Increased Cardiac Glucose Uptake in Sepsis-Induced Myocardial Dysfunction: A Three- Tracer Positron Emission Tomography Imaging Observational Cohort Study

Purpose Sepsis-induced myocardial dysfunction (SIMD) is common in septic shock (SS), but its cardiac energy profile in the context of contractile impairment remains poorly understood. Previous evidence is limited and largely based on invasive methods, suggesting reduced myocardial fatty acid and glucose utilization. Methods In this pilot, single-center, prospective observational study, patients were recruited within 48 hours of admission for circulatory shock and classified into three groups based on clinical history and early echocardiography: (i) SS with SIMD, (ii) SS without SIMD, and (iii) acute heart failure with reduced ejection fraction (AHFrEF) without SS. Sequential cardiac PET imaging was performed using three tracers (acetate, palmitate, and fluorodeoxyglucose [FDG]). The primary objective was to compare myocardial energy profiles between groups; secondary objectives included assessing cross-compensation of glucose and fatty acids in SS with SIMD and its association with contractile impairment. Results Twenty-four patients underwent PET imaging with kinetic analyses. Myocardial glucose uptake was significantly higher in SS with SIMD than without (median [IQR]: 19.1 [11.3–31.8] vs. 1.3 [0.1–4.0] µmol/100g/min; p = 0.0071), and the uptake gap between fatty acids and glucose was narrowed in SS with SIMD compared with AHFrEF (p = 0.0168). Increased cardiac fatty acid esterification correlated with low left ventricular ejection fraction (LVEF) (median [IQR]: 40 [0.12–71.8] vs. 4.3 [0.0–13.5] %; p = 0.0134). Myocardial oxygen consumption (MVO₂) was elevated in SS, and lower LVEF was associated with reduced myocardial efficiency (MEE) (n = 16, R²=0.3203, p = 0.0223). Conclusion In septic shock, hearts with contractile dysfunction preferentially uptake glucose and fatty acids are diverted toward storage rather than oxidation. This metabolic shift contributes to impaired myocardial efficiency, reflecting an imbalance between cardiac work and energy consumption. Trial Registration This eMESH trial (NCT05202938) was prospectively registered at ClinicalTrials.gov on January 10th, 2022 prior to first patient inclusion.