REVERSE study: CRT produces long-term improvements in disease progression in mildly symptomatic heart failure patients. Five-year results from the REsynchronization reVErses Remodeling in Sys

List of Authors: Cecilia Linde MD PhD1*, Michael R Gold MD PhD2, William T Abraham MD3, Martin St John Sutton MD4, Stefano Ghio MD5, Jeff Cerkvenik, MS6, and Claude Daubert MD7, on behalf of the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) Study Group.

The benefit of cardiac resynchronization therapy (CRT) among patients with left ventricular systolic dysfunction, ventricular conduction delay and mild heart failure (HF) is well established. However, little is known regarding the long-term stability of these effects. REVERSE was a prospective, randomized, double-blind, parallel-controlled multinational study designed to determine whether CRT limited the progression of heart failure (HF) compared to optimal medical therapy alone in 610 subjects with NYHA Class I and II heart failure (HF), QRS ≥120 ms, and LVEF ≤40%. Patients were implanted with a CRT-P or CRT-D and were randomized to CRT ON or CRT OFF. Patients were unblinded at 12 months (US and Canada) or 24 months (Europe) according to the study protocol where-after all subjects were programmed to CRT ON and followed through 5 years. We have previously reported that CRT compared to control induced significant reverse remodeling accompanied by a significant reduction in HF hospitalizations. The aim of this study is to describe the 5 year results in 419 assigned to CRT ON. 

Methods and results
There were 610 patients randomized in REVERSE of whom 419 were randomized to have CRT ON and used in this analysis. Patients were followed annually by NYHA class, 6-minute walk, quality of life, echocardiography, adverse events, HF-related hospitalizations and mortality, with endpoint data assessed by blinded core laboratories. The average follow up time was 54.8+13.0 months, with good compliance: 95%, 89%, and 86% of non-deceased patients completing follow-ups at 3, 4, and 5 years post-randomization respectively.

Reverse remodeling was maximal within 2 years and thereafter sustained. The annualized mortality was 2.9%, yielding a 5-year mortality of 13.5%. The total 5-year rate of death or first heart failure (HF)-related hospitalization was 28.1%, with a stable event rate over time and an annual rate of 6.4%. 

In subjects with mild HF, CRT produced reverse left ventricular remodeling accompanied by very low mortality and need for heart failure hospitalization. These effects are sustained over at least 5 years. The results warrants for wider use of CRT in mild heart failure patients.