CLINICAL RESEARCH: GLYCOPROTEIN IIB/IIIA INHIBITION IN ACUTE MI
Frequency, correlates, and clinical implications of myocardial perfusion after primary angioplasty and stenting, with and without glycoprotein IIb/IIIa inhibition, in acute myocardial infarction
Costantino O. Costantini, MD*,
Gregg W. Stone, MD, FACC*,*,
Roxana Mehran, MD, FACC*,
Eve Aymong, MD*,
Cindy L. Grines, MD, FACC ,
David A. Cox, MD, FACC ,
Thomas Stuckey, MD, FACC ,
Mark Turco, MD, FACC||,
Bernard J. Gersh, MD, FACC¶,
James E. Tcheng, MD, FACC**,
Eulogio Garcia, MD,
John J. Griffin, MD, FACC,
Giulio Guagliumi, MD,
Martin B. Leon, MD, FACC* and
Alexandra J. Lansky, MD, FACC*
* Cardiovascular Research Foundation and Lenox Hill Hospital, New York, New York, USA
William Beaumont Hospital, Royal Oak, Michigan, USA
Mid Carolina Cardiology, Charlotte, North Carolina, USA
Moses Cone Hospital, Greensboro, North Carolina, USA
|| Washington Adventist Hospital, Takoma Park, Maryland, USA
¶ Mayo Clinic, Rochester, Minnesota, USA
** Duke University Medical Center, Durham, North Carolina, USA
Hospital Gregorio Maranon, Madrid, Spain
Virginia Beach General Hospital, Virginia Beach, Virginia, USA
Ospedali Riuniti di Bergamo, Bergamo, Italy
Manuscript received December 9, 2003;
revised manuscript received February 28, 2004,
accepted March 16, 2004.
* Reprint requests and correspondence: Dr. Gregg W. Stone, Cardiovascular Research Foundation, 55 East 59th Street, 6th Floor, New York, New York 10022, USA.
gstone{at}crf.org
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Abstract
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OBJECTIVES: We sought to determine the prognostic importance of myocardial reperfusion after various contemporary interventional strategies in patients with acute myocardial infarction (AMI).
BACKGROUND: The frequency, correlates, and clinical implications of myocardial perfusion after primary angioplasty in AMI have not been examined in a large-scale prospective study. Similarly, whether glycoprotein (GP) IIb/IIIa inhibitors and/or stents improve myocardial perfusion beyond balloon angioplasty has not been investigated.
METHODS: Tissue-level perfusion assessed by the myocardial blush grade was evaluated in 1,301 patients with AMI randomized to balloon angioplasty versus stenting, each with or without abciximab.
RESULTS: Despite Thrombolysis In Myocardial Infarction flow grade 3 restoration in 96.1% of patients, myocardial perfusion was normal in only 17.4% of patients, reduced in 33.9%, and absent in 48.7%. Myocardial perfusion status post-coronary intervention stratified patients into three distinct risk categories, with 1-year mortality rates of 1.4% (normal blush), 4.1% (reduced blush), and 6.2% (absent blush) (p = 0.01). Among patients randomized to angioplasty, angioplasty + abciximab, stenting, and stenting + abciximab, normal myocardial perfusion was restored in 17.7%, 17.0%, 17.5%, and 17.6%, respectively (p = 0.95), which was associated with similar 1-year rates of mortality in patients randomized to stenting versus angioplasty (4.5% vs. 4.8%, p = 0.91) and abciximab versus no abciximab (4.3% vs. 5.0%, p = 0.63).
CONCLUSIONS: Restoration of normal tissue-level perfusion is a powerful determinate of survival after primary PCI in AMI and is achieved in a minority of patients. Neither stents nor GP IIb/IIIa inhibitors significantly enhance myocardial perfusion compared to balloon angioplasty alone, underlying the similar long-term mortality with these different mechanical reperfusion strategies.
