/2012 Endothelin Receptors in Cardiovascular Diseases: The Role of eNOS Stimulation

https://pharmaceuticalintelligence.com/2012/10/04/endothelin-receptors-in-cardiovascular-diseases-the-role-of-enos-stimulation/

Lev-Ari, A. 10/4/2012 Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production, stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography

https://pharmaceuticalintelligence.com/2012/10/04/inhibition-of-et-1-eta-and-eta-etb-induction-of-no-production-and-stimulation-of-enos-and-treatment-regime-with-ppar-gamma-agonists-tzd-cepcs-endogenous-augmentation-for-cardiovascular-risk-reduc/

Lev-Ari, A. 8/29/2012 Positioning a Therapeutic Concept for Endogenous Augmentation of cEPCs — Therapeutic Indications for Macrovascular Disease: Coronary, Cerebrovascular and Peripheral

https://pharmaceuticalintelligence.com/2012/08/29/positioning-a-therapeutic-concept-for-endogenous-augmentation-of-cepcs-therapeutic-indications-for-macrovascular-disease-coronary-cerebrovascular-and-peripheral/

Lev-Ari, A. 8/28/2012 Cardiovascular Outcomes: Function of circulating Endothelial Progenitor Cells (cEPCs): Exploring Pharmaco-therapy targeted at Endogenous Augmentation of cEPCs

https://pharmaceuticalintelligence.com/2012/08/28/cardiovascular-outcomes-function-of-circulating-endothelial-progenitor-cells-cepcs-exploring-pharmaco-therapy-targeted-at-endogenous-augmentation-of-cepcs/

Lev-Ari, A. 8/27/2012 Endothelial Dysfunction, Diminished Availability of cEPCs, Increasing CVD Risk for Macrovascular Disease – Therapeutic Potential of cEPCs

https://pharmaceuticalintelligence.com/2012/08/27/endothelial-dysfunction-diminished-availability-of-cepcs-increasing-cvd-risk-for-macrovascular-disease-therapeutic-potential-of-cepcs/

Lev-Ari, A. 8/24/2012 Vascular Medicine and Biology: CLASSIFICATION OF FAST ACTING THERAPY FOR PATIENTS AT HIGH RISK FOR MACROVASCULAR EVENTS Macrovascular Disease – Therapeutic Potential of cEPCs

https://pharmaceuticalintelligence.com/2012/08/24/vascular-medicine-and-biology-classification-of-fast-acting-therapy-for-patients-at-high-risk-for-macrovascular-events-macrovascular-disease-therapeutic-potential-of-cepcs/

Lev-Ari, A. 7/19/2012 Cardiovascular Disease (CVD) and the Role of agent alternatives in endothelial Nitric Oxide Synthase (eNOS) Activation and Nitric Oxide Production

https://pharmaceuticalintelligence.com/2012/07/19/cardiovascular-disease-cvd-and-the-role-of-agent-alternatives-in-endothelial-nitric-oxide-synthase-enos-activation-and-nitric-oxide-production/

Lev-Ari, A. 4/30/2012 Resident-cell-based Therapy in Human Ischaemic Heart Disease: Evolution in the PROMISE of Thymosin beta4 for Cardiac Repair

https://pharmaceuticalintelligence.com/2012/04/30/93/

Lev-Ari, A. 5/29/2012 Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes

https://pharmaceuticalintelligence.com/2012/05/29/445/

Lev-Ari, A. 7/2/2012 Macrovascular Disease – Therapeutic Potential of cEPCs: Reduction Methods for CV Risk

https://pharmaceuticalintelligence.com/2012/07/02/macrovascular-disease-therapeutic-potential-of-cepcs-reduction-methods-for-cv-risk/

 

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3D Cardiovascular Theater – Hybrid Cath Lab/OR Suite, Hybrid Surgery, Complications Post PCI and Repeat Sternotomy

Curator: Aviva Lev-Ari, PhD, RN

This article has THREE Parts: 

Part One:  Hybrid Cath Lab/OR Suite for Hybrid Surgery

Part Two: Cardiac Surgery 

Part Three: Invasive Interventions with Complications

1. Repeat Sternotomy Post CABG and/or Aortic Valve Replacement

2. Complications Post PCI – Pump Catheter in Use

The voice of Series A Content Consultant, Justin D Pearlman, MD, PhD, FACC

The leading cause of death and disability from any cause is cardiovascular disease, principally, heart attacks and strokes. Both the heart and brain typically allow only 10 minutes or so of inadequate blood supply before starting a committed course of permanent tissue injury, progressing in severity as time goes by without successful interruption of the disease process. Thus there is great time urgency to get patients to a definitive treatment that can stop the injury and restore adequate nutrient blood supply. Many patients can benefit from a catheterization to identify blockages and insert a small balloon within the blockage to expand the narrow channel, often followed by placement of a stent (wire cage) to maintain the expanded vessel diameter. Chemicals released over time from drug-eluting stents can prevent tissue in growth that may obstruct stents. These emergeny interventions are not always successful. There may be complications from the attempt to access an entry artery, and the blockages may not be amenable to a balloon. When such limitations are encountered, the next chance to help is surgical, with continued time pressure.

