Archive for July, 2018

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

Posted in Cardiac and Cardiovascular Surgical Procedures, Implantation, Mitral Valve: Repair and Replacement, Replacement, TMVR - Transcatheter Mitral Valve Repair, tagged Left ventricular outflow tract (LVOT) obstruction (LVOTO) on July 25, 2018| Leave a Comment »

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

Reporter: Aviva Lev-Ari, PhD, RN

Left ventricular outflow tract obstruction (LVOTO) is a recognised feature of this condition which arises when blood leaving the outflow tract is impeded by systolic anterior motion of the mitral valve. LVOT obstruction was defined as a resting LVOT gradient of ≥30 mm Hg, with severe obstruction defined as ≥50 mm Hg (15).

Left ventricular outflow tract (LVOT) obstruction can occur at the valvular, subvalvular, or supravalvular level. In general, there is an obstruction to forward flow which increases afterload, and if untreated, can result in hypertrophy, dilatation, and eventual failure of the left ventricle. In the United States, most cases of LVOT obstruction are congenital in individuals younger than 50 years of age.

Jonathon Leipsic, M.D., FSCCT, professor of radiology and cardiology at the University of British Columbia, Vancouver, Canada, and an expert in transcatheter valve imaging. He spoke about his experiences with TAVR and TMVR trials and devices planning at the the Society of Cardiovascular Computed Tomography (SCCT) 2018 meeting.

Watch the VIDEO “What to Look for in CT Structural Heart Planning Software.”

Issues of Concern

Common Causes of Left Ventricular Outflow Tract Obstruction

Subaortic Stenosis (SAS)

Subaortic stenosis is narrowing at the level of the aortic valve. It may be due to a discrete ridge or fibrous ring encircling the LVOT. This fibrous membrane may extend onto the aortic valve cusps and make contact with the ventricular side of the anterior mitral leaflet. The obstruction may be focal or more diffuse, resulting in a tunnel leading out of the left ventricle. The discrete form is most common. Complex subaortic stenosis can also be seen which leads to abnormal adherence to the anterior leaflet of the mitral valve to the septum and the presence of endocardial tissue in the LVOT. These type of obstructions are commonly seen in patients with ventral septal defects (VSDs).

Clinical Significance

Left ventricular outflow tract obstructions involve stenotic lesions starting in the anatomic left ventricular outflow tract and stretching to the descending portion of the aortic arch.

Obstruction can be valvar, subvalvar, or supravalvar. Obstructions to forward flow can present alone or in concert. All of these lesions result in increased afterload on the left ventricle and if severe, result in hypertrophy and eventual dilatation and failure of the left ventricle. These lesions are usually congenital in the vast majority of individuals younger than 50 years. All patients with left ventricular outflow tract obstruction at a high risk for developing infective endocarditis and prophylaxis should be instituted.

Bicuspid Aortic Valve (BAV)

Bicuspid aortic valve is one of the most common congenital cardiovascular malformations, present in about 1% to 2% of the population and more common in males. BAV can be inherited, and family clusters have been documented. In those cases, inheritance patterns are usually autosomal dominant with variable penetrance. A mutation in the NOTCH1 gene has also been described.

BAVs arise from abnormal vasculogenesis and cusp formation, resulting in the formation of 1 smaller cusp and one larger cusp. More commonly, the right and left coronary cusps are fused. BAV is usually progressive, and most valves function normally until later in life. The abnormal valve formation leads to increased leaflet stress, more turbulent flow and restricted motion which leads to accelerated valve changes including scarring, calcification, aortic stenosis, and regurgitation. BAV is associated with dilation of the ascending aorta and increased risk of aortic dissection.

Clinical Features

The most common complication of BAV is aortic stenosis.

SOURCE

Left Ventricular Outflow Tract Obstruction

Viliane Vilcant; Ofek Hai.

https://www.ncbi.nlm.nih.gov/books/NBK470446/

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UPDATED on 12/26/2020 – CABG: a Superior Revascularization Modality to PCI in Patients with poor LVF, Multivessel disease and Diabetes, Similar Risk of Stroke between 31 days and 5 years, post intervention

Posted in Atherogenic Processes & Pathology, Bio Instrumentation in Experimental Life Sciences Research, CABG, Cardiac and Cardiovascular Surgical Procedures, Cerebrovascular and Neurodegenerative Diseases, Frontiers in Cardiology and Cardiovascular Disorders, Left Main Coronary Artery Disease (LMCAD), Origins of Cardiovascular Disease, PCI, Stroke on July 25, 2018| Leave a Comment »

UPDATED on 12/26/2020 – CABG: a Superior Revascularization Modality to PCI in Patients with poor LVF, Multivessel disease and Diabetes, Similar Risk of Stroke between 31 days and 5 years, post intervention

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED ON 1/16/2025

Surgery outperforms PCI in NSTEMI patients with multivessel CAD

Michael Walter | January 08, 2025 | Cardiovascular Business | Cardiac Surgery

Bypass surgery is associated with better long-term outcomes than percutaneous coronary intervention (PCI) when treating patients who present with non-ST-segment elevation myocardial infarction (NSTEMI) and multivessel disease, according to new research published in European Heart Journal.[1]

Researchers tracked more than 57,000 patients with NSTEMI and multivessel coronary artery disease (CAD) who underwent treatment from 2005 to 2022. The mean patient age was 68.7 years old, 75.8% were men and the median follow-up period was 7.1 years. All data came from the SWEDEHEART registry, which monitors heart patients treated in Sweden.

“Our findings indicate that CABG is associated with lower risks of all-cause mortality and myocardial infarction compared with PCI,” wrote first author Elmir Omerovic, a cardiologist and professor of cardiology with the University of Gothenburg in Sweden, and colleagues. “Specifically, the long-term risk of all-cause mortality was 41% lower in the CABG group, and the risk of myocardial infarction was 34% lower. The mortality benefit of CABG over PCI was evident at each yearly follow-up interval.”

Additionally, exploring the role of hybrid revascularization approaches and personalized medicine strategies could provide valuable insights into optimizing treatment for this complex patient population.”

Original Research

SOURCES

https://cardiovascularbusiness.com/topics/clinical/cardiac-surgery/surgery-outperforms-pci-nstemi-patients-multivessel-cad?utm_source=newsletter&utm_medium=cvb_cardiac

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UPDATED on 4/28/2023

Statin loading before coronary artery bypass grafting: a randomized trial

Get access

UPDATED on 12/26/2020

Five-Year Outcomes after PCI or CABG for Left Main Coronary Disease

List of authors.

Gregg W. Stone, M.D.,
A. Pieter Kappetein, M.D., Ph.D.,
Joseph F. Sabik, M.D.,
Stuart J. Pocock, Ph.D.,
Marie-Claude Morice, M.D.,
John Puskas, M.D.,
David E. Kandzari, M.D.,
Dimitri Karmpaliotis, M.D.,
W. Morris Brown, III, M.D.,
Nicholas J. Lembo, M.D.,
Adrian Banning, M.D.,
Béla Merkely, M.D.,
et al.,
for the EXCEL Trial Investigators^*

Abstract

BACKGROUND

Long-term outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents, as compared with coronary-artery bypass grafting (CABG), in patients with left main coronary artery disease are not clearly established.

METHODS

We randomly assigned 1905 patients with left main coronary artery disease of low or intermediate anatomical complexity (according to assessment at the participating centers) to undergo either PCI with fluoropolymer-based cobalt–chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). The primary outcome was a composite of death, stroke, or myocardial infarction.

RESULTS

At 5 years, a primary outcome event had occurred in 22.0% of the patients in the PCI group and in 19.2% of the patients in the CABG group (difference, 2.8 percentage points; 95% confidence interval [CI], −0.9 to 6.5; P=0.13). Death from any cause occurred more frequently in the PCI group than in the CABG group (in 13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2 to 6.1). In the PCI and CABG groups, the incidences of definite cardiovascular death (5.0% and 4.5%, respectively; difference, 0.5 percentage points; 95% CI, −1.4 to 2.5) and myocardial infarction (10.6% and 9.1%; difference, 1.4 percentage points; 95% CI, −1.3 to 4.2) were not significantly different. All cerebrovascular events were less frequent after PCI than after CABG (3.3% vs. 5.2%; difference, −1.9 percentage points; 95% CI, −3.8 to 0), although the incidence of stroke was not significantly different between the two groups (2.9% and 3.7%; difference, −0.8 percentage points; 95% CI, −2.4 to 0.9). Ischemia-driven revascularization was more frequent after PCI than after CABG (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI, 3.7 to 10.0).

