Abstract: Objectives. To assess feasibility and short-term clinical outcomes associated with resorbable magnesium scaffold (RMS) implantation in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). Background. RMS implantation has demonstrated favorable clinical outcomes in stable coronary artery disease patients. However, to date, data are lacking in the setting of STEMI. Methods. This is a single-center prospective non-randomized pilot study. Patients admitted for STEMI were enrolled according to prespecified inclusion and exclusion criteria. The primary endpoint was device-oriented composite endpoint (DOCE), including cardiac death, target-vessel myocardial infarction, and target-lesion revascularization (TLR) within 30 days of the index procedure. Secondary endpoints were procedural success, any probable/definite scaffold thrombosis, and DOCE at subsequent follow-up. Results. From December 1, 2016 to October 30, 2017, a total of 18 patients were included. Follow-up data were available for 17 patients (94%). There was no primary endpoint event. Procedural success was 100%. Patients were followed for a median of 153 days (range, 59-326 days). Over that extended follow-up period, 1 case of TLR occurred 102 days after the index procedure. There was no case of definite or probable scaffold thrombosis. Conclusions. This pilot study is the first to assess feasibility and clinical outcomes associated with RMS implantation in selected STEMI patients. The results seem reassuring, with favorable short-term clinical outcomes and absence of definite/probable scaffold thrombosis, and should prompt further research including randomized controlled trials evaluating RMS implantation in the setting of STEMI.
J INVASIVE CARDIOL 2018;30(6):202-206. Epub 2018 April 15.
Key words: absorbable metal scaffold, resorbable magnesium scaffold, STEMI, BRS, bioresorbable scaffold, Magmaris
Bioresorbable scaffold (BRS) implantation has been introduced as a novel approach to treat coronary disease, with the theoretical advantage of overcoming the limitations of permanent stents. However, the polymeric BRS devices recently experienced a series of serious setbacks, demonstrated by several studies showing higher rate of device failure (mainly scaffold thromboses) for Absorb BRS (Abbott Vascular) as compared to conventional drug-eluting stent (DES).1 These negative findings led to its commercial withdrawal. However, the new-generation Magmaris resorbable magnesium scaffold (RMS; Biotronik) has been associated with favorable clinical outcomes up to a 2-year clinical follow-up period in stable patients, and absence of definite or probable scaffold thrombosis (ST).2
On the other hand, some authors have speculated that ST-segment elevation myocardial infarction (STEMI) might constitute a specifically good target group for BRS implantation due to the pathophysiologic nature of the disease,3,4 and several studies have shown favorable results associated with polymeric BRS implantation in STEMI patients.5-8 However, no data are currently available for the use of RMS in STEMI patients.
This single-center non-randomized pilot study aims to evaluate the feasibility and safety of Magmaris implantation in the setting of primary percutaneous coronary intervention (PCI) for STEMI. The present study was investigator initiated and sponsored. Inclusion criteria were adult patients presenting with acute STEMI (<12 hours) as defined by current guidelines9 eligible for primary PCI with RMS implantation. Exclusion criteria included reference vessel diameter <2.8 mm or >4.0 mm; culprit lesion length >25 mm; cardiogenic shock; age >65 years; presence of severe coronary calcifications and/or tortuosity; bifurcation lesion with an intended double-stent strategy; contraindication to 12-month duration of dual-antiplatelet therapy; and severe renal dysfunction. The prespecified target sample size for this pilot/feasibility study was 20 patients.
Clinical and procedural characteristics and in-hospital outcomes were systematically and prospectively collected for all patients. Follow-up was obtained prospectively and systematically through monthly outpatient clinic visits, or phone calls with a questionnaire. The primary endpoint of interest was a device-oriented composite endpoint (DOCE) including cardiac death, target-vessel myocardial infarction, and target-lesion revascularization (TLR) as defined by the Academic Research Consortium criteria10 within 30 days of the index procedure. Secondary endpoints were procedural success, defined as BRS implantation at the “culprit” lesion with <30% final residual stenosis and distal TIMI 3 flow, any definite/probable ST, and DOCE at subsequent follow-up. All clinical adverse events were reviewed and adjudicated by an independent expert (FP).
