Mandrola's 5 Things to Look for at the Upcoming ESC 2023

John M. Mandrola, MD


August 21, 2023

I am excited to visit Amsterdam for the 2023 European Society of Cardiology congress (ESC). The last time Amsterdam hosted the big show, I commuted to the congress on a bike. I hope to do the same this year.

The science will not disappoint. Electrophysiologists will like the Hot-Lines. I struggled to pick just five studies.

GLP-1 Agonists Continue Their Rise

We have long known the glucagon-like peptide-1 agonists (GLP-1) drug class reduces cardiovascular outcomes in patients with diabetes and induces serious weight loss in patients with obesity. Just before ESC, Novo Nordisk announced positive results of the SELECT trial, a cardiovascular outcomes trial of semaglutide in patients with obesity.

The first Hot Line session at ESC begins with results from STEP-HFpEF, a randomized controlled trial (RCT) testing semaglutide vs placebo in patients with obesity and heart failure with preserved ejection fraction (HFpEF). The choice of dual primary endpoints — weight loss and quality of life — suggests this will be another positive study for the drug class. Think about it: if you induce weight loss in a patient with HFpEF, their quality of life is very likely to improve. Secondary endpoints will also look at typical outcomes such as death and hospitalizations for heart failure.

This class of drugs still creates some tension in my brain. Yes, outcomes are impressive, but I wish we could induce the same weight loss with lifestyle changes and without slowing food transport in the gut.

AF Screening Is Not a Sure Win

The main challenge to atrial fibrillation (AF) screening may actually be that our technology is too good.

In years past, we discovered AF when patients had the arrhythmia long enough to be detected on a standard ECG, usually due to symptoms. In these patients, warfarin and now direct acting oral anticoagulants proved beneficial.

Modern-day AF screening tools often pick up much shorter duration episodes of atrial arrhythmia. I frequently get a notification from our pacemaker center that a patient has short-duration atrial high-rate episodes. Observational studies report that these associate with a higher rate of stroke but, clearly, this is a different condition than true clinical AF. No one — and I mean literally no one — knows what to do with these short-duration episodes of atrial high rates.

The NOAH-AFNET-6 trial tested whether or not treatment of these shorter episodes of atrial arrhythmia would reduce stroke. In this RCT of more than 2000 patients, one group received edoxaban (Savaysa) and the other group aspirin 100 mg. The primary endpoint was stroke, systemic embolism, or cardiovascular death.

We know from a press release that the trial was stopped early for futility. At ESC, we will hear the actual results, and I look forward to the discussion. There remains one similar ongoing large RCT in this space, called ARTESiA. What to do with short-duration AF may be the biggest question in electrophysiology today.

Upgrading Cardiac Devices Faces the RCT Test

If AF screening is the number one topic in EP, cardiac pacing to avoid heart failure is a close second. On last week's episode of the "This Week in Cardiology" podcast, I discussed the lack of data supporting generator changes for implantable cardioverter-defibrillators (ICDs) . The "upgrade" of a standard pacemaker to a cardiac resynchronization therapy (CRT) for heart failure is another common but poorly studied procedure.

AT ESC, Béla Merkely, MD, will present results of the BUDAPEST-CRT trial. This trial randomly assigned patients with a conventional pacemaker or ICD who had a high percentage of RV pacing and symptomatic heart failure due to a reduced ejection fraction (≤ 35%) to either a CRT ICD upgrade or a standard ICD.

The MADIT-CRT trial showed that if you are going to implant an ICD in eligible patients who have a wide QRS, it's best to use a CRT-D vs a standard ICD. The problem is that those data, from 2009, have been translated to patients who already have devices. BUDAPEST-CRT is important because an upgrade procedure is more complicated than a de novo procedure; old results may not translate to this situation.

The primary endpoint will be a point of discussion. It includes a composite of time to first heart failure event, all-cause death, or less than 15% reduction in left ventricular end systolic volume. Mixing clinical and echocardiographic endpoints complicates interpretation.

Complete Revascularization at the Time of MI

The COMPLETE trial, published in 2019, found that the strategy of complete revascularization was superior to a culprit-only approach in patients who present with ST-elevation myocardial infarction (STEMI) and have multivessel disease. These were mostly male patients, age 62 years on average, with few comorbid conditions. 

At ESC, we learn results of the FIRE trial, which tests the complete vs culprit-only revascularization strategies in patients older than age 75 years. FIRE includes patients with both STEMI and non-STEMI. The authors will likely emphasize the use of physiology-guided approach in the complete revascularization arm.

I think a far more important point of emphasis is the matter of studying strategies in older patients who surely have more comorbidities. Their results may not be the same as for younger, healthier patients. No matter the results, this trial will teach us a lot about translating evidence to more complicated patients.

Of note, also in the revascularization post-MI space, we will learn the results of the MULTISTARS AMI trial, comparing a strategy of immediate complete revascularization during the index procedure vs a staged complete revascularization done later.

Pulsed Field Ablation Faces an RCT Test — Sort of

Atrial fibrillation is among the most common cardiac conditions requiring admission to the hospital. The ubiquity and increasing prevalence of AF has transformed the ablation market into a massive treasure hunt.

The new technology to destroy atrial tissue in the hopes of reducing AF is called pulsed field ablation. PFA destroys atrial myocytes by delivering electricity and creating pores in cell membranes. PFA is promoted as safer because it promises to select only cardiac cells, which limits damage to the esophagus and phrenic nerves. Yet early registry data on PFA have not convinced me that overall safety differs much from standard thermal ablation techniques. PFA is not available in the US but is widely used in Europe. Many of my colleagues in Europe are enthusiastic about it.

Vivek Reddy, MD, will present results of the ADVENT trial, a noninferiority RCT comparing PFA to traditional thermal ablation (either radiofrequency or cryoballoon) for AF ablation. The primary endpoints include acute procedural success and freedom from AF after a blanking period. There will also be safety endpoints as well as a subset of patients who will have brain imaging to assess for micro-emboli. I will be asking what obvious advantage PFA has that justifies studying it in a noninferiority design.

Closing Note

There are many more important studies and presentations coming out of ESC. Please feel free to alert me if you think one is especially important. Also, follow the team from | Medscape Cardiology.

John Mandrola practices cardiac electrophysiology in Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. 

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