Heart-type fatty acid binding protein is an independent predictor of death and ventricular dysfunction after coronary artery bypass graft surgery

Abstract

Background: Heart-type fatty acid binding protein (hFABP) functions as a myocardial fatty acid transporter and is released into the circulation early after myocardial injury. We hypothesized that hFABP is superior to conventional cardiac biomarkers for predicting early perioperative myocardial injury after coronary artery bypass graft (CABG) surgery.

Methods: A prospective cohort study of 1298 patients undergoing primary CABG with cardiopulmonary bypass (CPB) was performed at 2 institutions. Four plasma myocardial injury biomarkers (hFABP; cardiac troponin I [cTnI]; creatine kinase, MB [CK-MB] fraction; and myoglobin) were measured at 7 perioperative time points. The association among perioperative cardiac biomarkers and ventricular dysfunction, hospital length of stay (HLOS), and up to 5-year postoperative mortality (median 3.3 years) was assessed using Cox proportional hazard models. We defined in-hospital ventricular dysfunction as a new requirement for 2 or more inotropes, or new placement of an intraaortic balloon pump, or ventricular assist device either during the intraoperative period after the patient separated from CPB or postoperatively in the intensive care unit.

Results: The positive and negative predictive values of mortality for hFABP are 13% (95% confidence interval [CI], 9%-19%) and 95% (95% CI, 94%-96%), respectively, which is higher than for cTnI and CK-MB. After adjusting for clinical predictors, both postoperative day (POD) 1 and peak hFABP levels were independent predictors of ventricular dysfunction (P < 0.0001), HLOS (P < 0.05), and 5-year mortality (P < 0.0001) after CABG surgery. Furthermore, POD1 and peak hFABP levels were significantly superior to other evaluated biomarkers for predicting mortality. In a repeated-measures analysis, hFABP outperformed all other models of fit for HLOS. Patients with POD2 hFABP levels higher than post-CPB hFABP levels had an increased mortality compared with those patients whose POD2 hFABP levels decreased from their post-CPB level (hazard ratio, 10.9; 95% CI, 5.0-23.7; P = 7.2 × 10(-10)). Mortality in the 120 patients (10%) with a later hFABP peak was 18.3%, compared with 4.7% in those who did not peak later. Alternatively, for cTnI or CK-MB, no difference in mortality was detected.

Conclusion: Compared with traditional markers of myocardial injury after CABG surgery, hFABP peaks earlier and is a superior independent predictor of postoperative mortality and ventricular dysfunction.

Trial registration: ClinicalTrials.gov NCT00281164.

Figure 1

Time course of median biomarker levels (±SE). Myoglobin levels shown as one-tenth of actual value. Pre = preoperatively; post = postprotamine dose; CK-MB = creatinine kinase, MB fraction; cTnI = cardiac troponin I; hFABP = heart-type fatty acid binding protein; MYO = myoglobin; CPB = cardiopulmonary bypass.

Figure 2

Kaplan-Meier survival curve for time of peak heart-type fatty acid binding protein (hFABP) level. Difference in survival for patients with a decrease in hFABP level between POD2 and immediately after cardiopulmonary bypass (CPB) and those with an increased hFABP on POD2 compared with immediately after CPB (shaded area = 95% confidence interval). P value refers to the level of difference between curves. POD = postoperative day.

Figure 3

Hospital length of stay discharge curve for time of peak heart-type fatty acid binding protein (hFABP) level. Difference in discharge from hospital for patients with a decrease in hFABP level between POD2 and immediately after cardiopulmonary bypass (CPB) and those with an increased hFABP on POD2 compared with immediately after CPB (shaded area = 95% confidence interval). P value refers to the level of difference between curves. For example, at a hospital length of stay of 10 days, 40% of patients with a high hFABP level on postoperative day (POD) 2 are still hospitalized versus 20% with a low hFABP level.