Withdrawal of Neurohumoral Blockade After Cardiac Resynchronization Therapy

Abstract

BACKGROUND The necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear. OBJECTIVES The aim of this study was to investigate the feasibility and safety of neurohumoral blacker withdrawal in patients with normalized ejection fractions after cardiac resynchronization therapy. METHODS In this prospective, open-label, randomized controlled pilot trial with a 2 x 2 factorial design, subjects were randomized to withdrawal of renin-angiotensin-atdosterone system inhibitors and/or beta-btockers versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling, defined as an increase in left ventricular end-systolic volume index of >15% at 24 months. The secondary endpoint was a composite safety endpoint of all-cause mortality, heart failure-related hospitalizations, and incidence of sustained ventricular arrhythmias at 24 months. RESULTS Eighty subjects were consecutively enrolled and randomized among 4 groups (continuation of neurohumorat blacker therapy, n = 20; withdrawal of renin-angiotensin-aldosterone system inhibitors, n = 20; withdrawal of betabtockers, n = 20; and withdrawal of renin-angiotensin-aldosterone system inhibitors and beta-blockers, n = 20). Of the 80 subjects, 6 (73%) met the primary and 4 (5%) the secondary endpoint. However, re-initiation of neurohumorat btockers occurred in 17 subjects because of hypertension or supraventricutar arrhythmias. CONCLUSIONS The incidence of the primary and secondary endpoints over a follow-up period of 2 years was tow in both the control group and in the groups in which neurohumorat btockers were discontinued. However, neurohumorat blacker withdrawal was hampered by cardiac comorbidities.