Background and aims

Transient increases (overshoot) in respiratory gas analyses have been observed during exercise recovery, but their clinical significance is not clearly understood. An overshoot phenomenon of the respiratory exchange ratio (RER) is commonly observed during recovery from maximal cardiopulmonary exercise testing (CPET), but it has been found reduced in patients with heart failure with reduced ejection fraction (HFrEF). The aim of the study was to analyze the clinical significance of these RER recovery parameters and to understand if these may improve the risk stratification of patients with HFrEF.

Methods

This cross-sectional study includes HFrEF patients who underwent functional evaluation with maximal CPET for the heart transplant checklist at our Sports and Exercise Medicine Division. RER recovery parameters, including RER overshoot as the percentual increase of RER during recovery (RER mag), have been evaluated after CPET with assessment of hard clinical long-term endpoints (MACEs/deaths and transplant/LVAD-free survival).

Results

A total of 190 patients with HFrEF and 103 controls were included (54.6 ± 11.9 years; 73% male). RER recovery parameters were significantly lower in patients with HFrEF compared to healthy subjects (RER mag 24.8 ± 14.5% vs 31.4 ± 13.0%), and they showed significant correlations with prognostically relevant CPET parameters. Thirty-three patients with HFrEF did not present a RER overshoot, showing worse cardiorespiratory fitness and efficiency when compared with those patients who showed a detectable overshoot (VO₂ peak: 11.0 ± 3.1 vs 15.9 ± 5.1 ml/kg/min; VE/VCO₂ slope: 41.5 ± 8.7 vs 32.9 ± 7.9; ΔPETCO₂: 2.75 ± 1.83 vs 4.45 ± 2.69 mmHg, respectively). The presence of RER overshoot was associated with a lower risk of cardiovascular events and longer transplant-free survival.

Conclusion

RER overshoot represents a meaningful cardiorespiratory index to monitor during exercise gas exchange evaluation; it is an easily detectable parameter that could support clinicians to comprehensively interpreting patients’ functional impairment and prognosis. CPET recovery analyses should be implemented in the clinical decision-making of advanced HF.

Graphical Abstract

RER Overshoot during CPET recovery phase in HFrEF

Transient increases, also called overshoot, in respiratory exchange ratio (RER) have been observed during exercise recovery in healthy subjects and patients with chronic diseases. A total of 190 patients with HFrEF who underwent CPET for heart transplant checklist were analyzed and compared with 103 controls, using a protocol to monitor gas exchange during recovery phase. RER overshoot was significantly lower in patients with HFrEF than controls, and some patients with HFrEF (17.4%) presented no overshoot. The presence of RER overshoot was associated with higher aerobic capacity and cardiorespiratory efficiency with lower risk of cardiovascular events and longer transplant/LVAD-free survival. HFrEF, heart failure with reduced ejection fraction; CPET, cardiopulmonary exercise testing; LVAD, left ventricular ejection fraction.

背景和目标

在运动恢复期间观察到呼吸气体分析的短暂增加（超调），但其临床意义尚不清楚。呼吸交换比（RER）的超调现象在最大心肺运动试验（CPET）恢复期间常见，但在射血分数降低的心力衰竭（HFrEF）患者中发现呼吸交换比（RER）的超调现象降低。该研究的目的是分析这些 RER 恢复参数的临床意义，并了解这些参数是否可以改善 HFrEF 患者的风险分层。

方法

这项横断面研究包括在我们的运动和运动医学部门根据心脏移植清单接受最大 CPET 功能评估的 HFrEF 患者。 RER 恢复参数，包括 RER 超调，即恢复期间 RER 百分比增加 (RER mag)，在 CPET 后进行了评估，并评估了硬临床长期终点（MACE/死亡和移植/无 LVAD 生存）。

结果

总共纳入了 190 名 HFrEF 患者和 103 名对照者（54.6 ± 11.9 岁；73% 为男性）。与健康受试者相比，HFrEF 患者的 RER 恢复参数显着较低（RER mag 24.8 ± 14.5% vs 31.4 ± 13.0%），并且它们与预后相关的 CPET 参数显着相关。 33 名 HFrEF 患者没有出现 RER 超调，与表现出可检测到的超调的患者相比，显示出更差的心肺健康和效率（VO ₂峰值：11.0 ± 3.1 vs 15.9 ± 5.1 ml/kg/min；VE/VCO ₂斜率：41.5 ± 8.7 与 32.9 ± 7.9；ΔPETCO ₂：分别为 2.75 ± 1.83 与 4.45 ± 2.69 mmHg。 RER 超调的存在与较低的心血管事件风险和较长的无移植生存期相关。

结论

RER 超调代表运动气体交换评估期间需要监测的有意义的心肺指标；它是一个易于检测的参数，可以支持临床医生全面解释患者的功能障碍和预后。 CPET 恢复分析应在晚期心力衰竭的临床决策中实施。

图形概要

HFrEF 中 CPET 恢复阶段的 RER 过冲

在健康受试者和慢性病患者的运动恢复过程中，观察到呼吸交换比 (RER) 出现短暂增加（也称为超调）。使用监测恢复阶段气体交换的方案对总共 190 名因心脏移植检查表而接受 CPET 的 HFrEF 患者进行了分析，并与 103 名对照者进行了比较。 HFrEF 患者的 RER 超调显着低于对照组，部分 HFrEF 患者 (17.4%) 没有出现超调。 RER 超调的存在与较高的有氧能力和心肺效率、较低的心血管事件风险和较长的无移植/LVAD 生存期相关。 HFrEF，射血分数降低的心力衰竭； CPET，心肺运动试验； LVAD，左心室射血分数。