Primary Angioplasty of Unprotected Left Main Coronary Artery
for Acute Anterolateral Myocardial Infarction
November 2004
Despite the advancements in acute myocardial infarction (AMI) treatment, AMI caused by acute unprotected left main coronary artery (LMCA) occlusion rapidly progresses to cardiogenic shock and death unless there are substantial preexisting intercoronary collaterals and adequate reperfusion can be readily established.1–3 Primary angioplasty expands the population amenable to reperfusion to patients ineligible for thrombolysis and is more effective for treating patients at high risk,4,5 the benefits being most impressive for shock patients.6
Acute LMCA occlusion is a rare angiographic finding.3,7 Even to date, there is no consensus as to the best management of this dismal group of patients and cardiologists are continuously searching for more effective approaches. The purposes of this study were to determine the effects of primary angioplasty and the impact of overt cardiogenic shock on arrival and angiographic features on the outcome of these difficult patients.
Methods
Study patients. Between January 1992 and December 2000, 1,736 consecutive patients with AMI treated at Kokura Memorial Hospital underwent emergency cardiac catheterization within 12 hours of symptom onset. Patients met the following AMI criteria: 1) electrocardiographic ST-segment elevation or depression and/or a new onset of complete left bundle branch block; 2) symptoms of myocardial ischemia lasting > 20 minutes; and 3) creatine kinase (CK) elevation to > 2 times the normal value. Total or subtotal occlusion of the LMCA with TIMI grade 0, 1, or 2 flow at initial coronary angiography causing acute anterolateral myocardial infarction (AAMI) was present in 38 of the 1,736 (2.2%) patients.8 These 38 patients were given primary coronary angioplasty and constituted the study population: 17 (45%) were discharged and 21 (55%) died in-hospital, defined as the survival and mortality groups.
The infarction was complicated by overt cardiogenic shock on arrival in 28 patients (74%), and 10 patients (26%) were stable, defined as with/without shock groups. Cardiogenic shock was defined as systolic blood pressure 18 mmHg. Clinical signs of heart failure on admission were graded according to the Killip classification.9Primary angioplasty. Patients were given 162 mg of chewable aspirin and heparin (10,000 U) was administered immediately after sheath insertion. Hemodynamic stabilization was attempted by intra-aortic balloon pumping in all patients and, when necessary, a percutaneous cardiopulmonary bypass support system (PCPS); both were placed under fluoroscopic control.
In performing direct angioplasty, the highest priority was to restore the normal TIMI grade 3 flow to the coronary artery branch that supplied the biggest left ventricular myocardial mass. Direct angioplasty was attempted regardless of the coronary anatomy. Bail-out stenting of the LMCA in patients with a suboptimal angiographic result after one or more dilations with appropriately sized balloons and adjunctive stent implantation were introduced for the treatment of AMI in 1994. This further evolved into routine stenting or stenting even after achieving an optimal angiographic result by conventional angioplasty. Direct balloon angioplasty and coronary stenting were accomplished with standard techniques, including high-pressure balloon dilation to expand the stent after deployment.
Following angioplasty, all patients were admitted to the coronary care unit where 500 IU/hour intravenous heparin drip for at least 48 hours and 162 to 243 mg/day oral aspirin were given; 200 mg/day ticlopidine was added in patients who had stents. Coronary artery bypass graft surgery (CABG) was performed when needed for further revascularization.
Angiographic analysis. All coronary angiograms were analyzed with special emphasis on contrast media flow: a) the antegrade flow was assessed according to the TIMI study flow classification;8 b) the collateral flow was graded according to the Rentrop classification;10 c) a right coronary artery (RCA) supplying the posterior portion of the interventricular septum and the inferior wall of the left ventricle was considered dominant, and that not supplying the left ventricular myocardium small. A RCA with antegrade TIMI flow grade 2 or less was considered occluded.
Reperfusion was considered successful if residual lumen diameter stenosis was Causes of mortality. In-hospital mortality was divided into cardiac and non-cardiac mortality. In addition, cardiac mortality causes were classified into pump failure, myocardial rupture and arrhythmia. Pump failure comprised cardiogenic shock (if hemodynamic status could not be restored) and congestive heart failure (if dying with pulmonary edema, pleural effusion, hepatomegaly, ascites and peripheral edema).
Statistical analysis. Values are expressed as mean ± SD. Categorical variables were analyzed by the chi-square test. Serial paired numerical data were compared by the paired “t” test, and other continuous variables by the unpaired “t” test. Survival estimates were computed by the Kaplan-Meier method, and survival curves were compared by the log rank test. Follow-up was obtained from the medical record or telephone contact with patients or their physicians; one-year follow-up was complete in all patients. A p value Patient characteristics (Table 1). Patient age ranged from 40 to 90 years (mean 68.3 ± 10.3 years). Survival patients were less likely to have cardiogenic shock and to require ongoing cardiopulmonary resuscitation (CPR) for shock prior to the institution of mechanical support that included intra-aortic balloon support and PCPS in extreme cases. Peak CK was lower and pH and base excess on arrival to the emergency room significantly higher in the survival group than in the mortality group. The time from onset of symptoms to angioplasty, and the incidence of stenting and emergency CABG between the two groups were not different.
