247 - Hemodynamic phenotypes in congenital diaphragmatic hernia (CDH) versus non-CDH acute pulmonary hypertension in newborns

Publication Number: 4243.247

Stephanie M. Boyd, The University of Sydney and The Children's Hospital at Westmead, Balmain, New South Wales, Australia; John Wren, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Adrianne R. Bischoff, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States; Patrick McNamara, University of Iowa, Iowa city, IA, United States

Background: Hemodynamic phenotypes are recognised as important modulators of therapeutic response in newborns with congenital diaphragmatic hernia (CDH) and all-cause acute pulmonary hypertension (PH). Comparison of hemodynamic phenotype, including pulmonary hemodynamics and ventricular performance, in pulmonary vasodilator-naive infants with CDH vs. non-CDH PH has not previously been reported.

Objective: To compare hemodynamic phenotype of newborns with early PH with and without CDH and to investigate targeted neonatal echocardiography (TNE) response to inhaled nitric oxide (iNO).

Design/Methods: Single center retrospective case-control study of infants ≥ 35weeks' (December 2019 - September 2022) with PH on TNE at < 72hrs of age. Comparison of TNE indices in infants with CDH vs. non-CDH PH was performed. The primary outcome was baseline right ventricular dysfunction, defined as ≥2 abnormal of [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (FAC), RV systolic excursion velocity (RVs')]. Secondary outcomes included indices of: PH [systolic eccentricity index, ductal shunting, tricuspid regurgitant jet velocity], left heart size, left ventricular dysfunction using ejection fraction (EF) by Simpson's biplane (LVEF < 55%) and speckle tracking echocardiography. Univariate analysis between CDH vs. non-CDH groups and subgroup analyses of TNE response in iNO-treated infants were performed.

Results: Ten infants with CDH and 30 non-CDH were included. Respiratory severity scores were similar between the two groups. Nine (90%) with CDH had suprasystemic PH compared to 14 (47%) without (p=0.02, Table 1). RV dysfunction occurred in 5 (50%) infants with CDH and 7 (23%) with non-CDH and was associated with overall mortality (X2=5.03, p=0.02). Ten patients received iNO (3 CDH, 7 non-CDH). Although 9 (90%) had ongoing PH on TNE post-iNO, TAPSE (p=0.03) and RV output (p=0.04) increased post-iNO [Figure 1, Figure 2]. Although LVEF and strain were similar between groups, infants with CDH had decreased LV end-diastolic volume (p < 0.001), LV length in end-diastole (p < 0.001) and LV output (74.5 ± 32.7 vs.110.4 ± 39.8 mL/kg/min, p=0.01), with a smaller LV outflow tract (0.48 ± 0.07 vs. 0.56 ± 0.05 cm, p< 0.001).

Conclusion(s): In infants with PH, those with CDH have evidence of reduced LV size, volume and output. Clinical improvement with iNO in resistance-mediated CDH and non-CDH PH in neonates may reflect improved RV performance rather than reduced pulmonary pressure. Further evaluation in pulmonary vasodilator-naive infants with CDH is needed to facilitate a precision medicine approach to intensive care.

Table 1: Baseline clinical and echocardiography parameters in infants with acute pulmonary hypertension (PH) with congenital diaphragmatic hernia (CDH) and non-CDH (PH)
CDH = congenital diaphragmatic hernia; FiO2 = fraction of inspired oxygen; LVsEI = left ventricular systolic eccentricity index; PVR = pulmonary vascular resistance; PAAT = pulmonary artery acceleration time; RVET = right ventricular ejection time; TAPSE = tricuspid annular plane systolic excursion; RV = right ventricular; FAC = fractional area change; s' = systolic excursion velocity; RVO.= right ventricular output; LV = left ventricular; EF = ejection fraction; LVO = left ventricular output; GLS = global longitudinal strain; E/e' = mitral E/mitral annular e' velocity; EDV = end diastolic volume; LD = length in end-diastole (endocardium); LVOT = left ventricular outflow tract
Respiratory severity score is calculated by: mean airway pressure x FiO2
Values are number (percentage), mean (standard deviation) or median (interquartile range). Data analysed using independent t-tests for parametric data and Mann-Whitney U tests for non-parametric data.

Figure 1: Change in (A) Tricuspid annular plane systolic excursion (TAPSE) (mm) following inhaled nitric oxide (iNO) (n = 10) and (B) Right ventricular output (RVO) (mL/kg/min) following inhaled nitric oxide (iNO) (n=10).
Data analyzed using paired t-tests.

Figure 2: Line graphs demonstrating individual patient values prior to and following inhaled nitric oxide (iNO) for (A) Tricuspid annular plane systolic excursion (TAPSE) (mm) (n = 10) and (B) Right ventricular output (RVO) (mL/kg/min) (n=10).