CONCLUSIONS

In patients with left main coronary artery disease of low or intermediate anatomical complexity, there was no significant difference between PCI and CABG with respect to the rate of the composite outcome of death, stroke, or myocardial infarction at 5 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776. opens in new tab.)

https://www.nejm.org/doi/full/10.1056/NEJMoa1909406

Is the Tide Turning on the ‘Grubby’ Affair of EXCEL and the European Guidelines?

Taggart was chair of the surgical committee for the Abbott-sponsored EXCEL trial, which compared two procedures for patients who had blockages in their left main coronary artery: percutaneous coronary intervention (PCI) using coronary stents, and coronary artery bypass graft surgery (CABG). The investigators designed the trial to compare outcomes for the two treatments using a composite endpoint of death, stroke, and myocardial infarction (MI). The 3-year follow-up data had been published in NEJM without controversy — or, at least, without public controversy.

But when it came time to publish the 5-year follow-up, there was a significantly higher rate of death in the stent group, and both Taggart and the journal editors were concerned that this finding was being downplayed in the manuscript.

In their comments to the authors, the journal editors had recommended including the mortality difference (unless clearly trivial) ‘”in the concluding statement in the final paragraph.” Yet, the concluding statement of the published paper read that there “was no significant difference between PCI and CABG.”

Over a year after the BBC received the leaked data, the EXCEL investigators published an analysis of the primary outcome using the universal definition of MI data in the Journal of the American College of Cardiology.

It shows 141 events in the PCI arm compared to 102 in the CABG arm. The investigators acknowledge that the rates of procedural MI differ depending on the definition used. According to their analysis, the protocol definition was predictive of mortality after both treatments, whereas the universal definition of procedural MI was predictive of mortality only after CABG. Not everyone agrees with this interpretation, and an accompanying editorial questioned these conclusions.

As for the guidelines, the tide may be turning.

In a joint statement with EACTS on October 6, 2020, the ESC agreed to review its guidelines for left main disease in the light of emerging, longer-term outcome data from the trials of CABG vs PCI.

SOURCE

https://www.medscape.com/viewarticle/939944?src=WNL_infoc_201226_MSCPEDIT_excel2&uac=93761AJ&impID=2758606&faf=1#vp_5

UPDATED on 9/4/2019

SYNTAX at 10 Years: Bypass vs PCI Still a Toss-Up Overall

But CABG beats stenting for important subgroups

SYNTAX was funded by Boston Scientific.

Thuijs, Stone, and Taggart disclosed no conflicts.

Baumbach reported receiving institutional research support from Abbott Vascular; and consultation and speaker fees from AstraZeneca, Sinomed, Microport, Abbott Vascular, Cardinal Health, KSH, Medtronic.

Pagano is the Secretary General of the European Association for Cardiothoracic Surgery.

LAST UPDATED 09.03.2019

Overall, mortality curves did not diverge over time for SYNTAX participants now included in the trial’s extension study SYNTAXES: by 1o years, all-cause death reached 27.0% among those randomized to percutaneous coronary intervention (PCI) and 23.5% of the CABG arm (HR 1.17, 95% CI 0.97-1.41), according to Daniel Thuijs, MD, of Erasmus University Medical Centre in Rotterdam, the Netherlands.

However, people with three-vessel disease had particularly high mortality when assigned to PCI in lieu of CABG (27.7% vs 20.6%, HR 1.41, 95% CI 1.10-1.80), whereas peers with left main disease were no worse off after either procedure (26.1% vs 26.7%, HR 0.90, 95% CI 0.68-1.52), Thuijs told the audience during a late-breaking trial session at the European Society of Cardiology’s annual congress. The study was also published online in The Lancet.

Primary Source

European Society of Cardiology

Source Reference: Thuijs DJFM, et al “SYNTAX Extended Survival (SYNTAXES) trial: ten-year survival in patients randomized to percutaneous coronary intervention versus coronary artery bypass grafting in the randomized SYNTAX trial” ESC 2019.
Secondary Source

European Society of Cardiology

Source Reference: Stone GW “Ten-year survival in patients randomized to PCI versus CABG: the SYNTAX extended study (SYNTAXES) study” ESC 2019.
Additional Source

The Lancet

Source Reference: Taggart DP, Pagano D “Expansion or contraction of stenting in coronary artery disease?” Lancet 2019; DOI: 10.1016/S0140-6736(19)32040-9.

SOURCE

https://www.medpagetoday.com/meetingcoverage/esc/81944?xid=nl_mpt_DHE_2019-09-04&eun=g99985d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%202019-09-04&utm_term=NL_Daily_DHE_Active

Lancet Study, 2/2018

Interpretation

CABG had a mortality benefit over PCI in patients with multivessel disease, particularly those with diabetes and higher coronary complexity. No benefit for CABG over PCI was seen in patients with left main disease. Longer follow-up is needed to better define mortality differences between the revascularisation strategies.

JACC Study, 7/2018

CONCLUSIONS

This individual patient-data pooled analysis demonstrates that 5-year stroke rates are significantly lower after PCI compared with CABG, driven by a reduced risk of stroke in the 30-day post-procedural period but a similar risk of stroke between 31 days and 5 years. The greater risk of stroke after CABG compared with PCI was confined to patients with multivessel disease and diabetes. Five-year mortality was markedly higher for patients experiencing a stroke within 30 days after revascularization.

European Journal of Cardiothoracic Surgery Study, 6/2018

CONCLUSIONS

Despite a longer length of hospital stay, patients with impaired LVF requiring intervention for coronary artery disease experienced a greater post-procedural survival benefit if they received CABG compared to PCI. We have demonstrated this at 30 days, 90 days, 1 year, 3 years, 5 years and 8 years following revascularization. At present, CABG remains a superior revascularization modality to PCI in patients with poor LVF.

New Studies on Clinical Outcomes from two Revascularization Strategies: CABG and PCI

J Am Coll Cardiol. 2018 Jul 24;72(4):386-398. doi: 10.1016/j.jacc.2018.04.071.

Stroke Rates Following Surgical Versus Percutaneous Coronary Revascularization.

Head SJ¹, Milojevic M², Daemen J³, Ahn JM⁴, Boersma E³, Christiansen EH⁵, Domanski MJ⁶, Farkouh ME⁶, Flather M⁷, Fuster V⁸, Hlatky MA⁹, Holm NR⁵, Hueb WA¹⁰, Kamalesh M¹¹, Kim YH⁴, Mäkikallio T¹², Mohr FW¹³, Papageorgiou G¹⁴, Park SJ⁴, Rodriguez AE¹⁵, Sabik JF 3rd¹⁶, Stables RH¹⁷, Stone GW¹⁸, Serruys PW¹⁹, Kappetein AP².

Author information

Abstract

BACKGROUND:

Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are used for coronary revascularization in patients with multivessel and left main coronary artery disease. Stroke is among the most feared complications of revascularization. Due to its infrequency, studies with large numbers of patients are required to detect differences in stroke rates between CABG and PCI.

OBJECTIVES:

This study sought to compare rates of stroke after CABG and PCI and the impact of procedural stroke on long-term mortality.

METHODS:

We performed a collaborative individual patient-data pooled analysis of 11 randomized clinical trials comparing CABG with PCI using stents; ERACI II (Argentine Randomized Study: Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease) (n = 450), ARTS (Arterial Revascularization Therapy Study) (n = 1,205), MASS II (Medicine, Angioplasty, or Surgery Study) (n = 408), SoS (Stent or Surgery) trial (n = 988), SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial (n = 1,800), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) trial (n = 600), FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900), VA CARDS (Coronary Artery Revascularization in Diabetes) (n = 198), BEST (Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease) (n = 880), NOBLE (Percutaneous Coronary Angioplasty Versus Coronary Artery Bypass Grafting in Treatment of Unprotected Left Main Stenosis) trial (n = 1,184), and EXCEL (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial (n = 1,905). The 30-day and 5-year stroke rates were compared between CABG and PCI using a random effects Cox proportional hazards model, stratified by trial. The impact of stroke on 5-year mortality was explored.

