Brain and cognition effects of cardio resynchronization therapy in heart failure

University Of Florida, Gainesville FL

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Abstract

? DESCRIPTION (provided by applicant): Heart failure is a major public health problem contributing to various comorbid medical conditions, physical and cognitive disability. There is increasing evidence that heart failure adversely affects the brain. We have previously shown that heart failure is associated with cognitive impairments, particularly so-called executive functions. We have also shown that CRT improves cognitive performance in patients with heart failure. The proposed study will delineate mechanisms underlying the effects of heart failure on brain function and determine if cognitive benefits of cardio-resynchronization therapy (CRT) are due to enhanced cerebral metabolic and hemodynamic function. There are several potential interacting contributions to brain and cognitive changes in heart failure, including neuro-inflammation, reduced cerebral perfusion and changes in cerebral hemodynamics. Neuroimaging provides access to several potentially powerful biomarkers of alterations in brain structure, function (e.g., fMRI) and hemodynamics (ASL and transcranial Doppler), as well as pathophysiology (DTI and MRS). We know from work we have published in patients with cerebrovascular disease that regional structural damage to white matter and neuropsychological performance predict recovery over time. To date, no published studies have examined neuronal, metabolic and vascular brain changes after CRT, nor have there been studies examining cognitive, functional, and structural brain changes pre-CRT and their impact on recovery. Recent advances in neuroimaging technologies allow for the imaging of patients with CRT devices. We hypothesize that: 1) Patients with cognitive impairment, no dementia who undergo CRT will improve in behaviors dependent on fronto-subcortical systems including processing speed, memory encoding, working memory and task switching. 2) Patients who undergo CRT will exhibit improvements in fMRI indices including default network attributes and task dependent fMRI response. 3) Patients with baseline neuropsychological deficits in cognitive tests of intentional/executive behaviors will be more likely to improve after CRT in the absence of white matter disease in fronto-subcortical systems, implying that the mechanism of impairment is changes in cerebral hemodynamics. 4) Cerebral hemodynamics and metabolite profiles will normalize after CRT. The groups will have equal proportions of cognitive impairment and no cognitive impairment, enabling us to clarify the mechanisms of brain dysfunction in heart failure and their relation to cognition. This study will capitalize on a powerful quasi-experimenta manipulation that will provide a unique window into the effects of heart failure and CRT on the brain.