{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T21:16:10Z","timestamp":1783545370865,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,17]],"date-time":"2021-04-17T00:00:00Z","timestamp":1618617600000},"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>Aim: Evaluate prevalence of heart failure (HF) medications and their association with ventricular arrhythmia (VA) and survival among patients implanted with primary prevention implantable cardiac defibrillator (ICD)\/cardiac resynchronization therapy + defibrillator (CRTD) devices. Methods: Association of treatment and dose (% guideline recommended target) of beta-adrenergic receptor antagonist (BB), angiotensin-antagonists (AngA), and mineralocorticoid-antagonists (MRA), after ICD\/CRTD implant with VA and mortality was retrospectively analyzed. Results: Study included 186 HF patients; 42.5% and 57.5% implanted with ICD and CRTD, respectively. During 3.8 (2.1;6.7) years; 52 (28%) had VA and 77 (41.4%) died. Treatment (% of patients) included: BB (83%), AngA (87%), and MRA (59%). Median doses were 25(12.5;50)% of target for all medications. BB treatment &gt;25% target dose was associated with reduced VA incidence. In the multivariable model including age, gender, diabetes, heart rate, and medication doses, increased BB dose was associated with reduced VA (hazard ratio (HR) 0.443 95% CI 0.222\u20130.885; p = 0.021). In the multivariable model for overall mortality including age, gender, renal disease, VA, and medical treatment, VA was associated with increased mortality (HR 2.672; 95% CI 1.429\u20134.999; p = 0.002) and AngA treatment was associated with reduced mortality (HR 0.515; 95% CI 0.285\u20130.929; p = 0.028). Conclusions: In this cohort of real-life HF patients discharged after ICD\/CRTD implant, prevalence of guideline-based HF medications was high, albeit with low doses. Higher BB dose was associated with reduced VA, while AngA was associated with improved survival.<\/jats:p>","DOI":"10.3390\/jcm10081753","type":"journal-article","created":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T22:15:13Z","timestamp":1618784113000},"page":"1753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of Guideline-Based Medical Therapy with Malignant Arrhythmias and Mortality among Heart Failure Patients Implanted with Cardioverter Defibrillator (ICD) or Cardiac Resynchronization-Defibrillator Device (CRTD)"],"prefix":"10.3390","volume":"10","author":[{"given":"Tal","family":"Hasin","sequence":"first","affiliation":[{"name":"Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Hebrew University, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, Hebrew University, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilia","family":"Davarashvili","sequence":"additional","affiliation":[{"name":"Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Hebrew University, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Michowitz","sequence":"additional","affiliation":[{"name":"Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Hebrew University, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, Hebrew University, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka","family":"Farkash","sequence":"additional","affiliation":[{"name":"Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Hebrew University, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haya","family":"Presman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Glikson","sequence":"additional","affiliation":[{"name":"Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Hebrew University, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, Hebrew University, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5365-9947","authenticated-orcid":false,"given":"Moshe","family":"Rav-Acha","sequence":"additional","affiliation":[{"name":"Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Hebrew University, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, Hebrew University, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0140-6736(98)11181-9","article-title":"CBIS II Authors. The Cardiac Insufficiency Bisoprolol Study II (CIBISII): A randomized trial","volume":"353","author":"Brunhuber","year":"1999","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1016\/S0140-6736(99)04440-2","article-title":"MERIT-HF Investigators. Effect of metoprolol CR\/XL in chronic heart failure: Metoprolol CR\/XL randomized intervention trial in congestive heart failure (MERIT-HF)","volume":"353","author":"Hjalmarson","year":"1999","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1056\/NEJM200105313442201","article-title":"Effect of Carvedilol on Survival in Severe Chronic Heart Failure","volume":"344","author":"Packer","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"The SOLVD Investigators (1991). Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N. Engl. J. Med., 325, 293\u2013302.","DOI":"10.1056\/NEJM199108013250501"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators (1993). Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet, 342, 821\u2013828.","DOI":"10.1016\/0140-6736(93)92693-N"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1056\/NEJMoa010713","article-title":"A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure","volume":"345","author":"Cohn","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/S0140-6736(09)61913-9","article-title":"Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): A randomized, double-blind trial","volume":"374","author":"Konstam","year":"2009","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJM199909023411001","article-title":"The effect of spironolactone on morbidity and mortality in patients with severe heart failure","volume":"341","author":"Pitt","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1009492","article-title":"Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms","volume":"364","author":"Zannad","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1161\/01.CIR.0000144474.65922.AA","article-title":"Effect of candesartan on cause-specific mortality in heart failure patients: The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program","volume":"110","author":"Solomon","year":"2004","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/S0735-1097(98)00609-3","article-title":"Effect of angiotensin converting enzyme inhibitors on sudden cardiac death in patients following acute MI","volume":"33","author":"Domanski","year":"1999","journal-title":"JACC"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Al_Gobari, M., El Khatib, C., Pillon, F., and Gueyffer, F. (2013). B-blockers for the prevention of sudden cardiac death in heart failure patients. BMC Cardiovasc. Disord., 13.","DOI":"10.1186\/1471-2261-13-52"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1161\/CIRCHEARTFAILURE.112.000003","article-title":"Effect of mineralocorticoid receptor antagonsists on risk of sudden cardiac death in patients with LV dysfunction","volume":"6","author":"Bapoje","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/jce.13192","article-title":"Mortality Effect of ICD in Primary Prevention of Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials","volume":"28","author":"Luni","year":"2017","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1056\/NEJMoa1609758","article-title":"Declining Risk of Sudden Death in Heart Failure","volume":"377","author":"Shen","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1056\/NEJMoa1608029","article-title":"Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure","volume":"375","author":"Thune","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jacc.2018.04.070","article-title":"Medical Therapy for Heart Failure with Reduced Ejection Fraction","volume":"72","author":"Greene","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1016\/j.jacc.2019.02.015","article-title":"Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction","volume":"73","author":"Greene","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1008","DOI":"10.1016\/S2214-109X(18)30306-1","article-title":"Prescribing patterns of evidence-based heart failure pharmacotherapy and outcomes in the ASIAN-HF registry: A cohort study","volume":"6","author":"Teng","year":"2018","journal-title":"Lancet Glob. Health"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1002\/ejhf.887","article-title":"Physicians\u2019 guideline adherence is associated with better prognosis in outpatients with heart failure with reduced ejection fraction: The QUALIFY international registry","volume":"19","author":"Komajda","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_21","first-page":"1786","article-title":"2012 ACC\/AHA\/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities","volume":"126","author":"Epstein","year":"2012","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1093\/eurheartj\/eht150","article-title":"2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy","volume":"34","author":"Brignole","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1093\/eurheartj\/ehx026","article-title":"Determinants and clinical outcome of uptitration of ACE-inhibitors and beta-blockers in patients with heart failure: A prospective European study","volume":"38","author":"Ouwerkerk","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1093\/europace\/euz065","article-title":"2019 HRS\/EHRA\/APHRS\/LAHRS focused update to 2015 expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing","volume":"21","author":"Stiles","year":"2019","journal-title":"Europace"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1056\/NEJMoa043399","article-title":"Amiodarone or an Implantable Cardioverter\u2013Defibrillator for Congestive Heart Failure","volume":"352","author":"Bardy","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1056\/NEJMoa033088","article-title":"Prophylactic Defibrillator Implantation in Patients with Nonischemic Dilated Cardiomyopathy","volume":"350","author":"Kadish","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1056\/NEJMoa1211107","article-title":"Reduction in Inappropriate Therapy and Mortality through ICD Programming","volume":"367","author":"Moss","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/0002-9149(91)90098-6","article-title":"Characterization of spontaneous termination of sustained ventricular tachycardia associated with coronary artery disease","volume":"67","author":"Callans","year":"1991","journal-title":"Am. J. