Cardiac resynchronization therapy (CRT)—with or without an implantable cardioverter-defibrillator—improves quality of life, functional status, exercise capacity, morbidity, and mortality in patients in New York Heart Association (NYHA) class III and IV heart failure (HF) with a prolonged QRS. Additionally, CRT contributes to improving left ventricular (LV) structure and function in these patients. So what about patients with asymptomatic or mildly symptomatic HF? Might CRT improve their well-being through LV reverse remodeling?

To answer this question, US and European researchers conducted the randomized, double-blind Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial.1 A total of 610 patients with NYHA class II or I (previously symptomatic) HF were enrolled. Participants had a QRS ≥120 ms with an average of 153 ms, making the QRS slightly less than other trials of patients with more advanced disease. Patients all had an LV ejection fraction ≤40%. So, moderately sick HF patients with moderately broad QRS intervals. All patients received a CRT device with or without a defibrillator and were randomized either to active CRT (CRT ON) or no CRT (CRT OFF, which was the control group) plus optimal medical therapy.

The primary endpoint was a global score based on all-cause mortality, HF hospitalizations, crossover due to worsening HF, NYHA class, and patient global assessment; patients were scored as improved, unchanged, or worsened. The prospectively-powered secondary endpoint was LV end-systolic volume index.

REVERSE at 5 Years

TABLE: 5-Year Results from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) Study Annualized mortality 2.9% Minnesota score 8.2 ± 17.8 units 5-year mortality 13.5% Kansas City score 8.2 ± 17.2 units 5-year rate of death 6.4% Mean decrease in LVESV index 23.5 ± 34.1 mL/m2* 5-year rate of first HF hospitalization 28.1% Mean decrease in LVEDV index 25.4 ± 37.0 mL/m2* 6-minute hall walk 18.8 ± 102.3 m Mean increase in LVEF 6.0 ± 10.8%* * p < 0.0001 LVESV = left ventricular end-systolic volume; LVEDV = left ventricular end-diastolic volume; LVEF = left ventricular ejection fraction

After the randomized phase, all study subjects were programmed to CRT ON and prospectively followed through 5 years in this prespecified substudy. Annual assessment included NYHA class, 6-minute walk, quality of life, echocardiography, adverse events, HF-related hospitalizations, and mortality, with endpoint data assessed by blinded core laboratories. Investigators sought to determine whether reverse remodeling, functional status, mortality, and HF hospitalizations were maintained over time in the 419 patients assigned to CRT ON from the original randomization. Results are found in the TABLE.

Average follow-up was 54.8±13.0 months, with good compliance: 95%, 89%, and 86% of non-deceased patients completed follow-up at 3, 4, and 5 years post-randomization, respectively.

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

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Reference

1. Linde C, Gold MR, Abraham WT, et al. Eur Heart J. 2013 May 2. [Epub ahead of print]

To listen to an interview with Cecilia Linde, MD, about CRT for HF, visit youtube.cswnews.org . The interview was conducted by Steven E. Nissen, MD.

Keywords: Follow-Up Studies, Heart Failure, Ventricular Remodeling, Stroke Volume, Ventricular Dysfunction, Left, Hospitalization, Defibrillators, Implantable, Disease Progression, Echocardiography, Cardiac Resynchronization Therapy

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