Добавил:
kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз: Предмет: Файл:

Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3720_Библиотеки_им_академика_М_И_Перельмана

.pdf
Скачиваний:
0
Добавлен:
31.08.2026
Размер:
30 Мб
Скачать
TABLE 19.2 Clinical Trials Evaluating STENTYS Stents for Treatment of ST-Segment Elevation Myocardial Infarction
https://t.me/med1917
Study Name/Year Study Type n Stents Evaluated Follow-Up
APPOSITION I (2011) [75]
APPOSITION II (2012) [76]
APPOSITION III (2013)
[77,78]
Multicenter single arm
Multicenter ran­domized controlled (1:1)
Prospective multi­center single arm
25 STENTYS BMS 6 months Technical success 100%
80 STENTYS BMS vs. balloon-
expandable BMS
1000 STENTYS BMS and DES 2 years TIMI 3 flow 95% 1 year
6 month Device success 97.6% vs. 100%, P ¼ NS
Procedural Outcomes (STENTYS vs. Control)
TIMI flow 3 96% Distal embolization 4% 3-day/6-month malapposition 8%/0%
Acute in-stent lumen gain (mm) 2.0.6 vs. 2.2 0.7, P ¼ NS
Postprocedure / 3-day in-stent lumen loss (mm) L0.12 ± 0.29 vs. 0.04 ± 0.2, P [ .01 Postprocedure strut malapposition 2.2% vs. 6%, P < .001 3-day strut malapposition 0.58% vs.
5.46%, P < .001
Clinical End Points (STENTYS vs. Control)
Restenosis 25% Ischemia-driven TLR 12% Other MACE 0%
MACE 0% vs. 2.3%, P ¼ NS
MACE 9.3% ST 3.5% Mortality 3.1% MI 2%
2 years
MACE 11.2% Cardiac mortality 2.3% ST 3.9%
ST with/without postdilatation 6.4%/
2.8%, P [ .009
Dedicated Thrombus-Containing Stent Platforms Chapter | 19 295
Continued
TABLE 19.2 Clinical Trials Evaluating STENTYS Stents for Treatment of ST-Segment Elevation Myocardial Infarctiondcont’d
https://t.me/med1917
296 Cardiovascular Thrombus
Study Name/Year Study Type n Stents Evaluated Follow-Up
APPOSITION IV (2016) [79]
APPOSITION
a
V
[80]
Multicenter ran­domized controlled (3:2)
Multicenter ran­domized
152 STENTYS sirolimus DES vs.
balloon-expandable zotaroli­mus DES
880 STENTYS BMS vs. balloon-
expandable BMS
1 year Procedure success 95.6% vs. 98.4%,
NA NA NA
controlled
Procedural Outcomes (STENTYS vs. Control)
P ¼ NS cTFC 28 vs. 28, P ¼ NS TIMI 3 flow 41.1% vs. 45.9, P ¼ NS Complete STR 38% vs. 52%, P ¼ NS
4 months
In-stent MLD (mm) 3.39 ± 0.46 vs.
3.13 ± 0.35, P [ .03
In-segment MLD (mm) 3.24 0.45 vs. 3.1 0.36, P ¼ NS
Malapposed struts 0.07% vs. 1.16%, P [ .02 Covered struts >20 mm 94.3% vs.
89.1%, P [ .003
9 months
In-stent MLD (mm) 3.27 ± 0.55 vs.
2.93 ± 0.43, P [ .01 In-segment MLD (mm) 3.13 ± 0.53 vs. 2.88 ± 0.44, P [ .05 Malapposed struts 0% vs. 0.57%, P [ .002
Covered struts >20 mm 96.7% vs.
97.2%, P ¼ NS
Clinical End Points (STENTYS vs. Control)
1 year
MACE 10.3% vs. 5%, P ¼ NS Cardiac mortality 2.3% vs. 0, P ¼ NS Recurrent MI 1.2% vs.
3.3%, P ¼ NS TLR 8.2% vs. 1.7%, P ¼ NS ST 3.5% vs. 1.7%, P ¼ NS
Bold results indicate statistically significant findings. BMS, bare metal stent; cTFC, corrected TIMI frame count; DES, drug eluting stent; MACE, major adverse cardiac events; MI, myocardial infarction; MLD, mean luminal diameter; NA, not available; NS, not significant; ST, stent thrombosis; STR, ST-segment resolution; TIMI, thrombolysis in myocardial infarction; TLR, target lesion revascularization.
a
Not yet completed or published.
