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J Am Coll Cardiol, 2003; 42:1173-1177, doi:10.1016/S0735-1097(03)00920-3
© 2003 by the American College of Cardiology Foundation
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ACUTE MYOCARDIAL INFARCTION

The incidence, predictors, and outcomes of early reinfarction after primary angioplasty for acute myocardial infarction

Steven J. Kernis, MD*, Kishore J. Harjai, MD, FACC*, Gregg W. Stone, MD, FACC{dagger}, Lorelei L. Grines, PhD*, Judith A. Boura, MS*, Michael W. Yerkey, MD*, William O’Neill, MD, FACC* and Cindy L. Grines, MD, FACC*,*

* Cardiology Division, William Beaumont Hospital, Royal Oak, Michigan, USA
{dagger} Cardiology Division, Lenox Hill Hospital, New York, New York, USA

Manuscript received March 5, 2003; revised manuscript received May 14, 2003, accepted May 21, 2003.

* Reprint requests and correspondence: Dr. Cindy L. Grines, Division of Cardiovascular Medicine, William Beaumont Hospital, 3601 West 13 Mile Road, Royal Oak, Michigan 48073-6769, USA.
cgrines{at}beaumont.edu


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
OBJECTIVES: We sought to identify the incidence, predictors, and clinical consequences of one-month reinfarction (RE-MI) in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI).

BACKGROUND: One-month reinfarction after AMI significantly increases long-term mortality; however, little is known about the incidence and predictors of RE-MI in patients undergoing primary angioplasty.

METHODS: We analyzed data from 3,646 patients who underwent primary PCI in the Primary Angioplasty in Acute Myocardial Infarction (PAMI) studies. We studied the incidence, correlates, and clinical outcomes of 30-day RE-MI.

RESULTS: Reinfarction within one month of index hospitalization occurred in 77 (2.1%) of patients. In multivariate analysis, admission Killip class >1 (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.09 to 3.76), left ventricular ejection fraction <50% (OR 2.49, 95% CI 1.30 to 4.74), final coronary stenosis >30% (OR 2.57, 95% CI 1.28 to 5.15), and presence of coronary dissection (OR 2.40, 95% CI 1.36 to 4.24) and thrombus (OR 2.36, 95% CI 1.23 to 4.53) on the final angiogram were independent correlates of RE-MI. One-month reinfarction was independently associated with death (OR 7.14, 95% CI 3.28 to 15.5) and ischemic target vessel revascularization (I-TVR) (OR 15.0, 95% CI 8.68 to 26.0) at six months.

CONCLUSIONS: We conclude that, although early RE-MI is uncommon in patients treated by primary PCI, it is a significant independent predictor of death and I-TVR at six months. Admission Killip class >1 and left ventricular systolic dysfunction were associated with higher incidence of RE-MI. Our results suggest that optimal revascularization during primary PCI may decrease RE-MI rates.

Abbreviations and Acronyms
  AMI = acute myocardial infarction
  CK = creatinine kinase
  I-TVR = ischemic target vessel revascularization
  LVEF = left ventricular ejection fraction
  PAMI = Primary Angioplasty in Acute Myocardial Infarction
  PCI = percutaneous coronary intervention
  RE-MI = reinfarction
  TIMI = Thrombolysis In Myocardial Infarction

Reinfarction (RE-MI) after acute myocardial infarction (AMI) leads to increased morbidity and mortality (1–4). Before the advent of revascularization therapy using thrombolytics or primary angioplasty, nearly one-quarter of all Q-wave myocardial infarction patients suffered RE-MI within 10 years (5). With increased use of aspirin and beta-blockers, thrombolytic therapy led to a reduction in one-year RE-MI rates by about 2% per year between 1987 and 1994 (4–10). Donges et al. (3) studied AMI patients enrolled in a large registry and found that 4.7% of patients had in-hospital RE-MI and that the incidence of RE-MI was lower in patients treated with percutaneous coronary intervention (PCI) compared with thrombolytics.

Little is known about RE-MI occurring early after AMI in the era of primary angioplasty. Because primary angioplasty is associated with better Thrombolysis In Myocardial Infarction (TIMI) flow in the infarct-related artery, the incidence of RE-MI is expected to be lower than that noted historically in thrombolytic studies. More recently, Keeley et al. (11) performed a pooled analysis of 23 randomized trials of PCI versus thrombolytics and found a significant decrease in RE-MI with PCI. We performed this analysis to study the incidence, clinical, and angiographic predictors, and clinical consequences of one-month RE-MI in patients undergoing primary angioplasty.


