Sarcomere positive and negative hypertrophic cardiomyopathy – two distinct pathophysiological entities? (Dr Zakariye Ashkir)

The prediction, prevention and treatment of clinical events in hypertrophic cardiomyopathy (HCM) can be challenging due to marked heterogeneity seen in disease expression and clinical manifestations.

Recent studies suggest that HCM patients with sarcomeric mutations may be phenotypically distinct and exhibit a higher burden of clinical events that those without.

Whether or not pathophysiological mechanisms that contribute to adverse outcomes differ among HCM patients based on genotype status is unknown.

Cardiovascular magnetic resonance (CMR) provides a safe and reproducible way to comprehensively assess the heart for numerous microstructural and metabolic abnormalities that define the HCM phenotype. These include myocyte disarray, fibrosis, microvascular dysfunction and changes in oxygenation and energetics.

We hypothesize that sarcomere positive HCM will exhibit quantitative and qualitative differences in structural and metabolic substrates on CMR when compared to sarcomere negative disease.

The proposed study will compare the prevalence, extent and distribution of myocyte disarray, fibrosis, microvascular dysfunction and changes in oxygenation and metabolism in HCM with and without sarcomeric mutations while assessing their relationship with arrhythmic events.

Novel genetic insights into mechanisms that promote adverse outcomes are likely to arise from this work and could assist the development of targeted therapeutics for the management of HCM patients.