Overview of targeted therapy in pediatric pulmonary arterial hypertension

CCB: calcium channel blocker; RV: right ventricle; ERA: endothelin receptor antagonist; PDE-5i: phosphodiesterase type 5 inhibitor; IV: intravenous; PAP: pulmonary artery pressure; WHO: World Health Organization; BNP: brain natriuretic peptide; NT-proBNP: N-terminal pro-BNP; 6MWD: six-minute walk distance; RA: right atrium; LV: left ventricle; TAPSE: tricuspid annular plane systolic excursion; FAC: fractional area change; CI: cardiac index; AVT: acute vasoreactivity testing; mRAP: mean right atrial pressure; PVRI: pulmonary vascular resistance indexed to body surface area; WU: Wood unit; PACI: pulmonary arterial compliance index; PH: pulmonary hypertension.
* AVT is performed via cardiac catheterization and involves the administration of a short-acting vasodilator (typically inhaled nitric oxide) followed by measurement of the hemodynamic response. "Reactive" is generally defined as a decrease in mean PAP by at least 10 mmHg to a value of <40 mmHg with no decrease in cardiac output. For additional details, refer to UpToDate content on PH in children.
¶ The severity of PH is assessed using the clinical criteria outlined in the table. Categorization as low- or high-risk is not precise and is based in part on the clinical judgment of the treating clinician. For the low-risk category, all standard criteria should generally be met; for the high-risk category, patients typically meet multiple criteria, though all criteria need not be met. As a general principle, echocardiography and cardiac catheterization should be performed prior to starting PH therapy. Some patients have intermediate findings and do not fall clearly into a low- or high-risk category; consensus regarding management of such patients is lacking and practice varies considerably.
Δ CCBs should not be used in patients with depressed RV function. Patients with depressed RV function are often classified as high-risk and are managed accordingly. Refer to UpToDate topic on management of PH in children for additional details.
◊ Oral ERAs that have been used in children include bosentan and ambrisentan; PDE5 inhibitors that are used for treatment of PH include sildenafil and tadalafil; inhaled prostanoids include iloprost and treprostinil. The choice between these agents is based largely on patient and provider preference. For additional details, refer to UpToDate content on PH in children.
§ In pediatric patients, epoprostenol is primarily used acutely in critically ill or unstable patients due the short half-life of the drug and ease of titration. By contrast, treprostinil is used more commonly for long-term management of more stable patients.