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percutaneous Left Ventricular Assist Device (pLVAD) – An Israeli startup, Magenta Medical, behind the world’s smallest heart pump has raised $55 million

Posted in Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart on May 5, 2023| Leave a Comment »

percutaneous Left Ventricular Assist Device (pLVAD) – An Israeli startup, Magenta Medical, behind the world’s smallest heart pump has raised $55 million

Curator: Aviva Lev-Ari, PhD, RN

May 3, 2023 at 8am EST

Magenta Medical Closes $55M Funding Round Led by OrbiMed

Funding will further Magenta’s clinical programs in support of FDA approval for world’s smallest heart pump

Kadima, Israel – May 03, 2023 – Magenta Medical, developer of the world’s smallest heart pump, announced today a $55M financing round led by global healthcare investment manager OrbiMed, with participation from existing investors New Enterprise Associates (NEA), Pitango VC, and ALIVE – Israel HealthTech Fund. The financing will be used, among other things, to advance the clinical programs of the company’s product in the United States towards its first FDA approval.

Temporary mechanical circulatory support (MCS) is one of the fastest growing markets in interventional cardiology, encompassing devices that aim to augment the output of a failing heart, in the setting of dangerously low blood pressure, while resting the heart and providing a bridge to recovery over a period of hours or days. Existing temporary MCS devices provide limited flow, require an invasive surgical procedure, or both.

Magenta’s percutaneous Left Ventricular Assist Device (pLVAD) is a powerful heart pump that is initially folded, inserted through the groin using a small puncture, and expanded for activation inside the left ventricle. The flow of the pump is adjusted based on the clinical circumstances of the patient, up to the entire cardiac output, allowing the heart to rest and the patient to recover. Once the Magenta technology is approved, physicians will be able to rely on a single device to treat the full range of MCS patients, thus eliminating the need to escalate therapy to a new device and subject the patient to unnecessary and invasive replacement procedures.

“Magenta is proud to add OrbiMed to its growing roster of leading MedTech investors as a highly reputable partner for innovative medical device companies,” said Dr. David Israeli, CEO of Magenta Medical. “I am confident that together we can build an organization well-equipped to bring to the market high-impact technology that can potentially address multiple unmet needs in the general cardiology patient population, as well as in many under-served patient groups.”

The potential advantages of Magenta’s high-flow, low-profile device were recognized by the US FDA, resulting in Breakthrough Device Designation for two indications: high-risk percutaneous coronary intervention (HR-PCI) and cardiogenic shock (CS).

Magenta successfully completed a HR-PCI first-in-human (FIH) study in Tbilisi, Georgia, the results of which were presented at the recent 2022 Transcatheter Cardiovascular Therapeutics (TCT) conference in Boston, MA, by Dr. Duane Pinto of Beth Israel Deaconess Medical Center and Harvard Medical School. Building on this experience, Magenta is now preparing to launch its clinical programs in the US, starting with an imminent HR-PCI Early Feasibility Study.

“Having supported Magenta’s FIH study, I was thoroughly impressed with the unique combination of a low-profile device delivering best-in-class flow,” said Dr. Pinto. “Magenta’s device is inserted with ease percutaneously and can accommodate the full gamut of flows required by MCS patients in the various situations I encounter as an interventional cardiologist. Use of this technology can be mastered by a wide range of proceduralists to better address the unmet needs of contemporary patients, such as those with small or challenging vascular anatomies, especially if high flows are needed.”

“We are excited to have identified the merits of Magenta’s technology, with its strong disruptive potential, and are extremely pleased with the relationships that we have built with management, the founders, and the existing investors,” said Dr. David Bonita, General Partner at OrbiMed. “We look forward to advancing the clinical programs and accelerating the introduction of this important technology to the market in the US and globally.”

Magenta’s proprietary technology miniaturizes a powerful percutaneous Left Ventricular Assist Device to fit an 8 Fr delivery system – the smallest crimping profile of any such device. The pump is inserted percutaneously, over a guidewire, through the aorta and across the aortic valve, using commercially available 10 Fr introducer sheaths. Employing standard catheterization techniques and equipment for placement has important advantages in terms of ease-of-use, safety, physician access, and vascular access closure. Once deployed inside the heart, the speed of the pump can be adjusted to provide more than 5 L/min of mean blood flow at physiological blood pressures – the full cardiac output of an adult – allowing the heart to rest and the patient to recover. With peak flows exceeding 7 L/min, this is the most powerful known percutaneous pump, comparing favorably even with surgically placed catheter pumps that have more than twice Magenta’s insertion profile.

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About Magenta Medical

Magenta Medical Ltd. is a privately-held company dedicated to the development of miniaturized blood pumps intended to provide minimally-invasive support to the native heart during acute episodes of dysfunction that could lead to dangerously low blood pressure and compromised perfusion of vital organs. Magenta’s Elevate™ percutaneous left ventricular assist device is currently in clinical testing, with the ultimate goal of securing approval for at least two indications: patients undergoing high-risk coronary interventions and patients with cardiogenic shock. Magenta Medical was founded by two serial entrepreneurs, Professor Ehud Schwammenthal and Mr. Yosi Tuval, who previously founded Ventor Technologies – a medical device company that was acquired by Medtronic in 2009. For more info, visit https://magentamed.com/.

About OrbiMed

OrbiMed is a healthcare investment firm, with approximately $17 billion in assets under management. OrbiMed invests globally across the healthcare industry through a range of private equity funds, public equity funds, and royalty/credit funds. OrbiMed’s team of over 100 professionals is based in New York City, San Francisco, Shanghai, Hong Kong, Mumbai, Herzliya and other key global markets.

Media Contact

Chaya Zabihi

GK for Magenta Medical

chaya@gkpr.com

SOURCE

From: Chaya Zabihi <chaya@gkpr.com>
Date: Tuesday, May 2, 2023 at 2:29 PM
To: Aviva Lev-Ari <avivalev-ari@alum.berkeley.edu>
Subject: Re: Embargo: Magenta Medical raises significant funding round for world’s smallest heart pump

3 May, 2023 13:10

Gali Weinreb

Magenta has developed a miniaturized catheter-mounted axial flow-pump for mechanical circulatory support of the left ventricle.

Israeli company Magenta Medical has announced the completion of a $55 million financing round led by OrbiMed Advisors and with the participation of previous investors NEA, Pitango and Alive.Magenta has developed a miniaturized catheter-mounted axial flow-pump for mechanical circulatory support of the left ventricle, based on Magenta’s core technology of a self-expanding impeller and pump head. The self-expanding impeller is comprised of a thin memory-shape metallic frame and a soft, flexible material that forms the body of the blades.Magenta Medical was founded in 2012 by CMO Prof. Ehud Schwammenthal and CTO Dr. Yosi Tuva, who had previously founded heart valve developer Ventor, which was sold to Medtronic in 2009 for $350 million. Magenta’s CEO is Dr. David Israeli, a former senior executive at Medtronic and Pitango, which invested in the company. Magenta has raised $100 million to date.

Dr. Israel told “Globes” that Magenta has changed its focus in recent years but not its technology – only the use it is aiming for. The pump was first developed to treat heart failure and was intended to be implanted in the renal veins to regulate blood pressure and evacuate salts and fluids – an improved replacement for diuretic drugs that are the standard treatment for heart failure, but they are not always helpful, and may have side effects. This product was already advanced, so with the company’s previous fundraising, it believed it could get the product approved without additional fundraising.

The reason for the change was the realization that the road to approval was longer than it seemed at first, because there is no such product on the market, and it was necessary to develop the protocol from start to finish, together with the FDA, and then overcome another hurdle of proving the economic value of the product to obtain insurance indemnity. So even though the product worked well, and despite (or rather because) there being no similar solutions on the market, the road looked too long and uncertain.

Meanwhile, another area began to capture the company’s attention: using a coronary artery pump to support patients arriving at the hospital with acute heart failure or undergoing high-risk interventional catheterization. The pump supports the heart’s activity and can even replace it until it recovers.

The field called Temporary Mechanical Circulatory Support has been growing in recent years led by Johnson & Johnson unit Abiomed. Magenta believes that as other products have already trod the regulatory path and then received insurance indemnity, the way forward in this sector is clearer while there remains plenty of room in the market for their distinct product.

RELATED ARTICLES

NEA makes first Israeli investment in Magenta Medical

The product has undergone trials with 15 patients in Georgia and is now undergoing a trial with 15 more patients in the US.

Published by Globes, Israel business news – en.globes.co.il – on May 3, 2023.

SOURCE

https://en.globes.co.il/en/article-heart-pump-co-magenta-medical-raises-55m-1001445415

World’s Smallest Heart Pump Yields $55M For Startup

By Ariel Grossman, NoCamels May 04, 2023 2 minutes

An Israeli startup behind the world’s smallest heart pump has raised $55 million.

Magenta Medical’s device will be used to support patients arriving at the hospital with heart failure, or undergoing high-risk treatments to alleviate their symptoms.

The pump can support the heart’s activity, and even replace it for several days until it recovers, by temporarily opening clogged arteries in the hearts of cardiac patients, and improving symptoms like chest pain and shortness of breath.

The pump is folded up and inserted through a catheter via the groin. Once it has been guided to the heart’s left ventricle (which is responsible for pumping oxygenated blood all over the body), and the catheter has been removed, it expands by up to three and a half times.

Inside the heart, the speed of the pump can be adjusted to provide more than five liters of blood a minute – the full cardiac output of an adult at rest. The company says the pump is more powerful than others, with peak flows exceeding seven liters per minute.

Existing temporary devices provide a more limited flow of oxygenated blood to the body’s tissues or require an invasive surgical procedure – or both.

Magenta Medical’s product has undergone trials with 15 patients in Georgia, USA. The company is now preparing to launch its clinical programs in the US. The financing will be used to advance the clinical programs of the product towards its first FDA approval.

The funding was raised by global healthcare investment manager OrbiMed, with participation from existing investors New Enterprise Associates, Pitango VC, and ALIVE – Israel HealthTech Fund.

“Magenta is proud to add OrbiMed to its growing roster of leading MedTech investors as a highly reputable partner for innovative medical device companies,” said CEO Dr. David Israeli.

“I am confident that together we can build an organization well-equipped to bring to the market high-impact technology that can potentially address multiple unmet needs in the general cardiology patient population, as well as in many under-served patient groups.”

Magenta Medical was founded in 2012, and is based in Kadima Zoran, central Israel.

SOURCE

https://nocamels.com/2023/05/worlds-smallest-heart-pump-yields-55m-for-startup/

https://www.amazon.com/dp/B07MKHDBHF

On Amazon.com since 12/24/2018

In Cardiology, “Interventional” is reserved for procedures that directly produce physical changes. Surgical interventions for cardiovascular diseases include heart or heart and lung transplant, implantation of cardiac assist devices, shock devices and pacemakers, bypass grafts for coronary or other arteries, valve repairs or replacement, removal of plaque (endarterectomy), removal of tumors, and repair or palliation of injuries or of congenital anomalies. All of these interventions are continually studied and improved, with a major effort at minimizing the risk, reducing recovery time and reducing the size of entry scar, for example by use of video scopes instead of direct visualization, and mechanical devices and robotics instead of direct manual access. Interventional Cardiology refers to an often competing non-surgical approach in which access is limited to entry by vein or artery (catheterization). The two teams have joined forces to achieve a major success in replacing aortic valves by femoral artery access without opening the chest at all (TAVR), with on-going progress towards a similar approach to mitral valve replacement.
This book addresses disease prevalence, personalized patient and doctor experiences with Cardiac Surgery, the role of transfusion, status of the MedTech market, and a review of major accomplishments from pathology, anesthesiology, radiology, cardiology and surgery. The contributions of specific groups, such as the Texas Heart Institute, the Dalio Institute at New York Presbyterian/Weill Cornell, the Cleveland Clinic, and the Scripps Institute are reviewed. Individual contributions from Eric Topol, Arthur Moss, Paul Zoll, Tim Wu, and Earl E. Bakken (Medtronic co-founder) are included. Discoveries in relevant biology, including ATP (the metabolic paycheck) and plasma metabolomics, and novel technologies such as tethered-liquid perfluorocabon surface biocoating to prevent clotting. Additional curations present views of cardiothoracic surgeons, vascular surgeons and of Catheterization lab interventionists. Business aspects are addressed by review of costs, prevalence, payment methods, prevention impact and business models. Decision support tools are also reviewed, and changes in guidelines. Voices of three Open Heart Surgery Survivors are included. Chapters 4-6 addressed clinical trial data in coronary disease, biomarkers of cardiovascular disorders, coagulation including top roles of nitric oxide, C-reative protein, protein C, aprotinin and thrombin. Chapters 7-8 covered amyloidosis, atherosclerosis, valve disease, flow reserve, atrial fibrillation and roles for advanced imaging. Chapters 9-10 covered unstable angina, transplants, and ventricular assist devices. Chapters 11-14 span interventions on the aorta, peripheral arteries, and coronary arteries, valve surgery and percutaneous valve repair or replacement, plus the growing role of prosthetics and repair by stem cells and tissue engineering.
As catheter techniques evolved to compete with bypass surgery they progressed from balloon cracking of obstructive lesions (POBA=plain old balloon angioplasty) to placement of stents (wire fences). Surgeons sometimes use in-stent valves, and now devices analogous to in-stent valves can be placed by catheter for valve replacement in patients with too much co-morbidity to go through heart surgery. Aortic valve replacement by stent (TAVR) has had sufficient success to be considered for all patients who have sufficient impairment to merit intervention. The diameter is large, so a vascular surgeon participates in the arterial access and repair of the access site.
Minimally invasive repair of abdominal aorta aneurysm: atherosclerosis offers potentially somewhat protective stiffening of the arterial wall, it can promote clots, athero-emboli, and failure of the remodeling can lead to an outward ballooning, or aneurysm, that promotes both clot formation and wall or lining tears or rupture, cause of sudden death.

