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Published on: July 14, 2021
Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart
Pieter Martens1,2, Dieter Nuyens3, Maximo Rivero-Ayerza3
1Department of Cardiology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600, Genk, Belgium. pieter.martens2@zol.be.
Insights
Sacubitril/valsartan significantly reduced ventricular tachycardia/fibrillation (VT/VF) burden and appropriate implantable cardioverter-defibrillator (ICD) therapies in heart failure patients. This benefit may stem from cardiac reverse remodeling.
Area of Science:
- Cardiology
- Pharmacology
- Medical Devices
Background:
- Sacubitril/valsartan demonstrated reduced sudden cardiac death in the PARADIGM-HF trial.
- Mechanisms underlying sacubitril/valsartan's antiarrhythmic effects require further elucidation.
Purpose of the Study:
- To investigate the impact of sacubitril/valsartan on ventricular arrhythmias in heart failure (HF) patients.
- To explore the relationship between cardiac reverse remodeling and changes in arrhythmic burden.
Main Methods:
- Retrospective analysis of 151 HF patients with reduced ejection fraction (LVEF) on sacubitril/valsartan.
- Device-registered arrhythmic events (VT/VF, appropriate therapy, NsVT, PVC burden) were analyzed pre- and post-initiation.
- Cardiac reverse remodeling defined as ≥5% LVEF improvement.
Main Results:
- Sacubitril/valsartan initiation led to significant reductions in VT/VF burden and appropriate ICD therapies (p < 0.001).
- Non-sustained VT (NsVT) burden per patient also significantly decreased (p < 0.001).
- Reduced PVC burden correlated with improved biventricular pacing, and reverse remodeling was linked to lower NsVT and PVC burden.
Conclusions:
- Initiation of sacubitril/valsartan is associated with decreased ventricular arrhythmias (VT/VF) and fewer ICD interventions.
- The observed antiarrhythmic effects may be attributed to sacubitril/valsartan-induced cardiac reverse remodeling.
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.
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