Effects of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in reduced ejection fraction patients under continuous remote monitoring of implantable defibrillator devices

Heart Rhythm. 2018 Mar;15(3):395-402. doi: 10.1016/j.hrthm.2017.11.012. Epub 2017 Nov 14.


Background: Angiotensin-neprilysin inhibition compared to angiotensin inhibition decreased sudden cardiac death in patients with reduced ejection fraction heart failure (rEFHF). The precise mechanism remains unclear.

Objective: The purpose of this study was to explore the effect of angiotensin-neprilysin inhibition on ventricular arrhythmias compared to angiotensin inhibition in rEFHF patients with an implantable cardioverter-defibrillator (ICD) and remote monitoring.

Methods: We prospectively included 120 patients with ICD and (1) New York Heart Association functional class ≥II; (2) left ventricular ejection fraction ≤40%; and (3) remote monitoring. For 9 months, patients received 100% angiotensin inhibition with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), beta-blockers, and mineraloid antagonist. Subsequently, ACEi or ARB was changed to sacubitril-valsartan in all patients, who were followed for 9 months. Appropriate shocks, nonsustained ventricular tachycardia (NSVT), premature ventricular contraction (PVC) burden, and biventricular pacing percentage were analyzed.

Results: Patients were an average age of 69 ± 8 years and had mean left ventricular ejection fraction of 30.4% ± 4% (82% ischemic). Use of beta-blockers (98%), mineraloid antagonist (97%) and antiarrhythmic drugs was similar before and after sacubitril-valsartan. Sacubitril-valsartan significantly decreased NSVT episodes (5.4 ± 0.5 vs 15 ± 1.7 in angiotensin inhibition; P <.002), sustained ventricular tachycardia, and appropriate ICD shocks (0.8% vs 6.7% in angiotensin inhibition; P <.02). PVCs per hour decreased after sacubitril-valsartan (33 ± 12 vs 78 ± 15 in angiotensin inhibition; P <.0003) and was associated with increased biventricular pacing percentage (from 95% ± 6% to 98.8% ± 1.3%; P <.02).

Conclusion: Angiotensin-neprilysin inhibition decreased ventricular arrhythmias and appropriate ICD shocks in rEFHF patients under home monitoring compared to angiotensin inhibition.

Keywords: Arrhythmia; Heart failure; Implantable cardioverter–defibrillator; Remote monitoring; Resynchronization; Sacubitril-valsartan.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Angiotensins / antagonists & inhibitors*
  • Defibrillators, Implantable*
  • Electrocardiography, Ambulatory / methods*
  • Female
  • Humans
  • Male
  • Neprilysin / antagonists & inhibitors*
  • Prospective Studies
  • Stroke Volume / drug effects*
  • Tachycardia, Ventricular / drug therapy*
  • Tachycardia, Ventricular / metabolism
  • Tachycardia, Ventricular / physiopathology
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / physiology


  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensins
  • Neprilysin