Sustained clinical benefit of cardiac resynchronization therapy in non-LBBB patients with prolonged PR-interval: MADIT-CRT long-term follow-up

Objective: In MADIT-CRT, patients with non-LBBB (right bundle branch block or nonspecific ventricular conduction delay) and a prolonged PR-interval derived significant clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) compared to an implantable cardioverter defibrillator (ICD)-only. We aimed to study the long-term outcome of non-LBBB patients by baseline PR-interval with CRT-D versus ICD-only. Methods: Non-LBBB patients (n = 534) were dichotomized based on baseline PR-interval: normal PR (PR < 230 ms), and markedly prolonged PR (PR ≥ 230 ms). The primary end point was heart failure (HF) or death. Secondary end points were HF only and all-cause death. Results: In patients with a prolonged PR-interval, CRT-D treatment related to a 67 % significant reduction in the risk of HF/death (HR = 0.33, 95 % CI 0.16–0.69, p = 0.003), 69 % decrease in HF (HR = 0.31, 95 % CI 0.14–0.68, p = 0.003), and 76 % reduction in the risk of death (HR = 0.24, 95 % CI 0.07–0.80, p = 0.020) compared to ICD-only (median follow-up 5.8 years). In normal PR-interval patients, CRT-D therapy was associated with a trend towards increased risk of HF/death (HR = 1.49, 95 % CI 0.98–2.25, p = 0.061), and significantly increased mortality (HR = 2.27, 95 % CI 1.16–4.44, p = 0.014). Significant statistical interaction with the PR-interval was demonstrated for all end points. Results were consistent for QRS 130–150 ms and QRS > 150 ms. Conclusion: In MADIT-CRT, non-LBBB patients with a prolonged PR-interval derive sustained long-term clinical benefit with reductions in heart failure or death from CRT-D implantation, compared to an ICD-only. Our findings support implantation of CRT-D in non-LBBB patients with prolonged PR-interval irrespective of baseline QRS duration.