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(Circulation. 2004;109:958-961.)
© 2004 American Heart Association, Inc.

Brief Rapid Communications

Impaired Myocardial Perfusion Is a Major Explanation of the Poor Outcome Observed in Patients Undergoing Primary Angioplasty for ST-Segment–Elevation Myocardial Infarction and Signs of Heart Failure

Giuseppe De Luca, MD; Arnoud W.J. van’t Hof, MD; Menko-Jan de Boer, MD; Jan C.A. Hoorntje, MD; A.T. Marcel Gosselink, MD; Jan-Henk E. Dambrink, MD; Jan Paul Ottervanger, MD; Felix Zijlstra, MD; Harry Suryapranata, MD

From the Department of Cardiology, ISALA Klinieken, De Weezenlanden Hospital, Zwolle, The Netherlands.

Correspondence to Dr Harry Suryapranata, ISALA Klinieken, De Weezenlanden Hospital, Department of Cardiology, Groot Wezeland 20, 8011 JW Zwolle, The Netherlands. E-mail h.suryapranata{at}diagram-zwolle.nl

Received November 2, 2003; revision received November 24, 2003; accepted January 14, 2004.

	Abstract

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Background— The aim of the present study was to investigate the prognostic implication of myocardial perfusion in patients with ST-segment–elevation myocardial infarction (STEMI) and signs of heart failure, treated with primary angioplasty.

Methods and Results— Our population is represented by 1548 consecutive patients undergoing primary angioplasty for STEMI. Congestive heart failure was defined as Killip class >1 at admission. Killip class was linearly associated with myocardial perfusion, enzymatic infarct size, predischarge ejection fraction, and 1-year mortality rate. Myocardial blush was an independent predictor of 1-year mortality (RR [95% CI]=2.92 [1.37 to 6.23], P=0.005) in patients with advanced Killip class at presentation.

Conclusions— Our study shows that patients with heart failure complicating STEMI have impaired myocardial perfusion, which accounts for the poor outcome observed in these patients. Further efforts should be aimed at improving myocardial perfusion, beyond epicardial recanalization, to further improve the outcome of these high-risk patients.

Key Words: angioplasty • heart failure • perfusion

	Introduction

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The benefits of primary angioplasty in patients with ST-segment–elevation myocardial infarction (STEMI) have been demonstrated in randomized trials.¹ However, the outcome in patients with STEMI and heart failure at presentation remains poor, particularly in those with cardiogenic shock.^2–6

The aim of the present study was to investigate the implication of myocardial perfusion on outcome in patients with STEMI and signs of heart failure, treated with primary angioplasty.

	Methods

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From April 1997 to October 2001, 1548 consecutive patients with STEMI underwent primary angioplasty at our institution. The institutional review board approved our study, and all patients gave informed consent. Congestive heart failure was defined as Killip class >1 at admission.⁷ Angiograms were analyzed by an independent core laboratory (DIAGRAM, Zwolle, the Netherlands).^8,9 Angiographic success was defined as postprocedural TIMI 3 flow and a residual stenosis <50%. Myocardial blush grade (MBG) and enzymatic infarct size were evaluated, as previously described.⁸ Distal embolization was defined as an abrupt "cutoff" in one of the coronary branches of the infarct-related artery, distal to the angioplasty site.¹⁰ Intra-aortic balloon pump (IABP) was routinely used in patients with severe multivessel disease and/or proximal left anterior descending artery occlusion, left main stenosis, or patients at higher risk for reocclusion, independent of the grade of Killip class at presentation.

Continuous data were expressed as median and interquartile ranges and categorical data as percentages. ANOVA and the ² test were appropriately used for continuous and categorical variables, respectively. Multivariate analysis was performed by use of the Cox proportional hazard method to identify independent predictors of 1-year mortality in patients with heart failure at presentation.

