Comparative effectiveness of different treatment strategies for paediatric heart failure: a narrative review

Background Pediatric heart failure (HF) remains a high-morbidity condition with distinct cellular and clinical profiles compared to adult populations. Energy deficiency and metabolic inflexibility drive myocardial dysfunction in children, where congenital heart disease and cardiomyopathies predominate. Current management relies heavily on adult data extrapolation, creating significant gaps in evidence-based pediatric care. Purpose This study evaluates the comparative effectiveness of emerging pharmacological agents and mechanical circulatory support (MCS) innovations to define an optimized, patient-centered therapeutic hierarchy for children with advanced heart failure. Methods A comprehensive review of recent clinical trials, multicenter registries, and longitudinal studies was conducted. Data were synthesized regarding the efficacy of neurohormonal blockade, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and ventricular assist devices (VAD), including the Berlin Heart EXCOR and HeartMate 3. Outcomes focused on ventricular recovery, bridge-to-transplant (BTT) success, and mortality. Results Pharmacological analysis indicates that while angiotensin receptor-neprilysin inhibitors (ARNI) and SGLT2i show promise in improving left ventricular ejection fraction and NT-proBNP levels, they do not consistently demonstrate superiority over traditional ACE inhibitors in large pediatric cohorts. In mechanical support, registry data confirm a 1-year survival rate of approximately 79%. The Berlin Heart EXCOR remains the definitive support for infants, showing a 38.1% recovery rate in specific myocarditis cases. Conversely, the HeartMate 3 has expanded off-label use in older children, demonstrating reduced pump thrombosis and stroke risk through fully magnetically levitated rotor technology. Successful weaning from MCS is predominantly observed in acute myocardial injury rather than chronic dilated or structural phenotypes. Conclusion Optimal pediatric HF outcomes require a shift from adult-centric protocols toward etiology-specific interventions. Integration of standardized anticoagulation and early referral for MCS are critical for improving survival. While new drug classes offer symptomatic benefits, rigorous pediatric-specific randomized trials remain essential to establish long-term safety and neurodevelopmental outcomes.Figure 1figure 2