| Characteristics of clinical, electrocardiographic (ECG), and imaging risk markers for prediction of sudden death in high versus relatively low risk populations are examined in this thesis. The high-risk population, myotonic muscular dystrophy, is an inherited multi-system disorder associated with myotonia, progressive skeletal muscle weakness, and sudden cardiac death. 1, 2 Cytosine-thymine-guanine (CTG) repeats on chromosome 19 in the 3' untranslated region of a serine-threonine protein kinase gene underlie type I myotonic muscular dystrophy (MMD-I), the more common form of the disease. 3 Type II MMD is associated with CCTG tetra-nucleotide repeats in intron 1 of the zinc finger protein 9 gene (ZNF9). 4 The presence of severe baseline ECG abnormalities is associated with sudden death in adults with MMD-I,2 and points to progression of atrioventricular (AV) block or ventricular arrhythmia as the predominant mode of cardiac mortality in this population. Additionally, patients with MMD and atrial fibrillation (AF) appear to have an elevated risk for development of AV block.2, 5 However, these abnormalities are commonly observed in patients with MMD, and provide a low positive predictive value for identification of risk for sudden death. We have previously shown that myocardial scar imaging can identify the substrate for inducible ventricular tachycardia (VT) in patients with non-ischemic cardiomyopathy.6 This technique has since been validated by other groups, and was later shown to identify non-ischemic cardiomyopathy patients at high risk of sudden death. 7, 8 This thesis describes a) the trends and clinical predictors of time dependent ECG variations in MMD, b) magnetic resonance imaging findings regarding cardiac function and diffuse fibrotic changes in MMD, and c) the association between elevation at various ST points and sudden death, and the heterogeneity of this association in the biracial population of the Atherosclerosis Risk in Communities (ARIC) study. The topics are broad and encompass two different populations; however, an underlying common theme is the characterization of risk factors for sudden death. The strengths and weaknesses of each population under study, the study designs, and implications upon results and future utility of findings will be discussed. |
