John Mandrola, MD


August 21, 2017

BARCELONA, SPAIN — Plateau. Lull. Increment. All are apt descriptors for cardiology in recent years.

We inch along. Our scientific sessions seem to overpromise and underdeliver. I remember the thrombolytic trials, the ICD trials. These were big; they changed the field. AF ablation is a good example of more recent inertia: not a darn thing has changed in a decade, except, perhaps, a coming to grips with the fact that you can't fix old age, obesity, and alcohol excess with a catheter.

I have a feeling, though, the European Society of Cardiology Congress 2017 could be an exception. When the world meets in Barcelona, Spain we might see some real progress.

At ESC, they call them hotlines—the late-breaking clinical trials selected for maximum attention.
My colleague at | Medscape Cardiology Steve Stiles has this piece with all the details. I'll offer a (slightly) biased quick view.


The hottest of the hotlines will be the presentation of CANTOS,[1] a randomized controlled trial (RCT) that tests an anti-inflammatory drug in heart disease. Novartis, the company that makes canakinumab, a monoclonal antibody targeting interleukin 1-beta, has already told us (in a press release) that their drug reduced the risk of the composite of cardiovascular death, nonfatal MI, and nonfatal stroke in patients with prior MI and high CRP levels.

Of course, one mostly gets anchoring bias—not details—from a press release. At the ESC meeting, we will hear the details. Key will be the absolute risk reductions in this trial of more than 10K patients. CANTOS is a potential biggie because anyone who cares for patients with heart disease understands that acute and chronic inflammation plays a causative role.

The next real breakthrough therapy for heart disease will likely be far upstream from the cath lab.

Atrial Fibrillation

Speaking of inflammation, atrial fibrillation (AF) continues to burden patients and healthcare systems the world over. Numerous hotline studies will address different aspects of this symptom of atrial structural disease.

Professor IC Van Gelder from University Medical Center Groningen leads off on Sunday with results of the RACE 3 study, an RCT looking at aggressive upstream therapy for patients with persistent AF and mild heart failure. Will the addition of aldosterone antagonists, statins, dietary restrictions, counseling, and cardiac rehab to conventional rhythm-control strategies deliver more sinus rhythm? If positive, RACE 3 could be a biggie; it would accelerate the move to treat both risk factors and cardiac rhythm in patients with AF. Right now, too many AF clinicians give lip service to upstream therapies.

The scenario is common: a patient with heart failure and an ICD is cruising along fine until she develops AF. Patients with impaired cardiac reserve often struggle with the loss of atrial-ventricular synchrony and tachycardia. Treatment of these patients can be tough, and too often, the AF begins a downward spiral. Dr Nassir Marrouche from the University of Utah will present the multicenter (48 sites) CASTLE-AF[2] trial, which enrolled about 420 patients with systolic heart failure and an ICD and AF to either AF ablation or conventional therapy. The crucial aspect of this study, the part that could change the world of ablation, is the choice of primary outcomes. Unlike other AF trials, which measure AF recurrences or AF burden, which are mere surrogates, CASTLE AF trialists chose as their primary end point the composite of all-cause mortality or worsening of heart failure requiring unplanned hospitalization.

In REHEARSE-AF, UK researchers will assess the utility of the AliveCor smartphone device for AF screening. Since most of what I do in my AF clinic is calm fearful patients, I remain doubtful on screening—for most everything. AF screeners . . . please show me outcome data. Picking up AF episodes  is not enough. Does it change outcomes or simply make fear extraction harder?


Everyone knows the best way to lower morbidity and mortality from heart disease is prevention.

Squeezed between AF and inflammation on Sunday, we will hear results of the Bayer/Janssen-sponsored COMPASS trial, a huge (n=27,402) RCT looking at the use of rivaroxaban for secondary prevention of major adverse cardiac events in patients with known atherosclerosis. We know from a February press release that COMPASS was terminated early due to efficacy. But we don't know which of COMPASS's three arms (rivaroxaban 2.5 mg twice daily + aspirin; rivaroxaban 5 mg twice daily alone; or aspirin alone) was effective. Again, details on absolute risk reduction and safety will be key. Rivaroxaban costs a lot more than aspirin and therefore a change in practice will require big improvements in outcomes.

