Expert Care and Long-term Support for CDH-Related Pulmonary Hypertension

While a number of risk factors can lead to poor outcomes in babies with congenital diaphragmatic hernia (CDH), pulmonary hypertension (PH) is the leading cause of morbidity and mortality. The presence of PH at 3 weeks of age is a significant predictor of survival in CDH. Therefore, early recognition, treatment and management of CDH-related PH is critical.

Cardiologists in our Pulmonary Hypertension Program work closely with colleagues in the Division of Pulmonary Medicine as well as other specialties, such as the Pulmonary Hypoplasia Program and the Newborn and Infant Chronic Lung Disease Program, to manage CDH patients who have PH. Our team takes an early and aggressive approach to treatment, and our protocols have been extremely successful.

Although the normal ranges of pulmonary artery (PA) pressures are lower in children than in adults, the current definition of pediatric PH is the same as in adults: a mean pulmonary artery pressure > 25 mm Hg with an increased pulmonary vascular resistance > 3 WUi and a normal left ventricular filling pressure. These values are greater than two standard deviations above the mean for children, and clearly define a pulmonary vascular bed that is high in resistance and low in the capacity to increase pulmonary blood flow if metabolically needed. This decrease in capacity is associated with right ventricular (RV) failure, both the hallmark of PH and the principal cause of morbidity and mortality.

Overlapping mechanisms of PH and lung hypoplasia From CDH

Most PH in children with CDH is not caused by vasoconstriction, and is not the classic persistent pulmonary hypertension of the newborn (PPHN) associated with prenatal insults as in meconium aspiration. Instead, lung hypoplasia from CDH is associated with PH because of four overlapping mechanisms:

• Developmental arrest
• Abnormal myofibroblast proliferation and arteriolar occlusion
• Left ventricular (LV) diastolic dysfunction, possibly associated with hypoplasia
• Inflammatory lung destruction (from hyperoxia, ventilator shear forces, infection and/or micro-aspiration)

In addition to repeated physical exams, our team utilizes serial B-type natriuretic peptide to follow RV dysfunction. We rely on echocardiograms to assess heart chamber size, shunt direction, ventricular septal position of the wall between the two chambers, pulmonary vein stenosis, and estimation of RV or PA pressure. Cardiac catheterization is also used in some cases to:

• Evaluate shunts (ASD, VSD, PDA) that are contributing to pulmonary over-circulation
• Evaluate LV-end diastolic pressure to understand the contribution of left heart disease to CDH-PH
• Evaluate stenosis in the pulmonary artery or pulmonary vein
• Evaluate patients for long-term PH-specific medical therapy (treprostinil)
• Perform stenting of a PDA to preserve RV function at the expense of lower extremity cyanosis

The sheer number of patients in our program has led to significant discoveries that have, in turn, led to improved survival and a lower incidence and severity of pulmonary hypertension in children with lung hypoplasia.

Improving outcomes for pediatric PH patients

There are currently no FDA-approved therapies for pediatric PH; however, our program has more than 20 years of experience with the careful use of all therapies that are FDA-approved for adult PH. Available treatments for pediatric PH patients at CHOP include:

• Extracorporeal membrane oxygenation (ECMO) for cardiorespiratory failure
• Pulmonary vasodilators (which can be administered orally, subcutaneously, by IV or inhaled)
• Some catheter-based approaches to preserve right heart function
• Medications, such as surfactant replacement and inhaled nitric oxide therapy

The sheer number of patients in our program has led to significant discoveries that have, in turn, led to improved survival and a lower incidence and severity of PH in children with lung hypoplasia. Use of conventional mechanical ventilation and high-frequency oscillatory ventilation allowing permissive hypercapnia, aggressive treatment of pulmonary hypertension, and early use of ECMO as indicated has increased our survival to > 85%.

Children born with CDH often have long-term problems with breathing, feeding, heart function, hearing and brain development. Our Pulmonary Hypoplasia Program (PHP) includes a multidisciplinary team of experts who work together to provide complete, long-term care for children with pulmonary hypoplasia and pulmonary hypertension. Our cardiologists see all PHP children as outpatients and assist in managing the cardiac complications of lung hypoplasia.

Our work is extremely gratifying. Though pulmonary hypertension remains a complex disease, we continue to see strong, positive patient outcomes attributed to the expertise of our team as well as our strong connections with families and the extended support we provide throughout their medical journey.

By Catherine Avitabile, MD, Attending Cardiologist, Division of Cardiology