Effects of cardiac medications on ventricular function in patients with Duchenne muscular dystrophy–related cardiomyopathy

Abstract

Introduction/Aims The DMD Care Considerations Working Group Guidelines 2010 recommended treating cardiac dystrophinopathy with angiotensin‐converting enzyme‐inhibitor (ACEi) and beta‐blocker (BB) therapy to prevent the progressive decline in left ventricular function expected from earlier, natural history studies. The aim of this research was to audit change in measures of left ventricular function over 8 years to 4 years before and 4 years after deploying an ACEi/BB combination systematically at a dedicated “cardiology‐muscle” clinic. Methods This is an institutionally registered, retrospective, case‐file–based audit of serial echocardiographic measures of left ventricular fractional shortening accumulated over the period 1995 to 2015. Results Data from 104 genetically confirmed Duchenne muscular dystrophy (DMD) patients, aged 22.2 ± 5.3 years at data censure, were included. Mean age at first detection of left ventricular dysfunction was 15.1 ± 4.2 years, but older in those on maintenance steroid therapy (16.8 ± 4.2 vs 14.5 ± 4.1 years; P = .04). Group mean fractional shortening fell by 1.5%/year over the 4 years before therapy, but this decreased to 0.9%/year over the first 4 years after starting therapy. Analysis of limited left ventricular ejection fraction measures showed similar but nonsignificant changes. Neither age at detection of left ventricular dysfunction nor fractional shortening percent at time of therapy initiation affected the beneficial response. Discussion The results support the international DMD recommendations of the time. This combination of cardiac medications helps stabilize heart function. For the best long‐term effects, therapy needs to be initiated no later than on first detection left ventricular impairment.

Early prophylaxis of cardiomyopathy with beta-blockers and angiotensin receptor blockers in patients with Duchenne muscular dystrophy

“…The median age of the first detection of LV systolic dysfunction (LV-EF<55%) by echocardiography was 15.9 years (IQR, 13.7–18.1 years) in this study. This age is quite similar to that reported by previous study reporting a decrease in LV fractional shortening to below 28% in DMD patients at the age of 15.1±4.2 years [ 1 ] without any prophylactic ACEi or beta-blockers. This result is consistent with the findings of a randomized controlled trial reporting that beta-blockers had no beneficial effect as a prophylactic medication [ 5 ].…”

“…To the Editor, Cardiomyopathy in patients with Duchenne muscular dystrophy (DMD) is often apparent on echocardiography at the age of 15 1) . Based on the benefits of angiotensin-converting enzyme inhibitors (ACEi) in teen patients with DMD 2) , major guidelines and expert working groups have recommended the initiation of treatment with ACEi by the age of 10 years regardless of whether left ventricular (LV) systolic function is normal 3,4) .…”

A scalable, clinically severe pig model for Duchenne muscular dystrophy

“…a 19% ( P <0.001) reduced LV ejection fraction, which is consistent with early stages of dilatative cardiomyopathy (DCM). Additionally, LV fractional shortening, another diagnostic parameter for DMD-related DCM ( Murphy et al, 2021 ), was 27% ( P <0.01) smaller in DMD Y/− versus WT pigs. Systolic cardiac dysfunction has also been described in the GRMD model, but only in adult animals between age 30 and 45 months ( Guo et al, 2019 ).…”

Arrhythmias and cardiac MRI associations in patients with established cardiac dystrophinopathy

“… 6 10 These drugs slow but cannot prevent further decline in LV function, although over a longer time frame in patients with DMD. 11 Increasingly, therefore, more potent drugs are being deployed, particularly when there is evidence of progressive LV dysfunction despite standard of care medications. 12 The object is to preserve LV function for as long as possible, delay the onset of heart failure symptoms and prolong quality survival.…”