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Rheolytic Thrombectomy for Acute Myocardial Infarction Complicated by Cardiogenic Shock
Abstract: Objectives. We sought to investigate the prognostic impact of rheolytic thrombectomy (RT) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). Background. Very few data exist on thrombus removal before stenting in patients with AMI and CS treated with primary percutaneous coronary intervention (PCI). Methods. Of 4023 patients who underwent PCI for AMI between 1995 and 2012, we focused on 371 patients presenting with CS at admission and separated them into two groups: the first included 63 patients treated with RT (RT group), and the remaining 308 underwent standard PCI (non-RT group). The primary endpoint was the composite of cardiac death, reinfarction, stroke, and target-vessel revascularization (TVR) at 2-year follow-up (MACE). Results. The primary endpoint rate was lower in the RT-group (57.1% RT vs 70.8% non-RT; P=.04). The difference between groups was driven by a lower TVR rate (9.5% RT vs 23.4% non-RT; P=.02) and reinfarction (1.6% RT vs 9.1% non-RT; P=.04), while no difference between groups was revealed in mortality (46.0% RT vs 49.4% non-RT; P=.68) or stroke rate (1.6% RT vs 3.2% non-RT; P=.70). At multivariable analysis, the variables related to the risk of the primary endpoint were age (hazard ratio [HR], 1.036; 95% confidence interval [CI], 1.022-1.048; P<.001), three-vessel disease (HR, 1.504; 95% CI, 1.163–1.946; P=.01), RT (HR, 0.689; 95% CI, 0.476–0.998; P=.049), and successful primary PCI (HR, 0.367; 95% CI, 0.266–0.505; P<.001). Conclusion. RT reduces 2-year MACE rate in patients with large thrombus burden and AMI complicated by CS.
J INVASIVE CARDIOL 2016;28(12):E193-E197. Epub 2016 May 15.
Key words: acute myocardial infarction, cardiogenic shock, stroke, thrombus, rheolytic thrombectomy
In patients with acute myocardial infarction (AMI), thrombus removal before infarct artery stenting protects coronary microcirculation from distal embolization and improves coronary blow flow, facilitating stent deployment.1-3 Despite this strong rationale, optical coherence tomography studies have shown that the available devices for thrombus removal cannot remove completely the thrombus complicating a disrupted or eroded coronary plaque in the setting of AMI.4 Large randomized studies on manual thrombus aspiration powered for clinical outcome have shown no benefit of manual thrombus aspiration,5,6 while three randomized studies on rheolytic thrombectomy (RT) have produced conflicting results in terms of clinical outcome and infarct size.7-9 The AiMI trial showed increased 1-month mortality and major adverse cardiovascular event (MACE) rate in patients treated with RT as compared with control.7 Conversely, the JETSTENT trial showed a strong clinical benefit of RT with 1-year decreased mortality and MACE rate as compared with control.8 The third study that included only patients without a history of myocardial infarction showed a significant reduction in infarct size in patients randomized to RT as compared with control.9 The inconclusive or conflicting results of the trials on manual thrombus aspiration and RT may be explained by limitations in study design, technique, non-uniformity of patient treatment, and biased patient selection. The latter frequently results in the exclusion of high-risk patients from randomization and enrollment of low-risk patients for whom it may be difficult or even impossible to show the benefit of thrombus removal. This study sought to determine the impact of RT before infarct artery stenting in patients with AMI complicated by cardiogenic shock (CS).
Methods
Patients and procedures. Consecutive patients treated with primary percutaneous coronary intervention (PCI) for AMI complicated by CS were included in the prospective Florence primary PCI registry. Details of this registry have been previously published.10-12 All baseline and procedural data, as well as angiographic and clinical follow-up data, were entered online, directly into the registry. The data were monitored and adjudicated as part of the regular registry validation.
Criteria for primary PCI were: (1) chest pain persisting >30 minutes with ST-segment elevation on the electrocardiogram (ECG) ≥0.1 mV in two or more contiguous leads; (2) admission within 6 hours of symptom onset, as well as admission between 6 and 24 hours in patients with evidence of continuing ischemia; and (3) no fibrinolytic treatment administered. Angiographic exclusion criteria for primary PCI were: (1) infarct-related artery diameter stenosis <70% on visual assessment; and (2) inability to identify the infarct-related artery. Cardiogenic shock was defined as systolic blood pressure <90 mm Hg (without inotropic or intraaortic balloon counterpulsation [IABP] support) that was thought to be secondary to cardiac dysfunction and associated with signs of end-organ hypoperfusion such as cold or diaphoretic extremities or altered mental status or anuria. Cardiogenic shock diagnosis was to be confirmed at cardiac catheterization by the measurement of systolic blood pressure <90 mm Hg and left ventricular filling pressure ≥20 mm Hg, or an echocardiographic left ventricular ejection fraction (LVEF) <30%.
