Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results from the RAFT-AF trial

Abstract

Background: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and can be challenging to treat. Pharmacologic based rhythm-control of AF has not proven to be superior to rate-control. Ablation-based rhythm-control was compared to rate-control to evaluate if clinical outcomes in patients with HF and AF could be improved. Methods: This was a multicenter, open-label trial with blinded outcome evaluation using a central adjudication committee. Patients with high burden paroxysmal (>4 episodes in six months) or persistent (duration < three years) AF, New York Heart Association class II-III HF, and elevated NT-proBNP were randomized to ablation-based rhythm-control or rate-control. The primary outcome was a composite of all-cause mortality and all HF events, with a minimum follow up of two years. Secondary outcomes included left ventricular ejection fraction (LVEF), six-minute walk test and NT-proBNP. Quality of life was measured using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the AF Effect on quality of life (AFEQT). The primary analysis was time-to-event using Cox proportional hazards modeling. The trial was stopped early due to a determination of apparent futility by the Data Safety Monitoring Committee. Results: From December 1, 2011, to January 20, 2018, 411 patients were randomized to ablation-based rhythm-control (n=214) or rate-control (n=197). The primary outcome occurred in 50 (23.4%) patients in the ablation-based rhythm-control group and 64 (32.5%) patients in the rate-control group (hazard ratio 0.71 95% CI (0.49, 1.03), p=0.066). LVEF increased in the ablation-based group (10.1±1.2% vs 3.8±1.2%, p=0.017); six-minute walk distance improved (44.9±9.1 meters 27.5±9.7 meters, p=0.025) and NT-proBNP demonstrated a decrease (mean change -77.1% vs -39.2%, p<0.0001). MLHFQ demonstrated greater improvement in the ablation-based rhythm-control group (LSMD of -5.4, 95%CI (-10.5, -0.3), p=0.0036), as did the AFEQT score (LSMD of 6.2, 95%CI (1.7, 10.7), p=0.0005). Serious adverse events were observed in 50% of patients in both treatment groups. Conclusions: In patients with high burden AF and HF, there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm-control versus rate-control, however, there was a non-significant trend for improved outcomes with ablation-based rhythm control over rate-control.

Management of Atrial Fibrillation Across the Spectrum of Heart Failure With Preserved and Reduced Ejection Fraction

“…Furthermore, there were signals of greater efficacy in HFrEF for the primary end point (P=0.059) compared with HFpEF (P=0.67) with corroboratory evidence of improved quality of life, 6-minute walk distance, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and EF, suggesting a beneficial effect at least in the HFrEF subset. 65 Overall, these studies point to a role for catheter ablation in select patients with less advanced HFrEF and AF to restore sinus rhythm and to improve quality of life, but further studies are needed to better define optimal patient selection and, in particular, the impact of age on outcomes such that younger patients appear to derive more benefit, as noted in CABANA. 67 Although controversy remains concerning the impact of ablation on mortality in HFrEF, improvements in quality of life and functional status are clinically relevant outcomes for patients, and most studies have shown improvement in these important functional measures with ablation.…”

“…Furthermore, there were signals of greater efficacy in HFrEF for the primary end point ( P =0.059) compared with HFpEF ( P =0.67) with corroboratory evidence of improved quality of life, 6-minute walk distance, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and EF, suggesting a beneficial effect at least in the HFrEF subset. 65…”

“…In contrast to signals for efficacy in HFrEF from this trial, there was no suggestion of efficacy for the primary end point, quality of life, or 6-minute walk distance in the HFpEF subset. 65 Patients with paroxysmal AF and HFpEF have an intermediate severity of atrial myopathy with a high rate of progression to severe LA myopathy with permanent AF 5 (Figure 6), but the role of catheter ablation in modifying progression is unclear until dedicated trials in HFpEF are performed.…”

Herzinsuffizienz und Vorhofflimmern – eine Zwillingsepidemie

“…Die aktuelle RAFT-AF-Studie [9] hat in einem randomisierten Design die ablationsbasierte Rhythmuskontrollstrategie mit der konventionellen Frequenzkontrollstrategie verglichen (paroxysmales oder persistierendes VHF, NYHA II-III und erhöhtes NT-proBNP, über 40 % der Patienten in beiden Gruppen mit einer EF > 45 %, also erhaltenen LV-Funktion). Die Studie wurde frühzeitig termi-…”

Evidence Builds for Catheter Ablation for Atrial Fibrillation and Heart Failure

“…In this issue of Circulation , Parkash et al 12 report the results of the RAFT-AF trial (Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation). In this modest-sized randomized trial, 411 patients with high-burden paroxysmal or persistent AF, symptomatic heart failure (60% with ejection fraction ≤45%), and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) were randomized to catheter ablation or rate control.…”