John Mandrola, MD


August 27, 2019

US cardiology meetings have been shortened; attendance has plateaued. European Society of Cardiology (ESC) congresses do not suffer from this ailment. This year in Paris, the ESC Congress remains a 5-day meeting with a massive 32,000 attendees from 150 countries.

Steve Stiles from | Medscape Cardiology has a detailed preview; here are my thoughts.

Preannounced Studies Dominate the First Hotline Session

I'll start with the trials where we already have topline results. If the PARAGON-HF trial,[1] which compared the angiotensin receptor neprilysin inhibitor sacubitril/valsartan to valsartan in nearly 5000 patients who have heart failure with preserved ejection fraction delivered positive results, millions of people may have been helped.

But a press release from Novartis announced that PARAGON-HF "narrowly missed statistical significance for its composite primary end point of reducing cardiovascular death and total heart failure hospitalizations." When reviewing the details, it will be vital to have our spin[2] detectors tuned to high.

In heart failure with reduced ejection fraction, guideline-directed medical therapy now includes three classes of drugs. At ESC, results of the DAPA-HF trial may usher in a fourth: inhibitors of sodium-glucose cotransporter 2 proteins. The study compared dapagliflozin to placebo in about 4700 patients with systolic heart failure. Only 42% of enrolled patients had diabetes.[3] We also know from an AstraZeneca press release that the trial "met its primary composite endpoint with a 'statistically significant' and 'clinically meaningful' reduction in CV death or worsening HF." Cardiologists will need to learn more about this class of drug.

The THEMIS[4] study randomly assigned more than 19,000 patients with type 2 diabetes and stable coronary artery disease (CAD) to ticagrelor or placebo. In a February press release, study sponsor AstraZeneca announced that ticagrelor was associated with a statistically significant reduction in a composite of major adverse cardiovascular events compared to aspirin alone. The key question: Are the results clinically significant? To make that call, we will need to know effect size and bleeding rates.

What's Hot in Atrial Fibrillation

In my view, the most important tool in treating patients with atrial fibrillation (AF) is education. I'm looking forward to the second late-breaking AF session in which we learn the results of two trials on the integrated management of patients with AF: one in the primary care clinic and the other in a clinic led by nurses. Also in that session, Professor Prashanthan Sanders from the University of Adelaide will present results of the HELP-AF study, which evaluated a home-based education and learning program for AF. Since AF will never be conquered with catheters or devices alone, these are vital studies.

ESC includes many papers on AF screening. One that stands out is the HUAWEI Heart study. This sounds a lot like the yet-to-be published Apple heart study in that it uses mobile technology to screen for AF with photoplethysmography-based smart devices. Huawei is the controversial Chinese company whose cellphones were popular in Europe. The study is co-led by Gregory Y.H. Lip, MD—maybe it will change my skeptical view on AF screening.[5]

In the United States, left atrial appendage occlusion is increasing, possibly because of direct-to-consumer ads for the Watchman device. European doctors have implanted closure devices much longer than US docs, and ESC has a number of abstracts and posters on the topic. One in particular is the PRAGUE-17 trial, an RCT comparing left atrial appendage closure to direct acting oral anticoagulants. Look for a summary column from me about this.

Finally in AF, the superstar Professor Isabelle C. Van Gelder from Groningen, the Netherlands, will deliver the Rene Laennec Lecture on Clinical Cardiology. The title: "Atrial Fibrillation: Not Just an Arrhythmia." Please, Professor, teach the world that treating this condition requires much more than suppressing the surrogate marker of AF episodes on an ECG.

Hs-Tn and Other Clinical Cardiology  Challenges Face Big Tests

In the United States, high-sensitivity troponin (hsTn) assays are disrupting the previous belief that detectable troponin equals rule in for myocardial infarction (MI). The large pragmatic High-STEACs study, which evaluated implementation of a hsTn I assay in consecutive patients presenting with suspected MI,[6] found that the assay prompted reclassification of 17% of patients with myocardial injury or infarction but was not associated with reduced MI or cardiovascular death at 1 year.

At ESC, we will hear results of the HiSTORIC Trial, which uses the High STEACS treatment pathway. The planned enrollment is 39,000 patients, and the primary outcomes are time in the emergency department before discharge and MI in the month after discharge.

But wait, there's more: The Australian RAPID-TnT study[7] is a prospective pragmatic trial of about 5400 patients suspected of having acute coronary syndrome (ACS) randomly assigned to a 0/1-hour hs-TnT protocol or standard troponin reporting evaluated at 3 and 6 hours.

