Clinical Investigation
Symptoms in Patients With Heart Failure are Prognostic Predictors: Insights From COMET

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Abstract

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.

Section snippets

Methods

COMET was a multicenter, randomized (1:1), double-blind, parallel-group trial comparing the effect of carvedilol and metoprolol tartrate on morbidity and mortality in patients with CHF. Detailed descriptions of the study design, baseline characteristics, and results have been published elsewhere.5, 6 The study was performed in 15 European countries, involving 315 centers. Recruitment began 1996 and ended 1999. Follow-up for mortality and morbidity was concluded in 2002.

The main inclusion

Baseline Characteristics

The population (n = 3029) consisted mainly of men (79%) with a mean age of 62 years. The patients were evenly distributed between NYHA II and III (Table 1).

Classification of NYHA III/IV in Relation to Self-Reported Symptoms

Patient ratings of breathlessness and fatigue in relation to their NYHA classification are presented in Fig. 1, Fig. 2. Some patients did not rate their symptoms as severe, as might be expected. For example, among patients classified as NYHA III, 54% scored 3 or worse (walking at normal pace on a flat surface) in breathlessness and 46% scored

Discussion

Our data suggest that symptoms are an important target for therapy in their own right and that their severity, particularly breathlessness but also fatigue, predicts an increased risk of hospitalization and death. Unlike more sophisticated investigations, information on the severity of symptoms is readily available and may be much less operator-dependent than physical signs. Studies suggest that clinicians often disagree on the presence of physical signs. Gadsboll et al2 reported the

Acknowledgments

We appreciate the assistance from Kevin Goode, PhD, Kingston-upon-Hull, for making the figures.

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