Successful Thrombus Aspiration During Primary Percutaneous Coronary Intervention Reduces Infarct Size and Preserves Myocardial Viability: A Cardiac Magnetic Resonance Imaging Study

ABSTRACT: Background. The purpose of this study was to evaluate the influence of thrombus aspiration during primary percutaneous coronary intervention (PCI) on myocardial viability in patients with ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance imaging (MRI). Methods and Results. We performed cardiac MRI in 62 patients who underwent primary PCI for STEMI with manual thrombus aspiration. We divided the patients into two groups: those who had thrombus aspiration during primary PCI, which resulted in a successful procedure (n = 47 patients; TA group) and those who had thrombus aspiration and an unsuccessful procedure (n = 15 patients; non-TA group). Thrombus aspiration was defined as successful or unsuccessful, based on the histological evidence of atherothrombotic material in the aspirate samples. The infarct volume was quantified using delayed-contrast enhancement on cardiac MRI. The reference volume was defined as transmural myocardial volume at the infarcted segment. Myocardial viability was assessed by a transmurality index defined as the ratio of the infarct volume to the reference volume. Although baseline characteristics and the reference volume were comparable between the two groups (24.5 ± 12.5 ml for TA group versus 29.0 ± 9.6 ml for non-TA group; p = 0.21), the infarct size was significantly smaller in the TA group than in the non-TA group (12.2 ± 7.1 ml versus 17.4 ± 7.1 ml, respectively; p = 0.01). The transmurality index was also significantly lower in the TA group (49.3 ± 10.6% versus 60.9 ± 13.9%, respectively; p = 0.001). Conclusion. Patients with successful TA showed more reduced infarct size and preserved myocardial viability than patients without TA. These effects of TA may lead to preserved left ventricular systolic function and better clinical outcomes.

J INVASIVE CARDIOL 2011;23:172–176

Key words: cardiac magnetic resonance imaging; thrombus aspiration; myocardial viability

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Primary percutaneous coronary intervention (PCI) is the preferred treatment for ST-segment elevation myocardial infarction (STEMI) and is effective in opening the infarct-related artery.^1,2 Despite a brisk coronary flow in the infarct-related epicardial artery, microvascular obstruction with diminished myocardial perfusion occurs in a large proportion of patients after primary PCI, and this event is associated with an increased infarct size, reduced recovery of ventricular function, and increased mortality. Microvascular obstruction is induced by embolization of plaque or thrombotic material downstream in the infarct-related artery. This process diminishes myocardial reperfusion as well as other mechanisms such as blood cell plugging, ischemic damage, microvessel constriction and myocardial hemorrhage. In several randomized controlled trials, thrombus aspiration has improved myocardial reperfusion and clinical outcomes compared with conventional PCI.^3–8 However, the substantial effect of successful thrombus aspiration on myocardial viability has not been fully elucidated.

Contrast-enhanced magnetic resonance imaging (MRI) represents the gold-standard technique to quantify infarct size and to evaluate regional functional viability.^9,10 The transmural extent of infarcted myocardium quantified by contrast-enhanced MRI in patients with STEMI can predict the potential for regional contractile recovery in the chronic phase.¹¹ Moreover, preserved regional contractile function is associated with better clinical outcomes in patients with myocardial infarction.¹² Thus, contrast-enhanced MRI must be useful for the evaluation of the therapeutic effect on infarct size and myocardial viability in patients with STEMI. Accordingly, the aim of our study was to evaluate the impact of successful thrombus aspiration on infarct size and myocardial viability in the infarct-related region in patients with STEMI using contrast-enhanced MRI.

Methods

A total of 62 consecutive patients who were admitted to the Kobe City Medical Center General Hospital for STEMI and underwent cardiac MRI at 2 months after the onset of STEMI were consecutively enrolled into this study. The inclusion criteria were as follows: 1) symptoms suggesting acute myocardial ischemia lasting more than 30 minutes; 2) arrival to the hospital within 24 hours of the onset of symptoms; 3) ST-segment elevation of ≥ 1.0 mm in ≥ 2 contiguous leads on the admission electrocardiogram (ECG); 4) elevation in creatine kinase to at least twice the upper limit of the normal range with a concomitant rise in MB isozyme; 5) initial angiography demonstrating Thrombolysis in Myocardial Infarction (TIMI) grades 0–2; and 6) the procedure of thrombus aspiration performed during PCI. The exclusion criteria were as follows: 1) previous history of myocardial infarction or coronary bypass surgery; 2) presence of left bundle-branch block or pacemaker-induced rhythm on the admission ECG; and 3) left main stem lesion. Written informed consent was obtained from each patient. Patients were divided into two groups: the thrombus aspiration group (TA group), in which thrombus aspiration resulted in a successful procedure (n = 47 patients), and the non-thrombus aspiration group (non-TA group), in which thrombus aspiration resulted in an unsuccessful procedure (n = 15 patients) (Figure 1). Thrombus aspiration was defined as successful or unsuccessful based on the histological evidence of atherothrombotic material in the aspirate samples.

