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EDITORIAL COMMENT

Snowshoe Versus Ice Skate forScaffolding of Disrupted Vessel Wall*

Patrick W. Serruys, MD, PHD,y Pannipa Suwannasom, MD,z Shimpei Nakatani, MD,z Yoshinobu Onuma, MD, PHDz

T he advance of coronary stent technology andscaffolding devices in coronary interventionprocedures aims at reducing both short-

term and long-term adverse cardiac events. However,periprocedural myocardial infarction (PMI) still occursduring the coronary procedure. In the report by Kawa-moto et al. (1) in this issue of JACC: CardiovascularInterventions, the investigators present the clinicalimpact of “average” abluminal strut surface area(ASSA) on PMI (based on extended historical MI defini-tion) and long-term clinical outcome. The results fromthis group showed that compared with the Cypherstent (Cordis, Johnson and Johnson, Warren, New Jer-sey) with an ASSA of 67 mm2, the Absorb device(Abbott Vascular, Santa Clara, California) has a largerASSA of 133 mm2 and is associated with PMI ratestwice as high as those in Cypher group. There was nosignificant difference in long-term clinical outcomesbetween the 2 devices.

SEE PAGE 900

The results of the present study may warrant aword of caution in interpretation. First, the pro-pensity analysis can lead to misleading statements.Previously, it has been suggested in a propensitymatched nonrandomized comparison conducted byour group that Absorb bioresorbable vascular scaffoldwas associated with a higher incidence of post-procedural side branch occlusion (SBO) compared

*Editorials published in JACC: Cardiovascular Interventions reflect the

views of the authors and do not necessarily represent the views of JACC:

Cardiovascular Interventions or the American College of Cardiology.

From the yInternational Center for Circulatory Health, National Heart and

Lung Institute, Imperial College London, London, United Kingdom; and

the zDepartment of Interventional Cardiology, Thoraxcenter, Erasmus

Medical Center, Rotterdam, the Netherlands. Drs. Serruys and Onuma are

members of advisory board of Abbott Vascular. All other authors have

reported that they have no relationships relevant to the contents of this

paper to disclose.

with the metallic everolimus-eluting stent. The dif-ference was more pronounced with small sidebranches with a reference vessel diameter #0.5 mm(2). However, there was no significant difference inthe incidence of post-procedure creatine kinase-myocardial band elevation. The hypothesis has beentested again in the ABSORB II (ABSORB II Random-ized Controlled Trial: A Clinical Evaluation toCompare the Safety, Efficacy, and Performance ofAbsorb Everolimus Eluting Bioresorbable VascularScaffold System Against Xience Everolimus ElutingCoronary Stent System in the Treatment of SubjectsWith Ischemic Heart Disease Caused by De NovoNative Coronary Artery Lesion) randomized controltrial (3) in which all 3 cardiac biomarkers wereexplored and analyzed in a core lab. There was nosignificant difference in the normalized value for eachenzyme. To our surprise, the randomized datashowed that the SBO (core lab analysis) occurredmore often in the metallic stent group (39 of 503side branches [8%]) than in the bioresorbable scaf-fold group (52 of 998 side branches [5%]), but thisdifference did not reach a statistical significance,p ¼ 0.07.

Second, despite their hypothesis that greater ASSAis associated with PMI rate, mechanical complicationssuch as SBO were not reported. SBO should beassessed rigorously by an independent core lab usingquantitative coronary angiography whenever possible(e.g., side branch diameter $0.5 mm, the lower limitof automated edge detection).

Finally, it is unclear whether the cardiac bio-markers were systematically obtained. Generally, theincidence of PMI depends on the availability, type ofpost-procedural cardiac biomarkers, and enzymaticcriteria used, as well as the frequency of cardiac bio-markers sampling. PMI remains a debatable issuewith a heterogeneous incidence due to a diversity ofdefinitions. The incidence of PMI could vary from 1%

FIGURE 1 Strut Width: Absorb Versus Xience Stent

(A, E) The yellow, blue, and green vertical lines correspond to the various levels of the optical coherence tomography cross-section of Absorb

(B to D) and Xience stent (F to H) showing the various degrees of embedment of the 2 respective devices. B and F demonstrate the strut width

at the hinges level. The hinge strut width (yellow double-headed arrow) of the Absorb scaffold (B) can measure up to 883 mm, whereas

the strut of the Xience stent (F) is only 428 mm. C and G demonstrate strut width at the ring and link level. The ring strut width is represented

with blue line and link strut width is labeled by a blue bracket. E and H demonstrate strut width at the crown peak level with a green arrow,

and the link strut width is labeled by a green bracket.

