Arm Exercise versus Pharmacologic Stress Testing for Clinical Outcome Prediction

手臂锻炼与药物压力测试的临床结果预测

• 批准号: 9546164
• 负责人: Wade Hampton Martin
• 金额: --
• 依托单位: ST. LOUIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9546164
• 关键词: Address; American; Anatomy; Angiography; Armadillo Repeat; Arteriographies; Award; Blood flow; Cardiac; Cardiovascular system; Chemicals; Clinical; Clinical Trials; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Detection; Diagnostic; Diagnostic tests; Dilatation - action; EKG ST Segment Depression; Electrocardiogram; Enrollment; Evaluation; Exclusion; Exercise; Exercise stress test; Exposure to; Funding; Goals; Healthcare Systems; Heart; Heart Rate; Image; Injections; Ionizing radiation; Laboratories; Left; Left Ventricular Ejection Fraction; Leg; Logistics; Lower Extremity; Measures; Mental Depression; Metabolic; Modeling; Myocardial Infarction; Myocardial Ischemia; Myocardial perfusion; Outcome; Participant; Patients; Pharmacology; Physiological; Provider; Publishing; Radiation exposure; Radioactivity; Randomized; Recovery; Reporting; Rest; Role; Site; Statistical Data Interpretation; Stress; Stress Tests; Sum; Symptoms; System; Techniques; Test Result; Testing; Thallium Myocardial Perfusion Imaging Stress Test; Time; United States; United States Department of Veterans Affairs; Veterans; X-Ray Computed Tomography; arm; clinical decision-making; clinical diagnostics; clinical predictors; clinically relevant; cohort; cooperative study; coronary calcium scoring; cost; cost effective; disability; exercise capacity; heart imaging; imaging modality; imaging study; mortality; nephrotoxicity; nuclear imaging; perfusion imaging; predict clinical outcome; predictive modeling; prognostic; prognostic value; prospective; recruit; response; standard of care; statistics; treadmill; trial comparing

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.

跑步机运动能力和腿部运动的其他生理反应强大 死亡率的预测因素并提供重要的临床和诊断信息。 退伍军人由于下肢或其他残疾而无法进行跑步机锻炼。 多年来，药物心肌灌注显像 (MPI) 一直是护理标准 进行评估，但未能提供强有力的预后和临床相关信息 运动测试，需要暴露于电离辐射，而且价格贵几倍 与运动心电图 (ECG) 相比，我们最近完成了优异评审奖。 大量观察回顾性证据表明手臂运动心电图压力测试 评分至少相当于药理学 MPI，可稳健预测死亡率和其他 无法进行腿部运动的退伍军人的临床结果测量主要假设。 目前的建议是：1）手臂运动心电图压力测试分数或最佳拟合模型 没有或有冠状动脉钙评分 (-/+ CACS) 均不劣于 Duke 跑步机得分 -/+ CACS、最佳拟合模型跑步机心电图和 regadenoson (r) MPI 压力测试， 所有这些都以随机顺序在相同的退伍军人中进行，作为阻塞性的初步评估 冠状动脉疾病 (oCAD)，以及 2) 手臂运动心电图压力测试分数或最佳拟合 模型 -/+ CACS 不劣于杜克跑步机分数 -/+ CACS，最佳拟合模型 对同一退伍军人进行跑步机心电图和 rMPI 压力测试，以预测主要临床症状 终点（心血管 (CV) 死亡率、心肌梗塞或治疗后 90 天的复合终点 压力测试冠状动脉血运重建）和全因死亡率的次要临床终点 我们对所有退伍军人的具体目标是圣路易斯退伍军人。 管理（VA）压力测试实验室，不排除运动或 心脏计算机断层扫描血管造影（CTA），是执行 比较手臂运动心电图压力测试分数和最佳结果的单中心前瞻性临床试验 型号 -/+ CACS 与杜克跑步机评分 -/+ CACS（如果能够进行跑步机锻炼）， 以及最适合的跑步机心电图和 rMPI 模型，所有这些均在同一退伍军人中执行，用于 确定 oCAD 的诊断终点，定义为严重（≥70%）闭塞 心外膜、移植物或 ≥50% 左主干冠状动脉管腔，由心脏 CTA 或 有创冠状动脉造影以及主要和次要临床终点的预测 待评估的手臂运动评分系统包含上述变量。 静息代谢当量、1 分钟心率恢复和手臂的手臂运动能力 运动引起的 ST 压低≥1 mm 需要评估的 Regadenoson MPI 变量包括 异常 MPI 研究以及总应力和差异分数、瞬态的最佳拟合模型 我们计划缺血性扩张、门控左心室射血分数和心率反应。 每年招收 75 名退伍军人，为期 4 年，并再跟踪整个队列一年。 将使用 SAS 使用单变量和多变量 Logistic 进行统计分析 我们将评估手臂运动评分 -/+ CACS 的非劣效性。 它们与 oCAD 的关联以及临床终点的预测，非劣效性界限为 0.05 长期目标是开展多中心前瞻性随机 VA 合作研究 评估手臂运动心电图压力测试的普遍性 -/+ CACS 用于诊断和 退伍军人管理局和美国医疗保健系统的预后评估。