{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:20:27Z","timestamp":1793337627642,"version":"4.5.0"},"reference-count":127,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Sudden cardiac death (SCD) accounts for a substantial proportion of mortality in heart failure with reduced ejection fraction (HFrEF), frequently triggered by ventricular arrhythmias (VA). This review aims to analyze the pathophysiological mechanisms underlying VA and SCD in HFrEF and evaluate the effectiveness of guideline-directed medical therapy (GDMT) in reducing SCD. Beta-blockers, angiotensin receptor\u2013neprilysin inhibitors, and mineralocorticoid receptor antagonists have shown significant efficacy in reducing SCD risk. While angiotensin-converting enzyme inhibitors and angiotensin receptor blockers exert beneficial impacts on the renin-angiotensin-aldosterone system, their direct role in SCD prevention remains less clear. Emerging treatments like sodium-glucose cotransporter 2 inhibitors show promise but necessitate further research for conclusive evidence. The favorable outcomes of those molecules on VA are notably attributable to sympathetic nervous system modulation, structural remodeling attenuation, and ion channel stabilization. A multidimensional pharmacological approach targeting those pathophysiological mechanisms offers a complete and synergy approach to reducing SCD risk, thereby highlighting the importance of optimizing GDMT for HFrEF. The current landscape of HFrEF pharmacotherapy is evolving, with ongoing research needed to clarify the full extent of the anti-arrhythmic benefits offered by both existing and new treatments.<\/jats:p>","DOI":"10.3390\/jcm13051316","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T06:50:23Z","timestamp":1708930223000},"page":"1316","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Anti-Arrhythmic Effects of Heart Failure Guideline-Directed Medical Therapy and Their Role in the Prevention of Sudden Cardiac Death: From Beta-Blockers to Sodium-Glucose Cotransporter 2 Inhibitors and Beyond"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0537-9262","authenticated-orcid":false,"given":"Wael","family":"Zaher","sequence":"first","affiliation":[{"name":"Department of Cardiology, Centre Hospitalier EpiCURA, Route de Mons 63, 7301 Hornu, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3837-3462","authenticated-orcid":false,"given":"Domenico Giovanni","family":"Della Rocca","sequence":"additional","affiliation":[{"name":"Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Laarbeeklan 101, Jette, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Pannone","sequence":"additional","affiliation":[{"name":"Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Laarbeeklan 101, Jette, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1280-7042","authenticated-orcid":false,"given":"Serge","family":"Boveda","sequence":"additional","affiliation":[{"name":"Heart Rhythm Management Department, Clinique Pasteur, 31076 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9351-0760","authenticated-orcid":false,"given":"Carlo","family":"de Asmundis","sequence":"additional","affiliation":[{"name":"Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Laarbeeklan 101, Jette, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian-Battista","family":"Chierchia","sequence":"additional","affiliation":[{"name":"Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Laarbeeklan 101, Jette, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0078-9393","authenticated-orcid":false,"given":"Antonio","family":"Sorgente","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centre Hospitalier EpiCURA, Route de Mons 63, 7301 Hornu, Belgium"},{"name":"Heart Rhythm Management Centre, Postgraduate Program in Cardiac Electrophysiology and Pacing, Universitair Ziekenhuis Brussel-Vrije Universiteit Brussel, European Reference Networks Guard-Heart, Laarbeeklan 101, Jette, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/0002-8703(88)90891-5","article-title":"Cardiac failure and sudden death in the Framingham Study","volume":"115","author":"Kannel","year":"1988","journal-title":"Am. 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