Rheolytic thrombectomy (AngioJet; Boston Scientific) was introduced in 2001, and routinely performed if there was angiographic evidence of thrombus grade 3 to 5 after infarct artery wiring according to the Thrombolysis in Myocardial Infarction (TIMI) classification.13 Most patients were also treated with stenting of the infarct-related artery (IRA), and PCI was prevalently supported with IABP. In patients with multivessel disease, multivessel PCI during the same procedure or staged PCI were left at the discretion of the operator.
Abciximab was used routinely after 1998, and unfractionated heparin was given to achieve an activated clotting time of 200 to 250 seconds. After 2010, the use of bivalirudin was allowed. All patients received 325 mg oral loading dose of aspirin. Antiplatelet therapy also included ticlopidine, clopidogrel, or prasugrel. Medical therapy for ST-elevation myocardial infarction and heart failure was given in accordance with standard and recommended practice.
All patients had scheduled clinical and electrocardiographic examinations at 6 months, 1 year, and yearly thereafter. Patients were scheduled for angiographic follow-up at 6-9 months if not contraindicated by moderate or severe renal insufficiency. All possible information derived from hospital readmissions or by the referring physician, relatives, or municipality live registries was entered into the prospective database.
The primary endpoint of the study was the composite of cardiac death, myocardial infarction, stroke, and target-vessel revascularization at 2-year follow-up. All deaths were considered cardiac unless an unequivocal non-cardiac cause could be documented. The diagnosis of non-Q wave myocardial infarction was based on an increase of creatine kinase myocardial band isoenzyme or troponin I >3 times the upper limit of normal, or for patients with elevated values on admission as a re-elevation of creatine kinase-MB or troponin I values. A Q-wave myocardial infarction was defined as the development of new Q-waves in 2 or more electrocardiographic leads, and in addition to creatine kinase-MB or troponin I elevation. Stroke was defined as an acute neurological defect lasting more than 24 hours. Target-vessel revascularization was defined as a repeat PCI or coronary surgery of the infarct-related artery due to recurrent ischemia or angiographic restenosis. Angiographic restenosis was defined as >50% luminal narrowing at the segment site including the stent and 5 mm proximal and distal to the stent edges of the target vessel on the follow-up angiography. Angiographic parameters were assessed using an automated edge-contour detection computer analysis system (Innova 2100IQ; General Electric Healthcare Technologies). Stent thrombosis was defined according to the Academic Research Consortium criteria.10Primary PCI success was defined as <30% residual stenosis of the infarct-related artery and a final TIMI grade 3 flow.
To preserve comparable parameters and avoid bias, final outcomes analysis was performed at 2-year follow-up for each patient.
Statistical analysis. Discrete data were summarized as frequencies, whereas continuous data were summarized as mean ± standard deviation or median and interquartile range (IQR) when appropriate. The Fisher’s exact test or Pearson’s Chi-squared test were used for comparison of categorical variables, and the unpaired and paired 2-tailed Student’s t-tests were used to detect difference among continuous variables. Survival curves were generated using the Kaplan-Meier method, and the difference between groups was assessed by a long rank test.
To analyze the independent effect of RT on the primary endpoint, a multivariable Cox regression backward stepwise analysis was used. The variables included in the model were age, female gender, diabetes mellitus, multivessel disease, previous myocardial infarction, LVEF, abciximab use, drug-eluting stent use, RT, year of index procedure, and successful primary PCI. An interaction test was made by Cox regression analysis. All tests were two sided, and a P-value <.05 was considered statistically significant. Analysis were performed with SPSS software, version 19 (IBM Corporation).
Results
From January 1995 to December 2012, a total of 4023 consecutive patients underwent primary PCI. Out of these, 371 patients (9%) had CS on admission. RT was performed in 63 patients, while the remaining 308 patients underwent standard PCI. Table 1 summarizes the clinical and procedural characteristics of the two groups. Overall, the mean age of patients was 70 years, the majority of patients had multivessel disease, and more than one-fourth had at least 1 chronic total occlusion. The target vessel was the left anterior descending artery or the left main artery in the majority of patients. The two groups were similar in all baseline characteristics except the history of myocardial infarction, which was more frequent in the non-RT group (19.8% non-RT vs 4.8% RT; P=.01).
The post-PCI reference vessel diameter of the infarct-related artery was larger in the RT group (3.33 ± 0.436 mm RT vs 3.18 ± 0.484 mm non-RT; P=.01).
Overall, the PCI success rate was similar in the two groups (88.9% RT vs 84.7% non-RT; P=.56), multivessel PCI was performed during the index procedure in 30% of patients, and the majority of patients received mechanical support with IABP support. Abciximab use was more frequent in the RT group than the non-RT group (77.8% vs 44.2%, respectively; P<.001).
Table 2 summarizes the clinical and angiographic outcome. The clinical follow-up rate at 2 years was 100%. The primary endpoint rate was lower in the RT group than the non-RT group (57.1% vs 70.8%, respectively; P=.04). The difference between groups was driven by a lower rate of target-vessel revascularization (9.5% RT vs 23.4% non-RT; P=.02) and reinfarction (1.6% RT vs 9.1% non-RT; P=.04), while no difference between groups was revealed in mortality or stroke.
