Cardiac Atrophy and ACE Inhibitors in Duchenne Cardiomyopathy: 10 Years is the Right Age to Start Therapy?

Abstract

<h3>Purpose</h3> <b>Background</b> Dilated cardiomyopathy (DCM) is a leading cause of morbidity and mortality in patients affected by Duchenne muscular dystrophy (DMD). DCM is commonly characterized by a hypokinetic and dilated phenotype, typically involving left ventricle (LV). Nowadays, angiotensin converting enzyme inhibitors (ACEi) are indicated in all patients older than 10 years but the mechanism of action is still unknown. Characteristics of left ventricular (LV) remodelling are unclear, and no data are currently available on the time of onset. <b>Aim:</b> characterize left ventricular remodelling before 10 years of age and the effects of ACEi on it. <h3>Methods</h3> We conducted a retrospective single center analysis on all consecutive patients affected by DMD-DCM before 10 years of age, without LV dilation. We reanalysed all echocardiographic data about LV dimension and function, at the first cardiovascular assessment (before ACEi), at one year after treatment, and at the last follow up. To evaluate LV remodelling, we derived the relative wall thickness (RWT). RWT< 0.32 was the cut off to define the cardiac atrophy. <h3>Results</h3> 45 patients have been enrolled. Median age at first CV assessment was 10.3 y (±2.9). 72% of patients presented a reduced RWT (< 0.32) at first CV evaluation (average value 0.29 ± 0.05). After 1 year of treatment the percentage of patient with cardiac atrophy was unchanged (p = 0.52): 6 patients progressed and 6 regressed. At last follow up (35.5 months, ±7.7) the prevalence of cardiac atrophy was slightly increased (78% - p = 0.15): 9 patients (28%) developed cardiac atrophy during follow-up, despite ACEi therapy, while 6 (19%) regressed. Notably, neither progression nor regression were statistically significant (p= 0.15, p = 0.4 respectively). All patients were treated with ACEi: 48% was treated with Enalapril, 26% with Ramipril, 17% with perindopril, and the remaining with Fosinopril or Lisinopril. Median age at ACEi start was 11.2 (± 2.9). <h3>Conclusion</h3> Our data suggest that cardiac atrophy is already present, before 10 years of age. ACEi seems to slow progression but not invert the process.