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S0735-1097(97)00513-5","article-title":"Mechanisms for spontaneous termination of monomorphic sustained ventricular tachycardia: Results of activation mapping of reentrant circuits in the epicardial border zone of subacute canine infarcts","volume":"31","author":"Schmitt","year":"1998","journal-title":"JACC"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1056\/NEJM199912163412503","article-title":"A Randomized Study of the Prevention of Sudden Death in Patients with Coronary Artery Disease","volume":"341","author":"Buxton","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1056\/NEJMoa013474","article-title":"Prophylactic Implantation of a Defibrillator in Patients with Myocardial Infarction and Reduced Ejection Fraction","volume":"346","author":"Moss","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1016\/S0735-1097(03)00297-3","article-title":"Amiodarone versus implantable defibrillator: Randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia. (AMIOVIRT)","volume":"41","author":"Strickberger","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1062-1458(02)00817-6","article-title":"Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy. The cardiomyopathy trial (CAT)","volume":"11","author":"Antz","year":"2002","journal-title":"ACC Curr. J. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jacc.2012.03.023","article-title":"Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: Results from the HF-ACTION trial","volume":"60","author":"Fiuzat","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1016\/j.amjcard.2011.02.321","article-title":"Relation of Ventricular Tachycardia\/Fibrillation to Beta-Blocker Dose Maximization Guided by Pacing Mode Analysis in Nonpacemaker-Dependent Patients with Implantable Cardioverter\u2013Defibrillator","volume":"107","author":"Deftereos","year":"2011","journal-title":"Am. J. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1161\/CIRCEP.112.971101","article-title":"Predictors of sustained ventruclar arrhythmias in cardiac resynchronization therapy","volume":"5","author":"Friedman","year":"2012","journal-title":"Circ. Arrhythmia Electrophysiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.amjcard.2005.04.046","article-title":"MADIT II research group. Effects of beta-blockers on implantable cardioverter defibrillator therapy and survival in patients with ischemic cardiomyopathy","volume":"96","author":"Brodine","year":"2005","journal-title":"Am. J. Casrdiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"f217","DOI":"10.1093\/europace\/euy077","article-title":"Importance of beta-blocker dose in prevention of ventricular tachyarrhythmias, heart failure hospitalizations, and death in primary prevention implantable cardioverter-defibrillator recipients: A Danish nationwide cohort study","volume":"20","author":"Ruwald","year":"2018","journal-title":"Europace"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/00015385.2018.1547469","article-title":"Reduced occurrence of appropriate therapy for ventricular arrhythmias after beta-blocker uptitration following implant of primary prevention CRTD","volume":"75","author":"Martens","year":"2020","journal-title":"Acta Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1177\/10742484050100i403","article-title":"Antiarrhythmic action of beta-blockers: Potential mechanisms","volume":"10","author":"Dorian","year":"2005","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_42","first-page":"1","article-title":"Anti arrhythmic mechanism of BB therapy","volume":"146","author":"Grandi","year":"2019","journal-title":"Phramacol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"St\u00f6ckigt, F., Brixius, K., Lickfett, L., Andri\u00e9, R., Linhart, M., Nickenig, G., and Schrickel, J.W. (2012). Total beta-adrenoceptor knockout slows conduction and reduces inducible arrhythmias in the mouse heart. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049203"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jchf.2015.09.002","article-title":"Heart Rate or Beta-Blocker Dose? Association with Outcomes in Ambulatory Heart Failure Patients with Systolic Dysfunction","volume":"4","author":"Fiuzat","year":"2016","journal-title":"JACC Heart Fail."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1161\/CIRCRESAHA.111.245092","article-title":"Treatment of chronic heart failure with beta-adrenergic receptor antagonists: A convergence of receptor pharmacology and clinical cardiology","volume":"109","author":"Bristow","year":"2011","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1016\/j.jacc.2017.04.001","article-title":"Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure","volume":"69","author":"Kotecha","year":"2017","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/8\/1753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:49:19Z","timestamp":1760161759000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/8\/1753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,17]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["jcm10081753"],"URL":"https:\/\/doi.org\/10.3390\/jcm10081753","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,17]]}}}