RESULTS:

The analysis included 11,518 patients randomly assigned to PCI (n = 5,753) or CABG (n = 5,765) with a mean follow-up of 3.8 ± 1.4 years during which a total of 293 strokes occurred. At 30 days, the rate of stroke was 0.4% after PCI and 1.1% after CABG (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.20 to 0.53; p < 0.001). At 5-year follow-up, stroke remained significantly lower after PCI than after CABG (2.6% vs. 3.2%; HR: 0.77; 95% CI: 0.61 to 0.97; p = 0.027). Rates of stroke between 31 days and 5 years were comparable: 2.2% after PCI versus 2.1% after CABG (HR: 1.05; 95% CI: 0.80 to 1.38; p = 0.72). No significant interactions between treatment and baseline clinical or angiographic variables for the 5-year rate of stroke were present, except for diabetic patients (PCI: 2.6% vs. CABG: 4.9%) and nondiabetic patients (PCI: 2.6% vs. CABG: 2.4%) (p for interaction = 0.004). Patients who experienced a stroke within 30 days of the procedure had significantly higher 5-year mortality versus those without a stroke, both after PCI (45.7% vs. 11.1%, p < 0.001) and CABG (41.5% vs. 8.9%, p < 0.001).

CONCLUSIONS:

This individual patient-data pooled analysis demonstrates that 5-year stroke rates are significantly lower after PCI compared with CABG, driven by a reduced risk of stroke in the 30-day post-procedural period but a similar risk of stroke between 31 days and 5 years. The greater risk of stroke after CABG compared with PCI was confined to patients with multivessel disease and diabetes. Five-year mortality was markedly higher for patients experiencing a stroke within 30 days after revascularization.

Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

coronary artery bypass graft; left main; mortality; multivessel; percutaneous coronary intervention; stenting; stroke

PMID:

30025574

DOI:

10.1016/j.jacc.2018.04.071

SOURCE

https://www.ncbi.nlm.nih.gov/pubmed/30025574

Lancet Study

Head SJ, Milojevic M, Daemen J, Ahn JM, Boersma E, Christiansen EH, Domanski MJ, Farkouh ME, Flather M, Fuster V, Hlatky MA, Holm NR, Hueb WA, Kamalesh M, Kim YH, Mäkikallio T, Mohr FW, Papageorgiou G, Park SJ, Rodriguez AE, Sabik JF, Stables RH, Stone GW, Serruys PW, Kappetein AP. Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. Lancet. 2018 Feb 22 [Epub ahead of print]. doi: 10.1016/S0140-6736(18)30423-9. PMID: 29478841

DOI: https://doi.org/10.1016/S0140-6736(18)30423-9

|

Article Info

Summary

Full Text

Tables and Figures

References

Supplementary Material

Summary

Background

Numerous randomised trials have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for patients with coronary artery disease. However, no studies have been powered to detect a difference in mortality between the revascularisation strategies.

Methods

We did a systematic review up to July 19, 2017, to identify randomised clinical trials comparing CABG with PCI using stents. Eligible studies included patients with multivessel or left main coronary artery disease who did not present with acute myocardial infarction, did PCI with stents (bare-metal or drug-eluting), and had more than 1 year of follow-up for all-cause mortality. In a collaborative, pooled analysis of individual patient data from the identified trials, we estimated all-cause mortality up to 5 years using Kaplan-Meier analyses and compared PCI with CABG using a random-effects Cox proportional-hazards model stratified by trial. Consistency of treatment effect was explored in subgroup analyses, with subgroups defined according to baseline clinical and anatomical characteristics.

Findings

We included 11 randomised trials involving 11 518 patients selected by heart teams who were assigned to PCI (n=5753) or to CABG (n=5765). 976 patients died over a mean follow-up of 3·8 years (SD 1·4). Mean Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score was 26·0 (SD 9·5), with 1798 (22·1%) of 8138 patients having a SYNTAX score of 33 or higher. 5 year all-cause mortality was 11·2% after PCI and 9·2% after CABG (hazard ratio [HR] 1·20, 95% CI 1·06–1·37; p=0·0038). 5 year all-cause mortality was significantly different between the interventions in patients with multivessel disease (11·5% after PCI vs 8·9% after CABG; HR 1·28, 95% CI 1·09–1·49; p=0·0019), including in those with diabetes (15·5% vs 10·0%; 1·48, 1·19–1·84; p=0·0004), but not in those without diabetes (8·7% vs 8·0%; 1·08, 0·86–1·36; p=0·49). SYNTAX score had a significant effect on the difference between the interventions in multivessel disease. 5 year all-cause mortality was similar between the interventions in patients with left main disease (10·7% after PCI vs 10·5% after CABG; 1·07, 0·87–1·33; p=0·52), regardless of diabetes status and SYNTAX score.

Interpretation

CABG had a mortality benefit over PCI in patients with multivessel disease, particularly those with diabetes and higher coronary complexity. No benefit for CABG over PCI was seen in patients with left main disease. Longer follow-up is needed to better define mortality differences between the revascularisation strategies.

SOURCE

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30423-9/fulltext

European Journal of Cardiothoracic Surgery Study, 6/2018

Eur J Cardiothorac Surg. 2018 Jun 22. doi: 10.1093/ejcts/ezy236. [Epub ahead of print]

Comparison of the survival between coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with poor left ventricular function (ejection fraction <30%): a propensity-matched analysis.

Shah S¹, Benedetto U², Caputo M², Angelini GD², Vohra HA².

Author information

Abstract

OBJECTIVES:

Existing evidence comparing the outcomes of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in patients with poor left ventricular function (LVF) is sparse and flawed. This is largely due to patients with poor LVF being underrepresented in major research trials and the outdated nature of some studies that do not consider drug-eluting stent PCI.

METHODS:

Following strict inclusion criteria, 717 patients who underwent revascularization by CABG or PCI between 2002 and 2015 were enrolled. All patients had poor LVF (defined by ejection fraction <30%). By employing a propensity score analysis, 134 suitable matches (67 CABG and 67 PCI) were identified. Several outcomes were evaluated, in the matched population, using data extracted from national registry databases.

RESULTS:

CABG patients required a longer length of hospital stay post-revascularization compared to PCI in the propensity-matched population, 7 days (lower-upper quartile; 6-12) and 2 days (lower-upper quartile; 1-6), respectively (Mood’s median test, P = 0.001). Stratified Cox-regression proportional-hazards analysis of the propensity-matched population found that PCI patients experienced a higher adjusted 8-year mortality rate (hazard ratio 3.291, 95% confidence interval 1.776-6.101; P < 0.001). This trend was consistent amongst urgent cases of revascularization: patients with 3 or more vessels with coronary artery disease and patients where complete revascularization was achieved. Although sub-analyses found no difference between survival distributions of on-pump versus off-pump CABG (log-rank P = 0.726), both modes of CABG were superior to PCI (stratified log-rank P = 0.002).

CONCLUSIONS:

Despite a longer length of hospital stay, patients with impaired LVF requiring intervention for coronary artery disease experienced a greater post-procedural survival benefit if they received CABG compared to PCI. We have demonstrated this at 30 days, 90 days, 1 year, 3 years, 5 years and 8 years following revascularization. At present, CABG remains a superior revascularization modality to PCI in patients with poor LVF.

PMID:

29933433

DOI:

10.1093/ejcts/ezy236

SOURCE

https://www.ncbi.nlm.nih.gov/pubmed/30025574

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Omega-3 fats Supplements Effect on Cardiovascular Health: EPA and DHA has little or no effect on Mortality or Cardiovascular Health

Posted in Atherogenic Processes & Pathology, Cardiovascular Research, Frontiers in Cardiology and Cardiovascular Disorders, Nutrition, Nutritional Supplements: Atherogenesis, Nutritional Supplements: Atherogenesis, lipid metabolism, Obesity, Plant extract, tagged (long-chain omega-3 (LCn3), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), from plants (alpha-linolenic acid (ALA), omega-3 polyunsaturated fatty acids on July 24, 2018| Leave a Comment »

Omega-3 fats Supplements Effect on Cardiovascular Health: EPA and DHA has little or no effect on Mortality or Cardiovascular Health

Reporter: Aviva Lev-Ari, PhD, RN

Cochrane Database Syst Rev. 2018 Jul 18;7:CD003177. doi: 10.1002/14651858.CD003177.pub3. [Epub ahead of print]

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.

Abdelhamid AS¹, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KH, AlAbdulghafoor FK, Summerbell CD, Worthington HV, Song F, Hooper L.