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Chapter 7: Ventricular Failure: Assist Devices, Surgical and Non-Surgical

7.1 Trends in the Industry

The Voice of Series A Content Consultant: Justin D. Pearlman, MD, PhD, FACC

In addition to minimally invasive treatments for coronary disease and valve disease, there are minimally invasive alternatives to heart transplant for the dangerously weak heart (extreme heart failure) which can otherwise result in Cardiogenic Shock. These involve various means to augment or complement the pumping function of the heart, such as a Ventricular Assist Device (VAD) .

With respect to the performance of Mitral Valve Replacement, the current practice favors bioprosthetic valves over mechanical valve replacement for most patients, initially just used for elderly to avoid need for coumadin, but now used at younger ages due to improvements in longevity of the bioprosthetic valves, plus less damage to red cells.

7.1.1 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/

7.1.2 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/

7.1.3 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/

7.2 Left Ventricular Failure

7.2.1 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/

7.2.2 Treatment Options for Left Ventricular Failure – Temporary Circulatory Support: Intra-aortic balloon pump (IABP) – Impella Recover LD/LP 5.0 and 2.5, Pump Catheters (Non-surgical) vs Bridge Therapy: Percutaneous Left Ventricular Assist Devices (pLVADs) and LVADs (Surgical)

Author: Larry H Bernstein, MD, FCAP And Curator: Justin D Pearlman, MD, PhD, FACC

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/

7.2.3 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/

7.2.4 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/

7.2.5 CELLWAVE Randomized Clinical Trial: Modest improvement in LVEF at 4 months – “Shock wave–facilitated intracoronary administration of BMCs” vs “Shock wave treatment alone”

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/04/23/cellwave-randomized-clinical-trial-modest-improvement-in-lvef-at-4-months-shock-wave-facilitated-intracoronary-administration-of-bmcs-vs-shock-wave-treatment-alone/

7.2.6 Three-Dimensional Fibroblast Matrix Improves Left Ventricular Function post MI

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

https://pharmaceuticalintelligence.com/2013/11/02/three-dimensional-fibroblast-matrix-improves-left-ventricular-function/

7.3 Right Ventricular Failure

7.3.1 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/

Amyloidosis and Right Ventricular Hypertrophy

Amyloidosis inserts abnormal proteins into tissues – in the heart, that results in an insidious decline cardiac function marked by increased stiffness (requiring high filling pressures that wet the lungs) and decreased contractility or inotropy (pumping ability). resulting in poor circulation of nutrients to tissues and organs. Amyoloidosis is suspected when imaging shows thickened heart muscle and thickened valves with reduced function, but thickened muscle also occurs as a reaction to incomplete control of elevated blood pressures, as well as by other infiltrative disorders.

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Digital Therapeutics: A Threat or Opportunity to Pharmaceuticals

Posted in Artificial Heart, Artificial Intelligence - Breakthroughs in Theories and Technologies, Artificial Intelligence - General, Artificial intelligence applications for cardiology, Artificial Intelligence Applications in Health Care, Artificial Intelligence in Health Care - Tools & Innovations, Artificial Intelligence in Medicine - Application for Diagnosis, Artificial Intelligence in Medicine - Applications in Therapeutics, Artificial Pancreas for Type1 Diabetes, Artificial Vascular Structures, Biological Engineering, Digital HealthCare – biotech & internet joint ventures, Disease Biology, Drug Carrier Design, Drug Delivery Platform Technology, Drug Development/Formulation using 3D Printing, Electronic Health Record, Health Economics and Outcomes Research, Health Law & Patient Safety, HealthCare IT, Healthcare Reform, Intelligent Information Systems, Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Mobile Healthcare, Organ-on-a-Chip, Personal Health Applications: Tech Innovations serves HealhCare, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Transformative Technologies in Healthcare, Voices of Patients and Healthcare Providers, Wearable Tech + Digital Health, tagged digital solution, digital therapeutics, Pharmaceuticals, Therapy, treatment on March 18, 2019| Leave a Comment »

Digital Therapeutics: A Threat or Opportunity to Pharmaceuticals

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

3.3.7

3.3.7 Digital Therapeutics: A Threat or Opportunity to Pharmaceuticals, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Digital Therapeutics (DTx) have been defined by the Digital Therapeutics Alliance (DTA) as “delivering evidence based therapeutic interventions to patients, that are driven by software to prevent, manage or treat a medical disorder or disease”. They might come in the form of a smart phone or computer tablet app, or some form of a cloud-based service connected to a wearable device. DTx tend to fall into three groups. Firstly, developers and mental health researchers have built digital solutions which typically provide a form of software delivered Cognitive-Behaviour Therapies (CBT) that help patients change behaviours and develop coping strategies around their condition. Secondly there are the group of Digital Therapeutics which target lifestyle issues, such as diet, exercise and stress, that are associated with chronic conditions, and work by offering personalized support for goal setting and target achievement. Lastly, DTx can be designed to work in combination with existing medication or treatments, helping patients manage their therapies and focus on ensuring the therapy delivers the best outcomes possible.

Pharmaceutical companies are clearly trying to understand what DTx will mean for them. They want to analyze whether it will be a threat or opportunity to their business. For a long time, they have been providing additional support services to patients who take relatively expensive drugs for chronic conditions. A nurse-led service might provide visits and telephone support to diabetics for example who self-inject insulin therapies. But DTx will help broaden the scope of support services because they can be delivered cost-effectively, and importantly have the ability to capture real-world evidence on patient outcomes. They will no-longer be reserved for the most expensive drugs or therapies but could apply to a whole range of common treatments to boost their efficacy. Faced with the arrival of Digital Therapeutics either replacing drugs, or playing an important role alongside therapies, pharmaceutical firms have three options. They can either ignore DTx and focus on developing drug therapies as they have done; they can partner with a growing number of DTx companies to develop software and services complimenting their drugs; or they can start to build their own Digital Therapeutics to work with their products.

Digital Therapeutics will have knock-on effects in health industries, which may be as great as the introduction of therapeutic apps and services themselves. Together with connected health monitoring devices, DTx will offer a near constant stream of data about an individuals’ behavior, real world context around factors affecting their treatment in their everyday lives and emotional and physiological data such as blood pressure and blood sugar levels. Analysis of the resulting data will help create support services tailored to each patient. But who stores and analyses this data is an important question. Strong data governance will be paramount to maintaining trust, and the highly regulated pharmaceutical industry may not be best-placed to handle individual patient data. Meanwhile, the health sector (payers and healthcare providers) is becoming more focused on patient outcomes, and payment for value not volume. The future will say whether pharmaceutical firms enhance the effectiveness of drugs with DTx, or in some cases replace drugs with DTx.

Digital Therapeutics have the potential to change what the pharmaceutical industry sells: rather than a drug it will sell a package of drugs and digital services. But they will also alter who the industry sells to. Pharmaceutical firms have traditionally marketed drugs to doctors, pharmacists and other health professionals, based on the efficacy of a specific product. Soon it could be paid on the outcome of a bundle of digital therapies, medicines and services with a closer connection to both providers and patients. Apart from a notable few, most pharmaceutical firms have taken a cautious approach towards Digital Therapeutics. Now, it is to be observed that how the pharmaceutical companies use DTx to their benefit as well as for the benefit of the general population.

References:

https://eloqua.eyeforpharma.com/LP=23674?utm_campaign=EFP%2007MAR19%20EFP%20Database&utm_medium=email&utm_source=Eloqua&elqTrackId=73e21ae550de49ccabbf65fce72faea0&elq=818d76a54d894491b031fa8d1cc8d05c&elqaid=43259&elqat=1&elqCampaignId=24564

https://www.s3connectedhealth.com/resources/white-papers/digital-therapeutics-pharmas-threat-or-opportunity/

http://www.pharmatimes.com/web_exclusives/digital_therapeutics_will_transform_pharma_and_healthcare_industries_in_2019._heres_how._1273671

https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/exploring-the-potential-of-digital-therapeutics

https://player.fm/series/digital-health-today-2404448/s9-081-scaling-digital-therapeutics-the-opportunities-and-challenges

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

Posted in congestive heart failure, Frontiers in Cardiology and Cardiovascular Disorders, Heart Failure (HF), Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Devices R&D and Inventions, Origins of Cardiovascular Disease on May 9, 2018| 1 Comment »

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

UPDATED on 5/11/2022

For heart failure patients with mildly reduced or preserved ejection fraction in the DELIVER trial, dapagliflozin (Farxiga) helped reduce the risk of cardiovascular death and worsening heart failure, AstraZeneca announced, paving the way for a new indication in the future.

But how many real-world heart failure patients would actually be eligible for SGLT2 inhibitors based on trial criteria? (Journal of Cardiac Failure)

SOURCE

https://www.medpagetoday.com/cardiology/prevention/98631?xid=nl_mpt_DHE_2022-05-10&eun=g99985d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20Evening%202022-05-10&utm_term=NL_Daily_DHE_dual-gmail-definition

UPDATED on 8/28/2021

Empagliflozin in Heart Failure with a Preserved Ejection Fraction

List of authors.

Stefan D. Anker, M.D., Ph.D.,
Javed Butler, M.D.,
Gerasimos Filippatos, M.D., Ph.D.,
João P. Ferreira, M.D.,
Edimar Bocchi, M.D.,
Michael Böhm, M.D., Ph.D.,
Hans-Peter Brunner–La Rocca, M.D.,
Dong-Ju Choi, M.D.,
Vijay Chopra, M.D.,
Eduardo Chuquiure-Valenzuela, M.D.,
Nadia Giannetti, M.D.,
Juan Esteban Gomez-Mesa, M.D.,
for the EMPEROR-Preserved Trial Investigators^*

Abstract

BACKGROUND

Sodium–glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain.

METHODS

In this double-blind trial, we randomly assigned 5988 patients with class II–IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure.

RESULTS

Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin.

CONCLUSIONS

Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951. opens in new tab).

UPDATED on 2/12/2019

Almost 25% of HFrEF patients prescribed drugs that could worsen their condition

February 11, 2019 | Anicka Slachta | Heart Failure

Prescription of Potentially Harmful Drugs in Young Adults With Heart Failure and Reduced Ejection Fraction

Paulino A. Alvarez, MD

Correspondence information about the author MD Paulino A. Alvarez

Email the author MD Paulino A. Alvarez

Chau N Truong, MPH

Alexandros Briasoulis, MD PhD

Cecilia Ganduglia-Cazaban, MD PhD

DOI: https://doi.org/10.1016/j.amjcard.2019.01.052

The Voice of Dr. Justin D. Pearlman

The selection of medications for patients with multiple conditions (co-morbidities) always raises conflicts. This is true in general, and especially true for patients with heart failure.

For example, patients with heart failure with reduced ejection fraction (HFrEF) have increased risk of atrial fibrillation, whereby sustained rapid ventricular response may worsen the failure due to tachycardiomyopathy. In essence, sustained high heatrates deplete supplies and weaken the heart, which can take months of controlled rates to recover.

Medications to control the rate are problematic. Digoxin increases the death rate. Beta blockers and diltiazem decrease the heartrate but also decrease contractility (EF), and in combination may stop the heart (complete heart clock, cardiac arrest). Anti-arrhythmic agents also decrease contractility. Use of beta blockers is encouraged because benefits often outweigh the harm, though in some cases the decline in contractility results in unacceptably low blood pressure. Some patients with rate control issues do not tolerate beta blockers but do better on diltiazem instead. Thus the list of medications that may worsen heart failure constitute “relative contraindications” which means concerning but still possibly useful.

In other words, some of the medications that may worsen ejection fraction have net benefit, and may be used with caution.

Non-steroidal anti inflammatory agents (NSAIDs) are another example. They relieve pain and add function to patients limited by arthritis. High dose ibuprofen tapered over one month can stop pericarditis, as an alternative to colchicine which may be limited by causing intractable diarrhea. Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease prostaglandin synthesis and, thus, may precipitate fluid retention in patients with heart failure. They also increase blood pressure, impair renal function and promote thrombosis (clotting). Use of NSAIDS has not been shown to curtail joint damage to joints, and daily use for 18 months or more promotes coronary disease. Overall, NSAIDs appear to be over utilized.

The high incidence of use of medications that may cause or worsen reduced EF heart failure is a concern of caution. Such use merits continual monitoring for net harm versus benefit on an individual basis. The study in AJC documenting the high incidence of use of medications that worsen heart failure in patients already known to have reduced ejection fraction is helpful as a reminder of caution highlighting the importance of individualizing medication choices, but should not be rigidly interpreted as absolute contraindication or presumed error.

SOURCE

From: Justin MDMEPhD <jdpmdphd@gmail.com>

Date: Tuesday, February 12, 2019 at 7:53 AM

To: Aviva Lev-Ari <aviva.lev-ari@comcast.net>

Subject: Re: Almost 25% of HFrEF patients prescribed drugs that could worsen their condition

UPDATED on 1/15/2019

Andrew Perry, MD, interviews John Gorcsan III, MD

by Andrew Perry, MDJanuary 12, 2019

In this episode, Andrew Perry, MD, discusses the utility of ejection fraction (EF) with John Gorcsan III, MD, an expert in echocardiography and strain imaging at Washington University School of Medicine in St. Louis.