Dedicated Thrombus-Containing Stent Platforms Chapter | 19 297
https://t.me/med1917
APPOSITION I was a prospective multicenter nonrandomized study that evaluated the feasibility and safety of the STENTYS stent in a small cohort of 25 patients with STEMI [75]. Using clinical follow-up and intravascular ultrasound or optical coherence tomography performed immediately after stent deployment, after 3 days, and at 6 months, the study demonstrated very high technical, device, and procedural success rates (96%e100%). Malapposition rates were low at 3 days and absent at 6 months. Although the rates of restenosis and ischemia-driven target-lesion revascularization were relatively high (25% and 12%, respectively), no additional MACEs were reported at 6 months. The study concluded that the use of the STENTYS stent is safe and feasible in STEMI patients, but restenosis remained an issue to be resolved.
The APPOSITION II trial [76] was a multicenter (nine European centers) randomized controlled trial that compared the STENTYS BMS with a balloon-expandable BMS in 80 patients with STEMI. The study showed a clear and prominent advantage in complete apposition with STENTYS compared with the control group. However, this did not translate into a statistically signicant reduction in clinical events (MACEs) at 6-month follow-up. The APPOSITION III trial [77] was a prospective, postmarket (i.e., after regulatory approval in Europe) nonrandomized multicenter (50 hospitals across Europe) study that assessed the long-term outcomes of STENTYS (either BMS or paclitaxel-eluting stent at the operators discretion) in 1000 STEMI patients. Successful reperfusion, evident by TIMI 3 ow of 95%, was the rule. At 1-year follow-up the incidence of MACE was 9.8% with a denite/probable 3.5% incidence of stent thrombosis. At 2-year follow-up [78] the rate of MACE was 11.2%, while the rate of denite/probable stent thrombosis was 3.9%. Interest­ingly, patients that underwent postdilatation following STENTYS implantation had signicantly lower rates of 2-year stent thrombosis. The APPOSITION IV trial [79] was a multicenter (12 sites in ve countries) randomized controlled study that evaluated the sirolimus-eluting STENTYS stent compared with a zotarolimus-eluting balloon-expandable stent used in STEMI. Angiographic follow-up (quantitative coronary angiography) and optical coherence tomography were performed at 4 and 9 months. This study showed signicantly less malapposition and uncovered struts at 4 months after implantation and similar rates of apposition and coverage between groups at 9 months. Luminal dimensions were signicantly larger in the STENTYS group, with late loss being equivalent between groups, both at 4 and at 9 months. Furthermore, numerically higher rates of MACE were observed in the STENTYS group, yet they did not reach statistical signicance, as this study was not powered to discern differences in hard clinical outcomes.
Thus the next study, APPOSITION V, was designed as the first randomized controlled trial powered to detect dif­ferences in clinical end points between STENTYS BMS and balloon-expandable BMS patients undergoing primary PCI for STEMI [80]. The planned enrollment was 880 patients with 1:1 randomization. The primary end point was defined as target-vessel failure at 12 months. However, enrollment was discontinued in July 2014 because of slow enrollment, and the findings not yet reported as of this writing [81] (Fig. 19.5).
STENTYS for Revascularization of Saphenous Vein Grafts
The ADEPT trial [82] evaluated STENTYS stents for PCI of SVGs. This trial compared the STENTYS BMS versus the STENTYS paclitaxel-eluting stent in 57 patients undergoing SVG revascularization. Follow-up was 6 months post-PCI. The primary end point was angiographic in-stent lumen loss, while the secondary end point was MACE. There was no difference in the primary outcome between the two groups (BMS 0.7 1.36 mm vs. DES 0.4 0.7 mm, P ¼ .88). Similarly, MACE rates did not differ: 11.1% (BMS) versus 10% (DES), P ¼ NS. Furthermore, these ndings are consistent with other SVG interventional studies using various available stent types [83,84].
CONCLUSIONS AND RECOMMENDATIONS
This chapter describes a nd analyzes data on novel dedicated thrombus-containing stent platforms for utilization as addi­tional tools in the armamentarium of the interventional cardiologist. The chapter focuses on the two most distinct and widely investigated stent platforms: the MGuard and STENTYS devices. The development of these stents for settings with signicant thrombus burden relies on a strong pathophysiological rationale. Concordantly, preliminary studies and sub­sequent clinical trials showed strong signals of better procedural outcomes without additional technical complexity or time consumption. However, these outcomes are considered surrogate markers rather than hard clinical end points (e.g., mortality). Studies that investigated hard clinical outcomes and those that compared them with other available stents were scarce, were underpowered, and showed only weak tendency toward improvement. Consequently, current data are insufcient to highly substantiate an evidence-based denition of the indications for these stents, and hence their selection as well as adjunctive therapeutic measures should be custom tailored based on the clinical setting, patient, and technical characteristics, while considering the operators experience and preferences. Nonetheless, based on the available data as presented, our recommendations for the application of dedicated thrombus-capturing stents are as follows: consider
298 Cardiovascular Thrombus
https://t.me/med1917
(A) (B) (C)
(D) (E) (F) (G)
FIGURE 19.5 (A) An ostial occlusion in the left anterior descending artery (LAD) (white arrow) during ST-segment elevation myocardial infarction.
