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

描述(申请人提供)：抗逆转录病毒疗法(ART)的引入将人类免疫缺陷病毒(HIV)感染转变为一种慢性病。HIV患者的肺动脉高压(PAH)是导致发病率和死亡率的重要原因，被认为是任何PAH亚型中预后最差的，其主要症状通常包括呼吸困难和运动受限(ExLT)，这通常被归因于其他疾病。在这项赠款申请中，我们提出了一项前瞻性研究，以了解HIV患者的心肺反应和PAH，结合运动磁共振成像(MRI)和心肺测试。我们进一步提出了对HIV炎症参数的创新评估，这将为心肺功能障碍和PA压力升高的机制提供洞察力。我们的假设是，HIV-ExLT患者通常表现出运动后RV功能/PA压的改变(ExPH)，后者的表型代表着进展为静止期PAH的高危队列。在目标1中，我们将建立一种可测量RV功能、平均动脉压(MPAP)和最大摄氧量(VO2max)的ExMR和CPT方案，以确定运动收缩储备(Δ)异常的患病率和区分患者。在目标2中，我们将研究静息RV容量、收缩储备的纵向变化和进展的预测因素，重点是CD8 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，我们将跟踪观察确诊或新诊断的静息HIV-PAH患者，评估静息RV功能、容量和纤维化的变化，并在12个月时将这些变化与有创血流动力学参数的变化相关联。我们将尝试描述这一患者群体中进展的预测因素。我们的建议对RFA-HL-14-023高度响应，将使我们能够及早识别右心疾病，回答与艾滋病毒运动的心肺反应有关的基本问题，并导致适当设计的结果试验，以预防PAH和相关的功能限制。

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 (Δ 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.