Background: In prehypertrophic Fabry disease, low myocardial T1 values, reflecting sphingolipid storage, are associated with early structural and ECG changes. The correlations between T1 values and functional parameters have not been explored. Furthermore, the potential prognostic role of T1 in predicting disease worsening is still unknown. Methods: ECG, 2D echocardiography, cardiopulmonary test, and cardiac magnetic resonance were performed in 44 Fabry patients without left ventricular hypertrophy (35.7±14.5 years, 68.2% females). After a 12-month follow-up, clinical stability was evaluated using Fabry Stabilization Index. Results: At baseline, T1 values showed a negative correlation with left ventricular mass ( r =−0.79; P <0.0001), maximum wall thickness ( r =−0.79; P <0.0001), Sokolow-Lyon Index ( r =−0.54; P <0.0001), left atrial volume ( r =−0.49; P <0.0002), and Mainz Severity Score Index ( r =−0.61; P 20%) at follow-up. Higher left ventricular wall thickness (odds ratio, 2.61; CI, 1.04–6.57; P =0.04), left atrial volume (odds ratio, 1.24; CI, 1.02–1.51; P =0.03), and lower T1 values (odds ratio, 0.98; CI, 0.96–0.99; P =0.03) at baseline were independently associated with clinical worsening at follow-up. Conclusions: In prehypertrophic Fabry disease, low T1 values correlate with early electrocardiographic, morphological cardiac changes, and worsening of global disease severity but are not associated with functional abnormalities. The presence of low T1 values is a risk factor for disease worsening, thus representing a potential new tool in prognostic stratification and therapeutic approach.

Background—: The diagnostic reliability and pathophysiologic relevance of different noninvasive diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) are undefined. We tested the association between noninvasive diagnostic criteria for ARVC and the presence of low-voltage areas (LVAs) detected at electroanatomic voltage mapping (EAM). Methods and Results—: Noninvasive diagnostic criteria, including ECG, signal-averaged ECG (SAECG), and cardiac magnetic resonance (CMR) criteria, were compared with the presence and location of LVAs detected at right ventricular (RV) EAM in 17 patients (9 men) aged 50±16 years with biopsy specimen-proven ARVC. LVAs were found in 15 (88%) patients. Patients with surface ECG abnormalities showed a higher degree of RV involvement than those without ECG abnormalities (number of LVAs, 1.8±0.5 versus 0.9±0.6, respectively; P <0.01). A significant association was found between SAECG abnormalities and LVAs in the RV outflow tract ( P =0.03) but not between SAECG parameters and LVAs in other RV regions. Among CMR findings, RV delayed enhancement was more significantly associated with the distribution of LVAs (free wall, P <0.01; outflow tract, P <0.01; posteroinferior wall, P =0.02). Regional RV dysfunction also showed a good correlation with LVAs, with the most significant association being found with the free wall ( P =0.01), whereas RV fat infiltration at CMR was not correlated with LVAs. Conclusion—: In patients with ARVC, SAECG abnormalities correlate with the presence of LVAs selectively in the RV outflow tract, whereas surface ECG abnormalities are associated with a more diffuse RV involvement. Myocardial delayed enhancement is the CMR finding more strongly associated with LVAs, thus supporting the appropriateness of its inclusion among diagnostic criteria for ARVC.