Background Nearly-universal cardiomyopathy in Duchenne muscular dystrophy (DMD) contributes to heart failure and death. As DMD patients show myocardial fibrosis well before functional impairment, we postulated that earlier treatment using drugs with anti-fibrotic effect may be beneficial. Methods and Results Three groups of 10 utrn+/−;mdx or “het” mice with skeletal myopathy and cardiomyopathy that closely mimics clinical DMD were studied. One het group received spironolactone and lisinopril starting at 8 weeks-of-life (het-treated-8), a second received the same starting at 4 weeks-of-life (het-treated-4), and the third het group was untreated. At 20 weeks, all mice had normal EFs though circumferential strain rate was abnormal (−0.21±0.08) in untreated hets. This improved to −0.40±0.07 in het-treated-8 mice (p=0.003), and further improved to −0.56±0.10 in het-treated-4 mice (p=0.014 for het-treated-4 vs. het-treated-8). Treated mice showed less cardiomyocyte damage, with a 44% reduction in intra-cardiomyocyte serum IgG localization in het-treated-8 mice (p<0.0001), and further 53% reduction in het-treated-4 mice (p=0.0003 vs. het-treated-8); matrix metalloproteinases were similarly reduced. Cardiac, limb and diaphragm function by ex vivo muscle testing remained at 80% of normal with early treatment compared to a decline to 40% of normal skeletal muscle function without treatment. Conclusions These findings offer clinically-available medications with proven anti-fibrotic effect as a new therapeutic strategy in DMD. Early initiation greatly attenuated myocardial disease and, for the first time with these drugs, improved skeletal myopathy. Thus, early initiation of such agents warrants further clinical evaluation to maintain ambulatory, respiratory and cardiac function for DMD and related myopathies.

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Objectives: Increased numbers of end-stage heart failure patients and improved technology have led to increased use of left ventricular assist devices as a viable alternative to heart transplants. Given the current economic climate, we compared costs of heart transplant versus device placement. Materials and Methods: Medical records of patients who received heart transplants or left ventricular assist devices were cross-referenced with institutional financial data. The device cohort was limited to those receiving durable (not temporary) devices. Index admission, 1-year readmission, and overall 1-year charges were compared using standard statistical methods. Results: Of 184 identified patients with end-stage heart failure surgical therapy, 121 received left ventricular assist devices, 43 had heart transplants, and 20 received left ventricular assist devices as bridge to heart transplant; these latter patients were excluded from our analyses. At index admission, mean charges were $863 433 ± $398 427 for device patients and $725 877 ± $488 685 for transplant patients (P = .05). One-year mean readmission rates were similar (4.65/transplant patient and 4.53/device patient; P = .94), with corresponding 1-year survival rates of 87.8% and 78.0% (P = .04). Total readmission charges during year 1 were $169 732 ± $242 366 for device patients and $201 682 ± $297 565 for transplant patients (P = .08), with corresponding overall charges at 1 year of $1 029 732 ± $450 498 and $927 559 ± $562404 (P = .49). Conclusions:During the first year, heart transplant and left ventricular assist device placement have similar costs. Initial index admission costs seem to favor heart transplant, with device pump costs accounting for some of the difference. From a 1-year survival perspective, heart transplant may be more effective; however, with lack of suitable donors, left ventricular assist devices are valuable in the armamentarium of advanced heart failure surgical options.