Letters to the Editor
279
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
a r t i c l e
i n f o
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 activation 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, clopidogrel and intravenous unfractionated heparin (N5000 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 b0.5 ng/mL for TFPI. Intraassay and inter-assay coefficients of variation were 8.2% and 10.1%, respectively.
⁎ 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: [email protected] (A. Sambola).
Comparisons of continuous and categorical variables were evaluated 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 b0.05. 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 (N75th percentile) had a greater area at risk and a larger infarct size, and a higher proportion had a left ventricular ejection fraction b50%. 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 N75th 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 inflammation and injury during myocardial ischemia/reperfusion, and pointed to the role of TF and possibly TFPI in myocardial damage [8].
280
Letters to the Editor
Table 1 Patient characteristics at baseline and after primary PCI according to infarct size. Infarct sizea b 10% of LVM n = 40
Variables Age, ya Male, % Current smoker, % Treated hypertension, % Diabetes mellitus, % Hyperlipidemia, % Peripheral vasculopathy, % Anterior MI, % Killip class 2–3, % Time from symptoms to PCI, hoursa Troponin T, μg/mLa Peak CK-mb, μmol/L LVEF (mm)a TIMI flow b3 after PCI, % Blush grade b3, % Rentrop grade N 0, % Multivessel disease, % Number of diseased vessels, % 1 2 3 TFPI at baselinea ng/mL ASA, % Clopidogrel, % β-blockers, % ACE inhibitors, % Statins, %
58 27 29 18 5 20 1 14 3 3 3.12 142 54 1 15 12 18
(50–68) (67.5) (72.5) (45) (12.5) (50.0) (2.5) (35.0) (7.7) (2.3–4) (2.1–6.1) (84.8–311) (50–59) (2.5) (37.5) (60) (47.1)
26 (65.0) 9 (22.5) 5 (12.5) 240.5 (163.7–422.2) 40 (100) 40 (100) 35 (87.5) 25 (62.5) 39 (97.5)
Infarct size ≥10% of LVM n = 41 59 (52–72) 37 (90.2) 29 (70.7) 19(46.3) 9 (21.9) 22(53.7) 4 (9.8) 19 (46.3) 7 (17.5) 4 (3.1–5.6) 7.3 (5.2–12.3) 304 (226–405) 43 (38–53) 6 (14.6) 22 (55.0) 32 (45.1) 16 (47.1) 21 (51.2) 13 (31.7) 7 (14.6) 476.7 (168.6–876.9) 41 (100) 41 (100) 33 (82.5) 24 (60.0) 34 (85.0)
p 0.510 0.012 0.860 0.904 0.261 0.742 0.175 0.299 0.190 0.012 b 0.001 0.001 b 0.001 0.052 0.284 0.177 0.430 0.505
b 0.001
0.531 0.818 0.048
ACE: angiotensin converting enzyme; ASA: acetylsalicylic acid; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention. a Median (interquartile range).
Table 2 Characteristics of patients with plasma tissue factor pathway inhibitor levels N75th percentile at baseline. Variables
Tissue factor pathway inhibitor b740.9 ng/mL n = 62
Tissue factor pathway inhibitor ≥740.9 ng/mL n = 19
p
Age, ya Male, % Current smoker, % Treated hypertension, % Diabetes mellitus, % Hyperlipidemia, % Peripheral vasculopathy, % Anterior MI, % Time from symptoms to aPCI, min Troponin T, IUa Peak CK mb, μmol/La LVEF, mma LVEF b50%, % Area at risk, LVM % Final infarct size, LVM % Infarct size N10%, LVM % TIMI flow grade b3 after PCI, % Blush b3, % Rentrop N 0% Multivessel disease, % Number of diseased vessels, % 1 2 3 ASA, % Clopidogrel, % GPIIa/IIIb, % β-blockers, % ACE inhibitors, % Statins, %
60 15 43 31 11 30 4 23 205 5.2 206 52 7 10.5 7 10.8 4 26 28
56 (50–62) 2 (10.5) 15 (78.9) 6 (31.6) 3 (15.8) 12 (63.2) 1 (5.3) 10 (52.6) 240 (165–300) 7.48 (4.9–11.2) 269.4 (226–407) 43.5 (39–53) 23 (65.7) 17.5 (15.5–36.5) 15 (10–26) 19.8 (13.6) 3 (15.8) 11 (57.9) 16 (59.3)
0.349 0.201 0.417 0.158 0.844 0.260 0.851 0.288 0.551 0.086 0.148 0.110 b0.001 0.047 0.004 0.006 0.205 0.415 0.131
37 16 9 62 62 56 50 40 57
(51–73) (24.1) (69.3) (50.0) (17.7) (48.4) (6.5) (37.1) (150–287.5) (2.4–7.6) (107–385) (42.5–57.5) (22.6) (2–23) (1–16) (11.6) (6.5) (42.6) (43.8)
(59.7) (24.2) (14.5) (100) (100) (70) (82.0) (65.6) (93.4)
10 7 2 19 19 20 18 9 16
(52.6) (36.8) (10.5) (100) (100) (74) (94.7) (43.4) (84.2)
0.692
0.444 0.173 0.155 0.214
ACE: angiotensin converting enzyme; ASA: acetylsalicylic acid; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention. a Median (interquartile range).
