{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:22:12Z","timestamp":1771611732865,"version":"3.50.1"},"reference-count":20,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T00:00:00Z","timestamp":1603929600000},"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>Background: Myocarditis can manifest with lone ventricular tachyarrhythmias (LVT). Elective inflammation of conduction tissue (CT) is supposed but unproved. Methods: Forty-two of 420 patients with biopsy proven myocarditis presented with LVT. Twelve of them included CT sections in endomyocardial biopsies. Real-time polymerase chain reaction (PCR) for viral genomes, immunohistochemistry for viral antigens and Toll like receptor 4 (TLR4) were performed. Twelve myocarditis patients with infarct-like or cardiomyopathic phenotype and CT included in tissue section were used as controls. Results: Four of the 12 patients presented non-sustained ventricular tachycardia (nsVT), six with sustained ventricular tachycardia (sVT), two with ventricular fibrillation. CT was inflamed in all LVT patients and not in controls (p &lt; 0.001). PCR was positive for influenza-A virus in two, herpes simplex virus type 2 (HSV2) in one and adenovirus in one with positive CT immunostaining for viral antigens. In eight patients, negative PCR and TLR4 overexpression suggested an immune-mediated pathway. Patients with influenza-A myocarditis and CT infection responded to oseltamivir, those with HSV2 (Herpes Virus 2) and adenovirus infection died. The eight patients with immune-mediated myocarditis were treated with steroids and azathioprine. Seven of them had no more VT(ventricular tachyarrhythmias)during six-month follow-up. Conclusions: Arrhythmic phenotype of myocarditis is associated with CT inflammation\/infection. Molecular characterization of CT damage may lead to pharmacologic control of arrhythmias in 75% of cases.<\/jats:p>","DOI":"10.3390\/jcm9113470","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T21:21:00Z","timestamp":1604006460000},"page":"3470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inflammation of Conduction Tissue in Patients with Arrhythmic Phenotype of Myocarditis"],"prefix":"10.3390","volume":"9","author":[{"given":"Andrea","family":"Frustaci","sequence":"first","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy"},{"name":"Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, 00149 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Verardo","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, 00149 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Alfarano","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Chimenti","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, Sapienza University, 00161 Rome, Italy"},{"name":"Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, 00149 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.jacc.2009.02.007","article-title":"International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper","volume":"53","author":"Friedrich","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jcmg.2013.10.011","article-title":"CMR sensitivity varies with clinical presentation and extent of cell necrosis in biopsy-proven acute myocarditis","volume":"7","author":"Francone","year":"2014","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1161\/CIRCEP.114.002569","article-title":"Pathology and Function of Conduction Tissue in Fabry Disease Cardiomyopathy","volume":"8","author":"Frustaci","year":"2015","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/ehjci\/jev014","article-title":"Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"16","author":"Lang","year":"2015","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1161\/CIRCULATIONAHA.13.001414","article-title":"Contribution and risks of left ventricular endomyocardial biopsy in patients with cardiomyopathies: A retrospective study over a 28-year period","volume":"128","author":"Chimenti","year":"2013","journal-title":"Circulation"},{"key":"ref_7","first-page":"1","article-title":"Myocarditis: A histopathologic definition and classification","volume":"1","author":"Aretz","year":"1985","journal-title":"Am. J. Cardiol. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1002\/ejhf.796","article-title":"Myocardial expression of Toll-like receptor 4 predicts the response to immunosuppressive therapy in patients with virus-negative chronic inflammatory cardiomyopathy","volume":"19","author":"Chimenti","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_9","first-page":"64","article-title":"Beitragezurnormalen und pathologischenAnatomie des Herzens","volume":"14","author":"Monckeberg","year":"1910","journal-title":"Verh. Dtsch. Pathol. Ges."},{"key":"ref_10","first-page":"3","article-title":"Referat\u00fc ber die Herzstorungen in ihrenBeziehungenzu den SpezifischenMuskelsystem des Herzens","volume":"14","author":"Aschoff","year":"1910","journal-title":"Verh. Dtsch. Pathol. Ges."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tcm.2014.08.009","article-title":"Insights into cardiac conduction system formation provided by HCN4 expression","volume":"25","author":"Liang","year":"2015","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1161\/CIRCULATIONAHA.106.174287","article-title":"Contemporary definitions and classification of the cardiomyopathies: An American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention","volume":"113","author":"Maron","year":"2006","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1016\/j.hrthm.2017.10.036","article-title":"AHA\/ACC\/HRS Guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death","volume":"15","author":"Stevenson","year":"2018","journal-title":"Heart Rhythm"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1093\/eurheartj\/ehp249","article-title":"Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: The TIMIC study","volume":"30","author":"Frustaci","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.jacc.2010.01.004","article-title":"Fulminant myocarditis associated with pandemic H1N1 influenza A virus in children","volume":"55","author":"Bradley","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1161\/CIRCULATIONAHA.107.186093","article-title":"The role of endomyocardial biopsy in the management of cardiovascular disease: A scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology","volume":"116","author":"Cooper","year":"2007","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.carpath.2011.10.001","article-title":"2011 consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology","volume":"21","author":"Leone","year":"2012","journal-title":"Cardiovasc. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1161\/CIRCULATIONAHA.107.743427","article-title":"Complication Rate of Right Ventricular Endomyocardial Biopsy via the Femoral Approach","volume":"118","author":"Holzmann","year":"2008","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s15010-016-0892-0","article-title":"Transitory Ventricular Tachycardia Associated with Influenza a Infection of Cardiac Conduction Tissue","volume":"44","author":"Frustaci","year":"2016","journal-title":"Infection"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e009448","DOI":"10.1161\/CIRCIMAGING.119.009448","article-title":"Arrhythmic Phenotype of Myocarditis Sustained by a Prominent Infiltration of Conduction Tissue","volume":"12","author":"Frustaci","year":"2019","journal-title":"Circ. Cardiovasc. 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