Procedures were performed as per standard guidelines; use of predilation and postdilation was strongly encouraged, but left to the operator’s discretion. Use of intracoronary imaging was left at the operator’s discretion. Dual-antiplatelet therapy was recommended for a 12-month duration.
The study was performed in accordance with the Declaration of Helsinki and with good clinical practice, and was approved by the local ethics committee. All patients provided written informed consent. There was no funding source for this study. The study is registered with www.clinicaltrials.be (B076201732324).
Descriptive data for continuous variables are presented as mean ± standard deviation, median (range), or number (%), as indicated in the tables. Data analyses were performed using GraphPad Prism for Mac OS X (GraphPad Software, Inc).
From December 15, 2016 to October 30 2017, a total of 70 STEMI patients were admitted for primary PCI at our center, and 18 patients were included according to inclusion/exclusion criteria. Baseline demographics and clinical characteristics of patients are presented in Table 1. Follow-up data were available for 17 patients (94%); 1 foreign patient included in the study during a holiday trip in Belgium was lost to follow-up. Mean age was 48.5 ± 10 years and 78% were male. Table 2 summarizes procedural details. Procedures were performed through transradial access in 78% of cases. A single scaffold was implanted in 15 patients, while 3 patients required implantation of a second scaffold (in 1 case for distal edge dissection and in 2 cases for insufficient scaffold length). Predilation and postdilation rates were 94% and 89%, respectively. All patients were treated with aspirin and ticagrelor, and thrombus aspiration was performed in 5 patients (28%). None of the included patients discontinued dual-antiplatelet therapy during the follow-up period. Recruitment was discontinued earlier than expected due to slow enrollment and lack of funding.
Clinical outcomes are shown in Table 3. There was no primary endpoint event (30-day DOCE). Procedural success was 100%. Patients were followed for a median of 153 days (range, 59-326 days). Over that extended follow-up period, no case of probable or definite ST was observed. One case of TLR was recorded 102 days after the index procedure (Figure 1). The index procedure of the TLR case consisted of proximal thrombotic left anterior descending artery subocclusion (reference vessel diameter, 4.0 mm) in a 41-year-old diabetic male. Predilation was performed with a semicompliant 3.0 x 15 mm balloon, followed by implantation of a 3.5 x 25 mm Magmaris scaffold and final postdilation with a 4.0 x 12 mm non-compliant balloon at 16 atm all along the scaffold length, with a good final angiographic result. Glycoprotein IIb/IIIa inhibitors were administered during the procedure due to the thrombotic burden. Over 3 months post procedure, the patient presented with recurrent/unstable angina. No treatment discontinuation or any other triggering factors were documented. Coronary angiography revealed what appeared to be early diffuse in-scaffold restenosis, which was treated with implantation of a conventional 4.0 x 32 mm metallic DES with a good final angiographic result. Unfortunately, no intracoronary imaging could be performed during the TLR procedure for logistical reasons.
We report the first clinical experience with the new-generation Magmaris RMS in the setting of primary PCI for selected STEMI patients. The results of this prospective case series/pilot study seem reassuring, with favorable short-term clinical outcomes. The main findings of our initial clinical experience were a 30-day DOCE rate of 0%, and absence of ST over a mean follow-up period of 5 months. One case of TLR occurred 3 months after the index procedure. Procedural success rate was 100%, and procedural complication rates were very limited, with 1 case of distal edge dissection requiring implantation of a second scaffold.