	Results

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Demographic, clinical, and angiographic characteristics according to Killip class at presentation are reported in Table 1. Patients with Killip class >1 were older, with higher prevalence of female gender, anterior myocardial infarction, and multivessel disease. A higher prevalence of distal embolization was observed in patients with advanced Killip class. Killip class was linearly associated with the rate of MBG 2 to 3, angiographic success, and, consequently, with enzymatic infarct size, predischarge ejection fraction, and 1-year mortality rates (Table 1 and Figure 1).

View this table: [in this window] [in a new window]   TABLE 1. Demographic, Clinical, and Angiographic Characteristics According to Killip Class at Presentation

View larger version (19K): [in this window] [in a new window]   Figure 1. Relation between Killip class at admission, myocardial blush, the rate of distal embolization (available in 1111 patients), and 1-year mortality rates.

The prognostic implication of myocardial perfusion beyond optimal epicardial recanalization in patients with heart failure at presentation is shown in Figure 2. In fact, in the analysis restricted to patients with optimal epicardial recanalization (TIMI 3 flow and residual stenosis <50%), myocardial perfusion significantly affected 1-year mortality rates (RR [95% CI]=2.54 [1.01 to 6.68], P=0.049). As reported in Table 2, at multivariate analysis restricted to patients with heart failure at presentation, MBG 0 to 1 was found to be an independent predictor of 1-year mortality rates (RR [95% CI]=2.92 [1.37 to 6.23], P=0.005).

View larger version (14K): [in this window] [in a new window]   Figure 2. Graph shows additional prognostic role of myocardial perfusion in patients with heart failure at presentation and angiographic success.

View this table: [in this window] [in a new window]   TABLE 2. Predictors of 1-Year Mortality Rates at Multivariate Analysis in Patients With Advanced Killip Class (>1)

	Discussion

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The main finding of the present study is that among patients with STEMI undergoing primary angioplasty, poor myocardial perfusion is a major explanation of poor outcome observed in patients with heart failure at presentation. The Killip classification still represents a simple and accurate tool for early risk stratification of patients with STEMI.⁷

Despite the significant improvement in survival of patients undergoing primary angioplasty, the mortality rate in patients with heart failure at presentation remains disappointingly high, particularly in those with cardiogenic shock.^2–6

Data from registry studies have shown that in patients with Killip class II and III⁴ or cardiogenic shock,² mechanical revascularization was associated with a significantly better survival in comparison with a less aggressive strategy. The role of adjunctive IABP in these high-risk patients remains controversial,³ with benefits observed mainly in patients treated with thrombolysis and not in those treated with primary angioplasty. Thus, IABP may potentially play an important role in terms of coronary flow and perfusion, mainly in the presence of residual stenosis (after thrombolysis), and less after mechanical recanalization. This finding has been confirmed in our previous report.¹¹ Furthermore, there are no data available on the impact of IABP on MBG, whereas the potential role of other ventricular assist devices has yet to be investigated.¹²

A major explanation of the poor outcome observed in patients with more advanced Killip class is the linear association found in our study between myocardial perfusion and the degree of heart failure at presentation. A linear association between Killip class and postprocedural TIMI 3 flow was also observed in the Shock Trial Registry.² As shown by our previous report,⁸ an optimal myocardial reperfusion beyond optimal epicardial flow is required to further improve clinical outcome, particularly in high-risk patients. In our study, among patients with heart failure at presentation and angiographic success, optimal myocardial perfusion (MBG 2 to 3) significantly affected 1-year mortality rates. Several factors may explain our results. In patients with heart failure at presentation, a larger infarction may be associated with more severe damage of microcirculation, and thus impaired perfusion. On the other hand, the larger infarct size shown by our study may be a consequence of impaired perfusion. Several factors may be regarded as being responsible for impaired myocardial perfusion after primary angioplasty. For several years, microvascular reperfusion damage has been regarded as the main determinant of the no-reflow phenomenon.¹³ Several additional pharmacological therapies have been studied to reduce the ischemia-reperfusion injury. Previous reports showed significant benefits from intracoronary administration of adenosine or verapamil in reducing microvascular reperfusion damage and infarct size and improving outcome.^14,15 Recent interests have been focused on nitric oxide synthase inhibitors.¹⁶ Results of a randomized trial¹⁷ showed that inhibition of the complement cascade at the level of C5, which may determine a reduction in iNOS response to ischemia and reperfusion, was associated with lower rates of shock and deaths in high-risk patients undergoing primary angioplasty.