Letters to the Editor
281
and PI09/1014). No additional external funding was received for this study. The authors wish to thank Mrs. Adoración Quiroga for the technical assistance, Santiago Pérez-Hoyos from the Preventive Medicine Department of University Hospital Vall d'Hebron for his help in statistical analysis. We are indebted to Christine O'Hara for the help with the English version of the manuscript.
References
Fig. 1. Receiver operating characteristic curve for differentiating between large (LVM N 10%) versus small myocardial infarction (LMV b 10%) by baseline TFPI. The ability of baseline TFPI levels N75th percentile to predict large infarct was also assessed by ROC curve and was comparable to peak CK mass (AUC 0.69; 95% CI 0.57 to 0.80, p = 0.003), time from symptoms to PCI (AUC 0.69; 95% CI 0.58 to 0.81, p = 0.002) and area at risk (AUC 0.74; 95% CI 0.58 to 0.89, p = 0.009, p = 0.009) to predict a large infarct.
We recently reported a strong association between TF Ag and cardiovascular complications in patients with STEMI, and pointed out that the TF pathway is associated with thrombogenic phenomena in patients with STEMI [9]. In conclusion, TFPI appeared as an early biomarker of myocardial damage and may contribute to explaining final infarct size in patients with STEMI. Future studies are required to ascertain whether TFPI can aid with therapeutic decision-making in STEMI. This study was supported by a research grant from the Spanish Government (Fondo de Investigación Sanitaria; References PI061658
0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.240
[1] Golino P, Ravera A, Ragni M, Cirillo P, Piro O, Chiariello M. Involvement of tissue factor pathway inhibitor in the coronary circulation of patients with acute coronary syndromes. Circulation 2003;108:2864–9. [2] Hadamitzky M, Langhans B, Hausleiter J, et al. The assessment of area at risk and myocardial salvage after coronary revascularization in acute myocardial infarction: comparison between CMR and SPECT. JACC Cardiovasc Imaging 2013;3:358–69. [3] Candell-Riera J, Llevadot J, Santana C, et al. Prognostic assessment of uncomplicated first myocardial infarction by exercise echocardiography and TC tetrofosmin gatedSPECT. J Nucl Cardiol 2001;8:122–8. [4] Empana JP, Canoui-Poitrine F, Luc G, et al. Contribution of novel biomarkers to incident stable angina and acute coronary syndrome: the PRIME Study. Eur Heart J 2008;29(16):1966–74. [5] Junmin Y, Zhao J, Liu W. Combined effects of irbesartan and carvedilol on expression of tissue factor pathway inhibitor in rats after myocardial infarction. Heart Vessels 2011;26:646–53. [6] Figueras J, Monasterio J, Lidón RM, Sambola A. Lower tissue factor inhibition in patients with ST-segment elevation than in patients with non-ST-elevation acute myocardial infarction. Thromb Res 2012;130:458–62. [7] Ott I, Andrassy M, Zieglgänsberger D, Geith S, Schömig A, Neumann FJ. Regulation of monocyte procoagulant activity in acute myocardial infarction: role of tissue factor and tissue factor pathway inhibitor-1. Blood 2001;97:3721–6. [8] Erlich JH, Boyle EM, Labriola J, et al. Inhibition of the tissue factor-thrombin pathway limits infarct size after myocardial ischemia–reperfusion injury by reducing inflammation. Am J Pathol 2000;157:1849–62. [9] Sambola A, García Del Blanco B, Francisco J, et al. Prognostic impact of tissue factor pathway on long-term ischemic events of ST-elevated myocardial infarction treated with a primary percutaneous coronary intervention. Int J Cardiol 2013;168(3):2916–8.
