Consensus Document Provides Roadmap To Uptake Of TAVI In US 3

Following the recent approval by the FDA of transcatheter aortic valve replacement (TAVR), the ACC, AATS, SCAI, and STS, in conjunction with several other medical organizations, have released a critical consensus document to guide use of the new landmark procedure.

“We have tried to collate the evidence into a coherent road map for judicious use, rational dispersion, and careful post-marketing scrutiny of this promising technology,” said Sanjay Kaul, vice chair of the writing committee, in a press release. “It is now the collective responsibility of all the stakeholders to optimize its full potential for improving the duration as well as the quality of survival in patients with severe symptomatic aortic valvular stenosis.”

Here are some of the key recommendations identified by the committee:

–Careful patient selection

–Team-based approach given the complexity of procedure coupled with the high-risk profile of suitable patients, many of whom have extensive comorbid conditions that require ongoing management

–Specialized heart centers and physician expertise in treating valve disorders; this includes use of proctors as needed to serve on the heart care team during the first few cases, as well as proper facilities (hybrid operating rooms or modified cath labs)

–TAVR screening tests to inform treatment decisions

–Enhanced patient and family education in the risk and benefits of this procedure

–Ongoing evaluation and participation in national TAVR registry to assess real world outcomes

The document also emphasizes the groups for whom TAVR is not recommended:

–An acceptable surgical risk for conventional surgical AVR

–Known bicuspid aortic valve

–Severe mitral annular calcification or severe MR

–Moderate AS

–Other (e.g., severe AR and subaortic stenosis)

Click here to read the press release from the ACC, AATS, SCAI, and STS…

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Robert Harrington Leaving Duke for Stanford University 1

Robert Harrington will be leaving his position as the director of the Duke Clinical Research Institute, a position he has held since 2006, to become the new chair of the department of medicine at Stanford University. Harrington was also the Richard S. Stack MD Distinguished Professor at Duke University School of Medicine.

The news was publicly announced by Philip Pizzo, the dean of the Stanford University School of Medicine, in The Dean’s Newsletter.

Harrington said he planned to stay active in the cardiology world at Stanford. He told CardioBrief:

As you might imagine, I love the DCRI and my job here but this was really a unique opportunity that came at a great time in our life.

Click here to read the press release from Duke and the announcement from the Stanford Dean’s office…

Appropriate Use Criteria for Revascularization Updated Reply

The ACC, AHA, and other organizations have released updated appropriate use criterial for coronary revascularization. The 2012 Appropriate Use Criteria for Coronary Revascularization Focused Update incorporates data from the SYNTAX trial on the indications for PCI and CABG in patients with symptomatic, multivessel disease, as well as data from the CathPCI registry.

Here are some of the key ratings:

  • PCI for low burden left main disease alone or with blockages in other arteries with a low disease burdenuncertain
  • PCI for intermediate or high burden left main disease: inappropriate
  • PCI for low burden three-vessel disease: appropriate
  • PCI for intermediate or high burden three-vessel disease: uncertain
  • CABG remains appropriate for patients with two vessel disease including the proximal LAD and all three vessel and left main disease.

Click here to read the press release from the ACC, AATS, and SCAI…

Very Large Observational Study Finds Significant Mortality Advantage for CABG Over PCI in High Risk Patients Reply

Although PCI has a small, early mortality benefit compared to CABG in high risk patients, after the first year a striking survival advantage for CABG develops, according to results of the ASCERT study, presented on Monday at the annual meeting of the Society of Thoracic Surgeons (STS) meeting.

Fred Edwards presented the high-risk subset of ASCERT (ACCF-STS Database Collaboration on the Comparative Effectiveness of Revascularization Strategies), an NHLBI-funded study based on linked data from the STS, the ACC, and CMS administrative data. (The full results of ASCERT will be presented in March at the ACC scientific sessions.) The study population included patients 65 or older with 2 or 3 vessel disease who underwent CABG or PCI in the period from 2004 through 2007. 189,793 patients were followed in the study; 103,549 received PCI and 86,244 underwent CABG.