They explore how EF came to be used in clinical practice, the importance of it in heart failure and the variation in measurement. The interview also covers strain imaging and what it adds to ejection fraction, particularly in the setting of severe mitral regurgitation.

https://www.medpagetoday.com/cardiology/arrhythmias/77390?xid=nl_mpt_DHE_2019-01-15&eun=g99985d0r&pos=111111&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%202019-01-15&utm_term=NL_Daily_DHE_Active

UPDATED on 1/9/2019

HFrEF: NT-proBNP decrease marks reverse remodeling, better outcomes

Source: JACC Heart Fail

Curated by: Jenny Blair, MD

January 08, 2019

Takeaway

In heart failure (HF) with reduced ejection fraction (HFrEF), a drop in pro-B-type natriuretic peptide (NT-proBNP) to <1000 mg/mL reflects reverse remodeling and improved ejection fraction (EF).

Authors suggest that response to treatment based on change in NT-proBNP might outweigh treatment strategy.

Why this matters

Whether lower NT-proBNP levels reflect changes in cardiac structure and function has been unclear.

Key results

12-month changes with guided therapy vs without:

No significant between-group differences in left ventricular (LV) end-systolic volume index (ESVi), NT-proBNP, EF.

Changes among subgroup whose NT-proBNP fell to <1000 pg/mL (n=52):

ESVi and end-diastolic volume index (EDVi) reductions: 17.3 and 15.7 mL/m², respectively;

EF: 9.9%±8.8% vs 2.9%±7.9% in nontarget achievers (P<.001);

Death or HF hospitalization: 0% vs 30% in nontarget achievers (P<.001);

Greater improvement in global longitudinal strain, less mitral regurgitation.

Greater reduction in NT-proBNP correlated with significantly greater EF, ESVi, EDVi improvements.

Study design

Randomized parallel-group multicenter GUIDE-IT Echo Substudy.

268 adults with HFrEF, EF ≤40%, NT-proBNP >2000 pg/mL randomly assigned to NT-proBNP-guided therapy vs usual care.

Outcome: 12-month change in LV ESVi on echocardiography.

Funding: Roche Diagnostics.

Limitations

Duration of NT-proBNP <1000 not assessed.

SOURCE

http://univadis.com/player/ymdmniqsi?m=unv_eml_essentials_enl_v4-q42018_20190109&partner=unl&rgid=5wrwznernxgefmacwqyebgmyb&ts=2019010900&o=tile_1_id&utm_source=Retention&utm_medium=newsletter&utm_campaign=unv_eml_essentials_enl_v4-q42018_20190109_01

Expert Opinion by Cardiologist Justin D. Pearlman MD PhD FACC

Pearls From: Ted Feldman, MD – A glimmer of hope for HFpEF treatment?

Evanston Hospital in Illinois

by Nicole Lou, Contributing Writer, MedPage TodayMay 08, 2018

SOURCE ARTICLE

https://www.medpagetoday.com/cardiology/chf/72759?xid=nl_mpt_DHE_2018-05-09

WATCH VIDEO

https://www.medpagetoday.com/cardiology/chf/72759?xid=nl_mpt_DHE_2018-05-09

Heart Failure with preserved Ejection Fraction (or HFpEF) – Experimental Therapy: Inter-atrial shunt implantable device for relieving pressure overload and improve the prognosis of patients with a 50% ejection fraction

Heart Failure with reduced Ejection Fraction (HFrEF)

HFpEF is similar in frequency and sadly, similar in prognosis to heart failure with reduced ejection fraction, and everybody thinks about the EF 20% or 30% patient as having a poor prognosis and doesn’t realize that the EF 40% or 45% or 50% patient with clinical heart failure has the same prognosis.

Patients with mitral stenosis and elevated left atrial pressure, which is the genesis of HFpEF, if they had an ASD historically, this decompressed the left atrium and they presented much, much later in the course of the disease with any signs of heart failure.

Inspiration for design of the Left inter-atrial shunt implant device

Minimally invasive transcatheter closure is the primary treatment option for secundum atrial septal defects (ASD). The AMPLATZER™ Septal Occluder is the proven standard of care in transcatheter ASD closure

Left inter-atrial shunt implant device, Dr. Ted Feldman calls IASD.

It’s like an ASD occluder, a little nitinol disc, but it has a hole in the middle. We did some baseline hemodynamic modeling using a simulator and calculated that we would get a small shunt with an eight millimeter opening, that that would be enough to reduce left atrial pressure overload during exercise without overloading the right side of the heart, without creating too big a shunt.

Preliminary results: We found that peak exercise wedge pressure was significantly decreased in the patients with the device compared to those without a shunt. We found that the shunt ratio, the amount of flow across the shunt was a Qp:Qs, pulmonary to systemic flow ratio, of 1.2 preserved at 30 days and 6 months and that most of these patients feel better.

Ted Feldman, MD, Evanston Hospital in Illinois

The mechanism, I think we’ve established, that we do decompress the left atrium with exertion and now we need to demonstrate that the clinical outcomes in a larger population are robust enough to carry this into practice.

Expert Opinion by Cardiologist Justin D. Pearlman MD PhD FACC

The assertion of “no treatment for HFpEF” (elevated left ventricular diastolic filling pressure) does not give credit to evidence and support for benefit from triple therapy of beta blocker, acei/arb/arni, and aldosterone inhibitor, plus tight blood pressure control and additional afterload reduction if valve leaks contribute to the elevated diastolic filling pressures.
It is an interesting proposition to induce an 8 mm intra-atrial septum (IAS) shunt, which may indeed unload high pressure in the left atrium and hence unload the left ventricle during diastole (when the mitral valve is open so the left ventricle and left atrium equalize pressures) if patients are very carefully selected and do not have high pressures in the right atrium.
However, elevated left ventricular pressure is associated with reduced compliance (stiffness) of the left ventricle, for example due to high blood pressure, muscle hypertrophy and fibrosis. Adverse consequences include not only the high pressure which can back up to the lungs, making them boggy and therefore impair oxygen uptake resulting in shortness of breath worse laying down whereby more lung area is affected. The “back pressure” also promotes hepatic congestion and leg swelling. Each of those features of “diastolic failure” which underlies “HFpEF” may benefit from the proposed shunt if right atrial pressures are low, with or without preserved ejection fraction (pEF). However, there is an additional adverse consequence of a stiff left ventricle called “filling dependence” – if pressure is relieved, the left ventricle may under fill, reducing stroke volume and blood pressure, cardiac output (stroke volume times heart rate), thereby reducing organ perfusion. Low blood pressure with lightheaded spells is a common consequence. Over time, metarterioles to the brain can adjust to accommodate lower pressures. The kidneys as well as the brain are very sensitive to adequacy of cardiac output. A marked decline in renal function due to “pre-renal azotemia” is a common consequence that can limit any approach at lowering the diastolic filling pressure, which is seen commonly with use of diuretics to lower pressures.
The small opening is intended to allow pressure unloading without clots crossing over, but may still pose a risk for paradoxical emboli, which have been associated with

visual field cuts,
TIA and
migraine headaches

Paradoxical Embolism

Updated: Jun 10, 2016

Author: Igor A Laskowski, MD; Chief Editor: Vincent Lopez Rowe, MD more…

Background

The clinical manifestations of paradoxical embolism (PDE) are nonspecific,^[1]and the diagnosis is difficult to establish. Patients with PDE may present with neurologic abnormalities or features suggesting arterial embolism. The disease starts with the formation of emboli within the venous system, which traverse a patent foramen ovale (PFO) and enter the systemic circulation.^[2, 3, 4]PFOs have been found on autopsy in up to 35% of the healthy population.

PDE originates in the veins of the lower extremities and occasionally in the pelvic veins. Emboli may be of various types, such as clots, air, tumor, fat, and amniotic fluid.^[5]Septic emboli have led to brain abscesses. Projectile embolization is rare (eg, from a shotgun pellet).

Management of PDE is both medical and surgical in nature. PDE is considered the major cause of cerebral ischemic events in young patients. On rare occasions, it may occlude the pelvic aortic bifurcation. The largest documented thrombus in a PFO (impending PDE) was 25 cm in length.

PDE is confirmed by the presence of thrombus within an intracardiac defect on contrast echocardiography or at autopsy. It may be presumed in the presence of arterial embolism with no evidence of left-side circulation thrombus, deep venous thrombosis (DVT) with or without pulmonary embolism (PE), and right-to-left shunting through an intracardiac communication, commonly the PFO.^[6]

SOURCE for Paradoxical Embolism

https://emedicine.medscape.com/article/460607-overview

SOURCE for Dr. Pearlman’s Expert Opinion

From: Justin MDMEPhD <jdpmdphd@gmail.com>

Date: Wednesday, May 9, 2018 at 2:25 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Cc: “Dr. Larry Bernstein” <larry.bernstein@gmail.com>

Subject: Re: WHICH of our Heart Failure ARTICLES I should UPDATE with the following Pearls From: Ted Feldman, MD | Medpage Today

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

Posted in Acute Myocardial Infarction, Assist Devices: LV, CABG, Cardiac and Cardiovascular Surgical Procedures, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, congestive heart failure, FDA Regulatory Affairs, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Frontiers in Cardiology and Cardiovascular Disorders, Heart Failure (HF), Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Devices R&D and Inventions, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, RV, tagged Cardiogenic Shock, post-cardiotomy cardiogenic shock (PCCS) on July 6, 2016| Leave a Comment »

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

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 11/1/2022

Johnson & Johnson to acquire Abiomed in $16.6B deal

Michael Walter | November 01, 2022 | Economics

Johnson & Johnson has entered into a definitive agreement to acquire Abiomed in a deal valued at approximately $16.6 billion. The boards of directors of both companies have unanimously approved the transaction.

Johnson & Johnson agreed to an upfront payment of $380 per share. Abiomed shareholders will also receive a non-tradeable contingent value of up to $35 per share if certain milestones are met. For example, if the company receives FDA premarket application approval for the use of its Impella heart pumps to treat ST-elevation myocardial infarction (STEMI) patients without cardiogenic shock by Jan. 1, 2028, each shareholder will receive $7.50 per share. If Impella devices receive a Class 1 recommendation for the treatment of high-risk percutaneous coronary intervention or STEMI patients with or without cardiogenic shock by Dec. 31, 2029, shareholders will receive an additional $10 per share.

“The addition of Abiomed is an important step in the execution of our strategic priorities and our vision for the new Johnson & Johnson focused on pharmaceutical and MedTech,” Johnson & Johnson CEO Joaquin Duato said in a prepared statement. “We have committed to enhancing our position in MedTech by entering high-growth segments. The addition of Abiomed provides a strategic platform to advance breakthrough treatments in cardiovascular disease and helps more patients around the world while driving value for our shareholders.”

Michael R. Minogue, Abiomed’s chairman, president and CEO, said in the same statement. “It will enable us to leverage Johnson & Johnson’s global scale, commercial strength and clinical expertise to accelerate our mission of making heart recovery the global standard of care.”

This acquisition is expected to be finalized by the end of the first quarter of 2023.

SOURCE

https://cardiovascularbusiness.com/topics/healthcare-management/healthcare-economics/johnson-johnson-acquire-abiomed-166b-deal?utm_source=newsletter&utm_medium=cvb_breaking

Abiomed Impella® Therapy Receives FDA Approval for Cardiogenic Shock After Heart Attack or Heart Surgery

Entire Family of Impella Left Side Heart Pumps FDA Approved To Enable Heart Recovery

DANVERS, Mass., April 07, 2016 (GLOBE NEWSWIRE) — Abiomed, Inc. (NASDAQ:ABMD), a leading provider of breakthrough heart support technologies, today announced that it has received U.S. Food and Drug Administration (FDA) Pre-Market Approval (PMA) for its Impella 2.5™, Impella CP®, Impella 5.0™ and Impella LD™ heart pumps to provide treatment of ongoing cardiogenic shock. In this setting, the Impella heart pumps stabilize the patient’s hemodynamics, unload the left ventricle, perfuse the end organs and allow for recovery of the native heart. This latest approval adds to the prior FDA indication of Impella 2.5 for high risk percutaneous coronary intervention (PCI), or Protected PCI™, received in March 2015.

With this approval, these are the first and only percutaneous temporary ventricular support devices that are FDA-approved as safe and effective for the cardiogenic shock indication, as stated below:

The Impella 2.5, Impella CP, Impella 5.0 and Impella LD catheters, in conjunction with the Automated Impella Controller console, are intended for short-term use (<4 days for the Impella 2.5 and Impella CP and <6 days for the Impella 5.0 and Impella LD) and indicated for the treatment of ongoing cardiogenic shock that occurs immediately (<48 hours) following acute myocardial infarction (AMI) or open heart surgery as a result of isolated left ventricular failure that is not responsive to optimal medical management and conventional treatment measures with or without an intra-aortic balloon pump. The intent of the Impella system therapy is to reduce ventricular work and to provide the circulatory support necessary to allow heart recovery and early assessment of residual myocardial function.

The product labeling also allows for the clinical decision to leave Impella 2.5, Impella CP, Impella 5.0 and Impella LD in place beyond the intended duration of four to six days due to unforeseen circumstances.

The Impella products offer the unique ability to both stabilize the patient’s hemodynamics before or during a PCI procedure and unload the heart, which allows the muscle to rest and potentially recover its native function. Heart recovery is the ideal option for a patient’s quality of life and as documented in several clinical papers, has the ability to save costs for the healthcare system^1,2,3.

Cardiogenic shock is a life-threatening condition in which the heart is suddenly unable to pump enough blood and oxygen to support the body’s vital organs. For this approval, it typically occurs during or after a heart attack or acute myocardial infarction (AMI) or cardiopulmonary bypass surgery as a result of a weakened or damaged heart muscle. Despite advancements in medical technology, critical care guidelines and interventional techniques, AMI cardiogenic shock and post-cardiotomy cardiogenic shock (PCCS) carry a high mortality risk and has shown an incremental but consistent increase in occurrence in recent years in the United States.