The fastest way to make the transition from a diagnostic catheterization to a timely intervention is a hybrid intervention suite that offers non-invasive imaging, catheterization and surgery all in one location. The following articles present the current state of hybrid “do it all” intervention suites. Additional articles address the risks of bad outcomes from such interventions.

Part One 

Hybrid Cath Lab/OR Suite for Hybrid Surgery

In ACC.10 and i2 Summit, 59th Annual Scientific Session, 3/14-3/16, 2010, Alfred A. Bove, M.D., Ph.D., F.A.C.C., ACC President addressed the conference attendees:

Welcome to the all-new Hybrid Cath Lab/OR and 3D CV Theater. Recent developments in cardiac surgery and interventional cardiology have led to the creation of integrated, hybrid cath lab/operating rooms (OR), which provide significant advantages in the diagnosis and treatment of patients requiring cardiac procedures—helping to facilitate a rapid-response approach. These multimodality rooms are designed to support a variety of integrated surgical and endovascular procedures. We are excited to provide you with this opportunity to get a first-hand look—and feel—of the latest technologies. We hope you take the time to explore this interactive, multivendor venue. Learning is at the core of the ACC Annual Scientific Session and we invite you to expand your educational experience in this dynamic learning environment.

In the Hybrid Cath Lab/OR Suite, you’ll discover how integrating cutting edge angiographic and surgical equipment and technologies can facilitate a broad range of procedures within one location. Additionally, you will learn how hybrid suites are providing solutions that enable interventionalists and surgeons to work collaboratively to provide the best treatment options for patients. The adjoining 3D CV Theater features presentations by physicians currently performing intravascular and surgical procedures in hybrid suites. Each live presentation pairs a cardiologist with a surgeon, allowing you to hear perspectives from both sides on a variety of hybrid suite procedures and cases. In addition, the Theater offers video presentations of cases from around the world.

The ACC thanks the supporters of the Hybrid Suite for providing us with the opportunity to share this unique learning destination with you.

http://www.expo.acc.org/acc12/CUSTOM/images/ACC12/ACC.10%20Hybrid%20Suite%20Directory.pdf

Hybrid Cath Lab/OR Suite for Hybrid Surgery

Procedures Performed in a Hybrid Suite

The treatment of cardiovascular diseases has undergone a paradigm shift within the last few years, from

  • open surgery to minimally invasive surgical procedures and from
  • limited percutaneous catheter-based interventions to hybrid interventions for the entire cardiovascular tree.

The Hybrid Suite

are perfect examples of procedures that could, and should, be carried out in a hybrid OR. High-risk patients who require less invasive interventions are the best candidates for treatment in a hybrid suite.

As cardiac surgery becomes less invasive, incisions are becoming smaller and smaller, and even totally endoscopic heart surgery is now possible. Cardiac surgeons have started to perform procedures that include catheter-based skills, such as transapical valve replacement. For these operations, surgeons need more sophisticated imaging techniques, fluoroscopy and contrast injections. The hybrid OR offers all these facilities. Perhaps the most obvious and easiest procedure that can be performed in a hybrid OR is coronary revascularization combining coronary artery bypass grafting with on-table intra-operative completion angiography for quality control. If the surgeon detects a problem during the procedure, he or she can revise the graft immediately and thereby prevent potential perioperative and long-term complications. Currently, cardiologists and cardiovascular surgeons have shown special interest in so-called hybrid coronary interventions, which are combinations of minimally invasive coronary artery bypass grafting and percutaneous coronary interventions. In these procedures, cardiovascular surgeons place a left-internal mammary artery bypass graft to the left-anterior descending artery through small incisions (MIDCAB) or completely endoscopically (TECAB), while any remaining obstructed coronary arteries are treated with stents by an interventional cardiologist. This procedure is an attractive alternative to multivessel open coronary artery bypass grafting. Transcatheter heart-valve replacement and repair are especially suited to a hybrid suite because percutaneous transfemoral and transapical aortic valve repairs include risks that can only be treated successfully by immediate surgical intervention, such as coronary artery obstruction, aortic dissection and aortic perforations.

In addition, endovascular aortic stent grafting for the repair of abdominal aortic aneurysms is a suitable procedure for a hybrid operating room. Endovascular aneurysm repair has become an established alternative to open repair and is increasingly used for thoracic aorta repair as well. Some

  • emergency procedures for traumatic lesions of the thoracic aorta and
  • fulminant pulmonary embolism may also be performed in a hybrid OR. Several
  • pediatric interventions can be carried out in a hybrid suite as well, such as implantation of closure devices for atrial and ventricular septal defects in small children and
  • treatments for hypoplastic left-heart syndrome.

http://www.expo.acc.org/acc12/CUSTOM/images/ACC12/ACC.10%20Hybrid%20Suite%20Directory.pdf

In a recent article we reported on the Change in Requirement for Surgical Support by Cath Labs for performance of Nonemergent PCI without Surgical Backup, that increases the autonomy of Interventional Cardiologists. In the Hybrid OR that change is irrelevant since the presence of a Cardiac Surgeon is a fact of the division of labor between the two types of specialties. Cardiac Surgeons are involved with  percutaneous transfemoral and transapical aortic valve repairs and intervention for endoscopic aorta, AAA and Thoracic AA grafting.

