ORIGINAL ARTICLE

Acute myocardial infarction due to left main coronary artery disease: A large multicenter national registry

Marcin Sadowski1, Wojciech Gutkowski1, Agnieszka Janion-Sadowska1, Mariusz Gąsior2, Marek Gierlotka2, Marianna Janion1, 3, Lech Poloński2

1Swietokrzyskie Cardiology Center, Kielce, Poland
2Silesian Center for Heart Diseases, Zabrze, Poland
3The Jan Kochanowski University, Kielce, Poland

Address for correspondence:

Dr Marcin Sadowski, Swietokrzyskie Cardiology Center,
ul. Grunwaldzka 45, 25–736 Kielce, Poland,
tel: +48 41 367 15 80,
e-mail: emsad@o2.pl
Received: 14.10.2012
Accepted: 15.11.2012

Introduction

Since analysis of data from the CASS registry [1] critical stenosis of unprotected left main coronary artery (ULMCA) has become a classic indication for coronary artery bypass grafting (CABG) in patients with stable angina pectoris. Effective and safe percutaneous coronary intervention (PCI) in ULMCA stenosis in stable patients is technically feasible, and long-term outcomes are highly satisfactory when drug-eluting stents are used [2, 3]. Patients at particularly high risk are those with acute myocardial infarction (MI) and ULMCA as an infarct-related artery. Optimal method for coronary revascularization in this population has not been assessed in randomized studies, however observational data and registries [4] encourage the use of percutaneous coronary intervention (PCI) in these highest-risk patients.

Because of the emphasis on studying gender-related differences in the prevalence and treatment of cardiovascular disease, unfavorable clinical characteristics and suboptimal treatment of women with acute coronary syndromes have been documented in Poland [5, 6].

In the present study a unique attempt was made to assess clinical course, treatment and prognosis in men and women with MI due to critical stenosis of the left main coronary artery.

Methods

Of 121,526 patients with acute coronary syndromes consecutively hospitalized between 2003 and 2006 a group of 643 (1.9%) patients was identified in whom coronary angiography confirmed critical stenosis of ULMCA which was responsible for the development of ST-segment elevation myocardial infarction (STEMI) or non ST-segment elevation myocardial infarction (NSTEMI). The study group consisted of 184 (28.6%) women and 459 (71.4%) men. Data of hospitalized patients were obtained from the Polish Registry of Acute Coronary Syndromes (PL-ACS). Data on post-discharge events were obtained from the National Health Fund and data regarding mortality from the Vital Statistics Office. In order to identify gender-related differences in the course of ULMCA lesions and treatment women and men in the present study were compared with respect to medical history, clinical symptoms, strategy of treatment, pharmacotherapy during in-hospital stay and medication prescribed at discharge. Study end-points were defined as in-hospital death, mortality at 30 days, 6 and 12 months. Multivariate analysis included such factors as age, gender, presence of arterial hypertension, diabetes mellitus, smoking, obesity, previous MI, TIMI-3 flow prior to intervention, effective PCI (TIMI-3 flow post intervention), use of intraaortic counterpulsation and CABG.

Statistical analysis

Continuous variables, depending on the distribution type, were presented as means ± standard deviation (SD) or median and interquartile range. The significance of differences between the two means was tested using Student’s t-test or Mann-Whitney U-test. If the data were non-normally distributed the Kruskal-Wallis one-way analysis of variance by ranks or the Mann-Whitney U-test was performed. Homogeneity of variances was checked by means of the F test. Qualitative variables were tested using the χ2 test. One year mortality was analyzed using the Kaplan-Meier method, and the significance of differences between the groups was tested using the log-rank test. Multivariate analysis of in-hospital and 12-month mortality was performed using multiple logistic regression. Results were presented as odds ratio (OR) and relative risk with 95% confidence interval (95% CI). A p value ≤ 0.05 was considered to be significant.

