Autonomic Dysfunction: A Driving Force for Myocardial Fibrosis in Young Duchenne Muscular Dystrophy Patients?

Abstract

Cardiac manifestations of Duchenne muscular dystrophy (DMD) include progressive cardiac dysfunction and an elevated resting heart rate (HR). We hypothesized this elevated HR reflects autonomic dysfunction that can be identified by heart rate variability (HRV) analyses which will be associated with myocardial fibrosis by cardiac magnetic resonance imaging (cMR). DMD patients (N = 74) and controls (N = 17) had time and frequency domain HRV analyses calculated via Holter monitoring. Cardiac magnetic resonance imaging was performed on DMD cases only. χ (2) test, T test, ANOVA, and logistic regression were used to perform comparisons between groups. A p value of <0.05 was used for statistical significance. DMD cases had higher resting average HR than controls (99.4 ± 8.9, 85.4 + 6.2, p < 0.001). Among HRV variables, decreases were seen in the following: standard deviation of R to R intervals, the percent RR intervals differing by >50 ms from previous RR interval, the root-meansquare of successive differences of RR intervals, the standard deviation of the mean R to R segment (SDANN), low frequency, and high frequency domain, all p values 0.001. Maximum HR and SDANN most significantly associated with positive LGE on cMR (p = 0.008, p = 0.016). DMD cases on beta blocker had an average HR lower than those not on beta blocker (p = 0.009), but with no difference in HRV analysis. DMD patients have reduced HRV and therefore autonomic dysfunction prior to the onset of heart failure which is associated with myocardial fibrosis.

Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association

“…This was followed by the finding that autonomic dysfunction before the onset of HF was associated with myocardial fibrosis, which suggests a role for earlier treatment. 173 These studies suggest similar benefits to those seen in adult HF, with improvement in LVEF and mortality, and possibly greater benefit than has been seen in pediatric populations of diverse HF pathogeneses.…”

“…134 Periodic ambulatory electrocardiographic monitoring has also been advocated for screening, follow-up, and symptom-directed assessment of arrhythmia in patients with DMD and BMD. 164,[169][170][171][172][173] Ambulatory electrocardiographic monitoring can be useful to detect the diminished heart rate variability indicative of sympathetic predominance and increased susceptibility to ventricular arrhythmias. 174,175 However, 2 recent retrospective studies of ambulatory electrocardiographic monitoring by guest on May 9, 2018 http://circ.ahajournals.org/ Downloaded from e210 results in 235 DMD patients 14±4 years of age and 91 patients 17±4 years of age found only LVEF <30% to 35% and increased age (eg, ≥17 years) were associated with abnormal ambulatory electrocardiographic findings, such as nonsustained atrial and ventricular tachycardias.…”

Autonomic Modulation in Duchenne Muscular Dystrophy during a Computer Task: A Prospective Control Trial

“…Moreover, the researched deficiencies in the musculoskeletal system [5] and cardiac autonomic dysfunction have been previously well researched in DMD [21, 22]. …”

“…Likewise, Thomas et al [21] studied heart rate autonomic dysfunction in DMD. These authors assessed HRV in DMD and in a healthy control group by 24-hour Holter monitoring.…”

“…Whilst recent literature has revealed lesser HRV in DMD [21, 22], the specific cardiac autonomic response of this population is unclear when undergoing stimulation through computer tasks. There is little research on virtual technology procedures in DMD.…”