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Abbreviations and Acronyms
| | AMI | = acute myocardial infarction | | CADILLAC | = Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications | | GP | = glycoprotein | | LAD | = left anterior descending artery | | LVEF | = left ventricular ejection fraction | | MBG | = myocardial blush grade | | PCI | = percutaneous coronary intervention | | RCA | = right coronary artery | | TIMI | = Thrombolysis In Myocardial Infarction |
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Restoration of normal epicardial (Thrombolysis In Myocardial Infarction [TIMI] flow grade 3) flow has been strongly related to survival following reperfusion therapy during evolving acute myocardial infarction (AMI) (1–4). Despite TIMI flow grade 3, however, echocardiographic and other imaging modalities have frequently documented reduced myocardial perfusion, a finding that may result in persistent ST-segment elevation and diminished survival (5–18).
The myocardial blush grade (MBG) is an angiographic surrogate of myocardial perfusion (9) and has been studied in several small- to moderate-sized single-center retrospective series of patients undergoing primary percutaneous coronary intervention (PCI) (9,11,12,15,16). The prognostic utility of restored myocardial perfusion has not, however, been examined or confirmed in a large-scale multicenter prospective study. Moreover, whether glycoprotein (GP) IIb/IIIa inhibitors and/or stents improve myocardial perfusion beyond that achieved by balloon angioplasty alone has not been investigated. We therefore evaluated the frequency, correlates, and clinical implications of myocardial blush from an international multicenter prospective study of patients with AMI randomized to contemporary mechanical reperfusion strategies: the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.
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Methods
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Patient population and trial design.
The details of the CADILLAC trial have been previously described (19). In brief, 2,082 patients with AMI and symptom onset within 12 h onset due to native coronary artery occlusion were randomized at 76 international centers in a 2 x 2 factorial design to primary balloon angioplasty ± abciximab versus primary stenting ± abciximab. Patients were enrolled with ST-segment elevation, new left bundle branch block, or other electrocardiographic abnormalities if angiography demonstrated an occluded infarct vessel with associated regional wall motion abnormality. The principal exclusion criteria were cardiogenic shock, bleeding diatheses, renal insufficiency, and coronary anatomy not suitable for stent placement. Among patients randomized to angioplasty, crossover to stenting (which occurred in 16% of patients) was permitted for a residual stenosis of >50% or severe dissection. Crossover to abciximab (which occurred in 6.0% of patients) was allowed for refractory slow or no reflow or persistent peri-stent thrombosis. Clinical follow-up continued for one year. Routine angiographic follow-up at seven months was prespecified in a subset of 900 eligible patients.
Angiographic analysis.
Core laboratory analyses were performed as previously described by technicians blind to clinical outcomes (20). Antegrade blood flow in the infarct vessel was evaluated using the TIMI scale (21). Left ventricular ejection fraction (LVEF) was calculated by the area-length method (22) and regional wall motion was determined by the centerline chord method (23).
Myocardial blush was not prespecified during the initial analysis, as this concept originated after the CADILLAC protocol was formalized. Therefore, after the initial angiographic analysis and return of the films to their original institutions, a voluntary recall of all 2,082 films was performed to evaluate myocardial perfusion at the angiographic core laboratory of the Cardiovascular Research Foundation. All angiograms were analyzed by a single observer (C.O.C.) and over-read for accuracy by a second physician (A.J.L. or G.W.S.) blind to clinical outcomes. The methodology for myocardial blush analysis used (derived from the original Zwolle description) (9) has been previously described and shown to have high intra- and interobserver reproducibility for prior technicians (11), and for the current reviewers (C kappa = 0.87 and 0.82 for intra- and interobserver variability, respectively). A total of 1,301 angiograms fulfilled all three of the following parameters and were considered technically adequate for blush analysis: 1) at least one view was present that isolated the myocardial infarct zone; 2) angiographic runs of sufficient duration were present to assess tissue-level perfusion (usually requiring complete filling of the coronary venous system); and 3) complete arterial opacification with backflow of contrast into the aorta was present, indicating adequate contrast filling of the epicardial coronary artery without occlusive catheter wedging.
Myocardial blush was graded in the distribution of the infarct artery as previously described (9,11), based on the maximal densitometric degree of contrast opacification: MBG-0/1 = no or minimal myocardial contrast opacification; MBG-2 = moderate contrast opacification but less than in either an ipsilateral or contralateral non-infarct artery; and MBG-3, normal myocardial blush or contrast opacification, comparable with the other coronary arteries. When myocardial blush persisted ("staining"), MBG-0 was assigned.
Data management and statistical analysis.
