Abstract Body: Background: General and exertional fatigue are common in clinical heart failure (HF) and associated with worse quality of life (QOL) and increased risk of HF re-admission and mortality. However, little is known about general and exertional fatigue in those with pre-HF.

Methods: We included 2,972 individuals at Visit 5 (2011-13) of the ARIC study without clinical HF but meeting criteria for pre-HF (stage B HF per ACC/AHA guidelines) by echocardiography or elevated cardiac biomarkers, and with complete fatigue data. Using previously defined PROMIS fatigue (general fatigue) and MRC Breathlessness (exertional fatigue) scale score thresholds, individuals were cross categorized into 4 groups: low/no fatigue, high general fatigue, high exertional fatigue, and the co-occurrence of high general and high exertional fatigue. Adjusting for sociodemographic and clinical characteristics, we determined the cross-sectional association of fatigue category with physical and mental QOL (SF-12 scale) using linear regression, and prospective associations with incident clinical HF using Cox regression. To reduce the contribution of indolent HF to results, we conducted a sensitivity analysis excluding individuals with an outpatient diagnosis of clinical HF from Centers for Medicare and Medicaid Services claims data.

Results: Participants were 60% female, 18% Black, and had a mean age of 76 years. Compared to the low/no fatigue category, all individuals in higher fatigue categories had lower physical QOL scores. The co-occurrence of high general and exertional fatigue was associated with the lowest QOL [β (95% CI) = -11 (-13, -10)] (Table). More modest, but significant, associations were seen for fatigue categories with mental QOL. Compared to the low/no fatigue category, those with high exertional fatigue, and those with the co-occurrence of high general and high exertional fatigue, had higher risk of incident clinical HF [HRs (95% CI) = 1.9 (1.4, 2.5) and 2.2 (1.5, 3.2), respectively]. Associations were similar after excluding individuals with an outpatient clinical HF diagnosis.

Conclusions: In those with pre-HF, worse fatigue category was associated with worse QOL and increased risk of incident clinical HF, independent of traditional risk factors. Assessment of general and exertional fatigue may provide prognostic information in individuals with pre-HF.