Applying Shared Decision Making to Sports Participation for a Patient With Hypertrophic Cardiomyopathy.

A patient with hypertrophic cardiomyopathy and a cardio-defibrillator implanted for primary prevention would like to compete on the ski team at his school. This case illustrates how a shared decision-making approach can be applied when counseling patients with hypertrophic cardiomyopathy about exercise and sports participation. (Level of Difficulty: Intermediate.).

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.

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.

Alterations in sarcomere function modify the hyperplastic to hypertrophic transition phase of mammalian cardiomyocyte development.

It remains unclear how perturbations in cardiomyocyte sarcomere function alter postnatal heart development. We utilized murine models that allowed manipulation of cardiac myosin-binding protein C (MYBPC3) expression at critical stages of cardiac ontogeny to study the response of the postnatal heart to disrupted sarcomere function. We discovered that the hyperplastic to hypertrophic transition phase of mammalian heart development was altered in mice lacking MYBPC3 and this was the critical period for subsequent development of cardiomyopathy. Specifically, MYBPC3-null hearts developed evidence of increased cardiomyocyte endoreplication, which was accompanied by enhanced expression of cell cycle stimulatory cyclins and increased phosphorylation of retinoblastoma protein. Interestingly, this response was self-limited at later developmental time points by an upregulation of the cyclin-dependent kinase inhibitor p21. These results provide valuable insights into how alterations in sarcomere protein function modify postnatal heart development and highlight the potential for targeting cell cycle regulatory pathways to counteract cardiomyopathic stimuli.