Natural history of cardiac involvement in women carrying pathogenic DMD gene variants: a 7-year longitudinal study

Cardiac involvement is increasingly recognized in women carrying pathogenic variants in the dystrophin (DMD) gene, both Duchenne and Becker-associated, but the long-term natural history of cardiac structure, function, and conduction abnormalities in this group is not well understood. We conducted a prospective 7-year follow-up study to investigate the evolution of ventricular function, myocardial fibrosis, and arrhythmias.

34 women with confirmed pathogenic DMD gene variants (19 predicted to cause Duchenne muscular dystrophy and 15 Becker muscular dystrophy) underwent assessments after a mean of 7 years. Evaluations included cardiac magnetic resonance imaging with late gadolinium enhancement, 24-h Holter monitoring, 12-lead electrocardiography (ECG), cardiac biomarkers, and clinical examinations.

At the group level, left ventricular ejection fraction (LVEF) remained stable over follow-up (p = 0.403). Six women had a ≥ 5% change in LVEF: three improved with treatment, and three declined by 5-8%. Fibrosis was present in 9 women at both baseline and follow-up; 3 showed visual progression, and no new cases were identified. Although the median ventricular premature contractions per hour (VPC/h) increased from 0.23/h to 6.38/h (p < 0.001), this increase is likely not clinically meaningful as age-related increases in ventricular ectopy are also seen in healthy populations, and high-burden arrhythmias-according to prespecified thresholds-remained uncommon. ECG parameters remained stable (PR, QRS, and QTc unchanged), with no new bundle-branch blocks or high-grade atrioventricular block detected. No association was observed between LVEF, VPC/h, and supraventricular premature contraction per hour over the 7-year follow-up period.

Over 7 years, women carrying pathogenic DMD gene variants have very little or no progression of cardiac findings (LVEF, fibrosis, and arrhythmias). Given these findings, frequent routine rhythm monitoring is not indicated. Follow-up should be risk-stratified: closer for women with symptoms, baseline high-burden ectopy, reduced LVEF, or pre-existing fibrosis; others can be reviewed at extended intervals.