A “pace-and-ablate” strategy substantially boosted survival for permanent atrial fibrillation (Afib) patients with a narrow QRS across the range of left ventricular ejection fraction (LVEF), the APAF-CRT trial showed.

While relatively small with 133 patients after being stopped early for efficacy at a median 29 months of follow-up, the trial showed a relative 74% survival advantage to intervention over that period, reported Michele Brignole, MD, of the Istituto Auxologico Italiano at San Luca Hospital in Milan, Italy at the European Society of Cardiology (ESC) virtual meeting and online in the European Heart Journal.

Death from any cause occurred in seven (11%) of those randomized to atrioventricular (AV) junction ablation plus cardiac resynchronization therapy (CRT) compared with 20 (29%) on rate control medication alone (HR 0.26, 95% CI 0.10-0.65).

Subgroup analysis showed no interaction with LVEF; a significant survival benefit accrued both above 35% and below it (HR 0.27 and 0.34, respectively).

Those findings add to the reduction in heart failure symptoms and hospitalization shown in the earlier phase of the trial.

“This is a new indication for CRT,” Brignole noted. “Until now, in patients with an arrhythmia indication, it is only for wide QRS…and for patients with an ejection fraction less than 35%. This means that the indication for CRT in patients with atrial fibrillation is completely different than the indication in sinus rhythm. Probably because these are two different diseases.”

It’s the first time a survival benefit has been proven compared with medications, but it wasn’t too surprising, said ESC Hot Line session discussant Michael Glikson, MD, of the Hebrew University in Jerusalem. The data “are in line with studies with shorter follow-up and they justify a relatively common practice today to implant CRT in these patients.”

How many of the patients had a normal or near-normal EF wasn’t clear, nor whether the study findings generalize to them, he cautioned.

The average LVEF was 41%. It was sub-normal for most, with 43% of participants below 35%. The trial included severely symptomatic Afib of more than 6 months’ duration that was unsuitable for ablation or had failed a previous attempt. Patients also had to have a QRS of 110 ms or less and at least one heart failure hospitalization in the prior year.

ESC guidelines for pacing being released at the meeting give a class IIb indication to CRT after AV nodal ablation for normal LVEF patients. The new data “does not really change this approach presented here because we don’t have enough information on patients with normal or near-normal ejection fraction who are undergoing AV nodal ablation,” said Glikson, who chaired the guideline writing group.

“For the first time, at this meeting, at this congress, we are building up the idea that really we have effective treatment for ejection fraction starting from very low levels to patients with a normal ejection fraction,” said session panelist Filippo Crea, MD, of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome.

Putting together the “major win” of empagliflozin (Jardiance) in heart failure with preserved ejection fraction (HFpEF) in EMPEROR-Preserved with those of APAF-CRT, gives the “full spectrum,” Crea said. “SGLT2 inhibitors work from very low ejection fraction up to 60% but they do not work after 60%.” And half of those with normal EF patients in EMPEROR-Preserved also had Afib.

Perhaps the strategy should be HF drugs up to an LVEF of 60%, then AV junction ablation and CRT beyond that for patients with Afib, whereas the rest without Afib may have amyloidosis or some other restrictive etiology that needs a different approach, Crea said.

Brignole agreed that there’s a different pathophysiology to heart failure in sinus rhythm. “We have two new therapies for diastolic dysfunction.”

The trial also can’t answer what to do with asymptomatic patients, Brignole acknowledged. However, he speculated that, if the study hypothesis is correct, it would be logical to extrapolate to asymptomatic cases as well. Longer follow-up would likely be needed, but it should be confirmed in a clinical trial, he suggested.

Another question that needs to be answered by a trial is the role of His bundle pacing, which is particularly attractive for a narrow QRS population like the one in APAF-CRT, Brignole said at the session.