Hypertrophic cardiomyopathy (HCM) is a disease, which is difficult to diagnose at an early stage and for which there is a pressing need for more effective treatment options. The purpose of this study was to compare the molecular profile of HCM to that of ischaemic cardiomyopathy (ISCM) and dilated cardiomyopathy (DCM) for identification of protein and pathway targets that could support the development of better diagnostic and treatment options for HCM. A high-throughput mass spectrometry workflow was applied to achieve deep quantitative coverage of left ventricular tissue from HCM, DCM, ISCM and non-heart-failure control patients. HCM had a diverse proteomic profile compared to that of DCM and ISCM. Differentially expressed proteins unique to HCM were identified based on an observed fold change of ≥1.5 or ≤0.67 and q-value ≤ 0.05. Candidate proteins of interest were found to be significantly associated with clinical features of HCM. The significant association between these proteins and HCM was validated in an independent dataset. This represents one of the largest and deepest proteomic datasets for myocardial tissue reported to date. The dataset highlights the diverse proteomic profile of HCM, relative to other cardiomyopathies, and reveals disease-relevant pathways and promising biomarker candidates that are uniquely associated with HCM.

Background: The aim of this study was to systematically review the recently published literature and determine the prevalence of left ventricular apical aneurysm (LVAA) formation in hypertrophic cardiomyopathy and its association with sudden cardiac death, systemic embolization, and heart failure. Methods: The protocol was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42023453640). MEDLINE and manual searches for articles published up to August 2023 were performed. Longitudinal, observational cohorts of unselected adult patients with hypertrophic cardiomyopathy were considered. Data were pooled using a random‐effects model. Results: A total of 321 articles fulfilled the search criteria, and 10 retrospective observational studies were selected for the meta‐analysis. The pooled prevalence of LVAA was 3% (95% CI, 2%–5%), and 57% of LVAAs were small (<2 cm). Small LVAAs had a lower prevalence of sudden cardiac death end points (4.71% [95% CI, 1.5%–9%) than bigger (≥2 cm) LVAAs (22% [95% CI, 15%–31%), with an odds ratio of 4.65 (95% CI, 2.14–10.10). The prevalence of systemic emboli was also higher in bigger LVAAs (17% [95% CI, 9%–28%) when compared with small LVAA (9% [95% CI, 4%–16%), with an odds ratio of 1.78 (95% CI, 0.53–5.99). Left ventricular thrombi were also more frequently detected in bigger LVAAs (30% [95% CI, 20%–42%) than small LVAAs (2% [95% CI, 0%–6%), with an odds ratio of 10.92 (95% CI, 3.75–31.84). There are scant data on heart failure deaths. Conclusions: The available data suggest that patients with bigger LVAAs (>2 cm) have the highest risk of poor outcomes and could be preferentially targeted for primary prevention of sudden cardiac death and systemic embolization.