Peripheral and cardiac determinants of exercise intolerance in classic Anderson-Fabry disease: insights from cardiopulmonary exercise testing and advanced echocardiography
- 1Department of Clinical Medicine and Surgery, Federico II University, Via Pansini 5, 80131 Naples, Italy
- 2Department of Public Health, Federico II University, Naples, Italy
Abstract
Background: Exercise intolerance is a common feature of Anderson-Fabry disease (AFD), but its underlying mechanisms remain incompletely understood.
Methods and results: We studied eighty-eight patients with classical AFD phenotype and preserved ejection fraction. Patients underwent cardiopulmonary exercise testing (CPET), lactate assessment, and advanced echocardiography including myocardial work and atrial strain analysis. Exercise tolerance was reduced across the cohort, with low peak VO2 measured as percent predicted (VO2%predicted) and early lactate accumulation. Peak VO2%predicted declined with worsening left ventricular geometry. Left ventricular diastolic parameters, myocardial work efficiency, and left atrial strain were associated with exercise capacity. In multivariable analysis, left atrial conduit strain emerged as a strong independent predictor.
Conclusions: Skeletal muscle energetic metabolism alterations primarily drive exercise intolerance in AFD and early cardiac dysfunction, assessed by advanced echocardiography further exacerbated it.
Graphical Abstract:
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BibTeX
@article{spinelli2026peripheral,
title = {{Peripheral and cardiac determinants of exercise intolerance in classic Anderson-Fabry disease: insights from cardiopulmonary exercise testing and advanced echocardiography}},
author = {Letizia Spinelli and Alessandra Cuomo and Antonio Bianco and Eleonora Riccio and Antonella Di Donato and Antonio Pisani and Guido Iaccarino},
journal = {Orphanet Journal of Rare Diseases},
year = {2026},
month = jul,
doi = {10.1186/s13023-026-04515-y},
url = {https://doi.org/10.1186/s13023-026-04515-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Peripheral and cardiac determinants of exercise intolerance in classic Anderson-Fabry disease: insights from cardiopulmonary exercise testing and advanced echocardiography
AU - Letizia Spinelli
AU - Alessandra Cuomo
AU - Antonio Bianco
AU - Eleonora Riccio
AU - Antonella Di Donato
AU - Antonio Pisani
AU - Guido Iaccarino
PY - 2026
DA - 2026/07/27
JO - Orphanet Journal of Rare Diseases
DO - 10.1186/s13023-026-04515-y
UR - https://doi.org/10.1186/s13023-026-04515-y
AB - Background: Exercise intolerance is a common feature of Anderson-Fabry disease (AFD), but its underlying mechanisms remain incompletely understood. Methods and results: We studied eighty-eight patients with classical AFD phenotype and preserved ejection fraction. Patients underwent cardiopulmonary exercise testing (CPET), lactate assessment, and advanced echocardiography including myocardial work and atrial strain analysis. Exercise tolerance was reduced across the cohort, with low peak VO2 measured as percent predicted (VO2%predicted) and early lactate accumulation. Peak VO2%predicted declined with worsening left ventricular geometry. Left ventricular diastolic parameters, myocardial work efficiency, and left atrial strain were associated with exercise capacity. In multivariable analysis, left atrial conduit strain emerged as a strong independent predictor. Conclusions: Skeletal muscle energetic metabolism alterations primarily drive exercise intolerance in AFD and early cardiac dysfunction, assessed by advanced echocardiography further exacerbated it. Graphical Abstract:
SN - 1750-1172
ER -