Results

There were 643 consecutive patients with acute MI due to critical stenosis or acute occlusion of ULMCA, STEMI — 47.4%, NSTEMI — 52.6%. Women more frequently presented later than 2 h after symptom onset and were older than men. There was higher proportion of women over 65 and with arterial hypertension, diabetes and obesity. Cardiac arrest before hospitalization was more frequent in men (Table 1). There was a similar percentage of women in STEMI and NSTEMI group (28.9% vs. 28.5%; p = 0.94). Isolated ULMCA disease was more frequent in STEMI group (30.6% vs. 16.0%; p < 0.0001) in contrast to NSTEMI group where mul­-tivessel disease was dominant (45.1% vs. 66.0%; p < 0.0001). In general, there were no significant differences in the treatment strategy (Table 2) and pharmacotherapy between men and women except of more frequent use of diuretics (41.8% vs. 32.2%; p = 0.021) and insulin (22.3% vs. 14.2%; p = 0.012) in women. In women and men who underwent PCI there were different treatment options: plain old balloon angioplasty (10.7% vs. 10.5%; p = NS), bare metal stent (BMS, 27.0% vs. 73.0%; p = 0.0005) and drug-eluting stent (DES, 50% vs. 50%). There were no differences in mortality between genders in all follow-up periods (Table 3). However, when considering STEMI and NSTEMI subgroups there was a clear difference in mortality in favor of NSTEMI both in in-hospital (27.2% vs. 10.4%; p < 0.0001) and in 12-month follow-up (38.4% vs. 24.6%; p < 0.0001). In patients treated with DES in-hospital (9.0% vs. 24.1%; p = 0.08) and 12-month (20.0% vs. 33.2%; p = 0.05) there was a tendency towards lower mortality with borderline significance. Complication rate (reinfarction, stroke, bleeding, target vessel revascularization) was relatively low and there were no significant differences between genders both in general population (Table 2) and in STEMI/NSTEMI subgroups (data not shown). In multivariable analysis cardiogenic shock, pulmonary edema, STEMI and advanced age significantly increased in-hospital and 1-year mortality. Female sex did not influence mortality. Successful PCI assessed as post-procedural TIMI 3 flow significantly improved prognosis (Table 4).

Table 1. Basic clinical characteristics.

Table 2. Treatment strategy.

Table 3. Mortality.

Table 4. Multivariate analysis — in-hospital and 12-month mortality.

Discussion

Critical ULMCA stenosis is rare (5–7% of patients undergoing coronary angiography), it is however associated with serious prognosis. European guidelines allow for PCI of the ULMCA in patients with single vessels disease and the lesion not extending to the bifurcation (Class IIa recommendation), in more complex cases PCI is upgraded to a Class IIb recommendation, whereas in patients with multiple vessel disease or SYNTAX Score ≥ 33 PCI of the ULMCA is contraindicated [7]. American guidelines say that PCI of the ULMCA can be considered in select patients (Class IIb recommendation) [8]. MI due to acute total occlusion of ULMCA, if not leading almost immediately to death, usually is complicated by severe ventricular arrhythmia and acute left ventricular failure as evidenced by pulmonary edema or shock with in-hospital and long-term mortality being very high. In stable patients CABG is the recommended modality offering good long-term outcomes. How­ever, in patients with the ULMCA as the infarct-related artery optimal revascularization strategy is not obvious. Primary PCI in these patients is feasible and restores blood flow in a shorter time than CABG. Short- and long-term outcomes and lower periprocedural risk of stroke, even with a higher rate of repeat revascularization within the treated vessel, offer a favorable alternative to surgical treatment [9]. There is increasing evidence showing that outcomes after PCI of the ULMCA in stable patients does not differ from that after CABG with respect to the rate of post-procedural death or MI. For this reason there is growing interest in angioplasty procedures in highest risk patients in whom the fastest reperfusion (TIMI grade 3 flow) is closely associated with better prognosis [10, 11].

