Pulmonary arterial hypertension associated
with congenital heart disease

Even patients with surgically repaired defects may develop pulmonary arterial hypertension¹

	Approximately 34% of patients with unclosed atrial septal defects (ASDs) and 12% of patients with closed ASDs may also have PAH.1
	Approximately 50% of patients with large (>1.5 cm) ventricular septal defects (VSDs) may also develop Eisenmenger syndrome, the most advanced form of PAH associated with congenital heart disease.2

Clinical classification of congenital systemic-to-pulmonary shunts associated with PAH2
Eisenmenger syndrome	Systemic-to-pulmonary shunts due to large defects, leading to severe increase in PVR and reversed (pulmonary-to-systemic) or bidirectional shunt   Cyanosis, erythrocytosis, and multiple organ involvement
PAH associated with systemic-to-pulmonary shunts	Moderate to large defects   PVR mildly to moderately increased   Systemic-to-pulmonary shunt still prevalent   No cyanosis present at rest
PAH with small defects	Small defects (usually VSDs <1 cm and ASDs <2 cm of effective diameter assessed by echocardiography)   Clinical picture very similar to IPAH
PAH after corrective cardiac surgery	Congenital heart disease corrected, but PAH still present immediately after surgery or recurs in absence of significant postoperative residual lesions

Eisenmenger syndrome

	Defined as a reversal of the left-to-right shunt resulting from severe pulmonary hypertension3
	One of the most debilitating of all congenital heart diseases4
	Accompanied by compromised hemodynamics1
	Marked by increased endothelin expression*1

*Statement is based on observations reported from in vitro or animal trials. The clinical significance in humans is unknown.

BREATHE-5 was the first randomized, double-blind, placebo-controlled trial in adult patients with PAH associated with Eisenmenger syndrome³

IPAH idiopathic pulmonary hypertension; PAH pulmonary arterial hypertension.

Tracleer is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in patients with WHO Class II-IV symptoms, to improve exercise ability and decrease the rate of clinical worsening. Patients with WHO Class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these potential benefits are sufficient to offset liver injury in WHO Class II patients, which may preclude future use as their disease progresses.

Important safety information

Because of the associated risks, Tracleer may be prescribed only through the Tracleer Access Program.

Potential for serious liver injury (including, after prolonged treatment, rare cases of liver failure and unexplained hepatic cirrhosis in a setting of close monitoring)—Liver monitoring of all patients is essential prior to initiation of treatment and monthly thereafter.

High potential for major birth defects—Pregnancy must be excluded and prevented through the use of reliable forms of birth control; monthly pregnancy tests should be obtained.

Contraindicated for use with cyclosporine A and glyburide.

Please see full prescribing information including BOXED WARNING.

Review the importance of diagnosing PAH early

1. Engelfriet PM, Duffels MGJ, Möller T, et al. Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart. 2007;93:682-687.
2. Simonneau G, Galiè N, Rubin LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004;43(suppl S):5S-12S.
3. Galiè N, Beghetti M, Gatzoulis MA, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation. 2006;114:48-54.
4. Diller GP, Dimopoulos K, Okonko D, et al. Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation. 2005;112:828-835.