“This approval sets a new standard for the entire cardiovascular community as clinicians continue to seek education and new approaches to effectively treat severely ill cardiac patients with limited options and high mortality risk,” said William O’Neill, M.D., medical director of the Center for Structural Heart Disease at Henry Ford Hospital. “The Impella heart pumps offer the ability to provide percutaneous hemodynamic stability to high-risk patients in need of rapid and effective treatment by unloading the heart, perfusing the end organs and ultimately, allowing for the opportunity to recover native heart function.”

“Abiomed would like to recognize our customers, physicians, nurses, scientists, regulators and employees for their last fifteen years of circulatory support research and clinical applications. This FDA approval marks a significant milestone in the treatment of heart disease. The new medical field of heart muscle recovery has begun,” said Michael R. Minogue, President, Chairman and Chief Executive Officer of Abiomed. “Today, Abiomed only treats around 5% of this AMI cardiogenic shock patient population, which suffers one of the highest mortality risks of any patient in the heart hospital. Tomorrow, Abiomed will be able to educate and directly partner with our customers and establish appropriate protocols to improve the patient outcomes focused on native heart recovery.”

Abiomed Data Supporting FDA Approval

The data submitted to the FDA in support of the PMA included an analysis of 415 patients from the RECOVER 1 study and the U.S. Impella registry (cVAD Registry™), as well as an Impella literature review including 692 patients treated with Impella from 17 clinical studies. A safety analysis reviewed over 24,000 Impella treated patients using the FDA medical device reporting (“MDR”) database, which draws from seven years of U.S. experience with Impella.

In addition, the Company also provided a benchmark analysis of Impella patients in the real-world Impella cVAD registry vs. these same patient groups in the Abiomed AB5000/BVS 5000 Registry. The Abiomed BVS 5000 product was the first ventricular assist device (VAD) ever approved by the FDA in 1991 based on 83 patient PMA study. In 2003, the AB5000 Ventricle received FDA approval and this also included a PMA study with 60 patients.

For this approval, the data source for this benchmark analysis was a registry (“AB/BVS Registry”) that contained 2,152 patients that received the AB5000 and BVS 5000 devices, which were originally approved for heart recovery. The analysis examined by the FDA used 204 patients that received the AB5000 device for the same indications. This analysis demonstrated significantly better outcomes with Impella in these patients.

The Company believes this is the most comprehensive review ever submitted to the FDA for circulatory support in the cardiogenic shock population.

Maini B, Gregory D, Scotti DJ, Buyantseva L. Percutaneous cardiac assist devices compared with surgical hemodynamic support alternatives: Cost-Effectiveness in the Emergent Setting.Catheter Cardiovasc Interv. 2014 May 1;83(6):E183-92.
Cheung A, Danter M, Gregory D. TCT-385 Comparative Economic Outcomes in Cardiogenic Shock Patients Managed with the Minimally Invasive Impella or Extracorporeal Life Support. J Am Coll Cardiol. 2012;60(17_S):. doi:10.1016/j.jacc.2012.08.413.
Gregory D, Scotti DJ, de Lissovoy G, Palacios I, Dixon, Maini B, O’Neill W. A value-based analysis of hemodynamic support strategies for high-risk heart failure patients undergoing a percutaneous coronary intervention. Am Health Drug Benefits. 2013 Mar;6(2):88-99

ABOUT IMPELLA
Impella 2.5 received FDA PMA approval for high risk PCI in March 2015, is supported by clinical guidelines, and is reimbursed by the Centers for Medicare & Medicaid Services (CMS) under ICD-9-CM code 37.68 for multiple indications. The Impella RP® device received Humanitarian Device Exemption (HDE) approval in January 2015. The Impella product portfolio, which is comprised of Impella 2.5, Impella CP, Impella 5.0, Impella LD, and Impella RP, has supported over 35,000 patients in the United States.

The ABIOMED logo, ABIOMED, Impella, Impella CP, and Impella RP are registered trademarks of Abiomed, Inc. in the U.S.A. and certain foreign countries. Impella 2.5, Impella 5.0, Impella LD, and Protected PCI are trademarks of Abiomed, Inc.

ABOUT ABIOMED
Based in Danvers, Massachusetts, Abiomed, Inc. is a leading provider of medical devices that provide circulatory support. Our products are designed to enable the heart to rest by improving blood flow and/or performing the pumping of the heart. For additional information, please visit: www.abiomed.com

FORWARD-LOOKING STATEMENTS
This release includes forward-looking statements. These forward-looking statements generally can be identified by the use of words such as “anticipate,” “expect,” “plan,” “could,” “may,” “will,” “believe,” “estimate,” “forecast,” “goal,” “project,” and other words of similar meaning. These forward-looking statements address various matters including, the Company’s guidance for fiscal 2016 revenue. Each forward-looking statement contained in this press release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others, uncertainties associated with development, testing and related regulatory approvals, including the potential for future losses, complex manufacturing, high quality requirements, dependence on limited sources of supply, competition, technological change, government regulation, litigation matters, future capital needs and uncertainty of additional financing, and the risks identified under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended March 31, 2015 and the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015, each filed with the Securities and Exchange Commission, as well as other information the Company files with the SEC. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at www.sec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this release and the Company undertakes no obligation to update or revise any of these statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.

For more information, please contact: Aimee Genzler Director, Corporate Communications 978-646-1553 agenzler@abiomed.com Ingrid Goldberg Director, Investor Relations igoldberg@abiomed.com

SOURCE
http://investors.abiomed.com/releasedetail.cfm?ReleaseID=964113

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

Posted in Cardiac and Cardiovascular Surgical Procedures, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics, Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Devices R&D and Inventions, tagged heart’s left atrial appendage embolization on April 5, 2016| Leave a Comment »

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

Boston Scientific halts EU sales of next-gen Watchman FLX anti-stroke device

APRIL 5, 2016 BY BRAD PERRIELLO LEAVE A COMMENT

Boston Scientific (NYSE:BSX) reportedly halted European sales of its the next generation of its anti-stroke device, the Watchman FLX, after receiving reports of device embolization.

Spokeswoman Trish Backes told TCTMD that there were 6 device embolizations in 207 (2.9%) European implantations of the Watchman FLX, an implant that designed to occlude the heart’s left atrial appendage. One of those patients died from complications related to an infection suffered after the device was retrieved.

The 1st-generation Watchman device showed a 30-day embolization rate of 0 to 0.7% in trials, and a post-approval registry called Ewolution showed a rate of 0.2%. The Watchman FLX device won CE Mark approval in the European Unionlast November; the original iteration won FDA approval in March 2015.

Watchman FLX will be taken off the shelves until Boston Scientific can determine what’s causing the unexpectedly high embolism rate, Backes told the website.

“With [the original] Watchman, we’re really confident. We’ve seen really low embolization rates,” she said. “With the robust clinical training program that we have in place for physicians before they start implanting the device, we feel really good about that. This doesn’t impact what we’re doing in the U.S. or what we’re doing with the current Watchman device. It’s not raising any concerns for us for the current device.”

Medical officers with the Marlborough, Mass.-based company, speaking at the annual conference of the American College of Cardiology, said they’ll look at whether physician training or implant technique are factors. The company said the sales halt for Watchman FLX will not affect its structural heart sales forecast of $175 million to $200 million this year.

Boston Scientific said earlier this week at ACC 2016 that a review of the 1st 1,000 Watchman patients found similar results as in pre-market trials.

Material from Reuters was used in this report.

SOURCE

http://www.massdevice.com/boston-scientific-halts-eu-sales-of-next-gen-watchman-flx-anti-stroke-device/?utm_source=newsletter-160405&utm_medium=email&utm_campaign=newsletter-160405&spMailingID=8750804&spUserID=MTI2MTQxNTczMjM5S0&spJobID=900546483&spReportId=OTAwNTQ2NDgzS0

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Steps to minimise replacement of cardiac implantable electronic devices

Posted in Atrial Fibrilation (a-Fib), Cardiac Pacing and Arrhythmias, Cardiac and Cardiovascular Surgical Procedures, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, Electrophysiology, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Frontiers in Cardiology and Cardiovascular Disorders, Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Devices R&D and Inventions on February 4, 2016| Leave a Comment »

UPDATED on 2/25/2019

https://www.medpagetoday.com/cardiology/prevention/78202?xid=nl_mpt_SRCardiology_2019-02-25&eun=g99985d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=CardioUpdate_022519&utm_term=NL_Spec_Cardiology_Update_Active

Medtronic recalled its dual chamber pacemakers (Adapta, Versa, Sensia, Relia, Attesta, Sphera, and Vitatron A, E, G, and Q series) due to a possible software error that can stop pacing.

Steps to minimise replacement of cardiac implantable electronic devices

Reporter: Aviva Lev-Ari, PhD, RN

Pacemaker battery scandal

SOURCE

http://www.bmj.com/content/352/bmj.i228

BMJ 2016; 352 doi: http://dx.doi.org/10.1136/bmj.i228 (Published 04 February 2016)Cite this as: BMJ 2016;352:i228

John Dean, consultant cardiologist 1,
Neil Sulke, consultant cardiologist 2

Author affiliations

Correspondence to: J Dean john.dean2@nhs.net

Much can and should be done to maximise the longevity of existing devices

Imagine spending £3000 on a new watch with a battery embedded in the mechanism that cannot be replaced or recharged. Although the battery is predicted to last 10 years or more, after six years you discover that it is running flat and you’re advised to replace the watch immediately, even though it may keep good time for a year or more.

This mirrors the dilemma faced by all patients with cardiac implantable electronic devices such as pacemakers and implantable cardioverter defibrillators (ICD). But for them the stakes are much higher as replacing the battery exposes them to a risk of serious complications, including life threatening infection.

Over half of all patients with pacemakers require a replacement procedure because the batteries have reached their expected life.1 Some 11-16% need multiple replacements.2 The situation is worse for recipients of an ICD, since the risks of infection at the time of implant and device replacement are higher than with pacemakers and the batteries have a shorter life.3

What is the risk of infection?

With no standard definition or reporting system, infection rates vary widely, and the commonly quoted risk of 0.5% for new implants and 1-5% for replacement procedures may be wrong.4 Infection, even if it seems superficial, usually necessitates extraction of the entire system. Simply treating the infection with antibiotics results in a much poorer outcome.5 The increased risk of infection associated with battery replacement makes it critical that we prolong the life of implantable devices as much as possible. The health economic grounds for minimising the number of replacements are also compelling.6

The current financial model discourages the development of longer life devices. Increasing longevity would reduce profits for manufacturers, implanting physicians, and their institutions. With financial disincentives for both manufacturers and purchasers it is hardly surprising that longer life devices do not exist.

Patients are often assumed to prefer smaller devices, but when offered the choice, over 90% would opt for a larger, longer lasting device over a smaller one that would require more frequent operations to change the battery.7 And given the risks that patients are exposed to during replacement, there is an urgent need to improve longevity by developing longer life batteries and using those in current devices more prudently.

What can be done now?

At present the main drive to improving longevity of pacemakers has been through programming changes aimed at reducing the amount of pacing8 or minimising the drain of current during pacing—for example, using high impedance leads. But devices are usually replaced when there is still substantial life left in the battery. For example, when a pacemaker reaches elective replacement indication, it is usually 3-12 months before it will reach its end of life. And even then, the battery may continue to function for several months. Early replacement may be reasonable for high risk patients (such as those who are entirely dependent on their pacemaker). However, we could delay replacement of the pulse generator until the batteries are virtually depleted in lower risk patients. The increasingly popular innovation of home monitoring of devices would facilitate this.

For ICDs the waste is even more striking; devices reach their elective replacement indication when they are still capable of delivering at least six full energy shocks. Each shock reduces the battery longevity by about 30 days. So for patients who receive no shock therapy we are prematurely discarding a device costing up to £25 000 (€33 000; $36 000), which could last at least another six months (current devices last four to seven years on average). We need to review the timing of replacement of implantable devices in all patients.

CONTINUE READING

http://www.bmj.com/content/352/bmj.i228

REFERENCES

↵

Kinderman M, Schwaab B, Berg M, Frohlig G. Longevity of dual chamber pacemakers: device and patient related determinants. Pacing Clin Electrophysiol2001;24:810-5.

CrossRef Medline
↵

Kurtz SM, Ochoa JA, Lau E, et al. Implantation trends and patient profiles for pacemakers and implantable cardioverter defibrillators in the United States: 1993-2006. Pacing Clin Electrophysiol2010;33:705-11.

CrossRef Medline
↵

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USPTO Guidance On Patentable Subject Matter

Posted in Academic Publishing, Advanced Drug Manufacturing Technology, Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cancer Screening, Cardiac & Vascular Repair Tools Subsegment, Clinical Diagnostics, Computational Biology/Systems and Bioinformatics, Curation, Diagnostic Immunology, Drug Delivery Platform Technology, Ecosystems & Industrial Concentration in the Medical Device Sector, Experimental validation, FDA Regulatory Affairs, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Health Law & Patient Safety, HealthCare IT, Imaging-based Cancer Patient Management, Immunodiagnostics, Infectious Disease Immunodiagnostics, Innovation in Immunology Diagnostics, Innovations in Neurophysiology & Neuropsychology, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, International Global Work in Pharmaceutical, ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics, Mass automation of plasma proteins, Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Mitral Valve: Repair and Replacement, Monoclonal Immunotherapy, Nanotechnology for Drug Delivery, Open Access Journals, Patents, PCI, Pharmaceutical Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Prescription Drugs Costs, Rapid automation of plasma protein pools, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Statistical Methods for Research Evaluation, Stents & Tools, Technology Advance Assessment of, Technology Capital Expenses, Technology Transfer: Biotech and Pharmaceutical, Valves & Tools, tagged Clinical trial, FDA, FDA innovation route, gene, gene expression, gene patents, genomics, Innovation, Innovation Act, innovative applications, mutation, nanotechnology, research, science, tachnology protection, Therapeutic innovations, US Supreme Court, USPTO on July 3, 2014| Leave a Comment »

USPTO Guidance On Patentable Subject Matter

Curator and Reporter: Larry H Bernstein, MD, FCAP

LH Bernstein

Revised 4 July, 2014

http://pharmaceuticalintelligence.com/2014/07/03/uspto-guidance-on-patentable-subject-matter

I came across a few recent articles on the subject of US Patent Office guidance on patentability as well as on Supreme Court ruling on claims. I filed several patents on clinical laboratory methods early in my career upon the recommendation of my brother-in-law, now deceased. Years later, after both brother-in-law and patent attorney are no longer alive, I look back and ask what I have learned over $100,000 later, with many trips to the USPTO, opportunities not taken, and a one year provisional patent behind me.