Study monitors verified 100% of case report form data, and all primary end point events were adjudicated by an independent committee blind to randomization. The primary end point was a composite of death, reinfarction, ischemic-driven target vessel revascularization, or disabling stroke.
Categorical data were compared using the Fisher exact test for pairwise comparisons and the chi-square test for three-way comparisons. Continuous variables are presented as median with interquartile ranges and were compared by the Kruskal-Wallis test. Time-to-event data are summarized and displayed as Kaplan-Meier estimates and compared with the log-rank test. Stepwise logistic regression analysis selecting baseline variables with an entry/stay criterion of p < 0.10 was employed to determine the independent predictors of normal myocardial blush post-PCI. Cox proportional hazards regression was used to identify independent correlates of one-year mortality. Variables entered into the model included age (as a continuous variable), gender, body mass index (as a continuous variable), diabetes, hypertension, prior AMI or bypass surgery, Killip class, infarct-artery, triple-vessel disease, time to reperfusion (as a continuous variable), baseline and final TIMI flow grades, final MBG, stent implantation, and abciximab use. As baseline left ventriculography was performed in only 79% of patients, LVEF was not included in the main multivariate modeling. Left ventricular ejection fraction was, however, included in secondary multivariate models and the results were reported separately.
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Results
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Frequency and correlates of myocardial blush after primary angioplasty.
Of the 2,082 randomized patients, the index angiograms from 1,500 patients (72%) were returned for reanalysis. Compared with patients whose films were not returned for reanalysis, patients whose films were returned were slightly older and presented 18 min later; baseline characteristics, device randomization, and clinical outcomes were otherwise similar (Table 1). Of the 1,500 films resubmitted for reanalysis, 1,301 (87%) were technically suitable for MBG determination; these made up the current study population.
At baseline, epicardial TIMI flow grade 3 was present in 21.8% of infarct vessels, whereas normal myocardial perfusion (MBG-3) was seen in only 1.2% of patients (p < 0.0001) (Fig. 1). Post-PCI, TIMI flow grade 3 was restored in 96.1% of patients, compared with normal blush in only 17.4% of patients (p < 0.0001) (Fig. 1). TIMI flow grade 3 was present in 100% of patients with normal (MBG-3) myocardial perfusion, in 99.3% with reduced (MBG-2) perfusion, and in 92.7% of patients with absent (MBG-0/1) perfusion (p < 0.0001).
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Figure 1 Baseline and final Thrombolysis In Myocardial Infarction (TIMI) flow rates (left) and myocardial blush grades (right) in 1,301 patients. Black bars = grade 0/1; hatched bars = grade 2; white bars = grade 3. PCI = percutaneous coronary intervention.
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As seen in Table 2, normal myocardial blush post-PCI was achieved slightly more frequently in women and current smokers, and when the infarct vessel was the right coronary artery (RCA). In contrast, absent myocardial blush post-PCI was more common in diabetics, when the infarct artery was the left anterior descending artery (LAD), with lower baseline LVEF, and when pre-PCI TIMI flow grade 3 was not present. Final MBG-3 condition was achieved in 6.1%, 13.2%, and 27.6% of patients when the infarct vessel was the LAD, left circumflex artery, and RCA, respectively (p < 0.0001). Final MBG was unrelated to procedural parameters such as implantation pressure, balloon size, or final luminal dimensions achieved (Table 3). Final MBG-3 condition was achieved in 19.9%, 17.3%, and 15.1% of patients with symptom onset to balloon times of <3 h,  3 h,  6 h, and >6 h (chi-square p value for trend = 0.26). By multivariate analysis, LAD infarct-related artery was the only independent predictor of MBG <3 (hazard ratio = 5.0 [95% confidence interval 3.2 to 7.7], p < 0.001).
Implications of myocardial perfusion status after primary angioplasty.
Mortality at both 30 days and 1 year strongly correlated with final MBG (Table 4, Fig. 2). Survival was greatest with normal blush, intermediate with reduced blush, and least with absent blush. Among the 96.1% of patients in whom TIMI flow grade 3 was restored, MBG was normal in 18.1%, reduced in 35.1%, and absent in 46.8%. As seen in Figure 2, normal, reduced, and absent myocardial perfusion grades separated patients with post-PCI TIMI flow grade 3 into three distinct strata with one-year mortality rates of 1.4%, 3.9%, and 5.7%, respectively (p = 0.02). Myocardial blush grade was statistically unrelated to subsequent rates of reinfarction, clinical or angiographic restenosis, and myocardial recovery, though infarct artery reocclusion tended to be increased with absent versus present blush (Table 4).
