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Cardiopulmonary exercise parameters in relation to all-cause mortality in patients with chronic heart failure
Bol E, de Vries WR, Mosterd WL, Wielenga RP, Coats AJ
International Journal of Cardiology 2000 Feb 15;72(3):255-263
clinical trial
2/10 [Eligibility criteria: No; Random allocation: Yes; Concealed allocation: No; Baseline comparability: No; Blind subjects: No; Blind therapists: No; Blind assessors: No; Adequate follow-up: No; Intention-to-treat analysis: No; Between-group comparisons: No; Point estimates and variability: Yes. Note: Eligibility criteria item does not contribute to total score] *This score has been confirmed*

In this study we analysed the all-cause mortality over a period of maximal 6 years in 60 male patients (age 63.4 +/- 8.3 years, mean +/- SD), suffering from chronic heart failure with resting left ventricular ejection fraction and E/O2 slope as independent factors. We assessed functional NYHA class (II: n = 36, III: n = 24), radionuclide left ventricular ejection fraction (29.2 +/- 10.4%) and peak values of heart rate, O2, CO2, E, anaerobic threshold and exercise duration with an incremental work load test on the treadmill. O2 relative to E was based on the individual slopes of the regression of O2 on E during the first 6 min of exercise. These slopes with other exercise-related variables and factors such as etiology, medication, and NYHA class were analysed with a Cox's Regression method. A survival time analysis (Kaplan-Meier survival curve) was done to establish the influence of E/O2 slope and left ventricular ejection fraction (both split into above and below median values), as well as their interaction, on survival. From all investigated exercise-related variables. E/O2 slope is the most powerful variable regarding prediction of all-cause mortality in our group of chronic heart failure patients. Concerning risk stratification, the subgroup (n = 18) with a relatively high left ventricular ejection fraction (> 28%) and flat E/O2 slope (< 27.6) had most survivors (77.8%) after about 3 years, while the subgroup (n = 12) with a relatively high left ventricular ejection fraction (> 28%), but a steep E/O2 slope (> 27.6) had least survivors (33.3%). This difference in percentage is highly significant (p = 0.0025). The fact that E/O2 slope and left ventricular ejection fraction show comparable main and interaction effects between measures of exercise tolerance (eg, anaerobic threshold, peak O2, exercise duration) on the one hand, and all-cause mortality on the other, suggests the existence of common sources of variance. Based on our analysis, it is unlikely that effects on all-cause mortality are mediated through phenomena related to exercise tolerance. Therefore, we hypothesize that the effects on exercise tolerance and all-cause mortality both depend on common factors, which cause both cardiac and peripheral organ (CQ muscular) dysfunctions. Moreover, this study clearly shows that E/O2 slope during incremental exercise is an important prognostic marker for risk stratification in chronic heart failure patients, NYHA class II and III.

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