CARDIAC INVOLVEMENT IN A LARGE KINDRED WITH MYOTONIC-DYSTROPHY - QUANTITATIVE ASSESSMENT AND RELATION TO SIZE OF CTG REPEAT EXPANSION

Objective.-To evaluate and quantitate cardiac involvement in myotonic dystrophy and assess whether the size of the trinucleotide (cytosine-t hymine-guanine [CTG]) repeat expansion is a significant predictor of c ardiac abnormalities. Design.-Case-control study of a large kindred wi th myotonic dystrophy. Patients.-Ninety-one bloodline members of the k indred underwent clinical and cardiac evaluation with electrocardiogra ms, echocardiography (with Doppler in the majority of cases), and gene tic and neurologic evaluations. Affected individuals were age-matched to normal family members. Main Outcome Measures.-Electrocardiographic conduction abnormalities, wall motion abnormalities, mitral valve prol apse, and global parameters of systolic and diastolic function were de termined by an observer blinded to all clinical data and genetic analy sis. Results.-Compared with age-matched normals, patients with myotoni c dystrophy (n=25) were more likely to have conduction abnormality (52 % vs 9%), mitral valve prolapse (32% vs 9%), and wall motion abnormali ty (28% vs 0%) (all P<.05). Left ventricular ejection fraction and str oke volume were reduced compared with normals matched for age and hear t rate (P<.05), whereas Doppler indexes of diastolic function were onl y marginally altered. Using multivariate analysis, the number of CTG r epeats (range, 69 to 1367; normal, less than or equal to 37) was the s trongest predictor of abnormalities in wall motion and electrocardiogr aphic conduction (odds ratio of 16.5 and 5.07 per 500 repeats, respect ively). The relation of mitral valve prolapse to the size of the CTG r epeat was of borderline significance, Patients with more extensive neu rologic findings (n=12) had a higher incidence of wall motion and/or e lectrocardiographic conduction abnormalities (83% vs 43%; P=.04). Conc lusions.-Cardiac involvement in myotonic dystrophy affects predominant ly the conduction system and myocardial function. Alterations in myoca rdial relaxation and diastolic properties, in contrast to skeletal mus cle myotonia, are minor. In this kindred, the number of CTG repeats wa s a significant predictor of cardiac dysfunction in myotonic dystrophy .