Heart failure guideline-directed medical therapy in young adults with dystrophin-related cardiomyopathy: the HOPE-MD registry

BACKGROUND: Duchenne (DMD) and Becker (BMD) muscular dystrophies often progress to dilated cardiomyopathy and heart failure with reduced ejection fraction (HFrEF), a major cause of death in affected patients. Although guideline-directed medical therapy (GDMT) improves HFrEF outcomes, its real-world use in dystrophinopathies is poorly defined. We assessed GDMT utilization and optimization in the study population. METHODS: HOPE-MD is a European, multicentre, retrospective registry including adults with genetically confirmed DMD or BMD and left ventricular ejection fraction (LVEF) ≤40%. GDMT was defined as concurrent use of a renin-angiotensin system inhibitor (RASi), beta-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter-2 inhibitor (SGLT2i). Doses were categorized as target (≥100%), intermediate (50-99%), or low (<50%). RESULTS: Among 274 patients (age, 28 years; LVEF, 35%; DMD, 80%), 44 (16%) received GDMT at baseline, with only one quarter at ≥50% of the target dose. Underutilization was greatest for MRAs (n=140, 51%) and SGLT2i (n=60, 22%), whereas RASi (n=246, 90%) and beta-blockers (n=235, 86%) were frequently prescribed. After 24 months (n=141), 40% received GDMT, and 22% received ≥50% of the target dose, primarily through MRA and SGLT2i initiation/uptitration. Contraindications accounted for only a small proportion of undertreatment. At a median follow-up of 2.2 (1.7-2.6) years, optimized GDMT was not associated with a statistically significant difference in the rates of death or HF hospitalization compared with low-dose or no GDMT (adjusted HR 0.70, 95% CI 0.28-1.74). CONCLUSIONS: GDMT use and dose escalation were suboptimal in European patients with DMD/BMD and HFrEF.