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The Function of the Left Ventricle After Complete Multivessel One-Stage Percutaneous Coronary Intervention in Patients With Acut
December 2004
Acute ST-segment elevation acute myocardial infarction (STEMI) is one of the main causes of morbidity, hospitalization and consequently increases healthcare costs. The primary goal of therapy in STEMI is to regain patency of the culprit vessel (TIMI 3 flow) and achieve myocardial reperfusion. Timely reperfusion of jeopardized myocardium represents the most effective way of restoring the balance between myocardial oxygen supply and demand. Primary percutaneous coronary intervention (PCI) was shown to be superior to thrombolytic therapy in terms of a higher patency rate (> 90%) of the infarct-related artery (IRA), and feasibility in patients with contraindications for thrombolysis and lower risk of serious bleeding. The use of coronary stents and platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor antagonists leads to further improvement of outcomes (mortality, recurrent AMI, recurrent ischemia, hospital stay and need for target vessel revascularization) and has become the standard preferred therapy in the setting of STEMI.1,2 The infarct-related impairment of left ventricular function, expressed as a reduction of the left ventricular ejection fraction (LVEF), positively correlates with adverse outcomes after STEMI and remains the single most important predictor of early and late complications and mortality.3,4
The accepted standard revascularization procedure in STEMI is primary PCI of IRA, which is considered a safe and efficient approach. However, approximately 30–60% of patients with STEMI have multivessel coronary artery disease (MVD). The multivessel 1-stage complete revascularization approach is possible, but clinical data are sparse and outcomes remain unclear. One-stage complete PCI might lead to faster and more substantial improvement of LVEF due to more efficient blood flow not only in the IRA-supplied area of myocardium, but also in the broader area of blood supply which may be ischemic due to significant stenoses in non-IRA vessels. It can also be beneficial because of a lower risk of bleeding complications associated with the single vascular access and the lower total doses of heparin and contrast media. Nevertheless, the safety of multivessel PCI in STEMI remains an issue because such a procedure could increase the risk for angiographic failure, which is a risk factor of mortality and in-hospital complications associated with STEMI.5 The economical aspect — shorter hospitalization in this 1-stage procedure compared with the 2-stage procedure — should also be considered.
The aim of this study was a prospective randomized comparison of the complete 1-stage revascularization procedure (simultaneous primary PCI of IRA and non-IRA stenoses) and the 2-stage procedure (primary PCI and further elective PCI of non-IRA) in the recovery of left ventricular function in the setting of STEMI and multivessel coronary heart disease. This study also seeks to evaluate both the time and magnitude of the recovery of left ventricular function in patients undergoing both approaches.
Patients and Methods
Patients with STEMI diagnosed according to accepted criteria6 were screened for enrollment in this study. All patients fulfilling the inclusion and exclusion criteria who granted informed consent were randomized to 1 of 2 groups: group A, 1-stage complete PCI; or group B, 2-stage PCI. Patients screened but not randomized were included in the registry.
Inclusion criteria. a) STEMI within 12 hours from onset of chest pain referred for primary PCI; b) at least 1 significant (> 70%) stenosis eligible for PCI in a coronary artery other than the IRA; c) successful PCI of the IRA; d) patient’s written informed consent.
Exclusion criteria. a) left main stenosis >= 50%; b) cardiogenic shock; c) target lesion in non-IRA not suitable for PCI (diffuse > 4 cm, diameter 300 seconds or > 200 seconds when abciximab was used. Other medications, including beta-blockers, nitrates and ACE-inhibitors, were administered at the discretion of the attending physician.
The procedures were performed by an experienced operator (> 100 urgent PCIs per year) in a tertiary care hospital with constant cardiosurgical support. Angiographic analyses, including initial and final TIMI grade flow, were performed offline by 2 independent observers blinded to the randomization results. Echocardiographic evaluations and clinical status assessment were done on admission and after 24 hours, 30 and 180 days post-PCI. LVEF was assessed according to the recommendations of the American Society of Echocardiography with a 16-segment model.7 The physicians performing echocardiographic evaluation were blinded to the treatment assignment and angiographic results. The study was approved by the institutional Ethics Committee.
The primary endpoint was the absolute improvement of echocardiographically measured LVEF. Two outcomes: recovery time (assessed after 30 and 180 days) and absolute magnitude of LVEF increase were assessed. We compared the percentage of patients who attained the absolute LVEF increase of 5% during 180-day follow-up .
The secondary objective was to assess the safety of 1-stage multivessel PCI. During the study, the following events were registered: all causes of death, AMI, urgent revascularization (including TVR), major and minor bleeding complications, worsening of the CCS class, unstable angina, cardiovascular hospitalization The following data were also recorded: the amount of contrast used, the number and characteristics of implanted stents, duration of procedures and fluoroscopy.
Statistical analysis was performed with Statistica for Windows 6.0 package. For matched samples, the Wilcoxon test was performed, and for unmatched samples, the Mann and Whitney U tests were used. The result was considered to be significant if the p value was 5%) compared to group B (44.7% versus 32.4%, p = 0.028).
