Late gadolinium enhancement: precursor to cardiomyopathy in Duchenne muscular dystrophy?

Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration caused by lack of the cytoskeletal protein dystrophin. Dystrophin deficiency causes muscle membrane instability, skeletal muscle wasting, cardiomyopathy, and heart failure. Advances in palliative respiratory care have increased the incidence of heart disease in DMD patients, for which there is no cure or effective therapy. Here we have shown that chronic infusion of membrane-sealing poloxamer to severely affected dystrophic dogs reduced myocardial fibrosis, blocked increased serum cardiac troponin I (cTnI) and brain type natriuretic peptide (BNP), and fully prevented left-ventricular remodeling. Mechanistically, we observed a markedly greater primary defect of reduced cell compliance in dystrophic canine myocytes than in the mildly affected mdx mouse myocytes, and this was associated with a lack of utrophin upregulation in the dystrophic canine cardiac myocytes. Interestingly, after chronic poloxamer treatment, the poor compliance of isolated canine myocytes remained evident, but this could be restored to normal upon direct application of poloxamer. Collectively, these findings indicate that dystrophin and utrophin are critical to membrane stability-dependent cardiac myocyte mechanical compliance and that poloxamer confers a highly effective membrane-stabilizing chemical surrogate in dystrophin/utrophin deficiency. We propose that membrane sealant therapy is a potential treatment modality for DMD heart disease and possibly other disorders with membrane defect etiologies.

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“…5,25,34,35). Fibrotic lesions are thought to result from myocyte necrosis and subsequent inflammatory response.…”

Section: Grmdmentioning

confidence: 99%

Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs

Townsend¹,

Turner²,

Yasuda³

et al. 2010

J. Clin. Invest.

102

111

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“…In addition, based on our findings, we hypothesize that a difficult and inaccurate preoperative echocardiographic evaluation of NMS patients is one reason for unexpected severe perioperative cardiac complications. In patients with advanced NMS, particularly in those with large and rigid thoracic deformities and low BMI, we would recommend that clinicians evaluate the risk of perioperative heart-related events with additional cardiac assessments, such as brain natriuretic peptide, creatine kinase 16) , multigated cardiac radionuclide ventriculography 17) , and cardiac magnetic resonance imaging 18,19) . In this study, several valvular abnormalities (including trivial valve regurgitation) were detected.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Preoperative Echocardiographic Evaluation and Spinal Deformity in Patients with Neuromuscular Scoliosis

Saito

Inoue

Imura

et al. 2018

Spine Surg Relat Res

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Abstract:Introduction: Echocardiography is an important component of perioperative cardiac risk stratification in patients with neuromuscular scoliosis (NMS). However, there are little data regarding the relationship between preoperative echocardiographic findings and spinal deformity. We retrospectively reviewed preoperative echocardiographic data to investigate the relationship between echocardiographic evaluation and spinal deformity in NMS.Methods: We reviewed 73 NMS patients (mean age: 13.3 years, male 66%) who underwent spinal correction surgery between 2008 and 2016. Echocardiographic data including ejection fraction (EF), valvar disease, and inferior vena cava diameter were collected from the preoperative exam. Demographic and radiographic data were also collected.Results: Preoperative diagnoses included Duchenne muscular dystrophy, Fukuyama congenital muscular dystrophy, other dystrophy, spinal muscular atrophy, and congenital myopathies. Mean Body Mass Index (BMI) was 15.6 kg/m 2 . Mean major Cobb angle before surgery was 86.6 ± 28.2°. Because of technical difficulty, complete echocardiographic data could only be collected and evaluated in 49.3% of patients. Neither right nor left sided cardiac evaluation could be completed in 20.5%. Patients in whom complete echocardiographic data could not be collected had significantly more extensive thoracic scoliosis with a more rigid curve and hypokyphosis, and were of lower weight and BMI than patients in whom complete data could be collected. Ten cases (13.7%) were diagnosed as having minor heart-related complications immediately after surgery, and they had higher right atrial pressures preoperatively.Conclusions: Echocardiography can be technically difficult in NMS patients with extensive spinal deformities. We found that perioperative cardiac function could only be evaluated by echocardiogram in about half of NMS patients undergoing spinal correction surgery. The absence of an adequate preoperative cardiac evaluation could render these patients more susceptible to perioperative heart-related complications. Echocardiography may not be sufficient to evaluate cardiac conditions in children with extensive NMS.

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“…In female carriers an ECG and echocardiogram should be performed at diagnosis or after the age of 16 years and at least every 5 years thereafter, or more frequently in patients with abnormalities on investigation or carriers with severe skeletal muscle symptoms or cardiac symptoms. detect cardiac fibrosis in patients with Duchenne muscular dystrophy [12,13]. The study showed, that late gadolineum enhancement was negative related to left ventricular ejection fraction.…”

mentioning

confidence: 91%

Early detection of cardiomyopathy in Duchenne muscular dystrophy, is there a role for MRI?

Baur

2008

Int J Cardiovasc Imaging

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Late gadolinium enhancement: precursor to cardiomyopathy in Duchenne muscular dystrophy?

Cited by 137 publications

References 26 publications

Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs

Chronic administration of membrane sealant prevents severe cardiac injury and ventricular dilatation in dystrophic dogs

The Relationship between Preoperative Echocardiographic Evaluation and Spinal Deformity in Patients with Neuromuscular Scoliosis

Early detection of cardiomyopathy in Duchenne muscular dystrophy, is there a role for MRI?

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