Echocardiography evaluation of bronchopulmonary dysplasia-associated pulmonary hypertension: a retrospective observational cohort study

Abstract

Background: Echocardiography has poor accuracy in grading the severity of pulmonary hypertension (PH) compared to cardiac catheterization. However, the relationship between degree of PH and prognostic outcomes remains uncertain. Our primary objective was to determine whether echocardiogram-assessed PH severity is associated with mortality and hospital readmission in the first year of life.

Methods: A retrospective cohort study of infants born less than 32 weeks of gestational age with bronchopulmonary dysplasia (BPD) underwent echocardiography was performed. Echocardiograms were performed at 36-38 weeks postmenstrual age. Data during hospitalization and post-discharge collected at 1-year age were analyzed with cox regression models and logistic regression models to identify the association of PH severity with mortality and readmission. Area under curve (AUC) was calculated to examine the accuracy of these models to reflect the likelihood of outcomes.

Results: Fifty-six of 237 (23.6%) infants were diagnosed as PH. Moderate and severe PH was significantly associated with mortality during the first one year of life (moderate PH vs. none HR =26.58, 95% CI: 4.40-160.78, P<0.001; severe PH vs. none HR =36.49, 95% CI: 5.65-235.84, P<0.001). Male, preeclampsia and inhaled nitric oxide were also associated with mortality. Mild PH was significantly associated with readmission (OR =2.42, 95% CI: 1.12-5.26, P=0.025), but not associated with mortality (HR =2.09, 95% CI: 0.43-10.18, P=0.36). The PH severity model based on echocardiography accurately informed mortality (AUC 0.79).

Conclusions: Echocardiogram-assessed PH severity is associated with prognostic outcomes, including mortality and readmission in very preterm infants with BPD. The severity of PH based on echocardiography is a potential predictor of mortality in the first year of life.

Keywords: Bronchopulmonary dysplasia (BPD); echocardiography; prognosis; pulmonary hypertension (PH).

Figure 1

Flow chart of the study population. BPD, bronchopulmonary dysplasia; PH, pulmonary hypertension; ECHO, echocardiogram; PMA, post-menstrual age.

Figure 2

Kaplan-Meier survival curves according to PH severity. Kaplan-Meier graphs demonstrating the probability of survival during the first year after birth of infants with mild, moderate or severe PH. PH, pulmonary hypertension.

Figure 3

Parameter estimates from multivariable cox regression. Adjusted hazard ratios from cox regression modeling mortality during the first one year of life based on PH severity, gender, IVF-ET, preeclampsia, SGA, NEC, EUGR, surfactant administration, diuretic administration, iNO and sildenafil administration. Moderate and severe PH had the largest estimated association with mortality during the first one year of life (moderate PH vs. none HR =26.58, 95% CI: 4.40–160.78, P<0.001; severe PH vs. none HR =36.49, 95% CI: 5.65–235.84, P<0.001). Male, preeclampsia and iNO were also significantly associated with survival outcomes (HR =5.34, 95% CI: 1.06–26.90, P=0.04; HR =4.38, 95% CI: 1.04–18.43, P=0.04 and HR =5.78, 95% CI: 1.08–31.08, P=0.04, respectively). PH, pulmonary hypertension; IVF-ET, in vitro fertilization and embryo transfer; SGA, small for gestational age; NEC, necrotizing enterocolitis; EUGR, extrauterine growth restriction; iNO, inhaled nitric oxide.

Figure 4

Receiver operating characteristic curves demonstrating that PH severity is a strong predictor of death in the first year of life. Cox regression models: PH severity model, model including selected covariates listed in the Figure 3 and model using the other selected covariates except PH severity. AUC of the PH severity model was 0.79 and could reach 0.85 when incorporating other covariates. PH, pulmonary hypertension; AUC, area under curve.