   Methods
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 Abstract
 Methods
Results
 Discussion
 References
 
Study population.   We analyzed data available in 3,646 patients treated by primary PCI in seven Primary Angioplasty in Acute Myocardial Infarction (PAMI) studies, including PAMI-1 (12), PAMI-2 (13), Stent PAMI (14), Local PAMI (15), Stent Pilot (10), PAMI No Surgery on Site, and Air PAMI (16) (Table 1).


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  		Table 1 PAMI Database

 
PAMI study protocol.   All patients enrolled presented within 12 h of onset of chest pain and electrocardiographic changes (ST elevation in two contiguous leads or left bundle branch block). The trials excluded patients presenting with cardiogenic shock, high bleeding risk, and those who did not give informed consent. The protocols of all seven studies were previously published. In brief, it was recommended that patients receive 325-mg chewable aspirin, a 5,000- to 10,000-U bolus of heparin, intravenous beta-adrenergic blockers, and nitroglycerin. Patients were taken emergently to the cath lab for coronary angiography and possible intervention. Those patients deemed unlikely to benefit from primary PCI (infarct-related artery with ≤70% stenosis or supplying a small area of myocardium) were treated medically without mechanical intervention. Patients found to have unprotected left main stenosis >60% or severe proximal three-vessel disease and spontaneous reperfusion were referred for coronary artery bypass grafting. In the absence of these contraindications, patients underwent PCI. Patients undergoing PCI were given heparin to achieve an activated clotting time between 350 and 400 s. Study monitors recorded six-month follow-up events.

Study outcome.   Reinfarction was defined as recurrence of clinical symptoms (or new electrocardiographic changes) and new elevation of creatine kinase (CK) or CK-MB within 30 days after hospital admission. We compared baseline clinical and angiographic characteristics of both groups and assessed independent correlates of RE-MI. Further, we evaluated the independent impact of RE-MI on six-month ischemic target revascularization (I-TVR) and six-month mortality.

Statistics.   Statistical analyses were completed on the categorical variables using a chi-square test or a Fisher exact test as appropriate. If the frequency of any cell was <5, then a Fisher exact test was used. The continuous variables were analyzed using a Wilcoxon rank test. Kaplan-Meier analysis was used to create survival curves for the cumulative incidence of death during six-month follow-up for RE-MI and no RE-MI patients. Log-rank p test was used to compare survival curves between RE-MI and no RE-MI groups. We did multivariate logistic regression to determine independent correlates of RE-MI. Clinical and angiographic variables that showed a univariate relation (p < 0.10) with RE-MI were included in the multivariate analysis. Step-down logistic regression was performed, dropping the least significant variable at each step, until only variables with a p value of <0.05 remained. To determine the independent correlation of RE-MI with death and I-TVR at six months, we completed similar multivariate analyses. Clinical and angiographic differences between study groups were used as potential covariates in both models.


   Results
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 Abstract
 Methods
 Results
Discussion
 References
 
Incidence of RE-MI.   Of 3,646 study patients, 77 (2.1%) suffered one-month RE-MI. The cumulative incidence of RE-MI within the first 30 days is shown in Figure 1.



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  		Figure 1 Reinfarction at 30 days.

 
Baseline characteristics.   Clinical and angiographic differences between no RE-MI and RE-MI groups are shown in Tables 2 and 3. Reinfarction patients had higher Killip class at presentation and were less likely to be smokers; RE-MI patients had lower TIMI 3 flow before and after PCI, lower left ventricular ejection fraction (LVEF), higher percent stenosis pre-PCI and post-PCI, higher rate of intracoronary thrombus and coronary dissection on the final angiogram, and lower PCI success.


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  		Table 2 Baseline Clinical Characteristics of Patients With and Without RE-MI

 

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  		Table 3 Angiographic Characteristics

 
Independent correlates of RE-MI.   In multivariate analysis, the following variables remained significant independent correlates of RE-MI: admission Killip class >1 (odds ratio [OR] 2.02, 95% confidence interval [CI] 1.09 to 3.76), LVEF <50% (OR 2.49, 95% CI 1.30 to 4.74), final coronary artery stenosis >30% (OR 2.57, 95% CI 1.28 to 5.15), coronary dissection on the final angiogram (OR 2.40, 95% CI 1.36 to 4.24), and intracoronary thrombus on the final angiogram (OR 2.36, 95% CI 1.23 to 4.53) (Fig. 2). The percent of patients suffering RE-MI increases significantly with an increasing number of independent risk factors. Patients with zero risk factors had a one-month RE-MI rate of 0.6% compared with a 22% incidence in those with four risk factors.