In acute decompensated heart failure, it's tough to beat basic loop diuretics. The GALACTIC trial will test whether goal-directed afterload reduction will reduce death or rehospitalization at 3 months. The intervention includes sublingual or spray nitroglycerin and transdermal nitrates together with hydralazine, followed by rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or neprilysin inhibitors/angiotensin receptor blockers to achieve maximal vasodilatation with a target systolic blood pressure of 90 to 110 mm Hg. The Swiss investigators face daunting priors: novel drugs[8,9,10] and intravenous vasodilators[11] have failed to show incremental benefit.

I am often asked how best to manage anticoagulation in patients with AF diagnosed with CAD. The Japanese AFIRE study[12] will pit rivaroxaban monotherapy vs rivaroxaban plus a single antiplatelet in about 2200 such patients. Rivaroxaban dosing is 15 mg in patients with normal renal function, and antiplatelet therapy includes aspirin, clopidogrel, or prasugrel.

Then there are the salt debates. The ideal sodium intake is controversial, though it is clear that reducing sodium intake reduces blood pressure. Less controversial are the benefits of potassium intake. The exact mechanism is not known, but high-quality evidence shows that potassium intake reduces blood pressure in people with hypertension; this associates with a reduction in stroke risk.[13] J. Jaime Miranda from Lima, Peru will present results of a stepped wedge population-level trial looking at an intervention to replace high-sodium salt for a salt substitute consisting of low-sodium and high-potassium content to reduce blood pressure in adults.[14]

We prescribe many cardiac drugs for life, yet most trials underpinning their use had short-term follow-up. This is why I'm eager for the SWEDEHEART analysis of secondary prevention medication after coronary artery bypass surgery and long-term mortality.

Interventional and Structural Highlights

Interventional cardiologists will gain high-level evidence for the best revascularization strategy for patients with multivessel CAD who present with ST-segment elevation MI (STEMI). A previous meta-analysis of 10 randomized controlled trials comparing complete vs infarct-related-artery-only revascularization found a lower rate of major adverse events with complete revascularization but no all-cause mortality advantage.[15] The authors concluded that larger trials were needed. Enter Shamir Mehta, MD, MSc, from McMaster University, who will present results of the COMPLETE Trial. This trial enrolled about 4000 patients with STEMI and multivessel disease to complete (staged) revascularization or culprit lesion alone.

One of the biggest questions last year centered on the treatment of patients with secondary mitral regurgitation: specifically, how to explain the results of the negative MITRA-FR trial[16] vs the stunningly positive COAPT trial.[17] One explanation was the shorter follow-up in MITRA-FR (1 year) than in COAPT (2 years). At ESC, MITRA-FR primary investigator Jean-Francois Obadia, MD, will present 2-year follow-up of the trial. This will be big news either way.

Remote ischemic preconditioning (RIPC)—or brief nonharmful ischemia to a remote organ—is intriguing. Previous evidence for RIPC before percutaneous coronary intervention looks promising but included small patient numbers[18] , [19] or measured surrogate outcomes.[20] What's more, RIPC for cardiac surgery was not proven beneficial.[21,22]  At ESC, we will learn results of the sham-controlled CONDI2/ERIC-PPCI trial, which enrolled more than 5400 patients with STEMI from multiple European centers.

ICD Use in Heart Failure

ICD use for primary prevention in heart failure used to be settled. Then, in 2016, the DANISH trial[23] showed that an ICD did not significantly reduce overall death rates in patients with nonischemic cardiomyopathy. ESC features multiple related studies. Benedikt Schrage, MD, from Hamburg, Germany, will present an observational analysis of prospective implantable cardioverter defibrillator (ICD) use in heart failure. And the DAPA investigators will also present results of their decade-old trial of ICD use early after primary PCI in patients with STEMI.[24] All-cause mortality was lower in the ICD group, but interpretation has been difficult because of early termination of the study.[25] There are multiple posters and abstracts dealing with ICD use in real-world settings.

I am not alone in having serious questions on prophylactic ICD use in contemporary practice.[26]

Finally, I am honored to be among the ESC’s army of electrophysiology Twitter Ambassadors  

And as always, | Medscape Cardiology team will be on site in Paris to deliver the best coverage. Stay tuned.

Follow us on  Twitter  and  Facebook . Meeting hashtag: #ESCCongress


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