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to 32% (3). For example, cardiac troponin T for thethird universal definition can lead to overestimationof PMI. Ideally, an assessment of 3 cardiac biomarkersis recommended.

Nevertheless, the study results could put forwardsome new mechanical and rheological hypotheses.The implantation of a device with a large “footprint”could potentially cause small SBO and subsequentcardiac biomarkers to rise. One can speculate that thelarge footprint of the ABSORB (scaffold area covers26% to 32% of the vessel wall area) could accidentallycover the ostium of small side branches, resulting inSBO. When measured using optical coherence to-mography, the width of the Absorb struts at thehinge point can be as large as 800 mm (Figure 1).Therefore, a side branch with a diameter of <0.8 mmcould be occluded by the device (Figure 2B). Thewidth of the strut could also influence the embed-ment of the strut. When the same force is applied, adevice with a smaller contact area would generate ahigher pressure to the vessel wall according to the

simple principle: Pressure ¼ Force/Area (Figures 2Cand 2D). Taking into account the fact that a moreaggressive post-dilation was applied in the Cyphergroup, the Cypher stent may have been moreembedded (Figure 2E) into the vessel wall than theAbsorb device was (Figure 2F). Embedded strutsimply penetration of the cutting edge of the metalsthrough fibrous, calcific, and necrotic plaques. Thedeep penetration of the strut into the vessel wallcould also disrupt and displace the edge of theostium of a side branch, with possible reduction orocclusion of its ostium (Figure 2A); additionallyinjury of the necrotic core can squeeze microparti-cles, which results in distal embolization and rise incardiac biomarkers (4).

On the other hand, the thick protruding strut of theAbsorb disrupts the laminar flow and induces flowdisturbances. In a flow simulation of a microenvi-ronment computed by optical coherence tomography/angiography fusion in a human coronary artery (5),the relatively high shear stress on top of the

FIGURE 2 Possible Mechanisms of PMI in Relation With Strut Width and Height

Strut width and side branch occlusion (SBO): (A) A deep embedment of metallic struts can displace plaque underneath (yellow) toward

the ostium of side branch in the close vicinity of the strut (red dotted line), resulting in SBO. A narrow strut (small footprint) enables strut

penetration through the vessel wall and more likely to create an injury than a wide strut when the same force was applied (e.g., intrastent

dissection) (white arrow) Conversely, SBO may result from the large footprint of the Absorb scaffold strut (B). For instance, the Absorb

strut at the hinge has a strut width of 833 mm (yellow arrow) and may be even larger than the ostium of side branch beneath (708 mm,

green dotted line). Strut width and embedment: The color coded stress strain graphics in C and D show the pressure (light blue) trans-

mitted to the vessel wall by the 2 devices with different surface scaffold areas. In C, the scoring balloon (LacrosseNSE, Goodman, Nagoya,

Japan) has a small surface area; as a consequence, the pressure exerted by the membrane of the balloon on the vessel wall (dark blue)

is very topical and “penetrating,” whereas the large rectangular strut of the scaffold (D) has a diffuse pattern of the stress strain rela-

tionship. In order to achieve similar expansion (and penetration) of both devices, more force should be applied on the large footprint of

the scaffold (F, snowshoe) than on the narrow footprint (E, ice skate) of the metallic stent. Strut width, embedment, and endothelial

shear stress: The footprint of the Cypher (G) is more easily embedded into the vessel wall than that of the wide Absorb strut (H).