(B) After ow restoration, marked vessel tapering is observed in the mid-LAD (white arrows). (C) Final result after implantation of two STENTYS nitinol self-expandable stents in the mid- and proximal LAD in overlapping fashion. White arrows identied by letters have their OCT assessments represented with the corresponding letters in (E) and (F); a marked discrepancy in stent areas is shown; distal and proximal references are shown in (D) and (G). OCT, optical coherence tomography. Adopted with permission from Attizzani GF, et al. J Am Coll Cardiol 2014;63(14):1355e67.
delivery of the MGuard stent for patients with STEMI, especially with a large thrombotic volume, and for patients un­dergoing revascularization of an SVG with signicant atherothrombotic burden. Furthermore, we believe that MGuard utilization should be considered in circumstances of failed aspiration thrombectomy or when implantation of BMS versus DES is not the main issue during the course of PCI, e.g., when the need to achieve acute optimal PCI results is at jeopardy because of a large thrombus load. The MGuard implantation is currently not recommended in highly calcied and/or highly tortuous vessels, because of increased risk of mesh or even stent dislodgment, or within coronary bifurcation lesions with large side branches, because of the risk of side-branch compromise by the double-layer design. In addition, as chronic kidney disease and cardiogenic shock patients were often excluded from studies evaluating MGuard, evidence for these patients is lacking. The relatively high rate of stent dislodgment, especially with the MGuard Prime, is of certain concern; however, according to our experience this problem can be avoided by utilization of meticulous stent delivery technique incorporated with proper guiding catheter support. Moreover, aggressive predilatation potentially may overcome this issue, but, plausibly, at the price of reduced antiembolic protection. When overlapping MGuard stent implantation is considered, it should be performed from the distal to the proximal segment of the artery because of the increased risk of mesh entanglement while passing through a previously implanted stent. As for the STENTYS stent platform, it should be strongly considered in STEMI or for SVG revascularization patients when proper vessel sizing is intricate, in very large arteries, or when a discrepancy between proximal and distal vessel reference diameter exists. Postdilatation is recom­mended in most cases of STENTYS implantation and adjunctive intracoronary imaging should be considered as well. In instances of distal edge dissection involving an MGuard or STENTYS stent, using the same stent type as the original is preferred. The apparent increased risk of restenosis, especially with the MGuard stent, should be kept in mind and highly suspected throughout extended follow-up period. An approach aimed at addressing this specic shortcoming with a drug­eluting MGuard stent is under development as of this writing. It should be emphasized that the dedicated thrombus­containing stents do not completel y abolish the risk of distal embolization; thus the use of additional devices with possibly additive thrombus-restr aining effect should be considered. To emphasize, the use of MGuard or STENTYS stents does not obviate the need for using distal protection devices in appropriate cases. Data regarding adjunctive pre- and postprocedural pharmacotherapy with these stents are sparse (e.g., recommended dual antiplatelet duration); therefore current recommendations are consistent with other equivalent stent types. Additional large prospective randomized controlled trials comparing these stent platforms with other commercially available stents are warranted to better dene the appropriate role of these unique stents in the landscape of contemporary interventional cardiology.
Dedicated Thrombus-Containing Stent Platforms Chapter | 19 299
https://t.me/med1917
REFERENCES
[1] Patel MR, Calhoon JH, Dehmer GJ, Grantham JA, Maddox TM, Maron DJ, Smith PK. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2016
appropriate use criteria for coronary revascularization in patients with acute coronary syndromes: a report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardi­ography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and the Society of Thoracic Surgeons. J Nucl Cardiol March 6, 2017. https://doi.org/10.1007/s12350-017-0780-8 [Epub ahead of
print]. [2] Matar F, Mroue J. The management of thrombotic lesions in the cardiac catheterization laboratory. J Cardiovasc Transl Res 2012;5(1):52e61. [3] Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995;92(3):657e71. [4] Gibson CM, de Lemos JA, Murphy SA, Marble SJ, McCabe CH, Cannon CP, Antman EM, Braunwald E. Combination therapy with abciximab
reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation 2001;103(21):2550e4. [5] Topaz O, Topaz A, Owen K. Thrombus grading for coronary interventions: the role of contemporary classications. Intervent Cardiol
2011;3:705e12. [6] White CJ, Ramee SR, Collins TJ, Escobar AE, Karsan A, Shaw D, Jain SP, Bass TA, Heuser RR, Teirstein PS, et al. Coronary thrombi increase
PTCA risk. Angioscopy as a clinical tool. Circulation 1996;93(2):253e8. [7] Singh M, Berger PB, Ting HH, Rihal CS, Wilson SH, Lennon RJ, Reeder GS, Bresnahan JF, Holmes Jr DR. Inuence of coronary thrombus on
outcome of percutaneous coronary angioplasty in the current era (the Mayo Clinic experience). Am J Cardiol 2001;88(10):1091e6. [8] Sianos G, Papafaklis MI, Daemen J, Vaina S, van Mieghem CA, van Domburg RT, Michalis LK, Serruys PW. Angiographic stent thrombosis after
routine use of drug-eluting stents in ST-segment elevation myocardial infarction: the importance of thrombus burden. J Am Coll Cardiol
2007;50(7):573e83. [9] Editorial TO. Revascularization of thrombus laden lesions in AMI-the burden on the interventionalist. J Invasive Cardiol 2007;19:324e5.
