Progressive left ventricular dysfunction and long-term outcomes in patients with Duchenne muscular dystrophy receiving cardiopulmonary therapies.

Objective: To describe the natural history of cardiomyopathy in patients with Duchenne muscular dystrophy (DMD) who are receiving contemporary therapies. Methods: This is a single-institution retrospective cohort study of 57 patients aged >15 years with DMD. Serial digital echocardiograms were performed over a median follow-up of 8 years. Left ventricular dysfunction (LVD) was defined as shortening fraction (SF) <29% plus focal wall motion abnormalities. Therapies included ACE inhibitors, beta-blockers and assisted ventilation. Results: The SF declined progressively in 53/57 patients (93%). LVD occurred in 40 of 57 patients (70%), with variable age at onset (median 18 years, IQR 14-21.5 years). Rate of SF decline (-1.51%±1.16%/year) was variable and unrelated to genotype. However, survival was shorter for patients with LVD onset at age <18 years vs onset at ≥18 years (death at 21.1±2.5 years vs 33.1±4.4 years; P<0.001). Death occurred in 27/57 (47%) patients at a median age of 26.3 years (IQR 20.6-31.5). Death was preceded by LVD in 22/27 patients (81%), 15 (68%) of whom developed class 4 heart failure (CHF). Time from CHF to death was brief (median 8.0 months). Conclusion: Despite contemporary therapies, SF declined progressively in almost all patients. Age at onset of LVD and age at death were variable and unrelated to genotype; however, survival was shortened for patients with LVD onset at age <18 years. Death was usually preceded by LVD. CHF was a sentinel event, with death occurring shortly thereafter.

Left ventricular dysfunction in duchenne muscular dystrophy and genotype.

Prognosis in patients with Duchenne muscular dystrophy (DMD) is guarded, and most deaths are due to cardiac or respiratory causes. It is unclear if some DMD gene mutations might be predictive of either mild or severe cardiac dysfunction. We studied 75 patients with DMD followed at our institution. Cardiac function, as assessed by yearly echocardiography, showed marked variability in left ventricular (LV) function. Some patients in their 3rd decade had no or minimal dysfunction, whereas others in their 2nd decade had very severe dysfunction. Therefore, 4 severity groups were defined ranging from no or mild LV dysfunction to severe LV dysfunction using patient age at first abnormal echocardiographic finding and degree of LV dysfunction. Genetic data were collected for all patients. Most patients had mutations from exon 1 to 20 to exon 41 to 55. The distribution of the 4 severity groups of LV dysfunction did not significantly differ between these 2 mutation groups. An analysis based on the number of exons involved (<5 vs ≥5 exons) also found no significant difference in cardiac severity. When patients having identical mutations were compared with their cardiac course, concordance was often not evident. Steroid therapy had no apparent protection for the development of cardiomyopathy. In conclusion, 75 patients with DMD showed marked variability in the severity of LV dysfunction. Neither the age of onset nor the severity of cardiomyopathy correlated with any of the mutation groups.

B-type natriuretic peptide and cardiac dysfunction in Duchenne muscular dystrophy.

Serum levels of B-type natriuretic peptide have moderate utility for detection of early ventricular dysfunction in adults and in experimental muscular dystrophy. To determine if B-type natriuretic peptide levels are useful in the detection of early left ventricular dysfunction in Duchenne muscular dystrophy patients, measurements were obtained in 21 patients being evaluated by echocardiography for left ventricular dysfunction. Two patients with clinical evidence of heart failure were excluded (mean B-type natriuretic peptide level of 352 pg/ml). Age range of the remaining 19 patients was 9-21 yrs. Fractional shortening was abnormal (<30%) in 14/19 and early diastolic tissue Doppler velocities were abnormal in 13/16. In these patients B-type natriuretic peptide levels were clearly normal (<30 pg/ml) in 15/19 and only mildly elevated (30-80 pg/ml) in 4/19. The 4 patients with mildly elevated B-type natriuretic peptide had significantly lower fractional shortening (12.6+/-5.9 versus 19.8+/-5.3, p<0.05). In conclusion, B-type natriuretic peptide levels are normal in the majority of Duchenne muscular dystrophy patients with asymptomatic left ventricular dysfunction and only mildly elevated when fractional shortening is markedly reduced.

Nephrolithiasis in patients with duchenne muscular dystrophy.

OBJECTIVES: To present the first series of patients with Duchenne muscular dystrophy (DMD) and nephrolithiasis. METHODS: A retrospective chart review was done to identify patients with DMD who were referred for urologic consultation because of nephrolithiasis from June 2004 to April 2006. RESULTS: Four patients were identified with DMD and nephrolithiasis. Of the 4 patients, 2 underwent treatment, and their stones were obtained for analysis. The other 2 patients had stones diagnosed by computed tomography. Their stones were passed but not retrieved. Stone analysis for the available patients revealed a mixed calcareous composition. All 4 patients had had a relatively small stone burden. The patients ranged in age from 18 to 31 years. CONCLUSIONS: Stone disease appears to have many of the same characteristics in patients with DMD as it does in the general population. Risk factors, including immobilization and corticosteroid use, are present. Additional studies are needed before conclusions can be made regarding the associations between DMD and nephrolithiasis.

Contribution of Doppler tissue imaging and myocardial performance index to assessment of left ventricular function in patients with Duchenne's muscular dystrophy.

Doppler tissue velocities (DTV) are abnormal in a variety of cardiac conditions when standard measures of ventricular function are normal. Detection of left ventricular dysfunction in Duchenne's muscular dystrophy (DMD) has relied on 2-dimensional imaging yet often these images are suboptimal. This study was undertaken to determine if DTV and the myocardial performance index (MPI) could provide additional diagnostic information in DMD. We determined in 31 patients and 13 age-matched control subjects the prevalence of both abnormal DTV of the mitral annulus and abnormal MPI. Mean values for early diastolic DTV were significantly lower for patients compared with control subjects (P < .001) and were abnormally low in 86% of patients. The MPI was abnormal in 79% of patients. All but one patient with DMD had either abnormal DTV or abnormal MPI yet 19% had normal fractional shortening. DTV and MPI are important additions to the echocardiographic evaluation of patients with DMD.