Effect of Multivessel Coronary Artery Disease With or Without a Concomitant Chronic Total Occlusion on 1-Year Survival in Patients Treated With Rescue Angioplasty

Primary percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (AMI) restores antegrade flow in the infarct-related artery and reduces death and recurrent myocardial infarction rates.¹ Direct access to primary PCI varies from 5%-92%² and fibrinolysis remains the main form of reperfusion therapy.^3,4 Unfortunately, pharmacological treatment does not achieve Thrombolysis in Myocardial Infarction (TIMI) 3 flow of the infarct-related artery in approximately half of all patients⁵ who show higher mortality rates in comparison with successful reperfusion.⁶ In these situations, PCI represents a useful rescue strategy.^7-12

Multivessel coronary artery disease (MVD) is present in 40%-60% of patients with AMI and seems to represent a risk factor of increased mortality and major adverse cardiac events in comparison with single-vessel disease (SVD).^13-15 Furthermore, the presence of a coronary chronic total occlusion (CTO) in a non-infarct related artery is an independent predictor of mortality¹⁶ and is associated with a worse clinical outcome^16,17 rather than the mere presence of MVD. Unfortunately, only limited data are available regarding the role of MVD in patients undergoing rescue PCI¹⁸ and the impact of a concurrent CTO has never been investigated in this clinical scenario. The aim of the present study is to describe the clinical characteristics, angiographic patterns, and procedural details of patients with MVD in comparison with patients with SVD undergoing rescue PCI and to evaluate the role of the concomitant presence of a CTO on 1-year survival.

Methods

Study population. From July 1997 to August 2010, a total of 551 consecutive patients with AMI underwent rescue PCI at our institution for failed fibrinolysis performed within the previous 12 hours. The diagnosis of AMI was established on the basis of typical chest pain lasting >30 minutes, unrelieved by sublingual nitrates, associated with ST-segment elevation (≥1 mV in ≥2 limb leads or ≥0.2 mV in ≥2 contiguous precordial leads) or left bundle-branch block of new onset on surface electrocardiogram (ECG). Failed thrombolysis was defined by a second 12-lead ECG obtained 60 minutes after the onset of fibrinolytic therapy, showing failure of the ST-segment elevation in the worst lead to have resolved by 50% as compared with baseline ECG as well as absence of chest pain relief. “Facilitated” PCIs without rescue criteria were not included. All patients had received intravenous aspirin 300-500 mg and unfractionated heparin 60 UI/kg body weight at the admitting hospital. At arrival in our department, patients were treated with 500 mg ticlopidine (until July 2002) or 300 mg clopidogrel (from August 2002). Abciximab was administered at the discretion of the operator: an intravenous preprocedural bolus of 0.25 mg/kg body weight followed by a continuous infusion of 0.125 µg kg^-1 min^-1 for 12 hours (up to a maximal dose of 10 µg/min). During PCI, intravenous bolusus of unfractionated heparin were given to maintain an activated clotting time of >200 seconds. All patients were discharged with aspirin (100 mg) indefinitely and ticlopidine (500 mg) or clopidogrel (75 mg) daily for 6-12 months. Follow-up protocol included evaluation at hospital discharge and a clinical visit thereafter at 1, 6, and 12 months. A stress test was scheduled at 6-11 months. Only patients with spontaneous or inducible ischemia underwent repeat coronary angiography.

Angiographic analysis. The number of critically narrowed coronary arteries was evaluated. MVD was defined as a stenosis >70% of the coronary lumen diameter in ≥1 of the non-infarct related epicardial arteries in vessels ≥2.5 mm or a left main stenosis >50%. A CTO was defined as a complete obstruction of a major vessel with TIMI flow grade 0 and an estimated duration >3 months; age of the occlusion was determined by the interval from the last episode of acute coronary syndrome or AMI consistent with the location of the coronary occlusion. Angiographic analysis was done on end diastolic frames demonstrating the stenosis on its more severe view. The view with the least foreshortening was selected for the analysis. Initial and final flow in the infarct-related artery were graded according to TIMI classification. Reperfusion failure was defined as final TIMI flow grade 0-1 in the infarct-related artery. Based on pre-PCI angiogram, patients were classified in 3 groups: SVD, MVD without CTO, and MVD with CTO. Additional revascularization procedures performed during 1-year follow-up were also recorded. They included PCI or coronary artery bypass surgery due to target vessel restenosis or reocclusion, non-infarct related coronary stenosis or occlusion, and progression of coronary artery disease in the presence of objective evidence of ischemia.

Endpoint. The primary endpoint of the study was the 1-year incidence of death in the 3 groups. Death at 30-day follow-up was also recorded and analyzed.

