Electrocardiogram evolution in Anderson-Fabry disease patients during follow-up

Abstract Background Anderson-Fabry disease (AFD) is a rare and progressive X-linked metabolic disorder caused by mutations in alfa galactosidase A gene, which leads to a pathologic, multiorgan, accumulation of ceramides with cytotoxic, proinflammatory and fibrotic effects. Cardiovascular involvement represents one of the main causes of death. Although ECG has proven to be useful for early AFD recognition, little evidence is available on the evolution of ECG alterations during follow-up. Purpose and Methods The aims of the study were to describe ECG changes during a long-term follow up, and to evaluate their association with the progression of cardiac involvement. The presence of interactions between ECG changes and specific AFD therapy (treatment status) were also evaluated. 219 AFD patients from a multicentre cohort underwent 12-lead ECG extensive analysis, transthoracic echocardiography, and complete clinical evaluation. Results After the exclusion of 3 patients with a permanent pacemaker, 5 with poor ECG quality, 2 with only one ECG, and 18 ≤18 years old, 181 AFD patients composed the final cohort (age 46 [IQR 35-58], 36% male, 67% classic phenotype). Treatment status (either enzyme replacement or chaperone molecules) was distributed as follows: chronic therapy for at least one year (24%), specific therapy started during the follow up (39%), no specific therapy (37%). During a median follow up of 62 months (IQR 33-83 months), several ECG parameters showed significant changes: atrial fibrillation detection (p<0.001), PQ interval (p=0.004), left atrial enlargement (p=0.001), a new right bundle branch block (RBBB, p<0.001), QRS interval (p<0.001) and QRS fragmentation (p=0.022), QTcB interval (p=0.001), and negative T waves development (p=0.001) mostly lateral and symmetric (p=0.016). Among these, PQ interval showed a significant interaction with treatment status being significantly altered only in patients in the chronic therapy and no specific therapy groups, being stable in patients who started the specific therapy during the follow up (p for interaction=0.048). In addition, PQ, QRS interval duration, a new RBBB, and a new pathologic QT interval were associated with the evolution of the echocardiographic maximal left ventricular (LV) wall thickness during the follow up on univariable analysis, with the QRS duration losing the statistical significance on multivariable analysis but still showing a trend (p=0.089) toward an association with an increased LV wall thickness. Conclusions In this multicentric cohort of AFD patients, different ECG parameters underwent significant changes during follow-up. Of these, PQ interval duration showed a significant interaction with the specific therapy status in that it did not increase in patients who started the therapy at the begin of the follow up. PQ interval, a new RBBB and pathologic QTc development were also significantly associated with the progression of LV hypertrophy on multivariable analysis.Table 1 and Table 2Figure 1