279
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
a r t i c l e
i n f o
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 activation 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, clopidogrel and intravenous unfractionated heparin (N5000 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 b0.5 ng/mL for TFPI. Intraassay and inter-assay coefficients of variation were 8.2% and 10.1%, respectively.
⁎ 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: [email protected] (A. Sambola).
Comparisons of continuous and categorical variables were evaluated 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 b0.05. 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 (N75th percentile) had a greater area at risk and a larger infarct size, and a higher proportion had a left ventricular ejection fraction b50%. 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 N75th 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 inflammation and injury during myocardial ischemia/reperfusion, and pointed to the role of TF and possibly TFPI in myocardial damage [8].
280
Letters to the Editor
Table 1 Patient characteristics at baseline and after primary PCI according to infarct size. Infarct sizea b 10% of LVM n = 40
Variables Age, ya Male, % Current smoker, % Treated hypertension, % Diabetes mellitus, % Hyperlipidemia, % Peripheral vasculopathy, % Anterior MI, % Killip class 2–3, % Time from symptoms to PCI, hoursa Troponin T, μg/mLa Peak CK-mb, μmol/L LVEF (mm)a TIMI flow b3 after PCI, % Blush grade b3, % Rentrop grade N 0, % Multivessel disease, % Number of diseased vessels, % 1 2 3 TFPI at baselinea ng/mL ASA, % Clopidogrel, % β-blockers, % ACE inhibitors, % Statins, %
58 27 29 18 5 20 1 14 3 3 3.12 142 54 1 15 12 18
(50–68) (67.5) (72.5) (45) (12.5) (50.0) (2.5) (35.0) (7.7) (2.3–4) (2.1–6.1) (84.8–311) (50–59) (2.5) (37.5) (60) (47.1)
26 (65.0) 9 (22.5) 5 (12.5) 240.5 (163.7–422.2) 40 (100) 40 (100) 35 (87.5) 25 (62.5) 39 (97.5)
Infarct size ≥10% of LVM n = 41 59 (52–72) 37 (90.2) 29 (70.7) 19(46.3) 9 (21.9) 22(53.7) 4 (9.8) 19 (46.3) 7 (17.5) 4 (3.1–5.6) 7.3 (5.2–12.3) 304 (226–405) 43 (38–53) 6 (14.6) 22 (55.0) 32 (45.1) 16 (47.1) 21 (51.2) 13 (31.7) 7 (14.6) 476.7 (168.6–876.9) 41 (100) 41 (100) 33 (82.5) 24 (60.0) 34 (85.0)
p 0.510 0.012 0.860 0.904 0.261 0.742 0.175 0.299 0.190 0.012 b 0.001 0.001 b 0.001 0.052 0.284 0.177 0.430 0.505
b 0.001
0.531 0.818 0.048
ACE: angiotensin converting enzyme; ASA: acetylsalicylic acid; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention. a Median (interquartile range).
Table 2 Characteristics of patients with plasma tissue factor pathway inhibitor levels N75th percentile at baseline. Variables
Tissue factor pathway inhibitor b740.9 ng/mL n = 62
Tissue factor pathway inhibitor ≥740.9 ng/mL n = 19
p
Age, ya Male, % Current smoker, % Treated hypertension, % Diabetes mellitus, % Hyperlipidemia, % Peripheral vasculopathy, % Anterior MI, % Time from symptoms to aPCI, min Troponin T, IUa Peak CK mb, μmol/La LVEF, mma LVEF b50%, % Area at risk, LVM % Final infarct size, LVM % Infarct size N10%, LVM % TIMI flow grade b3 after PCI, % Blush b3, % Rentrop N 0% Multivessel disease, % Number of diseased vessels, % 1 2 3 ASA, % Clopidogrel, % GPIIa/IIIb, % β-blockers, % ACE inhibitors, % Statins, %
60 15 43 31 11 30 4 23 205 5.2 206 52 7 10.5 7 10.8 4 26 28
56 (50–62) 2 (10.5) 15 (78.9) 6 (31.6) 3 (15.8) 12 (63.2) 1 (5.3) 10 (52.6) 240 (165–300) 7.48 (4.9–11.2) 269.4 (226–407) 43.5 (39–53) 23 (65.7) 17.5 (15.5–36.5) 15 (10–26) 19.8 (13.6) 3 (15.8) 11 (57.9) 16 (59.3)
0.349 0.201 0.417 0.158 0.844 0.260 0.851 0.288 0.551 0.086 0.148 0.110 b0.001 0.047 0.004 0.006 0.205 0.415 0.131
37 16 9 62 62 56 50 40 57
(51–73) (24.1) (69.3) (50.0) (17.7) (48.4) (6.5) (37.1) (150–287.5) (2.4–7.6) (107–385) (42.5–57.5) (22.6) (2–23) (1–16) (11.6) (6.5) (42.6) (43.8)
(59.7) (24.2) (14.5) (100) (100) (70) (82.0) (65.6) (93.4)
10 7 2 19 19 20 18 9 16
(52.6) (36.8) (10.5) (100) (100) (74) (94.7) (43.4) (84.2)
0.692
0.444 0.173 0.155 0.214
ACE: angiotensin converting enzyme; ASA: acetylsalicylic acid; LVEF: left ventricular ejection fraction; MI: myocardial infarction; PCI: percutaneous coronary intervention. a Median (interquartile range).