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  		Figure 2 Multivariate correlates of reinfarction (Re-MI).

 
The relation of RE-MI with six-month clinical outcomes.   Of the patients who had RE-MI, 16% died at six months compared with 3% of those without RE-MI (p < 0.0001). Similarly, I-TVR during six-month follow-up was performed in 54% of RE-MI patients and 9.1% of patients without RE-MI (p < 0.0001) (Fig. 3). Cumulative survival of patients with RE-MI was significantly worse than patients without RE-MI (p < 0.0001) (Fig. 4). Step-down, multivariate, logistic regression analysis revealed that RE-MI was a significant independent predictor of both six-month I-TVR (OR 15.0, 95% CI 8.68 to 26.0) and death (OR 7.14, 95% CI 3.28 to 15.5).



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  		Figure 3 Six-month clinical outcomes. ReMI = reinfarction; TVR = target vessel revascularization.

 


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  		Figure 4 Mortality at six-months. ReMI = reinfarction.

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
Early reinfarction after an AMI treated with primary PCI is relatively uncommon. In our analysis, 2.1% of patients suffered one-month RE-MI. This incidence is lower than that reported in the several large, randomized AMI thrombolytic trials in the last 20 years, with in-hospital RE-MI rates ranging from 2.5% to 4.3% (1,8,17), and one-month RE-MI rate of 3.4% (18). Our incidence is also lower than that seen in previous studies that included patients revascularized by primary angioplasty. In Global Utilization of Streptokinase and Tissue Plasminogen Activator in Occluded Arteries (GUSTO) IIb, 30 day RE-MI occurred in 4.5% of patients (19). A meta-analysis of 23 randomized trials conducted by Keeley et al. (11) reported that RE-MI occurred in 3% of patients undergoing primary angioplasty. Although our trial did not address a direct comparison of PCI versus thrombolysis, prior literature has shown that RE-MI occurs less frequently with primary PCI than it does with thrombolytics (19). We found that most cases of RE-MI occurred within four days of hospital admission.

Our study identified several independent determinants of RE-MI (Fig. 1). Admission Killip class >1, LVEF <50%, final coronary stenosis >30%, post-PCI coronary dissection, and post-PCI intracoronary thrombus were significant predictors of one-month RE-MI. Unlike previous trials (1,3–5,8,9,20), admission Killip class >1 was the only clinical characteristic that identified patients at higher risk of RE-MI. Rather, angiographic variables were the predominant predictors of one-month RE-MI. This is probably because previous studies had less detailed angiographic data. The availability of such data in PAMI studies likely overwhelms the predictive ability of clinical variables. Thus, the occurrence of reinfarction is a function of poor angiographic outcomes, and is less dependent upon clinical factors identified in prior studies, such as age, gender, or a history of diabetes.

Finally, we found RE-MI to be strongly associated with increased mortality and revascularization at six months. Those suffering one-month RE-MI had more than sevenfold increased adjusted mortality at six months. Moreover, the risk of I-TVR in RE-MI patients was 15-fold higher in adjusted incidence. These findings are in accord with several trials that all show strong associations between RE-MI and death (1). This increased mortality underscores the need for identification of high-risk patients, as well as effective primary revascularization by PCI (4).

Implications.   Angiographic predictors are stronger risk factors for RE-MI than clinical factors; RE-MI may be preventable by optimal coronary revascularization and treatment of dissection and thrombus.

Summary.   Reinfarction in the era of primary PCI for AMI is rare, and less common then that reported previously. We found one clinical characteristic and several angiographic variables that are associated with higher RE-MI risk; RE-MI, although infrequent, imparts a significantly higher risk of future revascularization and death. Reinfarction may be preventable, by optimal coronary revascularization and aggressive treatment of post-PCI dissection and thrombus.

Study limitations.   This study may suffer from bias related to its retrospective analysis design. Our results cannot be extrapolated to cardiogenic shock patients, as the PAMI studies excluded these patients. Furthermore, our results may be less representative of contemporary practice, due to lower rates of glycoprotein IIb/IIIa and thienopyridine medications, and lower stent use. The majority of RE-MI cases occurred in PAMI II where balloon angioplasty without stenting was the dominant treatment modality.


   Acknowledgments
 
The authors thank the people and institutions that participated in the PAMI trials.