Author information

Abstract

BACKGROUND:

Researchers have suggested that omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this.

OBJECTIVES:

To assess effects of increased intake of fish- and plant-based omega-3 for all-cause mortality, cardiovascular (CVD) events, adiposity and lipids.

SEARCH METHODS:

We searched CENTRAL, MEDLINE and Embase to April 2017, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to September 2016, with no language restrictions. We handsearched systematic review references and bibliographies and contacted authors.

SELECTION CRITERIA:

We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation and/or advice to increase LCn3 or ALA intake versus usual or lower intake.

DATA COLLECTION AND ANALYSIS:

Two review authors independently assessed studies for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression.

MAIN RESULTS:

We included 79 RCTs (112,059 participants) in this review update and found that 25 were at low summary risk of bias. Trials were of 12 to 72 months’ duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most studies assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet.Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (RR 0.98, 95% CI 0.90 to 1.03, 92,653 participants; 8189 deaths in 39 trials, high-quality evidence), cardiovascular mortality (RR 0.95, 95% CI 0.87 to 1.03, 67,772 participants; 4544 CVD deaths in 25 RCTs), cardiovascular events (RR 0.99, 95% CI 0.94 to 1.04, 90,378 participants; 14,737 people experienced events in 38 trials, high-quality evidence), coronary heart disease (CHD) mortality (RR 0.93, 95% CI 0.79 to 1.09, 73,491 participants; 1596 CHD deaths in 21 RCTs), stroke (RR 1.06, 95% CI 0.96 to 1.16, 89,358 participants; 1822 strokes in 28 trials) or arrhythmia (RR 0.97, 95% CI 0.90 to 1.05, 53,796 participants; 3788 people experienced arrhythmia in 28 RCTs). There was a suggestion that LCn3 reduced CHD events (RR 0.93, 95% CI 0.88 to 0.97, 84,301 participants; 5469 people experienced CHD events in 28 RCTs); however, this was not maintained in sensitivity analyses – LCn3 probably makes little or no difference to CHD event risk. All evidence was of moderate GRADE quality, except as noted.Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20, 19,327 participants; 459 deaths, 5 RCTs),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25, 18,619 participants; 219 cardiovascular deaths, 4 RCTs), and it may make little or no difference to CHD events (RR 1.00, 95% CI 0.80 to 1.22, 19,061 participants, 397 CHD events, 4 RCTs, low-quality evidence). However, increased ALA may slightly reduce risk of cardiovascular events (from 4.8% to 4.7%, RR 0.95, 95% CI 0.83 to 1.07, 19,327 participants; 884 CVD events, 5 RCTs, low-quality evidence), and probably reduces risk of CHD mortality (1.1% to 1.0%, RR 0.95, 95% CI 0.72 to 1.26, 18,353 participants; 193 CHD deaths, 3 RCTs), and arrhythmia (3.3% to 2.6%, RR 0.79, 95% CI 0.57 to 1.10, 4,837 participants; 141 events, 1 RCT). Effects on stroke are unclear.Sensitivity analysis retaining only trials at low summary risk of bias moved effect sizes towards the null (RR 1.0) for all LCn3 primary outcomes except arrhythmias, but for most ALA outcomes, effect sizes moved to suggest protection. LCn3 funnel plots suggested that adding in missing studies/results would move effect sizes towards null for most primary outcomes. There were no dose or duration effects in subgrouping or meta-regression.There was no evidence that increasing LCn3 or ALA altered serious adverse events, adiposity or lipids, although LCn3 slightly reduced triglycerides and increased HDL. ALA probably reduces HDL (high- or moderate-quality evidence).

AUTHORS’ CONCLUSIONS:

This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and high-quality evidence suggests that increasing EPA and DHA has little or no effect on mortality or cardiovascular health (evidence mainly from supplement trials). Previous suggestions of benefits from EPA and DHA supplements appear to spring from trials with higher risk of bias. Low-quality evidence suggests ALA may slightly reduce CVD event risk, CHD mortality and arrhythmia.

PMID:

30019766

DOI:

10.1002/14651858.CD003177.pub3

SOURCE

https://www.ncbi.nlm.nih.gov/pubmed/30019766

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

Posted in Atherogenic Processes & Pathology, Bio Instrumentation in Experimental Life Sciences Research, Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI), Frontiers in Cardiology and Cardiovascular Disorders, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Origins of Cardiovascular Disease, tagged Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) on July 23, 2018| Leave a Comment »

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

Reporter: Aviva Lev-Ari, RN

Early diagnosis and treatment could save lives by preventing the progression, and subsequent rupture, of these plaques. That is precisely why researchers designed the Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system, which allows not just high-acuity optical imaging via beta-sensitive probe, but also radioluminescent marking inside the artery to determine the extent of inflammation. Photoacoustic imaging also provides information about the often-complex biological makeup of the plaques (how much is calcified or comprised of cholesterol or triglycerides).

SOURCE

https://www.mdtmag.com/news/2017/06/pet-imaging-atherosclerosis-reveals-risk-plaque-rupture?cmpid=horizontalcontent

Unwanted DNA deletions by CRISPR gene editing technology

Posted in Biological Engineering, Biological Networks, Gene Regulation and Evolution, Cancer and Current Therapeutics, Cancer Genomics, Cancer Prevention: Research & Programs, Cell Biology, Clinical Genomics, DNA repair, Gene Regulation, Gene Regulation and Evolution, Gene Therapy & Gene Editing Development, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Genomic Endocrinology, Genomic Testing: Methodology for Diagnosis, Genomics Pharmacy, Molecular Genetics & Pharmaceutical, mRNA Therapeutics, Personalized and Precision Medicine & Genomic Research, Uncategorized, tagged CRISPR, DNA deletion, gene editing, gene therapy, rearrangements on July 22, 2018| Leave a Comment »

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

Researchers have embraced CRISPR gene-editing as a method for altering genomes, but some have reported that unwanted DNA changes may slip by undetected. The tool can cause large DNA deletions and rearrangements near its target site on the genome. Such alterations can confuse the interpretation of experimental results and could complicate efforts to design therapies based on CRISPR. The finding is in line with previous results from not only CRISPR but also other gene-editing systems.

CRISPR -Cas9 gene editing relies on the Cas9 enzyme to cut DNA at a particular target site. The cell then attempts to reseal this break using its DNA repair mechanisms. These mechanisms do not always work perfectly, and sometimes segments of DNA will be deleted or rearranged, or unrelated bits of DNA will become incorporated into the chromosome.

Researchers often use CRISPR to generate small deletions in the hope of knocking out a gene’s function. But when examining CRISPR edits, researchers found large deletions (often several thousand nucleotides) and complicated rearrangements of DNA sequences in which previously distant DNA sequences were stitched together. Many researchers use a method for amplifying short snippets of DNA to test whether their edits have been made properly. But this approach might miss larger deletions and rearrangements.

These deletions and rearrangements occur only with gene-editing techniques that rely on DNA cutting and not with some other types of CRISPR modifications that avoid cutting DNA. Such as a modified CRISPR system to switch one nucleotide for another without cutting DNA and other systems use inactivated Cas9 fused to other enzymes to turn genes on or off, or to target RNA. Overall, these unwanted edits are a problem that deserves more attention, but this should not stop anyone from using CRISPR. Only when people use it, they need to do a more thorough analysis about the outcome.

References:

https://www.nature.com/articles/d41586-018-05736-3?utm_source=briefing-dy

https://www.ncbi.nlm.nih.gov/pubmed/28561021

https://www.ncbi.nlm.nih.gov/pubmed/30010673

https://www.ncbi.nlm.nih.gov/pubmed/24651067

https://www.ncbi.nlm.nih.gov/pubmed/25398350

https://www.ncbi.nlm.nih.gov/pubmed/24838573

https://www.ncbi.nlm.nih.gov/pubmed/25200087

https://www.ncbi.nlm.nih.gov/pubmed/25757625

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The function of the junk jumping gene (LINE1) uncovered

Posted in Biological Networks, Biological Networks, Gene Regulation and Evolution, Clinical Genomics, Developmental biology, Gene Regulation, Gene Regulation and Evolution, Genetics & Innovations in Treatment, Genome Biology, Population genetics, Population Health Management, Genetics & Pharmaceutical, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, tagged development, Dux, embryo, jumping gene, LINE1, transposons on July 21, 2018| Leave a Comment »

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

Long interspersed nuclear elements 1 (LINE1) is repeated half a million times in the human genome, making up nearly a fifth of the DNA in every cell. But nobody cared to study it and may be the reason to call it junk DNA. LINE1, like other transposons (or “jumping genes”), has the unusual ability to copy and insert itself in random places in the genome. Many other research groups uncovered possible roles in early mouse embryos and in brain cells. But nobody quite established a proper report about the functions of LINE1.