The Cypher embedded strut does not disturb the lamina flow substantially whereas the Absorb strut protrudes more into the lumen,

thereby creating high endothelial shear stress (ESS) on top of the struts, resulting in platelet activation. Behind the protruding strut,

the flow reversal that creates low ESS results in local aggregation of activated platelet and promotes the thrombogenic process.

Modified with permission from Koskinas et al. (7) and Jimenez et al. (6). Red stars represent activated platelets; red lines represent

quiescent platelets. A ¼ area; ADP ¼ adenosine diphosphate; F ¼ force; P ¼ pressure; PMI ¼ periprocedural myocardial infarction;

TXA2 ¼ thromboxane A2.

Continued on the next page

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strut activates a platelet-signaling pro-coagulationpathway (Figure 2H), whereas the low shear stressmeasured behind and between the strut inducesreversal of the flow in a de-endothelialized area(5-7) (Figure 2H). The magnitude of flow disturbancedepends on the degree of protrusion of the strut intothe lumen. A low shear rate is known to induceplatelet aggregation, formation of microthrombi

with potential embolization, and micromyocardialnecrosis.

Although the clinical results and generating hypoth-esis from the current study are intriguing, the resultshould be cautiously interpreted and be confirmed in arandomized study, which is practically unexecutabledue to the unavailability of Cypher stent. In the future,the new generation of bioresorbable scaffolds with a

FIGURE 2 Continued

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thinner strut (100 mm) should be comparedwithmetallicstents having a similar thickness.

ACKNOWLEDGMENT The authors would like toacknowledge Dr. Hiroaki Hirase, Takaoka City Hos-pital and Goodman Co. for permission to use thecolor-coded stress strain in Figures 2C and 2D.

REPRINT REQUESTS AND CORRESPONDENCE: Dr.Patrick W. Serruys, International Center for Circula-tory Health, National Heart and Lung Institute,Imperial College London, London, United Kingdom.E-mail: patrick.w.j.c.serruys@gmail.com.

RE F E RENCE S

1. Kawamoto H, Panoulas VF, Sato K, et al. Impactof strut width in periprocedural myocardialinfarction: a propensity-matched comparison be-tween bioresorbable scaffolds and the first-generation sirolimus-eluting stent. J Am CollCardiol Intv 2015;8:900–9.

2. Muramatsu T, Onuma Y, Garcia-Garcia HM,et al., for the ABSORB-EXTEND Investigators.Incidence and short-term clinical outcomes ofsmall side branch occlusion after implantation ofan everolimus-eluting bioresorbable vascularscaffold: an interim report of 435 patients in theABSORB-EXTEND single-arm trial in comparisonwith an everolimus-eluting metallic stent in theSPIRIT first and II trials. J Am Coll Cardiol Intv2013;6:247–57.

3. Serruys PW, Chevalier B, Dudek D, et al.A bioresorbable everolimus-eluting scaffoldversus a metallic everolimus-eluting stent forischaemic heart disease caused by de-novo nativecoronary artery lesions (ABSORB II): an interim1-year analysis of clinical and procedural second-ary outcomes from a randomised controlled trial.Lancet 2015;385:43–54.

4. Kawamoto T, Okura H, Koyama Y, et al. Therelationship between coronary plaque character-istics and small embolic particles during coronarystent implantation. J Am Coll Cardiol 2007;50:1635–40.

5. Papafaklis MI, Bourantas CV, Farooq V, et al.In vivo assessment of the three-dimensionalhaemodynamic micro-environment following

drug-eluting bioresorbable vascular scaffold im-plantation in a human coronary artery: fusion offrequency domain optical coherence tomographyand angiography. EuroIntervention 2013;9:890.

6. Jimenez JM, Davies PF. Hemodynamicallydriven stent strut design. Ann Biomed Eng 2009;37:1483–94.

7. Koskinas KC, Chatzizisis YS, Antoniadis AP,Giannoglou GD. Role of endothelial shear stress instent restenosis and thrombosis: pathophysiologicmechanisms and implications for clinical trans-lation. J Am Coll Cardiol 2012;59:1337–49.

KEY WORDS bioresorbable scaffold,periprocedural MI, strut footprint