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: 9932925
• 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 2021-04-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9932925
• 关键词: Address; American; Anatomy; Angiography; Armadillo Repeat; Arteriographies; Award; Blood flow; Cardiac; Cardiovascular system; Chemicals; Clinical; Clinical Trials; Consumption; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Detection; Diagnostic; Diagnostic tests; Dilatation - action; EKG ST Segment Depression; Electrocardiogram; Enrollment; Evaluation; Exclusion; Exercise; Exercise Test; 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; 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 outcome measures; 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.

跑步机运动能力和其他生理反应的腿部锻炼是强大的 预测死亡率，并提供重要的临床和诊断信息。但不少 退伍军人不能进行跑步机锻炼，因为下肢或其他残疾。为 多年来，药物心肌灌注成像（MPI）一直是标准的护理 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下，而且要贵好几倍 运动心电图（ECG）。随着最近完成的优秀评审奖，我们 获得了大量的回顾性观察证据，表明手臂运动心电图负荷试验 评分至少与药理学MPI相当，可稳健预测死亡率和其他 不能进行腿部锻炼的退伍军人的临床结局指标。主要假设 目前的建议是：1）手臂运动心电图负荷测试分数或最佳拟合模型 无或有冠状动脉钙化评分（-/+ CACS）的患者均不劣于杜克 跑步机评分-/+ CACS，最佳拟合模型跑步机ECG和regadenoson（r）MPI负荷测试， 所有这些都是在相同的退伍军人中以随机顺序进行的，作为阻塞性疾病的初步评价。 冠状动脉疾病（oCAD），和2）手臂运动心电图负荷试验评分或最佳拟合 模型-/+ CACS不劣于杜克跑步机评分-/+ CACS，最佳拟合模型 在同一退伍军人中进行活动平板心电图和rMPI负荷测试，以预测主要临床 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）和全因死亡率的次要临床终点 和CV死亡率。我们对所有退伍军人的具体目标提到了圣路易斯退伍军人 管理（VA）压力测试实验室，并没有排除运动或 regadenoson应力测试或心脏计算机断层扫描血管造影术（CTA），是执行 一项单中心前瞻性临床试验，比较手臂运动ECG负荷试验评分和最佳 模型-/+ CACS和杜克跑步机评分-/+ CACS（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，都在同一退伍军人， 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，通过心脏CTA确定，或 有创冠状动脉造影，以及主要和次要临床终点的预测 上面描述手臂运动评分系统的评价纳入了变量 静息代谢当量、1分钟心率恢复和手臂运动能力 运动诱发ST段压低≥1 mm。要评价的Regadenoson MPI变量包括 异常MPI研究和最佳拟合模型的总和压力和差异分数，短暂的 缺血性扩张、门控左心室射血分数和心率反应。我们计划 每年招募75名退伍军人，为期4年，并对整个队列再进行一年的随访。 将使用SAS进行统计分析，使用单变量和多变量logistic， 考克斯回归模型。我们将评估手臂运动评分-/+ CACS的非劣效性， 其与oCAD的相关性以及临床终点的预测，非劣效性界值为 0.05.长期目标是开展一项多中心前瞻性随机VA合作研究 评估手臂运动心电图负荷试验-/+ CACS用于诊断和 在VA和美国医疗保健系统的预后评估。