Is bosentan indicated for an infant under one year of age with a ventricular septal defect?

Bosentan for Infants Under One Year with Ventricular Septal Defect

Bosentan is NOT indicated for routine treatment of isolated VSD in infants under one year of age; early surgical repair before 9 months is the definitive treatment. However, bosentan may be considered in the specific scenario where an infant has developed established pulmonary arterial hypertension (PAH) with elevated pulmonary vascular resistance that renders immediate surgery too high-risk, as a bridge to delayed repair after hemodynamic reassessment. 1

Primary Treatment Strategy

The cornerstone of management for VSD in infants is timely surgical repair, not medical therapy with bosentan. 1

• Surgery should be performed before 9 months of age to prevent irreversible pulmonary vascular disease; children repaired before this age achieve normal pulmonary artery pressure at one year regardless of preoperative vascular morphology or hemodynamics. 1
• No child repaired before 2 years of age had elevated PVR-to-SVR ratio 4-8 years after surgery, regardless of initial hemodynamic parameters. 1
• Most centers now perform complete VSD repair within the first months of life. 1

When Bosentan May Be Considered

Bosentan is only appropriate in the narrow clinical context where an infant with VSD has already developed significant PAH that makes immediate surgery contraindicated:

Hemodynamic Criteria for Medical Therapy Before Surgery

• If cardiac catheterization reveals PVRI ≥6 WU·m² or PVR/SVR ≥0.3 with minimal responsiveness to acute vasodilator testing, repair is not immediately indicated. 1
• In this scenario, it is reasonable to implement PAH-targeted therapy (which may include bosentan) followed by repeat catheterization with acute vasodilator testing after 4-6 months, and to consider repair if PVRI decreases to <6 WU·m². 1

Evidence for Bosentan in Pediatric PAH-CHD

• Bosentan lowers pulmonary artery pressure and pulmonary vascular resistance and is well tolerated in children with PAH associated with congenital heart disease. 1
• In a 12-week study, bosentan was well tolerated and lowered PAP and PVR in children with PAH related to CHD. 1
• However, the beneficial response progressively declined after 1 year, with a more rapid decline observed in children who tended to have more severe disease at baseline. 1
• Elevated transaminase levels occurred in only 2.7% of children treated with bosentan, compared to 7.8% in patients ≥12 years of age. 1

Critical Age-Related Considerations

The evidence for bosentan in children specifically addresses ages 1-17 years, NOT infants under one year. 1

• The 2015 AHA/ATS guidelines recommend oral PAH-targeted therapy (including endothelin receptor antagonists like bosentan) in children with lower-risk PAH, but this recommendation applies to children aged 1-17 years. 1
• An open-label study (BREATHE-3) evaluated bosentan in children 4-17 years of age with PAH, showing significant hemodynamic improvement after 12 weeks. 1
• There is no high-quality evidence specifically supporting bosentan use in infants under 1 year with isolated VSD.

Common Pitfalls to Avoid

• Do NOT delay surgical repair to trial medical therapy in an infant with isolated VSD and normal or mildly elevated PVR. Early surgery is curative and prevents the development of irreversible pulmonary vascular disease. 1
• Do NOT assume that oxygen responsiveness predicts surgical outcome; a ≥30% decrease in PVR-to-SVR ratio with oxygen did not correlate with operative survival or late PVR-to-SVR ratio in children with large VSD. 1
• Do NOT use bosentan as a substitute for timely surgical intervention in an infant who meets criteria for repair (PVRI <6 WU·m² or PVR/SVR <0.3). 1
• Do NOT overlook that certain lesions are more prone to early severe pulmonary vascular disease, including d-transposition of the great arteries, complete atrioventricular septal defect, and truncus arteriosus. 1

Monitoring Requirements if Bosentan is Used

If bosentan is initiated as a bridge to surgery in an infant with established PAH:

• Monthly liver function tests are mandated due to the risk of hepatic aminotransferase elevation. 1
• Monitor hemoglobin/hematocrit regularly as bosentan may cause mild anemia. 1
• Repeat cardiac catheterization after 4-6 months to reassess operability. 1
• The recommended target dose is 125 mg twice daily in older children, but dosing in infants under 1 year would require careful weight-based adjustment and is not well-established. 1

Alternative PAH-Targeted Therapies

If PAH-targeted therapy is needed in an infant with VSD and established PAH:

• Sildenafil has been studied more extensively in neonates and young infants, particularly for persistent pulmonary hypertension of the newborn. 1
• Inhaled nitric oxide may be used acutely to assess vasoreactivity during catheterization. 2
• Intravenous prostacyclin analogs should be initiated without delay for higher-risk PAH in infants who are critically ill. 1