Author + information
- Sophie Mavrogeni, MD⁎ (, )
- Konstantinos Bratis, MD,
- Antigoni Papavasiliou, MD,
- Eleni Skouteli, MD,
- Evangelos Karanasios, MD,
- Dimitris Georgakopoulos, MD,
- Genovefa Kolovou, MD and
- George Papadopoulos, MD
- ↵⁎Onassis Cardiac Surgery Center, 50 Esperou Street, 175-61 P. Faliro, Athens, Greece
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder, leading to reduced/abnormal dystrophin. Becker muscular dystrophy (BMD) is a milder form, caused by the same mutation, with a nearly normal life expectancy, but with a 50% chance of cardiac involvement (CI) (1). Although female carriers are usually free of symptoms, they may develop peripheral myopathy and cardiomyopathy, contributing to heart failure (HF) (1).
Our aim was to evaluate the possibility of myocardial damage in genetically confirmed mothers-carriers of Duchenne muscular dystrophy (DMDc) and Becker muscular dystrophy (BMDc) using cardiac magnetic resonance (CMR).
Thirty-five mothers, mean age 50 years (range: 32 to 68 years), without known comorbidities, except mild hypertension (systolic blood pressure 160 to 170 mm Hg in 1 DMDc and 1 BMDc), were studied. DMDc (n = 25) and BMDc (n = 10) were prospectively evaluated by CMR using a 1.5-T General Electric Signa HDxt (Milwaukee, Wisconsin). A standard steady-state free-precession (SSFP) sequence (FIESTA) (echo time = 1.5 ms, repetition time = 3.1 ms, flip angle = 70°, slice thickness = 8 mm) was used to measure the left ventricular ejection fraction (LVEF). To assess fibrosis, 0.2 mmol/kg gadolinium diethylenetriamine penta-acetic acid was administered, and late gadolinium-enhanced (LGE) images were taken 15 min later, using a 3-dimensional–T1-turbo field echo sequence (flip angle = 15°, echo time = 1.4 ms, repetition time = 5.5 ms, inversion time 225 to 275 ms as individually optimized to null myocardial signal, gap = 0, slice thickness = 6 mm). A threshold of >6 SD exceeding the mean was used to define LGE images (2). Summing the planimetered LGE areas in all short-axis slices yielded the total volume, expressed as a proportion of left ventricular (LV) myocardium (percentage of LGE).
Measurements were expressed as mean ± SD or mean (range). Statistical significance was investigated by unpaired Student t test. Correlation was sought with Pearson correlation coefficient. The Mann-Whitney test and Spearman correlation coefficient were used for nonparametric data. Statistical significance was considered p < 0.05.
Eight DMDc and 1 BMDc presented with muscle weakness, recognized by the subjects, but which did not affect daily activities. Cardiac symptoms were documented only in 5 of 25 DMDc. Creatine kinase (CK) was measured in all carriers. CK values of 290 ± 120 IU/l (normal values <190 IU/l) were identified in 15 of 35 (42.8%) carriers (13 [52%] DMDc and 2 [20%] BMDc). CMR documented decreased LVEF in 10 DMDc and subepicardial LGE images in posterolateral and/or septal LV wall in 18 DMDc and 5 BMDc (Figs. 1 and 2).⇓⇓ No difference in LGE morphology was identified between DMDc and BMDc. LGE images correlated negatively with LVEF (p < 0.001) and were greater in DMDc compared with BMDc (16 ± 2% vs. 3 ± 1%, p < 0.001, respectively). Carriers >40 years old had more extensive lesions compared with those <40 years old (14 ± 2% vs. 3 ± 1%, p < 0.001). The lack of comorbidities that could be possibly related to CMR findings strengthens the role of abnormal dystrophin in their pathogenesis. Carriers' characteristics are presented in Table 1.
According to previous studies, 12% of BMDc presented with muscle weakness, and CK was increased in 30% to 62% (1,3,4). In our study, although some BMDc had muscular symptoms and increased CK, the majority was asymptomatic with normal CK. The prevalence of CI on electrocardiography (ECG) and echocardiography and the possibility of dilated cardiomyopathy (dCMP) varied widely (3,4). CI in BMDc appears after the age of 16 years and may remain subclinical with advancing age in up to two-thirds of subjects. It can be manifested as ECG changes in two-fifths or as dCMP in up to one-fifth of cases (3). Our BMDc findings were in agreement with previous studies identifying normal ECG and echocardiographic results in the majority of subjects.
DMDc are more likely to develop dCMP at a young age (3). A 2002 consensus estimated that 10% of all DMDc or BMDc develop dCMP, even without skeletal muscle involvement (3). However, the impact of increased dCMP risk on life expectancy is still unclear (3). Although only a minority of our patients presented with muscular involvement, some DMDc already had LV impairment and rhythm disturbances. These findings were in agreement with previous studies supporting that CI is independent of muscular disturbances in DMDc (3).
Recently, CMR has been successfully used to identify myocardial fibrosis in subclinical DMDc or BMDc (4,5). However, except for case reports (4,5), there are not enough data about CMR in dystrophinopathy carriers. In our study, we identified myocardial fibrosis in the majority of carriers, with a significant superiority in severity of DMDc over BMDc and older carriers over younger carriers. The inverse correlation of fibrotic area, identified by LGE imaging, with LVEF supports the role of fibrosis in the development of HF (1,2). Furthermore, CMR proved to be of great significance documenting CI in a percentage higher than that identified by routine assessment.
The study limitations were that the population of studied carriers was small, young female carriers were not included, and long-term follow-up was not available.
To conclude, CMR documented myocardial fibrosis in the majority of dystrophinopathy carriers, although the usual assessment was mildly abnormal. However, the clinical implications of CMR and the necessity for early cardiac treatment need further evaluation.
- American College of Cardiology Foundation
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- Kenneson A.,
- Kolor K.,
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