Cardiovascular diseases remain the leading cause of mortality worldwide, and one of the key mechanisms driving the development of heart failure is pathological remodeling of the myocardium. This process involves complex structural, cellular, and metabolic alterations in which the immune system and its interactions with cardiomyocytes and fibroblasts play a central role. The aim of this work was to present the current state of knowledge on immunometabolism in cardiac remodeling and to discuss its pathophysiological relevance and therapeutic potential. This review focuses on the metabolism of cardiac macrophages, highlighting the differences between the pro-inflammatory (M1) and reparative (M2) phenotypes and their impact on inflammation, fibrosis, and myocardial regeneration. The roles of major metabolic pathways, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and glutaminolysis, are discussed, as well as the importance of the NLRP3 inflammasome and efferocytosis in regulating the inflammatory response. Furthermore, the review briefly incorporates recent insights into neutrophil, T cell, and regulatory T cell (Treg) metabolism and their contributions to inflammation, repair, and fibrotic remodeling. Particular attention is also given to cardiac fibroblasts and their metabolic reprogramming during fibrosis, with emphasis on the pivotal role of transforming growth factor-β (TGF-β) signaling. The review further discusses the role of microRNAs as mediators of intercellular communication integrating immunological and metabolic signals. The work is complemented by a discussion of therapeutic perspectives, including modulation of macrophage metabolism, fibrogenic signaling pathways, mitochondrial function, and miRNA-based therapies. Immunometabolism emerges as a promising research field whose further exploration may contribute to the development of novel, more precise strategies for the treatment of cardiovascular diseases.

Background/Objectives: High-sensitivity cardiac troponin I (hs-cTnI) has shown inconsistent diagnostic performance for acute cellular rejection (ACR) after heart transplantation. We evaluated whether time-normalized hs-cTnI kinetics provide incremental diagnostic value beyond the concurrent concentration for detecting ACR grade ≥ 2R and whether this association varies with time after transplantation. Methods: This retrospective single-center study included 1237 biopsy episodes from 139 heart transplant recipients. Two generalized linear mixed-effects logistic regression models with patient-specific random intercepts were compared. M1 included concurrent log₂-transformed hs-cTnI, whereas M2 additionally included the time-normalized change in log₂-transformed hs-cTnI per 7 days. Discrimination was assessed using leave-one-patient-out cross-validation with patient-level cluster bootstrap confidence intervals. Exploratory analyses examined early (≤90 days), late (>90 days), and continuous post-transplant time. Results: In the overall cohort, M1 showed modest discrimination (AUC 0.641, 95% CI 0.592–0.689), whereas M2 provided no improvement (AUC 0.635; ΔAUC −0.007). Within 90 days, neither model was informative (M1 AUC 0.503; M2 AUC 0.494). Beyond 90 days, M1 showed moderate discrimination (AUC 0.758, 95% CI 0.664–0.838), but M2 again provided no improvement (AUC 0.746; ΔAUC −0.012). Continuous-time modeling showed that the association between concurrent hs-cTnI and ACR strengthened with increasing time after transplantation, whereas the kinetic term remained non-informative. Conclusions: Time-normalized hs-cTnI kinetics did not provide incremental diagnostic value beyond concurrent hs-cTnI. Concurrent hs-cTnI may warrant further evaluation as an adjunctive late-period marker, but the 90-day threshold remains exploratory and requires external validation. Neither hs-cTnI concentration nor its kinetics should replace endomyocardial biopsy.

Background/Objectives: Cardiac troponin I (cTnI) has shown inconsistent diagnostic performance for acute cellular rejection (ACR) after heart transplantation. We evaluated whether time-normalized cTnI kinetics provide incremental diagnostic value beyond the concurrent concentration for detecting ACR grade ≥2R. Methods: This retrospective single-center study included 1237 biopsy episodes from 139 heart transplant recipients after exclusion of ambiguous measurements and episodes without a preceding confirmed cTnI value. Two generalized linear mixed-effects logistic regression models with patient-specific random intercepts were compared. M1 included concurrent log₂-transformed cTnI, whereas M2 additionally included the time-normalized change in log₂-transformed cTnI per 7 days. Discrimination was assessed using leave-one-patient-out cross-validation; 95% confidence intervals were obtained from 2000 patient-level cluster bootstrap resamples. Results: In the overall cohort, M1 showed modest discrimination (AUC 0.641, 95% CI 0.592–0.689), whereas M2 provided no improvement (AUC 0.635, 95% CI 0.584–0.685; ΔAUC −0.007, 95% CI −0.021 to 0.007). Within 90 days after transplantation, neither model was informative (M1 AUC 0.503; M2 AUC 0.494). Beyond 90 days, M1 showed moderate discrimination (AUC 0.758, 95% CI 0.664–0.838), but M2 again provided no improvement (AUC 0.746, 95% CI 0.654–0.828; ΔAUC −0.012, 95% CI −0.037 to 0.008). Conclusions: Concurrent cTnI showed no discrimination within 90 days and moderate discrimination thereafter in exploratory stratified analyses. The kinetic term provided no incremental value. cTnI cannot replace endomyocardial biopsy but may warrant further evaluation as an adjunctive late-period marker.