# Tailoring Therapy to Bronchopulmonary Dysplasia Phenotype: A Ten-Year Experience in Precision Medicine

## TL;DR

This study shows that reducing systemic afterload with captopril improves heart and lung function in infants with severe bronchopulmonary dysplasia and left heart dysfunction.

## Contribution

The study introduces systemic afterload reduction as a novel therapeutic approach for a specific BPD phenotype involving left heart dysfunction.

## Key findings

- Systemic afterload reduction with captopril significantly improved oxygenation and left heart function in infants with severe BPD.
- Infants showed significant improvements in cardiac indices and aortic pulsatility after captopril treatment.
- Pulmonary vasodilators like inhaled nitric oxide may worsen outcomes in this specific BPD phenotype.

## Abstract

What are the main findings?
Conventionally, pulmonary artery hypertension is known in infants with severe bronchopulmonary dysplasia.Diagnostic and therapeutic emphasis is on right-sided haemodynamic alterations.

Conventionally, pulmonary artery hypertension is known in infants with severe bronchopulmonary dysplasia.

Diagnostic and therapeutic emphasis is on right-sided haemodynamic alterations.

What are the implications of the main findings?
Systemic hypertension–systemic artery stiffness–left heart dysfunction complicating a subset of such infants are not well appreciated.Systemic afterload reduction with ACE inhibitors such as captopril is physiologically more suited to this phenotype.Pulmonary vasodilators such as inhaled nitric oxide may cause deterioration.

Systemic hypertension–systemic artery stiffness–left heart dysfunction complicating a subset of such infants are not well appreciated.

Systemic afterload reduction with ACE inhibitors such as captopril is physiologically more suited to this phenotype.

Pulmonary vasodilators such as inhaled nitric oxide may cause deterioration.

Aims: To assess the impact of systemic afterload reduction on cardiorespiratory health in infants with a severe bronchopulmonary dysplasia (BPD)–systemic hypertension–left heart dysfunction (LHD) phenotype. Methods: Ten-year data were prospectively collected and analysed. The cohort included extremely preterm infants with severe BPD–systemic hypertension–LHD pathophysiology, treated with systemic afterload reduction with captopril. Main outcome measures included improvement in oxygenation and echocardiographic measures of LHD. Results: Twenty-six infants with gestation of 26.5 ± 2 weeks and median (interquartile range) birthweight of 900 (582, 1083) g were administered captopril at the corrected gestation median (range) of 40 weeks (37–67). On reassessment after five weeks, oxygen requirements (43 ± 16% to 26 ± 7%, p = 0.0001) and paired pCO2 decreased (64 ± 9 to 53 ± 9 mm Hg, p = 0.0001). Significant improvements were seen in cardiac indices (diastolic: trans-mitral E/A ratio [1 ± 0.07 to 0.94 ± 0.07, p = 0.0004] and iso-volumic relaxation time [ms] [65 ± 3 to 56 ± 4, p < 0.0001], and systolic: mean velocity of circumferential fibre shortening [circ/s] [1.6 ± 0.2 to 1.9 ± 0.2, p < 0.0001] and left ventricular output [mL/kg/min] [177 ± 34 to 230 ± 54, p = 0.0002]). This coincided with improved aortic pulsatility (40 ± 13 to 50 ± 11 µm, p = 0.005). Conclusions: Systemic hypertension–LHD pathology amongst infants with severe BPD may be under-recognised. Systemic afterload reduction is physiologically suited in a subset of infants with severe BPD.