The assessment of preoperative inflammatory biomarker levels in relation to the prognosis of postoperative complications after heart transplantation

Heart transplantation (HTX) is the definitive therapy for end-stage heart failure. Although modern immunosuppressive therapeutical measures and continuously improving surgical and anesthetic techniques have reduced mortality rates in the early postoperative period to 10-15%, physicians must be aware of severe complications such as graft failure, acute rejection or infection. Cytokines are key pathophysiological elements of these events, therefore, an increasing amount of translational clinical research is addressing the potential prognostic role of these circulating serum proteins as biomarkers of these complications. 

The aim of this study was to investigate the prognostic potential of inflammation-related cytokines measured directly from preoperative serum samples for complications in the early postoperative period after HTX.

This prospective, longitudinal study was conducted using the serum samples of patients undergoing HTX at the Heart and Vascular Center of Semmelweis University, Budapest, Hungary between September 2016 and August 2022 (n=102). Peripheral blood samples were drawn from patients directly before HTX. Serum samples were analyzed for 32 pre-selected biomarkers, including serum proteins, such as general inflammatory cytokines, interleukins, chemokines and vascular inflammation markers, based on previous evaluation of the current literature. Biomarker levels were determined by LEGENDplex multiplex fluorescence flow cytometry assays. Multiple Cox regression analyses and logistic regression were used to assess prognostic associations between studied biomarkers and four defined endpoints, such as: mortality at the Intensive Care Unit (ICU), one-year all-cause mortality, infection that required antibiotic therapy and significant allograft rejection demonstrated on the histological result of the routine endomyocardial biopsies (EMB) in the immediate postoperative period. All models were adjusted to age (at the time of HTX) and preoperative renal function based on cystatine C plasma levels.

The mean age at the time of the HTX was 50±11 years, 75% of the patients were male. 30 patients have died during the first follow-up year after the HTX, from which 25 patients have deceased in the immediate postoperative period, which lasted in the average 26±29 days at the (ICU). Infection occurred in 47 cases, and 16 patients developed a significant allograft rejection.

IL-10 was found to be a significant predictor of mortality at the ICU (OR = 0.24, 95% CI 0.064-0.877, p = 0.031) and total 1-year mortality (HR = 0.39, 95% CI 0.173-0.874, p = 0.022). IGFBP-4 was identified to be prognostic for ICU mortality (OR = 5.1, 95% CI 1.218-21.438, p = 0.026). In the analysis of the postoperative infection endpoint, preoperative WBC count (OR = 2.74, 95% CI 1.054-7.147, p = 0.039), VCAM-1 (OR = 0.406, 95% CI 0.179-0.926, p = 0.032), and CRP (OR = 1.51, 95% CI 1.089-2.094, p = 0.013) levels were independent predictors. In addition, IGFBP-4 (OR = 0.187, 95% CI 0.038-0.915, p = 0.039) and CRP (OR = 1.583, 95% CI 1.044-2.4, p = 0.031) levels were significant independent predictors of allograft rejection.

In conclusion, numerous preoperative circulating biomarkers were successfully identified, which possess a great potential as independent prognostic markers for postoperative complications after HTX. These findings add to the growing body of the non-invasive biomarker research in the field of HTX.