My conclusion is

(1) that patents are for the protection of the innovator, who might realize legal protection, but the cost and the time investment can well exceed the cost of startup and building a small startup enterprize, that would be the next step.

(2) The other thing to consider is the capability of the lawyer or firm that represents you. A patent that is well done can be expected to take 5-7 years to go through with due diligence. I would not expect it to be done well by a university with many other competing demands. I might be wrong in this respect, as the climate has changed, and research universities have sprouted engines for change. Experienced and productive faculty are encouraged or allowed to form their own such entities.

(3) The emergence of Big Data, computational biology, and very large data warehouses for data use and integration has changed the landscape. The resources required for an individual to pursue research along these lines is quite beyond an individuals sole capacity to successfully pursue without outside funding. In addition, the changed designated requirement of first to publish has muddied the water.

Of course, one can propose without anything published in the public domain. That makes it possible for corporate entities to file thousands of patents, whether there is actual validation or not at the time of filing. It would be a quite trying experience for anyone to pursue in the USPTO without some litigation over ownership of patent rights. At this stage of of technology development, I have come to realize that the organization of research, peer review, and archiving of data is still at a stage where some of the best systems avalailable for storing and accessing data still comes considerably short of what is needed for the most complex tasks, even though improvements have come at an exponential pace.

I shall not comment on the contested views held by physicists, chemists, biologists, and economists over the completeness of guiding theories strongly held. Only history will tell. Beliefs can hold a strong sway, and have many times held us back.

I am not an expert on legal matters, but it is incomprehensible to me that issues concerning technology innovation can be adjudicated in the Supreme Court, as has occurred in recent years. I have postgraduate degrees in Medicine, Developmental Anatomy, and post-medical training in pathology and laboratory medicine, as well as experience in analytical and research biochemistry. It is beyond the competencies expected for these type of cases to come before the Supreme Court, or even to the Federal District Courts, as we see with increasing frequency, as this has occurred with respect to the development and application of the human genome.

I’m not sure that the developments can be resolved for the public good without a more full development of an open-access system of publishing. Now I present some recent publication about, or published by the USPTO.

DR ANTHONY MELVIN CRASTO

Dr. Melvin Castro – Organic Chemistry and New Drug Development

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USPTO Guidance On Patentable Subject Matter: Impediment to Biotech Innovation

Joanna T. Brougher, David A. Fazzolare J Commercial Biotechnology 2014 20(3):Brougher

jcbiotech-patents

Abstract In June 2013, the U.S. Supreme Court issued a unanimous decision upending more than three decades worth of established patent practice when it ruled that isolated gene sequences are no longer patentable subject matter under 35 U.S.C. Section 101.While many practitioners in the field believed that the USPTO would interpret the decision narrowly, the USPTO actually expanded the scope of the decision when it issued its guidelines for determining whether an invention satisfies Section 101.

The guidelines were met with intense backlash with many arguing that they unnecessarily expanded the scope of the Supreme Court cases in a way that could unduly restrict the scope of patentable subject matter, weaken the U.S. patent system, and create a disincentive to innovation. By undermining patentable subject matter in this way, the guidelines may end up harming not only the companies that patent medical innovations, but also the patients who need medical care. This article examines the guidelines and their impact on various technologies.

Keywords: patent, patentable subject matter, Myriad, Mayo, USPTO guidelines

Full Text: PDF

References

35 U.S.C. Section 101 states “Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.

” Prometheus Laboratories, Inc. v. Mayo Collaborative Services, 566 U.S. ___ (2012)

Association for Molecular Pathology et al., v. Myriad Genetics, Inc., 569 U.S. ___ (2013).

Parke-Davis & Co. v. H.K. Mulford Co., 189 F. 95, 103 (C.C.S.D.N.Y. 1911)

USPTO. Guidance For Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products.

http://www.uspto.gov/patents/law/exam/myriad-mayo_guidance.pdf

Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 131 (1948)

USPTO. Guidance For Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products.

http://www.uspto.gov/patents/law/exam/myriad-mayo_guidance.pdf

Courtney C. Brinckerhoff, “The New USPTO Patent Eligibility Rejections Under Section 101.” PharmaPatentsBlog, published May 6, 2014, accessed http://www.pharmapatentsblog.com/2014/05/06/the-new-patent-eligibility-rejections-section-101/

DOI: http://dx.doi.org/10.5912/jcb664

Science 4 July 2014; 345 (6192): pp. 14-15 DOI: http://dx.doi.org/10.1126/science.345.6192.14

IN DEPTH

INTELLECTUAL PROPERTY

Biotech feels a chill from changing U.S. patent rules

Kelly Servick*

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A 2013 Supreme Court decision that barred human gene patents is scrambling patenting policies.

PHOTO: MLADEN ANTONOV/AFP/GETTY IMAGES

A year after the U.S. Supreme Court issued a landmark ruling that human genes cannot be patented, the biotech industry is struggling to adapt to a landscape in which inventions derived from nature are increasingly hard to patent. It is also pushing back against follow-on policies proposed by the U.S. Patent and Trademark Office (USPTO) to guide examiners deciding whether an invention is too close to a natural product to deserve patent protection. Those policies reach far beyond what the high court intended, biotech representatives say.

“Everything we took for granted a few years ago is now changing, and it’s generating a bit of a scramble,” says patent attorney Damian Kotsis of Harness Dickey in Troy, Michigan, one of more than 15,000 people who gathered here last week for the Biotechnology Industry Organization’s (BIO’s) International Convention.

At the meeting, attorneys and executives fretted over the fate of patent applications for inventions involving naturally occurring products—including chemical compounds, antibodies, seeds, and vaccines—and traded stories of recent, unexpected rejections by USPTO. Industry leaders warned that the uncertainty could chill efforts to commercialize scientific discoveries made at universities and companies. Some plan to appeal the rejections in federal court.

USPTO officials, meanwhile, implored attendees to send them suggestions on how to clarify and improve its new policies on patenting natural products, and even announced that they were extending the deadline for public comment by a month. “Each and every one of you in this room has a moral duty … to provide written comments to the PTO,” patent lawyer and former USPTO Deputy Director Teresa Stanek Rea told one audience.

At the heart of the shake-up are two Supreme Court decisions: the ruling last year in Association for Molecular Pathology v. Myriad Genetics Inc. that human genes cannot be patented because they occur naturally (Science, 21 June 2013, p. 1387); and the 2012 Mayo v. Prometheus decision, which invalidated a patent on a method of measuring blood metabolites to determine drug doses because it relied on a “law of nature” (Science, 12 July 2013, p. 137).

Myriad and Mayo are already having a noticeable impact on patent decisions, according to a study released here. It examined about 1000 patent applications that included claims linked to natural products or laws of nature that USPTO reviewed between April 2011 and March 2014. Overall, examiners rejected about 40%; Myriad was the basis for rejecting about 23% of the applications, and Mayo about 35%, with some overlap, the authors concluded. That rejection rate would have been in the single digits just 5 years ago, asserted Hans Sauer, BIO’s intellectual property counsel, at a press conference. (There are no historical numbers for comparison.) The study was conducted by the news service Bloomberg BNA and the law firm Robins, Kaplan, Miller & Ciseri in Minneapolis, Minnesota.

USPTO is extending the decisions far beyond diagnostics and DNA?

The numbers suggest USPTO is extending the decisions far beyond diagnostics and DNA, attorneys say. Harness Dickey’s Kotsis, for example, says a client recently tried to patent a plant extract with therapeutic properties; it was different from anything in nature, Kotsis argued, because the inventor had altered the relative concentrations of key compounds to enhance its effect. Nope, decided USPTO, too close to nature.

In March, USPTO released draft guidance designed to help its examiners decide such questions, setting out 12 factors for them to weigh. For example, if an examiner deems a product “markedly different in structure” from anything in nature, that counts in its favor. But if it has a “high level of generality,” it gets dinged.

The draft has drawn extensive criticism. “I don’t think I’ve ever seen anything as complicated as this,” says Kevin Bastian, a patent attorney at Kilpatrick Townsend & Stockton in San Francisco, California. “I just can’t believe that this will be the standard.”

USPTO officials appear eager to fine-tune the draft guidance, but patent experts fear the Supreme Court decisions have made it hard to draw clear lines. “The Myriad decision is hopelessly contradictory and completely incoherent,” says Dan Burk, a law professor at the University of California, Irvine. “We know you can’t patent genetic sequences,” he adds, but “we don’t really know why.”

Get creative in using Draft Guidelines!

For now, Kostis says, applicants will have to get creative to reduce the chance of rejection. Rather than claim protection for a plant extract itself, for instance, an inventor could instead patent the steps for using it to treat patients. Other biotech attorneys may try to narrow their patent claims. But there’s a downside to that strategy, they note: Narrower patents can be harder to protect from infringement, making them less attractive to investors. Others plan to wait out the storm, predicting USPTO will ultimately rethink its guidance and ease the way for new patents.

Public comment period extended

USPTO has extended the deadline for public comment to 31 July, with no schedule for issuing final language. Regardless of the outcome, however, Stanek Rea warned a crowd of riled-up attorneys that, in the world of biopatents, “the easy days are gone.”

United States Patent and Trademark Office

Today we published and made electronically available a new edition of the Manual of Patent Examining Procedure (MPEP). Manual of Patent Examining Procedure uspto.gov http://www.uspto.gov/web/offices/pac/mpep/index.html Summary of Changes

PDF Title Page
PDF Foreword
PDF Introduction
PDF Table of Contents
PDF Chapter 600 –
PDF Parts, Form, and Content of Application Chapter 700 –
PDF   Examination of Applications Chapter 800 –
PDF Restriction in Applications Filed Under 35 U.S.C. 111; Double Patenting Chapter 900 –
PDF Prior Art, Classification, and Search Chapter 1000 –
PDF  Matters Decided by Various U.S. Patent and Trademark Office Officials Chapter 1100 –
PDF Statutory Invention Registration (SIR); Pre-Grant Publication (PGPub) and Preissuance Submissions Chapter 1200 –
PDF   Appeal Chapter 1300 –
PDF Allowance and Issue Appendix L –
PDF Patent Laws Appendix R –
PDF Patent Rules Appendix P –
PDF Paris Convention Subject Matter Index
PDF Zipped version of the MPEP current revision in the PDF format.

Manual of Patent Examining Procedure (MPEP)Ninth Edition, March 2014

The USPTO continues to offer an online discussion tool for commenting on selected chapters of the Manual. To participate in the discussion and to contribute your ideas go to:
http://uspto-mpep.ideascale.com.

Manual of Patent Examining Procedure (MPEP) Ninth Edition, March 2014
The USPTO continues to offer an online discussion tool for commenting on selected chapters of the Manual. To participate in the discussion and to contribute your ideas go to: http://uspto-mpep.ideascale.com.

Note: For current fees, refer to the Current USPTO Fee Schedule.
Consolidated Laws – The patent laws in effect as of May 15, 2014. Consolidated Rules – The patent rules in effect as of May 15, 2014. MPEP Archives (1948 – 2012)
Current MPEP: Searchable MPEP

See the user manual or quick reference guide for help with search features (e.g., default operators, proximity searches, and wild cards) and navigation.

The documents updated in the Ninth Edition of the MPEP, dated March 2014, include changes that became effective in November 2013 or earlier.
All of the documents have been updated for the Ninth Edition except Chapters 800, 900, 1000, 1300, 1700, 1800, 1900, 2000, 2300, 2400, 2500, and Appendix P.
More information about the changes and updates is available from the “Blue Page – Introduction” of the Searchable MPEP or from the “Summary of Changes” link to the HTML and PDF versions provided below. Discuss the Manual of Patent Examining Procedure (MPEP) Welcome to the MPEP discussion tool!

We have received many thoughtful ideas on Chapters 100-600 and 1800 of the MPEP as well as on how to improve the discussion site. Each and every idea submitted by you, the participants in this conversation, has been carefully reviewed by the Office, and many of these ideas have been implemented in the August 2012 revision of the MPEP and many will be implemented in future revisions of the MPEP. The August 2012 revision is the first version provided to the public in a web based searchable format. The new search tool is available at http://mpep.uspto.gov. We would like to thank everyone for participating in the discussion of the MPEP.

We have some great news! Chapters 1300, 1500, 1600 and 2400 of the MPEP are now available for discussion. Please submit any ideas and comments you may have on these chapters. Also, don’t forget to vote on ideas and comments submitted by other users. As before, our editorial staff will periodically be posting proposed new material for you to respond to, and in some cases will post responses to some of the submitted ideas and comments.Recently, we have received several comments concerning the Leahy-Smith America Invents Act (AIA). Please note that comments regarding the implementation of the AIA should be submitted to the USPTO via email t aia_implementation@uspto.gov or via postal mail, as indicated at the America Invents Act Web site. Additional information regarding the AIA is available at www.uspto.gov/americainventsact We have also received several comments suggesting policy changes which have been routed to the appropriate offices for consideration. We really appreciate your thinking and recommendations!