Geneticists gave attention to LINE1 when it was found to cause cancer or genetic disorders like hemophilia. But researchers at University of California at San Francisco suspected there was more characteristics of LINE1. They suspected that if it can be most harmless then it can be worst harmful also.

Many reports showed that LINE1 is especially active inside developing embryos, which suggests that the segment actually plays a key role in coordinating the development of cells in an embryo. Researchers at University of California at San Francisco figured out how to turn LINE1 off in mouse embryos by blocking LINE1 RNA. As a result the embryos got stuck in the two-cell stage, right after a fertilized egg has first split. Without LINE1, embryos essentially stopped developing.

The researchers thought that LINE1 RNA particles act as molecular “glue,” bringing together a suite of molecules that switch off the two-cell stage and kick it into the next phase of development. In particular, it turns off a gene called Dux, which is active in the two-cell stage.

LINE1’s ability to copy itself, however, seems to have nothing to do with its role in embryonic development. When LINE1 was blocked from inserting itself into the genome, the embryonic stem cells remained unaffected. It’s possible that cells in embryos have a way of making LINE1 RNA while also preventing its potentially harmful “jumping” around in the genome. But it’s unlikely that every one of the thousands of copies of LINE1 is actually being used to regulate embryonic development.

LINE1 is abundant in the genomes of almost all mammals. Other transposons, also once considered junk DNA, have turned out to have critical roles in development in human cells too. There are differences between mice and humans, so, the next obvious step is to study LINE1 in human cells, where it makes up 17 percent of the genome.

References:

https://www-theatlantic-com.cdn.ampproject.org/c/s/www.theatlantic.com/amp/article/563354/

https://www.ncbi.nlm.nih.gov/pubmed/29937225

https://www.nature.com/scitable/topicpage/transposons-the-jumping-genes-518

https://www.sciencedaily.com/releases/2018/06/180621141038.htm

https://www.ncbi.nlm.nih.gov/pubmed/16015595

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LIVE eProceedings Day One – The 14th Annual Personalized Medicine Conference: PREPARING FOR THE NEW POSSIBLE, November 14, 2018, HMS, Boston

Posted in Conference Coverage with Social Media, Personalized and Precision Medicine & Genomic Research on July 18, 2018| Leave a Comment »

LIVE eProceedings Day One – The 14th Annual Personalized Medicine Conference: PREPARING FOR THE NEW POSSIBLE,

November 14, 2018, HMS, Boston

Real Time Press Coverage: Aviva Lev-Ari, PhD, RN

#PMConf

@pharma_BI

@AVIVA1950

PART I

The Infrastructure for Innovation

“We need to make the transition to a predict, prevent and protect health system.”

— JOSHUA OFMAN, M.D., M.S.H.S.
Senior Vice President, Global Value, Access and Policy, Amgen

Keynote Speakers

David King, J.D.

Chairman, CEO

LabCorp

Elizabeth Nabel, M.D.

President

Brigham and Women’s Hospital

Health IT at Partners and Mayo Clinic is the largest investment at comparable levels – Digital Health: Payers, patient engagement
is $233Billion projected for 2020
AI & Machine Learning, partnership with GE –
Response to normal dose, automate disease prediction, treatment pathways, clinical trial eligibility assessment, prophylaxis plans, diagnosis and medical imaging
4 TRENDS in Academic Medicine:

Consolidation of Health Systems in MA – efficiency of large care (EMR), increasing market care in relations with suppliers
Outcomes of consolidations: reduced readmissions, collaborations MGH and BWH – 1.7 Billion of sponsored research, 17Billion assets under investment 3700 faculty appointed at HMS 452 research and clinical departments – Spaulding, MEEI, McLean
Infrastructure for innovations: PARTNERS Healthcare Innovations: Patient Engagement & Education – PM Opportunities
AllofUs – precision Initiative
BIOBANK – Partners Health
Providers – Payer: Why Work together? 7% fee paid to BlueCross BlueShield to administer claims. – New company acquired to handle claims and save 7% paid to BC/BS – recovery ALWAYS HealthCare – marketed
Retail Pharmacy – CVS Health – Aetna, OPTUM DeVita
FUTURE partnerships: Amazon, Berkshire Hathaway and JP Morgan
PATIENTS CHOICES are promoted while drug prices in the US is highest in the World
Medicare Part D – accepts price does not compete
Partners subsidize Genomics-based therapy [Millenial Physician-Scientists pushing ML and Genomics], mental health and primary care

Daniel O’Day

CEO

Roche Pharmaceuticals

7:00 a.m.

Registration and Continental Breakfast

Joseph B. Martin Conference Center at Harvard Medical School
77 Avenue Louis Pasteur, Boston, MA 02115

8:00 a.m.

Opening Remarks

SPEAKER | Edward Abrahams, Ph.D., President, Personalized Medicine Coalition

Evidence-based to interact with providers
Future of Health care: Infrastructure of innovations, technologies and business aspects for efficient Health care delivery
Strategies to stimulate Personalized Medicicne
DIagnostics regulations for patient protection
cost of drugs, therapy costs 7 figures
clinical trial design
Prevention of illness
clinical and economic utilities of genome sequences
moving health care to a better future
Advisory committee contributed vastly in topic selection for the agenda for the two days conference
Sponsores Intermountain Genomics

8:10 a.m.

Setting the Stage: Exploring the Promise of Personalized Medicine — A Keynote Address

SPEAKER | Elizabeth Nabel, M.D., President, Brigham and Women’s Hospital

8:55 a.m.

Shifting Systems: Identifying the Common Challenges and Notable Achievements of Government Efforts to Advance Personalized Medicine

Government executives have an enormous influence over the direction of health systems and can therefore play a role in developing personalized medicine — but they need to know what works and what doesn’t if their respective efforts to promote personalized medicine are going to succeed. With that in mind, government representatives from around the globe will discuss the competitive advantages various countries have in personalized medicine and explore the common challenges and notable achievements of government initiatives to advance the field during this panel discussion.

MODERATOR | Antonio L. Andreu, M.D., Ph.D., Scientific Director, EATRIS European Infrastructure for Translational Medicine, Amsterdam

General Medicine: Metabolomics, biological systems vs GENOMICS
Medical care – due to genomic testing, MDs will call to tell patients bad news

Ora Dar, Ph.D., Senior Expert, Medical Sciences, consultant to the Israel Innovation Authority

$300Miliion R&D sponsored clinical data on genomics, MDs are trained to place genomics data on EMR, epidemiology, sequencing of genetic diseases
Genetic testing early implementation in Israel due to marriage of 3rd degree of kin,
Private insurance vs Public Insurance for genomic testing, Healthcare Basket coverage of genomics is not complete
2nd largest HMO collect data from Patients arriving to their Annual Exam will be genomically sequenced = Healthy and ill Patients – data gathered

Tom Fowler, Ph.D., Deputy Chief Scientist, Genomics England

Building infrastructure, education, future, National approach to genomic testing, built in a National lab, scaling research
three areas: Technical Operations, samples from Urban Hospitals to rural areas, population Health and Population system, Patients need to be brought about, do they want genomic testing?
rapid change in knowledge been flexible for genomic testing
Fooled not to come on board for Genomics in Medicine
Stories of patients that had success with Genomic-based therapy

Marc LePage, President, CEO, Genome Canada

Social impact, adoption systems for focusing on rare diseases, following UK and US trends, 10 sites in Canada, aggregate the date at the National level, extract clinical data securely implementation and expertise needs transfer for having it in each hospital
better health care at a lower cost can be achieved if genomics will become part of the equation – Open science
Optimism and hope

Liisa-Maria Voipio-Pulkki, M.D., Ph.D., Director General, Chief Medical Officer, Ministry of Social Affairs and Health, Finland

Public sector is the majority of Health care systems, Expertise is as high as can be, entrepreneurship is on the rise in search for opportunities
Brought to Parliament decision on funding a Center for Genomics Research as an independent institute for experimental therapies
Barrier in Health Care system National Screening and communication with other parts of the Health Care system
TRUST: validation of algorithms, insurance disclosure, ethics of AI,
Train new generation of CLinical Trial
Evaluation of Health care systems – new methods are needed for that task
pharmacogenomics – recommended for the Health system, ICU cost is very high will not change due to evidence from a genomic test which is preventative in nature

10:10 a.m.

