Clinical and Genetic Aspects of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disease and characterized by extreme clinical and genetic heterogeneity. Information on the prognostic value of genotype is currently limited. In this thesis, we compared the clinical phenotype and outcome of genotype-positive and genotype-negative patients with HCM during long-term follow-up; genotype-positive status was an independent risk factor of mortality. In addition, we analyzed the clinical findings and outcome in patients with Dutch Myosin-Binding Protein C founder mutations and found no difference in comparison to patients with nonfounder mutations. Guidelines have encouraged HCM family screening since 2003. We evaluated the results of contemporary HCM family screening including genetic testing (GT). GT allowed the reassurance and discharge of many genotype-negative relatives. First cardiac evaluation revealed HCM in 30% of the relatives. During 7 years echocardiographic follow-up of the relatives without HCM, 16% developed subtle HCM. The 8-year prognosis of both relatives with and without HCM was overall good. Prior studies have identified pre-phenotypic markers in genotype-positive phenotype-negative relatives. We assessed the prognostic significance of anterior mitral valve leaflet (AMVL) length and global longitudinal strain (GLS) for the development of HCM in genotype-positive phenotype-negative relatives; both measurements had no prognostic value. Prior studies have demonstrated the usefulness of three-dimensional echocardiography (3DE) images in patients with HCM. We analyzed 3DE images in patients with HCM and healthy controls and identified a spiral pattern of left ventricular hypertrophy and enlarged papillary muscles in the patients with HCM. Patients with a cardiac implantable electronic device (CIED) often have continuous monitoring of atrial activity, allowing the detection of subclinical atrial fibrillation (AF). We found an annual 7% incidence of AF in patients with a CIED. Gender has been proposed to impact the phenotype and outcome of HCM. We observed that female patients with HCM presented at a later age in a worse condition than male patients. There was no independent association between gender and outcome. Cellular analysis revealed more severe cardiac remodeling in females than in males at the time of myectomy.

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