P338
Dystrophin deficient cardiomyopathy: predictors associated with the cardiac phenotype in a Duchenne registry population - A guide for device therapy

Patients with Duchenne muscular dystrophy (DMD) typically exhibit cardiac dysfunction. With increasing life expectancy due to advances in respiratory support, cardiomyopathy and associated dsyrhythmia are fast becoming the primary cause of morbidity and mortality in this patient group. Despite advances, the correlation between genotype and cardiac phenotype remains poorly understood and individual registries small, with implementation of device therapy often delayed due to poor diagnostic imaging. 

Methods and Aims: A single-center registry for DMD patients was established and data including genotyping, medical therapy and investigations such as cardiac MRI, nt-Pro BNP levels, echocardiogram were analysed. The aim was to potentially identify predictors associated with a more severe cardiac phenotype and thus help to guide provision of device therapy.  

A total of 19 patients (age 17 - 31) with DMD were reviewed (demographics table 1). All patients were evaluated with echocardiography on at least one occasion (mean EF 46.5%). Cardiac MRI was attempted in 6 patients however only completed in 2 due to contractures preventing access to scanning. 11 of 19 patients (58%) demonstrated an impaired left ventricular ejection fraction (EF) <50% (mean EF 42%). Proximal "hot spot" mutations/deletions (exon 2-19) were associated with a more pronounced reduction in EF, all patients with proximal mutations demonstrating an EF < 45% (mean 41%). 5 of 6 (83%) of those with >1 exon deletion mutations demonstrated more severely impaired EF (mean EF 41%) compared to those with single exon deletions (mean EF 52%). Interestingly, one patient with a proximal mutation (exon 3-6 deletion) remains mobilising to distances of 70 meters, however cardiac MRI revealed a moderate degree of fibrosis with an EF of 43%. Correlation between nt-Pro BNP levels with reduced EF was not uniform, however a level < 100 was associated with an EF >55% in 89% of patients studied. of those on steroid regimes, 6 (54%) had impaired LVEF compared to 5 (83%) of those not on steroid therapy. All patients were on at least one class of heart failure modification, with 79% on two and 37% on three agents. Only one patient in the registry has had an ICD implanted. He has had a device for 10 years in and in this time there have been no therapies delivered however runs of non-sustained ventricular tachycardia have been noted. 

Correlation between predictors and cardiac phenotype in a Duchenne population remains unreliable. Location and size of exon alteration appears to be indicative of more markedly impaired LV function, however larger studies are required to characterise this further and challenges remain with regard to accurate assessment of EF. The use of predictors in future may help to guide appropriate provision of device therapy.