John M. Mandrola, MD


November 06, 2018

When it comes to content, brevity is in.  Journal manuscripts, editorials, lectures have all been shortened. Add to that list scientific meetings.

When the American Heart Association (AHA) meets in Chicago, organizers will squeeze a former 5-day meeting into 3 days. They had no choice. In an era when most cardiologists answer to nonclinical administrators, long gone are the days when clinicians could take multiple "working" days off for a meeting.

Vitamin D Granted Another Appeal

The slate of six late-breaking sessions begins with the VITAL trial, which is aptly named because its findings could affect millions of people who take vitamin D and omega-3 fatty acid supplements in an effort to prevent heart disease and cancer. 

The vitamin D story, thus far, shows the challenge of getting health from a pill. To wit, low vitamin D levels are associated with worse outcomes. Easy, you say, just replace it with a pill. The problem is that normal vitamin D levels stem from going outside, usually to be active. Sick people often have limited mobility, so they don't get outside much. Put me down as doubtful that a pill can deliver the same benefits of regularly going outside to play in the sunlight.

That's not all. For my Bayesian-minded friends, the priors for vitamin D supplementation look terrible. "We did not find evidence to suggest that vitamin D supplementation alone reduces the incidence of cancer or cancer mortality, even after including long-term follow-up results," write authors of a 2018 systematic review of 30 studies and more than 18,000 participants.[1]

There is slightly more hope for vitamin D and heart health. While systematic reviews have found no signal of benefit,[2] most trials of vitamin D have been designed to study skeletal health and included relatively small samples of mostly older women.[3]

A Fish Pill Redux?

In REDUCE-IT, slightly more than 8000 patients with elevated triglycerides, high cardiovascular risk, and ongoing statin use received either 4 g of pure omega-3 eicosapentaenoic acid (EPA; Vascepa, Amarin) or a mineral oil placebo.  A press release from Amarin has confirmed positive results with a 25% relative risk reduction in the composite cardiac endpoint of death from cardiac causes, nonfatal myocardial  infarction, nonfatal stroke, coronary revascularization, or unstable angina necessitating hospitalization.

A positive result for omega-3 supplements is an outlier. This year, Cochrane reviewers could find little to no effect of omega-3 supplements for reducing heart events in 79 trials that included more than 112,000 participants.[4] ASCEND trial authors found no effect of omega-3 supplements in patients with diabetes.[5]

Deepak Bhatt, MD, from Harvard University in Boston, Massachusetts, will give us the details, but possible reasons REDUCE-IT found benefit while previous trials did not include higher dosing (4 g vs 1 g), purity (Vascepa includes only EPA), and the trialists' choice to include patients with high triglycerides. Scientifically, this latter point may earn REDUCE-IT landmark status. No, not because of small absolute reductions in cardiac events, but rather for opening up a long-running blind spot in cardiovascular research on the importance of reducing triglycerides.

Inflammation Is Back on the Big Stage

Last year in Barcelona, Spain, Eugene Braunwald, MD (Brigham and Women's Hospital, Boston), called the results of CANTOS,[6] which showed that the anti-inflammatory agent canakinumab reduced cardiac events independent of low-density lipoprotein cholesterol lowering, a historic moment. Why was cardiology's most senior thought leader so impressed? "Because it revealed a new direction [treating inflammation] for a very important cardiac condition, the most important of all, atherosclerosis."

A year on, proponents of the treat-inflammation-to-reduce-heart-events idea have more work to do to convince US Food and Drug Administration regulators. That is not surprising; single trials don't often change entrenched paradigms. But what if a second trial shows a different anti-inflammatory agent reduces heart events?

At AHA, Braunwald's Harvard colleague, Paul Ridker, MD, will present the results of CIRT, a National Institutes of Health–sponsored placebo-controlled randomized trial of low-dose methotrexate plus folate to reduce cardiovascular disease morbidity and mortality in 7000 patients with stable coronary artery disease and type 2 diabetes or metabolic syndrome. This is a big moment for cardiology.

Calm Mind, Calm Heart?

You cannot take care of patients with heart disease and deny the ill effects mental or emotional stress exert on the heart. Yoga works to calm both the body and mind, which is likely the way it helps patients with atrial fibrillation (AF).[7,8]

And, "There is promising evidence of yoga on improving cardio-metabolic health, but findings are limited by small trial sample sizes, heterogeneity, and moderate quality of RCTs [randomized controlled trials]," write authors of systematic review and meta-analysis of more than 30 studies comparing patients participating in yoga against nonexercise controls.[9]

At AHA, that problem ends. Dorairaj Prabhakaran, MD, from the Center for Chronic Disease Control in New Delhi, India, will present the results of Yoga-Care, a multi-center RCT looking at the effectiveness of a yoga-based cardiac rehab program in more than 4000 patients who recent had a myocardial infarction.

