Pasotti M et al. (2008) Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol 52: 1250–1260

Individuals with mutations in the LMNA gene usually present with dilated cardiomyopathy, atrioventricular block and/or various types of myopathy, and almost half die suddenly. Pasotti and colleagues have performed a retrospective, longitudinal study to identify risk factors for major cardiovascular events, including sudden cardiac death (SCD), in patients with LMNA mutations.

Genotypes of 164 individuals (in 27 families) were analyzed, and 94 had LMNA mutations. The median follow-up time was 57 months. Events included in the analysis were death from any cause, death from heart failure, SCD or appropriate implantable cardioverter-defibrillator intervention, and heart transplantation. No events occurred in the 34 patients with LMNA mutations who showed no signs of disease; these patients were younger than the symptomatic patients and fewer had a history of competitive sport for 10 years or more. NYHA functional class III–IV and participation in competitive sport for 10 years or more were strong predictors of events in patients with LMNA mutations. The hazard ratio for an event was 5.20 (P <0.001) for patients with one of these risk factors, and 26.3 (P <0.001) for patients with both these risk factors, compared with patients with none. Cox bivariable analysis identified splice-site mutations and competitive sport for 10 years or more as predictors of SCD. Compared with patients who had neither of these risk factors, the hazard ratio for SCD was 3.67 (P = 0.003) for patients with one of these risk factors and 7.68 (P <0.001) for patients with both.