Statistical analysis. A retrospective analysis of data prospectively collected according to our internal protocol was performed. Data are presented as mean ± standard deviation (SD) or percentages. Comparisons between groups were performed using t-test for continuous data and the chi-square test for categorical data. Logistic regression was performed to determine the independent correlates of death at 30-day follow-up. The Cox proportional hazards model was used to determine the independent correlates of the composite primary endpoint at 1 year. Survival curves were developed using the Kaplan-Meier method and compared with the log-rank test. Analyses were performed using the SPSS statistical package (Insightful Corporation). Statistical significance was accepted at P<.05.

Results

Study population. Mean age was 58 ± 11 years (range, 29-90 years); 75 patients (14%) were females. Diagnosis of previous myocardial infarction had been made in 28 patients (5%), while 26 patients (5%) had undergone previous revascularization. Cardiogenic shock was present in 35 patients (6%). Among the 551 patients, 361 (65%) had SVD, 137 (25%) had MVD without CTO, and 53 (10%) had MVD with a concomitant CTO. Baseline clinical characteristics are shown in Table 1. Patients with MVD were older and more often admitted with cardiogenic shock in comparison with SVD. Moreover, patients with MVD and CTO more often had previous myocardial infarction, lower ejection fraction and longer pain to PCI time compared with the other groups.

Angiographic and procedural variables. Angiographic and procedural details are reported in Table 2. AMI-related artery was left main in 7, left anterior descending (LAD) coronary artery in 319, circumflex artery in 53, right coronary artery (RCA) in 169, and saphenous vein coronary artery bypass graft in 3 patients. Patients with MVD had AMI-related LAD coronary artery less frequently, but a higher use of intra-aortic balloon pump in comparison with SVD. TIMI 2-3 flow grade after intervention was obtained in 525 cases (95%). Patients with MVD and CTO had a significantly higher incidence of reperfusion failure after PCI. Among 28 patients with the LAD as the infarct-related artery, 16, 8, and 4 had CTO of the RCA, circumflex, and both RCA and circumflex, respectively. Among 8 patients with the circumflex as the infarct-related artery, 6, 1, and 1 had CTO of the RCA, LAD, and both RCA and LAD, respectively. Among 14 patients with the RCA as the infarct-related artery, 7 had circumflex, 6 had LAD, and 1 had both circumflex and LAD as CTO. The 3 patients with saphenous vein graft to RCA, LAD, and circumflex as infarct-related artery had CTO of native vessel (or occluded graft) of circumflex, RCA, and both LAD and RCA, respectively. Postprocedural collateral circulation contribution from infarct-related artery to CTO was present in 20, absent in 22, and not determinable in 11 cases (because of failed procedure).

Multivessel rescue PCI was performed in 45 patients (33%) in the MVD group without CTO, and in 4 patients (8%) in the MVD group with CTO (P<.001). Additional revascularization procedures within 1 year after the index PCI were performed in 21 patients (6%), 25 patients (18%), and 8 patients (15%) in the groups with SVD, MVD without CTO, and MVD with CTO, respectively (P<.001). An unsuccessful attempt at CTO PCI was performed in 5 patients during 1-year follow-up. At 1-year follow-up, 38 patients (7%) were lost: 30 (8%) in the SVD group, 7 (5%) in the MVD without CTO group, and 1 (2%) in the MVD with CTO group (P=.14).

Clinical follow-up. There were 33 deaths (6%) at 30 days and 48 deaths (9%) at 1 year. Mortality rates at 30-day and 1-year follow-up were higher in patients with MVD and CTO in comparison with the other 2 groups, as shown in Table 2.

To determine the independent predictors at 30-day follow-up, the following variables were entered into the logistic regression model: age, sex, previous myocardial infarction, previous coronary artery bypass surgery or PCI, year of PCI, diabetes mellitus, cardiogenic shock, pain to PCI time, target vessel and treated segment, TIMI flow grade 2-3 vs 0-1 before and after procedure, SVD, MVD without and with CTO, multivessel rescue PCI during the index procedure, additional revascularization within 1 year, clopidogrel and abciximab administration, thrombectomy, type of intervention (balloon, bare-metal or drug-eluting stent). Stepwise logistic regression identified age, cardiogenic shock, and TIMI flow grade 0-1 after procedure, but not MVD without or with CTO, as predictors of death at 30-day follow-up (Table 3). To determine the independent predictors of death at 1-year follow-up, the same aforementioned variables were entered into the Cox proportional hazard model, which identified age, cardiogenic shock, TIMI flow grade 0-1 after procedure, and MVD with a CTO, but not MVD without CTO, as independent predictors of death at 1-year follow-up (Table 4). The adjusted 1-year overall survival rates were 96%, 91.4%, and 83.4% (P=.001) in the groups with SVD, MVD without CTO, and MVD with CTO, respectively. Adjusted Cox model estimates for cumulative survival rates are detailed in Figure 1.