AHA, ACC Change in Requirement for Surgical Support:  Class IIb -> Class III, Level of Evidence A: Supports Nonemergent PCI without Surgical Backup (Change of class IIb, level of Evidence B).

What is a Cardiovascular Hybrid Suite?

Cardiovascular hybrid suite is a state-of-the-art operating room equipped with a fully functional catheterization laboratory, thus allowing surgical procedures and catheter-based interventions to be carried out in the same room. Hybrid suites provide a place where treatments traditionally available only in a cath lab and procedures only available in an operating room can be performed together to provide patients with the best available combination of therapies for cardiovascular disease. These multidisciplinary, integrated cardiovascular procedural suites bring the best of two worlds together by combining all the advantages of a modern cath lab with an up-to-date cardiovascular surgery operating room (OR).

Hybrid suites began to evolve in the mid to late 1990s, when some groups of interventional cardiologists started sharing operating rooms with cardiovascular surgeons. The appeal of the hybrid suite concept has grown as have catheter based devices (stents, coils, balloons and lasers) have been developed that enable interventional cardiologists to advance the invasiveness and effectiveness and applications of percutaneous transcatheter interventions. The interest in these suites has also increased as cardiovascular surgeons have developed a variety of techniques for

  • Minimally invasive procedures, such as minimally invasive direct coronary artery bypass grafting (MIDCAB) or
  • Totally endoscopic coronary artery bypass grafting (TECAB).

With the advent of more tools, interventional cardiologists are becoming more like surgeons, and with less invasive tools, cardiovascular surgeons are becoming more like interventionalists. Rather than separating surgical procedures from interventional procedures performed in traditional operating rooms and cath labs, hybrid suites provide a high-tech environment that allows cardiologists and surgeons to work together to offer patients complex, minimally invasive therapies.

Some experts believe that hybrid suites represent the wave of the future in cardiovascular care and that most heart centers will eventually install hybrid suites to offer patients the latest cardiovascular procedures safely and effectively with minimal surgical trauma. The rooms can be costly to build and equip, but if a medical center is considering building a new operating room or cath lab, setting up a hybrid suite makes sense. Medical centers that have a hybrid suite available can clearly differentiate themselves in a positive way from centers that do not have such capabilities.

The Benefits of a Hybrid Suite for Medical Centers

While building a hybrid suite is more expensive than building a traditional operating room or cath lab, a hybrid suite can potentially be used for all types of cardiovascular procedures, including

  • traditional cardiac and vascular surgery,
  • interventional coronary procedures,
  • endovascular aortic procedures and
  • electrophysiology procedures.

Hybrid suites reinforce the trend in cardiovascular care toward less invasive, comprehensive hybrid procedures. Once a hybrid suite is in place, the demand for its use will likely grow due to increasing indications and referrals for these innovative treatments, many of which are increasingly covered by third-party payers.

http://www.expo.acc.org/acc12/CUSTOM/images/ACC12/ACC.10%20Hybrid%20Suite%20Directory.pdf

What Equipment is Needed?

Interventional cath labs usually have excellent imaging capabilities but lack the sterile facilities and staff needed for a formal OR, while operating rooms frequently lack high-level imaging equipment. Some of the essential equipment for a hybrid suite includes:

• A state-of-the-art imaging system capable of performing 3D rotational angiography, CT scanning, and ultrasound is advantageous. Floor-mounted and ceiling-mounted systems are available, but many hospitals use ceiling-mounted systems because access to the patient is slightly easier. Some ceiling-mounted systems provide 3D imaging from the surgeon’s position perpendicular to the patient. However, some hospitals prefer floor-mounted systems because having mechanical parts running above the operative field may cause dust to fall, resulting in infections. An important aspect is that the C-arm can be parked away when it is not used. This especially enhances access of the anesthesia team to the patient.

• An operating table that meets the needs of both surgeons and interventionalists by electronically integrating the table with the imaging system is also essential. These tables should have retractable rails for retractors and other surgical tools. To perform 3D imaging on the operating table, the C-arm of the imaging system should allow fast and precise rotation around the patient.

• A variety of other surgical and interventional systems and equipment may also be needed, including a robotic surgical system, a heart-lung machine, an image integration system, an endoscopic imaging system, a radiology display system, an audiovisual system to move images to different monitors and an anesthesia monitoring system, including transesophageal echocardiography. Some equipment like the integrated OR table and the angiography unit need to be fixed parts of the hybrid OR. Some equipment will be mobile in order to maintain some flexibility in workflow.

Hybrid1

Hybrid2

Hybrid3

Hybrid4

Hybrid5

Who are the Equipment Vendors?

