Cardiac Growth and Function Trajectories after Preterm Birth

Ut Southwestern Medical Center, Dallas TX

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Abstract

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.