Discussion

This study demonstrates that in patients undergoing rescue PCI: (1) MVD with a concurrent CTO determines higher 1-year mortality rates than SVD or MVD without a CTO; and (2) the coexistence of a CTO rather than the mere presence of MVD impacts on mortality. 

The presence of MVD identifies a high-risk group for worse outcome among patients undergoing primary^13-15 or rescue¹⁸ PCI. In our series, the whole prevalence of MVD (35%) was not different from data reported in the literature on patients undergoing rescue PCI. Patients with MVD without CTO were 25% of the study population. They had a higher risk profile at admission, including advanced age and high incidence of cardiogenic shock, both strong predictors of adverse outcome in patients with rescue PCI.^18,19 The patients in the group with MVD and CTO represented 10% of our cohort. In comparison with the two other groups, they had an increased prevalence of previous myocardial infarction in non-infarct related arteries, worse ejection fractions, and a higher percentage of unsuccessful rescue PCI procedures. These baseline and procedural findings are often associated with death or major adverse cardiac events. However, this higher risk profile does not justify the lower survival rate in patients undergoing rescue PCI with a concurrent CTO. In fact, after adjustment for the differences in baseline variables, the presence of a CTO in patients with MVD was still a strong predictor of mortality. Many different mechanisms may contribute to elucidate the negative influence of CTO on survival in patients with MVD undergoing rescue PCI. The longer ischemic time before intervention could play an important role, but it was not a predictor of mortality at multivariable analysis. The acute occlusion of a coronary artery providing collateral circulation to the non-infarct related CTO may lead to more pronounced myocardial damage.^17,20 

An important negative left ventricular remodelling process develops in patients with MVD and CTO during the first 2 years in patients undergoing primary PCI.^21,22 Our results partially extend the recent findings obtained in patients treated with primary PCI to patients undergoing rescue PCI.^21,22 The persistent and prolonged occlusion of the infarct-related artery in patients undergoing rescue PCI because of failed thrombolysis represents an additional detrimental factor, which may amplify the damage on ventricular function. Interestingly, we found MVD with CTO to be an independent predictor for late but not early mortality after rescue PCI. Conversely, Claessen et al²¹ found the presence of CTO in a non-infarct related coronary artery as a predictor for both early and late mortality in patients undergoing primary PCI. Differences in study population or selection criteria could explain this partial discrepancy, but overall we cannot exclude the role of an early high mortality in patients with failed thrombolysis.

Clinical implications. Our study demonstrates that patients with MVD and CTO represent a group at high risk of death after rescue PCI. Further randomized studies are needed to establish how they should be treated, ie, complete percutaneous/surgical urgent or staged revascularization, routine use of ventricular assistance devices, etc. Surely the presence of viable myocardium, which anticipates the improvement of left ventricular function after re-canalization of a CTO,²³ must be preliminarily assessed and revascularization should be complete, as Valenti et al²⁴ demonstrated that failed PCI of CTO is a marker of worse long-term outcome. However, our finding that MVD with CTO is a predictor of death at 1 year but not at 30 days seems to support the hypothesis that these complex procedures could be staged after the acute phase of rescue PCI.

Study limitations. This study is retrospective, but, for the first time, describes the outcome of a real-world cohort of patients with MVD with or without CTO undergoing rescue PCI. Although the bias of transfer decision could not be excluded, the percentages of patients with MVD with or without CTO were not different from those reported from studies on primary PCI.^16,17 Detailed information about changes in left ventricular ejection fraction during 1-year follow-up were not collected; however, this should be considered a weaker measurement of outcome than death. A number of these patients were treated before the introduction of drug-eluting stents, abciximab, and thrombectomy; however, none of these variables resulted as a predictor of outcome at multivariable analysis.^25,26 Finally, additional data on postprocedural drugs were not collected.

Conclusion

Patients submitted to rescue PCI with MVD and a concurrent CTO have higher mortality rates than those with SVD or MVD without CTO at 1-year follow-up. MVD with CTO and not MVD alone is a predictor of death at 1-year follow-up.

References

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From the Cardiologia Interventistica Ospedale S. Camillo Roma, Rome, Italy.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted July 16, 2012, provisional acceptance given August 23, 2012, final version accepted October 1, 2012.

Address for correspondence: Francesco De Felice, MD, Cardiologia Interventistica Ospedale S. Camillo Roma, Cardiologia Interventistica Ospedale S. Camillo, C.ne Gianicolense n 87, Rome 00152, Italy. Email: f.defelice@lycos.com