VO_2peak as a Key Marker of Cardiomyopathy Progression in Fabry Disease

PEAK oxygen uptake (VO_2peak) is significantly reduced in Fabry disease (FD), correlating with cardiomyopathy progression, highlighting its potential as a therapeutic marker.

Fabry disease is a rare, inherited disorder marked by the accumulation of sphingolipids in various organs, most notably the heart. Cardiac involvement is the primary driver of morbidity and mortality, with exercise intolerance being a common but poorly understood symptom. This study aimed to assess exercise capacity in FD and examine its relationship to cardiomyopathy severity.

This retrospective observational study evaluated 42 adults with FD who underwent cardiopulmonary exercise testing (CPEX) at a UK national referral centre between 2011 and 2023. Cardiomyopathy phases were classified on a four-point scale by expert consensus using imaging and biochemical data. The primary measure, peak oxygen uptake (VO_2peak), was compared against age-normalised and sex-normalised expected values, alongside forced expiratory volume in 1 second (FEV1) as a measure of respiratory function.

Results revealed a significant reduction in VO_2peak at all stages of cardiomyopathy, with an average deficit of 23% compared to normative values (p=0.006) even at phase I. VO_2peak declined progressively across cardiomyopathy phases (p=0.010), from 28.7±7.7 mL/kg/min in phase I to 21.2±6.1 mL/kg/min in phase IV. In contrast, normalised FEV1 showed no significant changes across phases (p=0.683). Impaired VO_2peak correlated with atrial dysfunction and elevated inflammatory markers, underscoring a likely cardiac origin for exercise intolerance.

The findings highlight VO_2peak as a potential clinical tool for assessing disease progression and therapeutic response in FD, given its sensitivity to early cardiac changes, even before overt cardiomyopathy develops. This reinforces the need for early, targeted interventions to mitigate the cardiac burden in FD. Future research should focus on validating VO_2peak as a marker of treatment efficacy and exploring its integration into routine clinical practice to optimise patient outcomes.

Reference

Roy A et al. Changes in peak oxygen consumption in fabry disease and associations with cardiomyopathy severity. Heart. 2024;DOI: 10.1136/heartjnl-2024-324553.