At 4 years there was a 22% risk reduction in adjusted mortality in the CABG group compared to the PCI group (RR = 0.78, CI 0.74-0.82). A similar pattern was observed in patients regardless of age, gender, diabetes status, and ejection fraction.

“Previous observational studies have shown a long-term survival advantage for CABG over PCI. These partial ASCERT results confirm that in important high-risk clinical subsets the CABG survival advantage can also be seen in a large nationwide population,” said Edwards in an STS press release.
Click to read the press release form the STS…

ACC 2012 Roster of Late-Breaking Clinical Trials Reply

The American College of Cardiology has released the roster of late-breaking clinical trials that will be presented in March at the ACC Scientific Sessions:

ACC.12 Opening Session and Late-Breaking Clinical Trials
Saturday, March 24, 2012, 8:00 a.m. – 10:00 a.m.

Effect of Transendocardial Autologous Bone Marrow Mononuclear Cell Delivery on Functional Capacity, Left Ventricular Function and Perfusion in Chronic Ischemic Heart Failure: The FOCUS Randomized Trial

  • Emerson C. Perin, James Willerson, Stephen Ellis, Timothy Henry, Carl Pepine, David Zhao, Dejian Lai, Barry Byrne, Antonis Hatzopoulos, Marc Penn, Jay Traverse, Adrian Gee, Marvin Kronenberg, Daniel Martin, James Thomas, Doris Taylor, Christopher Cogle, Sonia Skarlatos, Lem Moye, Robert Simari, Cardiovascular Cell Therapy Research Network (CCTRN), Houston, TX, USA

Evaluation of a Novel Antiplatelet Agent for Secondary Prevention in Patients with Atherosclerotic Disease: Results of the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P): TIMI 50 Trial

  • David A. Morrow, Brigham & Women’s Hospital, Boston, MA, USA

Late-Breaking Clinical Trials II
Sunday, March 25, 2012, 8:00 a.m. – 9:30 a.m.

Outcomes of Non-Primary PCI at Hospitals with and without On-site Cardiac Surgery:CPORT-E Trial. Final Medical Outcomes

Click to continue reading…

Lancet Editor Richard Horton Tweets Dark View of Contemporary Medicine 1

One brief message at a time, Lancet editor Richard Horton is tweeting his dark view of the contemporary medical establishment. If you have any interest at all in peeking behind the curtain to see what really goes on behind the scenes of top medical organizations then you need to follow Richard Horton’s Twitter feed. In sudden bursts of candor, humor, and cynicism, Horton has been tweeting thoughts that don’t often see the light of day.

Here’s his unvarnished opinion of the World Health Organization, for instance:

WHO is no longer a science-based organisation. WHO believes that scientists within the agency should be anonymous bureaucrats.

Science in WHO is seen as a dangerously subversive activity. Publication in journals brings the threat of disciplinary

And here’s a glimpse of the British side of the medical elite that we don’t normally see:

England is run by strange clubs. The Athenaeum is the one for high-ranking doctors. You can feel death oozing from the wood panels.

If you enter, you find cabals of Presidents/Professors plotting/sleeping in corners: an up-market rest home for the medical establishment.

And here’s the thread of tweets that prompted this post. It started a few weeks ago, and it’s about an ongoing editorial battle with authors and another highly respected journal. I can’t remember these sort of statements ever being made in public before, though these sort of stories are often discussed privately and always, to a journalist, off the record. The significance of these remarks is considerable. As Horton remarks at the end, the episode appears to lend evidence to the manipulation of journals by industry. (I’ve placed the tweets in chronological order to make them easier to read.)

When papers get salami sliced and divided between NEJM and us, it gets complicated. And sometimes nasty. And today, even threatening.

Now put to rest a terrible authorship dispute that has blocked an accepted paper for months. Crucial lesson: agree authors before starting.

The mother of all authorship disputes has broken out.

When papers get salami sliced and divided between NEJM and us, it gets complicated. And sometimes nasty. And today, even threatening.

