Sarcomere mutation negative hypertrophic cardiomyopathy is associated with ageing and obesity

Background Despite advances in our understanding of the genetic causes of hypertrophic cardiomyopathy (HCM), a large portion of this patient population do not carry sarcomere gene mutations when screened. It remains largely unknown why patients without sarcomere mutations develop asymmetric myocardial hypertrophy.Methods We performed a retrospective analysis of probands with HCM who underwent genetic testing to determine if clinical phenotypes were different depending on sarcomere mutation status. A medical history, three generation family history and clinical phenotyping were performed on 127 probands with HCM. Genetic screening was performed using clinically available HCM genetic testing panels.Results We found that probands with HCM with pathogenic sarcomere mutations were over three times more likely to have a family history of HCM (66% vs 17%, p<0.0001) and were diagnosed with HCM at a much younger age (32 vs 51 years old, p<0.0001). In contrast, probands with HCM without sarcomere mutations were significantly more obese (body surface area p=0.003, body mass index p=0.04 adjusted for age) and were more likely to present with left ventricular outflow tract obstruction (p=0.0483).Conclusion Patients with sarcomere mutation negative HCM present at an older age and are more obese compared with patients with sarcomere mutation positive HCM. The role of ageing and obesity in asymmetric myocardial hypertrophy warrants further investigation

Incremental prognostic value of visually estimated coronary artery calcium in patients undergoing positron emission tomography imaging

Objective Visually estimated coronary artery calcium (VECAC) from chest CT or attenuation correction (AC)/CT obtained during positron emission tomography (PET)–myocardial perfusion imaging (MPI) is feasible. Our aim was to determine the prognostic value of VECAC beyond conventional risk factors and PET imaging parameters, including coronary flow reserve (CFR).Methods We analysed 608 patients without known coronary artery disease who underwent PET–MPI between 2012 and 2016 and had AC/CT and/or chest CT images. We used Cox regression to estimate the association of VECAC categories (≤10, 11–400, >400 Agatston units (AU)) with the primary outcome of all-cause death, acute coronary syndrome or stroke (mean follow-up 4.3±1.8 years). C-statistics assessed the relationship between PET parameters and VECAC with the primary outcome.Results Mean age was 58±11 years, 65% were women and 67% were black. VECAC ≤10, 11–400 and >400 AU was observed in 68%, 12% and 20% of subjects, respectively. Compared with VECAC ≤10, VECAC categories 11–400 (HR 2.25, 95% CI 1.24 to 4.08) and >400 AU (HR 3.05, 95% CI 1.87 to 4.98) were associated with the primary outcome after adjusting for traditional risk factors, MPI findings and CFR. Adding VECAC to a model that included PET–MPI, CFR and clinical risk factors improved the prognostic value for the primary outcomes (c-statistic 0.71 to 0.75 with VECAC, p=0.01).Conclusions VECAC is a potent predictor of events beyond traditional risk factors and PET imaging markers, including CFR. These data further support the importance for routine VECAC implementation