There was only 1 reinfarction in the RT group, which occurred at the third day after the index PCI and was related to the target vessel. On the other hand, 28 reinfarctions occurred in the non-RT group. Of these, 20 events occurred before the 9th month and 8 events occurred after that point. In the non-RT group, 17 reinfarctions occurred in the target vessel territory.
Figure 1 shows the Kaplan-Meier curves for the primary endpoint-free survival of the two groups.
At multivariable analysis, the variables related to the risk of the primary endpoint were age (hazard ratio [HR], 1.036; 95% confidence interval [CI], 1.022-1.048; P<.001), three-vessel disease (HR, 1.504; 95% CI, 1.163-1.946; P=.01), RT (HR, 0.689; 95% CI, 0.476-0.998; P=.049), and successful primary PCI (HR, 0.367; 95% CI, 0.266-0.505; P<.001).
There was no interaction between the year of index of procedure and RT for the primary endpoint (P=.83).
Out of the 218 eligible survivors, a total of 208 (95.4%) underwent 6-9 month angiographic follow-up. Restenosis or reocclusion rate was lower in the RT group vs the non-RT group (14.2% and 20.8%, respectively; P=.49)
Discussion
The main findings of this study can be summarized as follows: (1) RT in the setting of AMI complicated by CS and associated with a large thrombotic burden is effective in decreasing the rate of target-vessel revascularization and reinfarction; and (2) RT is not associated with improvement in long-term survival in patients with AMI complicated by CS.
There are very few data on thrombus removal before infarct artery stenting in patients with CS. The efficacy of manual thrombus aspiration was assessed in two small series of patients (overall 199 patients) and neither study showed any clinical benefit of manual thrombus aspiration.14,15 With regard to RT, the JETSTENT randomized trial enrolled a small number of patients (20 patients) with CS and could not provide specific details on the outcomes of these patients.8 A retrospective study by Sianos et al focused on drug-eluting stent thrombosis and included 76 AMI patients with CS, showing that large thrombotic burden is a strong predictor of 2-year adverse events (HR, 1.88; 95% CI, 1.3-2.72; P=.01) and that RT is inversely related to the risk of major adverse events at 2-year follow-up (HR, 0.37; 95% CI, 0.17-0.78; P=.01).16 In a randomized study comparing the efficacy of manual thrombus aspiration with RT using optical coherence tomography, Parodi et al showed that although complete thrombus removal is not possible in most patients, large residual thrombus burden after RT is uncommon and RT is associated with better stent apposition and lower target-vessel revascularization rate than manual thrombus aspiration.4 The results of the present study are consistent with the results of the JETSTENT trial and the studies of Sianos et al and Parodi et al,8,16,4 and support the use of RT in AMI complicated by CS.
In fact, we consider the larger post-PCI reference vessel diameter of target vessels in the RT group a key point of this study, which could explain the benefit of RT in terms of restenosis and reinfarction. As already suggested in the above-mentioned clinical trials, we hypothesize that the true reference vessel diameter could be better defined after RT, allowing operators to better choose the stent, improving stent apposition and consequently reducing the target-vessel failure rate.
The utilization of abciximab was significantly higher in the RT group, with the difference due to the availability of both tools. However, we started using abciximab in 1998, at least 3 years before RT was available. The benefit of abciximab on clinical outcomes – not only target-vessel revascularization – in ACS patients treated with PCI is well noted. It is reasonable to suppose that abciximab could have improved the success rate of primary PCI in the RT group as well as the long-term clinical outcome. In spite of this, there was no difference on success of primary PCI between the groups, and abciximab use was tested in the multivariable Cox-regression analysis, proving negative for the composite primary endpoint.
The SHOCK trial, the only concluded randomized trial on CS complicating AMI, has shown that successful PCI is the strongest predictor of survival.17 As a consequence, all techniques and drugs that may decrease the risk of no-reflow, including RT in patients with large thrombus burden, should be considered in the percutaneous approach to this high-risk subset of AMI patients.
Study limitations. This is a retrospective analysis with all of the limitations inherent therein. However, as shown by the problems encountered by SHOCK investigators in patient recruitment, the feasibility of a randomized study comparing RT with standard PCI techniques is very unlikely. This study was an analysis of a 17-year registry of patients treated for CS. Although the multivariable analysis with interaction test excluded the effect of the year of index procedure on outcomes, techniques and drugs applied evolved widely through this long period. Comparative data regarding non-cardiac comorbidities and concomitant medications through the follow-up period are limited and possible bias due to incomplete information is possible. Although the multivariable analysis was an effort to exclude potential bias, we were unable to investigate the possible causative effects of treatment variation.
Conclusion
The results of this study support the use of RT in patients with large thrombus burden and AMI complicated by CS.
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From the Division of Cardiology, Careggi-Hospital, Florence, 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 January 11, 2016, provisional acceptance given February 1, 2016, final version accepted March 18, 2016.
Address for correspondence: David Antoniucci, MD, Division of Cardiology, Careggi Hospital, Viale Morgagni I-50139, Florence, Italy. Email: david.antoniucci@virgilio.it
