Preservation of Myocardial Microcirculation During Mechanical Reperfusion for Myocardial Ischemia with Either Abciximab or Eptif

Bar graph demonstrating no significant difference in myocardial blush grade (MBG) between the abciximab group and the eptifibatide group.
Bar graph demonstrating significantly lower myocardial blush grade (MBG) in patients with prior PTCA/stenting compared to patients without prior PTCA/stenting.
Demonstrates a trend toward lower myocardial blush grade (MBG) in smokers compared to nonsmokers. This trend was not statistically significant.
Bar graph demonstrating significantly lower myocardial blush grade (MBG) in patients with prior revascularization (PTCA or CABG) compared to patients without prior revascularization.
Author(s): 

George Stoupakis, James Orlando, Harmit Kalia, Joan Skurnick, Muhamed Saric, Rohit Arora

Although rapid restoration of coronary flow in an infarct related artery is associated with improved survival, it is becoming increasingly evident that myocardial perfusion, and not just epicardial flow, is vital to myocardial salvage and viability. For example, patients with TIMI 2 flow are found to have a higher mortality than those with TIMI 3 flow, possibly as a result of impaired microcirculation.1 Myocardial blush grade (MBG) is an angiographic method of assessing myocardial microcirculation and provides independent risk stratification among patients with normal epicardial TIMI 3 flow. Higher blush grades are associated with better myocardial perfusion and clinical outcomes.2 More recently, the glycoprotein (GP) IIb/IIIa inhibitor, abciximab, has been shown to significantly improve myocardial microcirculation, as assessed by MBG, in patients undergoing primary coronary intervention (PCI) for acute ST elevation myocardial infarction (MI).3 This benefit was most prominent in diabetics and is presumed to result from reduced platelet aggregation and distal microembolization. In addition to electrocardiographic ST segment resolution,4 the beneficial effect of abciximab on microcirculatory perfusion has also been established using Doppler flow wire,5 myocardial contrast echocardiography,6 corrected TIMI frame count (CTFC)6 and TIMI myocardial perfusion grades.7 The ESPRIT trial demonstrated the benefit of eptifibatide in patients undergoing PCI.8 However, the effect of eptifibatide on microvascular perfusion is relatively unknown.
Based on data from the ESPRIT trial, our institution decided on a cost-effective shift towards the use of eptifibatide in all patients presenting with stable angina or acute coronary syndrome. However, there is no study comparing the efficacy of the monoclonal antibody, abciximab, to the peptide, eptifibatide, on perfusion of myocardial microcirculation following PCI in either stable angina or acute coronary syndrome. Thus, to assess the efficacy of either GP IIb/IIIa receptor blocker, we performed a retrospective analysis comparing the effect on myocardial perfusion between the last 51 patients who routinely received abciximab for unstable or stable angina versus the first 50 patients who began to receive eptifibatide after the pharmacologic shift by our institution. The significance of prior revascularization on microcirculatory perfusion was also investigated. We hypothesized that there would be no difference in preservation of microcirculatory perfusion, as assessed by MBG, between both drugs.

