The Value of Biomarkers in Major Cardiovascular Surgery Necessitating Cardiopulmonary Bypass

Abstract

The use of biomarkers in cardiovascular surgery is an evolving field with promising potential; however, current research remains largely limited, requiring further validation for routine clinical application. This review explores the application of biomarkers in cardiovascular surgery, focusing on heart failure, cardiac ischemia, and organ dysfunction, including renal, cerebral, pulmonary, and splanchnic impairments. Additionally, it examines the significance of biomarkers in assessing the inflammatory state and oxidative stress during the perioperative period, particularly in the context of major surgical trauma and cardiopulmonary bypass (CPB). From January 2018 to June 2024, we reviewed 133 studies and four systematic reviews and meta-analyses using the Medline, Embase, and Central databases, screening for pre- or postoperative biomarker levels in patients undergoing cardiac surgery. Outcomes of interest were postoperative mortality, nonfatal myocardial infarction, stroke, congestive heart failure, and major adverse cardiovascular events (MACEs). Studies reporting multivariable-adjusted risk estimates were included. The findings revealed that cardiac troponins (cTns) and creatine kinase isoenzyme MB (CK-MB) remain the most widely utilized biomarkers for assessing myocardial injury post-surgery. These elevated biomarker levels were consistently associated with an increased risk of postoperative complications, including low cardiac output syndrome, prolonged ventilation, and mortality. Emerging biomarkers, such as heart-type fatty acid-binding protein (h-FABP) and high-sensitivity C-reactive protein (hs-CRP), demonstrated promising early detection and risk stratification results. In particular, h-FABP increased rapidly within one hour of myocardial injury, peaking at 4-6 hours and returning to baseline within 24 hours. This rapid clearance makes h-FABP a valuable tool for early myocardial injury detection, potentially allowing for timely interventions. Inflammatory biomarkers, including hs-CRP and pentraxin 3 (PTX3), were found to be associated with poor outcomes, such as increased morbidity and mortality. Elevated preoperative levels of these markers were indicative of a heightened inflammatory response, correlating with worse postoperative recovery and higher rates of complications. Furthermore, the neutrophil-to-lymphocyte ratio (NLR) emerged as a cost-effective and easily accessible predictor of postoperative outcomes. Elevated NLR values were linked to an increased risk of adverse events, including prolonged ventilation, low cardiac output syndrome, and overall mortality. Further, the practicality of measuring NLR through routine blood tests makes it viable for widespread clinical use. In conclusion, integrating biomarkers in cardiovascular surgery significantly advances predicting postoperative outcomes for cardiac surgery patients. Therefore, it is essential to categorize these biomarkers into two distinct groups in the future, inflammatory and non-inflammatory (related to organ damage), to improve understanding and enhance their clinical applicability. Future research should focus on standardizing the use of these biomarkers and exploring their combined predictive power to enhance risk stratification and improve patient prognosis.

Keywords: cardiac injury biomarkers; cardiac surgery; inflammatory biomarkers; renal injury biomarkers.

Fig. 1.

Deleterious outcomes of cardiovascular surgery.

Fig. 2.

Examples of biomarkers used in cardiovascular surgery to assess outcome. CRP, C-reactive protein; CK-MB, creatine kinase isoenzyme MB; NT-proBNP, N-terminal pro-B-type natriuretic peptide; MR-proANP, mid-regional pro-atrial natriuretic peptide; NGAL, neutrophil gelatinase-associated lipocalin; KIM-1, kidney injury molecule-1.

Fig. 3.

Timeline of myocardial injury biomarkers peak levels after cardiac surgery. SST-2, suppression of soluble tumorigenicity 2; h-FABP, heart-type fatty acid-binding protein; GDF-15, growth differentiation factor 15; CK-MB, creatine kinase isoenzyme MB; MR-proANP, mid-regional pro-A-type natriuretic peptide; cTnI, cardiac troponin I; NT-proBNP, N-terminal pro-B-type natriuretic peptide.

Fig. 4.

Serum and urinary biomarkers for early detection of acute kidney injury post cardiac surgery. KIM-1, kidney injury molecule-1; NGAL, neutrophil gelatinase-associated lipocalin.