Polymeric BRS devices have recently faced a series of negative results in stable coronary artery disease trials, leading to commercial withdrawal of the Absorb BRS. However, Magmaris is a new generation of metallic BRS, and has been associated with encouraging initial clinical results in stable patients up to 24 months of follow-up.2 STEMI pathophysiology in young patients is frequently the result of plaque rupture/erosion, rather than stenotic atherosclerotic disease,11,12 and might therefore constitute a good indication for BRS/RMS implantation.3 Furthermore, the young age of STEMI patients might further increase theoretical advantages of limiting permanent metallic stent implantation in proximal coronary arteries (ie, restoration of coronary vasomotion, very late stent thrombosis risk reduction).13 Some encouraging initial data concerning limitation of permanent metallic stent implantation in young STEMI patients (with BRS implantation or medical management alone) based on intracoronary imaging were recently published and rely on the same rationale.14
Polymeric BRS implantation in STEMI patients has been previously studied with acceptable results as compared with conventional DES implantation, although it was frequently associated with a greater numerical (but non-significant) rate of ST.15 The absence of ST in our study is reassuring in a prothrombotic environment such as that of acute MI. The Magmaris RMS was recently shown to be significantly less thrombogenic than the Absorb bioresorbable vascular scaffold in an ex vivo porcine arteriovenous shunt model, and performed as well or better than the Orsiro stent (Biotronik), which has a bioabsorbable sirolimus-eluting polymer coating.16 The mechanisms accounting for this reduced thrombogenicity remain unclear, but might prove to be an asset in the prothrombotic environment of STEMI.
During the extended follow-up period (147 ± 75 days), 1 case of TLR (early restenosis) was documented 102 days after the index procedure (Figure 1). Unfortunately, as previously mentioned, no intracoronary imaging was performed during the index procedure or during the redo TLR procedure. Therefore, the mechanism of target-lesion failure can only be speculated. Proper vessel sizing during STEMI might be impaired by vasospasm and thrombus burden, and it has been shown that up to 40% of stents implanted during STEMI show acute strut malapposition to some extent.17 In this regard, some authors have advocated delayed stenting during primary PCI to reduce the risk of stent/scaffold malapposition.14,18 Nevertheless, in the recent DANAMI-DEFER randomized trial, this strategy did not reduce the occurrence of death, heart failure, MI, or repeat revascularization as compared with conventional PCI.19 In the pooled BIOSOLVE-II and BIOSOLVE-III studies, target-lesion failure rate was 3.3% at 6-month follow-up, and 5.9% at 2-year follow-up for BIOSOLVE-II.2 One of the suspected mechanisms was strut malapposition, which was probably due to insufficient predilation and/or postdilation.
Another hypothesis to explain early restenosis is scaffold collapse, as recently reported in 1 case.20 Indeed, the Magmaris RMS has a degradation time of approximately 12 months, but the major reduction in radial strength and scaffolding ability occurs from 3 months.
The current recommended implantation technique is the “4P” strategy of patient selection, predilation, proper vessel sizing, and postdilation.21 However, proper postdilation of the scaffold may be difficult, as radiopaque markers are hardly visible in a significant proportion of patients despite the use of stent-enhancement technologies (Figure 2C). Therefore, implantation should ideally be facilitated with intracoronary imaging (Figure 2) and/or the use of anatomical landmarks, such as the side branch, for scaffold postdilation. Use of intracoronary imaging was limited in our series (17%), but should be encouraged during the initial learning curve to optimize RMS implantation, and probably even more so in STEMI patients.
Study limitations. The small number of patients, absence of a control group, and selection bias due to inclusion/exclusion criteria of this pilot study do not allow us to reach definitive conclusions. Longer follow-up periods are needed to assess potential long-term advantages of the RMS.
The results of this pilot study, which is the first to assess the feasibility and clinical outcomes of Magmaris RMS implantation in STEMI patients, seem reassuring, with favorable short-term outcomes and no definite/probable ST. These results should prompt further research including randomized controlled trials evaluating RMS implantation in the setting of STEMI.
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*Authors contributed equally.
From the 1Department of Cardiology, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium; and 2Department of Cardiology, Hôpital Cochin, AP-HP, Paris, France.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Picard reports personal fees from Biotronik. The remaining authors have no conflicts of interest regarding the content herein.
Manuscript submitted January 6, 2018, provisional acceptance given January 22, 2018, final version accepted February 6, 2018.
Address for correspondence: Quentin de Hemptinne, MD, Department of Cardiology, CHU Saint-Pierre, Université Libre de Bruxelles, 322 rue Haute, 1000 Bruxelles, Belgium. Email: firstname.lastname@example.org