Novel cardiopulmonary exercise testing variables to differentiate neuromuscular deconditioning from disease

项目摘要 心脏运动试验（CPET）是一种客观、无创的综合功能测量方法， 肺、心血管和神经肌肉系统。CPET评估次最大和峰值运动 反应，告知呼吸困难和/或疲劳的原因，疾病预后和/或进展，术前或术后 手术风险分层或运动训练处方。据估计，CPET的临床使用已增加 在2005年至2015年期间增长了81%。CPET解释最常见的问题是区分 心血管疾病和神经肌肉失调，肌肉质量低、虚弱和/或易疲劳。 我们已经开发了一种解决这个问题的方法，使用改进的CPET与集成等速（IK） 肌肉力量的测量，独立评估神经肌肉性能， 影响标准CPET变量的测量。改进后的CPET比标准CPET增加<10 min 并使用市售设备。修改后的CPET产生4个新的IK变量：1）基线峰值 等速功率：去调节肌肉较弱; 2）耐受指数：峰值IK功率在 V时O2峰值。有氧去调节降低了有氧运动可以支持的可用峰值IK功率。 3）疲劳指数：在给定的工作速率下峰值IK功率的损失。有氧失调增加 疲劳性; 4）动力储备：在V ~（？）O ~ 2峰值时急剧增加动力的能力。动力储备表明， 神经肌肉性能不限于运动耐量。改进后的CPET方法重现性好， 老年人、正常受试者和运动员以及心力衰竭或COPD患者耐受。修改后的CPET 可以区分神经肌肉失调作为运动限制的原因， 肺限制（通过标准CPET评估）。为了告知临床解释，该项目将开发 描述18- 80岁男女IK变量正常参考值的预测模型。 神经肌肉性能的阈值（具有相应的灵敏度和特异性）将是 开发和优化来区分一个去适应的人群。调节神经肌肉的变量 将识别与去调节相关的性能测量（例如，V ~ O2峰值，舒张功能障碍， 血管反应性、腿部瘦体重、腿部力量和功率、肌肉氧化能力和肌肉活检 形态学）。最后，将通过测量IK变量对去条件化的区分能力来测试IK变量对去条件化的区分能力。 IK变量对去适应个体运动训练反应的敏感性和IK的特异性 在患者中使用有创CPET区分外周与中枢血流动力学运动限制的变量 心脏衰竭射血分数正常这项研究将改变实用和诊断能力 CPET和改善临床决策和广泛的慢性疾病的严重程度分层 在这些州，解除条件限制是一个共同的特征。

PROJECT SUMMARY Cardiopulmonary exercise testing (CPET) is an objective, non-invasive, measure of the integrated function of the pulmonary, cardiovascular and neuromuscular systems. CPET evaluates submaximal and peak exercise responses, informing on causes of dyspnea and/or fatigue, disease prognosis and/or progression, pre- or post- surgical risk stratification, or exercise training prescription. Clinical use of CPET is estimated to have increased by 81% between 2005 and 2015. The most common problem for CPET interpretation is discriminating between cardiovascular disease and neuromuscular deconditioning e.g., low muscle mass, weakness and/or fatigability. We have developed a solution to this problem, using a modified CPET with integrated isokinetic (IK) measurements of muscle power, which independently assesses neuromuscular performance without affecting measurement of standard CPET variables. The modified CPET adds <10min to the standard CPET and uses commercially available equipment. The modified CPET produces 4 new IK variables: 1) Baseline peak isokinetic power: deconditioned muscles are weak; 2) Tolerance index: the fraction of peak IK power at V̇O2peak. Aerobic deconditioning reduces the available peak IK power that can be supported by aerobic metabolism; 3) Fatigue index: The loss of peak IK power for a given work rate. Aerobic deconditioning increases fatigability; 4) Power reserve: The capacity for acute power increase at V̇O2peak. A power reserve indicates that neuromuscular performance is not limiting to exercise tolerance. The modified CPET is reproducible and well tolerated by elderly, normal subjects and athletes, and those with heart failure or COPD. The modified CPET can differentiate neuromuscular deconditioning as a cause of exercise limitation from cardiovascular or pulmonary limitations (assessed by standard CPET). To inform clinical interpretation, this project will develop predictive models describing normal reference values for IK variables in men and women aged 18-80yr. Threshold values of neuromuscular performance (with corresponding sensitivity and specificity) will be developed and optimized to discriminate a deconditioned population. Variables that moderate neuromuscular performance measures associated with deconditioning will be identified (e.g. V̇O2peak, diastolic dysfunction, vascular reactivity, leg lean mass, leg strength and power, muscle oxidative capacity and muscle biopsy morphology). Finally, the discriminative ability of IK variables for deconditioning will be tested by measuring sensitivity of IK variables in response to exercise training in deconditioned individuals and the specificity of IK variables to discriminate peripheral vs. central hemodynamic exercise limitations using invasive CPET in patients with heart failure and preserved ejection fraction. This study will transform the utility and diagnostic capabilities of CPET and improve clinical decision-making and severity stratification across a wide range of chronic disease states where deconditioning is a common feature.