In the saga of our salami sliced paper at NEJM and Lancet, both journals are now saying, it’s us or no go. This is getting silly.

NEJM/Lancet salami story, Part 164: US author writes to report “significant disagreement” among authors. We are told to suspend review…

Authors on both versions of what seems to be largely the same paper with our two journals to gather and resolve their dispute. We wait…

Lancet/NEJM salami latest. From Principal Investigator. “Approval [of the drug in question] has already occurred in the US, yet…

…private insurers are slow to place it on their formulary. A major publication is typically how this occurs in the US, and it is…

important to be in a journal typically recognised by US-based companies. This would include NEJM…Therefore, this publication is critical..

…to [company A's] ability to “market” their product. Lancet, on the other hand, will aid [company Y] quite nicely.”

Is this first-hand evidence of journals being manipulated by pharma-sponsored authors for commercial goals?

NHLBI Launches Two Large Cardiac Arrest Treatment Trials Reply

The NHLBI today announced the launch of two large clinical trials evaluating treatments for out-of-hospital cardiac arrest.

The Continuous Chest Compressions (CCC) trial will randomize 23,600 people with out-of-hospital cardiac arrest to either standard CPR or continuous chest compressions, both delivered by paramedics or fire fighters. In recent years, studies published in the New England Journal of MedicineJAMA, and the Lancet have provided evidence that continuous chest compressions may be preferable to traditional CPR. Graham Nichol is the principal investigator.

“The CCC trial will help to determine if continuous compressions is equal to or better than standard professional CPR when paramedics, who are better able to provide assisted breathing than bystanders, intervene,” said Nichol, in an NHLBI press release.

The Amiodarone, Lidocaine, or neither (Placebo) for Out-Of-Hospital Cardiac Arrest Due to Ventricular Fibrillation or Tachycardia study (ALPS) will randomize 3,000 people with shock-resistant VF to amiodarone, lidocaine or placebo. Although amiodarone and lidocaine are often given when shock treatment fails in VF patients, a beneficial effect of the drugs has never been demonstrated in this setting. Peter Kudenchuk is the principal investigator.

Both trials are part of the NIH-supported Resuscitation Outcomes Consortium (ROC), which the NIH describes as “the first large-scale clinical research network in the world designed to study, improve, and standardize how EMS teams deliver very early, pre-hospital interventions to improve patient survival after cardiac arrest or trauma.”

Click here to read the NHLBI press release…

Big Drop in Incidence and Fatality of MIs in England Reply

Since 2002 in England the incidence of acute MI has dropped by one-half and the case fatality rate by one-third, according to a new study published in BMJ. The overall decline in deaths from MI are about equally due to improvements in the prevention of MI and the treatment of MI.

Kate Smolina and colleagues analyzed data from 861,134 acute MI patients in England from 2002 through December 2010. Over the course of the study period, the MI event rate declined:
Click to continue reading…

Huge Study Finds Risk Factors Do In Fact Predict Risk 1

An enormous new meta-analysis confirms the important role that risk factors play over a lifetime in the development of cardiovascular disease. In a paper published in the New England Journal of Medicine, Jarett Berry and colleagues report on the new meta-analysis from the Cardiovascular Lifetime Risk Pooling Project, which contains data from 18 epidemiological studies including more than one-quarter of a million people whose risk factors– blood pressure, cholesterol level, smoking status, and diabetes status– were measured every decade between 45 and 75 years of age.

At age 55, compared to people with two or more risk factors, people with an optimal risk factor profile had a greatly reduced risk of death from CV disease  or CHD through the age of 80:
Click to continue reading…

FDA Rejects Proposed Chronic Kidney Disease Indication for Vytorin Reply

The FDA rejected a new indication for Merck’s Vytorin and Zetia (ezetimibe plus simvastatin and ezetimibe alone) in chronic kidney disease patients. As a consolation prize, however, the agency approved a new label for Vytorin that will incorporate the results of SHARP (Study of Heart and Renal Protection), which found that Vytorin reduced the incidence of major vascular events in patients with chronic kidney disease.