Can Computer Decision Support Help Improve Care?

Nearly every time the dysrhythmia committee meets at my hospital, we discuss the care of patients with AF. Our problem: there's a growing epidemic of AF, and its management is expensive, often dangerous, and widely variable. The latter issue bedevils people charged with delivering cost-effective care.

Using medical science's best tool, the RCT, my friend Jeroen Hendriks, PhD, now at the University of Adelaide, Australia, has shown us the best way to care for patients with AF: Involve the patient, use evidence and computer decision support, and embrace a team-based nurse-led approach.[10]

AHA will feature numerous late-breaking trials on the use of computer-based and team-based approaches to improve the care of patients with heart disease. Brazilian investigators will report on whether a multifaceted intervention strategy of nudging docs with human and computer reminders will get them to more often use evidence-based strategies. Teams from McMaster University in Hamilton, Canada, and Harvard University will present separate trials of decision support in the care of patients with AF.

One paradox: advocacy for shared decision-making means accepting that fully informed patients might rationally choose not to use an anointed therapy.[11] What if better-informed decisions led to less use of evidence-based therapy?

A Sea-Change in Electrophysiology? 

One of the problems with myocardial infarction is that it's often incomplete. Surviving channels of viable myocardium within an infarct create a nidus for reentry and ventricular tachycardia (VT). This is a terrible problem not just because it is life-threatening but also because VT can cause recurrent implantable cardioverter defibrillator shocks—aka, suffering.

Shortly before he died, the luminary Mark Josephson, MD, scolded electrophysiologists for abandoning techniques for mapping and understanding arrhythmia.[12] Many VT ablationists had abandoned intricate mapping of VT simply because "homogenizing" the entire scar may be as effective.[13] Yet both these approaches require putting patients with significant heart disease through an invasive, lengthy, and risky procedure.

Philip Cuculich, MD, and his colleagues at Washington University in St. Louis, Missouri, may have a better way, one without catheters, anesthesia, and hours of procedure time. An effective way to do truly noninvasive ablation would change electrophysiology forever. The ENCORE-VT study will extend findings of their initial report of five cases[14] using stereotactic body radiation therapy to ablate VT in 20 patients with scar-related VT.

Marketing-Disguised-as-Science Award

Stanford scientist John Ioannidis, MD, PhD, has suggested that clinical evidence can often be an industry marketing tool.[15] Sadly, the AHA late-breakers provide a shining example. First an admission: I've used the Impella support device (Abiomed) during VT ablation. My interventional partners use it for treating patients in cardiogenic shock.

The device is expensive and invasive, and it should be studied in proper randomized clinical trials. Given the high death rates in cardiogenic shock, it would not take many patients to determine its efficacy in an RCT.

Instead of that, Abiomed offers, and AHA accepts as late-breaking science, a study called Door to Unload. In this two-armed feasibility study of 50 patients, one group gets the device and the operator waits 30 minutes to open the artery; the other group gets the device and the operator immediately stops the infarct. The primary endpoint is infarct size as assessed as a percentage of left ventricular mass using MRI, which is about as far from a real outcome as a surrogate endpoint can get.

Abiomed wins either way in this trial. We learn nothing about the device's utility, but the company gets big media attention—and Professor Ioannidis is vindicated.


The meeting will feature release of updated American College of Cardiology (ACC)/AHA guidelines on physical activity and the treatment of high cholesterol. Look for little noise about the physical activity recommendations but lengthy debates on the use of pills and pricy injectables.

The freedom of social media will enhance the debate over the cholesterol guidelines, which is good because it will force people to think and then go to the original data.

It makes little sense to ignore the "elephant in the room" concern with all guidelines that deal with industry products. So here goes:

I have participated in writing consensus statements and have come away impressed with the effort to be fair-minded. We once argued for many minutes about the use of 'a' or 'the' in a phrase.  But one need not imply mal-intent to consider the conflict of issues raised in Professor Ioannidis's recent editorial in the AHA journal Circulation-CV Quality and Outcomes,[16] in which he called for professional societies to abstain from authorship of guidelines. Among his many concerns is the fact that professional societies receive funding from industry—and industry surely has interests in how proprotein convertase subtilisin/kexin type 9inhibitor drugs will be handled in the document. One part of the discussion I will listen for is how the authors dealt with this issue.

Duality of interest is relevant here as ACC and AHA must square their strong policy positions on equitable access to affordable healthcare and their endorsement of recommendations on the use of PCSK9 inhibitors, which, even at reduced prices, have debatable incremental value.

As always, | Medscape Cardiology team will work hard to deliver the best coverage. Stay tuned. Follow us on Twitter and Facebook. Meeting hashtag: #AHA18


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