Clinical manifestations and long-term mortality in lamin A/C mutation carriers from a Japanese multicenter registry

Kenzaburo Nakajima, Takeshi Aiba, Takeru Makiyama, Suguru Nishiuchi, Seiko Ohno, Koichi Kato, Yuta Yamamoto, Takahiro Doi, Satoshi Shizuta, Kenji Onoue, Nobue Yagihara, Taisuke Ishikawa, Ichiro Watanabe, Hiroshi Kawakami, Yasushi Oginosawa, Nobuyuki Murakoshi, Akihiko Nogami, Kazutaka Aonuma, Yoshihiko Saito, Takeshi KimuraSatoshi Yasuda, Naomasa Makita, Wataru Shimizu, Minoru Horie, Kengo Kusano

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2707-2714
Number of pages8
JournalCirculation Journal
Volume82
Issue number11
DOIs
Publication statusPublished - 2018
Externally publishedYes

Keywords

  • Arrhythmias
  • Heart failure
  • Lamin A/C
  • Phenotypes
  • Prognosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Clinical manifestations and long-term mortality in lamin A/C mutation carriers from a Japanese multicenter registry'. Together they form a unique fingerprint.

Cite this