Advanced electrocardiography predicts cardiac involvement and incident arrhythmias in Fabry disease

BackgroundFabry disease (FD) is an X-linked disorder with progressive myocardial sphingolipid deposition, causing premature cardiovascular morbidity and mortality. Advanced electrocardiography (A-ECG) has the potential to predict cardiac involvement. ObjectivesTo evaluate the predictive power of A-ECG in identifying: 1) early cardiac involvement defined as low myocardial T1 on cardiovascular magnetic resonance (CMR), 2) adverse cardiovascular outcomes, and 3) heart age. MethodsIn this longitudinal multi-centre study, patients underwent same-day CMR and digital ECG, analysed using in-house software, including conventional ECG, derived vectorcardiographic, and singular value decomposition measures of waveform complexity parameters. Significant A-ECG variables were identified using stepwise forward regression and incorporated in a multivariable logistic regression A-ECG score. A Youden index was applied to identify best threshold score and bootstrapping performed to calculate the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, and 95% confidence intervals (CI). ResultsIn 155 patients (40% male, age 46{+/-}14 years, 39% on enzyme replacement therapy), left ventricular mass was higher in males compared to females (106 vs. 59 g/m2, p<0.001), 80% had low native T1, and 51% (70/136) had late gadolinium enhancement. A-ECG heart age was higher than chronological age in all patients (57{+/-}20 vs. 46{+/-}14 years, p<0.001). The heart age gap was strongly associated with T1 lowering and progressive LVH. Multivariable A-ECG scores for detecting low T1 had an AUC [95%CI] of 0.82 [0.75-0.89], sensitivity 72 [55-95] %, and specificity 85 [66-71] %; any arrhythmia 0.89 [0.82-0.95], 82 [68-94] %, 88 [70-96] %; or atrial fibrillation 0.89 [0.80-0.96], 92 [77-100] %, 83 [76-92] %, respectively. No predictors of heart failure hospitalisation or mortality were found. ConclusionA-ECG analysis has good diagnostic performance for predicting low native T1 and the occurrence of arrhythmias in Fabry disease but not for heart failure hospitalisation or death.