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Volume 27
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Review

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

by
Vincenzo Quagliariello
1,*,
Massimiliano Berretta
2,
Fabrizio Maurea
3,
Maria Laura Canale
4,
Andrea Paccone
1,
Irma Bisceglia
5,
Andrea Tedeschi
6,
Marino Scherillo
7,
Jacopo Santagata
1,
Stefano Oliva
8,
Christian Cadeddu Dessalvi
9,
Pietro Forte
1,
Cristiana D’Ambrosio
10,
Tiziana Di Matola
11,
Domenico Gabrielli
12 and
Nicola Maurea
1
1
Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
2
Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy
3
Radiology Division, University of L’Aquila, 67100 L’Aquila, Italy
4
U.O.C. Cardiologia, Ospedale Versilia, 55041 Lido di Camaiore, Italy
5
Servizi Cardiologici Integrati, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, 00152 Roma, Italy
6
Cardiology, “Guglielmo da Saliceto” Hospital, 29121 Piacenza, Italy
7
Cardiologia Interventistica e UTIC, A.O. San Pio, Presidio Ospedaliero Gaetano Rummo, 82100 Benevento, Italy
8
Cardio-Oncology Unit, IRCCS Istituto Tumori, “Giovanni Paolo II”, 70124 Bari, Italy
9
Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy
10
Cardiology Division, “F. Veneziale”, Molise Regional Health Company (ASREM), 86170 Isernia, Italy
11
UOC Biochimica Clinica, AORN Ospedali dei Colli-Monaldi-Cotugno-CTO, 80131 Napoli, Italy
12
U.O.C. Cardiologia, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, Roma-Fondazione per il Tuo Cuore-Heart Care Foundation, 50121 Firenze, Italy
 
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*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(11), 4842; https://doi.org/10.3390/ijms27114842
Submission received: 4 May 2026 / Revised: 20 May 2026 / Accepted: 25 May 2026 / Published: 27 May 2026
(This article belongs to the Special Issue Cardioimmunology: Inflammation and Immunity in Cardiovascular Disease—2nd Edition)
Versions Notes

Abstract

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.
Keywords: cardio-oncology; immune checkpoint inhibitors; myocarditis; H-FABP; troponin; early biomarkers; cardiotoxicity cardio-oncology; immune checkpoint inhibitors; myocarditis; H-FABP; troponin; early biomarkers; cardiotoxicity

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MDPI and ACS Style

Quagliariello, V.; Berretta, M.; Maurea, F.; Canale, M.L.; Paccone, A.; Bisceglia, I.; Tedeschi, A.; Scherillo, M.; Santagata, J.; Oliva, S.; et al. 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. Int. J. Mol. Sci. 2026, 27, 4842. https://doi.org/10.3390/ijms27114842

AMA Style

Quagliariello V, Berretta M, Maurea F, Canale ML, Paccone A, Bisceglia I, Tedeschi A, Scherillo M, Santagata J, Oliva S, et al. 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. International Journal of Molecular Sciences. 2026; 27(11):4842. https://doi.org/10.3390/ijms27114842

Chicago/Turabian Style

Quagliariello, Vincenzo, Massimiliano Berretta, Fabrizio Maurea, Maria Laura Canale, Andrea Paccone, Irma Bisceglia, Andrea Tedeschi, Marino Scherillo, Jacopo Santagata, Stefano Oliva, and et al. 2026. "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" International Journal of Molecular Sciences 27, no. 11: 4842. https://doi.org/10.3390/ijms27114842

APA Style

Quagliariello, V., Berretta, M., Maurea, F., Canale, M. L., Paccone, A., Bisceglia, I., Tedeschi, A., Scherillo, M., Santagata, J., Oliva, S., Cadeddu Dessalvi, C., Forte, P., D’Ambrosio, C., Di Matola, T., Gabrielli, D., & Maurea, N. (2026). 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. International Journal of Molecular Sciences, 27(11), 4842. https://doi.org/10.3390/ijms27114842

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