Detection of long-term progression of myocardial fibrosis in Duchenne muscular dystrophy in an affected family: A cardiovascular magnetic resonance study

Department of Internal Medicine II, University of Ulm, Ulm, Germany.
European journal of radiology (Impact Factor: 2.37). 10/2011; 80(1):115-9. DOI: 10.1016/j.ejrad.2010.07.005
Source: PubMed


Detection of myocardial fibrosis and left ventricular dysfunction in Duchenne muscular dystrophy (DMD) is the corner stone for further therapeutic studies. Little is known about the ability of cardiac magnetic resonance imaging (CMR) to evaluate progression of myocardial fibrosis. Aim of our study was to provide CMR data in a previously genotyped DMD family and to evaluate whether progression of myocardial fibrosis could be visualized.
DMD genotypes were available in 14 family members. CMR was performed in 4/5 carrier females, in 2/2 affected males and in one healthy family member with normal genotype. Functional images and late gadolinium enhanced (LGE) images in contiguous short-axis orientation were acquired at baseline and follow-up of 1231 days CMR examination could be repeated in three carrier females, in one affected male and in the healthy subject previously scanned. Mean decrease of left ventricular ejection fraction during the follow-up period was 10.5±11.0%, mean progression of LGE volume 11.7±9.5%.
Myocardial fibrosis seems to occur prior to global left ventricular dysfunction in DMD diseased males and carrier females. CMR could be used to evaluate progression of myocardial fibrosis and left ventricular function and may thus serve as an important diagnostic tool in the evaluation of therapeutical options in DMD.

