{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T16:33:15Z","timestamp":1794069195956,"version":"4.8.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Leducq Foundation for Cardiovascular Research","award":["18CVD05"],"award-info":[{"award-number":["18CVD05"]}]},{"name":"Towards Precision Medicine with Human iPSCs for Cardiac Channelopathies"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>To those of us involved in clinical research it seldom happens to begin working on a rather obscure disease, still largely unexplored, and to follow its ripening into a medical entity of large interest to clinicians and basic scientists alike, and moreover to do so for exactly 50\u2009years. This is what has been my privilege in the relentless pursuit of the intriguing disease known as the long QT syndrome (LQTS). This essay begins with the encounter with my first patient affected by LQTS when just a handful of cardiologists had seen similar cases and continues with the series of efforts, some sound some amateurish, which eventually led\u2014together with many brilliant partners and associates\u2014to describe and understand the natural history of the disease and the most effective therapies. It then touches on how our International Registry for LQTS, with its well-documented family trees, constituted the necessary springboard for the major genetic discoveries of the 1990s. From the explosion of genetic data, my own interest focused first on the intriguing genotype\u2013phenotype correlation and then on \u2018modifier genes\u2019, in the attempt of understanding why family members with the same disease-causing mutation could have an opposite clinical history. And from there on to iPS-derived cardiomyocytes, used to unravelling the specific mechanisms of action of modifier genes and to exploring novel therapeutic strategies. This long, and highly rewarding, journey continues because the fascination and the attraction of the unknown are irresistible.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehaa769","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T19:14:44Z","timestamp":1599506084000},"page":"1063-1072","source":"Crossref","is-referenced-by-count":44,"title":["1970\u20132020: 50 years of research on the long QT syndrome\u2014from almost zero knowledge to precision medicine"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-1048","authenticated-orcid":false,"given":"Peter J","family":"Schwartz","sequence":"first","affiliation":[{"name":"Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics , Via Pier Lombardo, 22, Milan 20135, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,15]]},"reference":[{"key":"2022102513382189800_ehaa769-B1","article-title":"Inherited cardiac arrhythmias","author":"Schwartz","year":",.","journal-title":"Nat Rev Dis Prim"},{"key":"2022102513382189800_ehaa769-B2","author":"Grant","year":"1957"},{"key":"2022102513382189800_ehaa769-B3","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1161\/01.CIR.57.6.1074","article-title":"QT interval prolongation as predictor of sudden death in patients with myocardial infarction","volume":"57","author":"Schwartz","year":"1978","journal-title":"Circulation"},{"key":"2022102513382189800_ehaa769-B4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0002-8703(57)90079-0","article-title":"Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death","volume":"54","author":"Jervell","year":"1957","journal-title":"Am Heart J"},{"key":"2022102513382189800_ehaa769-B5","first-page":"1155","article-title":"Aritmie rare dell\u2019et\u00e0 pediatrica. I. Tachicardia parossistica ripetitiva","volume":"15","author":"Romano","year":"1963","journal-title":"Minerva Pediatr"},{"key":"2022102513382189800_ehaa769-B6","first-page":"103","article-title":"A new familial cardiac syndrome in children","volume":"54","author":"Ward","year":"1964","journal-title":"J Ir Med Assoc"},{"key":"2022102513382189800_ehaa769-B7","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1161\/01.RES.18.4.416","article-title":"Functional distribution of right and left stellate innervation to the ventricles","volume":"18","author":"Yanowitz","year":"1966","journal-title":"Circ Res"},{"key":"2022102513382189800_ehaa769-B8","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1152\/ajplegacy.1969.217.3.703","article-title":"A sympathetic reflex elicited by experimental coronary occlusion","volume":"217","author":"Malliani","year":"1969","journal-title":"Am J Physiol"},{"key":"2022102513382189800_ehaa769-B9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0002-8703(75)90008-3","article-title":"Electrical alternation of the T-wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long Q-T syndrome","volume":"89","author":"Schwartz","year":"1975","journal-title":"Am Heart J"},{"key":"2022102513382189800_ehaa769-B10","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1056\/NEJM197110142851607","article-title":"Unilateral cervicothoracic sympathetic ganglionectomy for the treatment of long QT interval syndrome","volume":"285","author":"Moss","year":"1971","journal-title":"N Engl J Med"},{"key":"2022102513382189800_ehaa769-B11","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1161\/01.CIR.84.2.503","article-title":"Left cardiac sympathetic denervation in the therapy of congenital long QT syndrome. A worldwide report","volume":"84","author":"Schwartz","year":"1991","journal-title":"Circulation"},{"key":"2022102513382189800_ehaa769-B12","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1161\/01.CIR.0000125523.14403.1E","article-title":"Left cardiac sympathetic denervation in the management of high-risk patients affected by the long-QT syndrome","volume":"109","author":"Schwartz","year":"2004","journal-title":"Circulation"},{"key":"2022102513382189800_ehaa769-B13","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1093\/eurheartj\/eht089","article-title":"The long QT syndrome: a transatlantic clinical approach to diagnosis and therapy","volume":"34","author":"Schwartz","year":"2013","journal-title":"Eur Heart J"},{"key":"2022102513382189800_ehaa769-B14","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1093\/europace\/eut272","article-title":"Executive summary: HRS\/EHRA\/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes","volume":"15","author":"Priori","year":"2013","journal-title":"Europace"},{"key":"2022102513382189800_ehaa769-B15","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ccep.2012.01.002","article-title":"The role of the sympathetic nervous system in the long QT syndrome: the long road from pathophysiology to therapy","volume":"4","author":"Schwartz","year":"2012","journal-title":"Card Electrophysiol Clin"},{"key":"2022102513382189800_ehaa769-B16","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/0002-8703(75)90089-7","article-title":"The long Q-T syndrome","volume":"89","author":"Schwartz","year":"1975","journal-title":"Am Heart J"},{"key":"2022102513382189800_ehaa769-B17","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1161\/01.CIR.62.6.1256","article-title":"Left stellectomy in the prevention of ventricular fibrillation caused by acute myocardial ischemia in conscious dogs with anterior myocardial infarction","volume":"62","author":"Schwartz","year":"1980","journal-title":"Circulation"},{"key":"2022102513382189800_ehaa769-B18","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/0002-8703(85)90233-9","article-title":"The effect of antiarrhythmic drugs on life-threatening arrhythmias induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity","volume":"109","author":"Schwartz","year":"1985","journal-title":"Am Heart J"},{"key":"2022102513382189800_ehaa769-B19","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1161\/01.CIR.69.4.790","article-title":"Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. 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