Merck said that the indication was not approved because the “independent contributions of ezetimibe and simvastatin were not assessed.” In a press release, Merck stated:

Because SHARP studied the combination of simvastatin and ezetimibe compared with placebo, it was not designed to assess the independent contributions of each drug to the observed effect; for this reason, the FDA did not approve a new indication for VYTORIN or for ZETIA® (ezetimibe) and the study’s efficacy results have not been incorporated into the label for ZETIA.

The FDA decision appears to run counter to the advice it received from its own advisory committee last November, which voted 16-0 in favor of an indication for Vytorin in pre-dialysis patients. However, the committee also recommended against an indication for dialysis patients. The committee did not vote on an indication that would have included the entire SHARP population of pre-dialysis and dialysis patients.

Since its initial presentation in November 2010 and its subsequent publication in the Lancet in June 2011, the interpretation of SHARP has been the subject of considerable debate, much of it carried over from the earlier, even more intense debate about ARBITER 6, which centers on what, if any, additional benefit ezetimibe confers to statin therapy. In the end, the FDA appeared to adopt the perspective of James Stein, who provided the following perspective to CardioBrief on SHARP when it was initially presented:

… this study does not answer the question of whether or not they would have gotten the same result if they used simvastatin alone (ie, if ezetimibe had anything to do with the observed results) or if ezetimibe is safe, since a short study of individuals with advanced kidney disease is not the right context to study drug safety.  But, it is a nice study to re-assure us that even in people with advanced kidney disease, statins are helpful, and it is a mark in favor of ezetimibe,  because it is a RCT that used ezetimibe and reduced events.  It just does not tell us if simvastatin alone would have done the same thing.

Click here to read the press release from Merck…

Whistleblower Lawsuit Filed Against 5 Cardiologists in Pennsylvania Reply

The US government has joined a cardiologist in a whistleblower lawsuit against Hamot Medical Center  in western Pennsylvania  and a group of cardiologists with whom he once practiced, Ed Palattella reports in the Erie Times-News.

Cardiologist Tullio Emanuele, who now practices in Kentucky, has accused five former colleagues, members of Medicor Associates Inc. and its affiliate, Flagship Cardiac, Vascular and Thoracic Surgery of Erie, of billing Medicare for unnecessary angioplasty and other procedures. Hamot Medical Center  is now affiliated with the University of Pittsburgh Medical Center.

The lawsuit, according to the Times-News, alleges that the contracts the cardiologists had with Hamot Medical Center were “sham arrangements intended to disguise the actual purpose of Hamot to pay kickbacks to Medicor and Flagship CVTS in exchange for patient referrals.”
Click to continue reading…

Black Tea Found To Lower Blood Pressure Reply

A new study published in Archives of Internal Medicine provides the best evidence yet that drinking black tea can lower blood pressure. Jonathan M. Hodgson and colleagues randomized 95 regular tea drinkers to either 3 cups per day of either black tea (containing 429 mg of polyphenols and 96 mg of caffeine) or placebo.

At 3 and 6 months, the mean 24-hour ambulatory BP was lower in the tea group than in the placebo group:
Click to continue reading…

St Jude Medical Statement on the Riata ICD Lead Summit 2

In response to the guest post summarizing the Riata ICD Lead Summit, St. Jude Medical sent the following statement to CardioBrief:

We recognize that the phenomenon of externalized conductors presents a complex patient management scenario for physicians who may be able to visualize an anomaly, but it is important to remember that most leads with externalized conductors continue to function properly.
Click to continue reading…

Rita Redberg and Roger Blumenthal Clash Over Statins for Primary Prevention in the Wall Street Journal 8

The debate over whether statins should be used for primary prevention moved to the Wall Street Journal with opposing perspectives from cardiologists Roger Blumenthal and Rita Redberg.

Blumenthal argues that “there is a mountain of high-quality scientific evidence” to support the use of statins in people without known heart disease but “demonstrated to be at high risk for heart disease.”

