EXercise MRI evaluation of HIV-PAH Longitudinal Determinants(EXHALTED)

 描述（由申请人提供）：抗逆转录病毒治疗（ART）的引入已将人类免疫缺陷病毒（HIV）感染转变为慢性疾病。HIV中的肺动脉高压（PAH）是发病和死亡的重要原因，被认为是PAH任何亚型中预后最差的，表现症状通常包括呼吸困难和运动受限（ExLT），通常归因于其他疾病。在这项拨款申请中，我们提出了一项前瞻性研究，以了解心肺反应和PAH的艾滋病毒使用超声心动图结合运动磁共振成像（MRI）和心肺测试。我们进一步提出了创新的评估炎症参数的艾滋病毒，将提供深入了解心肺功能障碍和PA压力升高的机制。我们的假设是，HIV-ExLT患者通常表现出运动时RV功能/PA压力（ExPH）的改变，后一种表型代表进展为静息PAH的高风险队列。在目标1中，我们将制定ExMR和CPT方案，允许测量RV功能、平均PA压（mPAP）和运动时的VO 2 max，以确定患病率并区分运动收缩储备异常（<$RVEF）患者。在目标2中，我们将研究静息RV体积、收缩储备和进展预测因子的纵向变化，重点关注CD 8 T细胞免疫激活和耗竭的测量及其与PAH进展的关系。在目标3中，我们将随访确诊或新诊断的静息HIV-PAH患者，并评价静息RV功能、体积和纤维化的变化，并将这些变化与12个月时侵入性血流动力学参数的变化相关联。我们将尝试描述该患者人群中进展的预测因素。我们的提案对RFA-HL-14-023具有高度响应性，将允许早期识别右心疾病，回答与HIV患者运动心肺反应相关的基本问题，并导致适当设计的结局试验，以预防PAH和相关功能限制。(End摘要）

 DESCRIPTION (provided by applicant): The introduction of antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection into a chronic disease. Pulmonary arterial hypertension (PAH) in HIV is an important cause of morbidity and mortality is thought to have the the worst prognosis of any subtype of PAH with presenting symptoms often including dyspnea and exercise limitation (ExLT), commonly attributed to other disorders. In this grant application, we propose a prospective study to understand the cardiopulmonary responses and PAH in HIV using echocardiography in conjunction with exercise magnetic resonance imaging (MRI) and cardiopulmonary testing. We further propose innovative assessment of inflammatory parameters in HIV that will provide insights into the mechanisms of cardiopulmonary dysfunction and elevated PA pressures. Our hypothesis is that HIV- ExLT patients commonly exhibit alteration in RV function/PA pressure with exercise (ExPH), with the latter phenotype representing a high-risk cohort for progression to resting PAH. In Aim 1, we will institute a protocol of ExMR and CPT that will allow measurement of RV function, mean PA pressure (mPAP) and VO2max in response to exercise to define the prevalence and distinguish patients with abnormal exercise contractile reserve (¿ RVEF). In aim 2 we will investigate longitudinal changes in resting RV volume, contractile reserve and predictors of progression with a focus on measures of CD8 T cell immune activation and exhaustion and their relationship to progression of PAH. In aim 3, we will follow patients with established or newly diagnosed resting HIV-PAH and evaluate changes in resting RV function, volume and fibrosis and correlate these changes with alteration in invasive hemodynamic parameters at 12 months. We will attempt to delineate the predictors of progression in this patient population. Our proposal is highly responsive to RFA-HL-14-023 and will allow early identification of right heart disease, answer fundamental questions pertaining to cardiopulmonary response with exercise in HIV and lead to appropriately designed outcome trials to prevent PAH and associated functional limitations. (End of Abstract)