FDA Guidance for Industry:Electronic Source Data in Clinical Investigations

Electronic Source Data

The FDA published its new Guidance for Industry (GfI) – “Electronic Source Data in Clinical Investigations” in September 2013.
The Guidance defines the expectations of the FDA concerning electronic source data generated in the context of clinical trials. Find out more about this Guidance.
http://www.gmp-compliance.org/enews_4288_FDA%20Guidance%20for%20Industry%3A%20Electronic%20Source%20Data%20in%20Clinical%20Investigations
_8534,8457,8366,8308,Z-COVM_n.html

After more than 5 years and two draft versions, the final version of the Guidance for
Industry (GfI) – “Electronic Source Data in Clinical Investigations” was published in
September 2013. This new FDA Guidance defines the FDA’s expectations for sponsors,
CROs, investigators and other persons involved in the capture, review and retention of
electronic source data generated in the context of FDA-regulated clinical trials.In an
effort to encourage the modernization and increased efficiency of processes in clinical
trials, the FDA clearly supports the capture of electronic source data and emphasizes
the agency’s intention to support activities aimed at ensuring the reliability, quality,
integrity and traceability of this source data, from its electronic source to the electronic
submission of the data in the context of an authorization procedure. The Guidance
addresses aspects as data capture, data review and record retention. When the
computerized systems used in clinical trials are described, the FDA recommends
that the description not only focus on the intended use of the system, but also on
data protection measures and the flow of data across system components and
interfaces. In practice, the pharmaceutical industry needs to meet significant
requirements regarding organisation, planning, specification and verification of
computerized systems in the field of clinical trials. The FDA also mentions in the
Guidance that it does not intend to apply 21 CFR Part 11 to electronic health records
(EHR). Author: Oliver Herrmann Q-Infiity Source: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM328691.pdf Webinar: https://collaboration.fda.gov/p89r92dh8wc

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

Posted in Acute Myocardial Infarction, Bone marrow derived cells, Cardiac & Vascular Repair Tools Subsegment, Cell Biology, Signaling & Cell Circuits, Computational Biology/Systems and Bioinformatics, Curation, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Delivery Platform Technology, Experimental validation, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Hematopoiesis, Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Molecular Genetics & Pharmaceutical, Origins of Cardiovascular Disease, PCI, Regenerative Biology and Medicine, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Stents & Tools, tagged ACS, AMI, Atrial fibrillation, cell regulatory processes, miRNA, myocardial remodelling, myocardial repair, NT-proBNP risk ratio, Omega 3 index, stem cells, ventricullar tachyarrhythmia on May 12, 2014| Leave a Comment »

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

Larry H Bernstein, MD, FCAP, Author and Curator, Volume Four, Co-Editor
Justin Pearlman, MD, PhD, FACC, Content Consultant for Series A: Cardiovascular Diseases
Aviva Lev-Ari, PhD, RN, Co-Editor of Volume Four and Editor-in-Chief, BioMed e-Series

This completes Chapter 4 in two parts on the most dynamic developments in the regulatory pathways guiding cardiovascular dynamics and function in health and disease. I have covered key features of these in two summaries, so I shall try to look further into important expected future directions and their anticipated implications.

1. Mechanisms of Disease

Signal Transduction: Akt Phosphorylates HK-II at Thr-473 and Increases Mitochondrial HK-II Association to Protect Cardiomyocytes

David J. Roberts, Valerie P. Tan-Sah, Jeffery M. Smith and Shigeki Miyamoto
J. Biol. Chem. 2013, 288:23798-23806. http://dx.doi.org/ 10.1074/jbc.M113.482026

Backgound: Hexokinase II binds to mitochondria and promotes cell survival.
Results: Akt phosphorylates HK-II but not the threonine 473 mutant. The phosphomimetic T473D mutant decreases its dissociation from mitochondria induced by G-6P and increases cell viability against stress.
Conclusion: Akt phosphorylates HK-II at Thr-473, resulting in increased mitochondrial HK-II and cell protection.
Significance: The Akt-HK-II signaling nexus is important in cell survival.

HK-II Phosphorylation

It has been demonstrated that an increased level of HK-II at mitochondria is protective and is increased by protective interventions but decreased under stress.

It has not been fully determined which molecular signals regulate the level of HK-II at mitochondria.

Thr-473 in HK-II is phosphorylated by Akt and this phosphorylation leads to increases in mitochondrial HK-II binding through inhibition of G-6P-dependent dissociation, conferring resistance to oxidative stress (Fig. 7).

Overexpression of WTHK-II increases mitochondrial HK-II and confers protection against hydrogen peroxide, which is enhanced significantly in HK-II T473D-expressing cells, whereas NHK-II, lacking the ability to bind to mitochondria, does not confer protection. Conversely, mitochondrial HK-II from mitochondria (Fig.6, A and B) inhibits the IGF-1-mediated increase in mitochondrial HK-II and cellular protection. Similar dose-dependent curves were obtained in mitochondrial HK-II against stress (15–25).

Gene Expression and Genetic Variation in Human Atria

Honghuang Lin PhD, Elena V. Dolmatova MD, Michael P. Morley, PhD, Kathryn L. Lunetta PhD, David D. McManus MD, ScM, et al.
Heart Rhythm 2013 http://dx.doi.org/10.1016/j.hrthm.2013.10.051

Background— The human left and right atria have different susceptibilities to develop atrialfibrillation (AF). However, the molecular events related to structural and functional changes that
enhance AF susceptibility are still poorly understood.
Objective— To characterize gene expression and genetic variation in human atria.
Results— We found that 109 genes were differentially expressed between left and right atrial tissues. A total of 187 and 259 significant cis-associations between transcript levels and genetic
variants were identified in left and right atrial tissues, respectively. We also found that a SNP at a known AF locus, rs3740293, was associated with the expression of MYOZ1 in both left and right
atrial tissues.
Conclusion— We found a distinct transcriptional profile between the right and left atrium, and extensive cis-associations between atrial transcripts and common genetic variants. Our results
implicate MYOZ1 as the causative gene at the chromosome 10q22 locus for AF.

Long-Term Caspase Inhibition Ameliorates Apoptosis, Reduces Myocardial Troponin-I Cleavage, Protects Left Ventricular Function, and Attenuates Remodeling in Rats With Myocardial Infarction

Y. Chandrashekhar, Soma Sen, Ruth Anway, Allan Shuros, Inder Anand,

J Am Col Cardiol 2004; 43(2) http://dx.doi.org/10.1016/j.jacc.2003.09.026

This study was designed to evaluate whether in vivo caspase inhibition can prevent myocardial contractile protein degradation, improve myocardial function, and attenuate ventricular remodeling.
Apoptosis is thought to play an important role in the development and progression of heart failure (HF) after a myocardial infarction (MI). However, it is not known whether inhibiting apoptosis can attenuate left ventricular (LV) remodeling and minimize systolic dysfunction.

A 28-day infusion of caspase inhibitor was administeredimmediately after an anterior MI. In addition, ﬁve sham-operated rats given the caspase inhibitor were compared with 17 untreated sham-operated animals to study effects in non-MI rats. Left ventricular function, remodeling parameters, and hemodynamics were studied four weeks later. Myocardial caspase 3 activation and troponin-I contractile protein cleavage were studied in the non-infarct, remote LV myocardium using Western blots. Apoptosis was assessed using immunohistochemistry for activated caspase-positive cells as well as the TUNEL method. Collagen volume was estimated using morphometry.

Caspase inhibition reduced myocardial caspase 3 activation. This was accompanied by less cleavage of troponin-I, an important component of the cardiac contractile apparatus, and fewer apoptotic cardiomyocytes. Furthermore, caspase inhibition reduced LV-weight-to- body-weight ratio, decreased myocardial interstitial collagen deposition, attenuated LV remodeling, and better preserved LV systolic function after MI.

Caspase inhibition, started soon after MI and continued for four weeks, preserves myocardial contractile proteins, reduces systolic dysfunction, and attenuates ventricular remodeling.

These ﬁndings may have important therapeutic implications in post-MI HF. J Am Col Cardiol 2004;43:295–301)

Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors

Lincoln T Shenje, Peter P Rainer , Gun-sik Cho , Dong-ik Lee , Weimin Zhong , Richard P Harvey , David A Kass , Chulan Kwon *, et al.
eLife 2014. http://dx.doi.org/10.7554/eLife.02164.001

Cardiac progenitor cells (CPCs) must control their number and fate to sustain the rapid heart growth during development, yet the intrinsic factors and environment governing these processes remain unclear. Here, we show that deletion of the ancient cell-fate regulator Numb (Nb) and its homologue Numblike (Nbl) depletes CPCs in second pharyngeal arches (PA2s) and is associated with an atrophic heart. With histological, fow cytometric and functional analyses, we fnd that CPCs remain undifferentiated and expansive in the PA2, but differentiate into cardiac cells as they exit the arch. Tracing of Nb- and Nbl-defcient CPCs by lineage-specifc mosaicism reveals that the CPCs normally populate in the PA2, but lose their expansion potential in the PA2. These fndings demonstrate that Nb and Nbl are intrinsic factors crucial for the renewal of CPCs in the PA2 and
that the PA2 serves as a microenvironment for their expansion.

2. Diagnostics and Risk Assessment

Classical and Novel Biomarkers for Cardiovascular Risk Prediction in the United States

Aaron R. Folsom
J Epidemiol 2013;23(3):158-162 http://dx.doi.org/10.2188/jea.JE20120157

Cardiovascular risk prediction models based on classical risk factors identiﬁed in epidemiologic cohort studies are useful in primary prevention of cardiovascular disease in individuals. This article brieﬂy reviews aspects of
cardiovascular risk prediction in the United States and efforts to evaluate novel risk factors. Even though many novel risk markers have been found to be associated with cardiovascular disease, few appear to improve risk prediction
beyond the powerful, classical risk factors. A recent US consensus panel concluded that clinical measurement of certain novel markers for risk prediction was reasonable, namely,

hemoglobin A1c (in all adults),
microalbuminuria (in patients with hypertension or diabetes), and
C-reactive protein,
lipoprotein-associated phospholipase,
coronary calcium,
carotid intima-media thickness, and
ankle/brachial index (in patients deemed to be at intermediate cardiovascular risk, based on traditional risk factors).

Diagnostic accuracy of NT-proBNP ratio (BNP-R) for early diagnosis of tachycardia-mediated cardiomyopathy: a pilot study

Amir M. Nia, Natig Gassanov, Kristina M. Dahlem, Evren Caglayan, Martin Hellmich, et al.
Clin Res Cardiol (2011) 100:887–896 http://dx.doi.org/10.1007/s00392-011-0319-y

Tachycardia-mediated cardiomyopathy (TMC) occurs as a consequence of prolonged high heart rate due to ventricular and supraventricular tachycardia. In animal models, rapid pacing induces severe biventricular remodeling with dilation and dysfunction [7]. On a cellular basis, cardiomyocytes exert fundamental morphological and functional roles.

When heart failure and tachycardia occur simultaneously, a useful diagnostic tool for early discrimination of patients with benign tachycardia-mediated cardiomyopathy (TMC) versus major structural heart disease (MSHD) is not available. Such a tool is required to prevent unnecessary and wearing diagnostics in patients with reversible TMC. Moreover, it could lead to early additional diagnostics and therapeutic approaches in patients with MSHD.

A total of 387 consecutive patients with supraventricular arrhythmia underwent assessment. Of these patients, 40 fulﬁlled the inclusion criteria
with a resting heart rate C100 bpm and an impaired left ventricular ejection fraction \40%. In all patients, successful electrical cardioversion was performed. At baseline, day 1 and weekly for 4 weeks, levels of NT-proBNP and echocardiographic parameters were evaluated.

NT-proBNP ratio (BNP-R) was calculated as a quotient of baseline NT-proBNP/follow-up NT-proBNP. After 4 weeks, cardiac catheterization was performed to identify patients with a ﬁnal diagnosis of TMC versus MSHD.

Initial NT-proBNP concentrations were elevated and consecutively decreased after cardioversion in all patients studied. The area under the ROC curve for BNP-R to detect TMC was 0.90 (95% CI 0.79–1.00; p \ 0.001) after 1 week and 0.995 (95% CI 0.99–1.00; p \ 0.0001) after 4 weeks. One week after cardioversion already, a BNP-R cutoff C2.3 was useful for TMC diagnosis indicated by an accuracy of 90%, sensitivity of 84% and speciﬁcity of 95%.

BNP-R was found to be highly accurate for the early diagnosis of TMC.

Omega-3 Index and Cardiovascular Health

Clemens von Schacky
Nutrients 2014; 6: 799-814; http://dx. doi.org/10.3390/nu602099

Fish, marine oils, and their concentrates all serve as sources of the two marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as do some products from algae.
To demonstrate an effect of EPA + DHA on heart health, a number of randomized, controlled intervention studies with clinical endpoints like overall mortality or a combination of adverse cardiac events were conducted in populations with elevated cardiovascular risk. One early intervention study with oily fish, rich in EPA + DHA, and some early studies with fish oil or fish oil concentrate or even purified EPA at doses ranging between 0.9 and 1.8 g/day indeed demonstrated effects in terms of fewer sudden cardiac deaths, fatal or non-fatal myocardial infarctions, or a combination of adverse cardiac events.