Redberg argues that “for most healthy people, data show that statins do not prevent heart disease, nor extend life or improve quality of life. And they come with considerable side effects. That’s why I don’t recommend giving statins to healthy people, even those with higher cholesterol.”
Click to continue reading…

Guest Post: Report from the Riata ICD Lead Summit 8

Second update: Click here to review the slides from the meeting (posted by the Minneapolis Heart Institute),

Update: Click here to read a statement from St Jude Medical in response to this post.

Editor’s Note: Edward J. Schloss (Twitter ID @EJSMD), the medical director of cardiac electrophysiology at the Christ Hospital in Cincinnati, OH, returned yesterday from the Riata ICD Lead Summit. Dr. Schloss has kindly forwarded his summary of the meeting to CardioBrief. “As the audience was restricted to clinicians and St. Jude personnel, this may be the first and only public account of this meeting,” wrote Dr. Schloss. (As the editor of CardioBrief, I would like to express my keen disappointment that a meeting of this general importance was closed to outside observers, including journalists, analysts, and representatives from other companies.)

 Report from the Riata ICD Lead Summit

by Dr. Edward J. Schloss

Sixty-three registered health care professionals and St. Jude Medical industry representatives gathered today at the Minneapolis Airport Marriott Hotel for the Riata ICD Lead Summit. This conference, organized by The Minneapolis Heart Institute Foundation and Mayo Clinic, was organized to review available data and develop a consensus regarding St. Jude ICD leads currently on recall or subject to increased scrutiny.

Course directors Robert G. Hauser, MD and David L. Hayes, MD presided over a series of lectures and panels of experts in the field.

Dr. Hayes first polled the conference attendees about the current landscape. A full 35% of attendees thought Riata leads posed a greater concern to them than the Medtronic Fidelis recall. In addition, 41% felt enough concern about the currently marketed Durata lead that they have elected not to implant this lead. The Durata lead, although not on recall, shares many design elements with the Riata ST.

Dr. Hauser reviewed available clinical and engineering data. The failures of Riata leads appears to be due to a unique “inside-out” form of lead insulation abrasion. In some, but not all cases, lead cables have been shown to externalize. Commonly, however, externalization is not associated with failure and vice versa. There is no single common sign of lead failure on electrical measurements.
Click to continue reading…

CT Angiography Found Less Helpful in Patients With High Calcium Scores Reply

Computed tomography angiography (CTA) has been proposed as a less invasive method to exclude obstructive coronary artery disease (CAD), but no consensus has been achieved about its clinical role in different patient subsets. Now a new report published in JACC from the CORE-64 (Coronary Artery Evaluation Using 64-Row Multidetector Computed Tomography Angiography) study shows that CTA may not be worthwhile in people with a calcium score of 600 or above or who already have a high pre-test probability of having CAD.
Click to continue reading…

Guest Post: A critical analysis of ABC & Bill Weir’s “lifesaving test” story 3

Editor’s Note: The following guest post by Gary Schwitzer is reprinted with permission from his HealthNewsReview blog, an indispensable resource for tracking the best and worst of healthcare journalism.

A critical analysis of ABC & Bill Weir’s “lifesaving test” story

by Gary Schwitzer

ABC News is in the midst of a major promotion of Dr. David Agus’ book, “The End of Illness.”  In the course of their reporting, they sent Nightline host Bill Weir to see Agus, whom he referred to as “a rock star of science.” Weir had tests as part of his reporting and writes:

As a way to illustrate the kind of technology he uses, Agus put me through a battery of various tests, including a full-body CT scan. It was all very fun and interesting right until the moment he showed me a picture of the calcification in my heart and told me that if I didn’t make some changes, I’d drop dead within five years.

So it was a $1,300 ride through that radiation doughnut that probably saved my life — a test most insurance company would probably reject and some doctors would resist, for fear of “false-positives.” This is the one main thing Agus is trying to change.

“Reimbursement for preventive medicine’s always difficult in our country,” he told me. “You know, the problem is most people change health plans all the time. So if you’re that health plan, why should you spend money on something that’s not going to affect a person until a decade from now? And so one of things we really have to change is we have to push prevention… a heart attack costs hundreds of thousands of dollars. A couple hundred dollar tests along with a drug can prevent it. Obviously it’s cost effective as a return on investment.”