The promise of vascular screening is prevention: find it; then treat it before it causes a disaster. On Monday at ESC, we will hear 15-year results of the Danish Viborg Vascular (VIVA) screening trial. VIVA is an RCT designed to evaluate the benefits of screening (for peripheral artery disease, abdominal aortic aneurysm, and hypertension) and modern vascular prophylaxis in a population of 50,000 men aged 65 to 74 years. I look forward to this study because screening makes sense, but when put to the RCT test, it often fails to deliver.[3]

I bet you thought cholesteryl ester transfer protein (CETP) inhibitors were dead. Well, it's possible, emphasis on possible, that anacetrapib could pull a Lazarus move. In June, Merck announced that the REVEAL outcomes study of anacetrapib vs placebo met its primary end point. "Generally consistent" with previous studies was the description of the safety profile. Remember, the drug accumulates in adipose tissue. Lending credence to the possibility of a CETP-inhibitor resurrection is a Monday presentation of a Mendelian randomization study looking at the effect of genetic variants that mimic CETP inhibitors and statins.


Speaking of Lazarus-like moves, Medtronic did not abandon renal denervation for resistant hypertension despite the disappointment of the sham-controlled SYMPLICITY HTN-3 trial. At the ESC meeting, we will hear results of the SPYRAL HTN-OFF MED study, another sham-controlled RCT looking at the safety and efficacy of the Symplicity Spyral multielectrode renal denervation system. The special aspect of this study is the absence of blood-pressure meds—which means less confounding. A note on renal ablation: it's antithetical to an electrophysiologist to burn without an adequate end point. I'll be looking for how the ablators in this study know what they are accomplishing with the lesions.

Another intervention with a controversial past is left atrial appendage (LAA) closure. LAACS is a Danish trial testing the possibility that surgical closure of the LAA during elective bypass or valve surgery will lead to fewer strokes or microcerebral infarcts. The novel aspect of LAACS is that patients will get pre- and post-MRI scans.

It's hard to believe we don't yet have a handle on the best way to perform cardiopulmonary resuscitation. Do you intubate or simply perform bag-valve-mask ventilation? This simple but highly relevant question is put to the test in the CAAM clinical trial; we will learn the results at the ESC meeting.

Another standout among the hotline late-breaking registry results is a report from Dr Ankur Kalra, from University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, OH, on leaflet thrombosis following transcatheter aortic-valve replacement (TAVR). At the ACC meeting earlier this year, Dr Raj Makkar from the University of California, Los Angeles presented sobering data on leaflet thrombosis from the RESOLVE and SAVORY registries.[4] This issue, I believe, is an existential one for the percutaneous treatment of aortic-valve disease. Leaflet thrombosis and valve longevity aren't a major issue for the elderly who have limited life-span, but it is when we offer TAVR to younger people.

Perhaps the most effective intervention for heart disease is diet. In the first hotline late-breaking registry-results session, we will hear results of two substudies from the Prospective Urban Rural Epidemiology (PURE) study.[5] What is the dose-response of fruit, vegetables, and legumes? And what about fats vs carbohydrates? One would think that in 2017, we could agree on something as fundamental as the ideal diet for heart health. No doubt these presentations will rekindle the debate between the fat-is-okay and plant-based low-fat camps.


Big meetings should begin with big keynote lectures. This year's ESC Congress does not disappoint. On Saturday evening, Dr Eric Topol from the Scripps Translational Institute opens the meeting with a talk on the Future of Cardiovascular Medicine in the Digital Era. Topol is the editor in chief of Medscape, and I've been blessed to learn from him the past few years.

Finally, if you are attending ESC, I will be debating Prof Horst Sievert, from the Cardiovascular Center Frankfurt, Germany, on Sunday, August 27. No, of course not, LAA occlusion is not ready for prime time.

We will have a strong team of news and features writers to cover the ESC meeting; stay tuned.

For more from | Medscape Cardiology, follow us on Twitter, Facebook, and Instagram.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.