Effects of Angiotensin Receptor-Neprilysin Inhibitor in Arrhythmogenicity Following Left Atrial Appendage Closure in an Animal Model

Wen Han Cheng, Isaiah C. Lugtu, Shih Lin Chang, Shin Huei Liu, Shih Ann Chen, Li Wei Lo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Purpose: Left atrial appendage (LAA) closure decreases atrial natriuretic peptide (ANP) levels, which indirectly increases the risk of arrhythmogenicity. We aimed to determine the effect of a combined angiotensin receptor-neprilysin inhibitor (ARNi) on arrhythmogenicity following LAA closure in an animal model. Methods: Twenty-four rabbits were randomized into four groups: (1) control, (2) LAA closure (LAAC), (3) heart failure (HF)-LAAC, and (4) HF-LAAC with sacubitril/valsartan (+ARNi). HF models were developed in the HF-LAAC and HF-LAAC+ARNi groups. Epicardial LAA exclusion was performed in the LAAC, HF-LAAC, and HF-LAAC+ARNi groups. ANP levels were measured. An electrophysiological study was performed. The myocardium was harvested for histopathological analysis. Results: The ANP level decreased in the LAAC group (785 ± 103 pg/mL, p = 0.03), failed to increase in the HF-LAAC group (917 ± 172 pg/mL, p = 0.3), and increased in the HF-LAAC+ARNi group (1524 ± 126 pg/mL, p < 0.01) compared to that in the control group (1014 ± 56 pg/mL). The atrial effective refractory period (ERP) was prolonged in the HF-LAAC group and restored to baseline in the HF-LAAC+ARNi group. Ventricular ERP was the longest in the HF-LAAC group. The atrial fibrillation window of vulnerability (AF WOV) was elevated in the LAAC, HF-LAAC, and HF-LAAC+ARNi groups, with the latter group having lower AF WOV than the two former groups. Ventricular fibrillation (VF) inducibility was the highest in the HF-LAAC group (51 ± 5%, p < 0.001), followed by the LAAC group (30 ± 4%, p = 0.006) and the HF-LAAC+ARNi group (25 ± 5%, p = 0.11) when compared to the control group (18 ± 4%). Atrial and ventricular fibrosis were noted in all groups except the control group. Conclusion: LAA closure decreased ANP, which in turn increased AF and VF inducibility. Atrial and ventricular arrhythmogenicity was suppressed by ARNi.

Original languageEnglish
Pages (from-to)759-768
Number of pages10
JournalCardiovascular Drugs and Therapy
Issue number4
StatePublished - Aug 2021


  • Angiotensin receptor neprilysin inhibition
  • Atrial arrhythmogenicity
  • Heart failure
  • Left atrial appendage closure
  • Ventricular arrhythmogenicity


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