ECG Changes during Adult Life in Fabry Disease: Results from a Large Longitudinal Cohort Study

Abstract

Background: Fabry disease (FD) is an X-linked, lysosomal storage disorder leading to severe cardiomyopathy in a significant proportion of patients. To identify ECG markers that reflect early cardiac involvement and disease progression, we conducted a long term retrospective study in a large cohort of FD patients. Methods: A total of 1995 ECGs from 133 patients with classical FD (64% females, 80% treated with enzyme replacement therapy), spanning 20 years of follow-up, were compared to ECGs from 3893 apparently healthy individuals. Generalized linear mixed models were used to evaluate the effect of age, FD and sex on: P-wave duration, PR-interval, QRS-duration, QTc, Cornell index, spatial QRS-T angle and frontal QRS-axis. Regression slopes and absolute values for each parameter were compared between FD patients and control subjects. Results: At a younger age (<40 years), the Cornell index was higher and frontal QRS-axis more negative in FD patients compared to controls (p < 0.05). For the other ECG parameters, the rate of change, more than the absolute value, was greater in FD patients compared to controls (p < 0.05). From the fifth decade (men) or sixth (women) onwards, absolute values for P-wave duration, QRS-duration, QTc and spatial QRS-T angle were longer and higher in FD patients compared to control subjects. Conclusions: ECG abnormalities indicative of FD are age and sex dependent. Tracking the rate of change in ECG parameters could be a good way to detect disease progression, guiding treatment initiation. Moreover, monitoring ECG changes in FD can be used to evaluate the effectiveness of treatment.

Increased cardiac involvement in Fabry disease using blood-corrected native T1 mapping

“…However, identifying early cardiac involvement is challenging. ECG is cheap and widely accessible technique with parameters of LVH showing alterations in early adulthood 16 . However, low native T1 has been shown to precede the development of LVH 10 , thus CMR plays an important role here.…”

Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking

“…Moreover, El Sayed et al performed an interesting comparison between AFD patients and a matched healthy subjects' cohort, showing that frontal QRS-axis is the earliest marker of cardiac disease being already significant in both male and female AFD patients aged 18–29 years. On the other hand, in addition to the description of the parameters changes over time, we provide distinct ECG patterns for each of the study group, which are able to describe the progressive cardiac involvement by the disease ( 39 ).…”