{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:23:13Z","timestamp":1793690593222,"version":"4.5.1"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Truncating variants in the\n                      <jats:italic>TTN<\/jats:italic>\n                      gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by \u226510% or normalization to \u226550%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Median follow-up was 49 (18\u2013105) months. Men developed LVSD more frequently and earlier than women (45\u00b114 versus 49\u00b116 years, respectively;\n                      <jats:italic>P<\/jats:italic>\n                      =0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04\u20133.44];\n                      <jats:italic>P<\/jats:italic>\n                      =0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30\u20132.04];\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis (\n                      <jats:italic>P<\/jats:italic>\n                      =0.07).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.119.006832","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T05:00:12Z","timestamp":1600837212000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":187,"title":["Clinical Phenotypes and Prognosis of Dilated Cardiomyopathy Caused by Truncating Variants in the\n                    <i>TTN<\/i>\n                    Gene"],"prefix":"10.1161","volume":"13","author":[{"given":"Mohammed Majid","family":"Akhtar","sequence":"first","affiliation":[{"name":"Department of Inherited Cardiovascular Diseases, Bart\u2019s Heart Centre, St. Bartholomew\u2019s Hospital, London, United Kingdom (M.M.A., M.L., L.R.L., P.M.E.)."},{"name":"Institute of Cardiovascular Science, University College London, United Kingdom (M.M.A., M.L., L.R.L., P.M.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Lorenzini","sequence":"additional","affiliation":[{"name":"Department of Inherited Cardiovascular Diseases, Bart\u2019s Heart Centre, St. Bartholomew\u2019s Hospital, London, United Kingdom (M.M.A., M.L., L.R.L., P.M.E.)."},{"name":"Institute of Cardiovascular Science, University College London, United Kingdom (M.M.A., M.L., L.R.L., P.M.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Cicerchia","sequence":"additional","affiliation":[{"name":"Health in Code S.L. Scientific Department, A Coru\u00f1a, Spain (M.C., J.P.O., L.M.)."},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a, Complexo Hospitalario Universitario de A Coru\u00f1a, Sergas, Universidade da Coru\u00f1a, Spain (M.C., J.P.O., L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7966-0313","authenticated-orcid":true,"given":"Juan Pablo","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Health in Code S.L. Scientific Department, A Coru\u00f1a, Spain (M.C., J.P.O., L.M.)."},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de A Coru\u00f1a, Complexo Hospitalario Universitario de A Coru\u00f1a, Sergas, Universidade da Coru\u00f1a, Spain (M.C., J.P.O., L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0262-7774","authenticated-orcid":true,"given":"Thomas Morris","family":"Hey","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Odense University Hospital, Denmark (T.M.H., J.M.)."},{"name":"Odense Patient Data Explorative Network, University of Southern Denmark (T.M.H., J.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sabater Molina","sequence":"additional","affiliation":[{"name":"Inherited Cardiac Disease Unit, Hospital Universitario Virgen Arrixaca, Murcia, Spain (M.S.M., J.R.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Alejandra","family":"Restrepo-Cordoba","sequence":"additional","affiliation":[{"name":"Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Centro de Investigaci\u00f3n en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (M.A.R.-C., P.G.-P.)."},{"name":"Universidad Francisco de Vitoria, Pozuelo de Alarcon, Spain (M.A.R.-C., P.G.-P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Dal Ferro","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Azienda Sanitaria Universitaria Integrata of Trieste, Trieste Hospital, Italy (M.D.F., D.S., G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Stolfo","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Azienda Sanitaria Universitaria Integrata of Trieste, Trieste Hospital, Italy (M.D.F., D.S., 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E.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0719-1933","authenticated-orcid":true,"given":"Maria","family":"Franaszczyk","sequence":"additional","affiliation":[{"name":"Department of Medical Biology (M.F.), Cardinal Stefan Wyszynski Institute of Cardiology, Warsaw, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2043-356X","authenticated-orcid":true,"given":"Gemma","family":"Laucey","sequence":"additional","affiliation":[{"name":"Complejo Hospitalario de Navarra, Pamplona, Spain (G.L., M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2435-0155","authenticated-orcid":true,"given":"Diego","family":"Rangel-Sousa","sequence":"additional","affiliation":[{"name":"Heart Failure and Heart Transplantation Unit, Virgen del Rocio University Hospital, Sevilla, Spain (M.L.P.-P., 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