Effects of steroids and angiotensin converting enzyme inhibition on circumferential strain in boys with Duchenne muscular dystrophy: a cross-sectional and longitudinal study utilizing cardiovascular magnetic resonance

Abstract

Background: Steroid use has prolonged ambulation in Duchenne muscular dystrophy (DMD) and combined with advances in respiratory care overall management has improved such that cardiac manifestations have become the major cause of death. Unfortunately, there is no consensus for DMD-associated cardiac disease management. Our purpose was to assess effects of steroid use alone or in combination with angiotensin converting enzyme inhibitors (ACEI) or angiotension receptor blocker (ARB) on cardiovascular magnetic resonance (CMR) derived circumferential strain (εcc).

Methods: We used CMR to assess effects of corticosteroids alone (Group A) or in combination with ACEI or ARB (Group B) on heart rate (HR), left ventricular ejection fraction (LVEF), mass (LVM), end diastolic volume (LVEDV) and circumferential strain (εcc) in a cohort of 171 DMD patients >5 years of age. Treatment decisions were made independently by physicians at both our institution and referral centers and not based on CMR results.

Results: Patients in Group A (114 studies) were younger than those in Group B (92 studies)(10 ± 2.4 vs. 12.4 ± 3.2 years, p < 0.0001), but HR, LVEF, LVEDV and LVM were not different. Although εcc magnitude was lower in Group B than Group A (-13.8 ± 1.9 vs. -12.8 ± 2.0, p = 0.0004), age correction using covariance analysis eliminated this effect. In a subset of patients who underwent serial CMR exams with an inter-study time of ~15 months, εcc worsened regardless of treatment group.

Conclusions: These results support the need for prospective clinical trials to identify more effective treatment regimens for DMD associated cardiac disease.

Figure 1

Serial ejection fraction (EF) and circumferential strain (ε_cc). Red, indicates decreased EF and ε_cc magnitude; blue, indicates increase EF and ε_cc magnitude and black, indicates mean EF and ε_cc values. Panels A-C show EF of each subject plotted serially; there was no significant change in mean EF across all three groups. Individually 14/28 (50%) in Group A, 21/31(68%) in Group B and 5/11 (45%) in Group A to B transition had decrease EF, while 14/28 (50%), 10/31 (32%) and 6/11 (55%) of the individuals in the respective groups had increase EF. Panels D-F show ε_cc of each subject plotted serially; although all three groups had lower absolute ε_cc on the follow-up study, only Group B subjects had a significant decline (p = 0.007). Individually ε_cc magnitude decreased more consistently across all three groups, with 24/28 (86%) in Group A, 26/31 (84%) in Group B and 9/11 (82%) in Group A to B. Unlike EF, only a small fraction of the individuals have improvement of ε_cc magnitude on follow-up study with 4/28 (14%), 5/31 (31%) and 2/11 (18%) of the individuals in the respective group having an increase ε_cc value on follow-up study.