Cardiac Atrophy: A Novel Mechanism for Duchenne Muscular Dystrophy (Dmd)-Associated Cardiomyopathy

Khan, Shaida; Cheeran, Daniel; Garg, Sonia; Grodin, Justin L.; Morlend, Robert; Araj, Faris G.; Amin, Alpesh; Thibodeau, Jennifer T.; Drazner, Mark H.; Mammen, Pradeep P.A.

doi:10.1016/s0735-1097(17)34335-8

Cited by 2 publications

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“…These findings emphasize the importance of measuring strain in this patient population at an early stage of the disease. A study by Khan et al [50] and a previous study by Lee et al [51] have reported that individuals with DMD develop cardiac atrophy as evidenced by reduced LVMI. Our findings report a similar trend in the decline in LVM and LVMI.…”

Section: Strain and Volumetric Cardiac Function Decline In Dmdmentioning

confidence: 90%

Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging

Batra

Barnard

Lott

et al. 2022

BMC Cardiovasc Disord

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Background The lack of dystrophin in cardiomyocytes in Duchenne muscular dystrophy (DMD) is associated with progressive decline in cardiac function eventually leading to death by 20–40 years of age. The aim of this prospective study was to determine rate of progressive decline in left ventricular (LV) function in Duchenne muscular dystrophy (DMD) over 5 years. Methods Short axis cine and grid tagged images of the LV were acquired in individuals with DMD (n = 59; age = 5.3–18.0 years) yearly, and healthy controls at baseline (n = 16, age = 6.0–18.3 years) on a 3 T MRI scanner. Grid-tagged images were analyzed for composite circumferential strain (ℇcc%) and ℇcc% in six mid LV segments. Cine images were analyzed for left ventricular ejection fraction (LVEF), LV mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), LV atrioventricular plane displacement (LVAPD), and circumferential uniformity ratio estimate (CURE). LVM, EDV, and ESV were normalized to body surface area for a normalized index of LVM (LVMI), EDV (EDVI) and ESV (ESVI). Results At baseline, LV ℇcc% was significantly worse in DMD compared to controls and five of the six mid LV segments demonstrated abnormal strain in DMD. Longitudinal measurements revealed that ℇcc% consistently declined in individuals with DMD with the inferior segments being more affected. LVEF progressively declined between 3 to 5 years post baseline visit. In a multivariate analysis, the use of cardioprotective drugs trended towards positively impacting cardiac measures while loss of ambulation and baseline age were associated with negative impact. Eight out of 17 cardiac parameters reached a minimal clinically important difference with a threshold of 1/3 standard deviation. Conclusion The study shows a worsening of circumferential strain in dystrophic myocardium. The findings emphasize the significance of early and longitudinal assessment of cardiac function in DMD and identify early biomarkers of cardiac dysfunction to help design clinical trials to mitigate cardiac pathology. This study provides valuable non-invasive and non-contrast based natural history data of cardiac changes which can be used to design clinical trials or interpret the results of current trials aimed at mitigating the effects of decreased cardiac function in DMD.

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Section: Strain and Volumetric Cardiac Function Decline In Dmdmentioning

confidence: 90%

Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging

Batra

Barnard

Lott

et al. 2022

BMC Cardiovasc Disord

View full text Add to dashboard Cite

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“…Accordingly, the mechanism of maladaptive cardiac remodeling has been increasingly called into question. A cMRI study recently completed at UT Southwestern Medical Center suggests that adult DMD patients have small, atrophic hearts as compared to age-matched and weight-matched patients with non-ischemic cardiomyopathy or healthy patients enrolled in the Dallas Heart Study and this manuscript is currently under scientific review [39]. In an effort to further elucidate the mechanism leading to cardiac remodeling in DMD patients, the Mammen Laboratory at UT Southwestern Medical Center has discovered a proliferative defect in cardiomyocytes lacking dystrophin as early as four days postnatally in DMD mdx mice.…”

Section: Pathophysiology Underlying Dmd-associated Cardiomyopathymentioning

confidence: 99%

Clinical Management of DMD-Associated Cardiomyopathy

Lee-Gannon¹,

Lehrenbaum²,

Sheth³

et al. 2021

Cardiomyopathy - Disease of the Heart Muscle

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Over the past decade, cardiomyopathy has become the leading cause of mortality among patients with Duchenne muscular dystrophy (DMD). The majority of DMD patients over the age of 18 experience some degree of cardiac involvement. The primary cardiac manifestations of DMD include progressive left ventricular (LV) wall stress leading to LV dilatation and wall thinning, and the development of cardiac fibrosis, all of which culminate in decreased LV contractility and reduced cardiac output. Mortality in these patients is predominantly related to pump failure and fatal arrhythmias leading to sudden cardiac death. While basic guidelines for the management of cardiomyopathy in DMD patients exist, these recommendations are by no means comprehensive, and this chapter aims to provide further insight into appropriate clinical diagnosis and management of DMD-associated cardiomyopathy. Notably, earlier and more frequent cardiac assessment and care can allow for better outcomes for these patients. Pharmacological treatments typically include an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, beta-adrenergic receptor blockers, mineralocorticoid receptor antagonists, and corticosteroids. Non-pharmacological therapies include automated implantable cardioverter defibrillators and left ventricular assist devices, as well as in rare cases cardiac transplantation. Additionally, many emerging therapies show great promise for improving standards of care. These novel therapies, based primarily on applied gene therapy and genome editing, have great potential to significantly alter the DMD care landscape in the near future.

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Cardiac Atrophy: A Novel Mechanism for Duchenne Muscular Dystrophy (Dmd)-Associated Cardiomyopathy

Cited by 2 publications

References 0 publications

Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging

Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging

Clinical Management of DMD-Associated Cardiomyopathy

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