Early heart rate recovery after exercise predicts mortality in patients with chronic heart failure

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Abstract

Background

Patients with chronic heart failure (CHF) have multiple abnormalities of autonomic regulation that have been associated to their high mortality rate. Heart rate recovery immediately after exercise is an index of parasympathetic activity, but its prognostic role in CHF patients has not been determined yet.

Methods

Ninety-two stable CHF patients (83M/9F, mean age: 51 ± 12 years) performed an incremental symptom-limited cardiopulmonary exercise testing. Measurements included peak O2 uptake (VO2p), ventilatory response to exercise (VE/VCO2 slope), the first-degree slope of VO2 for the 1st minute of recovery (VO2/t-slope), heart rate recovery [(HRR1, bpm): HR difference from peak to 1 min after exercise] and chronotropic response to exercise [%chronotropic reserve (CR, %) = (peak HR  resting HR/220  age  resting HR) × 100]. Left ventricular ejection fraction (LVEF, %) was also measured by radionuclide ventriculography.

Results

Fatal events occurred in 24 patients (26%) during 21 ± 6 months of follow-up. HRR1 was lower in non-survivors (11.4 ± 6.4 vs. 20.4 ± 8.1; p < 0.001). All cause-mortality rate was 65% in patients with HRR1  12 bpm versus 11% in patients with HRR1 > 12 bpm (log-rank: 32.6; p < 0.001). By multivariate survival analysis, HRR1 resulted as an independent predictor of mortality (χ2 = 19.2; odds ratio: 0.87; p < 0.001) after adjustment for LVEF, VO2p, VE/VCO2 slope, CR and VO2/t-slope. In a subgroup of patients with intermediate exercise capacity (VO2p: 10–18, ml/kg/min), HRR1 was a strong predictor of mortality (χ2: 14.3; odds ratio: 0.8; p < 0.001).

Conclusions

Early heart rate recovery is an independent prognostic risk indicator in CHF patients and could be used in CHF risk stratification.

Introduction

The prevalence of congestive heart failure (CHF) has increased over the past few decades [1] and, despite progress in medical treatment with β-adrenergic blockers and angiotensin-converting enzyme (ACE) inhibitors [2], [3], [4], [5], mortality in patients with chronic heart failure remains high, and their mortality risk is difficult to estimate by currently available methods [6], [7], [8], [9].

One of the important pathophysiological causes of high mortality in CHF is neuroendocrine dysregulation [10], manifested mainly by an imbalance of autonomic control [11] and characterized by a marked increase in sympathetic activation [12], cardiac b1-adrenoreceptor down-regulation [13], parasympathetic withdrawal [14], [15], [16], baroreflex desensitivity [17], [18], [19] and decreased heart rate variability [3], [20]. An attenuated heart rate (HR) recovery after exercise is thought to be a marker of decreased parasympathetic activity [21], [22], and this attenuation in CHF is pronounced [23], [24], [25]. A blunted HR recovery has recently been shown to independently predict mortality among patients referred for exercise electrocardiogram (ECG), in large population-based studies [26], [27], [28], [29], [30]. However, the prognostic value of HR recovery in patients with CHF has not yet been established.

Objective of this study was to examine HR recovery immediately after cardiopulmonary exercise testing (CPET), as a predictor of mortality in CHF patients and compare its value with that of other known prognostic parameters.

Section snippets

Study population

The study population consisted of 92 consecutive CHF patients (83 men and 9 women) at optimal medical treatment, at the time of inclusion, stabilized at least for 1 month in New York Heart Association (NYHA) class  III, with a LVEF  45%, who were referred to our laboratory in the years 1996–1998, in order to perform a symptom-limited cardiopulmonary exercise test (CPET), as part of heart failure evaluation. The diagnosis of CHF was based on a thorough clinical evaluation and laboratory testing,

Results

Twenty-four patients (26%) died during the follow-up period. Thirteen patients died from end-stage heart failure, nine had a sudden cardiac death and two died from other causes. From patients who died, 3 were in NYHA class I, 16 were in NYHA class II and 5 were in NYHA class III. In the group of survivors, 27 were in NYHA class I, 37 were in NYHA class II and 4 were in NYHA class III. No statistical differences were found regarding age and BMI, between survivors and non-survivors.

Discussion

The results of our study show that early heart rate recovery after exercise is an independent predictor of mortality in patients with chronic heart failure. Specifically, HRR1 identified patients at high risk of death within a 2-year follow-up after initial evaluation, independent of other cardiopulmonary risk indicators, including VO2p, VE/VCO2 slope, AT, CR, VO2/t-slope and LVEF. To our knowledge, this is the first prospective study that has evaluated the prognostic significance of HR

Acknowledgements

We are indebted to Professor Karlmann Wasserman for his helpful and significant suggestions on the final form of this manuscript. We also thank Sotirios Gyftopoulos for his significant technical support.

This study was funded partly by a grant from the special account for research grants of the National and Kapodestrian University of Athens, Athens, Greece.

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