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

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.

Effect of Yoga as an Add-on Therapy in the Modulation of Heart Rate Variability in Children with Duchenne Muscular Dystrophy.

BACKGROUND: Duchene muscular dystrophy (DMD) is a progressive muscular disorder. Cardiac disorder is the second-most common cause of death in children with DMD, with 10%-20% of them dying of cardiac failure. Heart rate variability (HRV) is shown to be a predictor of cardio-autonomic function. Physiotherapy (PT) is advised for these children as a regular treatment for maintaining their functional status. The effect of yogic practices on the cardio-autonomic functions has been demonstrated in various neurological conditions and may prove beneficial in DMD. MATERIALS AND METHODS: In this study, 124 patients with DMD were randomized to PT alone or PT with yoga intervention. Home-based PT and yoga were advised. Adherence was serially assessed at a follow-up interval of 3 months. Error-free, electrocardiogram was recorded in all patients at rest in the supine position. HRV parameters were computed in time and frequency domains. HRV was recorded at baseline and at an interval of 3 months up to 1 year. Repeated-measures ANOVA was used to analyze longitudinal follow-up and least significant difference for post hoc analysis and P < 0.05 was considered statistically significant. RESULTS: In our study, with PT protocol, standard deviation of NN, root of square mean of successive NN, total power, low frequency, high-frequency normalized units (HFnu), and sympathovagal balance improved at varying time points and the improvement lasted up for 6-9 months, whereas PT and yoga protocol showed an improvement in HFnu during the last 3 months of the study period and all the other parameters were stable up to 1 year. Thus, it is evident that both the groups improved cardiac functions in DMD. However, no significant difference was noted in the changes observed between the groups. CONCLUSION: The intense PT and PT with yoga, particularly home-based program, is indeed beneficial as a therapeutic strategy in DMD children to maintain and/or to sustain HRV in DMD.

Assessment of cardiac autonomic function in patients with Duchenne muscular dystrophy using short term heart rate variability measures.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a hereditary neuromuscular disorder frequently associated with progressive cardiac dysfunction, and is one of the common causes of death in these children. Early diagnostic markers of cardiac involvement might help in timely intervention. In this study we compared the short term HRV measures of DMD children with that of healthy subjects. METHOD: One hundred and twenty-four genetically confirmed boys with DMD and 50 age matched controls were recruited. Error-free, electrocardiogram was recorded in all subjects at rest in the supine position. HRV parameters were computed in time and frequency domains. Time domain measures included standard deviation of NN interval (SDNN), and root of square mean of successive NN interval (RMSSD). Frequency domain consisted of total, low frequency and high frequency power values. Ratio of low frequency and high frequency power values (LF/HF) was determined using customized software. RESULTS: HRV parameters were significantly altered in DMD children as compared to healthy controls. Following parameters [mean (SD)] were reduced in DMD as compared to controls; RMSSD (in ms) [52.14 (33.2) vs 64.64 (43.2); p = 0.038], High frequency component (nu) [38.77 (14.4) vs 48.02 (17.1); p = 0.001] suggesting a loss of vagal tone. In contrast, measure of sympathovagal balance LF/HF [1.18 (0.87) vs 0.89 (0.79); p = 0.020] was increased in DMD group. CONCLUSION: In this cross sectional study we have demonstrated alteration in autonomic tone in DMD. Loss of vagal tone and an increase in sympathetic tone were observed in DMD children. Further prospective studies are required to confirm the utility of these measures as predictors of adverse cardiac outcome in DMD.

Influence of age and gender on autonomic regulation of heart.

Heart rate variability (HRV) is a non-invasive method to measure cardiac autonomic function. Impairments in HRV have been proposed as independent risk factor for increased cardiac mortality and morbidity. Cardio protective phenomenon in females has been hypothesized to be due to differential autonomic tone. Age related loss of vagal control has been reported as predisposing factor for the development of cardiovascular disease. In this study we assessed effect of age and gender on autonomic regulation of heart in healthy volunteers. HRV data of 189 subjects (114 males and 75 females) were analyzed in time and frequency domains using customized program. Artifact free 5 min electrocardiogram segment was used for analysis. It was ensured that none of the subject had medical illness such as diabetes, hypertension, thyroid disorders, cardiac disorders, diseases potentially related with autonomic neuropathy and major psychiatric illness by careful history and clinical examination. HRV recordings were done under standard laboratory condition. On correlation analysis SDNN, RMSSD, total power negatively correlated with age suggesting reduced autonomic regulation of heart with increase in age (SDNN: r = -0.444, p < 0.01; RMSSD: r = -0.552, p < 0.01; total power: r = -0.474, p < 0.01); similarly High frequency power (HF.nu) negatively correlated with age (r = -0.167, p = 0.02), denoting loss of vagal tone with aging. LF/HF ratio correlated positively with age (r = 0.19, p < 0.01) suggesting a relative increase of sympathetic activity with increase in age. On multiple regression analysis to control for effect of age and heart rate while comparing males and females, LF.nu showed significant reduction suggesting lower sympathetic tone in females (ß = -6.64; p < 0.01) and HF.nu showed increase at trend level (ß = 4.47; p = 0.053). In conclusion, there is overall reduction in autonomic control of heart with increase in the age. Sympathetic tone predominates and vagal tone diminishes with aging process. Females showed greater vagal tone than male. This differential autonomic tone indicate age, gender related predisposition to cardiovascular disease.