Neuro-Cardio-Autonomic Modulations in Children with Duchenne Muscular Dystrophy

Abstract

Background and Objective: Duchenne muscular dystrophy (DMD) is a degenerative X-linked muscle disease. Death frequently results from complications in cardiopulmonary systems. Preclinical/early diagnosis of cardiac autonomic abnormalities may aid initiate cardioprotective therapy and enhance prognosis. Methods: A cross sectional, prospective study of 38 DMD boys compared with 37 age-matched healthy controls was conducted. Lead II electrocardiography and beat-to-beat blood pressure were recorded to assess heart rate variability (HRV), blood pressure variability (BPV), and baroreceptor sensitivity (BRS) in a standardized environment. Data were analysed and correlated with disease severity and genotype. Results: In the DMD group, the median age at assessment was 8 years [IQR 7–9 years], the median age at disease onset was 3 years [IQR, 2–6 years], and the mean duration of illness was 4 years [IQR, 2.5–5]. DNA sequencing showed deletions in 34/38 (89.5 %) and duplications in 4/38 (10.5%) patients. The median heart rate in DMD children was significantly higher [101.19 (Range, 94.71–108.49)] /min compared to controls [81 (Range, 76.2–92.76)] /min (p < 0.05). All the assessed HRV and BPV parameters were significantly impaired in DMD cases except for the coefficient of variance of systolic blood pressure. Further, BRS parameters were also significantly reduced in DMD, excluding alpha-LF. A positive correlation was found between alpha HF with age at onset and duration of illness. Conclusion: This study demonstrates a distinct early impairment of neuro-cardio-autonomic regulation in DMD. Simple yet effective non-invasive techniques such as HRV, BPV, and BRS may help identify cardiac dysfunction in a pre-clinical state, paving the way for early cardio-protective therapies and limiting disease progression in DMD patients.

Alterações Eletrocardiográficas e do Sistema Nervoso Autônomo com a Mudança de Postura em Crianças e Adolescentes com Distrofia Muscular de Duchenne

“…Em saudáveis, a mudança de postura da supina para o ortostatismo resulta em redução do tônus vagal e ativação simpática pela menor distensão das terminações nervosas dos barorreceptores, com aumento da FC. 30,31 A taquicardia sinusal, inclusive ao repouso, pode ocorrer na DMD sem disfunção sistólica, sendo considerada um risco para miocardiopatia dilatada futura, 9,32,33 e pode associar-se ao desequilíbrio simpático vagal. 10 Inbaraj et al, 32 com uma casuística de 38 pacientes com DMD e 37 saudáveis com mediana de idade de 8 anos demonstraram, em concordância com os resultados deste estudo, taquicardia sinusal e diminuição da VFC no grupo com DMD, concluindo que essas alterações podem ser detectadas no estado pré-clínico.…”

“…30,31 A taquicardia sinusal, inclusive ao repouso, pode ocorrer na DMD sem disfunção sistólica, sendo considerada um risco para miocardiopatia dilatada futura, 9,32,33 e pode associar-se ao desequilíbrio simpático vagal. 10 Inbaraj et al, 32 com uma casuística de 38 pacientes com DMD e 37 saudáveis com mediana de idade de 8 anos demonstraram, em concordância com os resultados deste estudo, taquicardia sinusal e diminuição da VFC no grupo com DMD, concluindo que essas alterações podem ser detectadas no estado pré-clínico. Porém, a VFC foi feita somente com a derivação D2, diferente do presente estudo, no qual foram utilizadas 12 derivações e com correção manual de batimentos ectópicos, pausas e interferências.…”