Frequency and Outcomes of Postrandomization Atrial Tachyarrhythmias in the Resynchronization/Defibrillation in Ambulatory Heart Failure Trial

Abstract

Background— Whether adding cardiac resynchronization therapy (CRT-D) to an implanted cardioverter–defibrillator alters the risk of atrial fibrillation or other atrial tachyarrhythmias (AF/AT), or if postimplantation AF/AT modulate the benefits of CRT-D, remain unknown. Methods and Results— We studied 972 Resynchronization/Defibrillation in Ambulatory Heart Failure Trial (RAFT) participants without permanent AF, who were randomized to CRT-D (n=495) versus nonresynchronization defibrillator (implanted cardioverter–defibrillator; n=477) within the predefined stratum eligible for an atrial lead. Occurrence of postrandomization AF/AT was prospectively assessed, and Cox models were used to test the independent association between the postrandomization AF/AT and the RAFT primary composite outcome of all-cause mortality or hospitalization for heart failure. Over 41 (±19) months, postrandomization AF/AT occurred in 216 (45.3%) patients randomized to implanted cardioverter–defibrillator and 249 (50.3%) randomized to CRT-D. After adjusting for competing risk of death, randomization to CRT-D increased risk of postrandomization AF/AT (hazard ratio, 1.20; 95% confidence interval, 1.00–1.42; P =0.045). Postrandomization AF/AT, which remained paroxysmal in 69.5%, did not reduce biventricular pacing percentage. In adjusted models, postrandomization AF/AT was not associated with the primary outcome (hazard ratio, 1.04; 95% confidence interval, 0.84–1.30). However, AF/AT was associated with a borderline decreased risk of mortality (hazard ratio, 0.75; 95% confidence interval, 0.58–1.00) but increased risk of heart failure hospitalization (hazard ratio, 1.43; 95% confidence interval, 1.08–1.90). Conclusions— In RAFT, nearly half of the patients developed postrandomization AF/AT, and those randomized to CRT-D had borderline significant higher risk. Postrandomization AF/AT was associated with risk of heart failure hospitalization, but not with the primary composite outcome. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00251251.

Real‐world behavior of CRT pacing using the AdaptivCRT algorithm on patient outcomes: Effect on mortality and atrial fibrillation incidence

“…Many observational studies have suggested that CRT reduced AF, whereas some of the large CRT clinical trials (CARE HF and MADIT CRT) failed to demonstrate a significant reduction in the burden of AF 7,27 . RAFT even suggested an increase in AF in the CRT arm, although CARE HF and RAFT used clinical AF rather than device‐detected AF 9 . This study has demonstrated significant reductions in AF in patients with aCRT programmed ON.…”

“…Perhaps the more physiological AV intervals may explain the benefit of the algorithm. The RAFT investigators postulated that overly short programming of AV intervals may explain their observation of increased AF with CRT 9 …”

“…The RAFT investigators postulated that overly short programming of AV intervals may explain their observation of increased AF with CRT. 9 Looking beyond the individual components of the aCRT algorithm to the reported clinical benefits associated with aCRT may shed more light upon potential mechanisms of benefit. As previously reported, and replicated in the present analysis, aCRT is associated with a reduction in both AF incidence and daily AF burden.…”

“…Two individual patient data meta‐analyses have confirmed the mortality and HFH findings 3,5 . The effect of CRT on atrial fibrillation (AF), a common comorbidity in HF patients that has been linked to increased risk of mortality, stroke, and hospitalizations, is less certain 6‐9 . Despite the benefits of CRT, not all patients improve with therapy, with nearly one‐third of the patients having persistent HF symptoms and/or lack of left ventricular reverse remodeling.…”

“…3,5 The effect of CRT on atrial fibrillation (AF), a common comorbidity in HF patients that has been linked to increased risk of mortality, stroke, and hospitalizations, is less certain. [6][7][8][9] Despite the benefits of CRT, not all patients improve with therapy, with nearly one-third of the patients having persistent HF symptoms and/or lack of left ventricular reverse remodeling. Potential reasons for suboptimal response include both patient factors, such as arrhythmias and device factors, such as suboptimal atrioventricular (AV) timing.…”