Pediatric Primary Pulmonary Hypertension 

Idiopathic pulmonary artery hypertension (IPAH), previously referred to as primary pulmonary hypertension (PPH), is a relatively recently described entity with an unclear etiology.

IPAH is a serious syndrome, with significant morbidity and mortality. It can be associated with progressive elevation of pulmonary artery pressure and can lead to right ventricular failure. By definition, the cause is unexplained; this implies that associated causes of pulmonary hypertension have been ruled out.

The definition of pediatric IPAH, therefore, is the same as that of IPAH in adults: a mean pulmonary artery pressure greater than 25 mm Hg at rest with normal pulmonary capillary wedge pressure, in the absence of associated causes of pulmonary hypertension.

Some authors believe that including exercise hemodynamic abnormalities in the definition is important, especially in the pediatric population; therefore, a mean pulmonary artery pressure of greater than 30 mm Hg with exercise is also considered to be an abnormal response and is consistent with the definition of idiopathic pulmonary artery hypertension.

Because many of the symptoms of idiopathic pulmonary artery hypertension (IPAH) are nonspecific and the disorder is relatively rare, the diagnosis may be somewhat difficult to make (see Diagnosis).

The diagnostic assessment includes a variety of blood studies, coagulation studies, tests for collagen-vascular disease, and imaging studies, as well as a variety of other tests and procedures (see Workup).

The usual regimen for patients with IPAH includes warfarin (Coumadin), digoxin, and vasodilators, such as nifedipine, intravenous prostacyclin, or both. For those children who truly do not respond to long-term therapy and who are symptomatic, lung transplantation should be considered (see Treatment and Management).

For more information, see the Medscape Reference articles Primary Pulmonary Hypertension and Persistent Newborn Pulmonary Hypertension.

The exact pathogenesis and pathophysiology of idiopathic pulmonary artery hypertension (IPAH) are unclear. Pulmonary vasoconstriction appears to be the most widely accepted mechanism. Studies suggest that exposure to certain stimuli may initiate the characteristic vascular lesions in persons who are predisposed to the disorder. Triggers of pulmonary vasoconstriction in susceptible individuals include the following:

• High altitude
• Hypoxemia
• Drugs
• Toxins
• Sympathetic tone
• Autoimmune disorders

Other studies also invoke an imbalance of vasoactive mediators that favoring those causing vasoconstriction. Thromboxane, arachidonate metabolites, and prostacyclin, as well as other endothelial factors, have been invoked.

In addition, coagulation abnormalities may occur. This possibility is supported by the finding of microthrombi in the pulmonary vascular bed, which are noted at the time of lung biopsy, autopsy, or in explanted lungs at the time of lung transplantation. Whether this is a primary or secondary finding is unknown.

Much experimental work is being conducted in the area of endothelial metabolism of vasoactive substances. The hope is that this will lead to a better understanding of the control of the pulmonary circulation and to improved and more specific therapies for IPAH.

The frequency of IPAH in children is not known (nor is the frequency in adults known). Conceivably, more patients have the disease than previously suspected. As more knowledge of IPAH is currently available, the disease may be more easily recognized.

The incidence of familial IPAH has been thought to be 5-10%. The disorder appears to be autosomal dominant with incomplete penetrance.

The male-to-female ratio in adults is reported to be 1:1.7. In children, the ratio varies, with some studies showing an equal distribution between females and males in younger children, whereas other studies have shown a female preponderance of 1.5:1.

Before the age of vasodilator therapy, most children died within 1-2 years of diagnosis, whereas adults had a median survival of 2-3 years. Survival has improved, although morbidity and mortality remain significant. In 2009, the United Kingdom Pulmonary Hypertension Service for Children reported survival rates of 85.6% at 1 year, 79.9% at 3 years, and 71.9% at 5 years.^[1]

Morbidity and mortality rates vary and depend on the age, the degree of pulmonary hypertension, and the response to vasodilator therapy. Death may occur as a result of both acute and chronic right heart failure and its associated arrhythmias. Additionally, patients can be affected by the complications associated with low cardiac output.

Children who respond to short-term vasodilator drug testing have a 5-year survival rate of 90%, whereas children who do not initially respond have a 5-year survival rate of 33%. However, follow-up studies suggest that this latter number may be much higher. Studies of newer medications, as well as combination medications, have found a much improved longer-term prognosis, even for the acute nonresponder group, with some studies suggesting as high as an 80% 5-year survival rate.

Finally, the morbidity associated with chronic vasodilator therapy and frequent intravenous line infections in patients on long-term continuous intravenous prostacyclin as well as long-term anticoagulation are well known.

Patients must be educated with regard to central line care, signs and symptoms of line infection, and signs and symptoms of deteriorating condition.

In addition, patients on continuous intravenous prostacyclin develop tachyphylaxis and require interval dose increases. Families must learn the proper operation of the intravenous pump and all the nuances of mixing and infusing the drug.

Provide counseling in the methods of birth control for female patients of reproductive age who have moderate-to-severe pulmonary hypertension. Labor and delivery is life threatening in patients with significant pulmonary hypertension; therefore, pregnancy should be avoided.