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J Am Coll Cardiol. 2008 Oct 7;52(15):1250-60. doi: 10.1016/j.jacc.2008.06.044.

Long-term outcome and risk stratification in dilated cardiolaminopathies.

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1
Centre for Inherited Cardiovascular Diseases, Molecular Diagnostic Laboratory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Abstract

OBJECTIVES:

The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies.

BACKGROUND:

Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiology setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrioventricular block (AVB) constitute the majority of reported cases.

METHODS:

Longitudinal retrospective observational studies were conducted with 27 consecutive families in which LMNA gene defects were identified in the probands, all sharing the DCM phenotype.

RESULTS:

Of the 164 family members, 94 had LMNA gene mutations. Sixty of 94 (64%) were phenotypically affected whereas 34 were only genotypically affected, including 5 with pre-clinical signs. Of the 60 patients, 40 had DCM with AVB, 12 had DCM with ventricular tachycardia/fibrillation, 6 had DCM with AVB and Emery-Dreifuss muscular dystrophy type 2 (EDMD2), and 2 had AVB plus EDMD2. During a median of 57 months (interquartile range 36 to 107 months), we observed 49 events in 43 DCM patients (6 had a later event, excluded from the analysis). The events were related to heart failure (15 heart transplants, 1 death from end-stage heart failure) and ventricular arrhythmias (15 sudden cardiac deaths and 12 appropriate implantable cardioverter-defibrillator interventions). By multivariable analysis, New York Heart Association functional class III to IV and highly dynamic competitive sports for >or=10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted sudden cardiac death.

CONCLUSIONS:

Dilated cardiomyopathies caused by LMNA gene defects are highly penetrant, adult onset, malignant diseases characterized by a high rate of heart failure and life-threatening arrhythmias, predicted by New York Heart Association functional class, competitive sport activity, and type of mutation.

PMID:
18926329
DOI:
10.1016/j.jacc.2008.06.044
[Indexed for MEDLINE]
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