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

Mohamed El Sayed; Pieter G Postema; Mareen Datema; Laura van Dussen; Jan A Kors; Cato C Ter Haar; Hidde Bleijendaal; Henrike Galenkamp; Bert-Jan H van den Born; Carla E M Hollak; Mirjam Langeveld

doi:10.3390/diagnostics13030354

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

Diagnostics (Basel). 2023 Jan 18;13(3):354. doi: 10.3390/diagnostics13030354.

Authors

Mohamed El Sayed^{1

2}, Pieter G Postema^{3

4}, Mareen Datema^{1

2}, Laura van Dussen^{1

2}, Jan A Kors⁵, Cato C Ter Haar^{3

4}, Hidde Bleijendaal^{3

4

6}, Henrike Galenkamp^{7

8}, Bert-Jan H van den Born^{8

9

10}, Carla E M Hollak^{1

2}, Mirjam Langeveld^{1

2}

Affiliations

¹ Department of Internal Medicine, Division of Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
² Amsterdam Gastroenterology Endocrinology and Metabolism, Inborn Errors of Metabolism, 1105 AZ Amsterdam, The Netherlands.
³ Department of Cardiology, Heart Center, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
⁴ Amsterdam Cardiovascular Sciences, Heart Failure & Arrhythmias, 1105 AZ Amsterdam, The Netherlands.
⁵ Department of Medical Informatics, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
⁶ Department of Biostatistics & Bioinformatics, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
⁷ Department of Public and Occupational Health, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
⁸ Amsterdam Public Health, Health Behaviors and Chronic Diseases, 1105 AZ Amsterdam, The Netherlands.
⁹ Department of Vascular Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
¹⁰ Amsterdam Cardiovascular Sciences, Atherosclerosis & Ischemic Syndromes, 1105 AZ Amsterdam, The Netherlands.

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.

Keywords: Electrocardiogram (ECG); Fabry cardiomyopathy; Fabry disease; treatment evaluation.

Grants and funding

This work was supported by SPHINX, the Amsterdam Lysosome Center. The HELIUS study is conducted by the Amsterdam University Medical Centers, location AMC and the Public Health Service of Amsterdam. Both organizations provided core support for HELIUS. The HELIUS study is also funded by the Dutch Heart Foundation (grant number: 2010T084), the Netherlands Organization for Health Research and Development (ZonMw) (grant number: 200 500 003), the European Union, (FP-7) (grant number: 278 901), and the European Fund for the Integration of non-EU immigrants (EIF) (grant number: 2013EIF013). We are most grateful to the participants of the HELIUS study and the management team, research nurses, interviewers, research assistants and other staff who have taken part in gathering the data of this study.