A narrative review on sacubitril/valsartan and ventricular arrhythmias

Abstract

Sacubitril/valsartan, the first angiotensin receptor neprilysin inhibitor approved by the Food and Drug Administration for marketing, has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms in patients with chronic heart failure with a reduced ejection fraction. However, some researchers have also found that sacubitril/valsartan has an antiarrhythmic effect. The mechanism by which sacubitril/valsartan reduces the mortality associated with malignant ventricular arrhythmias is not precise. Many studies have concluded that ventricular arrhythmia is associated with a reduction in myocardial fibrosis. This article reviews the current understanding of the effects of sacubitril/valsartan on the reduction of ventricular arrhythmia and explains its possible mechanisms. The results of this study suggest that sacubitril/valsartan reduces the occurrence of appropriate implantable cardioverter-defibrillator shocks. Meanwhile, sacubitril/valsartan may reduce the occurrence of ventricular arrhythmias by affecting 3 pathways of B-type natriuretic peptide, Angiotensin II, and Bradykinin. The conclusion of this study is that sacubitril/valsartan reduces the number of implantable cardioverter-defibrillator shocks and ventricular arrhythmias in heart failure with reduced ejection fraction patients.

Figure 1.

Data analysis of the number of appropriate ICD shocks before and after taking sacubitril/valsartan. There are significant differences between the 2 groups in appropriate ICD shocks was observed, but with mild heterogeneity. CI = confidence interval, ICD = implantable cardioverter-defibrillator. Favors [control] = before taking sacubitril/valsartan. Favors [experimental] = after taking sacubitril/valsartan.

Figure 2.

Methods of selecting articles for inclusion in data analysis. ARNI = angiotensin receptor neprilysin inhibitor, ICD = implantable cardioverter-defibrillator, MeSH = Medical Subject Headings.

Figure 3.

Possible mechanisms underlying the antiarrhythmic effect of sacubitril/valsartan. 4,5-PIP2 = 4,5-bisphosphate phosphatidylinositol, Ang II = angiotensin II, AT1R = angiotensin type 1 receptor, BNP = B-type natriuretic peptide, B2R = B2 receptor, BK = bradykinin, BNP-R = B-type natriuretic peptide receptor, CaM = calmodulin, CaMKII = calmodulin-dependent protein kinase II, cGMP = cyclic guanosine monophosphate, DAG = diacylglycerol, EC = extracellular collagen, EDHF = endothelium-dependent hyperpolarizing factor, GC = guanylate cyclase, GP = G protein, GTP = guanosine triphosphate, IP3 = triphosphate, MMP I = matrix metalloproteinase I, NEP = neprilysin, NO = nitric oxide, PKC = protein kinase C, PGI2 = prostaglandin I2, PKG = protein kinase G, PLC = phospholipase C, PLN = phospholamban, SR = sarcoplasmic reticulum.