Evidence of early impairments in both right and left ventricular inotropic reserves in children with Duchenne's muscular dystrophy

Bosser, Gilles; Lucron, Hugues; Lethor, Jean-Paul; Burger, G; Beltramo, F.; Marie, Pierre-Yves; Marçon, F

doi:10.1016/j.amjcard.2003.12.005

Cited by 20 publications

(14 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The right ventricle, with its small mass and potentially smaller lesion sizes may be underrepresented in these studies. It is important to note that there remains little difference in hemodynamic function between the right and left ventricles of the mdx mouse; similar results are seen in DMD patients (6,58). The failure to observe interventricular hemodynamic differences may result from the tight coupling of the ventricles, in that dysfunction of the right ventricle will lead to dysfunction of the left ventricle.…”

Section: Discussionsupporting

confidence: 61%

Early right ventricular fibrosis and reduction in biventricular cardiac reserve in the dystrophin-deficient mdx heart

Meyers

Townsend

2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is a progressive disease of striated muscle deterioration. Respiratory and cardiac muscle dysfunction are particularly clinically relevant because they result in the leading causes of death in DMD patients. Despite the clinical and physiological significance of these systems, little has been done to understand the cardiorespiratory interaction in DMD. We show here that prior to the onset of global cardiac dysfunction, dystrophin-deficient mdx mice have increased cardiac fibrosis with the right ventricle being particularly affected. Using a novel biventricular cardiac catheterization technique coupled with cardiac stress testing, we demonstrate that both the right and left ventricles have significant reductions in both systolic and diastolic function in response to dobutamine. Unstimulated cardiac function is relatively normal except for a significant reduction in the ventricular pressure transient duration compared with controls. These biventricular analyses also reveal the absence of a dobutamine-induced increase in isovolumic relaxation in the right ventricle of control hearts. Simultaneous assessment of biventricular pressure demonstrates a dobutamine-dependent enhancement of coupling between the ventricles in control mice, which is absent in mdx mice. Furthermore, studies probing the passive-extension properties of the left ventricle demonstrate that the mdx heart is significantly more compliant compared with age-matched C57BL/10 hearts, which have an age-dependent stiffening that is completely absent from dystrophic hearts. These new results indicate that right ventricular fibrosis is an early indicator of the development of dystrophic cardiomyopathy, suggesting a mechanism by which respiratory insufficiency may accelerate the development of heart failure in DMD.

show abstract

Section: Discussionsupporting

confidence: 61%

Early right ventricular fibrosis and reduction in biventricular cardiac reserve in the dystrophin-deficient mdx heart

Meyers

Townsend

2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…7 The present study of the use of a -blocker in muscular dystrophy raises questions regarding the types of muscular dystrophy amenable to the therapy and the optimal timing of the therapy. Many types of muscular dystrophy involve the cardiac muscles, [20][21][22][23][24][25][26][27][28] but because the number of patients with Becker muscular dystrophy, Fukuyama muscular dystrophy, and Emery-Dreifuss muscular dystrophy was small in the present study, we could not conclude if there was a difference in the effectiveness of -blockers among them.…”

Section: Discussioncontrasting

confidence: 46%

Beta-Blocker Therapy for Cardiac Dysfunction in Patients With Muscular Dystrophy

Kajimoto

Ishigaki

Okumura

et al. 2006

Circ J

103

View full text Add to dashboard Cite

eart failure is one of the major causes of death in patients with Duchenne muscular dystrophy (DMD). 1 It has been shown that angiotensin-converting enzyme inhibitors (ACEI) and -blockers effectively improve symptoms and cardiac function, and decrease mortality in adult patients with congestive heart failure caused by ischemic heart disease or dilated cardiomyopathy. 2-5 However, whether these drugs are effective in the management of patients with muscular dystrophy has not been well studied. We investigated whether a -blocker, carvedilol, in addition to an ACEI is effective to improve cardiac function in patients with muscular dystrophy. Methods PatientsBetween August 1999 and December 2002, 28 patients, age 17±5 years (range 7-29 years), were started on cilazapril or enalapril because of ventricular dysfunction. Diagnoses were DMD in 25 patients; Fukuyama-type muscular dystrophy in 2 patients, and Emery-Dreifuss muscular dystrophy in 1. The decision to start an ACEI was based on echocardiographic findings; these drugs were started when left Circulation Journal Vol.70, August 2006 ventricular (LV) fractional shortening (FS) was <0.26. After the dosage of the ACEI reached its final value, the 28 patients were randomly allocated into 2 groups: carvedilol plus an ACEI (carvedilol group: 13 patients; age 18±6 years, range 7-27 years), or an ACEI only (ACEI group: 15 patients; age 15±4 years, range 8-29 years).Because all patients were physically not active, it was difficult to evaluate cardiac symptoms, so in the present study, they were considered to be present if patients complained of fatigue, palpitations, sweating, and/or chest discomfort.There were no significant differences in age, body weight, the ratio of patients with cardiac symptoms, ratio of patients with concomitant use of diuretics, heart rate, blood pressure, and plasma brain natriuretic peptide (BNP) levels between the 2 groups before drug administration (Tables 1,2 Background In muscular dystrophy, cardiac function deteriorates with time and heart failure is one of the major causes of death. Although the combination of angiotensin-converting enzyme inhibitors (ACEI) and -blockers improves cardiac function in adults, little is known about the efficacy of those drugs in patients with muscular dystrophy. Methods and ResultsThe effect of the -blocker, carvedilol, and/or ACEI on ventricular function in patients with muscular dystrophy was studied. Carvedilol and an ACEI were given to 13 patients (ACEI group; mean age 18 years, range 7-27 years), and an ACEI only to 15 patients (carvedilol group; mean age 15 years, range 8-29 years). Diagnoses included Duchenne muscular dystrophy (n=25), Fukuyama muscular dystrophy (n=2), and Emery-Dreifuss muscular dystrophy (n=1). Echocardiographic parameters of the left ventricle were measured during the 2-3 years of follow-up. In the carvedilol group, combination therapy of carvedilol and an ACEI for 2 years resulted in a significant increase in left ventricular fractional shortening (LVFS). In the ACEI group, th...

show abstract

“…Lower afterload of the RV compared to LV, may reduce and delay myocardial replacement fibrosis. The findings that RVEF is relatively preserved in DMD patient is also suggested by Bosser and colleagues in a small study of 19 DMD patients (mean age 13.6 ± 2.4 yr) undergoing equilibrium radionuclide angiography [21]. Their study showed that 95% of patients had normal rest RVEF (>45%) where as normal LVEF (50%) was present in 79% of patients.…”

Section: Discussionsupporting

confidence: 54%

Comparison of right and left ventricular function and size in Duchenne muscular dystrophy

Mehmood

Hor

Al‐Khalidi

et al. 2015

European Journal of Radiology

View full text Add to dashboard Cite

Evidence of early impairments in both right and left ventricular inotropic reserves in children with Duchenne's muscular dystrophy

Cited by 20 publications

References 26 publications

Early right ventricular fibrosis and reduction in biventricular cardiac reserve in the dystrophin-deficient mdx heart

Early right ventricular fibrosis and reduction in biventricular cardiac reserve in the dystrophin-deficient mdx heart

Beta-Blocker Therapy for Cardiac Dysfunction in Patients With Muscular Dystrophy

Comparison of right and left ventricular function and size in Duchenne muscular dystrophy

Contact Info

Product

Resources

About