Metabolomic phenotype of heart failure in cardio-oncology patients

Background Heart failure (HF) in cardio-oncology patients during anticancer therapy is usually regarded as an accelerated form of classical HF, which restricts early diagnosis and timely pathogenetically based treatment. Myocardial decompensation in these patients appears to involve distinct molecular mechanisms detectable before overt HF, and metabolomic profiling may help identify a specific cardio-oncological HF phenotype. Aim To characterize the metabolomic profile of HF in cardio-oncology patients versus HF patients without cancer and assess its utility for early cardiotoxicity detection and justification of early personalized cardioprotective therapy. Materials and Methods The study enrolled 102 patients. The cardio-oncology group (Onco, n=59) included patients with hematological malignancies (34 lymphomas, 25 multiple myeloma) examined before treatment and after three cycles of anticancer therapy; baseline risk was stratified using ESC-ICOS tools (24 low, 17 intermediate, 12 high, 6 very high). Various forms of cardiotoxicity were documented in 15 patients (left ventricular dysfunction n=8, arterial hypertension n=4, arrhythmias n=2, pulmonary embolism n=1). The control HF group comprised 43 patients with chronic HF without cancer (left ventricular ejection fraction 56%, NT-proBNP >968 pg/mL). All patients underwent targeted metabolomic analysis. Results Significant differences in metabolomic profiles were found between Onco and HF patients. Arginine levels were higher in the Onco group (89.15 ± 33.89 vs. 73.27 ± 17.84; p=0.002), while ADMA and homoarginine did not differ significantly. No intergroup differences were seen for tryptophan, kynurenine, or kynurenic acid, whereas quinolinic acid and tryptamine were higher in the Onco group (p<0.005 and p<0.011), indicating a shift of kynurenine pathway activity toward a pro-inflammatory branch. All analyzed markers of mitochondrial fatty acid oxidation (C14-OH, C16:1-OH, C18:1-OH, C18-OH, C5-DC, cytidine) differed significantly (p<0.05), consistent with more pronounced impairment of mitochondrial β-oxidation in the HF group. Conclusions HF in cardio-oncology patients exhibits a distinct metabolomic phenotype that differs from classical HF and reflects key pathogenetic mechanisms of myocardial injury, enabling detection of subclinical cardiotoxicity. Metabolomic profiling opens new possibilities for early, pathogenetically oriented, personalized cardioprotective therapy, including pharmacological strategies targeting these metabolic alterations.