AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial. European Heart Journal, doi.org/10.1093/eurheartj/ehab569

It’s not every day - or even every year! - that a clinical trial demonstrates a 74% reduction in mortality. Developing a new intervention or drug with a clinically significant benefit is devilishly difficult. Sometimes the benefit is limited to soft end-points, such as hospital admissions or quality of life questionnaires which are to some extent open to bias. Not so death. One such trial, the APAF-CRT trial was presented by the principal investigator Dr Michele Brignole from Milan at the ESC congress 2021.

The trial included severely symptomatic patients with permanent atrial fibrillation (AF) that was deemed unsuitable for a primary AF ablation, narrow QRS complex and at least one heart failure (HF) hospitalization in the previous year. A total of 133 patients with a mean age of 73 years were randomized into a usual medical therapy or cardiac resynchronization therapy (CRT) with atrioventricular (AV) node ablation. The patients were followed up for a median of 29 months. The results were staggering: 20 patients (29%) died in the medical therapy arm, 7 patients (11%) died in the CRT + ablation arm, hazard ratio (HR) 0.26 (i.e. 74% mortality reduction), confidence interval (CI) 0.10-0.65; p=0.004. The benefit of CRT and ablation on all-cause mortality was not dependent on LV contractility or resting heart rate; it was similar in patients with EF lower or greater than 35% and with resting heart rate lower or higher than 102 bpm. The secondary endpoint combining mortality and HF hospitalization was also significantly lower in the CRT + ablation arm: 29% vs. 51%, HR 0.40, CI 0.22-0.73, p=0.002.

These were patients who are very common in cardiology clinics; often elderly women with many comorbidities, on multiple drugs, with breathlessness on even slight physical activity, history of admissions for HF, lowish blood pressure and fast atrial fibrillation. Pacemaker insertion - usually with a simple single-chamber device, rather than biventricular pacemaker - followed by AV node ablation has been long used in these patients for symptomatic relief. APAF-CRT trial now documents also a stunning prognostic benefit, provided a biventricular pacemaker is used. AV node ablation is of course an irreversible procedure that creates a life-long pacemaker dependency. It must only be used after careful consideration. However, in a selected group of highly symptomatic patients, AV node ablation in combination with CRT is literally life-saving.