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    • "Some exons’ duplications were more frequently associated with DCM [31]. In our study group, the only DMDc carrying exon’s 2 duplication had subepicardial LGE with normal LV function. "
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    ABSTRACT: Background This study was designed to assess whether cardiovascular magnetic resonance imaging (CMR) in Duchenne muscular dystrophy carriers (DMDc) may index any cell milieu elements of LV dysfunction and whether this cardiac phenotype may be related to genotype. The null hypothesis was that myocardial fibrosis, assessed by late gadolinium enhancement (LGE), might be similarly accounted for in DMDc and gender and age-matched controls. Methods Thirty DMDc patients had CMR and genotyping with 37 gender and age-matched controls. Systolic and diastolic LV function was assessed by 2D-echocardiography. Results Absolute and percent LGE were higher in muscular symptomatic (sym) than asymptomatic (asy) DMDc (1.77 ± 0.27 vs 0.76 ± 0.17 ml; F = 19.6, p < 0.0001 and 1.86 ± 0.26% vs 0.68 ± 0.17%, F = 22.1, p < 0.0001, respectively). There was no correlation between LGE and age. LGE was seen most frequently in segments 5 and 6; segment 5 was involved in all asy-DMDc. Subepicardial LGE predominated, compared to the mid-myocardial one (11 out of 14 DMDc). LGE was absent in the subendocardium. No correlations were seen between genotyping (type of mutation, gene region and protein domain), confined to the exon’s study, and cardiac phenotype. Conclusions A typical myocardial LGE-pattern location (LV segments 5 and 6) was a common finding in DMDc. LGE was more frequently subepicardial plus midmyocardial in sym-DMDc, with normal LV systolic and diastolic function. No genotype-phenothype correlation was found.
    Journal of Cardiovascular Magnetic Resonance 07/2014; 16(1):45. DOI:10.1186/1532-429X-16-45 · 4.56 Impact Factor
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    • "The youngest DMD patient in our cohort to have LGE was 7.6 years age despite normal LVEF which indicates that DMD-associated heart disease in the form of LGE can occur before age 10 years of age. Walcher et al. analyzed a small number of female carriers and affected males (7 patients in total) and concluded that LGE is present prior to the onset of global left ventricular dysfunction [34]. Bilchick et al. evaluated the prevalence and distribution of regional scar on dysfunctional myocardial segments in a small DMD patient population (16 patients) and concluded that overall scar prevalence in inferior, inferolateral and anterolateral segments was eight times higher than in inferoseptal, anteroseptal and anterior segments [35,36]. "
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    ABSTRACT: Duchenne muscular dystrophy (DMD), an X-linked disorder affects approximately 1 in 5000 males, is universally associated with heart disease. We previously identified myocardial disease by late gadolinium enhancement (LGE) in DMD subjects at various stages of disease, but the true prevalence is unclear. Cardiovascular magnetic resonance (CMR) is well established for both assessment of ventricular function and myocardial fibrosis by LGE. We sought to establish i) prevalence and distribution of LGE in a large DMD population and ii) relationship among LGE, age, LVEF by CMR and current living status. Current living status, demographic and CMR data including ventricular volumes, LVEF and LGE from 314 DMD patients undergoing evaluation at a single large tertiary referral center were analyzed. 113 of 314 (36%) of DMD subjects showed LGE positivity with prevalence increasing from 17% of patients <10 years to 34% of those aged 10-15 years and 59% of those > 15 years-old. Patients with LVEF >=55% were LGE positive in 30% of cases; this increased to 84%for LVEF <55%. LGE was more prevalent in the free wall (531/1243, 42.7%) vs. septal segments (30/565, 5.3%). Patients with septal involvement were significantly older and had lower LVEF than those with isolated free wall LGE. Ten percent (11/113) patients who had LGE died 10.8 months after CMR. Only one patient from the LGE negative group died. Patients who died had higher heart rate, larger left ventricular volume and mass, greater number of positive LGE segment and increase incident of septal LGE compared to those who remained alive. In DMD patients, LGE occurs early, is progressive and increases with both age and decreasing LVEF. Segmentally, the incidence of the number of positive LGE segments increase with age and lower LVEF. Older patients and those who died during the study period had more septal LGE involvement. The current studies suggest that the time course and distribution of LGE-positivity may be an important clinical biomarker to aid in the management of DMD-associated cardiac disease.
    Journal of Cardiovascular Magnetic Resonance 12/2013; 15(1):107. DOI:10.1186/1532-429X-15-107 · 4.56 Impact Factor
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    • "Given that cardiovascular magnetic resonance (CMR) is the most discriminating methodology to characterize cardiac structure and function, we sought to better characterize the myocardium in LGMD2I and 2B for several reasons. For example, some patients may warrant cardioprotective therapy if CMR abnormalities are observed at a time when systolic function is preserved by echocardiography, though this is not current practice in LGMD unlike in Duchenne muscular dystrophy (DMD) where angiotensin-converting enzyme (ACE) inhibitors are often started when EF is normal by echocardiography yet CMR reveals abnormalities in strain and evident myocardial fibrosis[20-22]. In addition, when considering patients for clinical trials, knowledge of predilection toward cardiomyopathy could influence protocol design for cardiac monitoring to reduce drug-related cardiotoxicity. "
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    ABSTRACT: Limb girdle muscular dystrophies (LGMD) are inclusive of 7 autosomal dominant and 14 autosomal recessive disorders featuring progressive muscle weakness and atrophy. Studies of cardiac function have not yet been well-defined in deficiencies of dysferlin (LGMD2B) and fukutin related protein (LGMD2I). In this study of patients with these two forms of limb girdle muscular dystrophy, cardiovascular magnetic resonance (CMR) was used to more specifically define markers of cardiomyopathy including systolic dysfunction, myocardial fibrosis, and diastolic dysfunction. Consecutive patients with genetically-proven LGMD types 2I (n = 7) and 2B (n = 9) and 8 control subjects were enrolled. All subjects underwent cardiac magnetic resonance (CMR) on a standard 1.5 Tesla clinical scanner with cine imaging for left ventricular (LV) volume and ejection fraction (EF) measurement, vector velocity analysis of cine data to calculate myocardial strain, and late post-gadolinium enhancement imaging (LGE) to assess for myocardial fibrosis. Sixteen LGMD patients (7 LGMD2I, 9 LGMD2B), and 8 control subjects completed CMR. All but one patient had normal LV size and systolic function; one (type 2I) had severe dilated cardiomyopathy. Of 15 LGMD patients with normal systolic function, LGE imaging revealed focal myocardial fibrosis in 7 (47%). Peak systolic circumferential strain rates were similar in patients vs. controls: εendo was -23.8 ± 8.5vs. -23.9 ± 4.2%, εepi was -11.5 ± 1.7% vs. -10.1 ± 4.2% (p = NS for all). Five of 7 LGE-positive patients had grade I diastolic dysfunction [2I (n = 2), 2B (n = 3)]. that was not present in any LGE-negative patients or controls. LGMD2I and LGMD2B generally result in mild structural and functional cardiac abnormalities, though severe dilated cardiomyopathy may occur. Long-term studies are warranted to evaluate the prognostic significance of subclinical fibrosis detected by CMR in these patients.
    Journal of Cardiovascular Magnetic Resonance 08/2011; 13(1):39. DOI:10.1186/1532-429X-13-39 · 4.56 Impact Factor
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