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Delayed Stenting for ST-Elevation Acute Myocardial Infarction in Daily Practice: A Single-Centre Experience
Accepted Manuscript Delayed stenting for ST-elevation acute myocardial infarction in daily practice: A single center experience Julien Pascal, MD, Aurélie Veugeois, MD, Michel Slama, MD, Saliah Rahal, MD, Loic Belle, MD, Christophe Caussin, MD, Nicolas Amabile, MD, PhD PII:
S0828-282X(15)01440-3
DOI:
10.1016/j.cjca.2015.09.015
Reference:
CJCA 1881
To appear in:
Canadian Journal of Cardiology
Received Date: 19 June 2015 Revised Date:
2 September 2015
Accepted Date: 11 September 2015
Please cite this article as: Pascal J, Veugeois A, Slama M, Rahal S, Belle L, Caussin C, Amabile N, Delayed stenting for ST-elevation acute myocardial infarction in daily practice: A single center experience, Canadian Journal of Cardiology (2015), doi: 10.1016/j.cjca.2015.09.015. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Delayed stenting for ST-elevation acute myocardial infarction in daily practice: A single center experience
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Running title: Delayed stenting strategy in STEMI Julien Pascal, MD1 Aurélie Veugeois, MD2, Michel Slama, MD3,4, SaliahRahal, MD4,
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Loic Belle, MD 5, Christophe Caussin, MD2 and Nicolas Amabile, MD, PhD2
1: Cardiology department, Centre Hospitalier Le Raincy-Montfermeil,
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Montfermeil, France
2: Department of Cardiology, Institut Mutualiste Montsouris, Paris, France 3: Cardiology department, CHU Antoine Beclère, Clamart, France 4: Cardiology Department, Centre Marie Lannelongue, LePlessis Robinson, France
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5: Cardiology Department, CH Annecy, Annecy, France
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Correspondence: Dr Nicolas Amabile, MD, PhD,
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Department of Cardiology, Institut Mutualiste Montsouris, 42 boulevard Jourdan, 75014 Paris, France Email: [email protected]; Phone +33 1 56 61 65 58
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ABSTRACT (249 words)
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Background: The minimalist immediate mechanical intervention (MIMI) strategy aims to restore normal anterograde flow in the culprit artery (by using manual thrombectomy and/or small size balloon predilation) and to defer potential stent implantation. This study
myocardial infarction (STEMI) management.
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evaluated the applicability and mid-term clinical results of the MIMI strategy for ST elevation
Methods: This observational study included consecutive patients admitted for ongoing
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STEMI (<24h evolution) in one institution between June 2010 and June 2013.
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Revascularization strategy was performed at the physician’s discretion. We compared retrospectively the « intentional immediate stenting » (Standard technique) and the « intentional delayed stenting » (MIMI technique).
Results: 20% of the 279 included patients were treated following the MIMI strategy. These
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patients were significantly younger, more frequently male and smoker compared to the Standard patients. The rate of acute reocclusion of the culprit artery related to STEMI in the MIMI group was 1.8%. Drug-eluting stents were more frequently used in the MIMI group
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(52% vs. 27% in Standard group, p<0.001). The culprit lesion was less frequently stented in the MIMI patients compared to other patients (28.5 vs. 9%, p<0.001). The 1-year actuarial
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survival free from major adverse cardiovascular events was higher in the MIMI than in the Standard group (96.3±1.8% vs. 83.8±2.5%, p=0.01). Conclusion: The MIMI strategy can be applied in some selected STEMI patients. In our center, this strategy is associated with less systematic culprit lesion stenting and more DES implantation. However, this needs to be evaluated further in a randomized trial.
KEY WORDS: STEMI; manual thrombectomy; deferred stenting; prognosis
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ACCEPTED MANUSCRIPT BRIEF SUMMARY: This study investigated clinical compared outcome in patients with acute STEMI treated with intentional delayed stenting (MIMI) strategy or immediate stenting standard strategy. DES were more frequently used in the MIMI group; the culprit lesion was
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not stented in 28.5% of these patients (vs. 9% in standard group, p<0.001). The 1-year actuarial survival free from MACE was higher in the MIMI than in the Standard group
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(96.3±1.8% vs. 83.8±2.5%, p=0.01).
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INTRODUCTION
Despite considerable progress in last decades with the advent of interventional cardiology and mechanical revascularization (1,2), stent implantation during ST-elevation myocardial infarction (STEMI) could be associated with coronary emboli or micro vascular obstruction,
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due to the highly thrombotic environment (2). This complication occurs in about 30% of patients admitted for STEMI and is associated with increased infarct size (3). Moreover, percutaneous coronary intervention (PCI) during STEMI remains a major risk factor for
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inadequate stent deployment or under sizing (due to large thrombus burden on culprit lesion that limits proper struts apposition on vessel wall and because of initial post
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deocclusion culprit vessel vasospasm), which can favor stent thrombosis, restenosis and subsequent need for target vessel revascularization (4-6). Indeed, large thrombus burden could limit proper struts apposition on culprit lesion and initial post reperfusion culprit vessel vasospasm may lead to underestimation of artery’s size.
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The concept of minimalist immediate mechanical intervention (MIMI) for STEMI management was proposed for the first time by Isaaz et al (7). The aim of this strategy is: 1)
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to restore the best anterograde flow in the culprit artery when it’s not achieved by upstream pre-cath lab medications, using wiring and/or manual thrombectomy and/or angioplasty
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with a small size (≤2 mm diameter) balloon catheter AND 2) to defer stent implantation whenever possible. Delayed stenting is attempted only after several days of systemic anticoagulation and antiplatelet therapy in order to reduce the thrombus burden in the infarct-related artery and get rid of the initial post deocclusion culprit vessel vasospasm. Stenting can be entirely omitted in cases where there is no residual stenosis following adequate medical and anticoagulation therapies received in the interval between reperfusion and planned deferred stenting (8).
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Although the theoretical risk of culprit artery reocclusion between the two procedures has been suspected, published data reported the feasibility and safety of this approach (9), but its short-term benefits are debated (10,11). Furthermore, there is no current data regarding the middle and long-term evolution of the patients managed by the MIMI approach.
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The aim of this study is to evaluate the applicability of this strategy in daily practice and
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assess its impact on cardiovascular short and middle-term outcome.
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METHODS
Study design and eligibility criteria This work was a retrospective observational study conducted in the Centre Chirurgical Marie Lannelongue between June 2010 and June 2013. All consecutive patients
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admitted for acute ongoing STEMI in the institution were screened for inclusion. There was no selection in terms of clinical presentation and admission time (business hours, week-ends
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and nights). Patients were eligible for inclusion if: 1) they had chest pain suggestive of
myocardial ischemia for at least 30 minutes before hospital admission 2) the time from the
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onset of symptoms to hospital admission was less than 24 hours 3) electrocardiogram (ECG) showed new ST-segment elevation or left bundle-branch block (12). Patients were excluded if they had any of the following criteria: absence of coronary angiography performed, normal coronary angiography (absence of significant coronary artery stenosis >30% on angiography
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(13), acute coronary syndromes occurring ≤ 1 month after cardiac surgery, non-ST elevation myocardial infarction or unstable angina. Baseline clinical, biological and angiography parameters were collected in a local database for each patient.
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The study complied with the Declaration of Helsinki. Our local Hospital‘s Ethics
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Committee approved the research protocol.
Coronary angiography and revascularization strategies All patients included in the study were routinely treated with double antiplatelet
therapy including aspirin with a P2Y12 inhibitor (clopidogrel or prasugrel or ticagrelor) and unfractionated or low molecular weight heparin. Adjunctive anti thrombotic therapy with Gp IIb/IIIa inhibitor (abciximab/ full dose bolus + 12h infusion) or bivalirudin infusion (full dose bolus + 8h infusion) was left to the operator’s discretion.
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After coronary angiography, PCI was performed with a 6 Fr guiding catheter in suitable patients, mostly through transradial access.
The initial objective was to achieve the best flow in the infarct related artery with
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mechanical manual thrombus aspiration (Eliminate®, TERUMO, Tokyo, Japan/ The number of passes was left at the operator’s discretion) and/or balloon predilation (Emerge® 1.5 to 2 mm diameter x 8 to 12 mm length, Boston Scientific, Nantick, MA, USA).
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An optimal reperfusion was defined as follows: 1) antegrade TIMI flow ≥2, 2) chest pain cessation, 3) reduction in ST elevation>50% on immediate post-intervention ECG (14).
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When at least one of these 3 was not reached, operators had to proceed with stenting (intentional immediate stenting / Standard strategy group).
When optimal reperfusion was achieved, the operator could choose either immediate culprit lesion treatment (Standard strategy) or deferred control (intentional
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delayed stenting / MIMI strategy group).
