Pulmonary hypertension in bronchopulmonary dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is a major complication in prematurely born infants. Pulmonary hypertension (PH) associated with BPD (BPD-PH) is characterized by alveolar diffusion impairment, abnormal vascular remodeling, and rarefication of pulmonary vessels (vascular growth arrest), which lead to increased pulmonary vascular resistance and right heart failure. About 25% of infants with moderate to severe BPD develop BPD-PH that is associated with high morbidity and mortality. The recent evolution of broader PH-targeted pharmacotherapy in adults has opened up new treatment options for infants with BPD-PH. Sildenafil became the mainstay of contemporary BPD-PH therapy. Additional medications, such as endothelin receptor antagonists and prostacyclin analogs/mimetics, are increasingly being investigated in infants with PH. However, pediatric data from prospective or randomized controlled trials are still sparse. We discuss comprehensive diagnostic and therapeutic strategies for BPD-PH and briefly review the relevant differential diagnoses of parenchymal and interstitial developmental lung diseases. In addition, we provide a practical framework for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH from the 2018 World Symposium on Pulmonary Hypertension, and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies. Finally, current gaps of knowledge and future research directions are discussed. IMPACT: PH in BPD substantially increases mortality. Treatment of BPD-PH should be conducted by an interdisciplinary team and follow our new treatment algorithm while still kept tailored to the individual patient. We discuss recent developments in BPD-PH, make recommendations on diagnosis, monitoring and treatment of PH in BPD, and address current gaps of knowledge and potential research directions. We provide a practical framework, including a new treatment algorithm, for the management of children with BPD-PH, incorporating the modified definition and classification of pediatric PH (2018 WSPH) and the 2019 EPPVDN consensus recommendations on established and newly developed therapeutic strategies for BPD-PH.

Fig. 1. Management of pulmonary hypertension in bronchopulmonary dysplasia.

BPD—bronchopulmonary dysplasia; ERA—endothelin receptor antagonist; iNO—inhaled nitric oxide; LV—left ventricle; RV—right ventricle; PAAT—pulmonary artery acceleration time; PH—pulmonary hypertension; S/D ratio—systolic to diastolic duration ratio; TAPSE—tricuspid annular posterior systolic excursion; TRV—tricuspid regurgitation velocity. *Screening for pulmonary hypertension by transthoracic echocardiography is indicated (1) if severe respiratory compromise is present in any preterm infant <28 weeks of gestation, (2) in any infant with established BPD at corrected age of 36 weeks gestation (p.m.) and before discharge, (3) in any infant with prolonged oxygen requirement, poor growth, and unsatisfactory clinical improvement. **Cardiac catheterization should be considered before (i) introduction of a second PH-specific medication and is advised if PH worsens under dual therapy or if unsatisfactory treatment response is seen in any infant with PH at a corrected postnatal age of >3 months.