{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:38:54Z","timestamp":1760708334717,"version":"3.38.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:sec><jats:title>Background\u2014<\/jats:title><jats:p>Current clinical diagnosis of long-QT syndrome (LQTS) includes genetic testing of family members of mutation-positive patients. The present study was designed to assess the clinical course of individuals who are found negative for the LQTS-causing mutation in their families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results\u2014<\/jats:title><jats:p>Multivariate Cox proportional hazards model was used to assess the risk for cardiac events (comprising syncope, aborted cardiac arrest [ACA], or sudden cardiac death [SCD]) from birth through age 40 years among 1828 subjects from the LQTS Registry who were found negative for their family LQTS-causing mutation. The median QTc of study subjects was 423 ms (interquartile range, 402\u2013442 ms). The cumulative probability of a first syncope through age 40 years was 15%. However, only 2 patients (0.1%) had ACA, and none died suddenly during follow-up. Independent risk factors for syncope in genotype-negative subjects included female sex (hazard ratio [HR], 1.60;<jats:italic>P<\/jats:italic>=0.002), prolonged QTc (HR=1.63 per 100 ms increment,<jats:italic>P<\/jats:italic>=0.02), family history of ACA or SCD (HR=1.89,<jats:italic>P<\/jats:italic>=0.002), and LQT2 versus LQT1 family mutation (HR=1.41,<jats:italic>P<\/jats:italic>=0.03). Subgroup analysis showed that the presence of the<jats:italic>K897T<\/jats:italic>polymorphism in the LQT2 gene in an affected family was associated with an 11-fold (<jats:italic>P<\/jats:italic>=0.001) increase in the risk of recurrent syncope in genotype-negative subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions\u2014<\/jats:title><jats:p>Our findings suggest that cardiac events among genotype-negative family members of LQTS patients are dominated by nonfatal syncopal episodes without occurrence of sudden cardiac death. The risk for nonfatal events in this population may be mediated by the presence of common polymorphisms in LQTS genes.<\/jats:p><\/jats:sec>","DOI":"10.1161\/circgenetics.111.960179","type":"journal-article","created":{"date-parts":[[2011,8,11]],"date-time":"2011-08-11T04:12:36Z","timestamp":1313035956000},"page":"491-499","source":"Crossref","is-referenced-by-count":9,"title":["Risk of Syncope in Family Members Who Are Genotype-Negative for a Family-Associated Long-QT Syndrome Mutation"],"prefix":"10.1161","volume":"4","author":[{"given":"Alon","family":"Barsheshet","sequence":"first","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur J.","family":"Moss","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"McNitt","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slava","family":"Polonsky","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coeli M.","family":"Lopes","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Zareba","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Robinson","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Ackerman","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesaia","family":"Benhorin","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth S.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Towbin","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Michael","family":"Vincent","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Qi","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilan","family":"Goldenberg","sequence":"additional","affiliation":[{"name":"From the Cardiology Division (A.B., A.J.M., S.M., S.P., W.Z., J.L.R., I.G.), Cardiovascular Research Institute (C.M.L.), and the Department of Pathology, University of Rochester Medical Center, Rochester, NY (M.Q.); the Department of Pediatrics, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN (M.J.A.); the Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (J.B.); Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University,..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.84.3.1136"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810013391404"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(99)00582-3"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.665406"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.03.043"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.08.028"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.02.068"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022147"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-17"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90358-5"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90359-3"},{"key":"e_1_3_4_13_2","first-page":"14","article-title":"An analysis of the time relations of electrocardiograms","volume":"7","author":"Bazett H","year":"1920","unstructured":"Bazett H. 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