Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure.

AIMS: Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding ß-myosin heavy chain (MYH7) or cardiac myosin-binding protein C (MYBPC3). The aim of the present study was to determine the prevalence and spectrum of mutations in both genes in German HCM and DCM patients and to establish novel genotype-to-phenotype correlations. METHODS AND RESULTS: Coding exons and intron flanks of the two genes MYH7 and MYBPC3 of 236 patients with HCM and 652 patients with DCM were sequenced by conventional and array-based means. Clinical records were established following standard protocols. Mutations were detected in 41 and 11% of the patients with HCM and DCM, respectively. Differences were observed in the frequency of splice site and frame-shift mutations in the gene MYBPC3, which occurred more frequently (P< 0.02, P< 0.001, respectively) in HCM than in DCM, suggesting that cardiac myosin-binding protein C haploinsufficiency predisposes to hypertrophy rather than to dilation. Additional novel genotype-to-phenotype correlations were found in HCM, among these a link between MYBPC3 mutations and a particularly large thickness of the interventricular septum (P= 0.04 vs. carriers of a mutation in MYH7). Interestingly, this correlation and a link between MYH7 mutations and a higher degree of mitral valve regurgitation held true for both HCM and DCM, indicating that the gene affected by a mutation may determine the magnitude of structural and functional alterations in both HCM and DCM. CONCLUSION: A large clinical-genetic study has unravelled novel genotype-to-phenotype correlations in HCM and DCM which warrant future investigation of both the underlying mechanisms and the prognostic use.

Congenital coronary artery fistulas in adults: concomitant pathologies and treatment.

BACKGROUND: Coronary artery fistula is a rare congenital malformation. Complications such as intracardiac shunts, endocarditis, myocardial infarction, aneurysm and sudden death can be observed. The purpose of this article is to present our experience with concomitant cardiac pathologies and discuss various therapeutic approaches including surgical and percutaneous intervention. MATERIALS AND METHODS: During 18,272 diagnostic cardiac catheterizations, coronary artery fistulas were identified incidentally in 10 patients (0.05%). There were 3 female and 7 male patients. The patients' ages ranged from 42 to 76 years. All patients with coronary artery fistula were preoperatively in New York Heart Association functional class and Canadian Cardiovascular Society class II or III. RESULTS: In addition to coronary artery fistula, coronary artery disease was detected in 4 patients (40%), a ventricular septal defect and an aneurysm of the sinuses of Valsalvae with aortic regurgitation in one patient (10%) and an anomalous origin of the LAD from the pulmonary trunk in one patient (10%) during cardiac catheterization. Four (40%) of the total of 10 patients had only coronary artery fistula. Surgical closure of the coronary artery fistula was performed in 7 patients (70%). An interventional fistula closure with a coil device was confirmed by cardiac catheterization in another 3 patients (30%). One patient of the latter group showed a small residual shunt from the LAD to the pulmonary trunk. No death or long-term morbidities could be observed. CONCLUSIONS: Coronary artery fistulas are incidentally diagnosed during coronary artery angiographies in adults and should be closed to prevent complications.