Aortic Stenosis in Homozygous Familial Hypercholesterolemia

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extreme elevations in low-density lipoprotein cholesterol levels and premature cardiovascular disease. OBJECTIVES: The objective of this study was to assess the prevalence, clinical presentation, and current therapeutic approaches for aortic stenosis in Canadian patients with HoFH. METHODS: Demographic data, lipid profiles, and genetic testing results for patients with HoFH were collected prospectively since 2008. Reports from echocardiography, cardiac catheterization, and surgical or transcatheter interventions involving the aortic valve and/or ascending aorta were retrieved from medical records. RESULTS: Data were available for 63 patients with either a clinical diagnosis (n = 14, 22.2%) or genetic confirmation (n = 49, 77.8%) of HoFH. The median age at diagnosis was 14.0 years (Q1-Q3: 6.0 to 31.0), the median highest recorded low-density lipoprotein cholesterol level was 13.0 mmol/L (Q1-Q3: 10.6-16.3), and 17 patients (27.0%) developed moderate-to-severe aortic stenosis. Extensive calcification of the aortic valve and ascending aorta, combined with severe valvular and/or supravalvular stenosis and coronary ostial stenosis, necessitated complex and often consecutive surgical procedures. Six transcatheter aortic valve replacements were performed in 4 patients, 4 of which failed. Thirteen patients (20.6%) underwent at least 1 surgical aortic valve procedure. Patients developed aortic stenosis at a young age despite intensive treatment, including lipoprotein apheresis started at an early age. CONCLUSIONS: Moderate-to-severe aortic stenosis was observed in 27.0% of patients in the Canadian HoFH Registry, with 20.6% requiring invasive intervention. The severe aortic phenotype associated with HoFH requires complex, multidisciplinary surgical management in specialized centers with appropriate expertise.