The use of exogenous phosphocreatine in surgical correction of valvular heart defects under cardiopulmonary bypass: a randomized, double-blind, placebo-controlled pilot study

Introduction: Myocardial ischemia and stunning during cardiac surgery remain a common and serious complication of the perioperative period with a significant negative impact on patient outcomes, especially in high-risk patients. Experimental and clinical studies have demonstrated that the administration of exogenous phosphocreatine can reduce mortality in patients with coronary artery disease, chronic heart failure, and after heart surgery. Objective: The study aimed to evaluate the efficacy and safety of using exogenous phosphocreatine in patients scheduled for multivalvular correction under cardiopulmonary bypass. Methods: A randomized, double-blind, placebo-controlled pilot study enrolled 139 patients scheduled for cardiac surgery, namely plastic/prosthetic replacement of 2 or 3 heart valves under cardiopulmonary bypass. The study group (n = 67) received phosphocreatine according to a specific regimen: 2 grams intravenously after induction of anesthesia, 2.5 grams as part of the cardioplegia solution, 2 grams after restoration of heart rhythm, and 4 grams upon admission to the intensive care unit (ICU). The control group (n = 72) received an equal volume of saline. The primary outcome measure was the concentration of troponin I on the first postoperative day. Secondary endpoints included the following indicators: hemodynamic data (cardiac index, pulmonary artery pressure and pulmonary capillary wedge pressure), the number of patients who required vasopressor or inotropic support, the vasoinotropic index, the duration of artificial ventilation, the frequency of acute kidney injury, the frequency of atrial fibrillation, the duration of stay in the ICU, hospitalization time, 30-day mortality, and long-term survival over three years. Results: Troponin I levels on the first postoperative day did not differ significantly between the groups and amounted to 9768.3 (6350.6–16486.6) pg/ml in the placebo group and 12156.3 (6696.8–20976.7) pg/ml in the study group, p = 0.292). There were also no significant differences in hemodynamic data throughout the study. The number of patients who required inotropic and vasopressor support was similar between the two groups: 64 (88.9%) patients in the placebo group and 59 (88.1%) patients in the study group, p = 0.695. Cardiac index 1.26 L/(min∙m²) was a predictor of the need for renal replacement therapy with a sensitivity of 100% and specificity of 93% (an AUC of 0.96 (p = 0.005)). The mean pulmonary artery pressure value of 24 mmHg was a predictor for the development of renal dysfunction, with a sensitivity of 92% and specificity of 52% (AUC = 0.78; p = 0.002). In univariate regression analysis, several factors independently influenced the need for inotropic support in the early postoperative period: CPB (cardiopulmonary bypass) duration (for 10 min OR = 1.57; 95% CI 1.11–2.44, р = 0.007) and troponin I levels in 6 h after CPB (for 5000 pg/ml OR = 1.33; 95% CI 1.05–1.86, p = 0.016). Long-term survival over 3 years after surgery was similar between the study groups (HR 1.10; 95% CI 0.35–3.40, p = 0.873). Conclusion: Administration of exogenous phosphocreatine to patients undergoing operations on 2 or 3 heart valves under cardiopulmonary bypass is safe, but does not have an additional cardioprotective effect. Exogenous phosphocreatine does not have a positive effect on clinical outcomes and long-term survival (3 years) in this category of patients.