Heart failure (HF) afflicts almost 5 million persons in the United States. A hallmark of HF is poor autonomic nervous system (ANS) control, especially high sympathetic (SYM) activity, which is linked to HF disease progression, dysrhythmias, and mortality risk. In a recent study, we found that HF is associated with severe gray matter injury in brain areas that control ANS outflow. These brain areas included the right and left insula, with the right insula more affected. However, it is unknown whether the extensive insular damage would be reflected in a larger HF sample, and it is unclear whether the right or the left insular injury is linked to the high SYM tone found in HF cases. The goals of this proposal are to determine whether the insular gray matter injury and abnormal reactivity to ANS challenges found earlier are reflected in a larger sample of HF patients, and if such insular injury is related to impaired SYM and/or parasympathetic (PS) outflow.
The specific aims of this study are to: 1) compare insular gray matter loss between HF and healthy controls using structural magnetic resonance imaging (MRI); 2) compare insular cortex responses in HF patients to SYM and PS components of ANS challenges (Valsalva maneuver and cold pressor) to healthy controls using functional MRI; and 3) correlate levels of plasma catecholamines to volume of insular injury in HF using structural MRI. The sample will consist of 80 subjects (40 HF and 40 age- and gender-matched healthy controls) who will undergo structural MRI, and physiological recording and functional MRI during ANS challenges with blood catecholamine analysis. We hypothesize that right insular damage will result in exaggerated catecholamine release, with more extensive levels related to greater damage, and that magnitude of PS physiologic effects will directly depend on extent of left insular injury. This study's findings will lead to a greater understanding of the relationship between central and peripheral autonomic nervous system activity in HF, and aid in the evaluation of the impact of central nervous system damage on HF disease status.
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