Pharmacologic treatment before PCI included the administration of aspirin and ticlopidine (a loading dose of 200 mg) or clopidogrel (a loading dose of 300 mg) and intravenous heparin (4000 IU). No patient received any thrombolytic therapy or the glycoprotein IIb/IIIa inhibitor abciximab before PCI. Thrombus aspiration was performed using the Rebirth Aspiration Catheter (Goodman Co. Ltd., Nagoya, Japan). The device is a simple, dual-lumen, monorail design, 6-French compatible catheter. The smaller lumen is to accommodate a standard 0.014-inch guidewire. The larger extraction lumen allows the removal of thrombus, which is aspirated with a 30-ml locking vacuum syringe. The catheter has a rounded distal tip designed to maximize thrombus aspiration and to protect the vessel wall during advancement and aspiration. Two or 3 passages across the lesion from proximal to distal were performed by slowly advancing the activated catheter. In both of the 2 groups, subsequent additional balloon angioplasty and coronary stenting were performed with bare-metal stents.

During the hospital stay, creatine kinase (CK) was routinely checked every 3 hours until it returned to normal or at least for the first 24 hours and daily thereafter. Standard therapies after PCI included aspirin, ticlopidine or clopidogrel, beta-blockers, lipid-lowering agents, and angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers.

By coronary angiography before and after PCI, TIMI flow grades were assessed as previously described by Ganz et al.¹³ Collateral flow was also assessed using the Rentrop classification.¹⁴ A 12-lead ECG was acquired at presentation and 90 minutes after PCI, and the ST segments on the post-procedural ECG were compared with those on the ECG at presentation. The degree of resolution of ST-segment elevation was categorized as complete (> 70%), partial (30–70%), or none (< 30%).¹⁵

Cardiac MRI to assess infarct size and transmurality of infarction was performed at 2 months after coronary revascularization using a 1.5 T scanner (Echospeed; GE Healthcare, Milwaukee, Wisconsin) in the supine position. Cine images were acquired with a steady-state free-precession pulse sequence (echo time of 1.8 ms, repetition time of 4 ms, flip angle of 30°, acquisition matrix of 256 x 128, and field of view of 35 cm). Approximately 15 minutes after intravenous administration of 0.2 mmol/kg gadolinium-DTPA, late gadolinium-enhancement images were acquired with the segmented inversion-recovery pulse sequence (echo time of 3.2 msec, repetition time of 6.6 msec, inversion time of 200–300 msec, flip angle of 20°, acquisition matrix of 256 x 128, and field of view of 35 cm). All images were acquired with ECG gating and breath-holding. Cine and late gadolinium-enhancement images were obtained in 10-mm short-axis slices from the mitral annulus to the apex, and 3 radial long-axis planes. The left ventricular (LV) volumes and left ventricular ejection fraction (LVEF) were calculated on the basis of short-axis images. Late gadolinium-enhancement was defined as any region with a signal intensity > 2 SD above a reference remote myocardial region, as previously reported by Gerber et al.¹⁶ All other measurements were performed by 2 fully blinded operators using an off-line dedicated workstation.

Infarct area was defined as the region of delayed-contrast enhancement and traced manually in the short-axis images to measure the total infarct volume (Figure 2). Infarct volume ratio (%) was defined as the ratio of the infarct volume to the LV mass. Isolated midwall or subepicardial hyperenhancement was excluded because this is not considered as infarct area.^17,18 We defined reference area as the region of transmural myocardium with subendocardial delayed-contrast enhancement. The reference area was also traced manually in short-axis images to measure the total reference volume (Figure 2). Each volume is the sum of the areas on cross-sectional images by Simpson’s method. Transmurality index was defined as the ratio of the infarct volume to the reference volume.

Categorical variables are presented as frequency values and were compared by Fisher’s exact test or the chi-square test. Continuous variables are expressed as means ± standard deviations, and were compared by Student’s t-test and Wilcoxon rank-sum test for non-normally distributed variables. A difference with a p-value < 0.05 was considered to be statistically significant. Data analyses were performed with SPSS software, version 17.0 (SPSS, Inc., Chicago, Illinois).

Results

Table 1 summarizes the baseline characteristics of the study patients. Both of the groups did not significantly differ for any of the clinical characteristics including peak CK level, pre-infarction angina or time from hospital entry to first balloon or aspiration.

Table 2 summarizes the angiographic and procedural findings. No significant differences were observed in terms of angiographic and procedural findings including culprit vessels, initial and final TIMI flow grade, and the diameter and length of stented segment. Coronary stenting was performed with bare-metal stents in all 62 cases.

