APAF-CRT: 'Ablate and Pace' for Permanent AF With Heart Failure, Narrow QRS

September 12, 2018

MUNICH — Patients with heart failure (HF) and narrow electrocardiographic QRS intervals aren't considered appropriate for cardiac resynchronization therapy (CRT), but evidence is growing that CRT may benefit some such patients who also have atrial fibrillation (AF).

In a small trial, atrioventricular (AV) junctional ablation plus biventricular CRT pacing in narrow QRS among patients with HF and permanent AF appeared to cut the risk for a clinical composite primary endpoint compared with rate-control medical therapy.

The benefit for the endpoint, death or hospitalization from HF or worsening HF, was driven primarily by fewer HF hospitalizations in patients in the "ablate and pace" group.

Entry to the Ablate and Pace in Atrial Fibrillation plus Cardiac Resynchronization Therapy (APAF-CRT) trial required that the patients have a history of HF hospitalization and be severely symptomatic from their arrhythmia and poor candidates for standard AF ablation.

Variable Effects by LVEF

A prespecified analysis showed the ablate-and-pace group's significant 62% reduction in risk for the primary endpoint was concentrated among patients with a left ventricular ejection fraction (LVEF) of 35% or less. No such benefit was seen in the subgroup with an LVEF greater than 35%.

On the other hand, patients with preserved LVEF in the ablate-and-pace group, but not those with reduced LVEF, showed significant alleviation of symptoms in the group that had undergone ablation with insertion of a biventricular (BiV) pacemaker for CRT.

"In the patients with an ejection fraction more than 35%, symptoms were mostly related to atrial fibrillation" and probably less to progressive contractile dysfunction, said Michele Brignole, from  Ospedali del Tigullio,  Lavagna, Italy.

In contrast, "the patients with an ejection fraction less than 35% had symptoms mainly due to heart failure, more hospitalization for heart failure, more pulmonary edema, and so on," he said.

In those patients with reduced  LVEF, he proposed, heart rate regularization from AV-junctional ablation manifested primarily as an improvement in the HF-hospitalization component of the primary endpoint.

That may explain why symptoms improved more in patients with preserved LVEF and HF hospitalizations were more likely to drop in those with reduced LVEF after AV-junctional ablation, he speculated during a panel discussion following his presentation of APAF-CRT here at the European Society of Cardiology (ESC) Congress 2018.

Brignole is also lead author on the trial's parallel August 26 publication in the European Heart Journal. Based on the current findings, the article states, AV-junctional ablation and CRT "should be offered to patients with symptomatic HF refractory to pharmacological therapy who cannot undergo catheter ablation of AF for the maintenance of sinus rhythm, or in whom ablation has failed."

APAF-CRT, "I think, provides convincing evidence, in a small cohort of patients, that biventricular pacing after AV-node ablation in narrow QRS is beneficial to patients as compared to medical therapy," Jagmeet P. Singh, MD, DPhil, Massachusetts General Hospital, Boston, told theheart.org | Medscape Cardiology.

But "it really doesn't answer that question of whether CRT is better than RV pacing in narrow-QRS patients," observed Singh, who was not involved in the study.

Given the known risk for cardiomyopathy with sustained right ventricular (RV) pacing, it seems plausible that BiV pacing should be preferred, he added, but probably "they would have needed a much larger cohort of patients to see a clinically significant difference between the two."

His sense, he said, "is that they probably would have found the same results, that BiV pacing is better than RV pacing, but the number needed to treat would be significantly higher."  

Enrollment Halted Early

In APAF-CRT, 102 patients with severely symptomatic AF that had persisted for more than 6 months, at least one HF hospitalization in the previous year, and a QRS duration of 110 ms or less were assigned to the ablate-and-pace approach or pharmacologic rate control; implantable defibrillators were allowed in either group when indicated.

The target enrollment had been 280 patients; entry to the trial was halted early when a planned interim analysis showed a protocol-defined critical difference in the primary endpoint.

In an intention-to-treat analysis, 10 patients in the ablate-and-pace group and 20 in the control group met the primary endpoint over a median of 16 months; events were adjudicated by committee.

Table 1. Hazard Ratio for Outcomes in APAF-CRT

Endpoints Hazard Ratio (95% CI) P Value
Primary endpoint,a all patients 0.38 (0.18 - 0.81) .013
LVEF ≤ 35% 0.18 (0.05 - 0.66) .010
LVEF > 35% 0.62 (0.23 - 1.70) .359
Death from any cause 0.30 (0.06 - 1.50) .147
HF hospitalization 0.30 (0.11 - 0.78) .024
Death or HF hospitalization 0.28 (0.11 - 0.72) .008
aHF death, HF hospitalization, or worsening HF.


During follow-up, 12 patients in the control group crossed over to receive AV-junctional ablation and CRT after a median of 135 days.

In an on-treatment analysis of symptomatic and functional responses in 50 ablate-and-pace and 42 control patients evaluated at 1 year, the former group showed a 36% relative improvement in self-assessed Specific Symptom Scale scores (P = .004), indicating a significant reduction in AF-related symptoms.

The ablate-and-pace group also had better scores on a physician-administered European Heart Rhythm Association (EHRA) assessment of AF symptoms, apparently driven by gains in patients with preserved LVEF.

Table 2. Rate of Achieving ≥1-Point Improvement in EHRA Symptoms and Physical Limitation Class by 1 Year

Endpoints Ablation + CRT (%) Rate Control Medication (%) P Value
All patients 76 43 .001
LVEF ≤ 35% 57 47 .75
LVEF > 35% 90 39 .001


"In the narrow-QRS population, it's still unclear whether biventricular pacing supersedes pure RV pacing," Singh said. "But personally if I had a patient with a low EF, and a narrow QRS, and refractory symptoms, I would be inclined toward implanting a biventricular pacemaker."

The investigator-initiated APAF-CRT trial was supported by a grant from Boston Scientific and sponsored by the nonprofit Centro Prevenzione Malattie Cardiorespiratorie Nuccia e Vittore Corbella. Neither Brignole nor the other authors had disclosures. Singh recently disclosed receiving grants or compensation for services from Abbott, Biotronik, Boston Scientific, EBR Systems, Medtronic, Impulse Dynamics USA, and LivaNova.

European Society of Cardiology (ESC) Congress 2018. Late Breaking Science in Arrhythmias and Electrophysiology. Presented August 26, 2018.

Eur Heart J.   Published online August 26, 2018. Abstract

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