Milrinone in late tetralogy of Fallot repair: physiologic rationale, clinical evidence, and perspectives from low- and middle-income countries—a state-of-the-art review

BACKGROUND: Milrinone is commonly used after congenital heart surgery, yet its role following late repair of tetralogy of Fallot remains poorly defined. In many low- and middle-income country settings, children present for repair at older ages after prolonged exposure to right ventricular pressure overload and chronic cyanosis, resulting in post-operative physiology that differs fundamentally from early infant repair. Extrapolation from heterogeneous paediatric cardiac surgery populations may therefore be inappropriate. This review examines the pathophysiologic substrate of late-presenting tetralogy of Fallot and explores how milrinone's pharmacologic profile intersects with dominant post-operative vulnerabilities. PHYSIOLOGIC CONSIDERATIONS: Restrictive right ventricular physiology, combined with pulmonary vascular hyperreactivity and impaired ventriculo-arterial coupling, creates a fragile right ventricular-pulmonary arterial unit with limited reserve after repair. As a phosphodiesterase-3 inhibitor, milrinone produces coordinated effects on right ventricular lusitropy, pulmonary vasodilation, and inotropy that directly target these mechanisms, supporting selective use when diastolic dysfunction and elevated afterload predominate. CURRENT EVIDENCE: The existing evidence base is derived largely from infant cohorts and mixed CHD populations, with few data addressing older children undergoing late tetralogy of Fallot repair and none specific to low- and middle-income countries. In the absence of lesion-specific evidence, routine or prophylactic use cannot be justified. Instead, a pragmatic, physiology-guided approach is proposed. CONCLUSION: The central question is not whether milrinone is beneficial after tetralogy of Fallot repair, but in whom, when, and why. Addressing this gap will require pragmatic trials or prospective registries focused on late tetralogy of Fallot repair that integrate physiologic and clinically meaningful outcomes. Until such data emerge, selective, mechanism-based use represents a rational strategy in resource-variable settings.