Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy

Trucco, Federica; Domingos, Joana; Tay, Chee Geap; Ridout, Deborah; Maresh, Kate; Munot, Pinki; Sárközy, Anna; Robb, Stephanie; Quinlivan, R.; Riley, Mollie; Burch, Michael; Fenton, Matthew J.; Wallis, Colin; Chan, Elaine; Abel, François; Muntoni, Francesco

doi:10.1016/j.chest.2020.04.043

Cited by 33 publications

(40 citation statements)

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“…Progressive respiratory impairment occurs invariably in boys affected by Duchenne muscular dystrophy (DMD) and represents one of the main causes of patient mortality 1 . Corticosteroids (CS), used as standard treatment, 2,3 have prolonged life expectancy and reduced respiratory complications in DMD 4,5 . In addition, new therapeutic options for DMD have emerged of which exon skipping is a promising one.…”

Section: Introductionmentioning

confidence: 99%

Genotype‐related respiratory progression in Duchenne muscular dystrophy—A multicenter international study

et al. 2021

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Introduction/Aims Mutations amenable to skipping of specific exons have been associated with different motor progression in Duchenne muscular dystrophy (DMD). Less is known about their association with long‐term respiratory function. In this study we investigated the features of respiratory progression in four DMD genotypes relevant in ongoing exon‐skipping therapeutic strategies. Methods This was a retrospective longitudinal study including DMD children followed by the UK NorthStar Network and international AFM Network centers (May 2003 to October 2020). We included boys amenable to skip exons 44, 45, 51, or 53, who were older than 5 years of age and ambulant at first recorded visit. Subjects who were corticosteroid‐naive or enrolled in interventional clinical trials were excluded. The progression of respiratory function (absolute forced vital capacity [FVC] and calculated as percent predicted [FVC%]) was compared across the four subgroups (skip44, skip45, skip51, skip53). Results We included 142 boys in the study. Mean (standard deviation) age at first visit was 8.6 (2.5) years. Median follow‐up was 3 (range, 0.3‐8.3) years. In skip45 and skip51, FVC% declined linearly from the first recorded visit. From the age of 9 years, FVC% declined linearly in all genotypes. Skip44 had the slowest (2.7%/year) and skip51 the fastest (5.9%/year) annual FVC% decline. The absolute FVC increased progressively in skip44, skip45, and skip51. In skip53, FVC started declining from 14 years of age. Discussion The progression of respiratory dysfunction follows different patterns for specific genotype categories. This information is valuable for prognosis and for the evaluation of exon‐skipping therapies.

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Section: Introductionmentioning

confidence: 99%

Genotype‐related respiratory progression in Duchenne muscular dystrophy—A multicenter international study

et al. 2021

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Section: Introductionmentioning

confidence: 99%

“…The introduction of care standards, advances in respiratory management, and routine use of maintenance corticosteroid drugs have prolonged time to loss of ambulation and survival in patients with Duchenne muscular dystrophy (DMD) 1‐5 . With multidisciplinary team management, the mean lifespan in patients is currently 25.3 to 31 years 4,5 . Almost all patients with DMD will have developed a dilated form of cardiomyopathy by 18 years of age, but corticosteroid therapy has been shown to delay the onset and modify the course of left ventricular (LV) dysfunction 1,5‐7 .…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5] With multidisciplinary team management, the mean lifespan in patients is currently 25.3 to 31 years. 4,5 Almost all patients with DMD will have developed a dilated form of cardiomyopathy by 18 years of age, but corticosteroid therapy has been shown to delay the onset and modify the course of left ventricular (LV) dysfunction. 1,[5][6][7] Despite this, cardiomyopathy remains a major contributor to death in patients already receiving steroid therapy and noninvasive ventilation.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 Almost all patients with DMD will have developed a dilated form of cardiomyopathy by 18 years of age, but corticosteroid therapy has been shown to delay the onset and modify the course of left ventricular (LV) dysfunction. 1,[5][6][7] Despite this, cardiomyopathy remains a major contributor to death in patients already receiving steroid therapy and noninvasive ventilation. 2,8 Angiotensin-converting enzyme inhibitor (ACEi), angiotensinreceptor blocking (ARB), and beta-blocker (BB) drugs are established in the treatment of asymptomatic LV dysfunction and heart failure in patients with idiopathic forms of dilated cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Prophylactic use of cardiac medications for delay of left ventricular dysfunction in Duchenne muscular dystrophy

Conway,

Thomas,

Ciafaloni

et al. 2023

Birth Defects Research

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BackgroundEpidemiological support for prophylactic treatment of left ventricular dysfunction (LVD) in Duchenne muscular dystrophy is limited. We used retrospective, population‐based surveillance data from the Muscular Dystrophy Surveillance, Tracking and Research Network to evaluate whether prophylaxis delays LVD onset.MethodsWe analyzed 455 males born during 1982–2009. Age at first abnormal echocardiogram (ejection fraction <55% or shortening fraction <28%) determined LVD onset. Prophylaxis was defined as cardiac medication use at least 1 year prior to LVD. Corticosteroid use was also coded. Kaplan–Meier curve estimation and Cox Proportional Hazard modeling with time‐varying covariates describe associations.ResultsLVD was identified among 40.7%; average onset age was 14.2 years. Prophylaxis was identified for 20.2% and corticosteroids for 57.4%. Prophylaxis showed delayed LVD onset (p < .001) and lower hazard of dysfunction (adjusted hazard ratio [aHR] = 0.39, 95%CL = 0.22, 0.65) compared to untreated. Compared to no treatment, continuous corticosteroids only (aHR = 1.01, 95%CL = 0.66, 1.53) and prophylaxis only (aHR = 0.67, 95%CL = 0.25, 1.50) were not cardioprotective, but prophylaxis plus continuous corticosteroids were associated with lower hazard of dysfunction (aHR = 0.37, 95%CL = 0.15, 0.80).ConclusionsProactive cardiac treatment and monitoring are critical aspects of managing Duchenne muscular dystrophy. Consistent with clinical care guidelines, this study supports clinical benefit from cardiac medications initiated prior to documented LVD and suggests further benefit when combined with corticosteroids.

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Cardiorespiratory Progression Over 5 Years and Role of Corticosteroids in Duchenne Muscular Dystrophy

Cited by 33 publications

References 44 publications

Genotype‐related respiratory progression in Duchenne muscular dystrophy—A multicenter international study

Genotype‐related respiratory progression in Duchenne muscular dystrophy—A multicenter international study

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

Prophylactic use of cardiac medications for delay of left ventricular dysfunction in Duchenne muscular dystrophy

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