[10] Yetgin T, Nakatani S, Onuma Y, van Geuns RJ. Alternative stents in ST-segment elevation myocardial infarction: improving the efcacy of primary
percutaneous coronary intervention. Future Cardiology 2015;11(3):347e57.
[11] van Werkum JW, Heestermans AA, Zomer AC, Kelder JC, Suttorp MJ, Rensing BJ, Koolen JJ, Brueren BR, Dambrink JH, Hautvast RW, et al.
Predictors of coronary stent thrombosis: the Dutch stent thrombosis registry. J Am Coll Cardiol 2009;53(16):1399e409.
[12] Topaz O. Editorial. Focus on the infarct related artery: a thrombus runs through it. Catheter Cardiovasc Interv 2002:340e1. [13] Gupta S, Gupta MM. No reow phenomenon in percutaneous coronary interventions in ST-segment elevation myocardial infarction. Indian Heart
Journal 2016;68(4):539e51.
[14] Brosh D, Assali AR, Mager A, Porter A, Hasdai D, Teplitsky I, Rechavia E, Fuchs S, Battler A, Kornowski R. Effect of no-reow during primary
percutaneous coronary intervention for acute myocardial infarction on six-month mortality. Am J Cardiol 2007;99(4):442e5.
[15] Gracida M, Romaguera R, Jacobi F, Gomez-Hospital JA, Cequier A. The MGuard coronary stent: safety, efcacy, and clinical utility. Vasc Health
Risk Manag 2015;11:533e9.
[16] van t Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F. Angiographic assessment of myocardial reperfusion in patients treated
with primary angioplasty for acute myocardial infarction: myocardial blush grade. Zwolle Myocardial Infarction Study Group. Circulation
1998;97(23):2302e6.
[17] Lee MS, Park SJ, Kandzari DE, Kirtane AJ, Fearon WF, Brilakis ES, Vermeersch P, Kim YH, Waksman R, Mehilli J, et al. Saphenous vein graft
intervention. JACC Cardiovasc Interv 2011;4(8):831e43.
[18] Hong MK, Mehran R, Dangas G, Mintz GS, Lansky A, Kent KM, Pichard AD, Satler LF, Stone GW, Leon MB. Are we making progress with
percutaneous saphenous vein graft treatment? A comparison of 1990 to 1994 and 1995 to 1998 results. J Am Coll Cardiol 2001;38(1):150e4.
[19] Topaz O, Perin EC,Jesse RL, Mohanty PK, Carr ME, Rosenschein U. Power thrombectomy in acute coronary syndromes. Angiology
2003;91:797e802.
[20] G DEL BF, Huber K, Noc M, Petronio AS, Arntz HR, Maioli M, Gabriel HM, Zorman S, M DEC, et al. Early glycoprotein IIb-IIIa inhibitors in
primary angioplasty-abciximab long-term results (Egypt-ALT) cooperation: individual patients data meta-analysis. J Thromb Haemost
2011;9(12):2361e70.
[21] Stone GW, Maehara A, Witzenbichler B, Godlewski J, Parise H, Dambrink JH, Ochala A, Carlton TW, Cristea E, Wolff SD, et al. Intracoronary
abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA
2012;307(17):1817e
[22] Fernandez-Rodriguez D, Regueiro A, Brugaletta S, Martin-Yuste V, Masotti M, Cequier A, Iniguez A, Serra A, Hernandez-Antolin R, Mainar V,
et al. Optimization in stent implantation by manual thrombus aspiration in ST-segment-elevation myocardial infarction: ndings from the EX-
AMINATION trial. Circ Cardiovasc Interv 2014;7(3):294e300.
