Heart failure (HF) patients show multiple neuropsychological and cardiovascular abnormalities which indicate changes in brain function. Brain injury, defined as loss of tissue and changes in tissue properties and function, occurs in areas which regulate mood, memory, blood pressure, heart rate, and breathing. All of these symptoms have been linked to increased morbidity and mortality in HF. However, the processes which elicit this brain injury are uncertain. Sleep-disordered breathing (SDB) characterized by repetitive hypoxia/reperfusion of oxygen and intermittent ischemia is common in HF, and may contribute significantly to brain damage found in the syndrome. However, the relationship between SDB and the extent and location of brain injury in HF patients is not established. We hypothesize that processes accompanying ischemia and hypoxia, and subsequent reperfusion associated with sleep-disordered breathing (SDB) in HF initiate and exacerbate the brain injury. We will 1) demonstrate that the extent of gray matter damage (assessed by structural magnetic resonance imaging, including mean diffusivity and fractional anisotropy) in HF depends on the presence of SDB (assessed via overnight polysomnography);2) show that nerve fibers (white matter - evaluated via structural MRI and fiber tracking techniques) interconnecting major autonomic control structures are injured in HF patients with SDB;and 3) Determine whether the extent of brain injury (gray matter damage and white matter integrity) relates to aspects of deoxygenation/oxygen reperfusion during SDB, and whether such disordered breathing is more injurious during particular sleep states, or with more-frequent oxygen reperfusion. Using 2-group comparative and correlational designs, 80 subjects (30 HF subjects with SDB, 30 HF subjects without SDB, 20 healthy controls without SDB) will undergo structural MRI and overnight polysomnography studies. Inclusion criteria for all subjects will be age 40 - 65 yrs;HF will be systolic dilated, and LVEF <0.40. Exclusion criteria for all subjects include claustrophobia, presence of loose metal (for example, pacemakers, braces, implanted hearing aids, or embolic coils). Statistical tests will consist of T-tests and Pearson's correlations with significance set at p <0.05. The objective is to determine whether SDB is associated with alterations in brain structure in HF, and whether oxygenation/reperfusion processes accompanying apnea could lead to brain injuries in the syndrome. Determining the ongoing detrimental processes which cause brain damage in HF is essential to develop innovative treatments to reduce or prevent brain injury which can exacerbate the autonomic, cognitive, and mood deficits in this high-risk patient population.

Public Health Relevance

/Relevance: Heart failure patients show multiple neuropsychological and cardiovascular abnormalities which indicate changes in brain function, and have been linked to increased morbidity and mortality in the syndrome. We reported brain injury, appearing as tissue loss or changes, and altered function in areas which regulate mood, memory, blood pressure, heart rate, and breathing;however, the processes underlying these brain alterations are uncertain. Sleep-disordered breathing imposes repetitive exposure to hypoxia and ischemia, is common in heart failure, and may contribute significantly to the brain damage. However, the relationship between sleep-disordered breathing and the extent and location of brain injury in heart failure patients is not established. Determining an association between sleep-disordered breathing components (such as the extent of decline in oxygen saturation, total duration of oxygen desaturation as reflected in apnea time, the number of oxygen reperfusions as indicated by number of arousals from apnea, and the patterns of sleep states) and extent of brain injury (evaluated by brain magnetic resonance imaging of gray and white matter) would allow health care providers to identify patients at increased risk for brain damage as well as to select and implement interventions which could alleviate the autonomic and neuropsychological impairment.

National Institute of Health (NIH)
National Institute of Nursing Research (NINR)
Research Project (R01)
Project #
Application #
Study Section
Nursing Science: Adults and Older Adults Study Section (NSAA)
Program Officer
Huss, Karen
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Nursing
Los Angeles
United States
Zip Code
Serber, Stacy L; Rinsky, Brenda; Kumar, Rajesh et al. (2014) Cerebral blood flow velocity and vasomotor reactivity during autonomic challenges in heart failure. Nurs Res 63:194-202
Pan, Alan; Kumar, Rajesh; Macey, Paul M et al. (2013) Visual assessment of brain magnetic resonance imaging detects injury to cognitive regulatory sites in patients with heart failure. J Card Fail 19:94-100
Kumar, Rajesh; Delshad, Sean; Woo, Mary A et al. (2012) Age-related regional brain T2-relaxation changes in healthy adults. J Magn Reson Imaging 35:300-8
Macey, Paul M; Wu, Paula; Kumar, Rajesh et al. (2012) Differential responses of the insular cortex gyri to autonomic challenges. Auton Neurosci 168:72-81
Kumar, Rajesh; Woo, Mary A; Macey, Paul M et al. (2011) Brain axonal and myelin evaluation in heart failure. J Neurol Sci 307:106-13
Macey, Paul M; Woo, Mary A; Kumar, Rajesh et al. (2010) Relationship between obstructive sleep apnea severity and sleep, depression and anxiety symptoms in newly-diagnosed patients. PLoS One 5:e10211
Vespa, P M; McArthur, D L; Xu, Y et al. (2010) Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy. Neurology 75:792-8
Kumar, Rajesh; Woo, Mary A; Birrer, Bramley V X et al. (2009) Mammillary bodies and fornix fibers are injured in heart failure. Neurobiol Dis 33:236-42
Woo, Mary A; Kumar, Rajesh; Macey, Paul M et al. (2009) Brain injury in autonomic, emotional, and cognitive regulatory areas in patients with heart failure. J Card Fail 15:214-23
Woo, Mary A; Macey, Paul M; Keens, Peter T et al. (2007) Aberrant central nervous system responses to the Valsalva maneuver in heart failure. Congest Heart Fail 13:29-35