1. Clinical Manifestations and Long-Term Mortality in Lamin A/C Mutation Carriers From a Japanese Multicenter Registry
- Author
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Takeshi Aiba, Takeru Makiyama, Yasushi Oginosawa, Ichiro Watanabe, Seiko Ohno, Nobuyuki Murakoshi, Kenzaburo Nakajima, Minoru Horie, Yoshihiko Saito, Kengo Kusano, Taisuke Ishikawa, Satoshi Shizuta, Satoshi Yasuda, Hiroshi Kawakami, Naomasa Makita, Kazutaka Aonuma, Koichi Kato, Nobue Yagihara, Takeshi Kimura, Takahiro Doi, Akihiko Nogami, Kenji Onoue, Wataru Shimizu, Suguru Nishiuchi, and Yuta Yamamoto more...
- Subjects
medicine.medical_specialty ,business.industry ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Middle age ,Sudden cardiac death ,LMNA ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Heart failure ,Cardiac conduction ,Mutation (genetic algorithm) ,Cardiology ,Medicine ,Missense mutation ,Cardiology and Cardiovascular Medicine ,business ,Stroke ,030217 neurology & neurosurgery - Abstract
Background Mutation in the lamin A/C gene (LMNA) is associated with several cardiac phenotypes, such as cardiac conduction disorders (CCD), atrial arrhythmia (AA), malignant ventricular arrhythmia (MVA) and left ventricular dysfunction (LVD), leading to sudden cardiac death (SCD) and/or end-stage heart failure. We investigated how these phenotypes are associated with each other and which of them are most important for total mortality. Methods and Results: A multicenter registry included 110 LMNA mutation carriers (age, 43±15 years, male: 62%) from 60 families. After genetic diagnosis of LMNA mutation (missense: 27%, non-missense: 73%), patients or subjects were followed to evaluate the manifestations of their phenotypes and the risk of total mortality; 90 patients could be followed (median: 5 [0-35] years). Prevalence of the 4 clinical phenotypes was significantly increased during follow-up. Among these phenotypes, AA was significantly associated with MVA. CCD was significantly associated with LVD. LVD, meanwhile, was significantly associated with CCD and MVA. Male sex was significantly associated with MVA. Furthermore, during follow-up, 17 patients died: 12 end-stage heart failure, 4 SCD and 1 stroke. LVD was the only independent predictor for all-cause death (OR: 41.7, 95% CI: 4.1-422.3; P=0.0016). Conclusions Several cardiac phenotypes were age-dependently increased in LMNA mutation carriers, suggesting that ICD or CRT-D could suppress SCD after middle age; however, LVD leading to end-stage heart failure was the only independent predictor for total mortality. more...
- Published
- 2018
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