[23] Jolly SS, Cairns JA, Yusuf S, Meeks B, Pogue J, Rokoss MJ, Kedev S, Thabane L, Stankovic G, Moreno R, et al. Randomized trial of primary PCI
with or without routine manual thrombectomy. N Engl J Med 2015;372(15):1389e98.
[24] Frobert O, Lagerqvist B, Olivecrona GK, Omerovic E, Gudnason T, Maeng M, Aasa M, Angeras O, Calais F, Danielewicz M, et al. Thrombus
aspiration during ST-segment elevation myocardial infarction. N Engl J Med 2013;369(17):1587e97.
[25] Topaz O. Editorial. Comparison between thrombus removal devices: aspirations meet reality. Catheter Cardiovasc Interv 2011;78:20e2. [26] Baim DS, Wahr D, George B, Leon MB, Greenberg J, Cutlip DE, Kaya U, Popma JJ, Ho KK, Kuntz RE. Randomized trial of a distal embolic
protection device during percutaneous intervention of saphenous vein aorto-coronary bypass grafts. Circulation 2002;105(11):1285e90.
26.
300 Cardiovascular Thrombus
https://t.me/med1917
[27] Moris C, Lozano I, Martin M, Rondan J, Avanzas P. Embolic protection devices in saphenous percutaneous intervention. EuroIntervention
2009;5(Suppl. D):D45e50.
[28] Sobieraj DM, White CM, Kluger J, Tongbram V, Colby J, Chen WT, Makanji SS, Lee S, Ashaye A, Coleman CI. Systematic review: comparative
effectiveness of adjunctive devices in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention of native vessels. BMC Cardiovasc Disord 2011;11:74.
[29] Gorog DA, Foale RA, Malik I. Distal myocardial protection during percutaneous coronary intervention: when and where? J Am Coll Cardiol
2005;46(8):1434e45. [30] Kaluski E, Tsai S, Klapholz M. Coronary stenting with MGuard: from conception to human trials. Cardiovasc Revasc Med 2008;9(2):88e94. [31] Figini F, Colombo A. The role of MGuard stent in primary coronary angioplasty. Minerva Cardioangiol 2014;62(1):29e38. [32] Stankovic G, Colombo A, Presbitero P, van den Branden F, Inglese L, Cernigliaro C, Niccoli L, Bartorelli AL, Rubartelli P, Reifart N, et al.
Randomized evaluation of polytetrauoroethylene-covered stent in saphenous vein grafts: the Randomized Evaluation of polytetrauoroethylene
COVERed stent in Saphenous vein grafts (RECOVERS) Trial. Circulation 2003;108(1):37e42. [33] Stone GW, Goldberg S, OShaughnessy C, Midei M, Siegel RM, Cristea E, Dangas G, Lansky AJ, Mehran R. 5-year follow-up of
polytetrauoroethylene-covered stents compared with bare-metal stents in aortocoronary saphenous vein grafts the randomized BARRICADE
(barrier approach to restenosis: restrict intima to curtail adverse events) trial. JACC Cardiovasc Interv 2011;4(3):300e9. [34] Schachinger V, Hamm CW, Munzel T, Haude M, Baldus S, Grube E, Bonzel T, Konorza T, Koster R, Arnold R, et al. A randomized trial of
polytetrauoroethylene-membrane-covered stents compared with conventional stents in aortocoronary saphenous vein grafts. J Am Coll Cardiol
2003;42(8):1360e9. [35] Turco MA, Buchbinder M, Popma JJ, Weissman NJ, Mann T, Doucet S, Johnson Jr WL, Greenberg JD, Leadley K, Russell ME. Pivotal, ran-
domized U.S. study of the Symbiottrade mark covered stent system in patients with saphenous vein graft disease: eight-month angiographic and
clinical results from the Symbiot III trial. Catheter Cardiovasc Interv 2006;68(3):379e88. [36] Costa Jr JR, Abizaid A, Dudek D, Silber S, Leon MB, Stone GW. Rationale and design of the MGuard for acute ST elevation reperfusion MASTER
trial. Catheter Cardiovasc Interv 2013;82(2):184e90. [37] Kaluski E, Groothuis A, Klapholz M, Seifart P, Edelman E. Coronary stenting with M-Guard: feasibility and safety porcine trial. J Invasive Cardiol
2007;19(8):326e30. [38] Kaluski E, Hauptmann KE, Muller R, Tsai S, Klapholz M, Grube E. Coronary stenting with MGuard: rst-in-man trial. J Invasive Cardiol
2008;20(10):511e5. [39] Jain A, Weerackody R, Kennon S, Rothman M. Prevention of thrombus embolization during primary percutaneous intervention using a novel mesh