Patients who were in the minimally invasive procedure group underwent a second
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coronary angiogram at physician’s discretion. Sustained anticoagulation by LMWH was provided to all patients from the MIMI group in the delay between the two procedures. In
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the absence of any significant residual stenosis on the repeat angiogram, the decision to forego stent implantation was considered. In case of multiple vessel disease, no PCI was performed in the non-infarct related
arteries during initial procedure, except in case of cardiogenic shock at admission (12). Nonculprit lesions revascularization was guided by the results of subsequent deferred noninvasive tests or fractional flow reserve measurement. Complete revascularization by CABG
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was considered in case of SYNTAX score>30 and after careful evaluation by a multidisciplinary Heart Team.
Coronary angiography analysis
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Two independent operators (JP & NA, blinded to clinical outcome) retrospectively reviewed coronary angiograms and analyzed culprit lesion characteristics, including
antegrade angiographic flow and thrombus grade in the culprit vessel according to the TIMI
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criteria (Gibson angiographic thrombus score) (15). Discordances were resolved by
consensus. The degree of stenosis was calculated by a dedicated quantitative coronary
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angiography (QCA) software (Centricity CA1000 / GE Healthcare, Buc, France) (14).
Clinical follow-up & endpoint definitions
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The patients included in the study were prospectively followed-up regarding cardiovascular adverse events and bleeding events 1) during the in-hospital period by reviewing medical records and discharge letters then 2) during the first year following STEMI
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through clinic visits in our institution, direct phone contact with the patients or contact with treating physicians in charge of the patients (in case they were not followed in our
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institution). The same methodology was applied for patients entirely managed in our institution and those transferred to other institutions after PCI. The primary endpoint was the freedom from MACE (major adverse cardiovascular
events) including cardiovascular death, recurrent myocardial infarction and ischemia-driven target vessel revascularization (TVR) (16). Acute culprit vessel reocclusion was defined as the recurrence of chest pain and ST modifications on ECG suggesting on-going ischemia with
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evidence of antegrade TIMI flow< 3 in the artery on control angiography. Bleeding events were defined according to the BARC criteria (17).
Statistical analysis.
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Statistical analysis was performed with SPSS 21.0 (SPSS software, Chicago, IL, USA) software. Data are expressed as mean ± Standard error of the mean (SEM) and the normality of their distribution was assessed by Kolmogornov-Smirnov test. Baseline parameters
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between patients from the 2 strategies groups were compared using the parametrical
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Student t test or non-parametrical U Mann-Whitney and χ² or Fisher exact test for quantitative and categorical variables respectively. Angiographic parameters evolution between procedures in the MIMI group was compared using the Friedman test for categorical variables and Student t test for continuous variables. Patient survival from MACE
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was analyzed and Kaplan-Meier curves were constructed. Differences between survival curves were evaluated using the log-rank test. Multivariable Cox models were used to assess the relation of clinical covariates with the incidence of the primary endpoint (MACE)
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within one year following the procedure. Given the observational nature of the study, and to minimize indication bias for undergoing MIMI procedure, propensity score analyses were
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conducted. Differences were considered significant at p <0.05. For detailed Statistical Analysis methods, see Supplementary Materials.
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RESULTS
Baseline characteristics The flow chart of the study is given in Figure 1. Between June 2010 and June 2013, 372 consecutive patients were referred to the institution for suspected ongoing STEMI.
279 patients eligible for PCI were treated by the MIMI strategy.
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Ninety-three of them were ruled out from the analysis due to exclusion criteria. 20% of the
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The baseline characteristics of the population are reported in Table 1. Patients were significantly younger, more frequently males, more frequently smokers, had a higher
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incidence of dyslipidemia and presented less frequently with cardiogenic shock in the MIMI group compared to the Standard group. Radial access was used in 85% of the cases in the whole cohort.
There was no significant difference regarding the delay between symptoms onset
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and PCI between groups. The initial pre-PCI TIMI flow was significantly higher and the culprit lesion stenosis percentages lower in the patients treated by the MIMI strategy compared to the others. Manual thrombus aspiration was used as the first option for culprit lesion
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recanalization in 70% of our patients and balloon angioplasty in 14% of the cases. The
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average number of thrombectomy catheter passes was higher in the patients from the MIMI group compared to the Standard group, leading to a higher TIMI flow and a lower degree of stenosis.
Evolution of culprit lesion characteristics in the MIMI patients The mean delay between initial and control angiogram was 4.3±3.2 days in the MIMI group. These patients were more frequently treated with anti GPIIb/ IIIa infusion and prasugrel than the patients from the Standard group (Table 1). One patient from the MIMI
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group (1.8%) experienced a culprit vessel reocclusion related to culprit lesion dissection (occurring 15 minutes after initial thrombectomy and before leaving the cath lab) that required urgent stent placement (vs. one case of acute stent thrombosis (0.4%) in the Standard group). There was no significant difference in hemorrhagic complications between
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groups: BARC 3 bleeding were observed in 1.8% of MIMI patients vs. 1.3% of Standard patients (p=0.56), BARC 2 bleeding in 3.6% of MIMI patients vs. 1.8% of Standard patients (p=0.41) and BARC 0+1 bleeding in 94.6 % of MIMI patients vs. 96.9% of Standard patients
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(p=0.43).
We observed a significant thrombus burden reduction in the MIMI patients between
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the two coronary angiographies (p<0.001 using Friedman test/Figure 2), but there was no difference between the degrees of stenosis by QCA (53±2% vs. 57±3%, p=0.69).
Revascularization options according to strategies
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We observed significant differences in the revascularization options between groups according to the management strategy (Table 2). Hence, there was a higher use of drug
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eluting stent (DES) in the MIMI group than in the Standard group among patients whose culprit lesion was stented (52 vs. 27%, p<0.001). Furthermore, the patients from the MIMI
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strategy group were more frequently treated by thrombectomy alone (28 vs. 12%, p=0.001) and underwent culprit lesion stenting less frequently than patients from the other group (70 vs. 85%, p=0.006).
Clinical outcome Clinical follow-up was achieved in 263 out of 279 patients (the 12 other patients were unreachable or provided incorrect personal information for follow-up). The median follow
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up was 44.4±28.8 months (43.8±30.5 in Standard group vs. 48±21.4 months in MIMI group, p=0.91). During this period, there were a total of 40 major adverse cardiovascular events (Table S1 in Supplementary Materials). The 1-year actuarial survival free from MACE was higher in the MIMI patients compared to the others (96.5±2.5 vs. 83.8±2.5%, p=0.01 log-rank
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analysis / Figure 3A). However, there was no significant difference regarding the 1-year actuarial survival free from TVR between the two groups (98.2±1.8 % vs. 95.7%±1.2%,
p=0.35 log rank analysis). Because of the impact of initial cardiogenic shock on outcome, we
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then excluded patients presenting with this condition (n=28) for a sub-analysis. Once again, we observed a higher 1-year survival from MACE in the MIMI patients compared to the
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others (Figure 3B).
Finally, we analyzed the predictors of MACE in this STEMI cohort to ascertain the role of the MIMI strategy as a protective factor in this situation. A first Cox multivariate regression analysis (without adjusting for the propensity score matching) revealed that
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cardiogenic shock at admission; age and multivessel disease were independently associated with adverse outcome. The use of MIMI strategy was not an independent protective factor
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against MACE in the whole cohort (HR= 0.28 [0.06-1.10], p=0.07/ Table 3). The propensity score analysis was performed by matching one MIMI with 2 standard
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patients (using a difference of probability of receiving MIMI of less than 5% between the MIMI and the controls). This analysis was performed with n=106 pairs and showed no significant difference between the two procedures (HR MIMI vs. standard: 0.34 (95%CI: 0.081.54), p=0.16). Furthermore, there was no significant difference between the two procedures in the multivariate analysis after adjustment for the propensity score (HR MIMI vs. standard: 0.34 (95%CI: 0.08-1.46), p=0.14).
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DISCUSSION
This retrospective study evaluated the impact of the minimalist immediate mechanical intervention for STEMI patients’ management in daily practice. The main findings of the current study are: 1) The MIMI strategy was frequently used (20% of our cohort) and
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safe (one reocclusion of the culprit artery in selected patients and no higher incidence of bleeding events); 2) The use of this strategy influenced the revascularization modalities with
cardiovascular events following this approach was low.
