Institute of Health Research, University of Exeter Medical School, Exeter, United Kingdom; Centre for Research on Health and Social Care Management, Bocconi University, Milan, Italy.
Heart Failure Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy.
JACC Heart Fail. 2018 Jul;6(7):596-604. doi: 10.1016/j.jchf.2018.03.017.
This study sought to validate exercise capacity (EC) as a surrogate for mortality, hospitalization, and health-related quality of life (HRQOL).
EC is often used as a primary outcome in exercise-based cardiac rehabilitation (CR) trials of heart failure (HF) via direct cardiorespiratory assessment of maximum oxygen uptake (Vopeak) or through submaximal tests, such as the 6-min walk test (6MWT).
After a systematic review, 31 randomized trials of exercise-based CR compared with no exercise control (4,784 HF patients) were included. Outcomes were pooled using random effects meta-analyses, and inverse variance weighted linear regression equations were fitted to estimate the relationship between the CR on EC and all-cause mortality, hospitalization, and HRQOL. Spearman correlation coefficient (ρ), R at trial level, and surrogate threshold effect (STE) were calculated. STE represents the intercept of the prediction band of the regression line with null effect on the final outcome.
Exercise-based CR is associated with positive effects on EC measured through Vopeak (+3.10 ml/kg/min; 95% confidence interval [CI]: 2.01 to 4.20) or 6MWT (+41.15 m; 95% CI: 16.68 to 65.63) compared to control. The analyses showed a low level of association between improvements in EC (Vopeak or 6MWT) and mortality and hospitalization. Moderate levels of correlation between EC with HRQOL were seen (e.g., R <52%; |ρ| < 0.72). Estimated STE was an increase of 5 ml/kg/min for Vopeak and 80 m for 6MWT to predict a significant improvement in HRQOL.
The study results indicate that EC is a poor surrogate endpoint for mortality and hospitalization but has moderate validity as a surrogate for HRQOL. Further research is needed to confirm these findings across other HF interventions.
本研究旨在验证运动能力（EC）作为死亡率、住院率和健康相关生活质量（HRQOL）的替代指标的有效性。
在心力衰竭（HF）的基于运动的心脏康复（CR）试验中，EC 通常通过直接心肺评估最大摄氧量（Vopeak）或通过亚最大测试（如 6 分钟步行测试（6MWT））作为主要结局。
经过系统回顾，纳入了 31 项基于运动的 CR 与无运动对照组（4784 例 HF 患者）的随机试验。使用随机效应荟萃分析对结果进行汇总，并拟合逆方差加权线性回归方程，以估计 CR 对 EC 与全因死亡率、住院率和 HRQOL 之间的关系。计算 Spearman 相关系数（ρ）、试验水平的 R 和替代阈值效应（STE）。STE 代表回归线预测带的截距，对最终结局无影响。
与对照组相比，基于运动的 CR 可显著提高通过 Vopeak（+3.10 ml/kg/min；95%置信区间 [CI]：2.01 至 4.20）或 6MWT（+41.15 m；95% CI：16.68 至 65.63）测量的 EC。分析表明，EC（Vopeak 或 6MWT）的改善与死亡率和住院率之间的相关性较低。EC 与 HRQOL 之间存在中度相关性（例如，R <52%；|ρ| <0.72）。估计的 STE 是 Vopeak 增加 5 ml/kg/min 和 6MWT 增加 80 m，以预测 HRQOL 的显著改善。
研究结果表明，EC 是死亡率和住院率的不良替代终点，但作为 HRQOL 的替代指标具有中等有效性。需要进一步的研究来证实这些发现是否适用于其他 HF 干预措施。