covered stent. Catheter Cardiovasc Interv 2009;74(1):88e93. [40] Piscione F, Danzi GB, Cassese S, Esposito G, Cirillo P, Galasso G, Rapacciuolo A, Leosco D, Briguori C, Varbella F, et al. Multicentre experience
with MGuard net protective stent in ST-elevation myocardial infarction: safety, feasibility, and impact on myocardial reperfusion. Catheter Car-
diovasc Interv 2010;75(5):715e21. [41] Dudek D, Dziewierz A, Rzeszutko L, Legutko J, Dobrowolski W, Rakowski T, Bartus S, Dragan J, Klecha A, Lansky AJ, et al. Mesh covered stent
in ST-segment elevation myocardial infarction. EuroIntervention 2010;6(5):582e9. [42] Dudek D, Dziewierz A, Kleczynski P, Giszterowicz D, Rakowski T, Sorysz D, Rzeszutko L, Legutko J, Bartus S, Dragan J, et al. Long-term follow-
up of mesh-covered stent implantation in patients with ST-segment elevation myocardial infarction. Kardiol Pol 2014;72(2):140e5. [43] Romaguera R, Gomez-Hospital JA, Sanchez-Elvira G, Gomez-Lara J, Ferreiro JL, Roura G, Gracida M, Homs S, Teruel L, Cequier A. MGuard
mesh-covered stent for treatment of ST-segment elevation myocardial infarction with high thrombus burden despite manual aspiration. J Intervent
Cardiol 2013;26(1):1e7. [44] Cerrato E, Rolfo C, Tomassini F, Montali N, Gambino A, Infantino V, Palacio Restrepo S, Baricocchi D, Nevola R, Gagnor A, et al. MGuard
Dacron mesh-covered stent implantation in patients with ST-elevation myocardial infarction and high thrombotic burden: in-hospital and long-term
outcome in a single high-volume center. G ital di cardiolog 2015;16(6):373e9. [45] Stone GW, Abizaid A, Silber S, Dizon JM, Merkely B, Costa RA, Kornowski R, Wojdyla R, Maehara A, Dressler O, et al. Prospective, randomized,
multicenter evaluation of a polyethylene terephthalate Micronet mesh-covered stent (MGuard) in ST-segment elevation myocardial infarction: the
MASTER trial. J Am Coll Cardiol 2012;60(19):1975e84. [46] Dudek DAA, Silber S, et al. One-year results from the MASTER trial, a prospective, randomized, multicenter evaluation of an embolic protection
stent (MGuard) in patients with STEMI undergoing primary PCI. In: 25th annual scientic symposium of transcatheter cardiovascular therapeutics.
San Francisco, CA, USA; 2013. [47] Stone GW. The MASTER II trial. Comparison of the MGuard embolic protection stent with standard stent in acute myocardial infarction. In: The
international conference for innovations meeting. Tel Aviv, Israel; 2014. [48] Lindefjeld DS, Guarda E, Mendez M, Martinez A, Perez O, Fajuri A, Marchant E, Aninat M, Torres H, Dussaillant G. Microvascular coronary ow
comparison in acute myocardial infarction angioplasty treated with a mesh covered stent (MGUARD stent) versus bare metal stent: MICAMI-
MGUARD. Cardiovasc Revasc Med 2013;14(1):4e8. [49] Costa RA, Abizaid A, Lotan C, Dudek D, Silber S, Dizon JM, Maehara A, Dressler O, Brener SJ, Stone GW. Impact of thrombus burden on
outcomes after standard versus mesh-covered stents in acute myocardial infarction (from the MGuard for acute ST elevation reperfusion trial). Am J
Cardiol 2015;115(2):161e6.
Dedicated Thrombus-Containing Stent Platforms Chapter | 19 301
https://t.me/med1917
[50] Dudek D, Brener SJ, Rakowski T, Dziewierz A, Abizaid A, Silber S, Yaacoby E, Dizon JM, Costa RA, Maehara A, et al. Efcacy of an embolic
protection stent as a function of delay to reperfusion in ST-segment elevation myocardial infarction (from the MASTER trial). Am J Cardiol 2014;114(10):1485e9.
[51] Cassese S, Esposito G, Mauro C, Varbella F, Carraturo A, Montinaro A, Cirillo P, Galasso G, Rapacciuolo A, Piscione F. MGUard versus bAre-
metal stents plus manual thRombectomy in ST-elevation myocarDial infarction pAtieNts-(GUARDIAN) trial: study design and rationale. Catheter Cardiovasc Interv 2012;79(7):1118e26.
