Medicine (RMH) - Theses
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ItemAtrial fibrillation and heart failure: the impact of atrial fibrillation on cardiac remodeling( 2013)Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular conditions that individually are associated with significant morbidity and mortality. Each has a tendency to promote the other, with grave outcomes resulting when they occur in combination. Despite the prevalence of concurrent AF-HF, pathophysiologic interactions between the two conditions remain to be well understood due in part to their complex and dynamic nature. Utilizing a wide range of complementary laboratory methods in the experimental setting, as well as start-of-the-art imaging and electrophysiologic techniques in a series of clinic studies, this thesis explores the relationship between AF and HF, focusing in particular on the influence of AF on left ventricular remodeling. Two highly novel findings include the following: (i) the irregular ventricular rhythm associated with AF has an adverse impact on ventricular calcium handling and contractile function independent of rate-related effects, and (ii) diffuse ventricular fibrosis resulting from tachycardia-mediated cardiomyopathy persists long after resolution of tachycardia and appears to correlate with AF burden, suggesting that fibrosis may be cumulative with successive periods of poor rate control. These results imply that a strategy of rate-control alone in the management of combined AF-HF is insufficient to protect the left ventricle from the adverse influence of AF, and add weight to the argument for early rhythm control. Further major findings relating to clinical management of combined AF-HF include the following: (i) the pattern of ventricular fibrosis as assessed by cardiac magnetic resonance (CMR) imaging is useful in selecting patients most likely to recovery LV function following catheter-based therapy for AF, and (ii) post-contrast CMR T1 mapping identifies changes in atrial myocardial tissue that parallel electrophysiologic remodeling and are suggestive of atrial fibrosis. Thus, CMR imaging may have a key role in individualizing therapy for patients with combined AF-HF, and place its routine use in clinical practice on the horizon.