No urgent operation due to procedural complication or stent thrombosis occurred in either group. There were no differences in the baseline characteristics such as total ischemic time and previous history between the two groups. However, the sum of 90-minute ST-segment elevation was significantly smaller in the TA group than in the non-TA group (4.2 ± 3.7 mm versus 6.9 ± 4.2 mm, respectively; p = 0.02), although the sum of initial ST-segment elevation was similar between the two groups (Table 3). Complete ST-segment resolution occurred more frequently in the TA group than in the non-TA group (55.3% versus 40.0%, respectively; p = 0.03). In addition, the infarct volume was significantly lower in the TA group (12.2 ± 7.1 ml versus 17.4 ± 7.1 ml; p = 0.01), whereas no difference was observed in the reference volume. In addition, transmurality index was significantly lower in the TA group (49.7 ± 10.3% versus 60.9 ± 13.9%; p = 0.001) (Table 3). There was a tendency toward preserved LVEF, lower LV end-systolic volume and lower infarct ratio in the TA group, although they were not statistically significant.

Discussion

The present study has shown that successful thrombus aspiration prior to balloon angioplasty during primary PCI results in increased ST-segment resolution, reduced infarct size and preserved regional myocardial viability assessed by cardiac MRI in patients with STEMI. There was a trend toward preserved LVEF in the TA group, suggesting that successful TA might contribute to improvement of global LV systolic function and clinical outcomes. Our study has given substantial evidence regarding the beneficial effects of successful thrombus aspiration in patients with STEMI on myocardial viability.

The clinical importance of embolization of atherothrombotic material from unstable plaques in patients with myocardial infarction with ST-segment elevation has been recognized.^19,20 Therefore, embolic protection during primary PCI in STEMI has been tested using various devices in small- or medium-sized trials. However, the effects to limit infarct size and improve clinical outcomes still remain controversial.^3–6,21,22 The controversy may be in part related to the device used. Indeed, most trials using manual aspiration devices have shown favorable effects of aspiration on myocardial perfusion variables,^3–6 while most trials with distal protection devices failed to show the clinical benefits.^21,22 Recently, the TAPAS (Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction Study) trial demonstrated that a strategy of thrombus aspiration provided good short-term clinical benefits in patients with STEMI assessed by ST-segment resolution, myocardial blush grade and cardiac events at 1-year follow-up.^7,8 On the other hand, there was no difference in peak CK between groups with and without thrombus aspiration and no further assessment of substantial infarct size in the TAPAS trial was attempted. The effects of thrombus aspiration to reduce infarct size and preserve myocardial viability have not been clearly demonstrated in patients with STEMI. In the present study, there was significant difference in the infarct size assessed by cardiac MRI despite no significant difference in peak CK between the TA and the non-TA groups. Although peak CK measurement is a simple and convenient biochemical measure of infarct size, it is not ideal for the estimation of infarct size because of the discrepancy of peak CK and pathological infarct size.²³ Thus, inaccurate evaluation of infarct size by peak CK measurement might partly cause the controversy in the effects of embolic protection.

Contrast-enhanced MRI allows accurate measurement of infarct size and myocardial viability by clearly differentiating necrotic and viable myocardium with delayed-enhancement imaging.²⁴ Therefore, contrast-enhanced MRI must be useful for the evaluation of the therapeutic effect on infarct size and myocardial viability in the infarct-related region. Recently, Sardella et al reported that thrombus aspiration significantly reduced infarct size in patients with STEMI at 3 months after the onset assessed by contrast-enhanced MRI. However, the relationship between thrombus aspiration and myocardial viability of the infarct-related region was not evaluated in their study. In our study, contrast-enhanced MRI clearly demonstrated that successful thrombus aspiration during primary PCI led to lower infarct size and lower infarct transmurality, which means higher myocardial viability. In addition, there was a trend toward preserved LVEF in patients after successful thrombus aspiration. Our results might account for the beneficial effects of thrombus aspiration on clinical outcomes in the previous studies.^3–8

Study limitations. The present study has several limitations. First, it represents a single-center, nonrandomized cohort study with a limited number of patients. However, the baseline characteristics of the study patients were similar between the 2 groups, minimizing a potential selection bias. Second, in the present study, patients were assigned into 2 groups based on the procedural success of thrombus aspiration. This group assignment is different from the previous studies based on intention to treat.^7,25 In the TAPAS trial, a total of 54 patients (10%) in the thrombus aspiration group were crossed over to the other group because of procedural problems such as the difficulty of device passage.⁸ Besides, atherothrombotic material could not be identified in 27% of patients in whom thrombus aspiration was performed. These patients might not obtain a maximal benefit from thrombus aspiration in infarct size reduction. In contrast, the group assignment in the present study allowed us to evaluate the substantial effects of successful thrombus aspiration on infarct size and myocardial viability.

Source of funding. S. Kaji was supported by a grant-in-aid for scientific research 17790519 from Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan.

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From the Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan, and the *Institute of Biomedical Research and Inno- vation, Kobe, Japan.
The authors report no conflicts of interest regarding the content herein.
Manuscript submitted November 4, 2010, provisional acceptance given Decem- ber 17, 2010, final version accepted February 11, 2011.
Address for correspondence: Shuichiro Kaji, MD, Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, 4-6, Minatojima-nakamachi, Chuo-ku, Kobe, Japan, 650-0046. E-mail: skaji@theia.ocn.ne.jp