Myocardial testosterone glucuronide and disease phenotypes in hypertrophic cardiomyopathy

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INTRODUCTION: The relationship between myocardial lipid metabolism and disease phenotypes, genetic variation, and prognostic factors in patients with hypertrophic cardiomyopathy (HCM) remains largely unexplored. This study aimed to clarify how metabolic remodelling relates to disease phenotypes in HCM. We used desorption electrospray ionization imaging mass spectrometry (DESI-IMS) to compare myocardial lipid signatures in patients who required septal reduction therapy (SRT) and those who did not. METHODS: In this prospective study, patients with HCM undergoing either right-ventricular biopsy or surgical septal myectomy were enrolled. Frozen 10 µm sections were analysed using DESI-IMS, and mass spectra were compared with volcano plots after signal-intensity normalization. Candidate ions showing |log2 fold change| ≥ 1 and P < .05 were annotated using the Human Metabolome Database. RESULTS: Overall, 61 patients were analysed (34 [55.7%] were female; mean age 64.5 ± 15.9 years). Of these, 43 (70.5%) had obstructive HCM and 20 underwent SRT (SRT, n = 20; non-SRT, n = 41). The SRT group displayed a 3.3-fold higher signal for m/z 463.23, identified as testosterone glucuronide (P < .001). SRT remained the only predictor of elevated testosterone-glucuronide intensity in confirmatory regression (β = 1.991, P = .004), even after adjusting for age at diagnosis and the presence of hypertension, which significantly differed in baseline characteristics between the SRT and non-SRT groups. CONCLUSION: DESI-IMS revealed selective accumulation of testosterone glucuronide in hypertrophied myocardium from patients needing SRT, suggesting that androgen-linked metabolic remodelling plays a role in advanced obstructive physiology in HCM.

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