Heart failure treatment optimization in patients with dystrophin-related muscular dystrophy and HFrEF

Abstract Background and aim Muscular dystrophy (MD) includes inherited disorders causing progressive muscle wasting, often with cardiac involvement. Duchenne (DMD) and Becker (BMD) dystrophies frequently lead to HFrEF, a major cause of mortality. While guideline-directed medical therapy for HF (GDMT) may improve survival and quality of life, data are lacking. This study evaluates GDMT utilization in MD patients with HFrEF in a contemporary multinational real-world cohort. Methods HOPE-MD (Heart failure OPtimization in patiEnts with Muscular Dystrophy) is an international registry (France, Sweden, the United Kingdom, Italy, and Switzerland) enrolling patients with DMD or BMD and HFrEF. GDMT was defined as concurrent therapy with a sodium-glucose cotransporter-2 inhibitor (SGLT2i), an angiotensin receptor-neprilysin inhibitor (ARNI)/angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blocker (ARB), a beta-blocker (BB), and a mineralocorticoid receptor antagonist (MRA). Drug utilization was assessed by dose categories: target (100%), intermediate (50–99%), or low (50%), per HF guidelines. Results Among 281 patients (31 ± 12 years; 98% male; LVEF 34% ± 6%; 80% DMD), median visit rate was 2.1 (IQR: 1.8–2.6) per year. At the first visit post-2021 ESC HF guidelines, 11%, 15%, 50%, and 79% were not prescribed ACEi/ARB/ARNI, BB, MRA, and SGLT2i, respectively. Few reached target doses of ACEi/ARB/ARNI (18%) and BB (15%), while MRA (43%) and SGLT2i (100%) were optimized more frequently. Only 16% of patients received target doses of all GDMT drugs. During follow-up, MRA (+34%, p0.001) and SGLT2i (+114%, p0.001) saw the greatest dose uptitration, whereas RASi and BB implementation remained modest. Approximately 40% of patients who were either untreated or receiving a low dose of MRA had no contraindications to initiating or uptitrating the treatment. Similarly, nearly 50% of those not treated with an SGLT2i had no contraindications to its use. Achieving GDMT was associated with fewer clinical events (HR 0.32 95% CI: 0.12–0.80, p=0.015) over a median follow-up of 12 0.5–18 months. Conclusions In this multinational cohort of MD patients with HFrEF, GDMT use was suboptimal, with many not receiving key medications or target doses. MRA and SGLT2i had the greatest dose optimization, but overall implementation remained limited. Achieving GDMT was associated with fewer clinical events, emphasizing the need for improved HF management in this population.