Angiographic findings and reperfusion status (Table 2). Although in the survival group the presence of collateral flow (Rentrop grade 2 or 3) to the infarct area and a dominant RCA were more frequent than in the mortality group, differences did not reach statistical significance. All survival patients had successful reperfusion which was significantly different from the mortality group, where 57.1% had successful reperfusion. Reperfusion failed in 9 patients, 7 (78%) from no-reflow without mechanical obstacles and 2 (22%) from persistent dissection or thrombosis. Of these 9 patients, 2 (22%) required CPR for shock, resulting in no-reflow after reperfusion.
Comparison of patients with and without cardiogenic shock (Table 3). The presence of collateral flow (Rentrop grade 2 or 3) to the infarct area and a dominant RCA were observed more frequently in stable patients. While the successful reperfusion rate was 67.9% in shock patients, it was 100% in stable-patients, ostial lesions being more prevalent in this group.
The hospital mortality rate was 71.4% in shock patients, all of whom died of pump failure, and 10.0% in without shock patients (one patient, who died from pneumonia). Cardiogenic shock significantly decreased 1-year survival (Figure 1).
Does successful reperfusion alter in-hospital mortality? Successful reperfusion significantly decreased the in-hospital mortality rate of this subset of patients regardless of hemodynamic status (Figure 2).
Discussion
This study was undertaken to investigate the impact of cardiogenic shock on the prognosis of AAMI caused by LMCA occlusion. Patients having emergency percutaneous intervention of LMCA occlusion who present with cardiogenic shock are, without doubt, the highest risk group of patients that the interventionalist faces in practice. Our results show that the combination of AAMI and LMCA occlusion was associated with cardiogenic shock in 74% (28/38) of patients, and these 28 shock patients had significantly higher in-hospital and 1-year mortality rates after infarction (71.4%). Obviously this represents a very high mortality rate but nonetheless, 8 of the 28 shock patients did survive hospitalization and 1-year after infarction. The fact that primary angioplasty for AAMI caused by LMCA occlusion effectively reduced in-hospital mortality, even presenting with overt cardiogenic shock confirms the existing evidence that successful reperfusion, regardless of how it is accomplished, improves the patient’s prognosis in general.
The results of this and other studies confirm that severe hemodynamic failure on admission is the major determinant of the prognosis.9,11 The mortality group was more likely to have cardiogenic shock, the extreme being represented by patients who required ongoing CPR before mechanical support could be instituted, and all of whom died without overcoming pump failure. It suggests severe extensive left ventricular injury already present at the time of admission and that patients requiring CPR for cardiogenic shock will not benefit from primary direct angioplasty.
The fact that all shock patients died of pump failure suggests that future treatment strategies should emphasize the necessity of more effective and complete reperfusion therapy and other supportive measures in the event that hemodynamic status fails to help infarct patients bridge their acute infarct period. Our results, however, are in agreement with the reported lower angioplasty success rates of patients with AMI and shock than of those without shock.4,12 A relatively large amount of angiographically visible thrombus was shown in all LMCA lesions. The presence of thrombus has been identified as a predictor of unfavorable results because of distal embolism or no-reflow phenomenon often leading to or sustaining cardiogenic shock,13,14 which frequently prevents completion of the procedure because of the ensuing cardiac arrest. Furthermore, the low blood pressure may result in suboptimal flow despite adequate dilatation. The major cause of unsuccessful reperfusion was no-reflow without mechanical reasons, an entity particularly resistant to therapy. The mechanisms are complex, multi-factorial and incompletely elucidated. Although relatively small but well conducted randomized trials showing that systemic abciximab, intracoronary verapamil, intravenous nicorandil and intracoronary adenosine might reduce the area of no-reflow are encouraging,15–18 and the distal protection device PercuSurge GuardWire is also being investigated to prevent no-reflow during primary angioplasty,19 the optimal management of no-reflow still remains unknown. Further investigation into the mechanisms and therapy of no-reflow might lead to enhanced survival rates of patients with AAMI and LMCA occlusion. Furthermore, new developments such as mild systemic hypothermia20 and cell transplantation21 have recently been shown to further improve immediate clinical outcomes. Thus, comprehensive management of these new developments might result in marked clinical benefit to patients with AAMI caused by LMCA occlusion.
