Cardiac Growth and Function Trajectories after Preterm Birth

早产后心脏的生长和功能轨迹

• 批准号: 10658639
• 负责人: Kara N Goss
• 金额: $ 82万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658639
• 关键词: Acceleration; Adolescence; Adolescent; Adult; Affect; Age; Biological Markers; Blood Vessels; Bronchopulmonary Dysplasia; Cardiac; Cardiopulmonary; Cardiovascular system; Characteristics; Child; Childhood; Chronology; Cohort Studies; Coupling; Data; Databases; Disease; EFRAC; Early Intervention; Echocardiography; Equation; Evaluation; Exercise; Failure; Female; Fibrosis; Future; Gadolinium; Gestational Age; Growth; Heart; Heart failure; High Prevalence; Impairment; Individual; Injury; Intervention; Intervention Studies; Knowledge; Left; Left Ventricular Mass; Live Birth; Longevity; Lung; Magnetic Resonance Imaging; Maps; Measures; Modeling; Myocardium; Neonatal; Neonatal Intensive Care Units; Population Heterogeneity; Pregnancy; Premature Birth; Process; Pulmonary Hypertension; Pulmonary artery structure; Pulmonary function tests; Race; Registries; Research; Right Ventricular Dysfunction; Right Ventricular Function; Risk; Risk Factors; Serum; Stroke Volume; Structure; Systemic hypertension; Time; Vascularization; Ventricular; Ventricular End-Diastolic Volumes; age group; cardiac magnetic resonance imaging; cardiovascular effects; cardiovascular health; coronary fibrosis; disease natural history; emerging adult; expectation; extreme prematurity; falls; functional decline; heart dimension/size; heart function; heart preservation; high risk; improved; indexing; male; neonatal exposure; neonatal resuscitation; novel; preclinical study; prospective; pulmonary vascular disorder; recruit; screening; sex; socioeconomics; young adult

Project Summary/Abstract: Our pioneering research in adolescents and adults born preterm has identified 3 distinct characteristics of the preterm heart that could increase risk for heart failure. These include (1) reduced cardiac size contributing to a blunted cardiac reserve during exercise, (2) increased left ventricular (LV) cardiac fibrosis, and (3) right ventricular (RV) dysfunction relative to the underlying pulmonary vascular disease, or impaired RV-pulmonary vascular (PV) coupling. However, how these findings may progress across the early lifespan is unknown. The objective of this proposal is (1) to develop cardiac growth and function curves using mixed effect quantile regression models to predict cardiovascular trajectories in children and adults born preterm, and (2) to identify risk factors and biomarkers for impaired growth and function. We propose cross-sectional repeated biventricular and pulmonary vascular assessments obtained at baseline and repeated after 2 years in children and young adults born <32 weeks preterm (age 8-30 years; n=150), compared to age-, sex-, and racially-matched term- born controls (n=150). Multivariate models of the natural history of disease will be developed using mixed effect quantile regression to predict growth and function trajectories. Aim 1: Identify novel characteristics that impair cardiac growth from childhood through early adulthood after preterm birth. We will use repeated measures of cardiac structure (e.g. LV end diastolic volume index and LV mass index by MRI) obtained at baseline and after 2 years. Multivariable models using mixed effect quantile regression will be used to develop cardiac growth curves for each sex, adjusting for effects of neonatal and common cardiovascular health modifiers. We hypothesize that preterm females will have a lower cardiac growth trajectory defined as growth at a consistent but lower growth percentile, while preterm males will have a growth failure defined as a progressive fall from a term growth curve. Aim 2: Determine whether biventricular cardiac fibrosis is associated with neonatal characteristics and progressive with chronological age after preterm birth. Using cardiac MRI with late gadolinium enhancement (LGE) and native T1 mapping, we will assess biventricular cardiac fibrosis. We hypothesize that fibrosis scores are elevated in preterm-born children and adults, associate with neonatal resuscitation, and progress with age. Aim 3: Assess whether RV-PV coupling declines with age due to worsening RV function. We will use serial noninvasive measures of RV-PV coupling (MRI RV stroke volume/end systolic volume), RV function (MRI ejection fraction, strain), and pulmonary vascular disease (ECHO tricuspid regurgitant jet velocity, pulmonary artery acceleration time, and pulmonary vascularization) to establish the trajectories of RV and PV disease after preterm birth. We hypothesize that preterm-born individuals demonstrate worsening RV-PV coupling with age due to worsening RV function rather than rising afterload (worsening PV disease), most notable in males and those with bronchopulmonary dysplasia. Study results will provide justification and potential targets for future early intervention studies to promote cardiac growth and preserve cardiac function after preterm birth.

项目概要/摘要： 我们对早产的青少年和成人进行的开创性研究确定了早产儿的3个明显特征， 早产儿心脏可能会增加心力衰竭的风险。这些包括（1）心脏尺寸减小， 运动期间心脏储备减弱，（2）左心室（LV）心脏纤维化增加，（3）右心室纤维化增加。 与基础肺血管疾病相关的心室（RV）功能障碍，或RV-肺功能受损 血管（PV）耦合。然而，这些发现如何在早期生命中发展尚不清楚。的 本研究的目的是（1）利用混合效应分位数建立心脏生长和功能曲线 回归模型预测早产儿和成人的心血管轨迹，以及（2）识别 生长和功能受损的风险因素和生物标志物。我们提出了横截面重复双心室 在儿童和青少年中进行基线和2年后重复的肺血管评估 早产<32周的成年人（年龄8-30岁; n=150），与年龄、性别和种族匹配的足月儿相比， 出生对照组（n=150）。将使用混合效应开发疾病自然史的多变量模型 分位数回归来预测生长和功能轨迹。目标1：识别损害的新特征 早产后从儿童期到成年早期的心脏生长。我们将反复使用 基线和治疗后获得的心脏结构（例如，通过MRI测量的LV舒张末期容积指数和LV质量指数） 2年使用混合效应分位数回归的多变量模型将用于开发心脏生长 每个性别的曲线，调整新生儿和常见的心血管健康调节剂的影响。我们 假设早产女性心脏生长轨迹较低， 但较低的生长百分位数，而早产男性将具有生长失败，定义为从 长期增长曲线目的2：确定双心室心肌纤维化是否与新生儿心肌梗死相关。 早产后的特征和随实际年龄的进展。使用晚期钆的心脏MRI 增强（LGE）和天然T1标测，我们将评估双心室心脏纤维化。我们假设 早产儿和成人的纤维化评分升高，与新生儿复苏有关， 随着年龄的进步。目的3：评估RV-PV耦合是否因RV功能恶化而随年龄增长而下降。我们 将使用RV-PV耦合（MRI RV每搏输出量/收缩末期容积）、RV 功能（MRI射血分数，应变）和肺血管疾病（ECHO三尖瓣返流喷射速度， 肺动脉加速时间和肺血管化），以建立RV和PV的轨迹 早产后的疾病。我们假设早产儿表现出RV-PV恶化 由于RV功能恶化而不是后负荷增加（PV疾病恶化），与年龄相结合，最显著 在男性和支气管肺发育不良者中。研究结果将提供依据和潜在目标 未来的早期干预研究，以促进心脏生长和保护心脏功能早产后。