Philips Healthcare

Phone: 800-934-7372

Email: healthcare@philips.com

Web: http://www.philips.com/healthcare

Philips is one of the world’s leading technology companies, with a long history of practical innovation and visionary design. In healthcare, we are committed to understanding the human and technological needs of patients and caregivers. We believe this understanding will help us deliver solutions that not only enable more confident diagnoses and more efficient delivery of care, but also improve the overall experience of care. We offer equipment, software and services for imaging, patient monitoring, resuscitation and much more.  A Hybrid OR can help make life simpler for the interdisciplinary teams who operate in this environment every day. As a world leader in cardiovascular X-ray, Philips has the experience and expertise to deliver the first class technology you need to perform minimally invasive procedures with speed, accuracy and confidence. A long history of innovation has enabled Philips to develop pioneering imaging solutions that really make a difference.

For example, Philips Allura Xper cardiovascular X-ray systems are designed to deliver enhanced imaging with superb performance for all cardiac projections, and our iE33 ultrasound system with Live 3D TEE and QLAB can assist interventional procedures and provide comprehensive quantitative information to support critical decisions. Our cardiology informatics solutions help you manage patient information throughout the cardiovascular care continuum. Philips solutions allow minimally invasive and catheter-based procedures to take place in the same suite as conventional cardiac surgery.

Phillips EchoNavigator – X-Ray and 3-D Ultrasound is described in:

Minimally Invasive Structural CVD Repairs: FDA grants 510(k) Clearance to Philips’ EchoNavigator – X-ray and 3-D Ultrasound Image Fused.

Intuitive Surgical, Inc. 

da Vinci.Surgery by Intuitive Surgical, Inc. 

Phone: 800-876-1310

Email: info@intusurg.com

Web: http://www.intuitivesurgical.com

Intuitive Surgical, Inc. is the global technology leader in robotic-assisted, minimally invasive surgery. The company’s da Vinci® Surgical System offers breakthrough capabilities that enable cardiac surgeons to use a minimally invasive approach and avoid median sternotomy.

Content of FDA Warning Letter, following  FDA Inspection on dates 04/01/2013 – 05/30/2013 – it discussed in

Hybrid Cath Lab/OR Suite’s da Vinci Surgical Robot of Intuitive Surgical gets FDA Warning Letter on Robot Track Record

 

MAVIG GmbH 

Phone: 631-266-2229,

585-247-1212 ext. 60

Email: info@mavig.com

Web: http://www.mavig.com

MAVIG’s specialty is ceiling/boom suspension systems for lighting (exam, surgical and LED), monitor-suspension systems—single, multibank (one to eight) systems and widescreen, overhead radiation shielding and contrast injector adapters. MAVIG also manufactures radiation protection products such as aprons, gloves, table-attachable lower body shields, adjustable- and fixed-height mobile and modular barriers.

Toshiba America Medical Systems, Inc.

Phone: 714-730-5000

Email: mktgcomm@tams.com

Web: http://www.medical.toshiba.com

Creating a hybrid lab may be complicated, but having an experienced partner that listens makes all the difference. Toshiba’s unique blend of hybrid experience and industry recognized Infinix™-i imaging systems for the Cath Lab.

Hybrid Cath Lab/OR Suite in Leading Hospitals in the US

  • The  Hybrid Cath Lab/OR Suite at New York Presbyterian Hospital/Columbia University Medical Center, New York, NY is presented in

Becoming a Cardiothoracic Surgeon: An Emerging Profile in the Surgery Theater and through Scientific Publications

  • The  Hybrid Cath Lab/OR Suite at Cleveland Clinic, Cleveland, Ohio is presented in

Heart Transplant (HT) Indication for Heart Failure (HF): Procedure Outcomes and Research on HF, HT @ Two Nation’s Leading HF & HT Centers

Speakers at 3D CV Theater, 2010 are working in Hospitals where Hybrid Cath Lab/OR Suite are in operations at the present time. The list include the following Hospitals with a Hybrid Cath Lab/OR Suite:

  • Vanderbilt Medical Center, Nashville, TN
  • University of Maryland Heart Center, Baltimore, MD
  • The Heart Center at Nationwide Children’s Hospital, Columbus, Ohio
  • The Robotic Surgical Center, East Carolina University Department of Surgery, Greenville, N.C.
  • University of Washington Medicine Regional Heart Center, Seattle, WA
  • Brigham and Women’s Hospital, Boston, MA
  • Saint Joseph’s Hospital and Peachtree Cardiovascular and Thoracic Surgery, Atlanta, GA
  • Emory University Hospital, Atlanta, GA
  • Beth Israel Deaconess Medical Center, Boston, MA
  • Boston Medical Center, Boston, MA
  • Mayo Graduate School of Medicine, Mayo Clinic, Rochester, MN
  • Lankenau Hospital, Lancaster, PA
  • Cardiac Non-Invasive Laboratory at Cedars-Sinai Medical Center, Los Angeles, CA
  • Robotic Surgery at St. Joseph’s Hospital, Atlanta, GA

Speakers at 3D CV Theater, 2010, included the following Cardiovascular Interventionists leading the adoption process of Hybrid Surgery in Hybrid Cath Lab/OR Suite into care modalities for cardiovascular disease:

Johannes O. Bonatti, M.D., is professor of surgery and director of coronary surgery and advanced coronary interventions at the University of Maryland Heart Center, Baltimore. He received his training in general surgery and cardiac surgery at the department of surgery at Innsbruck Medical University in Austria. Prior to his arrival at the University of Maryland, he worked at this institution as an attending surgeon and associate professor. Dr. Bonatti’s main interest is the development of minimally invasive, totally endoscopic coronary artery bypass grafting (TECAB) procedures using robotic technology.

