Abstract

Introduction: Fatigue is a common and distressing, but poorly understood symptom among patients with heart failure (HF). The underlying mechanisms of fatigue in HF have not been clearly elucidated, but may lie in both psychologic and physiologic factors. Whether fatigue remains associated with mortality independent of other common clinical attributes also remains unresolved. Accordingly, the current study sought to evaluate the prevalence, predictors, and prognostic value of clinically documented fatigue in newly diagnosed HF patients. Methods: This retrospective cohort study consisted of 12,285 newly diagnosed HF patients receiving health care services through the Geisinger Health System, with passive data collection through electronic medical records (EMR). Incident HF, fatigue, and other study variables were derived from coded data within EMRs. A collection of 87 candidate predictors were evaluated to ascertain the strongest independent predictors of fatigue using logistic regression. The collection of candidate variables was drawn from several domains including demographics, physical examination findings, medical history, laboratory results, and medications. Patients were followed for all-cause mortality for an average of 4.8 years. The associations between fatigue and six-month, 12-month, and overall mortality were evaluated with Cox proportional hazards regression. Results: Clinically documented fatigue was found in 4827 (39%) newly diagnosed HF patients. Among the 87 candidate predictors, 18 were independently associated with fatigue at a multivariable p-value threshold of 0.001. Depression was the strongest predictor of fatigue. Fatigue was often part of a symptom cluster, as other HF symptoms including dyspnea, chest pain, edema, syncope, and palpitations were significant predictors of fatigue. Volume depletion, low body mass index, and abnormal weight loss were also strong predictors of fatigue. Though fatigue was significantly associated with 6-month (HR=1.49, p<0.01), 12-month (HR=1.39, p<0.01), and all-cause mortality (HR=1.20, p<0.01) in unadjusted models, effect sizes were attenuated and non-significant after adjustment for clinical variables with HRs of 1.12 (p=0.16), 1.07 (p=0.26), and 1.00 (p=0.89), for 6-month, 12-month, and overall mortality, respectively. Conclusions: Fatigue is a commonly documented symptom among newly diagnosed HF patients with likely origins in both psychologic and physiologic factors. Though fatigue provided a prognostic signal in the short-term, this was largely explained by physiologic confounders.

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