Trajectory of left ventricular ejection fraction in response to therapies in patients with muscular dystrophy

Background Patients with muscular dystrophy (MD) are at elevated risk of serious cardiac complications and clinical assessment is limited due to inherent physical limitations. We assessed the utility of left ventricular ejection fraction (LVEF) derived from transthoracic echocardiogram (TTE) as a prognostic marker for major adverse cardiac events (MACE) in a mixed adult MD cohort. Methods One hundred and sixty-five MD patients (median age: 36 (interquartile range [IQR]: 23.0-49.0) years; 65 [39.4%] females) were enrolled in our prospective cohort study. Diagnoses included dystrophinopathies (n = 42), limb-girdle MD (n = 31), type 1 myotonic dystrophy (n = 71), and facioscapulohumeral MD (n = 21). Left ventricular ejection fraction, ventricular dimensions at end-diastole and end-systole, and serial measures (n = 124; follow-up period: 2.19 [IQR: 1.05-3.32] years) stratified patients for MACE risk. Results Cardiomyopathy was diagnosed in 60 (36.4%) patients of the broader cohort (median LVEF: 45.0 [IQR: 35.0-50.0] %). Ninety-eight MACE occurred over the 7-year study period. At baseline, patients with a LVEF < 55.0% had a high risk of MACE (adjusted odds ratio: 8.30; 95% confidence interval [CI]: 3.18-21.7), concordant with the analysis of LV dimensions. Forty-one percent of these patients showed an improvement in LVEF with the optimization of medical and device therapies. Relative to patients with preserved LVEF, patients with reduced LVEF were at an elevated risk of MACE (adjusted hazard ratio [aHR]: 7.21; 95% CI: 1.99-26.1), and improved LVEF resulted in comparable outcomes (aHR: 1.84; 95% CI: .49-6.91) associated with optimization of medical and device therapies. Reduction in QRS duration by CRT therapy was associated with an improvement in LVEF (average improvement: 12.8 [+/- 2.30] %; p = .04). Conclusions Reduction in LVEF indicates an increased risk of cardiovascular events in patients with MD. Baseline and serial LVEF obtained by TTE can prognosticate patients for MACE and guide clinical management.