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fewer stents implanted and increased use of DES; 3) The incidence of major adverse
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Culprit vessel occlusion during acute coronary syndromes is related to the addition of a thrombus to an unstable or ruptured atherosclerotic plaque. The presence of this highly thrombotic environment underlies most of the potential PCI pitfalls in this situation, such as coronary embolization, no reflow or poor stent deployment. The concept of a 2 steps-
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approach (initial thrombectomy followed by deferred stenting) has been recently developed by different groups (7,11,18-20) in order to overcome these limitations in STEMI patients. However, this strategy might not be applicable in all patients. In the current study, 20% of
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our patients were treated with the MIMI strategy. These subjects were younger, more
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frequently smoker and had a lower incidence of cardiogenic shock at admission than the patients from the Standard group. Moreover, we observed that the patients who were eligible for the MIMI approach had better post-recanalization angiographic results (as assessed by the degree of stenosis, TIMI antegrade flow and the thrombus grade) than the others. A less severe lesion at baseline, a larger thrombus burden or a more efficient thrombectomy on culprit lesion, might explain these results. According to previous reports, the number of culprit lesion reocclusion was very low among the MIMI patients (1.8%) (9,11), which might be related to an adequate culprit lesion initial preparation and a large
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use of anti GPIIb/ IIIa infusion. Hence, the MIMI strategy appears to be safe but might be only proposed to patients with adequate clinical profile and highly baseline thrombotic lesion, but should be avoided when a residual dissection is visible after recanalization. Our data show significant differences in revascularization modalities between the
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two groups. Hence, patients from the MIMI group were more frequently treated by lone thrombectomy than the others. This treatment was used in almost one third of the MIMI patients and is in line with previously reported data (20-22). These results suggest that
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correct thrombus removal by both mechanical and pharmacological methods could avoid unnecessary device implantation to treat culprit lesion during STEMI in a significant number
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of patients. Furthermore, when PCI was decided, DES were much more frequently implanted in the MIMI group than in the Standard group. Although current guidelines recommend DES use during STEMI, this option is frequently limited by different factors that could influence the risk for future stent thrombosis (23). First, the patient’s compliance to double
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antiplatelet therapy as well as the potential bleeding risks are sometimes difficult to assess during primary PCI for STEMI. Second, DES implantation during STEMI has been suspected to
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favor incomplete stent apposition and poor neointimal coverage, which could promote devices failure (4,6). Delayed stent implantation would thus take a step back on the patient's
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profile and history and evaluate more objectively the benefit/risk ratio of medical treatment. Furthermore, as the thrombus burden decreases and culprit vessel dimensions increase over time under medical optimal therapy (14), a deferred PCI strategy could help optimizing PCI results by choosing the adequate device dimensions and improve apposition. Although the deferred provisional stenting approach has shown some encouraging results regarding the short-term outcome (11,18,20), very few data reported the long-term safety of this procedure (20). Our study shows that the 1-year incidence of MACE was low,
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with a very limited number of TVR procedures (actuarial survival: 98.2±1.8%) in the MIMI group. These findings might be related to a more appropriate revascularization modality in this group (see above) and a higher use of DES. We observed a statistical difference in outcome between the two management strategies according to the results from Kelbaeck et
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al (20). However, this difference might also be explained by the risk profile of the patients in each group and the higher incidence of cardiogenic shock among subject treated by the Standard approach. Hence, the different multivariable analyses (including propensity-score
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matching analysis) did not prove any significant protective impact of the MIMI strategy, yet a very clear trend was observed. This lack of significance might be explained by the relatively
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small number of patients included in our series and advocate for the need of larger, randomized trials to evaluate the deferred stenting approach in this situation.
Our study has several limitations that warrant considerations. First, our results are
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based on data retrospectively collected from a single catheterization facility and were not obtained from a randomized trial. Since this work was designed as an observational study,
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some of the differences in patients’ baseline characteristics might have biased the results, such as the higher incidence of stent thrombosis (although no consensus exists regarding the
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best management for this particular condition), lower incidence of initial cardiogenic shock or younger age in the MIMI patients, suggesting a possible selection bias in this group. However, this strategy seems particularly interesting in young subjects, thus avoiding potentially damaging late effects of stenting. Similarly, in case of initial cardiogenic shock at presentation, repeated invasive procedures under unstable hemodynamic conditions seem difficult and this explains the uselessness of MIMI strategy in this situation. The relative small number of patients and events during follow-up might also limit some of our conclusions, as witnessed by the wide confidence intervals of the HR in our 15
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multivariable analysis. However this work aimed to evaluate the short and long-term safety of the MIMI strategy in daily practice and did not intend to prove its superiority over the immediate stenting regarding outcome. Finally, the MIMI strategy was initially described in France, where it became increasingly popular over time. Thus, French interventional
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cardiologists are experienced with this STEMI management approach and our findings might not be reproducible in countries where MIMI is not a commonly performed procedure (such
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as Canada).
In summary, this current observational study shows that the MIMI strategy was
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applicable and safe in some selected STEMI patients in daily practice. This 2 steps approach appeared to change the revascularization modality compared to Standard strategy and provided good short term and midterm clinical outcomes. Further larger studies are needed
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FUNDING: None
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to confirm the potential clinical benefits of this strategy in the future.
ACKNOWLEDGEMENT: We thank Lucile Offredo (INSERM U970, Paris Cardiovascular
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Research Centre) for her assistance in statistical analysis.
DISCLOSURES: None of the authors reports any conflict of interest in relation with this article
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FIGURE LEGENDS
FIGURE 1: Study workflow
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FIGURE 2: Regression of thrombus burden between coronary angiographies in the MIMI group patients, as assessed by the TIMI thrombus grade (p<0.001).
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FIGURE 3: Kaplan Meier estimates of MACE survival in patients treated with the MIMI or the Standard strategy in the whole cohort (A) and after exclusion of
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patients presenting with initial cardiogenic shock (B).
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TABLE 1: Baseline clinical, angiographic and procedural characteristics of the
Global Cohort
Standard group
MIMI group
N=279
N=223
N=56
Age (years)
62.0±0.9
63.1±1.0
Male gender, n(%)
214 (77)
164 (74)
Smoker, n(%)
195 (70)
147 (66)
48 (86)
0.004
Hypertension, n(%)
153 (55)
125 (56)
28 (50)
0.42
Diabetes, n(%)
59 (21)
44 (20)
15 (27)
0.25
Dyslipidemia, n(%)
188 (67)
144 (65)
44 (79)
0.046
BMI (kg.m-2)
27.9±1.5
28.2±1.9
26.8±0.5
0.72
Personal history of CAD, n(%)
44 (16)
36 (16)
8 (14)
0.73
Familial history of CAD, n(%)
51 (18)
42 (19)
9 (16)
0.63
Symptoms onset to PCI delay (min)
368±18
380±21
321±35
0.26*
Primary PCI, n(%)
246 (88)
200 (90)
46 (82)
0.12
Previous Thrombolysis, n(%)
33 (12)
23 (10)
10 (18)
0.12
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population (p value is for comparison between Standard and MIMI group).
15 (5)
15 (7)
0
0.04
LAD, n(%)
120 (43)
97 (44)
23 (41)
0.74
Circumflex, n(%)
36 (13)
27 (12)
9 (16)
0.43
RCA, n(%)
116 (42)
92 (41)
24 (43)
0.83
12 (4)
10 (5)
2 (4)
0.76
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STEMI characteristics
Cardiogenic shock at admission, n(%)
57.9±2.0
0.02
50 (89)
0.01
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Risk Factors
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Infarct related artery
Left Main, n(%)
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TABLE 1 (CONTINUED)
Global Cohort
Standard group
MIMI group
N=279
N=223
N=56
Single vessel disease, n(%)
105 (38)
81 (36%)
24 (43%)
Double vessel disease, n(%)
94 (34)
76 (34%)
Triple vessel disease, n(%)
78 (28)
66 (30%)
Stent thrombosis, n(%)
17 (6)
10 (4)
Initial TIMI antegrade flow
1.1±0.8
Initial TIMI thrombus grade
4.6±2.8
Initial culprit lesion QCA (%)
89±1
Balloon predilation, n(%)
P
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Baseline angiographic characteristics
20 (36%)
0.45
12 (21%)
0.03
1.0±0.1
1.4±0.2
0.02*
4.7±0.4
4.2±0.1
0.09*
90±1
84±2
0.007*
40 (14)
37 (17)
3 (5)
0.03
Thrombectomy, n(%)
195 (70)
154 (69)
41 (73)
0.54
Number of thrombectomy catheter passes
1.8±0.1
1.7±0.1
2.3±0.6
0.01
No thrombectomy or predilation, n(%)
44 (16)
32 (14)
13 (23)
0.1
Post recanalization TIMI antegrade flow
2.5±0.5
2.4±0.6
2.9±0.5
<0.001*
Post recanalization TIMI thrombus grade
3.9±0.4
4.2±0.5
2.7±0.1
0.002*
Post recanalization culprit lesion QCA (%)
65±1
68±2
57±3
<0.001*
Aspirin, n(%)
279 (100)
223 (100)
56 (100)
1.0
Prasugrel, n(%)
159 (57)
118 (53)
41 (73)
0.01
Clopidogrel, n(%)
108 (39)
94 (42)
14 (26)
0.02
3 (1)
2 (1)
1 (1)
0.65
128 (46)
87 (39)
41 (73)
<0.001
18 (7)
12 (5)
6 (11)
0.15
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Initial recanalization procedure
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7 (13)
Pharmacological management
Ticagrelor, n(%) Abciximab infusion, n(%) Bivalirudin, n(%)
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Table 1: *: U Mann Whitney test
Abbreviations: BMI: body mass index; CAD: coronary artery disease; LAD: left anterior descending artery; MIMI: minimalist immediate mechanical intervention; PCI: percutaneous coronary intervention; QCA: quantitative coronary angiography; RCA: right
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coronary artery; TIMI: Thrombolysis in Myocardial Infarction.