Networking Break

Light refreshments provided.

10:40 a.m.

Evaluating Patients’ Priorities: Understanding Perspectives on Personalized Medicine — A Fireside Chat

MODERATOR | Susan McClure, Founder, Publisher, Genome magazine; Board Member, Personalized Medicine Coalition

Emily Kramer-Golinkoff, Co-Founder, Emily’s Entourage, cystic fibrosis patient

Better advocate for a Patient is the Patient him/herself

Bryce Olson, Global Marketing Director, Health and Life Sciences Group, Intel Corporation; stage IV prostate cancer patient

Patient engage in their care, involvement in interpretation og ONES OWN Genome sequence is ate most engaging

11:10 a.m.

Automating Actionable: How Artificial Intelligence May Chart a Course for Personalized Medicine

Artificial intelligence may help inform personalized medicine in the future by perceiving which genes, proteins and other biological characteristics contribute to human disease. During this session, a diverse panel will discuss how artificial intelligence may accelerate drug development, improve clinical decision support and drive patient outcomes — and what that might mean for the future of health care.

MODERATOR | Colin Hill, Chairman, CEO, Co-Founder, GNS Healthcare

Data, right data
Investment is it in data acquisition or in AI
AI is not taking over, data is critical
Predictionds for 2025

Tom Miller, Managing Partner, GreyBird Ventures LLC

algorithms are behind the firewall of the Hospital, for privacy. the patient’s identity is not of central point, privacy is the key
Meta ontologies – not ready yet
Validation of AI algorithms
India shortage of Radiologists
China is a huge market – AI will do functions of MDs
Oncology will lead the way in innovations

Gregg Talbert, Ph.D., Global Head of Digital and Personalized Health Care Partnering, Roche

AI applied to capture unusual movement allowing to detect a forthcoming neurological event.
Data is enough to get started on mutations
Data falls short on Patient follow up (longitudinal data on Patients) curation of EMR IS NOT AN EASY OR AUTOMATED PROCESS, IMAGING SPACE: CURATION OF IMAGES is quite a problem,
lack of productivity in the Healthcare system: records on transfer of patient to hospitals
Clinical Trial data for drug approval, also for future use of the analyzed data
In developing markets – solutions needs to be not a replication of the Western World medicine
Prediction: Data problem will be resolved in some areas, drugs developed by synthethic biologytaget to diseases drugs developed by AI
Patients will drive processes in Healthcare
Roche participates in data sharing and transfer protocols

Darrell M. West, Ph.D., Vice President of Governance Studies and Director of Center for Technology Innovation, Douglas Dillon Chair in Governance Studies, The Brookings Institution

Interest in AI and in particular: Health care large part of the economy Technologies:
Radiology: SW used in detection of disease
Personalized Medicine and AI
Data mining of Text using AI
Vital signs monitoring – providers can spot Arrhythmias earlier
Data centers have rich data , data analysis is important in Financial institutions for upselling instruments. In healthcare there is room as well
Future of Work book authored by Dr. West – augmentation of skills not replacement of
NY, Cold Spring: Local vs National, local progressive regulation is worrisome, pattern will migrate from NY to MA, to CA, OR, WA.
Mobile technology in Africa is advance: Global money, smart phones
2015: AI will transform other technologies: Communications, smart phones,

12:25 p.m.

Seated Luncheon

1:40 p.m.

The Lay of the Lab: Exploring the State of the Clinical Laboratory Testing Industry— A Keynote Address

SPEAKER | David King, J.D., Chairman, CEO, LabCorp

Clinical outcomes at reduced cost
PM – field with success
challenges faced by PM
BRCA gene at Breast Cancer patient – drug approved by FDA for this cases only
Genetic conseling assist physicians
What is diagnostics: NOT ONLY a test,
NGS is part of diagnostics strategy – enormous potential vs biopsy
Genetic testing improve outcomes
Insurance covers BRCA I AND BRCAII – ONLY
COVERAGE OF GENETIC TESTING : RANDOMIZED, CONTROLLED TRIALS, published in peer reviewed literature and the test will prolong life – Test do not prolong life, therefore, the test does not improve outcomes – drugs do !!!
PM individualized treatment for a specific disease
drug improve outcomes
Validity od data is fundamental, credibility of testing
Right drug to right patient
Migraine drug to be used
Non respondent – further researched
MDs understanding, confidence of results
PM Promise: close education GAP,
convene on VALUE for individual cases not populations
assess value among initiatives
PM – beyond Oncology
Regulation of diagnostics

2:25 p.m.

The Diagnostics Discussion: Evaluating the Extent to Which the Regulatory and Reimbursement Environment for Diagnostic Tests May Help or Hinder Personalized Medicine

The U.S. Food and Drug Administration and the U.S. Centers for Medicare and Medicaid Services have been working for over a decade to develop regulatory and reimbursement pathways that promote the development of innovative diagnostic tests. Many observers, however, believe the current regulatory and reimbursement landscape still limits the field. This panel of business leaders will discuss the extent to which the existing frameworks and proposed policies may help or hinder personalized medicine.

MODERATOR | Joseph V. Ferrara, CEO, Boston Healthcare Associates

Regulatory action for reimbursement of test
new categories of tests: new payment if Innovation, PLA codes, 45 months approval, CPT codes

3. Michael Doherty, Senior Vice President, Head of Product Development, Head of Research & Development, Foundation Medicine – ex Genentech/Roche

Operate in regulated environment, how to establish a company for long term
companion diagnostics
payment collection is the burden of the company
challenge for future products, investment process changes

Julie Khani, President, American Clinical Laboratory Association

FDA will establish a center for Diagnostics, proposal for pre-certification like in Medical devices
congress is involved in the decision making
Labs are prohibited from providing the data

2. Kimberly Popovits, Chairman of the Board, CEO, President, Genomic Health – Oncology, Breast cancer molecular diagnostics

Genomic testing saved the Health care System billions of dollars
Genomic testing will not be placebo, 12 years study controlled arms
proprietary test vs. test offered by all labs — different markets
Utility agreed upon like “MedicalDevicesInnovation.org”
demonstrate a pathway of product development that was already followed

4. Mark P. Stevenson, Executive Vice President, Chief Operating Officer, Thermo Fisher Scientific

3:25 p.m.

Networking Break

Light refreshments provided.

Live Conference Coverage @Medcitynews Converge 2018 @Philadelphia: Promising Drugs and Breaking Down Silos

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Prevention: Research & Programs, Clinical & Translational, Disease Biology, Small Molecules in Development of Therapeutic Drugs, FDA Regulatory Affairs, Health Economics and Outcomes Research, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Uncategorized, Value-based Drug Pricing, tagged @science 2_0, anti-cancer drugs, Big data, cancer cost, cost benefit, Data analysis, data sharing, DNASeq Data Analysis, drug costs, health outcomes, ICER, insurers, Keytruda, Keytruda (pembrolizumab), managing cost and quality, medical information, Medicare, medicare costs, merck, Open access, Pfizer, pharma industry, Pharmaceutical, Quality of life, science communication on July 12, 2018| Leave a Comment »

Live Conference Coverage @Medcitynews Converge 2018 @Philadelphia: Promising Drugs and Breaking Down Silos

Reporter: Stephen J. Williams, PhD

Promising Drugs, Pricing and Access

The drug pricing debate rages on. What are the solutions to continuing to foster research and innovation, while ensuring access and affordability for patients? Can biosimilars and generics be able to expand market access in the U.S.?

Moderator: Bunny Ellerin, Director, Healthcare and Pharmaceutical Management Program, Columbia Business School
Speakers:
Patrick Davish, AVP, Global & US Pricing/Market Access, Merck
Robert Dubois M.D., Chief Science Officer and Executive Vice President, National Pharmaceutical Council
Gary Kurzman, M.D., Senior Vice President and Managing Director, Healthcare, Safeguard Scientifics
Steven Lucio, Associate Vice President, Pharmacy Services, Vizient

What is working and what needs to change in pricing models?

