Tissue factor pathway inhibitor is an early biomarker of myocardial injury in patients with ST-segment elevation acute myocardial infarction Antonia Sambola ⁎, Jaume Francisco, Bruno García -Del Blanco, Santiago Aguadé, Jaume Candell-Riera, Gerard Martí, Jaume Figueras, José A. Barrabés, Xavier Millán, David García-Dorado Cardiology Department, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain article info Article history: Received 3 December 2013 Accepted 30 December 2013 Available online 10 January 2014 Keywords: Tissue factor pathway inhibitor Acute myocardial infarction size SPECT Tissue factor pathway inhibitor (TFPI) is released from vascular endothelium injured by ischemia/reperfusion and by platelet activa- tion during ST-segment elevation acute myocardial infarction (STEMI) [1]. However, whether in the acute phase of myocardial infarction (MI) plasma TFPI levels are associated with the degree of reperfusion after primary PCI (P-PCI) and with infarct size remains unknown. Tc99m sestamibi is an established modality for the assessment of MI, particularly if Tc99m can be injected before opening of the occluded artery [2]. We aimed to determine whether plasma TFPI levels measured prior to primary PCI in patients with STEMI can predict infarct size determined by SPECT. Consecutive patients with a first acute STEMI and angiographic TIMI flow grade 0 at the culprit lesion who underwent a P-PCI were included. The study protocol adhered to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the human research committee of The Vall d'Hebron Research Institute. All patients and controls gave their written informed consent before inclusion. Pharmacologic treatment prior toP-PCI included aspirin, clopido- grel and intravenous unfractionated heparin (N 5000 IU). Use of the glycoprotein IIb/IIIa inhibitor abciximab was left to the operator's discretion. All patients received standard medication after P-PCI including: dual antiplatelet therapy, statins, beta-blockers and/or angiotensin-converting enzyme inhibitors. For the SPECT scan, patients received a 900 MBq-dose of 99mTctetrofosmin injected intravenously with the artery occluded prior to P-PCI, as previously described [3]. The gated SPECT scan for infarct size assessment (gSPECT-2) was scheduled with a median of 30.3 [IQR: 0 to 35] days. The initial perfusion defect, infarct size and area of salvaged myocardium were expressed as a proportion of the left ventricular mass (LVM). Venous blood was drawn just before P-PCI was started and plasma free TFPI antigen levels were measured by an ELISA kit (AssaYPro, Souffelweyersheim, France). Assay was b 0.5 ng/mL for TFPI. Intra- assay and inter-assay coefficients of variation were 8.2% and 10.1%, respectively. Comparisons of continuous and categorical variables were eval- uated by Mann–Whitney U test or Student's t test as required and the chi-square test respectively. Final infarct size was dichotomized into large or small categories using the 50th percentile as a cut-off value (large infarct size 10% of LVM). Correlation was measured as a Spearman rank correlation. A multivariate logistic regression model was used to assess the association between TFPI before P-PCI and infarct size. Receiver operating characteristic (ROC) curves were analyzed according to the area under the curve (AUC). A two-tailed p value of less than 0.05 was considered statistically significant. All results were considered significant for a p-value b 0.05. Eighty-one consecutive subjects (27 women, 25.2%) with STEMI were treated with P-PCI. Median age was 58 years (range: 37–93). Images with artery occluded were obtained in 69 of the 81 patients. Clinical and angiographic characteristics of patients with an infarct size above and below 10% of LVM are shown in Table 1 . TFPI levels were higher in patients with a large infarct than in those patients with a small infarct (IQ 476.7 [168.6 to 876.9] ng/mL vs 240.5 [163.7 to 422.2] ng/mL, p b 0.001). Characteristics of the study population according to TFPI levels are shown in Table 2. Patients with higher TFPI levels (N 75th percentile) had a greater area at risk and a larger infarct size, and a higher proportion had a left ventricular ejection fraction b 50%. In addition, a significant correlation was found between TFPI levels at baseline and size of the area at risk (r = 0.47, p = 0.006) as well as final infarct size (r = 0.49, p b 0.0001). TFPI levels just prior to PCI were strongly predictive of final infarct size. The crude OR per 1 SD increase in TFPI level for developing a large infarct (above the median) was 1.03 (95% CI 1.01–2.02, p = 0.04). By simple regression analysis, male sex, time from symptoms to PCI, area at risk, ejection fraction, CK-mb levels and TFPI N 75th percentile (OR 10.41, 95% CI 1.78–60.81, p = 0.001) were associated with final infarct size. After adjustment for these variables in a multivariate model, TFPI remained a strong, independent predictor of developing a large infarct (OR 9.15, 95% CI 1.58–52.95, p = 0.01). Receiver operating characteristic curve analysis confirmed baseline TFPI levels N 75th percentile as a predictor of a large infarct (Fig. 1). This study demonstrates that TFPI is an early biomarker of myocardial injury and may contribute to explaining final infarct size in patients with STEMI treated with P-PCI. TFPI levels before PCI were strongly and independently associated with area at risk and final infarct size, which indicates that elevated levels of TFPI integrate several major clinical and biochemical indicators of poor prognosis in patients with STEMI. These findings are consistent with those of other studies that showed that TFPI expression levels increased in a similar extent of myocardial damage, thereby suggesting that elevated TFPI levels in STEMI patients do not fully block the TF-mediated coagulation activity [4,5]. The significant increase in plasma TFPI levels during MI has been attributed to increased release from injured vascular endothelium, and might be a compensatory reaction to increased TF levels in STEMI [5–7]. In addition, Erlich et al., suggested that cardiomyocyte TF initiates extravascular thrombin generation, which enhances inflam- mation and injury during myocardial ischemia/reperfusion, and pointed to the role of TF and possibly TFPI in myocardial damage [8]. ⁎ Corresponding author at: Cardiovascular Institute, University Hospital Vall d'Hebron, P. Vall d'Hebron 119-129, 08035 Barcelona, Spain. Tel.: +34 932746002; fax: +34 932746063. E-mail address: asambola@vhebron.net (A. Sambola). 279 Letters to the Editor