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TABLE 2: Revascularizations strategies among groups (p value is for comparison between Standard and MIMI strategy groups).
Standard Strategy
MIMI Strategy
(N=223)
(N=56)
8 (3)
Culprit lesion stenting, n(%)
190 (85) BMS, n(%)
129 (58)
DES, n(%)
61 (27) 25 (12)
0.49
39 (70)
0.006
10 (18)
<0.001
29 (52)
<0.001
16 (28)
0.001
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No additional PCI on culprit lesion, n(%)
1 (2)
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CABG, n(%)
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p
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p
HR [95% CI]
Multivariable Analysis
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Univariable Analysis
0.02
1.03 [1.00-1.05]
Male gender
0.39
0.7 [0.4-1.5]
Previous personal CAD history
0.28
1.7 [0.7-4.2]
Symptoms onset to PCI delay (per min)
0.49
1.0 [0.99-1.01]
Diabetes Multivessel disease DES implantation
MIMI strategy
0.04
1.03 [1.00-1.05]
6.4[2.8-14.7]
0.001
4.3 [1.9-10.1]
0.68
1.2 [0.6-2.5]
0.001
2.0[1.3-3.1]
0.01
1.8 [1.2-2.7]
0.01
0.3 [0.1-0.8]
0.20
0.5 [0.2-1.4]
0.48
1.2 [0.6-2.4]
0.02
0.2 [0.05-0.81]
0.07
0.3 [0.05-1.1]
<0.001
0.95 [0.92-0.97]
0.32
0.98 [0.95-1.01]
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LVEF (per %)
<0.001
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Prasugrel use
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Cardiogenic Shock at admission
HR [95% CI]
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Age (per year)
p
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Delayed stenting for ST-elevation acute myocardial infarction in daily practice: A single center experience
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Running title: Delayed stenting strategy in STEMI
Julien Pascal, MD1 Aurélie Veugeois, MD2, Michel Slama, MD3,4, SaliahRahal, MD4,
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Loic Belle, MD 5, Christophe Caussin, MD2 and Nicolas Amabile, MD, PhD2
1: Cardiology department, Centre Hospitalier Le Raincy-Montfermeil,
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Montfermeil, France
2: Department of Cardiology, Institut Mutualiste Montsouris, Paris, France 3: Cardiology department, CHU Antoine Beclère, Clamart, France
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4: Cardiology Department, Centre Marie Lannelongue, LePlessis Robinson, France
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5: Cardiology Department, CH Annecy, Annecy, France
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Clinical follow-up & endpoint definitions
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The primary endpoint was the freedom from MACE (major adverse cardiovascular events) including cardiovascular death, recurrent myocardial infarction and ischemia-driven target vessel revascularization (TVR). Cardiovascular death was defined as any death due to
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proximate cardiac cause (eg, MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure-related death or death caused by non-coronary
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vascular causes, such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular diseases (1). Recurrent myocardial infarction was defined as increased troponin Ic over the upper limit of the normal value with ischaemic changes on ECG. Ischemia-driven target vessel revascularization was defined as
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the need for any repeat percutaneous intervention or surgical bypass of any segment of the target vessel following evidence of on-going ischemia in the myocardial wall supplied by this vessel (1). Acute culprit vessel reocclusion was defined as the recurrence of chest pain and
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ST modifications on ECG suggesting on-going ischemia with evidence of antegrade TIMI
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flow< 3 in the artery on control angiography. Bleeding events were defined according to the BARC criteria (2)
Statistical analysis.
Patient survival from MACE was analyzed and Kaplan-Meier curves were constructed. Differences between survival curves were evaluated using the log-rank test. Multivariable Cox models were used to assess the relation of clinical covariates with the incidence of the
ACCEPTED MANUSCRIPT primary endpoint (MACE) within one year following the procedure. Univariate Cox proportional hazards regression analyses were performed first, then all covariates with a pvalue of <0.1 were included in the multivariable regression model and backward stepwise elimination was performed to identify independent predictors of the primary endpoint. The
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validity of the proportionality assumption was verified for all covariates by the likelihood ratio test (LRT).
Given the observational nature of the study, and to minimize indication bias for
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undergoing MIMI procedure, propensity score analyses were conducted. The propensity of
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providing MIMI was estimated by logistic regression analysis using age, sex, STEMI symptoms duration, cardiogenic shock, DES use, left ventricular ejection fraction (LVEF), hypertension, diabetes, smoking status, hypercholesterolemia, past history of CAD, number of vessels diseased, initial TIMI flow as covariates on an a priori basis. Then, the association
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between the MIMI procedure and MACE was repeated after propensity score matching and after adjustment for the propensity score (3). Differences were considered significant at p
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<0.05.
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Standard Strategy
MIMI Strategy p (N=56)
MACE, n(%)
38 (18)
2 (3.5)
<0.01
Cardiovascular death, n(%)
16 (7.7)
1 (1.8)
0.11
Ischemia driven TVR, n(%)
9 (4.3)
1 (1.8)
0.39
Recurrent MI, n(%)
13 (6.3)
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(N=207)
0
0.06
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1.
Cutlip DE, Windecker S, Mehran R et al. Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions. Circulation 2007;115:2344-2351. Mehran R, Rao SV, Bhatt DL et al. Standardized Bleeding Definitions for
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2.
Cardiovascular Clinical Trials: A Consensus Report From the Bleeding Academic Research Consortium. Circulation 2011;123:2736-2747.
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Brookhart MA, Wyss R, Layton JB, Sturmer T. Propensity score methods for
confounding control in nonexperimental research. Circulation Cardiovascular
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quality and outcomes 2013;6:604-11.
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3.
S0828-282X(15)01440-3
DOI:
10.1016/j.cjca.2015.09.015
Reference:
CJCA 1881
To appear in:
Canadian Journal of Cardiology
Received Date: 19 June 2015 Revised Date:
2 September 2015
Accepted Date: 11 September 2015
Please cite this article as: Pascal J, Veugeois A, Slama M, Rahal S, Belle L, Caussin C, Amabile N, Delayed stenting for ST-elevation acute myocardial infarction in daily practice: A single center experience, Canadian Journal of Cardiology (2015), doi: 10.1016/j.cjca.2015.09.015. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Delayed stenting for ST-elevation acute myocardial infarction in daily practice: A single center experience
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Running title: Delayed stenting strategy in STEMI Julien Pascal, MD1 Aurélie Veugeois, MD2, Michel Slama, MD3,4, SaliahRahal, MD4,
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Loic Belle, MD 5, Christophe Caussin, MD2 and Nicolas Amabile, MD, PhD2
1: Cardiology department, Centre Hospitalier Le Raincy-Montfermeil,
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Montfermeil, France
2: Department of Cardiology, Institut Mutualiste Montsouris, Paris, France 3: Cardiology department, CHU Antoine Beclère, Clamart, France 4: Cardiology Department, Centre Marie Lannelongue, LePlessis Robinson, France
Words: 5063
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5: Cardiology Department, CH Annecy, Annecy, France
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Correspondence: Dr Nicolas Amabile, MD, PhD,
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Department of Cardiology, Institut Mutualiste Montsouris, 42 boulevard Jourdan, 75014 Paris, France Email: [email protected]; Phone +33 1 56 61 65 58
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ABSTRACT (249 words)
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Background: The minimalist immediate mechanical intervention (MIMI) strategy aims to restore normal anterograde flow in the culprit artery (by using manual thrombectomy and/or small size balloon predilation) and to defer potential stent implantation. This study
myocardial infarction (STEMI) management.
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evaluated the applicability and mid-term clinical results of the MIMI strategy for ST elevation
Methods: This observational study included consecutive patients admitted for ongoing
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STEMI (<24h evolution) in one institution between June 2010 and June 2013.
