Heart rate control as an additional therapeutic strategy in patients with decompensated heart failure

• Grant number: 12/06163-6
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2012
• End date: January 31, 2015
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Edimar Alcides Bocchi
• Grantee: Edimar Alcides Bocchi
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Marco Stephan Lofrano Alves

Abstract

Sympathetic hyperactivity and the consequent increased heart rate (HR) are physiological adaptative responses of the neuro-hormonal system to low cardiac output in heart failure (HF). However, excessive high HR can be inappropriate in these patients by increasing myocardial consume of oxygen and decreasing the time for left-ventricle diastolic filling, which results in left ventricle dysfunction, hemodynamic impairment and clinical deterioration. Several studies have shown that increased HR is an independent prognostic factor of survival in HF. Sub analysis of clinical trials using beta blockers (BB) suggest that HR control correlates with increased survival in patients presenting chronic stable HF. However, the use of BBs in decompensated HF (DHF) is limited due to hypotension and negative inotropic effect of these drugs. Recent clinical trials have demonstrated that HR control obtained by a new class of drugs named funny current inhibitors (I(f) inhibitors) is safe and improves survival of patients with stable HF and severe systolic dysfunction. Compared to BBs, I(f) inhibition has the advantage of "pure" negative chronotropic effect, without interfering on myocardial contractility or peripheral vascular resistance. The use of I(f) inhibitors has been recently advocated as a therapeutic option in stable HF patients under use of BBs and persistent elevated HR. However there is no available controlled studies on the use of I(f) inhibitors in patients with DHF. We hypothesise that HR control through I(f) inhibitors might contribute to improve hemodynamic, neuro-hormonal and clinical parameters of patients with DHF and potentially constitute a new therapeutic strategy for this disease. Thus, we propose a prospective, double-blind, randomized, placebo-controlled trial to test this hypothesis (AU)