Edema-troponin phenotypes identify distinct remodeling and functional profiles in acute myocarditis
F Martins Nunes, I Neves, L Moura, F Lemos De Sousa, R Faria, N Dias Ferreira, R Fontes-CarvalhoAbstract
Background
Acute myocarditis shows heterogeneous inflammatory and structural involvement. Troponin reflects necrosis, whereas CMR edema represents inflammatory burden; however, their combined use to define clinicaly meaningful phenotypes remains unexplored.
Purpose
We aimed to classify patients using integrated edema–troponin profiles and compare structural, functional and biochemical characteristics across phenotypes.
Methods
We studied 126 patients with acute myocarditis. Edema extent and troponin T were dichotomized at the medians (6 segments; 884 ng/L), generating four phenotypes: High-Edema/High-TnT (1), High-Edema/Low-TnT (2), Low-Edema/High-TnT (3) and Low-Edema/Low-TnT (4, reference). Global differences were assessed with Kruskal–Walis tests and pairwise Mann–Whitney U comparisons. Outcomes included LDH, NT-proBNP, indexed left ventricular mass (LVMi), left ventricular ejection fraction (LVEF) and follow-up late gadolinium enhancement (LGE) burden.
Results
Significant overal differences were observed for LDH (p<0.001), LVMi (p=0.003), LVEF (p=0.007), NT-proBNP (p=0.018) and LGE extent (p≈0.001). Phenotype 1 showed markedly higher LDH (p<0.001), increased LVMi (p<0.001), higher NT-proBNP (p=0.0019), lower LVEF (p=0.009) and greater fibrosis (p=0.001) versus phenotype 4. Phenotype 2 showed elevated NT-proBNP (p=0.033) and reduced LVEF (p=0.004). Phenotype 3 displayed increased LDH (p=0.001) but preserved structural and functional measures.
Discussion
Integrating edema and troponin demonstrated four biologicaly coherent phenotypes. High-Edema/High-TnT reflected concordant inflammatory-necrotic injury, explaining its greater remodeling, dysfunction and fibrosis, in line with existing CMR–pathology correlations. High-Edema/Low-TnT represented predominantly inflammatory injury with transient dysfunction, whereas Low Edema/High-TnT corresponded to a necrotic-dominant mismatch with minimal structural involvement. The Low-Edema/Low-TnT phenotype aligned with mild or resolving myocarditis. These findings highlight that edema and troponin capture complementary injury pathways.
Conclusion
A simple edema–troponin classification identifies clinicaly relevant myocarditis phenotypes with distinct biological, structural and functional profiles, offering a practical tool to refine early risk assessment.