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Revascularization strategy was performed at the physician’s discretion. We compared retrospectively the « intentional immediate stenting » (Standard technique) and the « intentional delayed stenting » (MIMI technique).
Results: 20% of the 279 included patients were treated following the MIMI strategy. These
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patients were significantly younger, more frequently male and smoker compared to the Standard patients. The rate of acute reocclusion of the culprit artery related to STEMI in the MIMI group was 1.8%. Drug-eluting stents were more frequently used in the MIMI group
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(52% vs. 27% in Standard group, p<0.001). The culprit lesion was less frequently stented in the MIMI patients compared to other patients (28.5 vs. 9%, p<0.001). The 1-year actuarial
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survival free from major adverse cardiovascular events was higher in the MIMI than in the Standard group (96.3±1.8% vs. 83.8±2.5%, p=0.01). Conclusion: The MIMI strategy can be applied in some selected STEMI patients. In our center, this strategy is associated with less systematic culprit lesion stenting and more DES implantation. However, this needs to be evaluated further in a randomized trial.
KEY WORDS: STEMI; manual thrombectomy; deferred stenting; prognosis
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ACCEPTED MANUSCRIPT BRIEF SUMMARY: This study investigated clinical compared outcome in patients with acute STEMI treated with intentional delayed stenting (MIMI) strategy or immediate stenting standard strategy. DES were more frequently used in the MIMI group; the culprit lesion was
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not stented in 28.5% of these patients (vs. 9% in standard group, p<0.001). The 1-year actuarial survival free from MACE was higher in the MIMI than in the Standard group
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(96.3±1.8% vs. 83.8±2.5%, p=0.01).
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INTRODUCTION
Despite considerable progress in last decades with the advent of interventional cardiology and mechanical revascularization (1,2), stent implantation during ST-elevation myocardial infarction (STEMI) could be associated with coronary emboli or micro vascular obstruction,
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due to the highly thrombotic environment (2). This complication occurs in about 30% of patients admitted for STEMI and is associated with increased infarct size (3). Moreover, percutaneous coronary intervention (PCI) during STEMI remains a major risk factor for
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inadequate stent deployment or under sizing (due to large thrombus burden on culprit lesion that limits proper struts apposition on vessel wall and because of initial post
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deocclusion culprit vessel vasospasm), which can favor stent thrombosis, restenosis and subsequent need for target vessel revascularization (4-6). Indeed, large thrombus burden could limit proper struts apposition on culprit lesion and initial post reperfusion culprit vessel vasospasm may lead to underestimation of artery’s size.
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The concept of minimalist immediate mechanical intervention (MIMI) for STEMI management was proposed for the first time by Isaaz et al (7). The aim of this strategy is: 1)
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to restore the best anterograde flow in the culprit artery when it’s not achieved by upstream pre-cath lab medications, using wiring and/or manual thrombectomy and/or angioplasty
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with a small size (≤2 mm diameter) balloon catheter AND 2) to defer stent implantation whenever possible. Delayed stenting is attempted only after several days of systemic anticoagulation and antiplatelet therapy in order to reduce the thrombus burden in the infarct-related artery and get rid of the initial post deocclusion culprit vessel vasospasm. Stenting can be entirely omitted in cases where there is no residual stenosis following adequate medical and anticoagulation therapies received in the interval between reperfusion and planned deferred stenting (8).
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Although the theoretical risk of culprit artery reocclusion between the two procedures has been suspected, published data reported the feasibility and safety of this approach (9), but its short-term benefits are debated (10,11). Furthermore, there is no current data regarding the middle and long-term evolution of the patients managed by the MIMI approach.
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The aim of this study is to evaluate the applicability of this strategy in daily practice and
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assess its impact on cardiovascular short and middle-term outcome.
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METHODS
Study design and eligibility criteria This work was a retrospective observational study conducted in the Centre Chirurgical Marie Lannelongue between June 2010 and June 2013. All consecutive patients
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admitted for acute ongoing STEMI in the institution were screened for inclusion. There was no selection in terms of clinical presentation and admission time (business hours, week-ends
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and nights). Patients were eligible for inclusion if: 1) they had chest pain suggestive of
myocardial ischemia for at least 30 minutes before hospital admission 2) the time from the
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onset of symptoms to hospital admission was less than 24 hours 3) electrocardiogram (ECG) showed new ST-segment elevation or left bundle-branch block (12). Patients were excluded if they had any of the following criteria: absence of coronary angiography performed, normal coronary angiography (absence of significant coronary artery stenosis >30% on angiography
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(13), acute coronary syndromes occurring ≤ 1 month after cardiac surgery, non-ST elevation myocardial infarction or unstable angina. Baseline clinical, biological and angiography parameters were collected in a local database for each patient.
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The study complied with the Declaration of Helsinki. Our local Hospital‘s Ethics
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Committee approved the research protocol.
Coronary angiography and revascularization strategies All patients included in the study were routinely treated with double antiplatelet
therapy including aspirin with a P2Y12 inhibitor (clopidogrel or prasugrel or ticagrelor) and unfractionated or low molecular weight heparin. Adjunctive anti thrombotic therapy with Gp IIb/IIIa inhibitor (abciximab/ full dose bolus + 12h infusion) or bivalirudin infusion (full dose bolus + 8h infusion) was left to the operator’s discretion.
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After coronary angiography, PCI was performed with a 6 Fr guiding catheter in suitable patients, mostly through transradial access.
The initial objective was to achieve the best flow in the infarct related artery with
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mechanical manual thrombus aspiration (Eliminate®, TERUMO, Tokyo, Japan/ The number of passes was left at the operator’s discretion) and/or balloon predilation (Emerge® 1.5 to 2 mm diameter x 8 to 12 mm length, Boston Scientific, Nantick, MA, USA).
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An optimal reperfusion was defined as follows: 1) antegrade TIMI flow ≥2, 2) chest pain cessation, 3) reduction in ST elevation>50% on immediate post-intervention ECG (14).
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When at least one of these 3 was not reached, operators had to proceed with stenting (intentional immediate stenting / Standard strategy group).
When optimal reperfusion was achieved, the operator could choose either immediate culprit lesion treatment (Standard strategy) or deferred control (intentional
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delayed stenting / MIMI strategy group).
Patients who were in the minimally invasive procedure group underwent a second
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coronary angiogram at physician’s discretion. Sustained anticoagulation by LMWH was provided to all patients from the MIMI group in the delay between the two procedures. In
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the absence of any significant residual stenosis on the repeat angiogram, the decision to forego stent implantation was considered. In case of multiple vessel disease, no PCI was performed in the non-infarct related
arteries during initial procedure, except in case of cardiogenic shock at admission (12). Nonculprit lesions revascularization was guided by the results of subsequent deferred noninvasive tests or fractional flow reserve measurement. Complete revascularization by CABG
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was considered in case of SYNTAX score>30 and after careful evaluation by a multidisciplinary Heart Team.
Coronary angiography analysis
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Two independent operators (JP & NA, blinded to clinical outcome) retrospectively reviewed coronary angiograms and analyzed culprit lesion characteristics, including
antegrade angiographic flow and thrombus grade in the culprit vessel according to the TIMI
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criteria (Gibson angiographic thrombus score) (15). Discordances were resolved by
consensus. The degree of stenosis was calculated by a dedicated quantitative coronary
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angiography (QCA) software (Centricity CA1000 / GE Healthcare, Buc, France) (14).
Clinical follow-up & endpoint definitions
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The patients included in the study were prospectively followed-up regarding cardiovascular adverse events and bleeding events 1) during the in-hospital period by reviewing medical records and discharge letters then 2) during the first year following STEMI
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through clinic visits in our institution, direct phone contact with the patients or contact with treating physicians in charge of the patients (in case they were not followed in our
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institution). The same methodology was applied for patients entirely managed in our institution and those transferred to other institutions after PCI. The primary endpoint was the freedom from MACE (major adverse cardiovascular
events) including cardiovascular death, recurrent myocardial infarction and ischemia-driven target vessel revascularization (TVR) (16). Acute culprit vessel reocclusion was defined as the recurrence of chest pain and ST modifications on ECG suggesting on-going ischemia with
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evidence of antegrade TIMI flow< 3 in the artery on control angiography. Bleeding events were defined according to the BARC criteria (17).
Statistical analysis.