Robert: He sees so many players in the onStevencology space discovering new drugs and other drugs are going generic (that is what is working). However are we spending too much on cancer care relative to other diseases (their initiative Going Beyond the Surface)

Steven: the advent of biosimilars is good for the industry

Patrick: large effort in oncology, maybe too much (750 trials on Keytruda) and he says pharma is spending on R&D (however clinical trials take large chunk of this money)

Robert: cancer has gotten a free ride but cost per year relative to benefit looks different than other diseases. Are we overinvesting in cancer or is that a societal decision

Gary: maybe as we become more specific with precision medicines high prices may be a result of our success in specifically targeting a mutation. We need to understand the targeted drugs and outcomes.

Patrick: “Cancer is the last big frontier” but he says prices will come down in most cases. He gives the example of Hep C treatment… the previous only therapeutic option was a very toxic yearlong treatment but the newer drugs may be more cost effective and safer

Steven: Our blockbuster drugs could diffuse the expense but now with precision we can’t diffuse the expense over a large number of patients

President’s Cancer Panel Recommendation

Six recommendations

promoting value based pricing
enabling communications of cost
financial toxicity
stimulate competition biosimilars
value based care
invest in biomedical research

Patrick: the government pricing regime is hurting. Alot of practical barriers but Merck has over 200 studies on cost basis

Robert: many concerns/impetus started in Europe on pricing as they are a set price model (EU won’t pay more than x for a drug). US is moving more to outcomes pricing. For every one health outcome study three studies did not show a benefit. With cancer it is tricky to establish specific health outcomes. Also Medicare gets best price status so needs to be a safe harbor for payers and biggest constraint is regulatory issues.

Steven: They all want value based pricing but we don’t have that yet and there is a challenge to understand the nuances of new therapies. Hard to align all the stakeholders together so until some legislation starts to change the reimbursement-clinic-patient-pharma obstacles. Possibly the big data efforts discussed here may help align each stakeholders goals.

Gary: What is the data necessary to understand what is happening to patients and until we have that information it still will be complicated to determine where investors in health care stand at in this discussion

Robert: on an ICER methods advisory board: 1) great concern of costs how do we determine fair value of drug 2) ICER is only game in town, other orgs only give recommendations 3) ICER evaluates long term value (cost per quality year of life), budget impact (will people go bankrupt)

4) ICER getting traction in the public eye and advocates 5) the problem is ICER not ready for prime time as evidence keeps changing or are they keeping the societal factors in mind and they don’t have total transparancy in their methodology

Steven: We need more transparency into all the costs associated with the drug and therapy and value-based outcome. Right now price is more of a black box.

Moderator: pointed to a recent study which showed that outpatient costs are going down while hospital based care cost is going rapidly up (cost of site of care) so we need to figure out how to get people into lower cost setting

Breaking Down Silos in Research

“Silo” is healthcare’s four-letter word. How are researchers, life science companies and others sharing information that can benefit patients more quickly? Hear from experts at institutions that are striving to tear down the walls that prevent data from flowing.

Moderator: Vini Jolly, Executive Director, Woodside Capital Partners
Speakers:
Ardy Arianpour, CEO & Co-Founder, Seqster @seqster
Lauren Becnel, Ph.D., Real World Data Lead for Oncology, Pfizer
Rakesh Mathew, Innovation, Research, & Development Lead, HealthShareExchange
David Nace M.D., Chief Medical Officer, Innovaccer

Seqster: Seqster is a secure platform that helps you and your family manage medical records, DNA, fitness, and nutrition data—all in one place. Founder has a genomic sequencing background but realized sequence information needs to be linked with medical records.

HealthShareExchange.org :

HealthShare Exchange envisions a trusted community of healthcare stakeholders collaborating to deliver better care to consumers in the greater Philadelphia region. HealthShare Exchange will provide secure access to health information to enable preventive and cost-effective care; improve quality of patient care; and facilitate care transitions. They have partnered with multiple players in healthcare field and have data on over 7 million patients.

Innovacer

Data can be overwhelming, but it doesn’t have to be this way. To drive healthcare efficiency, we designed a modular suite of products for a smooth transition into a data-driven world within 4 weeks. Why does it take so much money to move data around and so slowly?

What is interoperatibility?

Ardy: We knew in genomics field how to build algorithms to analyze big data but how do we expand this from a consumer standpoint and see and share your data.

Lauren: how can we use the data between patients, doctors, researchers? On the research side genomics represent only 2% of data. Silos are one issue but figuring out the standards for data (collection, curation, analysis) is not set. Still need to improve semantic interoperability. For example Flatiron had good annotated data on male metastatic breast cancer.

David: Technical interopatabliltiy (platform), semantic interopatability (meaning or word usage), format (syntactic) interopatibility (data structure). There is technical interoperatiblity between health system but some semantic but formats are all different (pharmacies use different systems and write different prescriptions using different suppliers). In any value based contract this problem is a big issue now (we are going to pay you based on the quality of your performance then there is big need to coordinate across platforms). We can solve it by bringing data in real time in one place and use mapping to integrate the format (need quality control) then need to make the data democratized among players.

Rakesh: Patients data should follow the patient. Of Philadelphia’s 12 health systems we had a challenge to make data interoperatable among them so tdhey said to providers don’t use portals and made sure hospitals were sending standardized data. Health care data is complex.

David: 80% of clinical data is noise. For example most eMedical Records are text. Another problem is defining a patient identifier which US does not believe in.

Please follow on Twitter using the following #hash tags and @pharma_BI

#MCConverge

#cancertreatment

#healthIT

#innovation

#precisionmedicine

#healthcaremodels

#personalizedmedicine

#healthcaredata

And at the following handles:

@pharma_BI

@medcitynews

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Live Conference Coverage @Medcitynews Converge 2018 Philadelphia:Liquid Biopsy and Gene Testing vs Reimbursement Hurdles

Posted in Big Data & Analytics, BioBanking, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Screening, Circulating Tumor Cells (CTC), Clinical Genomics, Diagnostics and Lab Tests, FDA, Health Economics and Outcomes Research, Healthcare costs and reimbursement, KRAS Mutation, Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood, Liquid Biopsy: Circulating Tumor Cells in Urine and Blood, Patient-centered Medicine, Personalized and Precision Medicine & Genomic Research, Scientific & Biotech Conferences: Press Coverage, Uncategorized, tagged biomarker panels, circulating cancer cells, circulating DNA, ctDNA Liquid Biopsy, healthcare reimbursement, liquid biopsy, therapeutic monitoring on July 12, 2018| Leave a Comment »

Live Conference Coverage @Medcitynews Converge 2018 Philadelphia:Liquid Biopsy and Gene Testing vs Reimbursement Hurdles

Reporter: Stephen J. Williams, PhD

9:25- 10:15 Liquid Biopsy and Gene Testing vs. Reimbursement Hurdles

Genetic testing, whether broad-scale or single gene-testing, is being ordered by an increasing number of oncologists, but in many cases, patients are left to pay for these expensive tests themselves. How can this dynamic be shifted? What can be learned from the success stories?

Moderator: Shoshannah Roth, Assistant Director of Health Technology Assessment and Information Services , ECRI Institute @Ecri_Institute
Speakers:
Rob Dumanois, Manager – reimbursement strategy, Thermo Fisher Scientific
Eugean Jiwanmall, Senior Research Analyst for Medical Policy & Technology Evaluation , Independence Blue Cross @IBX
Michael Nall, President and Chief Executive Officer, Biocept

Michael: Wide range of liquid biopsy services out there. There are screening companies however they are young and need lots of data to develop pan diagnostic test. Most of liquid biopsy is more for predictive analysis… especially therapeutic monitoring. Sometimes solid biopsies are impossible , limited, or not always reliable due to metastasis or tough to biopsy tissues like lung.

Eugean: Circulating tumor cells and ctDNA is the only FDA approved liquid biopsies. However you choose then to evaluate the liquid biopsy, PCR NGS, FISH etc, helps determines what the reimbursement options are available.

Rob: Adoption of reimbursement for liquid biopsy is moving faster in Europe than the US. It is possible in US that there may be changes to the payment in one to two years though.

Michael: China is adopting liquid biopsy rapidly. Patients are demanding this in China.

