Project Summary Heart failure (HF) affects an estimated 6.2 million adults in the United States.1 Importantly, this debilitating syndrome causes significant morbidity and mortality with nearly 80,000 HF-related deaths reported annually.1 Fatigue is a prevalent and distressing symptom for patients with HF and evidence suggests that it has significant prognostic and outcome implications.2,3,4 The presence and increased severity of fatigue in HF increases the risk of hospitalization5,6 and mortality7,8 and is associated with increased depression3,4,9,10, poorer quality of life11,12, worse self-care13, and reduced physical14,15,3, social14, and emotional functioning.16 Fatigue in HF has been characterized in the literature as two types 1) general fatigue and 2) exertional fatigue. 1) general fatigue and 2) exertional fatigue. General and exertional fatigue and their co-occurrence are important to understand because their predictors and associated outcomes may differ. Accurate identification of fatigue type may lead to different interventions to alleviate that fatigue. However, little evidence examines patient reported and clinical outcome differences between general and exertional fatigue, clinically relevant predictors of fatigue have not been identified, and differences in the fatigue experience between HFrEF and HFpEF have not yet been explored. This creates a cap in our understanding of the risk factors for, and associated outcomes of fatigue type in HF. Using a secondary data analysis, this study aims to characterize fatigue types, quantify the relationship between fatigue type and clinical and patient reported outcomes, and examine the cardiac structural and functional predictors of fatigue type in those with HFrEF and HFpEF in the Atherosclerosis Risk in Communities (ARIC) study. This will be accomplished through the following specific aims: AIM 1: Define distinct types of fatigue in individuals with chronic heart failure. AIM 2: Quantify the longitudinal association between fatigue type and HF readmission and mortality and quantify the cross-sectional association between fatigue type and quality of life. AIM 3: Determine the cross-sectional relationship between measures of cardiac structure and function (left ventricular (LV) structure, LV systolic function, LV diastolic function), HF phenotype (HFrEF vs HFpEF), and fatigue type (adjusting for age, sex, socioeconomic status, BMI, comorbidities, and medications). This study will address critical evidence gaps and provide an evidence base for future research to prevent and mitigate the effects of fatigue in HF. It will lay the foundation for a future program of symptom science research investigating multi- dimensional models of HF fatigue symptom science. This study aligns with the National Institute of Nursing Research's strategic plan focus to advance knowledge in symptom science with the goal of developing and testing innovative interventions to alleviate suffering from symptoms and improve ...