[52] Amoroso G, Vos NS, Van der Heyden JA, van der Schaaf RJ, Patterson MS, Vink MA, Herrman JP, Slagboom T. A prospective, postmarket study
with the Mguard Prime embolic protection stent in ST-segment elevation myocardial infarction: the International MGuard Prime Observational Study (IMOS Prime). Catheter Cardiovasc Interv 2015;86(Suppl 1):S28e33.
[53] Fernandez-Cisnal A, Cid-Alvarez B, Alvarez-Alvarez B, Cubero-Gomez JM, Ocaranza-Sanchez R, Lopez-Otero D, Souto-Castro P, Diaz de la
Llera LS, Trillo-Nouche R, Gonzalez-Juanatey JR. Real world comparison of the MGuard Stent versus the bare metal stent for ST elevation myocardial infarction (the REWARD-MI study). Catheter Cardiovasc Interv 2015;85(1):E1e9.
[54] Hana Vaknin-Assa AA, Lev EI, Greenberg G, Orvin K, Valze O, Paul G, Levi A, Kornowski R. Long term outcomes of MGuard stent deployment
in saphenous vein grafts and native coronary arteries: a single center experience. Isr Med Assoc J 2017 Mar;19(3):172e6.
[55] Maia F, Costa Jr JR, Abizaid A, Feres F, Costa R, Staico R, Siqueira D, Esteves V, Sousa A, Sousa JE. Preliminary results of the INSPIRE trial with
the novel MGuard stent system containing a protection net to prevent distal embolization. Catheter Cardiovasc Interv 2010;76(1):86e92.
[56] Swaye PS, Fisher LD, Litwin P, Vignola PA, Judkins MP, Kemp HG, Mudd JG, Gosselin AJ. Aneurysmal coronary artery disease. Circulation
1983;67(1):134e8.
[57] Topaz O, Rutherford MS,Mackey-Bojack S, Prinz AW, kata S, Salter D, Titus JL. Giant aneurysms of coronary arteries and saphenous vein grafts:
angiographic ndings and histopathologic correlates. Cardiovasc Pathol 2005;14:298e302.
[58] Chiusaroli A, Segreto A, De Salvatore S, Congiu S, Zicho D, Bizzarri F. Coronary artery aneurysms: case report and treatment overview. Eur Rev
Med Pharmacol Sci 2015;19(14):2572e4.
[59] Briguori C, Sarais C, Sivieri G, Takagi T, Di Mario C, Colombo A. Polytetrauoroethylene-covered stent and coronary artery aneurysms. Catheter
Cardiovasc Interv 2002;55(3):326e30.
[60] Szalat A, Durst R, Cohen A, Lotan C. Use of polytetrauoroethylene-covered stent for treatment of coronary artery aneurysm. Catheter Cardiovasc
Interv 2005;66(2):203e8.
[61] Danzi GB, Pomidossi GA, Casolo F, Centola M, Ferraresi R, Lotan C. A new device to seal large coronary aneurysms: a case report. J Med Case
Rep 2010;4:238. [62] Patil P, Sethi A, Kaul U. Stent thrombosis with an aneurysm 7 years after a drug eluting stent implantation. Indian Heart Journal 2014;66(2):216e9. [63] Crimi G, Bartolini D, Bellotti S, Iannone A, Rubartelli P. Percutaneous management of a coronary bifurcation aneurysm with mesh-covered stents
and the simultaneous kissing stent technique. Tex Heart Inst J 2015;42(4):397e9. [64] Romaguera R, Gomez-Hospital JA, Cequier A. Novel use of the Mguard mesh-covered stent to treat coronary arterial perforations. Catheter
Cardiovasc Interv 2012;80(1):75e8. [65] Giustino G, Mehran R. Role of new sirolimus self-apposing stent in coronary interventions. Minerva Cardioangiol 2015;63(1):45e57. [66] Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty.
N Engl J Med 1987;316(12):701e6. [67] Karalis I, Ahmed TA, Jukema JW. Late acquired stent malapposition: why, when and how to handle? Heart 2012;98(20):1529e36. [68] Attizzani GF, Capodanno D, Ohno Y, Tamburino C. Mechanisms, pathophysiology, and clinical aspects of incomplete stent apposition. J Am Coll
Cardiol 2014;63(14):1355e67. [69] Bezerra HG, Attizzani GF, Sirbu V, Musumeci G, Lortkipanidze N, Fujino Y, Wang W, Nakamura S, Erglis A, Guagliumi G, et al. Optical
coherence tomography versus intravascular ultrasound to evaluate coronary artery disease and percutaneous coronary intervention. JACC Car-
diovasc Interv 2013;6(3):228e36. [70] Guo N, Maehara A, Mintz GS, He Y, Xu K, Wu X, Lansky AJ, Witzenbichler B, Guagliumi G, Brodie B, et al. Incidence, mechanisms, predictors,
and clinical impact of acute and late stent malapposition after primary intervention in patients with acute myocardial infarction: an intravascular
ultrasound substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial.
