Heart failure (HF) is an important clinical and public health problem in the U.S, and a major health care burden. Although advances in therapies for HF have improved survival, recurrent hospitalization rates, prevalence, and mortality remain high. The clinical course of HF includes repeated exacerbations that account for repeat hospitalizations and poor clinical outcomes. Precipitating factors for HF exacerbations such as uncontrolled hypertension and medication noncompliance have been identified, and emotional stress may also be an important precipitating factor. Knowledge of these factors has important implications for prevention and treatment. However, the prevalence, time trajectory, and interactions among these precipitating factors are poorly understood. The impact of mental stress in HF patients may be of clinical relevance since exercise capacity and activity levels are reduced in heart failure. Poor prognosis in CAD patients with HF is heightened by increased sympathetic activity and blood pressure, by decreases in LV function often associated with myocardial ischemia, and by malignant arrhythmias. Research demonstrates that emotional stress influences each of these mechanisms. Beta natriuretic peptide (BMP), secreted by cardiac myocytes in response to ventricular stretch and volume overload, is a biological marker of HF presence and severity. Recent advances provide the opportunity to utilize BMP as a more objective biomarker to study effects of emotional stress on HF exacerbations. The direct effects of emotional stress on markers of poor prognosis in HF (hemodynamic, cardiac function, ischemia, and electrophysiologic mechanisms) in CAD patients can also be studied in the laboratory. This project consists of a prospective study of HF precipitants in CAD patients, and a laboratory study of pathophysiologic mechanisms of emotional stress in the same population.
Aims are: 1) to determine the prevalence and time trajectory of emotional stress as a precipitant of HF exacerbations as measured by >50% increases in the biomarker BMP. Secondary analyses will explore relationships between stress and measures of symptoms and functional status;(2) to determine the relationship of emotional stress to other precipitants (e.g., noncompliance with medications, uncontrolled hypertension, etc.) of HF exacerbations, and to determine if stress is a risk factor for HF worsening independent of other precipitants;and 3) to compare mental stress- induced changes in cardiac function, ischemia, and arrhythmic vulnerability in CAD patients with stress- related precipitants of HF exacerbations, to patients with non-stress precipitants, and to patients without exacerbations. This clinical research project will identify and enhanced understanding of the emotional stress and other precipitants of HF decompensation that will aid in preventive and treatment efforts.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Psychosocial Risk and Disease Prevention Study Section (PRDP)
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Kaufmann, Peter G
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Henry M. Jackson Fdn for the Adv Mil/Med
United States
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Keith, Felicia; Krantz, David S; Chen, Rusan et al. (2017) Anger, hostility, and hospitalizations in patients with heart failure. Health Psychol 36:829-838
Harris, Kristie M; Krantz, David S; Kop, Willem J et al. (2017) A New Clinically Applicable Measure of Functional Status in Patients With Heart Failure: The 60-Foot Walk Test. JACC Heart Fail 5:411-420
Endrighi, Romano; Waters, Andrew J; Gottlieb, Stephen S et al. (2016) Psychological stress and short-term hospitalisations or death in patients with heart failure. Heart :
Gottlieb, Stephen S; Harris, Kristie; Todd, John et al. (2015) Prognostic significance of active and modified forms of endothelin 1 in patients with heart failure with reduced ejection fraction. Clin Biochem 48:292-6
Wawrzyniak, Andrew J; Dilsizian, Vasken; Krantz, David S et al. (2015) High Concordance Between Mental Stress-Induced and Adenosine-Induced Myocardial Ischemia Assessed Using SPECT in Heart Failure Patients: Hemodynamic and Biomarker Correlates. J Nucl Med 56:1527-33
Bekkouche, Nadine S; Wawrzyniak, Andrew J; Whittaker, Kerry S et al. (2013) Psychological and physiological predictors of angina during exercise-induced ischemia in patients with coronary artery disease. Psychosom Med 75:413-21
Whittaker, Kerry S; Krantz, David S; Rutledge, Thomas et al. (2012) Combining psychosocial data to improve prediction of cardiovascular disease risk factors and events: The National Heart, Lung, and Blood Institute--sponsored Women's Ischemia Syndrome Evaluation study. Psychosom Med 74:263-70