Medical Progress
Medical Therapy for Pediatric Pulmonary Arterial Hypertension

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Diagnosis and Classification

PAH is defined hemodynamically as a mean pulmonary artery pressure (PAP) ≥25 mm Hg at rest, with a pulmonary capillary wedge pressure within reference range (≤15 mm Hg). Some definitions have also included the pulmonary vascular resistance, requiring the pulmonary vascular resistance index to be ≥3 Woods units x m2.4 A revision of the classification including most of the forms of PH was proposed in Dana Point in 2008.5 The clinical presentation of children with PH has been reviewed; this

Clinical Presentation and Diagnostic Evaluation

Symptoms of PAH in children are frequently misleading, and the diagnosis may be unrecognized for some time. A high degree of suspicion should be the rule, and PAH should be suspected in any child with undue shortness of breath, tiredness, or syncopal episodes.10 Although associated PAH is rare in children, except for PH related to congenital heart disease, all potential etiologies should be evaluated.10 PAH must be confirmed with catheterization, and pulmonary vasoreactivity testing should be

Therapeutic Approach

There are no evidence-based treatment recommendations for children with PAH, primarily because of the lack of results from randomized clinical trials in pediatric patients or including pediatric patients.3, 15 The aim of medical treatment is to dilate and reverse the abnormal remodeling of the pulmonary vascular bed and to restore endothelial function, by acting on the prostacyclin, endothelin, and NO pathways. In practice, a therapeutic algorithm similar to PAH in adults appears to guide

Creation of a Right-to-Left Shunt and Transplantation

Children not responding to conventional medical therapy may be candidates for atrioseptostomy or transplantation. Atrioseptostomy may benefit patients with severe PAH with recurrent syncope and intractable right heart failure unresponsive to medical therapy. Right-to-left shunting through an interatrial defect allows maintenance of cardiac output at the expense of increased hypoxemia and alleviates signs of right heart failure by decompression of the right heart.51 Transplantation should be

Conclusion

Advances in the understanding of pulmonary vasculature has led to new therapeutic options and improved survival rates in children with PAH. Timely diagnosis is crucial because earlier treatment leads to improved outcome. In children with PAH, an extensive work-up is necessary to determine the etiology, because the most successful strategy involves treatment of the underlying disorder. Initial evaluation includes acute vasodilator testing at cardiac catheterization, which determines initial

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    This research was funded both by Actelion and General Clinical Research Centers, National Center for Research Resources, National Institutes of Health (M01-RR0069).

    D.I. has served on scientific advisory boards for Actelion, Gilead, Pfizer, and United Therapeutics and has received research grant funding from Actelion and United Therapeutics. M.B. has served on advisory boards and consulted for Pfizer, Actelion Pharmaceuticals, Bayer Schering, GlaxoSmithKline, Novartis INO Therapeutics, Eli Lilly, and Mondobiotech, and has received lecture fees from Actelion Pharmaceuticals, Enycysive Pharmaceuticals, and Bayer Schering. C.T. has no conflicts of interest to disclose.

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