Heart-Type Fatty Acid-Binding Protein (H-FABP) as a Candidate Adjunctive Biomarker for Immune Checkpoint Inhibitor-Related Cardiotoxicity: Linking Early Immune-Metabolic Myocardial Injury with Translational Cardio-Oncology.

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of oncology but are increasingly associated with cardiovascular immune-related adverse events (irAEs), including myocarditis, heart failure, arrhythmias, and vascular complications. Among these, ICI-associated myocarditis represents the most severe manifestation, often characterized by high mortality and challenging early diagnosis. Detecting subclinical myocardial injury before irreversible cardiomyocyte necrosis occurs remains a major unmet need in contemporary cardio-oncology. This narrative expert review critically examines the biological rationale, preclinical evidence, and emerging clinical data supporting the potential role of heart-type fatty acid-binding protein (H-FABP) as an adjunctive biomarker of early immune-mediated myocardial injury during ICI therapy. H-FABP is a small cytosolic lipid chaperone abundantly expressed in cardiomyocytes and rapidly released into the circulation following subtle membrane destabilization and metabolic stress, frequently preceding detectable troponin elevation in other forms of myocardial injury. Experimental studies support a mechanistic association between H-FABP release, inflammasome activation, cytokine amplification, mitochondrial dysfunction, and immune-metabolic cardiomyocyte stress. Preliminary clinical observations further suggest that H-FABP elevations may occur during ICI treatment even in the absence of overt myocarditis or concomitant increases in high-sensitivity cardiac troponins (hs-cTns). Although H-FABP cannot replace hs-cTn, which remains the cornerstone biomarker for the diagnosis of clinically significant ICI-associated myocarditis, its rapid kinetics and sensitivity to early metabolic membrane injury support its potential role as an investigational adjunctive biomarker for early surveillance and risk stratification. This approach may be particularly relevant in patients receiving high-risk combination ICI regimens or in individuals with pre-existing cardiovascular disease. However, current evidence remains limited, and large prospective multicenter studies integrating H-FABP with hs-cTns, natriuretic peptides, cardiac magnetic resonance imaging, and clinical outcomes are required before routine clinical implementation can be considered.