In patients screened but not enrolled (registry), mean baseline LVEF was 42.3 ± 3.7% and subsequently increased to 43.8 ± 2.9% after 30 days (p 8
The influence of MVD on the recovery of LV function was assessed by Ottervanger et al.9 in 600 patients with AMI treated with primary PCI. They showed that despite the regained flow in the IRA, the presence of multivessel disease was correlated with lack of a significant improvement of LVEF. In our study, the one-stage complete revascularization was associated with significant improvement of the LVEF throughout the 6-month follow-up. The two-stage approach is also effective in terms of LVEF improvement, but observed increase of LVEF was more pronounced only after the complete revascularization (second stage of the PCI or CABG).
Angiographic failure of primary PCI is associated with higher short- and long-term mortality of AMI patients (7–37%). Multivessel coronary artery disease, particularly three-vessel disease is one of the risk factors of the angiographic failure of primary PCI in AMI. In comparison to patients with single-vessel disease MVD is associated with lower rate of successful PCI with higher incidence of persistent IRA total occlusion and post-procedural complications despite PCI confined to IRA only. Those patients had also a higher rate of urgent coronary artery bypass grafting (CABG) and trend towards higher in-hospital mortality as compared to patients with single-vessel disease.10
Analysis of 790 patients with AMI treated with primary PCI revealed that MVD is among the risk factors of low angiographic success rate (TIMI 50%).11 In the study of the TAMI trial cohort treated with thrombolytic therapy and undergoing subsequent coronary angiography, MVD defined as presence of > 75% luminal diameter stenosis in two or more coronary arteries was associated with higher prevalence of the CHD risk factors and global left ventricular ejection fraction in comparison to single-vessel disease. The non-infarct zone of the left ventricle was significantly more frequently hypokinetic or dyskinetic as compared to single-vessel disease.12 According to Ellis et al., the 3-vessel coronary artery disease was a risk factor of angiographic failure of primary PCI and was associated primarily with a failure to cross the lesion with the guidewire.13
Our finding indicate however that one-stage revascularization in AMI patients with MVD is feasible and safe. The study was neither designed nor powered to determine the incidence of clinical endpoints, however no significant differences in MACE was observed between the group undergoing 1-stage PCI and the group treated with the 2-stage procedure. This is of particular importance, since Moreno et al. found that in 312 patients with AMI treated with primary PCI, MVD was associated with higher in-hospital mortality (21 versus 7%), a higher rate of in-hospital complications (grade II or III atrioventricular block, severe mitral regurgitation, severe bleeding), and a greater need for target vessel revascularization (17 versus 3%) in comparison to single vessel disease. However those observations might have been associated with frequent prevalence of cardiogenic shock at admission. Our study excluded the patients with cardiogenic shock, so the safety of the 1-stage approach has to be further tested in this setting of high-risk patients. Another possible explanation for the higher mortality rate in MVD patients in the study by Moreno is the higher incidence of diabetes, hypertension, prior AMI, CABG and age.14 In our study, however, the frequency of the above-mentioned risk factors was similar in both groups. We acknowledge that in this study, the inclusion and exclusion criteria might have led to preselection of lower risk patients than in the study by Moreno et al. The high rate of MACE in both groups of the PRIMA trial which approaches 25% is driven primarily by TVR for in-stent restenosis and not by death or repeat AMI.
One-stage revascularization is associated with higher contrast medium load and longer procedure time in the setting of the acute phase of STEMI, but no increased incidence of adverse events and complications were noted in long-term follow-up. Two-stage PCI is associated with additional vascular access, stress to the patient, and prolonged hospitalization which increases costs. The mean index hospitalization time was significantly shorter in patients treated with 1-stage PCI, thus influencing the general cost of the treatment.
One of the limitations of 1-step multivessel PCI in the setting of AMI as reported by Hanratty15 is an overestimation of non-IRA stenosis severity on angiography which can affect clinical decision making. The primary cause of such an exaggeration is vasospasm, which is frequently found on coronary angiograms of AMI patients. The coronary angiograms in our study were recorded post-nitroglycerine injection and re-evaluated online by an independent interventional cardiologist blinded to the treatment assignment to prevent the described exaggeration.
The study has certain limitations, since not all patients with AMI and MVD could undergo complete 1-stage PCI and the final therapeutic decision always depends on operator preferences and experience. The registry data showed that a substantial number of patients (less than 50%) initially screened were excluded from the study primarily because their non-IRA stenoses were not eligible for PCI. Further studies are needed with prolonged follow-up periods and a larger number of patients. Also, the echocardiographic evaluation of LVEF is associated with high variability, is strongly operator-dependent and the 5% change in LVEF taken as an endpoint is within the error of measurement. The physicians performing the assessment of echo results were blinded to the treatment assignment to minimize bias. The small number of cases is also a limitation, since hard clinical endpoints could not be evaluated.
Conclusions
These results support the hypothesis that multivessel, complete 1-stage PCI in patients with STEMI and MVD leads to quicker and more substantial improvement of LVEF in comparison to standard 2-stage PCI. This approach seems safe and feasible, however the study was not powered to assess the MACE. In selected patients without cardiogenic shock, this approach may be more effective in improving left ventricular function than 2-stage complete revascularization. This approach also reduces the mean length of hospitalization, fluoroscopy time and the total amount of contrast used, which may be of clinical benefit.
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