Arrhythmias & electrophysiology
Early Atrial Remodeling Drives Arrhythmia in Fabry Disease
Authors' conclusion
These findings provide novel insights into underpinning mechanisms for atrial arrhythmia and a rationale for early P-wave changes in FD. These may be targeted to develop therapeutic strategies to reduce the arrhythmic burden in FD.
Study context
- Population
- Adults with Fabry disease (FD) at varying cardiomyopathy stages, compared with non-FD controlsadults with FD
- Participants
- 115 adults
- Exposure
- ECG P-wave characteristics in FD vs non-FD controls; GLA p. N215S iPSC-CMs vs wild-type iPSC-CMs
- FD adultsn = 115
- Outcome
- P-wave duration and PQ interval
- Follow-up
- Before the onset of cardiomyopathy
Methodological detailsgenome-edited using Clustered Regularly Interspaced Short Palindromic Repeats-Cas9, Bi-atrial in silico models
- Genome-edited using Clustered Regularly Interspaced Short Palindromic Repeats-Cas9
- Bi-atrial in silico models
Main finding
As reported in the abstract
- P-wave duration and PQ interval shortening in FD adults before the onset of cardiomyopathy
Observational data: associations, not effects.
Further findings
Premature atrial contractions and atrial fibrillation
- Higher incidence of premature atrial contractions and increased risk of atrial fibrillation in FD compared with healthy controls
α-Gal A and globotriaosylceramide in GLA p. N215S iPSC-CMs
- Deficient in α-Gal A and exhibited globotriaosylceramide accumulation
Electrophysiology, contraction and calcium handling of atrial iPSC-CMs
- More positive diastolic membrane potential, faster action potential upstroke velocity, greater incidence of delayed afterdepolarizations, greater contraction force, and alterations in calcium handling vs wild-type iPSC-CMs
In silico atrial simulations
- Similar P-wave morphology changes to those in early FD cardiomyopathy and increased atrial fibrillation vulnerability
Original publication
Early Atrial Remodeling Drives Arrhythmia in Fabry Disease. Circ Arrhythm Electrophysiol. Published 25 June 2025. doi:10.
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