Abstract
Sacubitril/Valsartan (LCZ696) reduced sudden cardiac death in the PARADIGM-HF trial. However, the mechanism by which LCZ696 reduces ventricular arrhythmias remains unclear. The aim of this study was to compare electrocardiographic (ECG) parameters and mechanical dispersion index, assessed by left ventricular (LV) global longitudinal strain (GLS), before and after LCZ696 therapy. We prospectively evaluated chronic Heart Failure (HF) patients with LV ejection fraction ≤40%, despite optimal medical and device therapy, in which LCZ696 therapy was started, while no additional HF treatment was expected to change. ECG and transthoracic echocardiographic data were gathered in the week before starting LCZ696 and at six months of therapy. A semiautomated analysis of LV GLS was performed and mechanical dispersion index was defined as the standard deviation from 16 time intervals corresponding to each LV segment. Of the 42 patients, 35 completed the six month follow-up, since two patients died and five discontinued treatment for adverse events. QTc interval (451.9 vs. 426.0 ms, p < 0.001), QRS duration (125.1 vs. 120.8 ms, p = 0.033) and mechanical dispersion index (88.4 vs. 78.1 ms, p = 0.036) were significantly reduced at six months. LCZ696 therapy is associated with a reduction in QTc interval, QRS duration and mechanical dispersion index as assessed by LV GLS.
Highlights
The PARADIGM-HF trial showed that Sacubitril/Valsartan (LCZ696), with the combination of neprilysin inhibitor and angiotensin II receptor blocker (ARB) could reduce both heart failure (HF) hospitalization and cardiovascular mortality by 20% in comparison with Enalapril [1]
LCZ696 has a Class I recommendation as a replacement for angiotensin-converting enzyme inhibitors (ACEI) for ambulatory patients with HF with reduced ejection fraction who remain symptomatic despite optimal treatment with an ACEI (or an angiotensin II receptor blocker (ARB), as an alternative, if they were not tolerant to ACEI), a beta-blocker (BB) and a mineralocorticoid receptor antagonist (MRA) [2]
A subanalysis of the PARADIGM-HF trial showed a reduction in sudden cardiac death by 20% in relation to Enalapril, which does not differ amongst patients with or without an implantable cardioverter defibrillator (ICD) [3]
Summary
The PARADIGM-HF trial showed that Sacubitril/Valsartan (LCZ696), with the combination of neprilysin inhibitor and angiotensin II receptor blocker (ARB) could reduce both heart failure (HF) hospitalization and cardiovascular mortality by 20% in comparison with Enalapril [1]. A subanalysis of the PARADIGM-HF trial showed a reduction in sudden cardiac death by 20% in relation to Enalapril, which does not differ amongst patients with or without an implantable cardioverter defibrillator (ICD) [3] This antiarrhythmic effect was confirmed in two other studies, in which LCZ696 therapy was associated with a significant reduction in episodes of non-sustained and sustained ventricular tachycardia, appropriate ICD shocks, premature ventricular contractions and an increase in biventricular pacing percentage [4,5]. The precise mechanism by which LCZ696 causes a decrease in ventricular arrhythmias remains unclear
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