As for the fears that CT scans could both scare and bankrupt a person by showing a scary speck that turns out to be nothing, Agus argues that is no reason to reject them entirely.

“There are false positives or false negatives with any technology,” he said. “It matters who does it and where it’s done. And so, like with anything, any person can pick up a camera and take a picture. But very few people are a Cartier-Bresson, one of the great photographers. It’s the same thing here.”

Rather than frightening the worried well with this one reporter’s anecdote, the piece could have explained what evidence-based recommendations state.  They could have explained different risk categories.
Click to continue reading…

FAME II: Additional Thoughts About FFR in the Real World 3

Earlier today I reported the news that enrollment in the FAME II study had been stopped early by the DSMB. From the initial presentation of the first FAME trial several years ago, I’ve been fascinated by the potential of this technology, since it offers the tantalizing prospect of helping identify atherosclerotic lesions that actually will benefit from an intervention. But FFR is not a free ride. The downside is that you have to perform a lesser intervention (angiography) in order to determine the validity of the greater intervention (PCI).

FAME II was designed, and will be promoted, as an answer to COURAGE, suggesting that PCI can be generally used in a stable CAD population if FFR detects an ischemic lesion. But it is important to remember that everyone in the trial underwent angiography and FFR prior to randomization, and only those with ischemic lesions were randomized. So it’s fair to conclude that yes, IF someone undergoes angiography it would make sense to give FFR, and if an ischemic lesion is found it would make sense to implant a stent.

BUT it doesn’t say anything about which patients actually should undergo angiography in the first place, and the use (or overuse) of angiography is probably the most important unresolved problem in cardiology today. So we’re back to the floodgate problem. If the floodgates (angiography) are open, then FAME II makes a lot of sense and is widely applicable. But if the floodgates are closed or only opened selectively,the trial really doesn’t help very much.

New Enrollment in FAME II Halted After Interim Analysis Shows Benefits of FFR 3

Following a positive interim analysis showing that fractional flow-reserve-guided PCI was superior to optimal medical treatment, an independent Data and Safety Monitoring Board (DSMB) has recommended that patient enrollment in the ongoing FAME II trial  be stopped. The news was announced by the trial sponsor, St. Jude Medical.

FAME II (Fractional Flow Reserve-Guided Percutaneous Coronary Intervention Plus Optimal Medical Treatment Versus Optimal Medical Treatment Alone in Patients With Stable Coronary Artery Disease) investigators had planned to randomize 1,832 patients with stable coronary artery disease to either PCI guided by FFR plus optimal medical treatment (OMT) or OMT alone. At the time of the announcement 1,219 patients had been randomized.

According to the company, the DSMB recommendation was based on an increase in the risk of major adverse cardiac events (MACE) in patients randomized to OMT alone. “In particular, patients receiving OMT alone experienced a highly statistically significant increased risk of hospital readmission and urgent revascularization, and the DSMB determined that this difference was highly unlikely to change with inclusion of more patients,” the company stated. There were no significant differences in the rates of death or MI.

It should be noted that all patients in FAME II underwent FFR prior to randomization, according to the original announcement of the trial. Patients who had hemodynamically significant lesions as assessed by FFR were then randomized to PCI or OMT. The trial was designed to address the limitations of COURAGE, in which CAD patients as documented by angiography were randomized to PCI or OMT. However, the followup to COURAGE, the ISCHEMIA trial, will randomize ischemic patients to PCI or OMT without prior angiography. FAME II does not appear to address the question of which patients should undergo angiography in the first place.

Click here to read additional commentary about FAME II.

Click here to read the St. Jude press release…

Cangrelor Proposed As Bridge To Surgery Reply

As a potent and reversible platelet inhibitor, cangrelor has been proposed for use in a bridging strategy for patients scheduled for surgery who are currently taking clopidogrel or another thienopyridine. To test this strategy, the BRIDGE investigators randomized 210 ACS or stent patients awaiting CABG and taking a thienopyridine to receive either cangrelor or placebo for at least 48 hours prior to surgery. The results have now been published in JAMA.