In addition to microvascular reperfusion damage, mounting interests have emerged on distal embolization.^10,18 In the present study, we observed a higher rate of distal embolization in patients with advanced Killip class, which may partially explain the poor perfusion observed in these patients. Thus, adjunctive pharmacological or mechanical therapy should be used to protect the microcirculation from distal embolization during mechanical reperfusion, particularly in patients with signs of heart failure at presentation. Previous reports^5,6 have also found that abciximab significantly improves the outcome in patients with cardiogenic shock treated by mechanical reperfusion. A recent retrospective analysis¹⁹ has shown the feasibility and efficacy of thrombus aspiration in patients with cardiogenic shock. Larger randomized trials are needed to evaluate the potential role of abciximab and distal protection devices on mortality rates in these high-risk patients.

Limitations
Because the benefits of adjunctive glycoprotein IIb/IIIa inhibitors have only been shown recently,²⁰ less than 5% of our patients received this additional drug, and no distal protection devices were used in this series. Thus, we could not address their impact on clinical outcome in these high-risk patients. The relatively low prevalence of Killip class >1 in our study may be related to the short total ischemic time. In our daily practice, the majority of patients with STEMI undergoing primary angioplasty are in Killip class I, as previously reported in our publications.^8,9 In fact, since 1993, all patients with STEMI admitted to our hospital have been treated with primary angioplasty, and thrombolytic therapy has no longer been used. Finally, our study only included patients undergoing primary angioplasty, thus excluding patients who may have died during transportation or before angioplasty.

	Conclusions

Top Abstract Introduction Methods Results Discussion Conclusions References

 
Our study shows that patients with heart failure complicating STEMI have impaired myocardial perfusion, which accounts for the poor outcome observed in these patients. Further efforts should be aimed at improving myocardial perfusion beyond the restoration of epicardial flow to further improve the outcome of these high-risk patients.

	References

Top Abstract Introduction Methods Results Discussion Conclusions References

 

1. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomized trials. Lancet. 2003; 361: 13–20.[CrossRef][Medline] [Order article via Infotrieve]
   
2. Hochman JS, Sleeper LA, White HD, et al. SHOCK Investigators: should we emergently revascularize occluded coronaries for cardiogenic shock: one-year survival following early revascularization for cardiogenic shock. JAMA. 2001; 285: 190–192.[Abstract/Free Full Text]
   
3. Barron HV, Every NR, Parsons LS, et al. Investigators in the National Registry of Myocardial Infarction 2: the use of intra-aortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction: data from the National Registry of Myocardial Infarction 2. Am Heart J. 2001; 141: 933–939.[CrossRef][Medline] [Order article via Infotrieve]
   
4. Wu AH, Parsons L, Every NR, et al. Second National Registry of Myocardial Infarction: hospital outcomes in patients presenting with congestive heart failure complicating acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2). J Am Coll Cardiol. 2002; 40: 1389–1394.[Abstract/Free Full Text]
   
5. Chan AW, Chew DP, Bhatt DL, et al. Long-term mortality benefit with the combination of stents and abciximab for cardiogenic shock complicating acute myocardial infarction. Am J Cardiol. 2002; 89: 132–136.[CrossRef][Medline] [Order article via Infotrieve]
   