As one of the international leaders in this field, he performed the largest series of robotic TECAB on the arrested heart, including single-, double- and triple-vessel TECAB. He has published significantly on procedure development and the implementation process of completely endoscopic coronary surgery using the da Vinci robotic system. Together with colleagues from interventional cardiology, Dr. Bonatti is working on integrated concepts for treatment of coronary artery disease. He was the first to perform a simultaneous hybrid coronary intervention using TECAB and placement of a coronary stent. He is organizing international meetings on hybrid interventions in cardiovascular medicine (http://www.icrworkshop.com). He has trained heart surgeons from around the world in the use of the da Vinci robot for heart surgery and he has introduced TECAB procedures in Austria, the Czech Republic, Greece, Turkey, India and Australia.

John G. Byrne, M.D., is the William S. Stoney Professor of Cardiac Surgery at Vanderbilt University School of Medicine and chair of the department of cardiac surgery at Vanderbilt Medical Center, Nashville, TN.

Before moving to Vanderbilt, he was associate chief and residency program director in the division of cardiac surgery at Brigham and Women’s Hospital, and associate professor of surgery at Harvard Medical School, Cambridge, MA. A graduate of the University of California, Davis, he received his medical degree in 1987 from Boston University. His postdoctoral training was completed at the University of Illinois affiliated hospitals and Brigham and Women’s Hospital in Boston.

Dr. Byrne is the author of more than 100 scientific articles on cardiac surgery and related areas. His patient care emphasis is

  • aortic root surgery,
  • coronary artery disease and
  • valve surgery

He is board-certified in general surgery and thoracic surgery.

John P. Cheatham, M.D., is director of cardiac catheterization and interventional therapy and codirector of The Heart Center at Nationwide Children’s Hospital, Columbus, Ohio. He is also the George H. Dunlap Endowed Chair in Interventional Cardiology and professor of pediatrics and internal medicine at The Ohio State University College of Medicine. Dr. Cheatham’s area of expertise is transcatheter intervention and hybrid therapy of newborns, children and adults with complex congenital heart disease. He has pioneered several new techniques and devices in non-surgical intervention and is a leader in developing hybrid therapies. He has been a principal investigator in numerous FDA-sponsored clinical trials evaluating non-surgical closure devices and stent therapy over the past two decades. Additionally, Dr. Cheatham designed the first hybrid cardiac catheterization suites and advanced imaging equipment at Nationwide Children’s Hospital. He serves as a consultant to various medical companies and proctors new transcatheter techniques and devices to other physicians around the world. Dr. Cheatham has implemented a formal physician exchange program with two of the leading medical institutions in China. In cooperation with China Red Cross, he is also the foreign director of the International Training Center for treatment of congenital heart disease in poor children. Dr. Cheatham has written more than 120 manuscripts, 16 book chapters, 300 national and international presentations and is co-editor of the book, Complications in Percutaneous Interventions for Congenital and Structural Heart Disease. After graduating from the University of Oklahoma College of Medicine, he completed his residency at Boston Children’s Hospital, followed by a fellowship in Pediatric Cardiology at Texas Children’s Hospital in Houston.

W. Randolph Chitwood, Jr., M.D., is senior associate vice chancellor for health sciences and chief of cardiovascular services at East Carolina University Department of Surgery, Greenville, N.C. Dr. Chitwood is a leading international pioneer in minimally invasive and robotic heart surgery. The Robotic Surgical Center at East Carolina University has trained more than 350 surgeons. His research activities relate to myocardial preservation, simulation in surgery and endoscopic/robotic cardiac surgery. He was the principal investigator of the FDA robotic mitral valve trials that led to approval for use in the U.S. He is the son and grandson of “southwestern Virginia mountain doctors” who set the guidelines for his professional life. He graduated from Hampden-Sydney College and received his medical degree from the University of Virginia. After medical school, he completed the surgical residency at Duke University Medical Center under David C. Sabiston, M.D., an influential surgical educator of the era. At Duke he spent 10 years training in general and cardiothoracic surgery, as well as basic science research.

After his chief residency at Duke in 1984, he was selected to begin and head the new cardiac surgery program at the East Carolina University School of Medicine. Because of his prolific publication record as a resident and clinical acumen, his initial appointment was as a full professor of surgery. Except for a two-year hiatus as the chief of cardiothoracic surgery at the University of Kentucky, he has spent his entire career at East Carolina University, where he also served as chairman of the department of surgery. In 2003, he was named to be in charge of the development of the East Carolina Heart Institute, which now includes an integrated department of cardiovascular sciences as well as a $200 million heart hospital, outpatient, research and education center.