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Statistical analysis was performed with SPSS 21.0 (SPSS software, Chicago, IL, USA) software. Data are expressed as mean ± Standard error of the mean (SEM) and the normality of their distribution was assessed by Kolmogornov-Smirnov test. Baseline parameters
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between patients from the 2 strategies groups were compared using the parametrical
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Student t test or non-parametrical U Mann-Whitney and χ² or Fisher exact test for quantitative and categorical variables respectively. Angiographic parameters evolution between procedures in the MIMI group was compared using the Friedman test for categorical variables and Student t test for continuous variables. Patient survival from MACE
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was analyzed and Kaplan-Meier curves were constructed. Differences between survival curves were evaluated using the log-rank test. Multivariable Cox models were used to assess the relation of clinical covariates with the incidence of the primary endpoint (MACE)
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within one year following the procedure. Given the observational nature of the study, and to minimize indication bias for undergoing MIMI procedure, propensity score analyses were
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conducted. Differences were considered significant at p <0.05. For detailed Statistical Analysis methods, see Supplementary Materials.
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RESULTS
Baseline characteristics The flow chart of the study is given in Figure 1. Between June 2010 and June 2013, 372 consecutive patients were referred to the institution for suspected ongoing STEMI.
279 patients eligible for PCI were treated by the MIMI strategy.
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Ninety-three of them were ruled out from the analysis due to exclusion criteria. 20% of the
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The baseline characteristics of the population are reported in Table 1. Patients were significantly younger, more frequently males, more frequently smokers, had a higher
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incidence of dyslipidemia and presented less frequently with cardiogenic shock in the MIMI group compared to the Standard group. Radial access was used in 85% of the cases in the whole cohort.
There was no significant difference regarding the delay between symptoms onset
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and PCI between groups. The initial pre-PCI TIMI flow was significantly higher and the culprit lesion stenosis percentages lower in the patients treated by the MIMI strategy compared to the others. Manual thrombus aspiration was used as the first option for culprit lesion
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recanalization in 70% of our patients and balloon angioplasty in 14% of the cases. The
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average number of thrombectomy catheter passes was higher in the patients from the MIMI group compared to the Standard group, leading to a higher TIMI flow and a lower degree of stenosis.
Evolution of culprit lesion characteristics in the MIMI patients The mean delay between initial and control angiogram was 4.3±3.2 days in the MIMI group. These patients were more frequently treated with anti GPIIb/ IIIa infusion and prasugrel than the patients from the Standard group (Table 1). One patient from the MIMI
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group (1.8%) experienced a culprit vessel reocclusion related to culprit lesion dissection (occurring 15 minutes after initial thrombectomy and before leaving the cath lab) that required urgent stent placement (vs. one case of acute stent thrombosis (0.4%) in the Standard group). There was no significant difference in hemorrhagic complications between
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groups: BARC 3 bleeding were observed in 1.8% of MIMI patients vs. 1.3% of Standard patients (p=0.56), BARC 2 bleeding in 3.6% of MIMI patients vs. 1.8% of Standard patients (p=0.41) and BARC 0+1 bleeding in 94.6 % of MIMI patients vs. 96.9% of Standard patients
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(p=0.43).
We observed a significant thrombus burden reduction in the MIMI patients between
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the two coronary angiographies (p<0.001 using Friedman test/Figure 2), but there was no difference between the degrees of stenosis by QCA (53±2% vs. 57±3%, p=0.69).
Revascularization options according to strategies
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We observed significant differences in the revascularization options between groups according to the management strategy (Table 2). Hence, there was a higher use of drug
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eluting stent (DES) in the MIMI group than in the Standard group among patients whose culprit lesion was stented (52 vs. 27%, p<0.001). Furthermore, the patients from the MIMI
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strategy group were more frequently treated by thrombectomy alone (28 vs. 12%, p=0.001) and underwent culprit lesion stenting less frequently than patients from the other group (70 vs. 85%, p=0.006).
Clinical outcome Clinical follow-up was achieved in 263 out of 279 patients (the 12 other patients were unreachable or provided incorrect personal information for follow-up). The median follow
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up was 44.4±28.8 months (43.8±30.5 in Standard group vs. 48±21.4 months in MIMI group, p=0.91). During this period, there were a total of 40 major adverse cardiovascular events (Table S1 in Supplementary Materials). The 1-year actuarial survival free from MACE was higher in the MIMI patients compared to the others (96.5±2.5 vs. 83.8±2.5%, p=0.01 log-rank
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analysis / Figure 3A). However, there was no significant difference regarding the 1-year actuarial survival free from TVR between the two groups (98.2±1.8 % vs. 95.7%±1.2%,
p=0.35 log rank analysis). Because of the impact of initial cardiogenic shock on outcome, we
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then excluded patients presenting with this condition (n=28) for a sub-analysis. Once again, we observed a higher 1-year survival from MACE in the MIMI patients compared to the
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others (Figure 3B).
Finally, we analyzed the predictors of MACE in this STEMI cohort to ascertain the role of the MIMI strategy as a protective factor in this situation. A first Cox multivariate regression analysis (without adjusting for the propensity score matching) revealed that
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cardiogenic shock at admission; age and multivessel disease were independently associated with adverse outcome. The use of MIMI strategy was not an independent protective factor
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against MACE in the whole cohort (HR= 0.28 [0.06-1.10], p=0.07/ Table 3). The propensity score analysis was performed by matching one MIMI with 2 standard
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patients (using a difference of probability of receiving MIMI of less than 5% between the MIMI and the controls). This analysis was performed with n=106 pairs and showed no significant difference between the two procedures (HR MIMI vs. standard: 0.34 (95%CI: 0.081.54), p=0.16). Furthermore, there was no significant difference between the two procedures in the multivariate analysis after adjustment for the propensity score (HR MIMI vs. standard: 0.34 (95%CI: 0.08-1.46), p=0.14).
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DISCUSSION
This retrospective study evaluated the impact of the minimalist immediate mechanical intervention for STEMI patients’ management in daily practice. The main findings of the current study are: 1) The MIMI strategy was frequently used (20% of our cohort) and
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safe (one reocclusion of the culprit artery in selected patients and no higher incidence of bleeding events); 2) The use of this strategy influenced the revascularization modalities with
cardiovascular events following this approach was low.
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fewer stents implanted and increased use of DES; 3) The incidence of major adverse
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Culprit vessel occlusion during acute coronary syndromes is related to the addition of a thrombus to an unstable or ruptured atherosclerotic plaque. The presence of this highly thrombotic environment underlies most of the potential PCI pitfalls in this situation, such as coronary embolization, no reflow or poor stent deployment. The concept of a 2 steps-
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approach (initial thrombectomy followed by deferred stenting) has been recently developed by different groups (7,11,18-20) in order to overcome these limitations in STEMI patients. However, this strategy might not be applicable in all patients. In the current study, 20% of
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our patients were treated with the MIMI strategy. These subjects were younger, more
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frequently smoker and had a lower incidence of cardiogenic shock at admission than the patients from the Standard group. Moreover, we observed that the patients who were eligible for the MIMI approach had better post-recanalization angiographic results (as assessed by the degree of stenosis, TIMI antegrade flow and the thrombus grade) than the others. A less severe lesion at baseline, a larger thrombus burden or a more efficient thrombectomy on culprit lesion, might explain these results. According to previous reports, the number of culprit lesion reocclusion was very low among the MIMI patients (1.8%) (9,11), which might be related to an adequate culprit lesion initial preparation and a large
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use of anti GPIIb/ IIIa infusion. Hence, the MIMI strategy appears to be safe but might be only proposed to patients with adequate clinical profile and highly baseline thrombotic lesion, but should be avoided when a residual dissection is visible after recanalization. Our data show significant differences in revascularization modalities between the
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two groups. Hence, patients from the MIMI group were more frequently treated by lone thrombectomy than the others. This treatment was used in almost one third of the MIMI patients and is in line with previously reported data (20-22). These results suggest that
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correct thrombus removal by both mechanical and pharmacological methods could avoid unnecessary device implantation to treat culprit lesion during STEMI in a significant number
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of patients. Furthermore, when PCI was decided, DES were much more frequently implanted in the MIMI group than in the Standard group. Although current guidelines recommend DES use during STEMI, this option is frequently limited by different factors that could influence the risk for future stent thrombosis (23). First, the patient’s compliance to double
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antiplatelet therapy as well as the potential bleeding risks are sometimes difficult to assess during primary PCI for STEMI. Second, DES implantation during STEMI has been suspected to
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favor incomplete stent apposition and poor neointimal coverage, which could promote devices failure (4,6). Delayed stent implantation would thus take a step back on the patient's
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profile and history and evaluate more objectively the benefit/risk ratio of medical treatment. Furthermore, as the thrombus burden decreases and culprit vessel dimensions increase over time under medical optimal therapy (14), a deferred PCI strategy could help optimizing PCI results by choosing the adequate device dimensions and improve apposition. Although the deferred provisional stenting approach has shown some encouraging results regarding the short-term outcome (11,18,20), very few data reported the long-term safety of this procedure (20). Our study shows that the 1-year incidence of MACE was low,
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with a very limited number of TVR procedures (actuarial survival: 98.2±1.8%) in the MIMI group. These findings might be related to a more appropriate revascularization modality in this group (see above) and a higher use of DES. We observed a statistical difference in outcome between the two management strategies according to the results from Kelbaeck et
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al (20). However, this difference might also be explained by the risk profile of the patients in each group and the higher incidence of cardiogenic shock among subject treated by the Standard approach. Hence, the different multivariable analyses (including propensity-score
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matching analysis) did not prove any significant protective impact of the MIMI strategy, yet a very clear trend was observed. This lack of significance might be explained by the relatively
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small number of patients included in our series and advocate for the need of larger, randomized trials to evaluate the deferred stenting approach in this situation.