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Figure 2 Cumulative survival according to final myocardial blush grade (MBG) in all patients (upper graph) and in those with post-procedure Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 (lower graph). PCI = percutaneous coronary intervention.
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As shown in Figure 3, MBG <3 was an independent multivariate predictor of late mortality (hazard ratio = 2.70 [95% confidence interval 1.06 to 6.86], p = 0.037). However, when index LVEF was included in the model (reduced in size to 989 patients to account for missing values), the hazard ratio for MBG <3 as a predictor of mortality decreased from 2.70 to 1.55, which was no longer significant (p = 0.42).
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Figure 3 Multivariate predictors of one-year mortality. CI = confidence interval; HR = hazard ratio; TIMI = Thrombolysis In Myocardial Infarction.
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Myocardial blush and mortality as a function of drug and device assignment.
As seen in Figure 4, myocardial perfusion status postintervention was similar in patients randomized to balloon angioplasty (n = 328), angioplasty + abciximab (n = 323), stenting alone (n = 320), or stenting + abciximab (n = 330). Final MBG was also independent of the use of stents or abciximab by treatment-received analysis (Table 3). Mortality at one year occurred in similar proportions of patients randomized to stenting versus angioplasty (4.5% vs. 4.8%, p = 0.91), and abciximab versus no abciximab (4.3% vs. 5.0%, p = 0.63).
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Figure 4 Incidence of final myocardial blush grade by randomized treatment strategy. Black bars = balloon angioplasty; bars with horizontal lines = angioplasty + abciximab; white bars = stent; bars with diagonal lines = stent + abciximab.
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Discussion
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The principal findings of this report, the largest analysis to date examining the implications of myocardial perfusion status after reperfusion in AMI, are that: 1) despite achievement of TIMI flow grade 3 in >96% of patients after primary PCI, normalized myocardial perfusion, as assessed by the MBG, was present in <20% of patients; 2) patients with AMI involving the LAD, and those with depressed baseline left ventricular function, are particularly unlikely to have normal myocardial perfusion restored after primary PCI; 3) abnormal myocardial perfusion post-PCI is a powerful correlate of early and late mortality, even in patients with TIMI flow grade 3; and 4) normal myocardial perfusion is restored in a similar proportion of patients after balloon angioplasty and stenting, with no incremental benefit present from adjunctive GP IIb/IIIa inhibition, underlying the similar early and late mortality after mechanical reperfusion with the four strategies evaluated in the CADILLAC trial.
The data from this large, prospective multicenter controlled trial confirm and validate previous retrospective and single center reports demonstrating that a significant proportion of patients with normal epicardial coronary flow after primary PCI have diminished tissue-level perfusion in the myocardial regions subtended by the infarct vessel. In the present series of 1,301 patients, despite achievement of TIMI flow grade 3 in >96% of infarct vessels, normal myocardial perfusion was restored in only 17.4% of patients, compared to 19% to 39% of patients in four earlier studies using a similar maximal contrast-based methodology to score blush (9,11,12,16). Conversely, absent myocardial perfusion was present in 48.7% of patients in the present study, compared to 29% to 40% in earlier reports (9,11,12,16). Whether the slightly lower rates of effective myocardial perfusion in the present study are due to patient selection or subtle differences in core lab methodology is uncertain. Nonetheless, it is clear that the majority of patients do not achieve normal tissue-level perfusion after primary PCI for AMI.
The infarct vessel was by far the most important determinate of post-PCI myocardial perfusion status. By multivariate analysis, normal blush was five times less likely to be obtained after primary PCI of the LAD, and was most often present after RCA intervention. Electrocardiographic ST-segment resolution is also less likely after primary PCI in anterior infarction (8,24). The likelihood of restoring normal myocardial blush after primary PCI also directly correlated with the baseline LVEF, which has not been considered in prior reports (9,11,12,16). Moreover, abnormal blush post-PCI was no longer significantly predictive of late mortality when baseline LVEF was added to the predictive model. Thus, although the mechanisms underlying reduced reperfusion success in patients with anterior MI and abnormal systolic function are unknown, reduced index LVEF, LAD involvement, and post-PCI MBG <3 are important covariates; larger studies are required to determine the degree to which abnormal blush contributes to mortality independent from these other risk factors. Conversely, in addition to the amount of myocardium at risk, the inability to restore normal microcirculatory blood flow after primary PCI may contribute to the poor prognosis of patients with reduced LVEF and anterior infarction.