Recent meta-analyses found no significant benefits on total mortality, cardiovascular mortality, and other adverse cardiac or cardiovascular events [13–18]. This is in contrast to findings in epidemiologic studies, where intake of EPA + DHA had been found to correlate generally with an up to 50% lower incidence of adverse cardiac events [18,19], and in even sharper contrast to epidemiologic studies based on levels of EPA + DHA, demonstrating e.g., a 10-fold lower incidence of sudden cardiac death associated with high levels of the
fatty acids, as compared to low levels.

This seemingly contradictory evidence has led the American Heart Association to recommend “omega-3 fatty acids from fish or fish oil capsules (1 g/day) for cardiovascular disease risk reduction” for secondary prevention, whereas the European Society for Cardiology recommends “Fish at least twice a week, one of which to be oily fish”, but no supplements for cardiovascular prevention.

A similar picture emerges for atrial fibrillation: In epidemiologic studies, consumption of EPA + DHA or higher levels of EPA + DHA were associated with lower risk for developing atrial fibrillation, while intervention studies found no effect. Pertinent guidelines do not mention EPA + DHA. A similar picture also emerges for severe ventricular rhythm disturbances.

Why is it that trial results are at odds with results from epidemiology? What needs to be done to better translate the epidemiologic findings into trial results? The current review will try to shed some light on this issue, with a special consideration of the Omega-3 Index.

Recent large trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the cardiovascular field did not demonstrate a beneficial effect in terms of reductions of clinical endpoints like

total mortality,
sudden cardiac arrest or
other major adverse cardiac events.

Pertinent guidelines do not uniformly recommend EPA + DHA for cardiac patients. In contrast,

in epidemiologic findings, higher blood levels of EPA + DHA were consistently associated with a lower risk for the endpoints mentioned.

The following points argue for the use of erythrocytes: erythrocyte fatty acid
composition has a low biological variability, erythrocyte fat consists almost exclusively of phospholipids, erythrocyte fatty acid composition reflects tissue fatty acid composition, pre-analytical stability, and other points. In 2004, EPA + DHA in erythrocyte fatty acids were defined as the Omega-3 Index and suggested as a risk factor for sudden cardiac death [39]. Integral to the definition was a specific and standardized analytical procedure, conforming the quality management routinely implemented in the field of clinical chemistry.

The laboratories adhering to the HS-Omega-3 Index methodology perform regular proficiency testing, as mandated in routine Clinical Chemistry labs. So far, the HS-Omega-3 Index is the only analytical procedure used in several laboratories. A standardized analytical procedure is a prerequisite to generate the data base necessary to transport a laboratory parameter from research into clinical routine. Moreover, standardization of the analytical procedure is the first important criterion for establishing a new biomarker for cardiovascular risk set forth by the American Heart Association and the US Preventive Services Task Force.

Because of low biological and analytical variability, a standardized analytical procedure, a large database and for other reasons,

blood levels of EPA + DHA are frequently assessed in erythrocytes, using the HS-Omega-3 Index methodology.

Table 1. Mean HS-Omega-3 Index values in various populations, Mean (±standard deviation (SD)). Please note that in every population studied, a lower value was found to be associated with a worse condition than a higher value. References are given, if not, unpublished, n = number of individuals measured.

All levels of fatty acids are determined by the balance of substance entering the body and those leaving the body. Neither a recent meal, even if rich in EPA + DHA, nor severe cardiac events altered the HS-Omega-3 Index. However, while long-term intake of EPA + DHA, e.g., as assessed with food questionnaires, was the main predictor of the HS-Omega-3 Index, long-term intake explained only 12%–25% of its variability. A hereditary component of 24% exists. A number of other factors correlated positively (+) or negatively (−), like age (+), body mass index (−), socioeconomic status (+), smoking (−), but no other conventional cardiac risk factors. More factors determining the level of the HS-Omega-3 Index, especially regarding efflux remain to be defined. Therefore, it is impossible to predict the HS-Omega-3 Index in an individual, as it is impossible to predict the increase in the HS-Omega-3 Index in an individual in response to a given dose of EPA + DHA. In Table 2, current evidence is presented on the relation of the HS-Omega-3 Index to CV events.

The HS-Omega-3 Index has made it possible to reclassify individuals from intermediate cardiovascular risk into the respective high risk and low risk strata, the third criterion for establishing a new biomarker for CV risk.

A low Omega-3 Index fulfills the current criteria for a novel cardiovascular risk factor.

Increasing the HS-Omega-3 Index by increased intake of EPA + DHA in randomized controlled trials improved a number of surrogate parameters for cardiovascular risk:

heart rate was reduced,
heart rate variability was increased,
blood pressure was reduced,
platelet reactivity was reduced,
triglycerides were reduced,
large buoyant low-density lipoprotein (LDL)-particles were increased and
small dense LDL-particles were reduced,
large buoyant high-density lipoproteins (HDL)2 were increased,
very low-density lipoprotein (VLDL1) + 2 was reduced,
pro-inflammatory cytokines (e.g., tumor necrosis factor alpha, interleukin-1β, interleukins-6,8,10 and monocyte chemoattractant protein-1) were reduced,
anti-inflammatory oxylipins were increased.

Importantly, in a two-year randomized double-blind angiographic intervention trial, increased erythrocyte EPA + DHA

reduced progression and increased regression of coronary lesions, an intermediate parameter.

Taken together, increasing the HS-Omega-3 Index improved surrogate and intermediate parameters for cardiovascular events. A large intervention trial with clinical endpoints based on the HS-Omega-3 Index remains to be conducted. Therefore, the fourth criterion, proof of therapeutic consequence of determining the HS-Omega- Index, is only partially fulfilled.

Neutral results of intervention trials can be explained by issues of bioavailability and trial design that surfaced after the trials were initiated.

In the future, incorporating the Omega-3 Index into trial designs by

recruiting participants with a low Omega-3 Index and
treating them within a pre-specified target range (e.g., 8%–11%),
will make more efficient trials possible and
- provide clearer answers to the questions asked than previously possible.

3. Stem Cells and Regenerative Biology

Adult Stem Cells Reverse Muscle Atrophy In Elderly Mice http://www.science20.com/profile/news_staff

Bioengineers at the University of California, Berkeley in a new study published in Nature say they have identified two key regulatory pathways that control how well adult stem cells repair and replace damaged tissue. They then tweaked how those stem cells reacted to those biochemical signals to revive the ability of muscle tissue in old mice to repair itself nearly as well as the muscle in the mice’s much younger counterparts. Irina Conboy, an assistant professor of bioengineering and an investigator at the Berkeley Stem Cell Center and at the California Institute for Quantitative Biosciences (QB3), led the research team conducting this study. Because the findings relate to adult stem cells that reside in existing tissue, this approach to rejuvenating degenerating muscle eliminates the ethical and medical complications associated with transplanting tissues grown from embryonic stem cells. The researchers focused on

the interplay of two competing molecular pathways that control the stem cells,

which sit next to the mature, differentiated cells that make up our working body parts. When the mature cells are damaged or wear out, the stem cells are called into action to begin the process of rebuilding.

old muscle tissue is left with

“We don’t realize it, but as we grow our bodies are constantly being remodeled,” said Conboy. “We are constantly falling apart, but we don’t notice it much when we’re young because we’re always being restored. As we age, our stem cells are prevented, through chemical signals, from doing their jobs.” The good news, the researchers said, is that

the stem cells in old tissue are still ready and able to perform their regenerative function
if they receive the appropriate chemical signals.

Studies have shown that when old tissue is placed in an environment of young blood, the stem cells behave as if they are young again. “Conversely, we have found in a study published last year that even young stem cells rapidly age when placed among blood and tissue from old mice,” said Carlson, who will stay on at UC Berkeley to expand his work on stem cell engineering.

Adult stem cells have a receptor called Notch that, when activated,
tells them that it is time to grow and divide
stem cells also have a receptor for the protein TGF-beta
that sets off a chain reaction activatingthemoleculepSmad3 and
- ultimately producing cyclin-dependent kinase (CDK) inhibitors, which regulate the cell’s ability to divide.
activated Notch competeswithactivatedpSmad3 for
- binding to the regulatory regions of the same CDK inhibitors in the stem cell

“We found that Notch is capable of physically kicking off pSmad3 from the promoters for the CDK inhibitors within the stem cell’s nucleus, which tells us that a precise manipulation of the balance of these pathways would allow the ability to control stem cell responses.” Notch and TGF-beta are well known in molecular biology, but Conboy’s lab is the first to connect them to the process of aging, and the first to show that they act in opposition to each other within the nucleus of the adult stem cell. Aging and the inevitable march towards death are, in part, due to the progressive decline of Notch and the increased levels of TGF-beta , producing a one-two punch to the stem cell’s capacity to effectively rebuild the body, the researchers said.

The researchers disabled the “aging pathway” that tells stem cells to stop dividing by using an established method of RNA interference that reduced levels of pSmad3. The researchers then examined the muscle of the different groups of mice one to five days after injury to compare how well the tissue repaired itself. As expected,

muscle tissue in the young mice easily replaced damaged cells with new, healthy cells. In contrast,
the areas of damaged muscle in the control group of old mice were characterized by fibroblasts and scar tissue. However,
muscles in the old mice whose stem cell “aging pathway”had been dampened showed levels of cellular regeneration that were
- comparable to their much younger peers, and that were 3 to 4 times greater than those of the group of “untreated” old mice.

Adult Stem Cells To Repair Damaged Heart Muscle

http://www.science20.com/profile/news_staff

In the first trial of its kind in the world, 60 patients who have recently suffered a major heart attack will be injected with selected stem cells from their own bone marrow during routine coronary bypass surgery. The Bristol trial will test

whether the stem cells will repair heart muscle cells damaged by the heart attack,
by preventing late scar formation and hence impaired heart contraction.

“ Cardiac stem cell therapy aims to repair the damaged heart as it has the potential to replace the damaged tissue.” We have elected to use a very promising stem cell type selected from the patient’s own bone marrow. This approach ensures no risk of rejection or infection. It also gets around the ethical issues that would result from use of stem cells from embryonic or foetal tissue.

In this trial (known as TransACT), all patients will have bone marrow harvested before their heart operation. Then either stem cells from their own bone marrow or a placebo will be injected into the patients’ damaged hearts during routine coronary bypass surgery. The feasibility and safety of this technique has already been demonstrated. As a result of the chosen double blind placebo-controlled design, neither the patients nor the surgeon knows whether the patient is going to be injected with stem cells or placebo. This ensures that results are not biased in any way, and is the most powerful way to prove whether or not the new treatment is effective.

Research of Stem Cells Repair Damaged Heart

By Kelvinlew Minhan | March 26th 2008

Under highly specific growth conditions in laboratory culture dishes, stem cells

can be coaxed into developing as new cardiomyocytes and vascular endothelial cells (Kirschstein and Skirboll, 2001).

Discoveries that have triggered the interest in the application of adult stem cells to heart muscle repair in animal models have been made by researchers in the past few years (Kirschstein and Skirboll, 2001). One study demonstrated that cardiac tissue can be regenerated in the mouse heart attack model through the introduction of adult stem cells from mouse bone marrow (Kirschstein and Skirboll, 2001). These cells were transplanted into the marrow of irradiated mice approximately 10 weeks before the recipient mice were subjected to heart attack thru tying off different major heart blood vessel, the left anterior descending (LAD) coronary artery. The survival rate was 26 percent at two to four weeks after the induced cardiac injury (Kirschstein and Skirboll, 2001). Another study of the region surrounding the damaged tissue in surviving mice showed the presence of donor-derived cardiomyocytes and endothelial cells (Kirschstein and Skirboll, 2001).

the mouse hematopoietic stem cells transplanted into the bone marrow had migrated to the border part of the damaged area, and differentiated into several types of tissue for cardiac repair.

Regenerating heart tissue through stem cell therapy

http://www.mayo.edu/research/discoverys-edge/regenerating-heart-tissue-stem-cell-therapy

Summary

A groundbreaking study on repairing damaged heart tissue through stem cell therapy has given patients hope that they may again live active lives. An international team of Mayo Clinic researchers and collaborators has done it by discovering a way to regenerate heart tissue.

“It’s a paradigm shift,” says Andre Terzic, M.D., Ph.D., director of Mayo Clinic’s Center for Regenerative Medicine and senior investigator of the stem cell trial. “We are moving from traditional medicine, which addresses the symptoms of disease to cure disease.” Treating patients with cardiac disease has typically involved managing heart damage with medication. In collaboration with European researchers, Mayo Clinic researchers have discovered a novel way to repair a damaged heart. In Mayo Clinic’s breakthrough process,

stem cells are harvested from a patient’s bone marrow.
undergo a laboratory treatment that guides them into becoming cardiac cells,
which are then injected into the patient’s heart in an effort to grow healthy heart tissue.

The study is the first successful demonstration in people of the feasibility and safety of transforming adult stem cells into cardiac cells. Beyond heart failure, the Mayo Clinic research also is a milestone in the emerging field of regenerative medicine, which seeks to fully heal damaged tissue and organs.

Creating a heart repair kit

Process of converting bone marrow cells to heart cells

This image shows the process used in the clinical trials to repair damaged hearts. Cardioprogenitor cells is another term for cardiopoietic cells, those that were transformed into cardiac cells.

Stem cells transforming to cardiac tissue

Transformation: The cardiopoietic cells on the left react to the cardiac environment, cluster together with like cells and form tissue.

Mayo Clinic researchers pursued this research, inspired by an intriguing discovery. In the early 2000s, they analyzed stem cells from 11 patients undergoing heart bypass surgery. The stem cells from two of the patients had an unusually high expression of certain transcription factors — the proteins that control the flow of genetic information between cells. Clinically, the two patients appeared no different from the others, yet their stem cells seemed to show unique capacity for heart repair.

