Left Ventricular Strain in Systemic Sclerosis-related Pulmonary Hypertension

项目摘要 系统性硬化症相关肺动脉高压（SSc-PH）患者的临床结局仍然较差。 尽管肺动脉高压（PAH）的治疗方法已经取得了许多进展， SSc-PH患者（传统分类为I组PAH）的死亡率继续升高， 特发性肺动脉高压患者。因此，有一个未满足的需要，以了解为什么会发生这种情况。本工作 确定左心室（LV）功能障碍是否在肺动脉压升高中起作用 in this patient患者population人口.这些发现的结果将表明：1）可能有更大的患病率 心脏受累的可能性高于该人群中的假设;和/或2）LV功能障碍是PAH的结果， 肺动脉压升高，导致右心室超负荷，损害LV收缩压 收缩性使用硬皮病研究翻译中心（CORT）数据库， 自2002年以来，在硬皮病项目中随访的SSc患者中，本提案的具体目标是： 评价SSc患者亚临床LV应变的纵向变化（目标1）;以及，识别和表征 通过聚类分析，使用LV菌株在SSc-PH中进行临床表型分析（目的2）。这项工作将考验我们的 假设SSc-PH患者在诊断为SSc之前将表现出既存LV功能障碍- PH，SSc-PH患者的LV应变降低率大于 我们还假设具有SSc-PH临床表型的患者， 与患者相比，与LV功能障碍相关的PH的3年生存率更低 没有左心室功能障碍的迹象F32奖，教学法，导师和研究经验 它提供，是我成为一名独立的肺科学家的关键一步。 血管临床研究目标1和2的结果将提出这样的观点，即SSc-PH患者需要 不同的治疗方法，并将为随后的K奖提供信息，重点关注：1）LV功能障碍的作用 评估对PAH治疗的反应; 2）LV功能障碍在SSc-PH风险预测中的作用;以及 潜在地，3）治疗和改善SSc-PH患者护理的新型疗法的原理。 这项工作将与国家心脏、肺和血液研究所的以下目标保持一致：1）识别因素 解释病理生物学和对治疗反应的个体差异; 2）发展和 优化新的诊断和治疗策略，以预防，治疗和治愈心脏，肺，血液和睡眠 疾病

Project Summary Clinical outcomes for patients with systemic sclerosis-related pulmonary hypertension (SSc-PH) remain poor. Although there have been many advancements in therapeutics for pulmonary arterial hypertension (PAH), patients with SSc-PH, conventionally classified as Group I PAH, continue to have increased mortality compared to patients with idiopathic PAH. Hence, there is an unmet need to understand why this occurs. In this work, we determine whether left ventricular (LV) dysfunction plays a role in contributing to elevated pulmonary pressures in this patient population. The results from these findings will indicate that: 1) There may be a greater prevalence of cardiac involvement than presumed in this population; and/or 2) LV dysfunction is a consequence of PAH from increased pulmonary arterial pressures and resultant right ventricular overload that impairs LV systolic contractility. Using the Scleroderma Center of Research Translation (CORT) database, a clinical registry of patients with SSc followed within the Scleroderma program since 2002, the specific aims of this proposal are to: evaluate the longitudinal changes in subclinical LV strain in SSc patients (Aim 1); and, identify and characterize clinical phenotypes in SSc-PH using LV strain by cluster analysis (Aim 2). This proposed work will test our hypothesis that patients with SSc-PH will exhibit preexisting LV dysfunction prior to diagnosis of SSc- PH and that the rate of reduction of LV strain will be greater in patients with SSc-PH in comparison to those who do not develop SSc-PH. We also hypothesize that patients with a clinical phenotype of SSc- PH associated with LV dysfunction will have poorer 3-year survival rates in comparison to patients without evidence of LV dysfunction. The F32 award, with the didactics, mentorship, and research experience it affords, is a critical step on my path to becoming an independent physician-scientist specialized in pulmonary vascular clinical research. Results from Aims 1 and 2 will raise the notion that patients with SSc-PH require a different approach to therapy and will inform a subsequent K award focusing on: 1) The role of LV dysfunction in assessing response to PAH therapy; 2) The role of LV dysfunction in risk prognostication in SSc-PH; and potentially, 3) The rationale for novel therapies to treat and improve care of patients with SSc-PH. This proposed work will align with the following goals of the National Heart, Lung, and Blood Institute in: 1) Identifying factors that account for individual differences in pathobiology and in responses to treatments; and, 2) Developing and optimizing novel diagnostic and therapeutic strategies to prevent, treat, and cure heart, lung, blood, and sleep diseases.