Master's student McGill University Montréal, Quebec, Canada
Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder caused by bi-allelic pathogenic variants in the LDLR gene or compound heterozygosity. It is characterized by extreme elevations in low-density lipoprotein cholesterol (LDL-C) levels (>10 mmol/L), with an estimated prevalence of approximately 1 in 387,000 individuals. The objective of this study was to assess the prevalence, clinical presentation and contemporary therapeutic approaches for aortic stenosis in Canadian patients with HoFH.
METHODS AND RESULTS:
Methods: In this retrospective cohort study, individuals with a diagnosis of HoFH and alive at the inception of the Canadian HoFH Registry in 2008 were identified and included. Demographic data, lipid profiles and genetic testing results were collected prospectively from 2008 onward. 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%) or genetic confirmation (n=50, 78%) of HoFH. The median age at diagnosis was 14 years (interquartile range [IQR]: 6-31) and the median highest recorded LDL-C levels was 13 mmol/L (IQR: 10.6-16.3). Over a median follow-up of 27 years (IQR: 11-39) from the time of diagnosis, 17 patients (27%) developed moderate-to-critical aortic stenosis based on echocardiographic and/or hemodynamic criteria, and 13 patients (21%) underwent at least one surgical aortic valve procedure. Extensive calcification of the aortic valve and ascending aorta, combined with severe valvular and/or supravalvular stenosis necessitated complex surgical procedures, including aortic valve replacement with concomitant ascending aorta surgery (e.g. Bentall, Cabrol, or Ross procedures), aortic patch enlargement (e.g. Manougian procedure), endarterectomy, and coronary artery bypass grafting. Four transcatheter aortic valve replacements (TAVR) were performed in three patients, two of which ultimately failed. Several patients required more than one surgery. The median age at the time of the first aortic intervention was 44 years (IQR: 32-55). The complexity of surgical procedures and the need for multiple interventions significantly increased mortality and morbidity.
Conclusion: Moderate-to-critical aortic stenosis was observed in 27% of patients in the Canadian HoFH Registry, with 21% requiring invasive intervention. The severe aortic phenotype associated with HoFH requires complex, multidisciplinary surgical management in specialized centres with appropriate expertise.
