Assessment of coronary reperfusion in patients with myocardial infarction using fatty acid binding protein concentrations in plasma

Abstract

Objective: To examine whether successful coronary reperfusion after thrombolytic treatment in patients with confirmed acute myocardial infarction can be diagnosed from the plasma marker fatty acid binding protein (FABP), for either acute clinical decision making or retrospective purposes.

Design: Retrospective substudy of the GUSTO trial.

Setting: 10 hospitals in four European countries.

Patients: 115 patients were treated with thrombolytic agents within six hours after the onset of acute myocardial infarction. Patency of the infarct related artery was determined by angiography within 120 minutes of the start of thrombolysis.

Main outcome measures: First hour rate of increase in plasma FABP concentration after thrombolytic treatment, compared with increase in plasma myoglobin concentration and creatine kinase isoenzyme MB (CK-MB) activity. Infarct size was estimated from the cumulative release of the enzyme alpha hydroxybutyrate dehydrogenase in plasma during 72 hours, or from the sum of ST segment elevations on admission. Logistic regression analyses were performed to construct predictive models for patency.

Results: Complete reperfusion (TIMI 3) occurred in 50 patients, partial reperfusion (TIMI 2) in 36, and no reperfusion (TIMI 0+1) in 29. Receiver operating characteristic (ROC) curve analyses showed that the best performance of FABP was obtained when TIMI scores 2 and 3 were grouped and compared with TIMI score 0+1. The performance of FABP as a reperfusion marker was improved by combining it with alpha hydroxybutyrate dehydrogenase infarct size, but not with an early surrogate of infarct size (ST segment elevation on admission). In combination with infarct size FABP performed as well as myoglobin (areas under the ROC curve 0.868 and 0.857, respectively) and better than CK-MB (area = 0.796). At optimum cut off levels, positive predictive values were 97% for FABP, 95% for myoglobin, and 89% for CK-MB (without infarct size, 87%, 88%, and 87%, respectively), and negative predictive values were 55%, 52%, and 50%, respectively (without infarct size, 44%, 42%, and 34%).

Conclusions: FABP and myoglobin perform equally well as reperfusion markers, and successful reperfusion can be assessed, with positive predictive values of 87% and 88%, or even 97% and 95% when infarct size is also taken into account. However, identification of non-reperfused patients remains a problem, as negative predictive values will generally remain below 70%.

Figure 1

The first hour increase in plasma fatty acid binding protein (FABP) release in patients with TIMI grade 0 (n = 23), TIMI 1 (n = 6), TIMI 2 (n = 36), and TIMI 3 (n = 50). In the TIMI 0+1, TIMI 2, and TIMI 3 patients the mean (SEM) increases were 50 (11), 283 (53), and 232 (45) µg/l/h.

Figure 2

(A) Receiver operating characteristic (ROC) curves (sensitivity v 1 − specificity) for the first hour increase of fatty acid binding protein (FABP) release, comparing TIMI grade 3 v TIMI 0+1+2 (empty triangles), TIMI 3 v TIMI 0+1 (filled circles), and TIMI 2+3 v TIMI 0+1 (empty squares). (B) ROC curves of the first hour increase rate of FABP (filled circles), the first hour increase rate of FABP and QHBDH₇₂ (empty squares), and the first hour increase rate of FABP plus the sum of ST segment elevations (empty triangles), for TIMI 2+3 v TIMI 0+1. QHBDH₇₂, cumulative release of α hydroxybutyrate dehydrogenase into plasma in the first 72 hours.

Figure 3

Comparison of fatty acid binding protein (FABP) with myoglobin (MYO) and creatine kinase MB isoenzyme (CK-MB). (A) Receiver operating characteristic (ROC) curves (sensitivity v 1 − specificity) of the first hour increase in release of FABP (empty squares), myoglobin (filled circles), or CK-MB (empty triangles), for TIMI grades 2+3 v TIMI 0+1. (B) ROC curves combining the first hour increase in release of FABP (empty squares), myoglobin (filled circles), or CK-MB (empty triangles) with QHBDH₇₂, for TIMI 2+3 v TIMI 0+1.

Figure 4

Scatterplots of infarct size estimated from the sum of ST segment elevations in the admission ECG and from cumulative release of α hydroxybutyrate dehydrogenase during 72 hours (QHBDH₇₂). The best fit straight line (drawn) is shown.