Our study has several limitations that warrant considerations. First, our results are
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based on data retrospectively collected from a single catheterization facility and were not obtained from a randomized trial. Since this work was designed as an observational study,
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some of the differences in patients’ baseline characteristics might have biased the results, such as the higher incidence of stent thrombosis (although no consensus exists regarding the
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best management for this particular condition), lower incidence of initial cardiogenic shock or younger age in the MIMI patients, suggesting a possible selection bias in this group. However, this strategy seems particularly interesting in young subjects, thus avoiding potentially damaging late effects of stenting. Similarly, in case of initial cardiogenic shock at presentation, repeated invasive procedures under unstable hemodynamic conditions seem difficult and this explains the uselessness of MIMI strategy in this situation. The relative small number of patients and events during follow-up might also limit some of our conclusions, as witnessed by the wide confidence intervals of the HR in our 15
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multivariable analysis. However this work aimed to evaluate the short and long-term safety of the MIMI strategy in daily practice and did not intend to prove its superiority over the immediate stenting regarding outcome. Finally, the MIMI strategy was initially described in France, where it became increasingly popular over time. Thus, French interventional
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cardiologists are experienced with this STEMI management approach and our findings might not be reproducible in countries where MIMI is not a commonly performed procedure (such
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as Canada).
In summary, this current observational study shows that the MIMI strategy was
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applicable and safe in some selected STEMI patients in daily practice. This 2 steps approach appeared to change the revascularization modality compared to Standard strategy and provided good short term and midterm clinical outcomes. Further larger studies are needed
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FUNDING: None
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to confirm the potential clinical benefits of this strategy in the future.
ACKNOWLEDGEMENT: We thank Lucile Offredo (INSERM U970, Paris Cardiovascular
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Research Centre) for her assistance in statistical analysis.
DISCLOSURES: None of the authors reports any conflict of interest in relation with this article
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Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous
randomised trials. Lancet 2003;361:13-20. 2.
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thrombolytic therapy for acute myocardial infarction: a quantitative review of 23
Kastrati A, Dibra A, Spaulding C et al. Meta-analysis of randomized trials on drug-
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eluting stents vs. bare-metal stents in patients with acute myocardial infarction. Eur Heart J 2007;28:2706-13.
Resnic FS, Wainstein M, Lee MK et al. No-reflow is an independent predictor of
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death and myocardial infarction after percutaneous coronary intervention. Am Heart J 2003;145:42-6. 4.
Sianos G, Papafaklis MI, Daemen J et al. Angiographic Stent Thrombosis After
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Routine Use of Drug-Eluting Stents in ST-Segment Elevation Myocardial Infarction: The Importance of Thrombus Burden. J Am Coll Cardiol 2007;50:573583.
Iqbal J, Sumaya W, Tatman V et al. Incidence and predictors of stent thrombosis: a
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single-centre study of 5,833 consecutive patients undergoing coronary artery
6.
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stenting. EuroIntervention 2013;9:62-9. Gonzalo N, Barlis P, Serruys PW et al. Incomplete Stent Apposition and Delayed
Tissue Coverage Are More Frequent in Drug-Eluting Stents Implanted During Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Than in Drug-Eluting Stents Implanted for Stable/Unstable AnginaInsights From Optical Coherence Tomography. JACC: Cardiovascular Interventions 2009;2:445-452.
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Isaaz K, Robin C, Cerisier A et al. A new approach of primary angioplasty for STelevation acute myocardial infarction based on minimalist immediate mechanical intervention. Coron Artery Dis 2006;17:261-9.
8.
Jolicoeur EM, Tanguay J-F. From Primary to Secondary Percutaneous Coronary
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Intervention: The Emerging Concept of Early Mechanical Reperfusion With Delayed Facilitated Stenting—When Earlier May Not Be Better. Canadian Journal of Cardiology;27:529-533.
Freixa X, Belle L, Joseph L et al. Immediate vs. delayed stenting in acute
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myocardial infarction: a systematic review and meta-analysis. EuroIntervention
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2013;8:1207-1216.
Belle L, Mangin L, Motreff P et al. Deferred stenting in primary percutaneous coronary intervention: the Minimal Intervention for Myocardial Infarction (MIMI) study. Eur Heart J 2013;34:331.
Carrick D, Oldroyd KG, McEntegart M et al. A randomized trial of deferred
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stenting versus immediate stenting to prevent no- or slow-reflow in acute STsegment elevation myocardial infarction (DEFER-STEMI). J Am Coll Cardiol
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2014;63:2088-98.
Task Force on the management of STseamiotESoC, Steg PG, James SK et al. ESC
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Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569-619.
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Brolin EB, Jernberg T, Brismar TB et al. Coronary plaque burden, as determined
by cardiac computed tomography, in patients with myocardial infarction and angiographically normal coronary arteries compared to healthy volunteers: a prospective multicenter observational study. PloS one 2014;9:e99783.
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Amabile N, Hammas S, Fradi S et al. Intra-coronary thrombus evolution during acute coronary syndrome: regression assessment by serial optical coherence tomography analyses. European Heart Journal- Cardiovascular Imaging 2015;16:433-440. Gibson CM, de Lemos JA, Murphy SA et al. Combination Therapy With Abciximab
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15.
Reduces Angiographically Evident Thrombus in Acute Myocardial Infarction: A TIMI 14 Substudy. Circulation 2001;103:2550-2554.
Cutlip DE, Windecker S, Mehran R et al. Clinical End Points in Coronary Stent
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Trials: A Case for Standardized Definitions. Circulation 2007;115:2344-2351. Mehran R, Rao SV, Bhatt DL et al. Standardized Bleeding Definitions for
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Cardiovascular Clinical Trials: A Consensus Report From the Bleeding Academic Research Consortium. Circulation 2011;123:2736-2747. 18.
Meneveau N, Séronde M, Descotes-Genon V et al. Immediate versus delayed
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angioplasty in infarct-related arteries with TIMI III flow and ST segment recovery: a matched comparison in acute myocardial infarction patients. Clin Res Cardiol 2009;98:257-264.
Kramer MC, Verouden NC, Li X et al. Thrombus aspiration alone during primary
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percutanous coronary intervention as definitive treatment in acute ST-elevation
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myocardial infarction. Catheterization and Cardiovascular Interventions 2012;79:860-867.
20.
Kelbaek H, Engstrøm T, Ahtarovski KA et al. Deferred stent implantation in
patients with ST-segment elevation myocardial infarction: a pilot study. EuroIntervention 2013;8:1126-1133.
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Escaned J, Echavarria-Pinto M, Gorgadze T et al. Safety of lone thrombus aspiration without concomitant coronary stenting in selected patients with acute myocardial infarction. EuroIntervention 2013;8:1149-1156.
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Souteyrand G, Amabile N, Combaret N et al. Invasive management without stents
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in selected acute coronary syndrome patients with a large thrombus burden: a prospective study of optical coherence tomography guided treatment decisions. EuroIntervention 2014.
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Steg PG, Fox KAA, Eagle KA et al. Mortality following placement of drug-eluting and bare-metal stents for ST-segment elevation acute myocardial infarction in
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the Global Registry of Acute Coronary Events. Eur Heart J 2009;30:321-329.
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23.
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FIGURE LEGENDS
FIGURE 1: Study workflow
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FIGURE 2: Regression of thrombus burden between coronary angiographies in the MIMI group patients, as assessed by the TIMI thrombus grade (p<0.001).
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FIGURE 3: Kaplan Meier estimates of MACE survival in patients treated with the MIMI or the Standard strategy in the whole cohort (A) and after exclusion of
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patients presenting with initial cardiogenic shock (B).
