Cardiac Growth and Function Trajectories after Preterm Birth

项目摘要/摘要： 我们对早产青少年和成人的开创性研究发现了早产儿的三个明显特征 早产心脏可能会增加心力衰竭的风险。这些措施包括(1)心脏体积缩小，有助于 运动时心脏储备迟钝，(2)左心室(LV)心肌纤维化增加，(3)右 与潜在的肺血管疾病或右肺功能受损相关的室(RV)功能障碍 血管(PV)偶联。然而，这些发现如何在早期寿命中取得进展还是个未知数。这个 这项建议的目标是(1)利用混合效应分位数绘制心脏生长和功能曲线 预测早产儿童和成人心血管轨迹的回归模型，以及(2)识别 生长和功能受损的风险因素和生物标志物。我们建议横断面重复双室 儿童和青少年在基线时和两年后重复进行的肺血管评估 早产32周的成年人(年龄8-30岁；n=150)与年龄、性别和种族相匹配的足月- 出生对照组(n=150)。将利用混合效应开发疾病自然病史的多变量模型 分位数回归预测生长和功能轨迹。目标1：找出损害健康的新奇特征 早产后从童年到成年早期的心脏发育。我们将使用重复的措施 在基线和治疗后测量心脏结构(如左心室舒张末期容量指数和左心室重量指数) 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 每种性别的曲线，调整新生儿和常见心血管健康调节剂的影响。我们 假设早产女性的心脏发育轨迹较低，定义为以一致的速度生长 但生长百分位数较低，而早产男性将有生长障碍，定义为从 长期增长曲线。目的2：确定双室心肌纤维化是否与新生儿相关 早产后的特点和随年龄增长而递增。应用心脏MRI对晚期Gd进行检查 增强扫描(LGE)和自然T1标测，我们将评估双室心肌纤维化。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，以及 与时俱进。目的3：评估RV-PV偶联是否因RV功能恶化而随年龄增长而下降。我们 将使用RV-PV耦合的一系列无创性测量(MRI RV每搏量/收缩末期容量)、RV 功能(MRI射血分数，劳损)和肺血管疾病(三尖瓣返流速度， 肺动脉加速时间和肺血管形成)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 加上由于RV功能恶化而不是后负荷增加(恶化的PV疾病)而导致的年龄，最值得注意的是 在男性和患有支气管肺发育不良的患者中。研究结果将提供理由和潜在的目标 用于未来的早期干预研究，以促进早产后心脏生长和保护心脏功能。

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.