Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers

详细信息    查看全文

• 作者：Saurabh Kumar ; BSc(Med)/MBBS ; PhD^a ; Samuel H. Baldinger ; MD^b ; Estelle Gandjbakhch ; MD ; PhD^c ; Philippe Maury ; MD^d ; Jean-Marc Sellal ; MD^e ; ^f ; ^g ; ^h ; Alexander F.A. Androulakis ; MDⁱ ; Xavier Waintraub ; MD^c ; Philippe Charron ; PhD^c ; ^j ; ^k ; Anne Rollin ; MD^d ; Pascale Richard ; PhD^l ; William G. Stevenson ; MD^a ; Ciorsti J. Macintyre ; MD^a ; Carolyn Y. Ho ; MD^a ; Tina Thompson ; RN^m ; Jitendra K. Vohra ; MDⁿ ; Jonathan M. Kalman ; MBBS ; PhDⁿ ; Katja Zeppenfeld ; MDⁱ ; Frederic Sacher ; MD^e ; ^f ; ^g ; Usha B. Tedrow ; MD ; MSc^a ; Neal K. Lakdawala ; MD^a ; ^{nlakdawala@partners.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：atrial fibrillation ; cardiomyopathy ; complete atrioventricular block ; genetics ; heart failure ; ventricular tachycardia
• 刊名：Journal of the American College of Cardiology
• 出版年：2016
• 出版时间：29 November 2016
• 年：2016
• 卷：68
• 期：21
• 页码：2299-2307
• 全文大小：777 K

文摘

Mutations in m>LMNAm> are variably expressed and may cause cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and ventricular arrhythmias (VA). Detailed natural history studies of m>LMNAm>-associated arrhythmic and nonarrhythmic outcomes are limited, and the prognostic significance of the index cardiac phenotype remains uncertain.

Objectives

This study sought to describe the arrhythmic and nonarrhythmic outcomes of m>LMNAm> mutation carriers and to assess the prognostic significance of the index cardiac phenotype.

Methods

The incidence of AVB, AA, sustained VA, left ventricular systolic dysfunction (LVD) (= left ventricular ejection fraction ≤50%), and end-stage heart failure (HF) was retrospectively determined in 122 consecutive m>LMNAm> mutation carriers followed at 5 referral centers for a median of 7 years from first clinical contact. Predictors of VA and end-stage HF or death were determined.

Results

The prevalence of clinical manifestations increased broadly from index evaluation to median follow-up: AVB, 46% to 57%; AA, 39% to 63%; VA, 16% to 34%; and LVD, 44% to 57%. Implantable cardioverter-defibrillators were placed in 59% of patients for new LVD or AVB. End-stage HF developed in 19% of patients, and 13% died. In patients without LVD at presentation, 24% developed new LVD, and 7% developed end-stage HF. Male sex (p = 0.01), nonmissense mutations (p = 0.03), and LVD at index evaluation (p = 0.004) were associated with development of VA, whereas LVD was associated with end-stage HF or death (p < 0.001). Mode of presentation (with isolated or combination of clinical features) did not predict sustained VA or end-stage HF or death.

Conclusions

m>LMNAm>-related heart disease was associated with a high incidence of phenotypic progression and adverse arrhythmic and nonarrhythmic events over long-term follow-up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis and subsequent follow-up, including anticipatory planning for therapies to prevent sudden death and manage HF, is warranted.