Letters to the Editor
281
and PI09/1014). No additional external funding was received for this study. The authors wish to thank Mrs. Adoración Quiroga for the technical assistance, Santiago Pérez-Hoyos from the Preventive Medicine Department of University Hospital Vall d'Hebron for his help in statistical analysis. We are indebted to Christine O'Hara for the help with the English version of the manuscript.
References
Fig. 1. Receiver operating characteristic curve for differentiating between large (LVM N 10%) versus small myocardial infarction (LMV b 10%) by baseline TFPI. The ability of baseline TFPI levels N75th percentile to predict large infarct was also assessed by ROC curve and was comparable to peak CK mass (AUC 0.69; 95% CI 0.57 to 0.80, p = 0.003), time from symptoms to PCI (AUC 0.69; 95% CI 0.58 to 0.81, p = 0.002) and area at risk (AUC 0.74; 95% CI 0.58 to 0.89, p = 0.009, p = 0.009) to predict a large infarct.
We recently reported a strong association between TF Ag and cardiovascular complications in patients with STEMI, and pointed out that the TF pathway is associated with thrombogenic phenomena in patients with STEMI [9]. In conclusion, TFPI appeared as an early biomarker of myocardial damage and may contribute to explaining final infarct size in patients with STEMI. Future studies are required to ascertain whether TFPI can aid with therapeutic decision-making in STEMI. This study was supported by a research grant from the Spanish Government (Fondo de Investigación Sanitaria; References PI061658
0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.240
[1] Golino P, Ravera A, Ragni M, Cirillo P, Piro O, Chiariello M. Involvement of tissue factor pathway inhibitor in the coronary circulation of patients with acute coronary syndromes. Circulation 2003;108:2864–9. [2] Hadamitzky M, Langhans B, Hausleiter J, et al. The assessment of area at risk and myocardial salvage after coronary revascularization in acute myocardial infarction: comparison between CMR and SPECT. JACC Cardiovasc Imaging 2013;3:358–69. [3] Candell-Riera J, Llevadot J, Santana C, et al. Prognostic assessment of uncomplicated first myocardial infarction by exercise echocardiography and TC tetrofosmin gatedSPECT. J Nucl Cardiol 2001;8:122–8. [4] Empana JP, Canoui-Poitrine F, Luc G, et al. Contribution of novel biomarkers to incident stable angina and acute coronary syndrome: the PRIME Study. Eur Heart J 2008;29(16):1966–74. [5] Junmin Y, Zhao J, Liu W. Combined effects of irbesartan and carvedilol on expression of tissue factor pathway inhibitor in rats after myocardial infarction. Heart Vessels 2011;26:646–53. [6] Figueras J, Monasterio J, Lidón RM, Sambola A. Lower tissue factor inhibition in patients with ST-segment elevation than in patients with non-ST-elevation acute myocardial infarction. Thromb Res 2012;130:458–62. [7] Ott I, Andrassy M, Zieglgänsberger D, Geith S, Schömig A, Neumann FJ. Regulation of monocyte procoagulant activity in acute myocardial infarction: role of tissue factor and tissue factor pathway inhibitor-1. Blood 2001;97:3721–6. [8] Erlich JH, Boyle EM, Labriola J, et al. Inhibition of the tissue factor-thrombin pathway limits infarct size after myocardial ischemia–reperfusion injury by reducing inflammation. Am J Pathol 2000;157:1849–62. [9] Sambola A, García Del Blanco B, Francisco J, et al. Prognostic impact of tissue factor pathway on long-term ischemic events of ST-elevated myocardial infarction treated with a primary percutaneous coronary intervention. Int J Cardiol 2013;168(3):2916–8.