Conversely, the in-hospital mortality rate of 10.0% and the 1-year mortality rate of 20.0% in stable patients is considered acceptable. No cardiac death was observed in this subgroup. Effective reperfusion by successful primary angioplasty of patients even with AAMI and LMCA occlusion could be achieved provided that overt cardiogenic shock was not present.
Study limitations. This study has three important limitations. First, it is a retrospective study of a small number of non-randomized patients with slightly differing treatments according to the epoch. Though stent implantation is now the routine reperfusion strategy at experienced centers because of having clinical benefits beyond primary angioplasty alone, it cannot improve survival rates as compared with primary angioplasty alone.22 Our study also showed that the incidence of stenting was not more frequent in the survival group compared with the mortality group. Second, these results were achieved in a single, experienced research center with the ability to perform interventional procedures swiftly 24 hours a day with on-site cardiac surgery, and may not be applicable to all institutions. Finally, inhibition of platelet glycoprotein IIb/IIIa receptor by antagonists has been shown to improve clinical outcomes of primary coronary angioplasty.23 However, the platelet glycoprotein IIb/IIIa receptor antagonists are still not available in our country. Moreover, whether adjunctive therapy with platelet glycoprotein IIb/IIIa receptor antagonists could improve the in-hospital outcome of patients with AAMI and LMCA occlusion remains to be determined.
The results of this study demonstrate that patients presenting with AAMI, LMCA occlusion and cardiogenic shock have poor survival rates regardless of primary angioplasty in conjunction with coronary stents. Nevertheless, primary angioplasty is a feasible and effective procedure and it may save lives in this clinical setting. The value of more aggressive intervention awaits further study.
Acknowledgement. We are indebted to Alfonso T. Miyamoto, MD, for his assistance with the manuscript.
1. Goldberg S, Grossman W, Markis JE, et al. Total occlusion of the left main coronary artery. Am J Med 1978;64:3–8.
2. Prachar H, Dittel M, Enenkel W. Acute occlusion of left main coronary artery without ventricular damage. Clin Cardiol 1991;14:176–179.
3. Spiecker M, Erbel L, Rupprecht HJ, Meyer J. Emergency angioplasty of totally occluded left main coronary in acute myocardial infarction and unstable angina pectoris-institutional experience and literature review. Eur Heart J 1994;15:602–607.
4. Grines CL, Browne KF, Marco J, et al. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993;328:673–679.
5. 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 2002;39:1713–1719.
6. Antoniucci D, Valenti R, Santoro GM, et al. Systematic direct angioplasty and stent-supported direct angioplasty therapy for cardiogenic shock complicating acute myocardial infarction: in-hospital and long-term survival. J Am Coll Cardiol 1998;31:294–300.
7. Erbel R, Meinertz T, Wessler I, et al. Recanalization of occluded left main coronary in unstable angina pectoris. Am J Cardiol 1984;53:1725–1727.
8. Chesebro JH, Knatterud G, Roberts R, et al. Thrombolysis in Myocardial Infarction (TIMI) trial, phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation 1987;76:142–154.
9. Killip T III and Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol 1967;20:457–459.
10. Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985;5:587–592.
11. Goldberg RJ, Gore JM, Alpert JS, et al. Cardiogenic shock after acute myocardial infarction: incidence and mortality from a community-wide perspective, 1975 to 1988. N Engl J Med 1991;325:1117–1122.
12. 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.
13. Ellis SG, Roubin GS, King SB, et al. Angiographic and clinical predictors of acute closure after native vessel coronary angioplasty. Circulation 1988;77:372–379.
14. Violaris AG, Melkert R, Hermann JR, Serruys PW. Role of angiographically identifiable thrombus on long-term luminal renarrowing after coronary angioplasty. Circulation 1996;93:889–897.
15. 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;33:1193–1199.
16. Neumann FJ, Blasini R, Schmitt C, et al. Effect of Glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation 1998;98:2695–2701.
17. Ito H, Taniyama Y, Iwakura K, et al. Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients reperfused anterior wall myocardial infarction. J Am Coll Cardiol 1999;33:654–660.
18. Marzilli M, Orsini E, Marraccini P, Testa R. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. J Am Coll Cardiol 2000;101:2154–2159.
19. Yip HK, Chen MC, Chang HW, et al. Transradial application of PercuSurge GuardWire device during primary percutaneous intervention of infarct-related artery with high-burden thrombus formation. Cathet Cardiovasc Intervent 2004;61:503–511.
20. Dixon SR, Whitbourn RJ, Dae MW, et al. Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction. J Am Coll Cardiol 2002;40:1928–1934.
21. Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2000;106:1913–1918.
22. Grines CL, Cox DA, Stone GW, et al. Coronary angioplasty with or without stent implantation for acute myocardial infarction. N Engl J Med 1999;341:1949–1956.
23. Brener SJ, Barr LA, Burchenal JEB, et al. on behalf of the ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators. Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998;98:734–741.
