Symptoms in patients with heart failure are prognostic predictors: Insights from COMET

Background: Although functional status, as assessed by the New York Heart Association classification, is known to be a powerful prognostic marker in chronic heart failure (CHF), the significance of individual symptoms such as breathlessness and fatigue are unknown. Objective: To assess the relative importance of self-reported severity of symptoms as predictors of outcomes in CHF. Methods and Results: All 3029 patients randomized in the Carvedilol or Metoprolol European Trial (ie, COMET) study were included in the analysis. Mean follow-up was 58 months. Symptoms were assessed by 5-point scales. In a univariate analysis, worse scores for breathlessness, orthopnea and fatigue were all significantly related to increased mortality (all P < .0001) and development of worsening heart failure. In a multivariate Cox regression analysis including 16 baseline covariates, only the symptom of breathlessness remained significantly related to mortality (risk ratio [RR] 1.14 per unit: 95% CI 1.04-1.26; P = .01). Fatigue, but not breathlessness, remained a significant predictor for developing worsening heart failure (RR 1.09 per unit;, 95% CI 1.02-1.18; P = .02). Conclusions: Fatigue and breathlessness, common symptoms in CHF, have important and independent long-term prognostic implications. Accordingly, symptoms need to be effectively evaluated not only because symptom alleviation is a target for treatment, but also because they guide prognosis in patients with CHF.