Because of the frequently described differences in the course of MI between men and women we analyzed a number of factors that might have an impact on the clinical manifestations of acute coronary syndromes caused by critical ULMCA stenosis in both sexes. Women were decidedly in the minority, they were older than men by 4.5 years on average and they were diagnosed signifi­­cantly more frequently with arterial hypertension, diabetes mellitus and obesity, and what’s perhaps most important time from the onset of pain to admission was longer than that for men. Most studies comparing cardiovascular risk factors in men and women confirm such risk distribution among patients admitted for MI [12]. It is noteworthy that the number of risk factors increases significantly with age, however in those both below and over 65 years of age there are still more women with arterial hypertension, diabetes mellitus and obesity whereas more smokers are encountered among men. In a large database of patients with acute coronary syndromes admitted to hospitals in 2001–2004 cardiovascular risk factors in men and women had similar rates of occurrence. Women made up about 30% of the study population, they were older than men by 6 years on average and had arterial hypertension (66.4% vs. 56.8%; p = 0.001) and diabetes (30.8% vs. 18.6%; p < 0.001), whereas there were more smokers among men (66.2% vs. 6.6%; p < 0.001) [13]. Although the statistics regarding patients with MI due to total occlusion of the left main coronary artery are limited, it seems that the distribution of major cardiovascular risk factors is similar to that in the population of MI patients in general. According to one of the few reports on patients undergoing angioplasty of the unprotected left main coronary artery stenosis women representing 27.8% of the study population were older and had been more frequently diagnosed with arterial hypertension and diabetes [14]. Significantly less women were found to be admitted to hospital within 2 h after the onset of chest pain (8.2% vs. 13.9%; p = 0.043). Delay to treatment in MI frequently occurs in women. This fact is believed to be caused by differences in the clinical manifestations of acute coronary syndromes between men and women. One study evaluating the symptoms of acute MI in females demonstrated that chest pain was absent in almost 50% of women, and shortness of breath (58%), weakness (55%) and fatigue (43%) were found instead [15]. Moreover, women’s low awareness of coronary risk not infrequently was the reason for ignoring the symptoms and not seeking medical care. Therefore, women even with typical symptoms of MI were admitted to emergency departments later than men [16, 17].

Mortality after elective PCI with DES in low risk patients with ULMCA (good left ventricular ejection fraction, favorable anatomy of the left main bifurcation) is low [18, 19] as compared with very high (exceeding often 40%) mortality in MI due to ULMCA stenosis [20–23]. These reports are rare because of the short time elapsed from the introduction of PCI in these patients. In the present study in-hospital and annual mortality is high but relatively low as compared with other studies. Most investigators emphasize poorer prognosis in females, however these differences are increasingly frequently interpreted as a result of age and a larger number of risk factors. Analysis of a large database of patients admitted to hospital due to MI confirmed higher in-hospital and early post discharge mortality among women and equalization of survival in both genders over longer follow-up. Investigators emphasize probable effects of the sex-specific clinical characteristics on these statistics, and they also agree that reliable evaluation is difficult because of the nonhomogeneity of the studies. It is however suggested that higher early post MI mortality among women may be associated with less frequent use of an invasive management strategy and delayed admission to hospital [24].

Several investigations show better survival in women which is related to progress in reperfusion therapy. A population of patients admitted to hospital due to MI was analyzed in three series: group I: 1981–1988 (fibrinolysis), group II: 1989–1995 (balloon angioplasty), group III: 1996–2001 (PCI with stenting). Mortality over 3-year follow-up was higher in women in the first two groups, whereas in group III there were no differences in mortality between men and women (12% vs. 10%; p = 0.66). The investigators emphasize that the number of men and women selected for reperfusion therapy was similar in all groups [25]. Analysis of patients undergoing angioplasty of the ULMCA generated similar results. Although over 18-months follow-up there was higher risk of cardiac death, MI and total mortality among women, in multivariate analysis female gender did not affect negatively the survival [14]. In the present study there were no significant differences in mortality between men and women in general group and within STEMI/NSTEMI and DES/BMS subgroups.

