Cardiopulmonary Exercise MRI in Heart Failure with Preserved Ejection Fraction

项目摘要 心血管疾病(CVD)是美国发病率和死亡率的主要原因， 保留射血分数(HFpEF)的心力衰竭患病率每年都在上升。目前，还没有单一的 无创性诊断试验对HFpEF的准确诊断。HFpEF的诊断是通过以下几个方面的结合 症状评估、血浆生物标志物和心脏成像。当病人严重失代偿时， HFpEF的诊断具有很高的可信度。然而，在出现呼吸困难的稳定门诊患者中， 用力和中等预测概率的HFpEF，诊断是极具挑战性的。因为不是- 有创检测诊断特异性有限，在这些病例中，有创血流动力学心肺 运动测试(ICPET)被认为是黄金标准。然而，iCPET是侵入性的，具有风险，并且 只在专门的中心演出。心血管磁共振成像(CMR)可以无创性评估心力衰竭相关心脏 以及血管异常，包括双室结构/功能、心肌组织成分、冠状动脉 微血管功能、主动脉扩张性/僵硬和脂肪堆积。作为心血管和肺病 HFpEF的症状是由于劳累而出现的，本建议的目的是使用安装在 核磁共振扫描仪检查心肺病理生理随运动强度递增 抵抗，然后是传统的血管扩张剂负荷成像方案。这项研究的目标是利用我们的 新的心肺运动MRI方案可以准确地早期诊断HFpEF，消除了 ICPET，并确定HFpEF进展的特定病理生理机制和预后信息 心血管疾病的不良后果。为了实现这一目标，我们将从三个医疗中心招募病人进行 临床上疑似“早期”HFpEF患者的心肺运动MRI前瞻性研究 转诊为iCPET，18个月后进行随访MRI扫描。我们的三个具体目标是1)调查 无创性成像与心肺MRI早期诊断HFpEF的相关性及诊断性能 对于射血分数正常和原因不明的呼吸困难的患者，使用iCPET作为参考标准；2) 探讨心肺运动MRI参数与心脑血管疾病健康结局的关系 包括疑似早期HFpEF的心血管死亡和住院情况；3)探讨 完成第二次体外循环对可疑早期高血压性肺功能的心肺结构和功能的影响 首次核磁共振检查18个月后进行运动核磁共振检查。这一创新的心肺运动MRI方案是 有望提高HFpEF的无创性诊断和预后，并最终有助于改善 提供更准确的诊断标准和非侵入性的治疗策略和预防性护理 在临床试验中监测新治疗策略的有效性的方法。

Project Summary Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States, with the prevalence of heart failure with preserved ejection fraction (HFpEF) rising every year. Currently, there is no single non-invasive diagnostic test for accurate diagnosis of HFpEF. HFpEF is diagnosed through a combination of symptom assessments, plasma biomarkers, and cardiac imaging. When patients are acutely decompensated, HFpEF can be diagnosed with high confidence. However, among stable outpatients presenting with dyspnea on exertion and an intermediate pre-test probability of HFpEF, diagnosis is extremely challenging. Since non- invasive testing has limited diagnostic specificity, in these cases, invasive hemodynamic cardiopulmonary exercise testing (iCPET) is considered the gold standard. However, iCPET is invasive, carries risk, and is performed only in specialized centers. Cardiovascular MRI (CMR) can non-invasively assess HF-related heart and vascular abnormalities including biventricular structure/function, myocardial tissue composition, coronary microvascular function, aortic distensibility/stiffness, and fat accumulation. As cardiovascular and pulmonary symptoms of HFpEF occur with exertion, the objective of this proposal is to use a supine ergometer mounted on the MRI scanner table to examine heart and lung pathophysiology with exercise of incrementally increasing resistance, followed by a conventional vasodilator stress imaging protocol. The goal of this study is to use our novel cardiopulmonary exercise MRI protocol to accurately diagnose “early” HFpEF, to eliminate the need for iCPET, and to identify specific pathophysiologies underlying HFpEF progression and prognostic information for adverse CVD outcomes. To achieve this, we will recruit patients from three medical centers to conduct a prospective study using cardiopulmonary exercise MRI in suspected “early” HFpEF patients who are clinically referred for iCPET, with a follow-up MRI scan 18 months later. Our three specific aims seek to 1) Investigate non-invasive imaging correlates and diagnostic performance of cardiopulmonary MRI for early HFpEF diagnosis in patients with normal ejection fraction and unexplained dyspnea, using iCPET as a reference standard; 2) Investigate the relationship between cardiopulmonary exercise MRI parameters and CVD health outcomes, including cardiovascular death and hospitalization in suspected early HFpEF; 3) Explore temporal changes in heart and lung structure and function in suspected early HFpEF by completing a second cardiopulmonary exercise MRI 18 months after the initial MRI exam. This innovative cardiopulmonary exercise MRI protocol is expected to improve non-invasive diagnosis and prognosis of HFpEF, and ultimately contribute to improved treatment strategies and preventative care by providing more accurate diagnostic criteria and a non-invasive method of monitoring the efficacy of new treatment strategies in clinical trials.