ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2026
Progressive Conduction System Disease Preceding Hypertrophy in IVS4 + 919G > A Fabry Variant: a Population-based Electrocardiographic Study.
Article in Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe IVS4 + 919G > A variant is the most prevalent late-onset Fabry variant in East Asian populations, but its electrophysiological trajectory remains incompletely defined.
methodsFrom a regional genetic screening program, 905 IVS4 + 919G > A carriers were identified among 457,581 patients and matched 1:2 to controls by age and sex. Electrocardiographic (ECG) parameters were compared across decades, and echocardiography correlated structural changes with ECG findings.
resultsThe cumulative prevalence of IVS4 + 919G > A was 0.198%. Age-specific prevalence in females was ∼2.5-fold higher than in males (0.11-0.15%), without significant change throughout different age categories. Female carriers demonstrated the catch-up phenomenon after the age of 60. Males exhibited a 9-fold risk of right bundle branch block (RBBB) and pacemaker implantation (PPM) compared with male controls (RBBB, HR 9.286, 95% CI 5.16-16.70, P < 0.001; PPM, HR 9.197, 95% CI 2.88-29.31, P < 0.001), and this precedes the onset of echocardiographic left ventricular hypertrophy. Risk of stroke and atrial fibrillation (HR 1.435, 95% CI 0.69-2.96, P = 0.289) was similar between male carriers and controls. PR interval was not shortening and prolongs instead. Combining left ventricular hypertrophy with conduction abnormalities, ECG detection achieved 88% sensitivity, exceeding echocardiographic criteria alone (51.5%).
conclusionsIVS4 + 919G > A variant is characterized by a progressive electrical phenotype dominated by conduction system disease preceding hypertrophy without excess major arrhythmic events. Electrocardiographic surveillance and phenotype-based risk stratification may be more informative than structural assessment alone for identifying individuals at risk of device therapy.
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