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While therapy with sacubitril\/valsartan (SV) reduces the risk of sudden cardiac death in patients with heart failure and systolic dysfunction, the effect on those with diastolic dysfunction remains unclear. We hypothesized that, in the animal model of hypertensive heart disease, treatment with SV reduces the susceptibility to ventricular arrhythmia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Young adult female spontaneous hypertensive rats (SHRs) were randomly separated into three groups, which were SHRs, SHRs treated with valsartan, and SHRs treated with SV. In addition, the age-matched and weight-matched Wistar Kyoto rats were considered as controls, and there were 12 rats in each group. In vivo ventricular tachyarrhythmia induction and in vitro optical mapping were used to measure the inducibility of ventricular arrhythmias and to characterize the dynamic properties of electrical propagation. The level of small-conductance Ca2+-activated potassium channel type 2 (KCNN2) was analysed in cardiac tissue. Compared with SHR with left ventricular hypertrophy, treatment with SV significantly improved cardiac geometry (relative wall thickness, 0.68 \u00b1 0.11 vs. 0.76 \u00b1 0.13, P &amp;lt; 0.05) and diastolic dysfunction (isovolumetric relaxation time, 59.4 \u00b1 3.2 vs. 70.5 \u00b1 4.2 ms, P &amp;lt; 0.05; deceleration time of mitral E wave, 46 \u00b1 4.8 vs. 42 \u00b1 3.8, P &amp;lt; 0.05). The incidence of induced ventricular arrhythmia was significantly reduced in SHR treated with SV compared with SHR (ventricular tachycardia, 1.14 \u00b1 0.32 vs. 2.91 \u00b1 0.5 episodes per 10 stimuli, P &amp;lt; 0.001; ventricular fibrillation, 1.72 \u00b1 0.31 vs. 5.81 \u00b1 0.42 episodes per 10 stimuli, P &amp;lt; 0.001). The prolonged action potential duration (APD) and increase of the maximum slope of APD restitution were observed in SHR, while the treatment of SV improved the arrhythmogeneity (APD, 37.12 \u00b1 6.18 vs. 92.41 \u00b1 10.71 ms at 250 ms pacing cycle length, P &amp;lt; 0.001; max slope 0.29 \u00b1 0.01 vs. 1.48 \u00b1 0.04, P &amp;lt; 0.001). These effects were strongly associated with down-regulation of KCNN2 (0.38 \u00b1 0.07 vs. 0.74 \u00b1 0.12 ng\/ml, P &amp;lt; 0.001). The treatment of SV also decreased the level of N-terminal pro-B-type natriuretic peptide, cardiac bridging integrator-1, and intramyocardial fibrosis of SHR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In conclusion, synergistic blockade of the neprilysin and the renin\u2013angiotensin system by SV in SHRs results in KCNN2-associated electrical remodelling in ventricle, which stabilizes electrical dynamics and attenuates arrhythmogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13013","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T05:44:50Z","timestamp":1600926290000},"page":"4040-4050","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Reverse Electromechanical Modelling of Diastolic Dysfunction in Spontaneous Hypertensive Rat after Sacubitril\/Valsartan Therapy"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5191-334X","authenticated-orcid":false,"given":"Yen-Ling","family":"Sung","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University , Hsinchu, 300 ,","place":["Taiwan"]},{"name":"Department of Electrical and Computer Engineering, National Chiao Tung University , Hsinchu ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8810-5127","authenticated-orcid":false,"given":"Ting-Tse","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University , Hsinchu, 300 ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Biomedical Park Branch , Hsinchu ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1255-4305","authenticated-orcid":false,"given":"Jhen-Yang","family":"Syu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University , Hsinchu, 300 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6020-2523","authenticated-orcid":false,"given":"Hung-Jui","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University , Hsinchu, 300 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4809-6481","authenticated-orcid":false,"given":"Kai-Yuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University , Hsinchu, 300 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0623-9146","authenticated-orcid":false,"given":"Yen-Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University College of Medicine , Taipei ,","place":["Taiwan"]},{"name":"Department of Internal Medicine, National Taiwan University Hospital , Taipei ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1270-3961","authenticated-orcid":false,"given":"Shien-Fong","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, College of Electrical and Computer Engineering, National Chiao Tung University , Hsinchu, 300 ,","place":["Taiwan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"2026012115025469300_ehf213013-bib-0001","article-title":"2013 ACCF\/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"62","author":"Yancy","year":"2013","journal-title":"J Am Coll 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