Severe dilated cardiomyopathy in females with dystrophinopathy : a case series of nine patients.

Females heterozygous for a variant in the DMD gene may develop dilated cardiomyopathy; however, progression to severe heart failure is uncommon, and heart transplantation in this population has rarely been reported. We describe nine females with dystrophinopathy and severe cardiac involvement: five underwent heart transplantation, one received a left ventricular assist device, one died from end-stage heart failure, and two remain on medical therapy. Overall, heart transplantation was well tolerated and effective, with 8-11 years of follow-up available for four patients. Immunostaining of explanted hearts from two patients showed mosaic dystrophin expression without evidence of skewed X-chromosome inactivation, suggesting additional genetic or environmental modifiers. These findings highlight the importance of regular cardiac surveillance in all females heterozygous for a DMD variant-particularly during pregnancy and the postpartum period and in families with severe cardiac involvement-and support heart transplantation as a viable option in end-stage heart failure.