Chieffo et al. [3] compared stenting on the left main bifurcation performed with two types of stents. In their study 45% of patients received DES and 34% — BMS. Serious complications developed in 15.8% of DES patients vs. 45.4% of BMS patients. Cardiac deaths were also more frequent in BMS patients (22.7%) than in DES patients (5.2%). In the present study there was a tendency towards lower mortality in patients with DES. Nevertheless the small sample size does not permit definitive conclusions or extrapolation to the general population.

Multivariate analysis provided extremely interesting results in an attempt to answer a question which factors have the most important effect on in-hospital and long-term mortality. Of all factors age and symptoms of acute left ventricular failure were the most important predictors of mortality. Cardiogenic shock is a real killer and treatment of this dangerous complication should be instituted in the first place in MI even if it is caused by occlusion of the ULMCA. Undoubtedly treating the underlying cause is important. Rapid restoration of coronary blood flow also at the microcirculatory level is the best treatment strategy. In the present study TIMI grade 3 flow resulted in a 5-fold decrease of annual mortality. Increasing evidence suggests that both treatment modalities (CABG and PCI) may be accepted as equivalent or complementary in patients with critical lesions in the left main coronary artery, because once a patient with MI has stabilized and the acute phase has passed, complete revascularization with CABG after PCI of the left main is still possible.

Limitations of the study

Despite our study presents important data, it has several limitations. First, its retrospective nature biases the conclusions. Second, the choice of treatment strategy was operator dependent. Third, small number of DES used resulted in insignificant differences in outcomes what is known to be false. Finally, we have no data on lesion location (ostial vs. bifurcation of the ULMCA) and manual thrombectomy prior to PCI which also have significant impact on mortality.

Conclusions

No significant differences in clinical course, treatment and prognosis between men and women were noted, although women were older and had more concomitant risk factors. Mortality remained very high in both genders. The most unfavorable prognostic factors were cardiogenic shock, pulmonary edema, STEMI and advanced age. Percutaneous coronary angioplasty is feasible and offers high success rate in this subset of patients.

