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Myocardial testosterone glucuronide and disease phenotypes in hypertrophic cardiomyopathy

Takenori Ikoma1,2, Keitaro Akita1, Kazuto Ohno1

  • 1Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Japan.

ESC Heart Failure
|February 19, 2026
PubMed

Insights

Hypertrophic cardiomyopathy (HCM) patients needing septal reduction therapy show higher myocardial testosterone glucuronide levels. This suggests androgen metabolism is linked to advanced obstructive HCM, impacting disease phenotypes.

Area of Science:

  • Cardiovascular Medicine
  • Metabolomics
  • Biochemistry

Background:

  • Myocardial lipid metabolism's role in hypertrophic cardiomyopathy (HCM) phenotypes is understudied.
  • Understanding metabolic changes in HCM is crucial for identifying disease drivers and prognostic factors.

Purpose of the Study:

  • To investigate the relationship between myocardial lipid metabolism and disease phenotypes in HCM patients.
  • To compare lipid signatures in HCM patients who underwent septal reduction therapy (SRT) versus those who did not.

Main Methods:

  • Desorption electrospray ionization imaging mass spectrometry (DESI-IMS) was used to analyze myocardial lipid profiles.
  • Frozen myocardial tissue sections from 61 HCM patients were analyzed.
  • Mass spectra were compared, and significant ions were annotated using the Human Metabolome Database.

Main Results:

  • Patients requiring SRT showed significantly higher levels of testosterone glucuronide (m/z 463.23) compared to non-SRT patients.
  • Testosterone glucuronide levels were strongly associated with the need for SRT, even after adjusting for clinical factors.
  • This finding highlights a specific metabolic alteration in advanced obstructive HCM.

Conclusions:

  • Selective accumulation of testosterone glucuronide in the hypertrophied myocardium of HCM patients needing SRT was identified.
  • Androgen-linked metabolic remodeling may contribute to the advanced obstructive physiology observed in HCM.
  • DESI-IMS is a valuable tool for uncovering metabolic signatures in cardiovascular diseases.
Abstract

Keywords:
Desorption electrospray ionization imaging mass spectrometryHypertrophic cardiomyopathySeptal reduction therapyTestosterone glucuronide

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