During the treatment period platelet reactivity was lower in the cangrelor group than in the placebo group. There was no significant difference in the rate of surgery-related bleeding.
Click to continue reading…

Resveratrol and Fraud 2

Last week a new case of scientific misconduct came to light. University of Connecticut resveratrol researcher Dipak Das was accused of serious scientific misconduct. (You can read my brief post about the case or, for all the gory details, you can follow the story on Retraction Watch.)

In this post I’d like to make two fairly simple points about the case:

1. Resveratrol and Fraud, the Bigger Issue

As far as we now know, this case of scientific misconduct occurred in the lab of one researcher with, at best, a modest reputation in his field. I don’t mean to suggest that the case should not be taken seriously, but it is  unclear whether it has any impact at all on the larger body of scientific research involving resveratrol and related areas. (It’s also possible that Das is only the first of dozens of rotten eggs yet to be discovered in this embryonic field.)

On the other hand, the case offers a great example of the far-reaching and dangerous fraud that so often supports the multi-billion dollar supplement industry. Because resveratrol is considered a nutritional supplement for regulatory purposes it is not subject to the rules and regulations that restrict the marketing of drugs. But, of course, all sorts of highly dramatic medical claims are made for these products. Here’s what Bill Sardi, the president of a company that makes Longevinex, a resveratrol product, claimed about reveratrol, in a statement distributed to media (attached below):

Resveratrol is an antidepressant, an anti-inflammatory, an anti-bacterial, anti-fungal, anti-viral, anti-cancer, cholesterol-lowering, liver-cleansing, brain enhancing molecule.  If Americans embraced resveratrol pills en masse, many prescription drugs would not be needed.

I’m not going to bother refuting this absurd statement. Instead I’ll quote a 2011 review article published in PLoS One:

The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources.

(Fun fact: one of the co-authors of the PLoS One review article was Dipak Das.)

2. Western Blots

The above quote from Bill Sardi is part of a long, rambling, often contradictory and bizarre defense of Dipak Das and resveratrol (reprinted below). Again, I have no intention of engaging all his points– I hope that regular readers of CardioBrief have been inoculated against this sort of hokum. But I do want to make sure one point doesn’t achieve any traction. The key item in the UConn report is that Das repeatedly manipulated western blot images. Sardi first argues that the western blots aren’t important at all:

The alleged faulty tests in no way altered the outcome of his research studies.  The western blot test was only one of many tests used to draw scientific conclusions in published studies.

But then Sardi tries out several new explanations, in the course of a few sentences rapidly cycling through different perspectives on the western blots. First, he states that  the images weren’t altered. Then he acknowledges that they were in fact altered, but that these alterations are standard practice. Then he accuses the university of willfully ignoring this “fact.”

I asked Dr. Das directly, did he altered western blot images, or directed others in his lab to do so.  While his initial answer was no, meaning he had not fabricated or altered any scientific finding, altering western blot images are a common practice in laboratories for reasons other than deception.  The university chose to present their findings in a derogatory manner.  Dr. Das explains that editors at scientific publications commonly request researchers enhance faded images of western blot tests so they can be duplicated in their publications.  Western blot tests are frequently altered to remove backgrounds, enhance contrast and increase dots-per-inch resolution so they are suitable for publication.  This had been fully explained to university officials long before. [sic]

The entire statement strikes me as a great example of the pathology of someone desperately seeking to deny, refute or minimize an inconvenient truth. One statement– that editors ask researchers to “enhance” western blots–  requires an immediate response. I contacted a member of the National Academy of Sciences who has published hundreds, if not thousands of western blots during the course of his distinguished career. His response was clear and unequivocal: “manipulating images is considered tampering with data.” He then clarified:

It is one thing to change the dots-per-inch (resolution) to fit a publication’s requirements – that is not crazy. But enhancing contrast and removing background is something that seems to me to be unacceptable. I certainly emphasize to students that that is unacceptable.  I know of cases where students might try to ‘clean-up’ data this way and I can imagine that in some cases a PI may not realize this has been done. But I have never heard an experienced investigator claim that a journal has asked them to remove background from a blot.  Now, maybe that has happened — I cannot say —  but certainly NEVER to me.