Larry S. Dean, M.D., is director of the University of Washington Medicine Regional Heart Center and is professor of medicine and of surgery at the University of Washington School of Medicine, Seattle. In addition to general cardiology, he is an expert in cardiac catheterization and interventional cardiology. He also conducts research on stents to keep blocked heart arteries open and on ways to prevent restenosis after stents are inserted. He is currently involved in the evaluation of percutaneous aortic valve replacement. Dr. Dean earned his M.D. from the University of Alabama School of Medicine, Birmingham, and served his internship and residency at the University of Washington. He then returned to the University of Alabama Hospital for fellowships in cardiovascular disease and in angioplasty. After nearly 15 years as a faculty member at the University of Alabama, he returned to the University of Washington to direct the Regional Heart Center. He is a fellow of the American College of Cardiology and is board-certified in internal medicine, cardiovascular disease and interventional cardiology. He is also a fellow of the American Heart Association and president-elect of the Society of Cardiovascular Angiography and Interventions.

Andrew Craig Eisenhauer, M.D., is director of the interventional cardiovascular medicine service at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School. His specialties are

  • interventional cardiology,
  • vascular medicine and
  • congenital and inherited diseases.

He earned his medical degree at New York University School of Medicine and served a residency at Peter Bent Brigham Hospital and a fellowship at Massachusetts General Hospital. He is certified in internal medicine, cardiovascular disease and interventional cardiology. His clinical interests are

  • endovascular therapy,
  • complex coronary disease,
  • peripheral vascular disease,
  • cerebrovascular disease,
  • congenital heart disease and structural heart disease

Douglas A. Murphy, M.D., is chief of cardiothoracic surgery at Saint Joseph’s Hospital and a cardiothoracic surgeon at Peachtree Cardiovascular and Thoracic Surgery, Atlanta. His areas of interest are robotically assisted heart surgery with an emphasis on repairing the mitral valve rather than replacing it. A graduate of the University of Pennsylvania Medical School, Philadelphia, he served an internship and residency at Massachusetts General Hospital, Boston, and at Emory University, Atlanta.

Khusrow Niazi, M.D., is an assistant professor at Emory University School of Medicine and director of peripheral and carotid intervention at Emory University Hospital Midtown, Atlanta. He earned his medical degree at King Edward Medical College, Lahore, Pakistan, and served an internship at Kettering Medical Center, Dayton, Ohio, and a fellowship at William Beaumont Hospital, Royal Oak, MI. He has published papers on stenting following rotational atherectomy, small vessel stenting for coronary arteries, imaging of lower extremities and treatment of peripheral arterial disease.

Jeffrey J. Popma, M.D., is director of innovations in interventional cardiology, a senior attending physician at Beth Israel Deaconess Medical Center and an associate professor of medicine at Harvard Medical School in Boston. Dr. Popma received his bachelor’s degree in economics from Stanford University, and his M.D. from Indiana University School of Medicine. He completed his internship, residency, chief residency and fellowship at University of Texas Southwestern Medical Center. He also completed an interventional cardiology fellowship at the University of Michigan. Dr. Popma is the past president of the Society for Cardiac Angiography and Intervention and is the co-chair of the ACC Interventional Council. He sits on the editorial boards of several publications, and reviews for several cardiology periodicals. Dr. Popma has more than 300 published peer-reviewed manuscripts.

Dr. Popma also directs the BIDMC Angiographic Core Laboratory and is principal investigator for more than 65 ongoing multicenter device studies within the research laboratory. Over the past 15 years, these trials have included a broad array of new technology, including bare-metal stents, drug-eluting stents, distal-protection devices, total-occlusion devices and carotid and peripheral revascularization procedures. His primary clinical interest currently is the use of percutaneous aortic valve replacement for patients with high-risk aortic stenosis.

Robert S. Poston, M.D., is chief of cardiac surgery at Boston Medical Center and associate professor of cardiothoracic surgery at Boston University School of Medicine. He has a strong background in minimally invasive cardiac bypass surgery and is a pioneer in using robotics, specifically the da Vinci Surgical System, to treat coronary artery disease. A graduate of the Johns Hopkins School of Medicine, Baltimore, Dr. Poston completed a residency in general surgery at the University of California, San Francisco, and continued his training with a research fellowship in cardiothoracic surgery at Stanford University School of Medicine, Palo Alto, CA, and a cardiothoracic residency at the University of Pittsburgh Medical Center.

Charanjit S. Rihal, M.D., is professor of medicine and director of the cardiac catheterization laboratory at Mayo Graduate School of Medicine, Mayo Clinic, Rochester, MN. A graduate of the University of Winnipeg, Dr. Rihal did his residency and fellowship at the Mayo Graduate School of Medicine and also earned an MBA at the Carlson School of Management, University of Minnesota. His medical interests are interventional cardiology, structural heart disease interventions and the management of quality and costs in healthcare.