Although survival is lowest in patients not achieving TIMI flow grade 3 after primary PCI (regardless of blush score) (9,11), the MBG grade is capable of stratifying patients with TIMI flow grade 3 into different long-term risk categories. Some (12,15,16) but not all (11) prior studies have suggested that the post-PCI prognosis of patients with MBG-3 and MBG-2 are similar, implying the critical distinction is the restoration of an "open" versus a "closed" microcirculation. In contrast, in the present larger study, three distinct strata of risk were identified, with the prognosis of patients with MBG-2 intermediate between MBG-3 and MBG-0/1. This is more than an academic observation. If the goal were merely to restore an open microcirculation, this criterion would have been met in 50% to 70% of patients in prior studies (9,12,16). Conversely, the current study suggests that as many as 83% of patients are not achieving optimal reperfusion after primary PCI. Indeed, in the present study the prognosis of patients with MBG-2 flow was closer to that of patients with MBG-0/1 than MBG-3 flow. Even in patients achieving TIMI flow grade 3, those with MBG-2 and MBG-0/1 flow had one-year rates of mortality threefold and fourfold higher, respectively, than those in whom normal tissue-level perfusion was restored. These data suggest that measures capable of enhancing myocardial perfusion after mechanical reperfusion therapy might improve survival in a significant proportion of patients.
In this regard, the CADILLAC trial offered the unique opportunity to assess the relative capability of four contemporary mechanical reperfusion strategies to optimize myocardial perfusion and thereby potentially enhance survival in AMI. Whereas stent implantation undoubtedly reduces restenosis and infarct-artery reocclusion compared to balloon angioplasty (4,19), initial concerns arose regarding increased rates of distal embolization after stenting, resulting in diminished microcirculatory perfusion and possibly increased mortality (4,25). Conversely, GP IIb/IIIa inhibitors may enhance myocardial perfusion when administered with thrombolysis (26), and improved tissue-level perfusion in a single small primary PCI study (27). In the present large randomized trial, however, comparing balloon angioplasty ± abciximab to stenting ± abciximab, the restoration of normal myocardial perfusion was nearly identical among the four groups, a finding that underlies the observation that one-year mortality was independent of treatment strategy in the current substudy as well as in the entire randomized cohort (28). These data provide reassurance that stenting does not mechanistically or clinically impair (nor enhance) survival compared to balloon angioplasty. Moreover, abciximab, when administered minutes before primary PCI, would not be expected to have an effect on mortality on the basis of enhanced tissue-level perfusion.
Of note, post-PCI myocardial perfusion status had no significant impact on global and regional myocardial recovery at seven months, in contrast to an earlier smaller study in which convalescent six-month ventricular function was measured with echocardiography (12). These data confirm and extend the "open-artery hypothesis" previously restricted to epicardial vessel patency (29): that the benefits of an intact microcirculation after reperfusion therapy on prolonging survival accrue independently of myocardial salvage.
Study limitations.
First, as the concept of blush had not been developed during the formulation of the CADILLAC trial, the current analysis was not prespecified. However, the angiographic techniques prespecified for the original protocol were similar to those required for blush analysis. As 72% of films were returned for blush analysis, and the baseline features and outcomes of patients with and without blush were roughly comparable, this analysis may be considered representative of the entire population. Moreover, the current study is the largest and only multicenter analysis of the predictors and prognostic implications of blush after primary PCI using contemporary techniques, and the only such study using data collected from a carefully controlled, randomized trial employing blinded core labs and clinical event adjudication committees. Second, the visually assessed densitometric evaluation of MBG is subjective, though the current and prior studies have reported very good intra- and interobserver variability (9,11,15). A computerized videodensitometric technique using background subtraction for blush determination has been validated, but requires sophisticated methodology and is not widely applicable (30). Third, the relative prognostic impact of MBG in relation to other markers of reperfusion success, such as ST-segment resolution, was not directly addressed in this investigation, but deserves further study. In this regard, some prior trials have found independent and non-overlapping prognostic utility of both MBG and ST-segment resolution (12,16). Finally, these data apply only to the study population; specifically, MBG may have greater prognostic utility in patients with cardiogenic shock (11), a group that was excluded from the current study.
