Effect of angiotensin/neprilysin inhibition on ventricular repolarization and clinical arrhythmogenesis

Background: The most common reason for sudden cardiac death in heart failure is malign ventricular arrhythmias. LCZ 696 improves hospitalization and sudden cardiac death outcomes in heart failure, however mechanisms in preventing sudden cardiac death are still unknown. There is little information available assessing effect of LCZ 696 on Tp-e interval and related calculations. In this study, we aimed to investigate the impact of Sacubitril/valsartan therapy on Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in heart failure patients and its reflections on clinical arrhythmogenesis. Methods: The study was designed as a prospective observational fashion. 265 patients with implantable cardioverter-defibrillator (ICD), who were on regular follow up at Samsun Training and Research Hospital Outpatient Heart Failure Clinic, were validated for the study. Clinical, echocardiographic, electrocardiogram and device data before initiation and six months after dose optimizing were obtained. Results: Stroke volume, cardiac output and ejection fraction significantly improved after LCZ 696 treatment. T wave related parameters, QT and QTC intervals significantly diminished. Furthermore, there was a negative correlation between baseline Tp-e interval duration and the absolute percentile increase of stroke volume(r:-0.234, p: 0.042) and cardiac output (r: -0.240, p: 0.037). Conclusion: In our study, switching Renin-Angiotensin-Aldosterone-System inhibitor with Angiotensin receptor/neprilysin inhibitor was associated with increase in left ventricle performance and decrease of sustained ventricular arrhythmias that required ICD shocks. These positive findings were accompanied by improvements in surface electrocaridogram changes such as Tp-e and related indices.