Timothy A. Shapiro, M.D., is director of the Interventional Cardiology Fellowship Program and campus chief, interventional cardiology, at Lankenau Hospital, Lancaster, PA. A graduate of Yale University School of Medicine, he served his residency and a fellowship at the Hospital of the University of Pennsylvania.

Robert J. Siegel, M.D., is director of the Cardiac Non-Invasive Laboratory at Cedars-Sinai Medical Center, cardiology director of the Cedars-Sinai Marfan Center, and Rexford S. Kennamer, M.D., chair in cardiac ultrasound at Cedars-Sinai Medical Center, Los Angeles. Dr. Siegel is also professor of medicine in residence at the David Geffen School of Medicine at University of California, Los Angeles. He previously served as senior staff fellow in cardiac pathology at the Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, MD. Internationally recognized as one of the leading experts in the field of cardiovascular ultrasound, Dr. Siegel specializes in cardiovascular ultrasound, including transthoracic, transesophageal and intravascular methodologies. His research interests include

  • valvular heart disease,
  • therapeutic applications of ultrasound energy,
  • transesophageal and intraoperative echocardiography, and the
  • development and use of hand-held portable echocardiographic systems for clinical innovations.

In addition, he is involved with clinical research studies related to the diagnosis, assessment and management of patients with

  • Marfan syndrome,
  • hypertrophic cardiomyopathy and
  • pericardial and valvular heart disease.

Dr. Siegel is a fellow, and has previously served as the president of the California Chapter of the American College of Cardiology and president of the Los Angeles Society of Echocardiography. He has been active in numerous cardiovascular societies, including the American Heart Association, the American College of Cardiology and the American Society of Echocardiography. Dr. Siegel received his medical degree at Baylor College of Medicine, Houston, where he developed an interest in cardiology. He completed his medical residency at Emory University and at Los Angeles County + USC Medical Center. He completed his cardiology fellowship at Harbor-UCLA Medical Center.

Over the last two years Dr. Siegel has worked extensively with live 3D transesophageal echo in the cardiac intervention center and the operating room. He and his echocardiologist colleagues, doctors Shiota, Biner, Tolstrup and Gurudevan, have worked closely at Cedars-Sinai Medical Center in Los Angeles with the interventional cardiologists, doctors Kar and Makkar, as well as with the cardiac surgeons, doctors Trento and Fontana. They use live 3D TEE extensively for the assessment of structural heart disease. In addition, it is used on a regular basis for the guidance of percutaneous procedures for mitral valve e-clip repair, mitral balloon valvuloplasty, aortic and pulmonic valve replacement, left atrial appendage exclusion by the Watchman device as well as for ASD closure.

Sudhir P. Srivastava, M.D., president of the International College of Robotic Surgery at St. Joseph’s Hospital, Atlanta, is a pioneer in performing beating heart totally endoscopic coronary artery bypass surgeries. Previously, he was assistant professor of surgery and director of robotic and minimally invasive cardiac surgery at the University of Chicago Medical Center. Dr. Srivastava specializes in robotically assisted totally endoscopic coronary artery bypass surgery. He has performed approximately 1,000 robotic cardiothoracic surgical procedures, of which 450  have been single- and multivessel beating heart totally endoscopic coronary bypass (BH TECAB) procedures. He has keen interest in hybrid coronary revascularization in TECAB patients to achieve complete revascularization.

Dr. Srivastava has helped launch robotic revascularization programs throughout the world. He has performed numerous live BH TECAB demonstrations both in the U.S. and abroad, and continues to be a presenter and invited speaker at numerous national and international scientific meetings. He earned his medical degree at the Jawahar Lal Nehru Medical College in Ajmer, India and immigrated to the U.S. in 1972. He completed his cardiothoracic surgery residency at the hospitals associated with the University of British Columbia, Vancouver, Canada.

Francis P. Sutter, D.O., F.A.C.S., is clinical professor of surgery at Thomas Jefferson University-Jefferson Medical College, Philadelphia, and chief of cardiothoracic surgery at Lankenau Hospital, Main Line Health System, Wynnewood, PA. A graduate of Philadelphia College of Osteopathic Medicine, his surgical residency and a cardiothoracic fellowship were completed at Thomas Jefferson University Hospital.

Mark R. Vesely, M.D., is an assistant professor of medicine at the University of Maryland School of Medicine. He completed medical school at the George Washington University and postgraduate training—an internal medicine residency and fellowships in cardiovascular disease and interventional cardiology—at the University of Maryland. He is board-certified in internal medicine, cardiovascular disease, nuclear cardiology and interventional cardiology. Dr. Vesely is the associate program director of the Interventional Cardiology fellowship at University of Maryland. His special interests include the partnered approach (interventional cardiologists and cardiac surgeons) for hybrid coronary revascularization and structural heart disease interventions. Additional research interests include investigation of techniques to minimize acute myocardial infarction injury with ventricular-assist devices and adult stem cell therapies.

