Patients with heart failure in the "intermediate range" of peak oxygen uptake: additive value of heart rate recovery and the minute ventilation/carbon dioxide output slope in predicting mortality

Abstract

Purpose: While patients with heart failure who achieve a peak oxygen uptake (peak VO2) of 10 mL·kg(-1)·min(-1) or less are often considered for intensive surveillance or intervention, those achieving 14 mL·kg(-1)·min(-1) or more are generally considered to be at lower risk. Among patients in the "intermediate" range of 10.1 to 13.9 mL·kg(-1)·min(-1), optimally stratifying risk remains a challenge.

Methods: Patients with heart failure (N = 1167) referred for cardiopulmonary exercise testing were observed for 21 ± 13 months. Patients were classified into 3 groups of peak VO2 (≤10, 10.1-13.9, and ≥14 mL·kg(-1)·min(-1)). The ability of heart rate recovery at 1 minute (HRR1) and the minute ventilation/carbon dioxide output (VE/VCO2) slope to complement peak VO2 in predicting cardiovascular mortality were determined.

Results: Peak VO2, HRR1 (<16 beats per minute), and the VE/VCO2 slope (>34) were independent predictors of mortality (hazard ratio 1.6, 95% CI: 1.2-2.29, P = .006; hazard ratio 1.7, 95% CI: 1.1-2.5, P = .008; and hazard ratio 2.4, 95% CI: 1.6-3.4, P < .001, respectively). Compared with those achieving a peak VO2 ≥ 14 mL·kg(-1)·min(-1), patients within the intermediate range with either an abnormal VE/VCO2 slope or HRR1 had a nearly 2-fold higher risk of cardiac mortality. Those with both an abnormal HRR1 and VE/VCO2 slope had a higher mortality risk than those with a peak VO2 ≤ 10 mL·kg(-1)·min(-1). Survival was not different between those with a peak VO2 ≤ 10 mL·kg(-1)·min(-1) and those in the intermediate range with either an abnormal HRR1 or VE/VCO2 slope.

Conclusions: HRR1 and the VE/VCO2 slope effectively stratify patients with peak VO2 within the intermediate range into distinct groups at high and low risk.

Figure 1.

Kaplan-Meier survival curves for peak oxygen uptake ( ${\stackrel{·}{\text{V}}\text{O}}_2$) subgroups.

Figure 2.

Kaplan-Meier survival curves for peak oxygen uptake ( ${\stackrel{·}{\text{V}}\text{O}}_2$) subgroups adding the minute ventilation/carbon dioxide production ( ${\stackrel{·}{\text{V}}}_{\text{E}}$/${\stackrel{·}{\text{V}}\text{co}}_2$) slope and heart rate recovery at first minute (HRR₁) for subjects in the intermediate range. (A) Peak ${\stackrel{·}{\text{V}}\text{O}}_2$ ≥ 14 mL·kg⁻¹·min⁻¹. (B) Peak ${\stackrel{·}{\text{V}}\text{O}}_2$ 10.1–13.9 mL·kg⁻¹·min⁻¹ and abnormal ${\stackrel{·}{\text{V}}}_{\text{E}}$/${\stackrel{·}{\text{V}}\text{co}}_2$ slope or HRR₁. (C) Peak ${\stackrel{·}{\text{V}}\text{O}}_2$ ≤ 10 mL·kg⁻¹·min⁻¹. (D) Peak ${\stackrel{·}{\text{V}}\text{O}}_2$ 10.1–13.9 mL·kg^−1·min⁻¹ and abnormal ${\stackrel{·}{\text{V}}}_{\text{E}}$/${\stackrel{·}{\text{V}}\text{co}}_2$ slope and HRR₁.