Clinical implications.
Despite high rates of normal antegrade epicardial flow, adequate tissue-level perfusion is restored in a minority of patients after primary PCI, a finding that has prognostic utility in risk-stratifying patients for subsequent mortality. In concert with earlier studies, the present investigation suggests that achievement of TIMI-3 flow, though still a necessary component, is no longer sufficient to define an optimal result of primary PCI or fibrinolytic therapy (17); restoration of normal tissue-level perfusion is also required. The causes of reduced microcirculatory perfusion after reperfusion therapy are multifactorial and include distal thromboemboli, vasoconstriction, interstitial edema, capillary leak syndrome, and possibly reperfusion injury, among others. Additional studies are required to determine whether modalities that acutely improve myocardial reperfusion success rates are able to further enhance survival after primary PCI. In this regard, small studies have shown promise for adjunctive thrombectomy and distal vascular protection devices (25), the proof of which awaits the completion of adequately powered randomized trials.
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Relationship Between Collateral Circulation and Successful Myocardial Reperfusion in Acute Myocardial Infarction: A Subanalysis of the PREMIAR Trial
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October 1, 2008;
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S. J. Brener, D. J. Moliterno, P. E. Aylward, A. W.J. van't Hof, W. Ruzyllo, W. W. O'Neill, C. W. Hamm, C. M. Westerhout, C. B. Granger, P. W. Armstrong, et al.
Reperfusion after primary angioplasty for ST-elevation myocardial infarction: predictors of success and relationship to clinical outcomes in the APEX-AMI Angiographic Study
Eur. Heart J.,
May 1, 2008;
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L. Galiuto, B. Garramone, A. Scara, A. G. Rebuzzi, F. Crea, G. La Torre, S. Funaro, M. Madonna, F. Fedele, L. Agati, et al.
The extent of microvascular damage during myocardial contrast echocardiography is superior to other known indexes of post-infarct reperfusion in predicting left ventricular remodeling: results of the multicenter AMICI study.
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A. Sato, M. Hiroe, T. Nozato, H. Hikita, Y. Ito, H. Ohigashi, M. Tamura, A. Takahashi, M. Isobe, and K. Aonuma
Early validation study of 64-slice multidetector computed tomography for the assessment of myocardial viability and the prediction of left ventricular remodelling after acute myocardial infarction
Eur. Heart J.,
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P. Sorajja, B. J. Gersh, D. A. Cox, M. G. McLaughlin, P. Zimetbaum, C. Costantini, T. Stuckey, J. E. Tcheng, R. Mehran, A. J. Lansky, et al.
Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction
Eur. Heart J.,
July 2, 2007;
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[Abstract]
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F. Fernandez-Aviles, J. J. Alonso, G. Pena, J. Blanco, J. Alonso-Briales, J. Lopez-Mesa, F. Fernandez-Vazquez, J. Moreu, R. A. Hernandez, A. Castro-Beiras, et al.
Primary angioplasty vs. early routine post-fibrinolysis angioplasty for acute myocardial infarction with ST-segment elevation: the GRACIA-2 non-inferiority, randomized, controlled trial
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B. C. Carey and J. C. Blankenship
A Sequential Approach to the Management of a Massive Intracoronary Thrombus in ST Elevation Myocardial Infarction: A Case Report
Angiology,
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J. A. Bittl
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Prognostic Implications of Creatine Kinase Elevation After Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction
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A Prasad and B J Gersh
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Heart,
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A. Prasad, G. W. Stone, T. D. Stuckey, C. O. Costantini, P. J. Zimetbaum, M. McLaughlin, R. Mehran, E. Garcia, J. E. Tcheng, D. A. Cox, et al.
Impact of diabetes mellitus on myocardial perfusion after primary angioplasty in patients with acute myocardial infarction
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Abstract
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