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TABLE 1: Baseline clinical, angiographic and procedural characteristics of the
Global Cohort
Standard group
MIMI group
N=279
N=223
N=56
Age (years)
62.0±0.9
63.1±1.0
Male gender, n(%)
214 (77)
164 (74)
Smoker, n(%)
195 (70)
147 (66)
48 (86)
0.004
Hypertension, n(%)
153 (55)
125 (56)
28 (50)
0.42
Diabetes, n(%)
59 (21)
44 (20)
15 (27)
0.25
Dyslipidemia, n(%)
188 (67)
144 (65)
44 (79)
0.046
BMI (kg.m-2)
27.9±1.5
28.2±1.9
26.8±0.5
0.72
Personal history of CAD, n(%)
44 (16)
36 (16)
8 (14)
0.73
Familial history of CAD, n(%)
51 (18)
42 (19)
9 (16)
0.63
Symptoms onset to PCI delay (min)
368±18
380±21
321±35
0.26*
Primary PCI, n(%)
246 (88)
200 (90)
46 (82)
0.12
Previous Thrombolysis, n(%)
33 (12)
23 (10)
10 (18)
0.12
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population (p value is for comparison between Standard and MIMI group).
15 (5)
15 (7)
0
0.04
LAD, n(%)
120 (43)
97 (44)
23 (41)
0.74
Circumflex, n(%)
36 (13)
27 (12)
9 (16)
0.43
RCA, n(%)
116 (42)
92 (41)
24 (43)
0.83
12 (4)
10 (5)
2 (4)
0.76
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STEMI characteristics
Cardiogenic shock at admission, n(%)
57.9±2.0
0.02
50 (89)
0.01
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Risk Factors
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Infarct related artery
Left Main, n(%)
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TABLE 1 (CONTINUED)
Global Cohort
Standard group
MIMI group
N=279
N=223
N=56
Single vessel disease, n(%)
105 (38)
81 (36%)
24 (43%)
Double vessel disease, n(%)
94 (34)
76 (34%)
Triple vessel disease, n(%)
78 (28)
66 (30%)
Stent thrombosis, n(%)
17 (6)
10 (4)
Initial TIMI antegrade flow
1.1±0.8
Initial TIMI thrombus grade
4.6±2.8
Initial culprit lesion QCA (%)
89±1
Balloon predilation, n(%)
P
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Baseline angiographic characteristics
20 (36%)
0.45
12 (21%)
0.03
1.0±0.1
1.4±0.2
0.02*
4.7±0.4
4.2±0.1
0.09*
90±1
84±2
0.007*
40 (14)
37 (17)
3 (5)
0.03
Thrombectomy, n(%)
195 (70)
154 (69)
41 (73)
0.54
Number of thrombectomy catheter passes
1.8±0.1
1.7±0.1
2.3±0.6
0.01
No thrombectomy or predilation, n(%)
44 (16)
32 (14)
13 (23)
0.1
Post recanalization TIMI antegrade flow
2.5±0.5
2.4±0.6
2.9±0.5
<0.001*
Post recanalization TIMI thrombus grade
3.9±0.4
4.2±0.5
2.7±0.1
0.002*
Post recanalization culprit lesion QCA (%)
65±1
68±2
57±3
<0.001*
Aspirin, n(%)
279 (100)
223 (100)
56 (100)
1.0
Prasugrel, n(%)
159 (57)
118 (53)
41 (73)
0.01
Clopidogrel, n(%)
108 (39)
94 (42)
14 (26)
0.02
3 (1)
2 (1)
1 (1)
0.65
128 (46)
87 (39)
41 (73)
<0.001
18 (7)
12 (5)
6 (11)
0.15
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Initial recanalization procedure
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7 (13)
Pharmacological management
Ticagrelor, n(%) Abciximab infusion, n(%) Bivalirudin, n(%)
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Table 1: *: U Mann Whitney test
Abbreviations: BMI: body mass index; CAD: coronary artery disease; LAD: left anterior descending artery; MIMI: minimalist immediate mechanical intervention; PCI: percutaneous coronary intervention; QCA: quantitative coronary angiography; RCA: right
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coronary artery; TIMI: Thrombolysis in Myocardial Infarction.
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TABLE 2: Revascularizations strategies among groups (p value is for comparison between Standard and MIMI strategy groups).
Standard Strategy
MIMI Strategy
(N=223)
(N=56)
8 (3)
Culprit lesion stenting, n(%)
190 (85) BMS, n(%)
129 (58)
DES, n(%)
61 (27) 25 (12)
0.49
39 (70)
0.006
10 (18)
<0.001
29 (52)
<0.001
16 (28)
0.001
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No additional PCI on culprit lesion, n(%)
1 (2)
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CABG, n(%)
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p
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p
HR [95% CI]
Multivariable Analysis
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Univariable Analysis
0.02
1.03 [1.00-1.05]
Male gender
0.39
0.7 [0.4-1.5]
Previous personal CAD history
0.28
1.7 [0.7-4.2]
Symptoms onset to PCI delay (per min)
0.49
1.0 [0.99-1.01]
Diabetes Multivessel disease DES implantation
MIMI strategy
0.04
1.03 [1.00-1.05]
6.4[2.8-14.7]
0.001
4.3 [1.9-10.1]
0.68
1.2 [0.6-2.5]
0.001
2.0[1.3-3.1]
0.01
1.8 [1.2-2.7]
0.01
0.3 [0.1-0.8]
0.20
0.5 [0.2-1.4]
0.48
1.2 [0.6-2.4]
0.02
0.2 [0.05-0.81]
0.07
0.3 [0.05-1.1]
<0.001
0.95 [0.92-0.97]
0.32
0.98 [0.95-1.01]
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LVEF (per %)
<0.001
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Prasugrel use
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Cardiogenic Shock at admission
HR [95% CI]
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Age (per year)
p
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Delayed stenting for ST-elevation acute myocardial infarction in daily practice: A single center experience
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Running title: Delayed stenting strategy in STEMI
Julien Pascal, MD1 Aurélie Veugeois, MD2, Michel Slama, MD3,4, SaliahRahal, MD4,
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Loic Belle, MD 5, Christophe Caussin, MD2 and Nicolas Amabile, MD, PhD2
1: Cardiology department, Centre Hospitalier Le Raincy-Montfermeil,
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Montfermeil, France
2: Department of Cardiology, Institut Mutualiste Montsouris, Paris, France 3: Cardiology department, CHU Antoine Beclère, Clamart, France
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4: Cardiology Department, Centre Marie Lannelongue, LePlessis Robinson, France
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5: Cardiology Department, CH Annecy, Annecy, France
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Clinical follow-up & endpoint definitions
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The primary endpoint was the freedom from MACE (major adverse cardiovascular events) including cardiovascular death, recurrent myocardial infarction and ischemia-driven target vessel revascularization (TVR). Cardiovascular death was defined as any death due to
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proximate cardiac cause (eg, MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, all procedure-related death or death caused by non-coronary
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vascular causes, such as cerebrovascular disease, pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular diseases (1). Recurrent myocardial infarction was defined as increased troponin Ic over the upper limit of the normal value with ischaemic changes on ECG. Ischemia-driven target vessel revascularization was defined as
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the need for any repeat percutaneous intervention or surgical bypass of any segment of the target vessel following evidence of on-going ischemia in the myocardial wall supplied by this vessel (1). Acute culprit vessel reocclusion was defined as the recurrence of chest pain and
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ST modifications on ECG suggesting on-going ischemia with evidence of antegrade TIMI
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flow< 3 in the artery on control angiography. Bleeding events were defined according to the BARC criteria (2)
Statistical analysis.
Patient survival from MACE was analyzed and Kaplan-Meier curves were constructed. Differences between survival curves were evaluated using the log-rank test. Multivariable Cox models were used to assess the relation of clinical covariates with the incidence of the
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validity of the proportionality assumption was verified for all covariates by the likelihood ratio test (LRT).
Given the observational nature of the study, and to minimize indication bias for
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undergoing MIMI procedure, propensity score analyses were conducted. The propensity of
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providing MIMI was estimated by logistic regression analysis using age, sex, STEMI symptoms duration, cardiogenic shock, DES use, left ventricular ejection fraction (LVEF), hypertension, diabetes, smoking status, hypercholesterolemia, past history of CAD, number of vessels diseased, initial TIMI flow as covariates on an a priori basis. Then, the association
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between the MIMI procedure and MACE was repeated after propensity score matching and after adjustment for the propensity score (3). Differences were considered significant at p
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Standard Strategy
MIMI Strategy p (N=56)
MACE, n(%)
38 (18)
2 (3.5)
<0.01
Cardiovascular death, n(%)
16 (7.7)
1 (1.8)
0.11
Ischemia driven TVR, n(%)
9 (4.3)
1 (1.8)
0.39
Recurrent MI, n(%)
13 (6.3)
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(N=207)
0
0.06
ACCEPTED MANUSCRIPT REFERENCES
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Brookhart MA, Wyss R, Layton JB, Sturmer T. Propensity score methods for
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3.