Arm Exercise versus Pharmacologic Stress Testing for Clinical Outcome Prediction

跑步机运动能力和对腿部运动的其他生理反应是强大的 预测死亡率，并提供重要的临床和诊断信息。然而，许多人 退伍军人因为腿部或其他残疾而不能进行跑步机锻炼。为 多年来，药物心肌灌注成像(Mpi)一直是治疗的标准。 但未能提供强有力的预后和临床相关信息 运动测试，需要暴露在电离辐射中，而且价格要贵几倍 而不是运动心电图仪。凭借最近完成的功绩审查奖，我们 获得了大量的回顾性观察证据，表明手臂运动的心电负荷测试 对于死亡率和其他疾病的可靠预测，得分至少相当于药理学MPI 不能进行腿部锻炼的退伍军人的临床结果的测量。主要假设 目前的建议是：1)手臂运动心电负荷测试分数或最适合模型 没有或有冠状动脉钙化评分(-/+CACs)不低于Duke 跑步机评分-/+CAC、最佳匹配模型跑步机心电和瑞格腺苷(R)MPI负荷测试， 作为对梗阻的初步评估，所有患者都以随机顺序在相同的退伍军人中接受治疗 冠状动脉疾病(OCAD)，以及2)手臂运动心电负荷测试得分或最佳匹配 模型-/+CAC不逊于Duke跑步机评分-/+CAC，最佳模型 同一退伍军人平板心电和RMPI负荷试验预测初诊 终点(心血管(CV)死亡率、心肌梗死或90天后 负荷试验、冠状动脉血运重建)和全因死亡率的继发性临床终点 和心血管病死率。我们对所有退伍军人的具体目标指的是圣路易斯退伍军人 管理局(VA)压力测试实验室，且不排除锻炼或 瑞格腺苷负荷试验或心脏计算机断层血管造影术(CTA) 一项比较手臂运动心电负荷试验和最佳试验结果的单部位前瞻性临床试验 模型-/+具有Duke跑步机评分的CAC-/+CAC如果能够进行跑步机锻炼， 和最适合的跑步机心电图和RMPI模型，都是在相同的退伍军人身上进行的， 确定OCAD的诊断终点，定义为严重(≥70%)闭塞 心外膜、移植物或≥50%左冠状动脉主干管腔，由心脏CTA或 有创冠状动脉造影术与临床主要和次要终点的预测 如上所述。要评估的手臂练习评分系统包含以下变量 静息代谢物的手臂运动能力、1分钟心率恢复和手臂 运动性ST段压低≥为1 mm。要评估的瑞格腺苷MPI变量包括 一过性MPI异常研究及其与总分和差值的最佳拟合模型 缺血性扩张、门控左心室射血分数和心率反应。我们计划 每年招收75名退伍军人，为期4年，并在接下来的一年里跟随整个队列。 统计分析将用SAS进行，使用单变量和多变量Logistic和 Cox回归模型。我们将评估手臂运动分数的非劣性-/+CAC 它们与OCAD的相关性和临床终点的预测，其非劣势边缘为 0.05。一个长期目标是开发一项多点前瞻性随机VA合作研究 评估手臂运动心电负荷试验-/+CACs诊断和诊断的普适性 退伍军人事务部和美国医疗保健系统的预后评估。

Treadmill exercise capacity and other physiologic responses to leg exercise are powerful predictors of mortality and provide important clinical and diagnostic information. However, many Veterans cannot perform treadmill exercise because of lower extremity or other disabilities. For many years, pharmacologic myocardial perfusion imaging (MPI) has been the standard of care for their evaluation but fails to provide powerful prognostic and clinically relevant information of exercise testing, requires exposure to ionizing radiation, and is several times more expensive than exercise electrocardiography (ECG). With a recently completed Merit Review award, we obtained substantial retrospective observational evidence that arm exercise ECG stress testing scores are at least equivalent to pharmacologic MPI for robust prediction of mortality and other measures of clinical outcome in Veterans who cannot perform leg exercise. Major hypotheses for the current proposal are: 1) arm exercise ECG stress testing scores or best fit models without or with coronary artery calcium scoring (-/+ CACS) are non-inferior to the Duke Treadmill Score -/+ CACS, best fit model treadmill ECG and regadenoson (r) MPI stress testing, all performed in the same Veterans in randomized order, as an initial evaluation for obstructive coronary artery disease (oCAD), and 2) arm exercise ECG stress testing scores or best fit models -/+ CACS are non-inferior to the Duke Treadmill Score -/+ CACS, best fit model treadmill ECG and rMPI stress testing in the same Veterans for predicting the primary clinical endpoint (composite of cardiovascular (CV) mortality, myocardial infarction, or 90-day post- stress test coronary revascularization) and secondary clinical endpoints of all-cause mortality and CV mortality. Our specific aim for all Veterans referred to the St. Louis Veterans Administration (VA) stress testing laboratory and are without exclusions for exercise or regadenoson stress testing or cardiac computed tomographic angiography (CTA), is to perform a single site prospective clinical trial comparing arm exercise ECG stress test scores and best models -/+ CACS with the Duke Treadmill Score -/+ CACS if able to perform treadmill exercise, and best fit treadmill ECG and rMPI models, all performed in the same Veterans, for identification of the diagnostic endpoint of oCAD, defined as a severely (≥70%) occluded epicardial, graft, or ≥50% left main coronary artery lumen, determined by cardiac CTA or invasive coronary arteriography, and prediction of the primary and secondary clinical endpoints described above. The arm exercise scoring system to be evaluated incorporates the variables arm exercise capacity in resting metabolic equivalents, 1-minute heart rate recovery and arm exercise-induced ST depression ≥1 mm. Regadenoson MPI variables to be evaluated include an abnormal MPI study and best fit models of summed stress and difference scores, transient ischemic dilatation, gated left ventricular ejection fraction, and the heart rate response. We plan to enroll 75 Veterans per year for 4 years and follow the entire cohort for an additional year. Statistical analyses will be performed with SAS using univariate and multivariate logistic and Cox regression models. We will evaluate non-inferiority of arm exercise scores -/+ CACS for their association with oCAD and prediction of clinical endpoints with a non-inferiority margin of 0.05. A long term goal is to develop a multi-site prospective randomized VA Cooperative Study to assess generalizability of arm exercise ECG stress testing -/+ CACS for diagnostic and prognostic evaluation in the VA and United States healthcare systems.