Conflict of interest: none declared

References

1. 1. Caracciolo EA, Davis KB, Sopko G et al. Comparison of surgical and medical group survival in patients with left main equivalent coronary artery disease. Long-term CASS experience. Circulation, 1995; 91: 2335–2344.
2. 2. Park SJ, Kim YH, Lee BK et al. Sirolimus-eluting stent implantation for unprotect left main coronary artery stenosis. J Am Coll Cardiol, 2005; 45: 351–356.
3. 3. Chieffo A, Stankowic G, Bonizzoni E et al. Early and mid-term results of drug-eluting stent implantation in unprotected left main. Circulation, 2005; 111: 791–795.
4. 4. Montalescot G, Brieger D, Eagle KA et al.; GRACE Investigators. Unprotected left main revascularization in patients with acute coronary syndromes. Eur Heart J, 2009; 30: 2308–2317.
5. 5. Sadowski M, Gąsior M, Gierlotka M, Janion M, Poloński L. Clinical characteristics of Polish women with ST-segment elevation myocardial infarction. Kardiol Pol, 2010; 68: 627–634.
6. 6. Sadowski M, Gąsior M, Gierlotka M, Janion M, Poloński L. Gender-related differences in mortality after ST-segment elevation myocardial infarction: A large multicentre national registry. EuroIntervention, 2011; 6: 1068–1072.
7. 7. Wijns W (Chairperson), Kolh P (Chairperson); Guidelines on myo­cardial revascularization. The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association for Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J, 2010; 31: 2501–2505.
8. 8. King SB 3rd, Smith SC Jr., Hirshfeld JW Jr. et al. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for Percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol, 2008; 51: 172–209.
9. 9. Lee MS, Bokhoor P, Park SJ et al. Unprotected left main coronary disease and ST-segment elevation myocardial infarction: A contemporary review and argument for percutaneous coronary intervention. J Am Coll Cardiol Cardiovasc Interv, 2010; 3: 791–795.
10. 10. Kandzari DE, Colombo A, Park SJ et al.; American College of Cardiology Interventional Scientific Council. Revascularization for unprotected left main disease: Evolution of the evidence basis to redefine treatment standards. J Am Coll Cardiol, 2009; 54: 1576–1588.
11. 11. Seung KB, Park DW, Kim YH et al. Stents versus coronary-artery bypass grafting for left main coronary artery disease. N Engl J Med, 2008; 358: 1781–1792.
12. 12. Rosengren A, Wallentin L, K Gitt A et al. Sex, age, and clinical presentation of acute coronary syndromes. Eur Heart J, 2004; 25: 663–670.
13. 13. Song XT, Chen YD, Pan WQ et al. Gender based differences in patients with acute coronary syndrome: Findings from Chinese Registry of Acute Coronary Events (CRACE). Chin Med J (Engl), 2007; 120: 1063–1067.
14. 14. Sheiban I, La Spina C, Cavallero E et al. Sex-related differences in patients undergoing percutaneous unprotected left main stenting. EuroIntervention, 2010; 5: 795–800.
15. 15. McSweeney JC, Cody M, O’Sullivan P et al. Women’s early warning symptoms of acute myocardial infarction. Circulation, 2003;108: 2619–2623.
16. 16. Gurwitz JH, McLaughlin TJ, Willison DJ et al. Delayed hospital presentation in patients who have had acute myocardial infarction. Ann Intern Med 1997; 126: 593–599.
17. 17. Sheifer SE, Rathore SS, Gersh BJ et al. Time to presentation with acute myocardial infarction in the elderly: Associations with race, sex, and socioeconomic characteristics. Circulation 2000; 102: 1651–1656.
18. 18. Chieffo A, Stankowic G, Bonizzoni E et al. Early and mid-term results of drug-eluting stent implantation in unprotect left main. Circulation, 2005; 111: 791–795.
19. 19. Brennan JM, Dai D, Patel MR et al. Characteristics and Long-Term Outcomes of Percutaneous Revascularization of Unprotected Left Main Coronary Artery Stenosis in the United States. A Report From the National Cardiovascular Data Registry, 2004 to 2008. J Am Coll Cardiol, 2012; 59: 648–654.
20. 20. Lee MS, Sillano D, Latib A et al. Multicenter international registry of unprotected left main coronary artery percutaneous coronary intervention with drug-eluting stents in patients with myocardial infarction. Catheter Cardiovasc Interv, 2009; 73: 15–21.
21. 21. Lee SW, Hong MK, Lee CW et al. Early and late clinical outcomes after primary stenting of the unprotected left main coronary artery stenosis in the setting of acute myocardial infarction. Int J Cardiol, 2004; 97: 73–76.
22. 22. Tan CH, Hong MK, Lee CW et al. Percutaneous coronary intervention with stenting of the left main coronary artery with drug-eluting stent in the setting of acute ST elevation myocardial infarction. Int J Cardiol, 2008; 126: 224–228.
23. 23. Prasad SB, Whitbourn R, Malaiapan Y et al. Primary percutaneous coronary intervention for acute myocardial infarction caused by unprotected left main stem thrombosis. Catheter Cardiovasc Interv, 2009; 73: 301–307.
24. 24. Vaccarino V, Krumholz HM, Berkman LF et al. Sex differences in mortality after myocardial infarction. Is there evidence for an increased risk for women? Circulation, 1995; 91: 1861–1871.
25. 25. Ishihara M, Inoue I, Kawagoe T et al. Trends in gender difference in mortality after acute myocardial infarction. J Cardiol, 2008; 52: 232–238.