Update: Tom Bartlett of the Chronicle of Higher Education talked to a number of experts in the field to determine the significance of Das’s work not the field. In addition, longtime blogger Derek Lowe posted a detailed dissection of Sardi’s statement. Both posts are worth reading.

Click here to read the statement from Bill Sardi…

The Safety of the Long Distance Runner Reply

Long distance runners may be lonely but they are not at high risk for sudden cardiac arrest, according to a study published in the New England Journal of Medicine. The RACER (Race Associated Cardiac Arrest Event Registry) investigators analyzed data from 10.9 million registered participants in marathons and half-marathons that took place in the US during the first decade of this century.

They identified 59 cases of  cardiac arrests; 40 occurred during marathons and 19 occurred during half-marathons. The mean age of the runners with cardiac arrest was 42 years of age. 51 were men and 8 were women.

The rate of cardiac arrest was 1 per 184,000 participants; the rate of death was  1 per 259,000 participants. The authors described this event rate as “relatively low” and compared it with collegiate athletics (1 death per 43,770), triathlons (1 death per 52,630 participants), and previously healthy middle-aged joggers (1 death per 7,620 participants).
Click to continue reading…

ASSERT Sheds Light on the Role of Subclinical AF in Stroke Reply

A new study published in the New England Journal of Medicine sheds some much-needed light on the precise role of subclinical atrial fibrillation (AF) in the prognosis and development of ischemic stroke. ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) followed 2580 patients with a newly implanted pacemaker or ICD and with no previous diagnosis of AF.

At 3 months, subclinical AF lasting longer than 6 minutes had been detected in 10.1% (261) of the subjects. During 2.5 years of follow-up, 51 patients in the study had an ischemic stroke or systemic embolism. Of these, 11 were in the group with subclinical AF by 3 months. Patients with subclinical AF had more than double the risk for stroke or systemic embolism:
Click to continue reading…

Director of UConn CV Research Center Accused of Scientific Misconduct 2

[See update at the end of the story] Following an extensive investigation, Depak Das, a professor in the Department of Surgery and director of the Cardiovascular Research Center at the University of Connecticut Health Center, has been accused of serious scientific misconduct. UConn has informed 11 scientific journals about the investigation.

Das had numerous publications on resveratrol and other nutrition-related cardiovascular subjects. According to an online biography, he was a founding editor and editor-in chief of the journal Antioxidant and Redox Signaling, and also served as associate editor of the American Journal of Physiology: Heat and Circulatory Physiology and consulting editor of Molecular and Cellular Biochemistry.

The news was announced by the UConn Health Center and has been reported by Retraction Watch, the Associated Press,  and the Connecticut Mirror.

The University said the investigation had been sparked by an anonymous allegation of research irregularities in 2008, resulting in a 60,000 page report that found Das guilty of 145 counts of fabrication and falsification of data. UConn said it worked closely with the US Office of Research Integrity during the investigation. UConn is now preparing to dismiss Das.
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Researchers Find Lower Sweet Spot for Potassium Levels in MI Reply

Current guidelines for the treatment of acute MI recommend that serum potassium be maintained between 4.0 and 5.0 mEq/L, and some believe that the upper limit could be raised to 5.5, but evidence is based on small, outdated studies. Now a new study published in JAMA suggests that the ideal potassium range should be adjusted downward.

Abhinav Goyal and colleagues performed a retrospective cohort study of 38,689 MI patients. They found a U-shaped relationship between the postadmission potassium level and in-hospital mortality, with the lowest rate of death found in patients with potassium levels between 3.5 and 4.5.

Postadmission Potassium Level and Mortality Rate (Adjusted Odds Ratio):

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