Exploring A Potential Relation Between Autonomic And Myocardial Function In Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a rare muscle wasting disorder with a high cardiovascular mortality rate. Remodeling of the myocardium presents early as fibrosis, later progressing to left ventricular (LV) dysfunction. Heart rate variability (HRV) is a measure of cardiac autonomic balance impaired in boys with DMD. However, the relation between HRV and LV function in DMD is not yet understood. PURPOSE: To (1) characterize HRV and LV function in boys diagnosed with DMD (n = 8; 15 ± 6 yrs. old) as compared to typically developing controls (n = 21; 14 ± 5 yrs. old) and (2) explore a potential relation. METHODS: HRV during quiet breathing was assessed for 5 minutes in the time-domain as root mean square of the successive differences (RMSSD). Mitral early (E) and late (A) diastolic filling velocities were measured using pulsed-wave Doppler echocardiography and the ratio calculated (E/A). Diastolic tissue velocity e' was measured as the average of the septal and lateral region using tissue Doppler imaging and used to calculate the E/e' ratio. LV systolic ejection time (LVET) and pre-ejection period (LVPEP) were assessed using Pulsed Doppler transmitral flow and aortic ejection flow in the apical long-axis view. Group differences were compared using Mann-Whitney U tests and correlations using Pearson’s test. RESULTS: RMSSD was reduced in the boys with DMD (DMD: 33 ± 21 vs. Con: 87 ± 42 ms, p = 0.002). The mitral E/A ratio was also reduced (DMD: 1.51 ± 0.26 vs Con: 2.51 ± 0.66, p < 0.001), driven by an increase in the A wave velocity (DMD: 0.51 ± 0.10 vs Con: 0.33 ± 0.08 m/s, p < 0.001). Average e' was reduced in the DMD group (DMD: 0.11 ± 0.02 vs Con: 0.15 ± 0.02 m/s, p < 0.001), which translated to an elevated E/e' (DMD: 7.33 ± 2.19 vs Con: 5.29 ± 1.06, p = 0.007). RMSSD was moderately associated with A wave velocity (r = -0.45,p = 0.02), average e' (r = 0.63,p < 0.001), and average E/e' (r = -0.63,p < 0.001) when all data were pooled. In a subset (n = 4) of boys with DMD, LVET (DMD: 354 ± 86 vs. Con: 479 ± 85 ms, p = 0.01) and LVPEP (DMD: 58 ± 4.1 vs. Con: 67 ± 11 ms, p = 0.06) were reduced, but with no change in LVPEP/LVET (DMD: 0.17 ± 0.05 vs. Con: 0.14 ± 0.03, p = 0.30). CONCLUSIONS: Preliminary findings suggest reduced vagal tone, global LV function, but no change in cardiac sympathetic activity in patients with DMD, with a possible relation between LV function and HRV. Supported by NIH 1R01HLI55764