Pediatric heart failure in the era of cardio-immunology: inflammatory–immune context phenotypes, diagnosis, and targeted management

Pediatric heart failure (PHF) is a heterogeneous syndrome whose etiologies, developmental biology, and clinical trajectories differ fundamentally from adult heart failure. Beyond age-specific hemodynamics and neurohormonal activation, inflammatory and immune programs can serve as primary drivers (e.g., myocarditis, multisystem inflammatory syndrome in children [MIS-C]) or as potent amplifiers of decompensation (e.g., postoperative inflammation after cardiopulmonary bypass, infection-associated stress). This review integrates contemporary pediatric heart failure practice with insights from cardio-immunology and proposes a pragmatic, bedside framework that: (i) links common triggers and clinical contexts to likely effector pathways; (ii) uses multimodal assessment to distinguish active immune-mediated injury from chronic remodeling; (iii) applies trajectory-based monitoring with feasible inflammatory–immune context bundles rather than research-grade immunophenotyping; and (iv) aligns immunomodulatory decisions with probability of immune causality, time window, and safety constraints to avoid indiscriminate immunosuppression. We highlight pediatric-specific challenges (reference ranges, sampling feasibility, imaging constraints, and limits of adult extrapolation), summarize emerging pharmacologic and device advances, and outline priorities for harmonized pediatric biomarker standards, prospective phenotype validation, and safer implementation of targeted immunomodulation. A graphical abstract summarizes the proposed phenotype-to-management framework.