Patients with hypertrophic cardiomyopathy requiring septal reduction therapy had a 3.3-fold higher myocardial signal for testosterone glucuronide compared to those who did not (P<0.001).
Observational (n=61)
Does myocardial lipid metabolism differ between hypertrophic cardiomyopathy patients who require septal reduction therapy and those who do not?
Desorption electrospray ionisation imaging mass spectrometry reveals selective accumulation of testosterone glucuronide in the hypertrophied myocardium of HCM patients requiring septal reduction therapy, suggesting a role for androgen-linked metabolic remodeling in advanced obstructive physiology.
Effect estimate: 3.3-fold higher signal
p-value: p=<0.001
Abstract Aims 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 ionisation 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 between July 2020 and February 2024 were enrolled. Frozen 10-μm sections were analysed using DESI-IMS, and mass spectra were compared with volcano plots after signal-intensity normalisation. Candidate ions showing |log2 fold-change| ≥ 1 and P 0.05 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). Across all spectra, 40 ions differed significantly between groups. The SRT group displayed a 3.3-fold higher signal for m/z 463.23, identified as testosterone glucuronide (P 0.001). SRT remained the only predictor of elevated testosterone glucuronide intensity in confirmatory regression (β = 1.991, P = 0.004), 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. Within the SRT cohort, higher testosterone glucuronide intensity was associated with a lower prevalence of dyslipidaemia, lower heart rate, lower haemoglobin A1c levels, and lower left ventricular ejection fraction (LVEF). These associations were significant both in unadjusted analyses (P = 0.005, 0.023, 0.002, and 0.021) and after adjustment for age (P = 0.042, 0.009, 0.014, and 0.049, respectively). There was a modest inverse relationship between log-transformed testosterone glucuronide intensity and LVEF (r = −0.537, P = 0.015). No region-restricted metabolites were detected in the spatial mapping using myectomy samples. Conclusions 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. The use of sizeable myectomy tissue strengthened the spatial metabolomic analysis and supports testosterone glucuronide as a potential biomarker of advanced obstructive phenotype and early systolic impairment. These findings encourage larger, genotype-integrated studies to validate testosterone glucuronide as a therapeutic or prognostic target in HCM.
Ikoma et al. (Wed,) conducted a observational in Hypertrophic cardiomyopathy (n=61). Septal reduction therapy (SRT) vs. No septal reduction therapy (non-SRT) was evaluated on Myocardial lipid signatures (testosterone glucuronide intensity) (3.3-fold higher signal, p=<0.001). Patients with hypertrophic cardiomyopathy requiring septal reduction therapy had a 3.3-fold higher myocardial signal for testosterone glucuronide compared to those who did not (P<0.001).