6. Antoniucci D, Valenti R, Migliorini A, et al. Abciximab therapy improves survival in patients with acute myocardial infarction complicated by early cardiogenic shock undergoing coronary artery stent implantation. Am J Cardiol. 2002; 90: 353–357.[CrossRef][Medline] [Order article via Infotrieve]
   
7. Killip T III, Kimball JT. Treatment of myocardial infarction in a coronary care unit: a two-year experience with 250 patients. Am J Cardiol. 1967; 20: 457–464.[CrossRef][Medline] [Order article via Infotrieve]
   
8. van’t Hof AW, Liem A, Suryapranata H, et al. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Circulation. 1998; 97: 2302–2306.[Abstract/Free Full Text]
   
9. Suryapranata H, van’t Hof AW, Hoorntje JC, et al. Randomized comparison of coronary stenting with balloon angioplasty in selected patients with acute myocardial infarction. Circulation. 1998; 97: 2502–2505.[Abstract/Free Full Text]
   
10. Henriques JP, Zijlstra F, Ottervanger JP, et al. Incidence and clinical significance of distal embolization during primary angioplasty for acute myocardial infarction. Eur Heart J. 2002; 23: 1112–1117.[Abstract/Free Full Text]
    
11. van’t Hof AW, Liem AL, de Boer MJ, et al. A randomized comparison of intra-aortic balloon pumping after primary coronary angioplasty in high risk patients with acute myocardial infarction. Eur Heart J. 1999; 20: 659–665.[Abstract/Free Full Text]
    
12. Lemos PA, Cummins P, Lee CH, et al. Usefulness of percutaneous left ventricular assistance to support high-risk percutaneous coronary interventions. Am J Cardiol. 2003; 91: 479–481.[CrossRef][Medline] [Order article via Infotrieve]
    
13. Eeckhout E, Kern MJ. The coronary no-reflow phenomenon: a review of mechanisms and therapies. Eur Heart J. 2001; 22: 729–739.[Free Full Text]
    
14. Taniyama Y, Ito H, Iwakura K, et al. Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. J Am Coll Cardiol. 1997; 30: 1193–1199.[Abstract]
    
15. Marzilli M, Orsini E, Marraccini P, et al. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation. 2000; 101: 2154–2159.[Abstract/Free Full Text]
    
16. Depre C, Vanoverschelde JL, Goudemant JF, et al. Protection against ischemic injury by nonvasoactive concentrations of nitric oxide synthase inhibitors in the perfused rabbit heart. Circulation. 1995; 92: 1911–1918.[Abstract/Free Full Text]
    
17. Granger CB, Mahaffey KW, Weaver WD, et al. Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to primary percutaneous coronary intervention in acute myocardial infarction: the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) Trial. Circulation. 2003; 108: 1184–1190.[Abstract/Free Full Text]
    
18. Sakuma T, Leong-Poi H, Fisher NG, et al. Further insights into the no-reflow phenomenon after primary angioplasty in acute myocardial infarction: the role of microthromboemboli. J Am Soc Echocardiogr. 2003; 16: 15–21.[CrossRef][Medline] [Order article via Infotrieve]
    
19. Taghizadeh B, Chiu JA, Papaleo R, et al. AngioJet thrombectomy and stenting for reperfusion in acute MI complicated with cardiogenic shock. Catheter Cardiovasc Interv. 2002; 57: 79–84.[CrossRef][Medline] [Order article via Infotrieve]
    
20. Montalescot G, Barragan P, Wittenberg O, et al. ADMIRAL Investigators: Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long-Term Follow-up: platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction N Engl J Med. 2001; 344: 1895–1903.[Abstract/Free Full Text]
    

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This Article Abstract Full Text (PDF) All Versions of this Article: 109/8/958    most recent 01.CIR.0000120504.31457.28v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Luca, G. Articles by Suryapranata, H. Search for Related Content PubMed PubMed Citation Articles by De Luca, G. Articles by Suryapranata, H. Related Collections Acute myocardial infarction Catheter-based coronary and valvular interventions: other