Research Article LCZ696 Therapy Reduces Ventricular Tachyarrhythmia Inducibility in a Myocardial Infarction-Induced Heart Failure Rat Model Po-Cheng Chang, 1,2 Shien-Fong Lin, 3 Yen Chu, 2,4 Hung-Ta Wo, 1,2 Hui-Ling Lee, 5 Yu-Chang Huang, 1,2 Ming-Shien Wen, 1,2 and Chung-Chuan Chou 1,2 1 Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan 2 Chang Gung University College of Medicine, Taiwan 3 Institute of Biomedical Engineering, National Chiao Tung University, Hsinchu, Taiwan 4 Division of oracic Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan 5 Department of Anesthesia, Chang Gung Memorial Hospital, Taipei, Taiwan Correspondence should be addressed to Chung-Chuan Chou; 2867@adm.cgmh.org.tw Received 6 April 2019; Revised 20 May 2019; Accepted 29 May 2019; Published 1 July 2019 Academic Editor: Brian Tomlinson Copyright © 2019 Po-Cheng Chang et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. LCZ696 (valsartan/sacubitril) therapy signifcantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the efects of LCZ696 in myocardial infarction (MI) patients, the efects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear. Methods. We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week afer MI to confrm the development of HF with lef ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. Te sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins. Results. Te HF-vehicle group did not show signifcant changes in LVEF. Both enalapril and LCZ696 therapy signifcantly improved LVEF. Te HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy signifcantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed signifcant downregulation of Na V 1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2. Conclusion. As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K + channel proteins. 1. Introduction Heart failure (HF) is one of the most frequent diagnoses in patients at admission, with a prevalence of 5.8 million in the United States and over 23 million worldwide [1]. Ventricular tachyarrhythmia is one of the major causes of death in patients with HF [2]. Systolic HF may occur in patients with pressure overload, with volume overload, or fol- lowing cardiac injury, such as myocardial infarction (MI), hypertension, myocarditis, or drug-induced cardiomyopathy. Among the causes of HF, MI is the top cause of systolic HF in developing and developed countries. Angiotensin- converting-enzyme inhibitors, angiotensin II receptor block- ers, beta blockers, and aldosterone antagonists have been widely used in HF patients to improve survival. Even if there had been the remarkable advances of medical therapy in the past decades, HF still carries substantial morbidity and mortality, with a 5-year mortality that is higher than those of many cancers. Ventricular arrhythmias (VAs) and worsening HF account for the major causes of sudden cardiac death in patients with HF. Angiotensin receptor-neprilysin inhibitors are one of the emerging HF pharmacological therapies. Hindawi Cardiovascular erapeutics Volume 2019, Article ID 6032631, 9 pages https://doi.org/10.1155/2019/6032631