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Because patients with heart failure (HF) experience multiple symptoms simultaneously, it is necessary to explore symptom clusters rather than individual symptoms to determine their impact on outcomes. Given gender differences in symptom experience, examination of potential gender differences in clusters is reasonable.The objective of the study was to compare symptom clusters between men and women with HF, differences in patient characteristics among symptom clusters, and the impact of symptom clusters on cardiac event-free survival.A total of 331 patients with HF recruited from HF clinics were included (35% were female and 62% were of New York Heart Association classes III/IV). Cluster analysis was used to identify symptom clusters between men and women based on ratings of distress related to 7 symptoms. Analysis of variance or χ2 test was used to compare characteristics of patient groups that were divided by the median split of total distress scores of each cluster. Cox proportional hazards regression was used to determine whether total scores of symptom distress in symptom clusters predicted time to first cardiac event.Two identical symptom clusters were identified in men and women: a physical symptom cluster composed of dyspnea, fatigue/increased need to rest, fatigue/low energy, and sleep disturbances and an emotional/cognitive symptom cluster composed of worrying, feeling depressed, and cognitive problems. Patients with higher distress from the physical symptom cluster were primarily females and of New York Heart Association classes III and IV (P < .05). Patients with higher distress from the emotional/cognitive symptom cluster were younger than those with lower distress (P < .05). The total symptom distress score in the emotional/cognitive cluster, but not the physical cluster, was an independent predictor of cardiac event-free survival (hazard ratio, 1.18; 95% confidence interval, 1.03-1.37).Although distress for individual symptoms may differ between men and women, they both experienced identical symptom clusters. Only the emotional/cognitive cluster predicted a higher risk for a cardiac event. These results suggested that interventions should be developed that consider symptom clusters. Targeting patients who have high distress from emotional/cognitive symptoms may be particularly important as they may be most vulnerable for adverse outcomes.