Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction

Clin Res Cardiol. 2019 Oct;108(10):1074-1082. doi: 10.1007/s00392-019-01440-y. Epub 2019 Feb 20.

Abstract

Background: Sacubitril/valsartan reduced the occurrence of sudden cardiac death in the PARADIGM-HF trial. However, limited information is available about the mechanism.

Methods: Heart failure (HF)-patients receiving sacubitril/valsartan for a class-I indication equipped with an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) with remote tele-monitoring were retrospectively analyzed. Device-registered arrhythmic-events were determined [ventricular tachycardia/fibrillation (VT/VF), appropriate therapy, non-sustained VT (NsVT; > 4beats and < 30 s), hourly premature ventricular contraction (PVC)-burden], following sacubitril/valsartan initiation (incident-analysis) and over an equal time period before initiation (antecedent-analysis). Reverse remodeling to sacubitril/valsartan was defined as an improvement of left ventricular ejection fraction of ≥ 5% between baseline and follow-up.

Results: A-total of 151 HF-patients with reduced LVEF (29 ± 9%) were included. Patients were switched from ACE-I or ARB to equal doses of sacubitril/valsartan (expressed as %-target-dose; before = 58 ± 30% vs. after = 56 ± 27%). The mean follow-up of both the incident and antecedent analysis was 364 days. Following the initiation, VT/VF-burden dropped (individual patients with VT/VF pre_n = 19 vs. post_n = 10, total-episodes of VT/VF pre_n = 51 vs. post_n = 14, both p < 0.001), resulting in reduced occurrence of appropriate therapy (pre_n = 16 vs. post_n = 6; p < 0.001). NsVT-burden per patient also dropped (mean episodes pre_n = 7.7 ± 11.8 vs. post_n = 3.7 ± 5.4; p < 0.001). There was no impact on atrial-fibrillation burden. PVC-burden dropped significantly which was associated with an improvement in BiV-pacing in patients with < 90% BiV-pacing at baseline. A higher degree of reverse remodeling was associated with a lower burden of NsVT and PVCs (both p < 0.05).

Conclusion: Initiation of sacubitril/valsartan is associated with a lower degree of VT/VF, resulting in less ICD-interventions. This beneficial effect on ventricular arrhythmias might be related to cardiac reverse remodeling.

Keywords: Heart failure; Pharmacology; Reverse remodeling; Sacubitril/valsartan; Ventricular arrhythmias.

MeSH terms

  • Aged
  • Aminobutyrates / therapeutic use*
  • Angiotensin Receptor Antagonists / therapeutic use
  • Arrhythmias, Cardiac / drug therapy*
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / physiopathology
  • Belgium / epidemiology
  • Biphenyl Compounds
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / prevention & control*
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Incidence
  • Male
  • Neprilysin
  • Retrospective Studies
  • Stroke Volume / physiology*
  • Survival Rate / trends
  • Tetrazoles / therapeutic use*
  • Treatment Outcome
  • Valsartan
  • Ventricular Function, Left / physiology*
  • Ventricular Remodeling / drug effects*

Substances

  • Aminobutyrates
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Drug Combinations
  • Tetrazoles
  • Valsartan
  • Neprilysin
  • sacubitril and valsartan sodium hydrate drug combination