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

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.

• Authors: Pieter Martens, Dieter Nuyens, Maximo Rivero-Ayerza, Hugo Van Herendael, Jan Vercammen, Wendy Ceyssens, Evert Luwel, Matthias Dupont, Wilfried Mullens
• Journal: Clinical research in cardiology : official journal of the German Cardiac Society (Clin Res Cardiol) Vol. 108 Issue 10 Pg. 1074-1082 (Oct 2019) ISSN: 1861-0692 [Electronic] Germany
• PMID: 30788621 (Publication Type: Journal Article)

Chemical References

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

Topics

• Aged
• Aminobutyrates (therapeutic use)
• Angiotensin Receptor Antagonists (therapeutic use)
• Arrhythmias, Cardiac (drug therapy, etiology, physiopathology)
• Belgium (epidemiology)
• Biphenyl Compounds
• Death, Sudden, Cardiac (epidemiology, prevention & control)
• Drug Combinations
• Female
• Follow-Up Studies
• Heart Failure (complications, drug therapy, 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)