That observation drove them to determine how to convert nonreparative stem cells to become reparative. Doing so required determining precisely how the human heart naturally develops, at a subcellular level. That painstaking work was led by Atta Behfar, M.D., Ph.D., a cardiovascular researcher at Mayo Clinic in Rochester, Minn. With other members of the Terzic research team, Dr. Behfar identified hundreds of proteins involved in the process of heart development (cardiogenesis). The researchers then set out to identify which of these proteins are essential in driving a stem cell to become a cardiac cell. Using computer models,

they simulated the effects of eliminating proteins one by one from the process of heart development.
That method yielded about 25 proteins.
- The team then pared that number down to 8 proteins that their data indicated were essential.

The research team was then able to develop the lab procedure that guides stem cells to become heart cells.

The treated stem cells were dubbed cardiopoietic, or heart creative. A proof of principle study about guided cardiopoiesis, whose results were published in the Journal of the American College of Cardiology in 2010, demonstrated that animal models with heart disease that had been injected with caridiopoietic cells had improved heart function compared with animals injected with untreated stem cells. Hailed as “landmark work,” by the journal’s editorial writer, the study showed it was indeed possible to teach stem cells to become cardiac cells. Stem cells from each patient in the cardiopoiesis group were successfully guided to become cardiac cells. The treated cells were injected into the heart wall of each of those patients without apparent complications.
“Ihis newprocessofcardiopoiesiswas achieved in 100 percent of cases, with a very good safety profile,” Dr.Terzic says. “We are enabling the heart toregainitsinitial structure and function,” Dr.Terzic says, “and we will not stop here.” The clinicaltrialfindingsareexpectedto be published in the Journal of the American College of Cardiology in 2013. Meanwhile, research to improve the injection process and effectiveness is underway.

Stem Cells from Humans Repair Heart Damage in Monkeys

Kevin Mayer

GEN News Highlights May1, 2014

GPCR Insights Brighten Drug Discovery Outlook

Ken Doyle, Ph.D.

GEN Apr 15, 2014 (Vol. 34, No. 8)

Recent years have seen major advances in understanding the structure-function relationships of G protein-coupled receptors (GPCRs). This large superfamily of transmembrane receptors comprises over 800 members in humans.

GPCRs regulate a wide variety of physiological processes including

sensation (vision, taste, and smell),
growth,
hormone responses, and
regulation of the immune and
autonomic nervous systems.

Their involvement in multiple disease pathways makes GPCRs attractive targets for drug discovery efforts.

These multifaceted proteins will be the subject of “GPCR Structure, Function and Drug Discovery,” a Global Technology Community conference scheduled to take place May 22–23 in Boston. The conference is expected to cover a broad range of topics including biased signaling, membrane protein structures, GPCR signaling dynamics, computational approaches to disease.

According to Bryan Roth, M.D., Ph.D., Michael Hooker Distinguished Professor at the University of North Carolina, Chapel Hill,

drugs that can selectively target various downstream GPCR pathways hold the most promise.

Dr. Roth’s laboratory studies approximately 360 different GPCRs with therapeutic potential using massively parallel screening methods. His research focuses on “functional selectivity,” which he describes as

“the ligand-dependent selectivity for certain signal transduction pathways in one and the same receptor.”

Dr. Roth notes that structural data have demonstrated that GPCRs exist in multiple conformations: “The structures of the 5-hydroxytryptamine 2B receptor and the recent high-resolution delta-opioid receptor structure have provided evidence for conformational rearrangements that contribute to functional selectivity.” Drugs that take advantage of this selectivity by preferentially stabilizing certain conformations may have unique therapeutic utility.

“Generally, we look at G protein versus arrestin-based signaling, although it’s also possible to examine how drugs activate one G protein-mediated signaling pathway versus another.

fluorescently tagged Arrestin and GPRC of interest

β-Arrestins constitute a major class of intracellular scaffolding proteins that regulate GPCR signaling by preventing or enhancing the binding of GPCRs to intracellular signaling molecules. Laura Bohn, Ph.D., associate professor at Scripps Florida, studies the roles that β-arrestins play in GPCR-mediated signaling.
a particular β-arrestin can play multiple, tissue-specific roles—shutting down the signaling of a receptor in one tissue while activating signaling in another.
different ligands can direct GPCR signaling to different effectors, which could result in different physiological effects,” comments Dr. Bohn. “Our challenge is in determining what signaling pathways to harness to promote certain effects, while avoiding others.”

Arrestin binding to active GPCR kinase (GRK)-phosphorylated GPCRs blocks G protein coupling

Using Designer Proteins

The multifunctional signaling abilities of β-arrestins has prompted large-scale study of their properties. Vsevolod Gurevich, Ph.D., professor of pharmacology at Vanderbilt University, studies

the structure,
function, and
biology of arrestin proteins.

β-arrestins have three main functions.

First, they prevent the coupling of GPCRs to G proteins, thereby blocking further G protein-mediated signaling (a process known as desensitization).
Second, the binding of a GCPR releases the β-arrestin’s carboxy-terminal “tail” and promotes internalization of the receptor.
Third, receptor-bound β-arrestins bind other signaling proteins, resulting in a second wave of arrestin-mediated signaling.

Dr. Gurevich’s laboratory studies β-arrestin biology through the use of three types of specially designed mutants—

enhanced phosphorylation-dependent,
receptor-specific, and
signaling-biased mutants.

an enhanced mutant of visual β-arrestin-1 partially compensates for defects of rhodopsin phosphorylation in vivo,

“Several congenital disorders are caused by mutant GPCRs that cannot be normally phosphorylated because they have lost GPCR kinase (GRK) sites. Enhanced super-active arrestins have the potential to compensate for these defects, bringing the signaling closer to normal.”

Dr. Gurevich explains the strategy involved in creating designer β-arrestins: “We identify residues critical for individual β-arrestin functions by mutagenesis, using limited structural information as a guide.
We also work on getting more structural information. In collaboration with different crystallographers, we solved the crystal structures of all four vertebrate β-arrestin subtypes in the basal state, as well as the structure of the arrestin-1-rhodopsin complex.”
Dr. Gurevich believes that designer β-arrestins “are the next step in research and therapy, moving way beyond what small molecules can achieve.
The difference in capabilities between redesigned signaling proteins, including β-arrestins, and conventional small molecule drugs is about the same as that between airplanes and horse-driven carriages.”
Dr. Gurevich observes that redesigned signaling proteins face considerable obstacles in terms of gene delivery, but that the efforts are worth it. “Using designer signaling proteins, we can tell the cell what to do in a language it cannot disobey,” asserts Dr. Gurevich.

Synthesis and Antihypertensive Screening of Novel Substituted 1,2- Pyrazoline Sulfonamide Derivatives

Avinash M. Bhagwat , Anilchandra R. Bha , Mahesh S. Palled , Anand P. Khadke , Anuradha M. Patil, et al.

Am. J. PharmTech Res. 2014; 4(2). http://www.ajptr.com/

Angiotensin II receptor antagonists, also known as angiotensin receptor blockers , AT1-receptor antagonists or sartans, are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system. Their main use is in hypertension, diabetic nephropathy and congestiveheart failure. These substances are AT1-receptor antagonists which

block the activationof angiotensin II AT1 receptors.

Blockade of AT1 receptors directly causes

1 vasodilation,

2 reduces secretion of vasopressin,

3 reduces production and secretion of aldosterone, amongst other actions –

4 the combined effect of which is reduction of blood pressure.

Irbesartan is a safe and effectiveangiotensin II receptor antagonist with an affinity for the AT1 receptor that is more than 8,500times greater than its affinity for AT2 receptor. This agent has a higher bioavailability (60-80%) than other drugs in its class . In both Losartan and Irbesartan structures imidazole moiety is being present. A structure analog of losartan and Irbesartan are designed by incorporating the heterocycles like pyrazoline group. We felt it would be interesting to explore the possibilities of 1,2-pyrazoline derivatives for Angiotensin II receptor antagonistic activity.

The Irbesartan structure was a modified Losartan structure, which had all the identity of a Losartan molecule but with groups that would fit the hydrophobic cavity with a tetramethylene group and an alkyl side chain that would fit in the pocket in the AT1 receptor. The hydroxyl methyl group of Losartan being replaced with carbonyl group of Irbesartan. With a view to introduce a hydrogen bonding interaction with AT1 receptor, these structures were further modified with a view of retaining both hydrogen bonding characteristics and as well as lipophilic groups. Losartan and Irbesartan structure contains a diphenyl molecule & imidazole ring.

In Losartan and Irbesartan diphenyl molecule is attached to the nitrogen of the imidazole ring. It is interesting to to see the activity of compounds containing two phenyl rings attached at two different positions namely3,5 position of 1, 2-pyrazoline ring. The sulphonamide derivatives known for its diuretics activity which reduces renal hypertension. We use to synthesize sulphonamide and pyrazoline in one molecule to check its possible Angiotensin II receptor antagonist property. For this reason chalcones were synthesized reacted with hydrazine hydrate to yield the corresponding 1,2-pyrazoline derivatives which further condensed with sulphanilamide and formaldehyde by mannich condensation reaction.

Acute Toxicity Study (LD50)

This study was carried out in order to establish the therapeutic and toxic doses of the newly synthesized 1,2 pyrazoline derivatives. To establish LD50 of these compounds the method described by Miller & Tainter was employed.

5. Synthetic Biology

Artists and biologists team up to ush boundaries of synthetic biology

Kenrick Vezina | May 1, 2014 | Genetic Literacy Project

Synthetic biologists are often accused of “playing God,” of tampering with his Creation. Well, if you’re going to Create then you might as well do so with the help of some creative individuals? That’s just what the biologists in the pages of the new book Synthetic Aesthetics, from MIT Press, aims to do. Its arrival is well-timed, with the

first synthetic yeast chromosome having been created last month amid a flurry of scientific milestones in biotechnology.

Alun Anderson has reviewed the new book for New Scientist. Unlike the typically defensive posture found in biotech broadly, he writes, the spirit captured by this book is “freewheeling” and collaborative, with 20 authors ranging from the arts and sciences putting their minds together to generate original ideas. Anderson notes that parts of the book “may irritate conventional scientists – some of the ideas were dreamed up while ‘performing a dance based on the myth of the Golem’, for example. But it certainly explains the key ideas of the field and leads you to many lateral conversations about what it may become.” The book is itself an offshoot of a larger project, which you can check out at its official page. It describes itself as an “experimental, international research project between synthetic biology, art, design and social science” It has roots at the University of Edinburgh, Scotland, and Stanford University, California. And the main project team is comprised of bioengineers Drew Endy (Stanford) and Alistair Elfick (Edinburgh), social scientists Jane Calvert (Edinburgh) and Pablo Schyfter (Edinburgh), and designer/artist Alexandra Daisy Ginsberg.

In the book Synthetic Aesthetics, Ginsberg provides a thought-provoking counterpoint to the engineering definition of “design”. Anderson explains in his review: An engineer might think of designing a bridge to a particular specification; a synthetic biologist of designing a microorganism with a new commercial application, pumping out green gasoline for example; but a real designer, a fashion designer, for example, is doing something else. As artist Daisy Ginsberg puts it, design “is about possibility”, the unimagined things that life could be.

Synthetic biology, she writes, has been addressing “humanity’s needs” – limitless fuel, for example – rather than “our needs as individual, diverse and complex humans”. This is refreshing: worries about the separation between the top-down design of the future and those who must live with the results are quite rare in science. These words ring true, given the intensely “problem oriented” approach to most synthetic biology research. This approach extends to the coverage of this research in the media, where even a research achievement with sweeping potential like the synthetic yeast chromosome ends up broken down into pragmatic chunks. (Yeast could mass-produce medicines! Help process fuels!) Alistair Elfick, one of the leads on the Synthetics Aesthetics project, has written a fascinating opinion piece at The Conversation to accompany the release of his book. In it, he puts forth the idea it’s time for synthetic biologists to stop thinking “like scientists,” lest they hamstring themselves.

Kenrick Vezina is Gene-ius Editor for the Genetic Literacy Project and a freelance science writer, educator, and naturalist based in the Greater Boston area. Sources:

”Synthetic biology gets reborn as an aesthetic dream,” Alun Anderson | New Scientist
“If synthetic biologists think like scientists, they may miss their eureka moment,” Alistair Elfick | The Conversation
Synthetic Aesthetics project

“Breakthrough biology: First synthetic chromosome for yeast created, capping month of biotech innovations,” Kenrick Vezina | Genetic Literacy Project

Read Full Post »

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

Posted in Abdominal Aorta, Acute Myocardial Infarction, Aortic Valve: TAVR, TAVI vs Open Heart Surgery, Atherogenic Processes & Pathology, Bio Instrumentation in Experimental Life Sciences Research, CABG, Cancer Surgery of the Heart, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cardiomyopathy, Carotid Artery, Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH), Congenital Heart Disease, Ecosystems & Industrial Concentration in the Medical Device Sector, Electrophysiology, Exec Compensation in the Cardiac & Vascular Repair Tools Subsegment, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Frontiers in Cardiology and Cardiovascular Disorders, Heart Transplant, Heart-Lung Transplant, ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics, Massachusetts Niche Suppliers and National Leaders, Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Mitral Valve: Repair and Replacement, Origins of Cardiovascular Disease, PCI, Peripheral Arterial Disease & Peripheral Vascular Surgery, Pre-Clinical Animal Model Development, Renal Denervation, Spontaneous Coronary Artery Dissection (SCAD), Stents & Tools, Technology Transfer: Biotech and Pharmaceutical, Thoracic Aorta, Translational Science, Valves & Tools on April 17, 2014| Leave a Comment »

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

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

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/

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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/

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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/

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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/

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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