No abstract

the proposed concept of a lifelong calculated follow-up is a useful strategy in the risk stratification of SD. Multiple FHSD is a very ominous risk factor with strong impact, predicting frequent SD episodes in the early period of life.

The effect of sotalol on exercise tolerance and incidence of arrhythmias was studied in 30 patients with hypertrophic cardiomyopathy (HCM). In this short-term, double-blind, crossover study, exercise time on sotalol (320 mg/day) was significantly longer than on placebo (10.6 ± 4.0 vs. 9.4 ± 3.6 min; p < 0.01). Sotalol eliminated supraventricular arrhythmias in 6 of 7 patients (p < 0.03) and suppressed ventricular arrhythmias in 7 of 13 patients in whom they were present on placebo (p < 0.05). Ventricular tachycardia was abolished in 4 of 8 patients, but appeared during sotalol treatment in 1 patient who was free of repetitive arrhythmias on placebo. Twenty-five patients who had better exercise tolerance on sotalol than on placebo and did not experience aggravation of arrhythmia entered a 6-month prospective, open-label treatment with sotalol (160-480 mg/day, mean ± SD377 ± 94). One patient was withdrawn after 1 month because of bronchospasm. Mean exercise time improved from 9.8 ± 3.6 min on placebo to 12.7 ± 3.2 min (p < 0.01) after 6 months of treatment with sotalol. During the prospective follow-up, sotalol abolished ventricular tachycardia in all 6 patients after 1 month (p = 0.022), and in 4 of 6 patients (p > 0.2) after 6 months of treatment. It is concluded that sotalol significantly improves exercise tolerance and is effective in suppressing both supraventricular and ventricular arrhythmias in patients with HCM.

Hypertrophic cardiomyopathy (HCM) is a frequent, autosomal-dominant cardiac disease and manifests predominantly as left ventricular hypertrophy. Mutations in the cardiac beta-myosin heavy chain gene (MYH7) are responsible for the disease in about 30% of cases where mutations were identified. We clinically evaluated a large group of 147 consecutive HCM patients from three cardiology centers in Germany, Poland, and Kyrgyzstan according to the same protocol. The DNA of the patients was systematically analyzed in the whole coding region of the MYH7 gene using PCR, single-strand conformation polymorphism analysis, and automated sequencing. Eleven different missense mutations (including seven novel ones) in 11 unrelated patients were identified, showing a mutation frequency of 7.5% in the study population. We further examined the families of five patients (three of German, one of Polish, and one of Kyrgyz origin) with 32 individuals in total. We observed a clear, age-dependent penetrance with onset of disease symptoms in the fourth decade of life. Genotype-phenotype correlations were different for each mutation, whereas the majority was associated with an intermediate/malign phenotype. In conclusion, we report a systematic molecular screening of the complete MYH7 gene in a large group of consecutive HCM patients, leading to a genetic diagnosis in 38 individuals. Information about the genotype in an individual from one family could be very useful for the clinician, especially when dealing with healthy relatives in doubt of their risk about developing HCM. The increasing application of genetic screening and the increasing knowledge about genotype-phenotype correlations will hopefully lead to an improved clinical management of HCM patients.

Heiko Witt should have been included as the eleventh author of this paper. His affiliation is Charité