David X. M. Zhao, M.D., Ph.D., is an associate professor of medicine and cardiac surgery, Harry and Shelley Page Chair in Interventional Cardiology, director of the Cardiac Catheterization Laboratories and interventional cardiology director of the Interventional Cardiology Fellowship Training Program, Vanderbilt University School of Medicine, Nashville, TN. He earned his medical degree at Shanghai Medical University, Shanghai, P.R. China, and his Ph.D. in immunology at Queensland University, Brisbane, Australia. His postdoctoral training was at Zhongshan Hospital, Shanghai Medical University, Shanghai, P.R. China, The Prince Charles Hospital, Brisbane, Australia, and Brigham and Women’s Hospital, Boston.

http://www.expo.acc.org/acc12/CUSTOM/images/ACC12/ACC.10%20Hybrid%20Suite%20Directory.pdf

Part Two

Cardiac Surgery

 

Cardiac Surgery @ Cleveland Clinic: Traditional OR & Hybrid Cath Lab/OR Suite

Nation #1 for 19 consecutive years – The Heart Center: Miller Family Heart & Vascular Institute @ Cleveland Clinic

The Sydell and Arnold Miller Family Heart & Vascular Institute is one of the largest, most experienced cardiovascular specialty groups in the world. Our physicians are committed to providing the most advanced diagnostic and treatment options, better outcomes and improved quality of life. U.S.News & World Reporthas ranked Cleveland Clinic as the No.1 heart program in America every year since 1995.

Departments & Centers:

Below we present two articles on Cardiac Surgery @ Mayo Clinic 

Cardiac Surgery @ Mayo Clinic: Traditional OR & Hybrid Cath Lab/OR Suite 

Coronary Reperfusion Therapies: CABG vs PCI – Mayo Clinic preprocedure Risk Score (MCRS) for Prediction of in-Hospital Mortality after CABG or PCI

Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Comparison of the 10-year and 15-year survivals after CABG demonstrated benefit from a change in graft sources used at the Mayo Clinic and widely adapted by others: vascular grafts from the left internal mammary artery (LIMA) instead of just leg veins, for multiple grafts (up to 3), LIMA-to-LAD plus grafts using LIMA or radial artery vs LIMA/saphenous vein (SV).

CABG Survival in Multivessel Disease Patients: Comparison of Arterial Bypass Grafts vs Saphenous Venous Grafts

Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Part Three 

Invasive Interventions with Complications

In the following article we covered multiple etiologies for cardiovascular complications related to invasive interventions: cardiovascular and peripheral arterial or peri- and post- cardiac surgery of the open heart type.

Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions

Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/07/23/cardiovascular-complications-of-multiple-etiologies-repeat-sternotomy-post-cabg-or-avr-post-pci-pad-endoscopy-andor-resultant-of-systemic-sepsis/

This article covers types of Cardiovascular Complications derived from the following THREE types of assault on the Human body, two related to cardiac invasive interventions, the last due to its systemic nature is taking a fatal Cardiac toll: the Sepsis condition causing cardiac failure.

Three types of Cardiovascular Complications:

I. Risk of Injury During Repeat Sternotomy – following CABG orAortic Valve Replacement, both done in Open Heart Surgery

II. Complications After Percutaneous Coronary intervention (PCI) and endovascular surgery for Peripheral Artery Disease (PAD)

  • (a) Post PCI, and
  • (b) PAD Endovascular Interventions: Carotid Artery Endarterectomy

III. Cardiac Failure During Systemic Sepsis

This article does NOT cover the following two types of Cardiovascular Complications:

1. Trauma Injury causing cardiac arrest, lung collapse or cardiogenic shock

2. Surgical Complication of Non-cardiac surgery type causing cardiac arrest, i.e, Surgery of Joint Replacement causing sepsis causing death or death caused by complications of surgery i.e., blood loss, viral infection, emboli, thrombus, stroke, or cardiogenic shock not related to Cardiovascular and Cardiac invasive interventions

The e-Reader is advised to consider the following expansion on the subject matter carrying the discussion to additional related clinical issues:

Larry H Bernstein, Advanced Topics in Sepsis and the Cardiovascular System at its End Stage

https://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-sepsis-and-the-cardiovascular-system-at-its-end-stage/

Bernstein, HL, Pearlman, JD and A. Lev-Ari  Alternative Designs for the Human Artificial Heart: The Patients in Heart Failure – Outcomes of Transplant (donor)/Implantation (artificial) and Monitoring Technologies for the Transplant/Implant Patient in the Community

https://pharmaceuticalintelligence.com/2013/08/05/alternative-designs-for-the-human-artificial-heart-the-patients-in-heart-failure-outcomes-of-transplant-donorimplantation-artificial-and-monitoring-technologies-for-the-transplantimplant-pat/

Pearlman, JD and A. Lev-Ari Cardiac Resynchronization Therapy (CRT) to Arrhythmias: Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion

https://pharmaceuticalintelligence.com/2013/07/22/cardiac-resynchronization-therapy-crt-to-arrhythmias-pacemakerimplantable-cardioverter-defibrillator-icd-insertion/

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