Left Ventricular Strain in Systemic Sclerosis-related Pulmonary Hypertension

系统性硬化症相关肺动脉高压中的左心室应变

基本信息

批准号：
10154807
负责人：
Justin Kwan Lui
金额：
$ 8.59万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10154807
关键词：
Active Learning Affect Aftercare Arterial Disorder Autopsy Award Biological Markers Biometry Blood Vessels Boston Cardiac Cardiopulmonary Chronic Clinical Clinical Research Cluster Analysis Collaborations Communities Cutaneous sclerosis Data Data Analyses Data Analytics Databases Development Plans Diagnosis Diffuse Disease Echocardiography Etiology Exhibits FDA approved Future Goals Heart Diseases Hematological Disease Impairment Individual Individual Differences Interstitial Lung Diseases K-Series Research Career Programs Leadership Left Left Ventricular Dysfunction Lung Lung diseases Measurement Medical center Mentors Mentorship Morbidity - disease rate Myocardial dysfunction National Heart, Lung, and Blood Institute Nature Outcome Patient Care Patient-Focused Outcomes Patients Physicians Physiologic intraventricular pressure Play Population Positioning Attribute Prevalence Prognosis Protocols documentation Public Health Schools Pulmonary Hypertension Pulmonary Vascular Resistance Pulmonary function tests Registries Research Research Infrastructure Research Personnel Research Training Right Ventricular Dysfunction Risk Role Scientist Scleroderma Serology Severities Side Sleep Disorders Survival Rate Systemic Scleroderma Testing Therapeutic Time Time Series Analysis Training Translational Research United States Department of Veterans Affairs Universities Vasodilator Agents Ventricular Ventricular septum Wedge Pressures Work Writing cardiovascular risk factor career clinical care clinical phenotype cohort comorbidity demographics education research experience health care service organization hemodynamics hypertension control implementation research improved mortality multidisciplinary novel diagnostics novel imaging technique novel therapeutic intervention novel therapeutics patient population patient registry pressure prevent primary pulmonary hypertension prognostic programs pulmonary arterial hypertension response responsible research conduct risk stratification skill acquisition tool treatment response

项目摘要

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.

项目摘要与全身性硬化有关的肺部高血压（SSC-PH）患者的临床结局仍然很差。尽管在肺动脉高压（PAH）治疗方面有许多进步，但 SSC-PH的患者（常规归类为I组PAH）的死亡率继续增加给特发性PAH的患者。因此，有未满足的需要了解为什么会发生这种情况。在这项工作中，我们确定左心室（LV）功能障碍是否在导致肺部压力升高的作用中起作用在这个患者人群中。这些发现的结果将表明：1）可能存在更大的患病率心脏参与比该人群中所假定的；和/或2）LV功能障碍是PAH的结果增加肺动脉压力和由此导致的右心过载，从而损害LV收缩期收缩力。使用硬皮病研究翻译中心（CORT）数据库，自2002年以来，在硬皮病计划中遵循SSC的患者，该提案的具体目的是：评估SSC患者亚临床LV菌株的纵向变化（AIM 1）；并且，识别和表征通过聚类分析使用LV菌株在SSC-PH中的临床表型（AIM 2）。这项建议的工作将测试我们假设SSC-PH患者将在诊断SSC-之前表现出已经存在的LV功能障碍与SSC-PH患者相比那些不发展SSC-PH的人。我们还假设患有SSC-临床表型的患者与患者相比没有LV功能障碍的证据。 F32奖，具有教学，指导和研究经验它提供的是我成为专门从事肺部独立医师科学家的道路上的关键步骤血管临床研究。 AIM 1和2的结果将提出这样的观念，即SSC-PH患者需要不同的治疗方法，并将告知随后的K奖，重点是：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风险预后中的作用；和 3）治疗和改善SSC-PH患者护理的新型疗法的基本原理。这提出了工作将与：1）确定因素相符这解释了病理生物学和对治疗的反应的个体差异； 2）开发和优化新颖的诊断和治疗策略，以预防，治疗和治愈心脏，肺，血液和睡眠疾病。