| الوصف: |
Background Muscular dystrophy (MD) is a group of inherited neuromuscular disorders with heart disease as a leading cause of morbidity and mortality. Dystrophinopathies such as Duchenne and Becker MD, limb-girdle MD, type 1 myotonic dystrophy (DM1), and facioscapulohumeral MD are most associated with heart disease. Patients present with a broad variety of neuromuscular systems, which complicates prognosis and challenges effective clinical management. Cardiac assessment as well as the impact of cardiac medical and device therapies on patient outcomes has remained an underrepresented facet of clinical research in patients with MD. Objectives To assess the value of cardiac monitoring and management on the clinical outcomes of adult patients with MD. This thesis aimed to further understand heart disease secondary to MD from a clinical perspective through a variety of cardiac assessment modalities while evaluating diagnostic and prognostic utility. Furthermore, the association between cardiac assessment, use of cardiac therapies, and MD patient prognosis was analyzed. Methods and Results In Chapter 3, the impact of cardiac medical and device therapies as a core component of a collaborative multidisciplinary care pathway for the care of patients with MD was explored. Cardiac intervention can markedly improve all-cause and cardiac-related clinical outcomes over a sustained period while also improving left ventricular (LV) systolic function. In Chapter 4, the utility of cardiac plasma biomarkers for the management of heart disease in patients with MD was explored. B-type natriuretic peptide and high-sensitive troponin I were able to effectively diagnose heart disease and prognosticate adverse events using novel cutoff values. In Chapter 5, the utility and morphology of 12-lead electrocardiogram (ECG) in patients with MD was explored. The identification of left bundle branch block (LBBB) and QRS fragmentation was associated with a diagnosis of cardiomyopathy, and LV hypertrophy by contemporary ECG criteria was determined to be of limited utility. In Chapter 6, the incidence of ventricular tachycardia (VT) in patients with DM1 was explored. There was a high prevalence of VT in the patient cohort, which highlighted the risk of sudden cardiac death to attention in patients with DM1. In Chapter 7, the value of cardiac resynchronization therapy (CRT) in patients with DM1 with LBBB was explored. Device intervention by CRT was shown to markedly reduce QRS complex duration and improve LV systolic function. In Chapter 8, the utility of transthoracic echocardiogram-derived left ventricular ejection fraction (LVEF) in a mixed adult MD cohort was explored. Baseline LVEF and trajectory by serial measures showed important diagnostic and prognostic utility for heart disease and major adverse cardiac events (MACE), respectively. In Chapter 9, the utility of cardiac magnetic resonance including advanced imaging techniques in a mixed adult MD cohort was explored. Longitudinal, circumferential, and radial strain amplitudes had important prognostic utility for MACE. Conclusions Heart disease is characterized by adverse remodeling and reduced systolic function and conduction abnormalities in patients with MD. Importantly, heart disease can be effectively monitored and managed through the use of medical and device therapies facilitated by various modalities of cardiac assessment within a multidisciplinary care model. Moreover, the use of novel methods as outlined in this thesis are feasible and accessible in modern clinical practice. Active monitoring and management can reduce the burden of disease to improved clinical outcomes in patients with MD. |