Methods

Patients. One hundred and one consecutive patients who presented to our hospital with myocardial ischemia (23 stable angina, 61 unstable angina, 17 non-q MI) who underwent intracoronary revascularization between July 2001 and April 2002 were reviewed for microcirculatory perfusion. Fifty-one patients received standard bolus (0.25 mg/kg) and infusion (0.125 mg/kg/minute for 12 hours) of abciximab while fifty patients received standard bolus (two 180 ug/kg boluses given 10 minute apart) and infusion (2 mg/kg/minute for 18–24 hours) of eptifibatide. Saphenous venous graft lesions and patients with end-stage renal disease were excluded because of their increased risk of distal embolization. Successful percutaneous transluminal coronary angioplasty (PTCA) with stenting was performed in all patients. Troponin I (cTnI) levels were drawn on admission and every 6–8 hours up until cardiac catheterization and measured using the Abbott Axsym System in our central laboratory. By this method, the serum cTnI in a normal healthy population is < 5.0 ng/ml. Two-dimensional echocardiography was performed in the apical four-chamber, parasternal long-axis, and parasternal short-axis view with area-length method used to calculate ejection fraction.
TIMI Flow Grades and Myocardial Blush Grades. Flow in the target vessel after the interventional procedure was graded using TIMI flow classification.9 Angiograms were evaluated for both TIMI flow and MBG by two experienced investigators who were blinded to all data apart from the coronary angiograms. Grading was assessed on cinefilm at 25 frames/second made in a General Electric digital coronary imaging catheterization laboratory. The best projection was selected in each patient to assess the myocardial region of the target vessel revascularized and to minimize superimposition of non-target-related territories. Blush was assessed distal to the stent of the culprit lesion. Left anterior oblique projections were chosen in 66%, right anterior oblique in 23%, anteroposterior in 9%, and a caudal view in 2%. Angiographic runs were long enough to allow for filling of the venous coronary system and backflow of contrast into the aorta had to be present to be certain of adequate contrast filling of the epicardial coronary arteries. Standard 6 French (Fr) guiding catheters were used in all angiograms. The duration of the cine filming was required to exceed 3 cardiac cycles in the washout phase to assess washout of the myocardial blush. Myocardial blush grades were defined as follows: 0, no blush or contrast density; 1, minimal blush or contrast density; 2, moderate blush or contrast density but less than that obtained during angiography of an ipsilateral or contralateral non-target-related coronary artery; and 3, normal blush or contrast density, comparable with angiography of an ipsilateral or contralateral non-target-related coronary artery.2 "Staining" of the myocardium by blush which persisted beyond the washout phase suggested leakage of the contrast medium into the extravascular space and was graded 0.10 The two observers agreed on MBG in 83% of the cases. In the remaining 17% of the cases, the difference was only one grade.
Statistical Analysis. Data are summarized as proportions or mean ± SEM. T-tests were used for group comparisons of age and left ventricular ejection fractions. Rank sum tests were used for group comparisons of myocardial blush grades and of peak cardiac enzyme levels. Fisher’s Exact tests were used for comparisons of proportions. Spearman’s rank correlation coefficient rS was used to assess the significance of associations among myocardial blush grades, cardiac enzyme levels and ejection fractions. Unless stated otherwise, 2-tailed p values are reported; the criterion for statistical significance was p < 0.05. A sample size of 100 patients (50 per arm) would provide 80% power to detect differences of 25–30% in the proportion of MBG 3 between the two groups in a two-sided test at an alpha level of 0.05.

Results

Baseline characteristics. Although the patients were not randomized, there were no significant differences between patients receiving abciximab (n = 51) and patients receiving eptifibatide (n = 50) with respect to age, gender, left ventricular ejection fraction, peak cardiac enzyme levels, history of hypertension, diabetes mellitus, hypercholesterolemia, tobacco use, or diagnosis (Table 1).
Myocardial Blush Grades. In the abciximab group, 34/51 (67.0%) had MBG of 3, 16/51 (31.0%) had MBG of 2 and 1/51 (2.0%) had MBG of 0-1, compared to 29/50 (58.0%) who had MBG of 3, 18/50 (36.0%) who had MBG of 2 and 3/50 (6.0%) who had MBG of 0-1 in the eptifibatide group (Figure 1). There was no statistically significant difference in MBG between both groups (p = 0.34). However, overall patients with a previous history of PTCA/stenting had lower MBG scores (MBG 0-2) compared to patients without a history of previous PTCA [15/26 (58.0%) versus 23/75 (31.0%); p = 0.03] (Figure 2). MBG scores in all previously revascularized patients, by either PTCA or coronary artery bypass grafting, were statistically significantly lower compared to patients without a history of previous revascularization [17/31 (55.0%) versus 21/70 (30.0%); p = 0.026] (Figure 3). Prior stenting of the target vessel occurred in 30% of the patients with a history of prior PTCA/stenting. Prior revascularization of the target vessel occurred in 71% of the patients with a history of prior CABG. There was no statistically significant difference in MBG scores in patients with diabetes, hypertension or hypercholesterolemia. However, there was a trend toward lower MBG scores (0-2) in smokers compared to nonsmokers, which was not statistically significant [13/27 (48.0%) versus 25/74 (34.0%)] (Figure 4).
Relationship of MBG to contractile function. Cardiac troponin I (cTnI) levels were measured on admission and serially every 8 hours up until cardiac catheterization. Table 2 demonstrates that myocardial blush grade inversely correlated with peak cTnI (r = -0.18, one-tailed p = 0.04) which would be significant in a one tailed but not two tailed test. Myocardial blush grade did not correlate with left ventricular ejection fraction (r = 0.09; p = 0.40). Left ventricular ejection fraction did not correlated with peak cTnI (-0.20; p = 0.09).

Discussion


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