X-Chromosomal (p21) Muscular Dystrophy and Left Ventricular Diastolic and Systolic Function

Brockmeier, Konrad; Schmitz, L.; Moers, Arpad von; Koch, Heike; Vogel, M; Bein, G

doi:10.1007/s002469900262

Cited by 22 publications

(7 citation statements)

References 35 publications

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“…These features correspond to the cardiac features in boys with DMD where there is also increased fibrosis with reduced systolic and diastolic function. 4 The mdx mouse ventricles also exhibit significantly elevated collagen content evident by Picrosirius red staining, as reported previously, 26 with no change evident in collagen I:III ratio. Using hydroxyproline assays, this increase in collagen has been further verified.…”

Section: Discussionsupporting

confidence: 55%

Long‐term administration of pirfenidone improves cardiac function in mdx mice

2006

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Duchenne muscular dystrophy, an X-linked recessive neuromuscular disorder due to lack of the protein dystrophin, manifests as progressive muscle degeneration and cardiomyopathy with increased fibrosis. The exact mechanisms involved in fibrosis are unknown, but a cytokine, transforming growth factor-beta (TGF-beta), is a likely mediator. This study tested whether the TGF-beta antagonist, pirfenidone, could reduce cardiac fibrosis. Eight-month-old mdx mice were treated for 7 months with 0.4%, 0.8%, and 1.2% pirfenidone in drinking water; untreated water was given to control mdx and C57 mice. Mice treated with 0.8% and 1.2% pirfendone had lowered cardiac TGF-beta mRNA and improved in vitro cardiac contractility (P < 0.05) to levels consistent with C57 mice, yet without a change in cardiac stiffness or fibrosis. These results show that the TGF-beta antagonist, pirfenidone, can improve cardiac function in mdx mice, potentially providing a new avenue for developing cardiac therapies for patients with Duchenne muscular dystrophy.

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Section: Discussionsupporting

confidence: 55%

Long‐term administration of pirfenidone improves cardiac function in mdx mice

2006

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“…Echocardiography may reveal myocardial thickening, regional wall motion abnormalities, dilation of the cardiac cavities, valve abnormalities, thrombus formation, and right and left ventricular systolic and diastolic dysfunction [2, 66, 67]. Heart failure is present in 10–20% of terminal DMD patients [68].…”

Section: Duchenne Muscular Dystrophymentioning

confidence: 99%

The Heart in Human Dystrophinopathies

2003

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Dystrophinopathies are due to mutations in the dystrophin gene on chromosome Xp21.1 and comprise the allelic entities Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilative cardiomyopathy (XLDCM). In all three entities, the heart is affected to various degrees, depending on the stage of the disease and the type of the mutation (cardiac involvement, CI). The pathoanatomic evidence of CI in dystrophinopathies is the replacement of myocardium by connective tissue or fat. In DMD/BMD, the left ventricular posterobasal and lateral walls are most extensively affected, sparing the right ventricle and the atrium. Degree and dynamics of CI vary among the three entities. In DMD/BMD, CI usually remains subclinical in the early stages of the disease. Typical initial manifestations of CI in DMD/BMD are sinus tachycardia, tall R1 in V1, prominent Q in I, aVL, V6 or in II, III, and aVF, increased QT dispersion and possibly autonomic dysfunction. Initially, echocardiography is normal or shows regional wall motion abnormalities in areas of fibrosis. With spreading of fibrosis, left ventricular dysfunction and ventricular arrhythmias additionally occur. In the final stages of the disease, systolic function may lead to heart failure and sudden death. Subclinical or clinical CI is present in about 90% of the DMD/BMD patients but is the cause of death in only 20% of the DMD and 50% of the BMD patients. XLDCM is a rapidly progressive, almost exclusively myocardial disorder, starting in teenage males as heart failure due to dilative cardiomyopathy (CMP), leading to death from intractable heart failure within 1–2 years after diagnosis. Therapy of arrhythmias and CMP in all three disorders follows the established cardiological recommendations. Due to its protective effect, ACE inhibitors are recommended already at the early stages of the disease. β-Blockers may be an additional option if indicated.

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“…Echocardiography allows qualitative assessment of LV contractility (24). The most frequently found abnormality in DMD is the LV contractility dysfunction (26), (27). This functional change generates systolic deficiency (37), which can be observed in our study through a decrease in EF.…”

Section: Discussionmentioning

confidence: 73%

“…It allows a qualitative assessment of left ventricular contraction (24), being a useful tool for the early diagnosis of left ventricular dysfunction and providing useful information for the treatment of DMD patients (25). The most common abnormalities seen in the echocardiogram are heart muscle contractility disorders (26,27). Electrocardiographic and echocardiographic changes are due to a degenerative process involving fibrosis and replacement of primary tissue by fatty tissue (28,29).…”

Section: Introductionmentioning

confidence: 99%

Analysis of cardiac exams: electrocardiogram and echocardiogram use In Duchenne muscular dystrophies

et al. 2014

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Introduction Duchenne Muscular Dystrophies (DMD) is a genetic muscle disorder that causes degeneration and atrophy of skeletal muscle and heart. Objective The aim of this survey is accomplish an evaluation electrocardiographic and echocardiography in the patients bearers of Duchene Muscular Dystrophies (DMD), to observe which alterations, which the degree of cardiac compromising these patient present and the effectiveness of these exams in the evaluation cardiologic. Methods Nine patients of the sex male bearers of DMD, with medium age of 14.12 ± 4.19 years, varying of 7 to 23 years were appraised. All were submitted to the evaluation physiotherapy and the cardiologic: electrocardiogram and echocardiogram. Results The experimental conditions of the present survey we propitiate the observation of the alterations echocardiography, as well as: significant increase in the diastolic diameter of the left ventricular (LV), increase in the systolic diameter of the left atrium (LA), and significant decrease of the ejection fraction of the LV, characterizing global systolic function reduced, and of the alterations electrocardiographic suggested possible overload of RV, septum hypertrophy, blockade of left previous fascicle and overload of atrium left. Compatible alterations of hypertrophy left ventricular were not observed. Conclusion The evidences corroborate with the data described in the literature in the characterization of an important heart compromising that these patient present, like this the evaluation cardiologic, through the complemented exams of the echocardiography and electrocardiography provide important information for the prognostic, the accompaniment, and the treatment of patient bearers of DMD.

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X-Chromosomal (p21) Muscular Dystrophy and Left Ventricular Diastolic and Systolic Function

Cited by 22 publications

References 35 publications

Long‐term administration of pirfenidone improves cardiac function in mdx mice

Long‐term administration of pirfenidone improves cardiac function in mdx mice

The Heart in Human Dystrophinopathies

Analysis of cardiac exams: electrocardiogram and echocardiogram use In Duchenne muscular dystrophies

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