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Patients with heart failure (HF) have notably poor health-related quality of life (HRQOL). A 5-point improvement in HRQOL is associated with reduction in hospitalization and mortality rates. Heart failure symptoms are associated with poor HRQOL, but little is known about whether changes in HF symptoms lead to changes in HRQOL over time. Therefore, we examined the association of changes in HF symptoms with changes in overall, physical, and emotional aspects of HRQOL over a 12-month period, controlling for typical covariates.Data on HF symptoms and HRQOL (Minnesota Living Heart Failure questionnaire) were collected from 94 patients with HF (mean age, 58 years; 58.5% female) at baseline and 12-month follow-up. Psychosocial factors (depressive symptoms, perceived control, and social support), behavioral factors (medication adherence and sodium intake), sociodemographic and clinical factors (age, comorbidities, and body mass index), and a physical factor (functional status) were collected at baseline. Multiple and logistic regression analyses were used to analyze the data.In complete models, changes in HF symptoms were associated with changes in the total HRQOL (P < .001) and the physical (P < .001) and emotional (P < .001) aspects of HRQOL over 12 months, controlling for all the factors. Changes in HF symptoms were significantly associated with the likelihood of at least a 5-point improvement in HRQOL (P = .001), controlling for covariates.Improvement in HF symptoms was associated with improvement in HRQOL over 12 months. Thus, development and delivery of interventions that target improvement in HF symptoms may improve HRQOL.