Reimbursement

Eugean: For IBX to make better decisions we need more clinical trials to correlate with treatment outcome. Most of the major cancer networks, like NCCN, ASCO, CAP, just have recommendations and not approved guidelines at this point. From his perspective with lung cancer NCCN just makes a suggestion with EGFR mutations however only the companion diagnostic is approved by FDA.

Michael: Fine needle biopsies are usually needed by the pathologist anyway before they go to liquid biopsy as need to know the underlying mutations in the original tumor, it just is how it is done in most cancer centers.

Eugean: Whatever the established way of doing things, you have to outperform the clinical results of the old method for adoption of a newer method.

Reimbursement issues have driven a need for more research into clinical validity and utility of predictive and therapeutic markers with regard to liquid biopsies. However although many academic centers try to partner with Biocept Biocept has a limit of funds and must concentrate only on a few trials. The different payers use different evidence based methods to evaluate liquid biopsy markers. ECRI also has a database for LB markers using an evidence based criteria. IBX does sees consistency among payers as far as decision and policy.

NGS in liquid biopsy

Rob: There is a path to coverage, especially through the FDA. If you have a FDA cleared NGS test, it will be covered. These are long and difficult paths to reimbursement for NGS but it is feasible. Medicare line of IBX covers this testing, however on the commercial side they can’t cover this. @IBX: for colon only kras or nras has clinical utility and only a handful of other cancer related genes for other cancers. For a companion diagnostic built into that Dx do the other markers in the panel cost too much?

Please follow on Twitter using the following #hash tags and @pharma_BI

#MCConverge

#cancertreatment

#healthIT

#innovation

#precisionmedicine

#healthcaremodels

#personalizedmedicine

#healthcaredata

And at the following handles:

@pharma_BI

@medcitynews

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Live Conference Coverage @Medcitynews Converge 2018 Philadelphia: The Davids vs. the Cancer Goliath Part 2

Posted in Best evidence, Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Image Processing/Computing, Imaging-based Cancer Patient Management, interventional oncology, Medical Imaging Technology, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Patents, Patient Experience, Population Health Management, Genetics & Pharmaceutical, Support Staff, Supportive therapies, Uncategorized, tagged cutaneous melanoma, Digital pathology, Glioblastoma, health outcomes research, health outomes, HIPAA, imaging, imaging software, Melanoma on July 12, 2018| Leave a Comment »

Live Conference Coverage @Medcitynews Converge 2018 Philadelphia: The Davids vs. the Cancer Goliath Part 2

Reporter: Stephen J. Williams, PhD

8:40 – 9:25 AM The Davids vs. the Cancer Goliath Part 2

Startups from diagnostics, biopharma, medtech, digital health and emerging tech will have 8 minutes to articulate their visions on how they aim to tame the beast.

Start Time	End Time	Company
8:40	8:48	3Derm
8:49	8:57	CNS Pharmaceuticals
8:58	9:06	Cubismi
9:07	9:15	CytoSavvy
9:16	9:24	PotentiaMetrics

Speakers:
Liz Asai, CEO & Co-Founder, 3Derm Systems, Inc. @liz_asai
John M. Climaco, CEO, CNS Pharmaceuticals @cns_pharma

John Freyhof, CEO, CytoSavvy
Robert Palmer, President & CEO, PotentiaMetrics @robertdpalmer
Moira Schieke M.D., Founder, Cubismi, Adjunct Assistant Prof UW Madison @cubismi_inc

3Derm Systems

3Derm Systems is an image analysis firm for dermatologic malignancies. They use a tele-medicine platform to accurately triage out benign malignancies observed from the primary care physician, expediate those pathology cases if urgent to the dermatologist and rapidly consults with you over home or portable device (HIPAA compliant). Their suite also includes a digital dermatology teaching resource including digital training for students and documentation services.

CNS Pharmaceuticals

developing drugs against CNS malignancies, spun out of research at MD Anderson. They are focusing on glioblastoma and Berubicin, an anthracycline antiobiotic (TOPOII inhibitor) that can cross the blood brain barrier. Berubicin has good activity in a number of animal models. Phase I results were very positive and Phase II is scheduled for later in the year. They hope that the cardiotoxicity profile is less severe than other anthracyclines. The market opportunity will be in temazolamide resistant glioblastoma.

Cubismi

They are using machine learning and biomarker based imaging to visualize tumor heterogeneity. “Data is the new oil” (Intel CEO). We need prediction machines so they developed a “my body one file” system, a cloud based data rich file of a 3D map of human body.

CUBISMI IS ON A MISSION TO HELP DELIVER THE FUTURE PROMISE OF PRECISION MEDICINE TO CURE DISEASE AND ASSURE YOUR OPTIMAL HEALTH. WE ARE BUILDING A PATIENT-DOCTOR HEALTH DATA EXCHANGE PLATFORM THAT WILL LEVERAGE REVOLUTIONARY MEDICAL IMAGING TECHNOLOGY AND PUT THE POWER OF HEALTH DATA INTO THE HANDS OF YOU AND YOUR DOCTORS.

CytoSavvy

CytoSavvy is a digital pathology company. They feel AI has a fatal flaw in that no way to tell how a decision was made. Use a Shape Based Model Segmentation algorithm which uses automated image analysis to provide objective personalized pathology data. They are partnering with three academic centers (OSU, UM, UPMC) and pool data and automate the rule base for image analysis.

CytoSavvy’s patented diagnostic dashboards are intuitive, easy–to-use and HIPAA compliant. Our patented Shape-Based Modeling Segmentation (SBMS) algorithms combine shape and color analysis capabilities to increase reliability, save time, and improve decisions. Specifications and capabilities for our web-based delivery system follow.

link to their white paper: https://www.cytosavvy.com/resources/healthcare-ai-value-proposition.pdf

PotentialMetrics

They were developing a diagnostic software for cardiology epidemiology measuring outcomes however when a family member got a cancer diagnosis felt there was a need for outcomes based models for cancer treatment/care. They deliver real world outcomes for persoanlized patient care to help patients make decisions on there care by using a socioeconomic modeling integrated with real time clinical data.

Featured in the Wall Street Journal, using the informed treatment decisions they have generated achieve a 20% cost savings on average. There research was spun out of Washington University St. Louis.

They have concentrated on urban markets however the CEO had mentioned his desire to move into more rural areas of the country as there models work well for patients in the rural setting as well.

Please follow on Twitter using the following #hash tags and @pharma_BI

#MCConverge

#cancertreatment

#healthIT

#innovation

#precisionmedicine

#healthcaremodels

#personalizedmedicine

#healthcaredata

And at the following handles:

@pharma_BI

@medcitynews

Read Full Post »

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Archive for July, 2018

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Issues of Concern

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UPDATED on 12/26/2020 – CABG: a Superior Revascularization Modality to PCI in Patients with poor LVF, Multivessel disease and Diabetes, Similar Risk of Stroke between 31 days and 5 years, post intervention

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Abstract

Is the Tide Turning on the ‘Grubby’ Affair of EXCEL and the European Guidelines?

Primary Source

European Society of Cardiology

Secondary Source

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Additional Source

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Interpretation

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CONCLUSIONS

European Journal of Cardiothoracic Surgery Study, 6/2018

CONCLUSIONS

New Studies on Clinical Outcomes from two Revascularization Strategies: CABG and PCI

Stroke Rates Following Surgical Versus Percutaneous Coronary Revascularization.

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METHODS:

RESULTS:

CONCLUSIONS:

KEYWORDS:

Lancet Study

Summary

Background

Methods

Findings

Interpretation

European Journal of Cardiothoracic Surgery Study, 6/2018

Comparison of the survival between coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with poor left ventricular function (ejection fraction <30%): a propensity-matched analysis.

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Omega-3 fats Supplements Effect on Cardiovascular Health: EPA and DHA has little or no effect on Mortality or Cardiovascular Health

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.

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

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LIVE eProceedings Day One – The 14th Annual Personalized Medicine Conference: PREPARING FOR THE NEW POSSIBLE,

November 14, 2018, HMS, Boston

PART I

The Infrastructure for Innovation

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Live Conference Coverage @Medcitynews Converge 2018 @Philadelphia: Promising Drugs and Breaking Down Silos

Promising Drugs, Pricing and Access

Breaking Down Silos in Research

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Live Conference Coverage @Medcitynews Converge 2018 Philadelphia:Liquid Biopsy and Gene Testing vs Reimbursement Hurdles

9:25- 10:15 Liquid Biopsy and Gene Testing vs. Reimbursement Hurdles

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