Why the Heart Matters in Congenital Diaphragmatic Hernia (CDH)

With CDH, a hole in the diaphragm allows abdominal organs to move into the chest. There, they can crowd the heart and lungs and keep the lungs from growing normally. © CHOP/CFDT A main characteristic of congenital diaphragmatic hernia (CDH) is pulmonary hypoplasia, a condition characterized by small, underdeveloped lungs. The small lungs also have fewer blood vessels, which can cause high blood pressure in the lungs, a condition called pulmonary hypertension. This pressure makes the heart work harder to get blood to the lungs, which can lead to heart failure.

Pulmonary hypertension (PH) is a notoriously challenging condition to treat. PH can be a progressive condition, worsening over time if left untreated. In CDH, persistent severe pulmonary hypertension beyond the first few weeks of life is associated with prolonged time needed on a ventilator, need for extracorporeal membrane oxygenation (ECMO), and an increased risk of death. Pulmonary hypertension is the leading cause of death in babies born with CDH.

There are medications available to treat PH, but patients with CDH need to be treated by an experienced team that includes cardiologists who understand the unique and complex heart problems of CDH patients. At Children’s Hospital of Philadelphia, we know how vital it is to provide early and aggressive treatment of PH in order to improve survival in babies born with CDH. 

Studies like echocardiograms and cardiac catheterizations help cardiologists safely direct therapy. We have pioneered the use of several therapies in CDH patients with severe PH. Our team’s extensive experience with these medications to decrease the blood pressure in the lungs and to support heart function is critical to the care of CDH patients. In some extreme cases, we have used a cardiac catheterization procedure to stent open the ductus arteriosus, a connection between the heart and the lungs from fetal life.

In addition to studying the neurodevelopmental and other long-term outcomes of patients with diagnoses that cause pulmonary hypoplasia, our team is working to find better treatments for pulmonary hypertension. We are currently studying a number of therapeutic approaches that seek to improve survival and long-term outcomes for babies with CDH and PH.

Some of our recent clinical findings for CDH and the heart include:

• “Use of Prostaglandin E1 to Treat Pulmonary Hypertension in Congenital Diaphragmatic Hernia” — The objective of this study was to evaluate the PH response in neonates with CDH and severe PH treated with prostaglandin E1 (PGE). PGE was well tolerated and associated with improved B-type natriuretic peptide (BNP) and echocardiographic indices of PH, suggesting successful unloading of the right ventricle. Journal of Pediatric Surgery, 2019.
• “Inhaled Nitric Oxide Is Associated with Improved Oxygenation in a Subpopulation of Infants with Congenital Diaphragmatic Hernia and Pulmonary Hypertension” — The objective of this study was to determine which patients with CDH and PH benefit from inhaled nitric oxide (iNO) treatment by comparing characteristics and outcomes of iNO responders to nonresponders. Results showed that iNO treatment is associated with improved oxygenation and reduced need for ECMO in a subpopulation of patients with CDH with PH and normal left ventricular systolic function. Journal of Pediatrics, 2019
• “Treprostinil Improves Persistent Pulmonary Hypertension Associated with Congenital Diaphragmatic Hernia” — The objective of this study was to evaluate the effect of continuous treprostinil in infants with severe PH associated with CDH on specific markers of PH severity and to report the safety and tolerability of treprostinil. In this cohort, treprostinil use was associated with improved severity of PH assessed by echocardiogram and decreased BNP, with no significant side effects. Journal of Pediatrics, 2018
• “The Left Ventricle in Congenital Diaphragmatic Hernia: Implications for the Management of Pulmonary Hypertension” — Journal of Pediatrics, 2018
• “Right ventricular function mirrors clinical improvement with use of prostacyclin analogues in pediatric pulmonary hypertension” — Pulmonary Circulation, 2018
• “Treatment of Pulmonary Hypertension in Congenital Diaphragmatic Hernia” — Platform presentation by Natalie E. Rintoul, MD, at ECMO and the Advanced Therapies for Cardiac and Respiratory Failure Conference 2020

We are hopeful that these studies will improve the standard of care for patients with CDH today and in the future.