CMR imaging predictors of reduced functional capacity in Fabry cardiomyopathy

Background Cardiac involvement in Fabry disease (FD) manifests as left ventricular hypertrophy (LVH), often complicated by myocardial fibrosis, leading to progressive functional limitation. We aimed to investigate the mechanisms underlying functional impairment in patients with FD cardiomyopathy by examining the relationship between cardiovascular magnetic resonance (CMR) derived parameters and exercise performance (assessed by cardiopulmonary exercise test, CPET). Methods 36 patients with genetic diagnosis of FD (21 men; mean age 51.6 ± 13.3 years) enrolled in the OPTIMA-FD study, all presenting with FD cardiomyopathy, defined by the presence of LVH, underwent CPET and CMR. Moderate-to-severe functional impairment was defined as a peak oxygen consumption (peak VO2) <70% of the predicted value for age and sex. Multivariable logistic regression analysis was performed to identify independent CMR predictors. Logarithmic regression models were used to assess nonlinear relationships between peak VO2 and left ventricular mass index (LVMI) and late gadolinium enhancement (LGE) extent. Results LGE burden was independently associated with moderate-to-severe functional impairment (p=0.020; OR 1.296, 1.042–1.613), indicating that each 1% increase in LGE corresponded to a 29.6% higher likelihood of reduced functional capacity. (Table) LVMI (p=0.446) and native T1 z-score (p=0.096) were not independent predictors. Logarithmic regression demonstrated a significant inverse relationship between LGE extent and peak VO2 (R²=0.258, p=0.013), indicating that increasing myocardial fibrosis was associated with progressively lower exercise capacity. In contrast, LVMI showed a non-significant inverse relationship with peak VO2 (R² = 0.051, p=0.187). (Figure 1) Conclusions In patients with FD cardiomyopathy, LGE is an independent determinant of functional impairment supporting central role of myocardial fibrosis as a key determinant of impaired exercise capacity in FD-cardiomyopathy and highlight the incremental value of a multiparametric CMR approach integrated with CPET for comprehensive functional evaluation.TableFigure