   References
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 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Hudson MP, Granger CB, Topol EJ, et al. Early reinfarction after fibrinolysis: experience from the global utilization of streptokinase and tissue plasminogen activator (alteplase) for occluded coronary arteries (GUSTO I) and global use of strategies to open occluded coronary arteries (GUSTO III) trials. Circulation. 2001;104:1229–1235[Abstract/Free Full Text]
  2. Marmor A, Sobel BE, Roberts R. Factors presaging early recurrent myocardial infarction ("extension"). Am J Cardiol. 1981;48:603–610[CrossRef][Medline]
  3. Donges K, Schiele R, Gitt A, et al. Incidence, determinants, and clinical course of reinfarction in-hospital after index acute myocardial infarction (results from the pooled data of the maximal individual therapy in acute myocardial infarction [MITRA], and the myocardial infarction registry [MIR]). Am J Cardiol. 2001;87:1039–1044[CrossRef][Medline]
  4. Kornowski R, Goldbourt U, Zion M, et al. Predictors and long-term prognostic significance of recurrent infarction in the year after a first myocardial infarction: SPRINT study group. Am J Cardiol. 1993;72:883–888[CrossRef][Medline]
  5. Berger CJ, Murabito JM, Evans JC, Anderson KM, Levy D. Prognosis after first myocardial infarction: comparison of Q-wave and non–Q-wave myocardial infarction in the Framingham Heart study. JAMA. 1992;268:1545–1551[Abstract]
  6. Rosamond WD, Chambless LE, Folsom AR, et al. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med. 1998;339:861–867[Abstract/Free Full Text]
  7. Gilpin E, Ricou F, Dittrich H, Nicod P, Henning H, Ross J Jr. Factors associated with recurrent myocardial infarction within one year after acute myocardial infarction. Am Heart J. 1991;121:457–465[CrossRef][Medline]
  8. Volpi A, de Vita C, Franzosi MG, et al. Predictors of nonfatal reinfarction in survivors of myocardial infarction after thrombolysis: results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI-2) data base. J Am Coll Cardiol. 1994;24:608–615[Abstract]
  9. Dwyer EM Jr., McMaster P, Greenberg H. Nonfatal cardiac events and recurrent infarction in the year after acute myocardial infarction. J Am Coll Cardiol. 1984;4:695–702[Abstract]
  10. Stone GW, Brodie BR, Griffin JJ, et al. Prospective, multicenter study of the safety and feasibility of primary stenting in acute myocardial infarction: in-hospital and 30-day results of the PAMI stent pilot trial: Primary Angioplasty in Myocardial Infarction Stent Pilot trial investigators. J Am Coll Cardiol. 1998;31:23–30[Abstract/Free Full Text]
  11. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361:13–20[CrossRef][Medline]
  12. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction: the Primary Angioplasty in Myocardial Infarction study group. N Engl J Med. 1993;328:673–679[Abstract/Free Full Text]
  13. Stone GW, Marsalese D, Brodie BR, et al. A prospective, randomized evaluation of prophylactic intraaortic balloon counterpulsation in high risk patients with acute myocardial infarction treated with primary angioplasty: Second Primary Angioplasty in Myocardial Infarction (PAMI-II) trial investigators. J Am Coll Cardiol. 1997;29:1459–1467[Abstract]
  14. Grines CL, Cox DA, Stone GW, et al. Coronary angioplasty with or without stent implantation for acute myocardial infarction: Stent Primary Angioplasty in Myocardial Infarction study group. N Engl J Med. 1999;341:1949–1956[Abstract/Free Full Text]
  15. Esente P, Kaplan AV, Ford JK, et al. Local intramural heparin delivery during primary angioplasty for acute myocardial infarction: results of the Local PAMI pilot study. Catheter Cardiovasc Intervent. 1999;47:237–242[CrossRef][Medline]
  16. Grines CL, Westerhausen DR, Jr., Grines LL, et al. A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: the Air Primary Angioplasty in Myocardial Infarction study. J Am Coll Cardiol 2003. In Press
  17. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Lancet. 1990;336:65–71[Medline]
  18. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acute myocardial infarction. Lancet. 1992;339:753–770[Medline]
  19. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med. 1997;336:1621–1628[Abstract/Free Full Text]
  20. Birnbaum Y, Herz I, Sclarovsky S, et al. Admission clinical and electrocardiographic characteristics predicting an increased risk for early reinfarction after thrombolytic therapy. Am Heart J. 1998;135:805–812[CrossRef][Medline]



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