Pulmonary hypertension and cardiac function in congenital diaphragmatic hernia: relationship to disease severity and outcomes

Abstract Objective To assess patterns of postnatal biventricular function and their relationship to prenatal and postnatal markers of disease severity in infants with congenital diaphragmatic hernia (CDH). To investigate clusters of micro RNA as 17-92 expressed in pulmonary hypoplasia in patients with CDH. Study Design Observational case-control study of cardiac function in infants with CDH in the first 5 days of life. Systolic and diastolic function in the right (RV) and left (LV) ventricles were assessed using speckle tracking-derived global strain and tissue Doppler imaging of myocardial velocities. In another cohort of CDH, Bronchoalveolar aspiration (BAL) fluid was obtained and metabolomic analysis was run for micro RNA 17-92 cluster. Specifically miR17, miR18a, miR19a, miR19b, miR20a, miR92 were analyzed. Correlation between cardiac function and prenatal observed:expected total fetal lung volume (TFLV), oxygenation index (OI), duration of intubation and length of stay were assessed. Results All measures of systolic and diastolic function were significantly reduced in the CDH group (n=25) compared to controls (n=20) at <48 hours, and improved by 72- 96 hours. LV global systolic longitudinal strain (LV GLS) correlated with prenatal TFLV (r2 0.32, p 0.03), OI (r2 0.35, P<0.001), duration of intubation (r2 0.24, p 0.04), and length of stay (r2 0.4, p 0.006). LV GLS at <48 hours was significantly lower in 6 CDH patients who did not survive and/or required ECMO compared to those who did not; -11.5 (5.3) % vs -16.9 (5.3) %, p 0.02. For the metabolomic analysis we found miR17, miE18a, miR19b, miR20a were found significantly higher in CDH (p<0.05) and miR19a lower (p<0.05). No significant correlation was found between miR92 expression and clinical outcomes. Conclusions Right and left ventricular function are impaired in the transitional period in infants with CDH. Early left ventricular systolic function correlates with prenatal and postnatal markers of clinical disease severity and may be an important determinant of disease severity and therapeutic target in CDH. These findings support regular assessment of cardiac function in CDH and investigational trials of targeted cardiovascular therapies. miR 17-92 cluster may represent a potential hallmark of PH in CDH however from our result doesn’t predict disease severity.