Circulation 2010;122(11):1077e84. [71] Alfonso F, Dutary J, Paulo M, Gonzalo N, Perez-Vizcayno MJ, Jimenez-Quevedo P, Escaned J, Banuelos C, Hernandez R, Macaya C. Combined
use of optical coherence tomography and intravascular ultrasound imaging in patients undergoing coronary interventions for stent thrombosis. Heart
2012;98(16):1213e [72] Dangas GD, Claessen BE, Caixeta A, Sanidas EA, Mintz GS, Mehran R. In-stent restenosis in the drug-eluting stent era. J Am Coll Cardiol
2010;56(23):1897e907. [73] Laborde JC, Borenstein N, Behr L, Ramcharitar S. Stentys coronary bifurcation stent. EuroIntervention 2007;3(1):162e5. [74] Giacchi G, La Manna A, Tamburino C, Capodanno D, Capranzano P. Self-apposing STENTYS(R) stent in acute myocardial infarction. Minerva
Cardioangiol 2014;62(1):59e70. [75] Amoroso G, van Geuns RJ, Spaulding C, Manzo-Silberman S, Hauptmann KE, Spaargaren R, Garcia-Garcia HM, Serruys PW, Verheye S.
Assessment of the safety and performance of the STENTYS self-expanding coronary stent in acute myocardial infarction: results from the
APPOSITION I study. EuroIntervention 2011;7(4):428e36.
20.
302 Cardiovascular Thrombus
https://t.me/med1917
[76] van Geuns RJ, Tamburino C, Fajadet J, Vrolix M, Witzenbichler B, Eeckhout E, Spaulding C, Reczuch K, La Manna A, Spaargaren R, et al. Self-
expanding versus balloon-expandable stents in acute myocardial infarction: results from the APPOSITION II study: self-expanding stents in ST­segment elevation myocardial infarction. JACC Cardiovasc Interv 2012;5(12):1209e19.
[77] Montalescot G. APPOSITION III - a post market study to assess the STENTYS self-expanding coronary stent in acute myocardial infarction in real
life. In: EuroPCR; 2014.
[78] KT K: a Post-market study to assess the STENTYS self-expanding coronary stent in acute myocardial infarction in real life. nal 2-years results. In:
TCT; 2014.
[79] van Geuns RJ, Yetgin T, La Manna A, Tamburino C, Souteyrand G, Motreff P, Koch KT, Vrolix M, A IJ AG, et al. STENTYS self-apposing
sirolimus-eluting stent in ST-segment elevation myocardial infarction: results from the randomised APPOSITION IV trial. EuroIntervention 2016;11(11):e1267e1274.
[80] Grundeken MJ, Lu H, Mehran R, Cutlip DE, Leon MB, Yeung A, Koch KT, Montalescot G, van Geuns RJ, Spaargaren R, et al. APPOSITION V:
STENTYS coronary stent system clinical trial in subjects with ST-segment elevation myocardial infarctionerationale and design. Am Heart J
2014;168(5):652e60. [81] STENTYS web site. Available at: http://www.stentys.com/17/3/articles/clinical-trials.html; 2016. [82] Ijsselmuiden AAG, Vermeersch P, Karjalainen P. Comparison between self-apposing bare metal and paclitaxel-eluting coronary stents for the
treatment of saphenous vein grafts: the ADEPT study. In: EuroPCR; 2014. [83] Mehilli J, Pache J, Abdel-Wahab M, Schulz S, Byrne RA, Tiroch K, Hausleiter J, Seyfarth M, Ott I, Ibrahim T, et al. Drug-eluting versus bare-metal
stents in saphenous vein graft lesions (ISAR-CABG): a randomised controlled superiority trial. Lancet (London, England) 2011;378(9796):1071e8. [84] Brilakis ES, Lichtenwalter C, de Lemos JA, Roesle M, Obel O, Haagen D, Saeed B, Gadiparthi C, Bissett JK, Sachdeva R, et al. A randomized
controlled trial of a paclitaxel-eluting stent versus a similar bare-metal stent in saphenous vein graft lesions the SOS (Stenting of Saphenous Vein
Grafts) trial. J Am Coll Cardiol 2009;53(11):919e28.
Chapter 20
https://t.me/med1917
Dissolution of Thrombus With Ultrasound: A Journey Through Physics, Basic Research, and Clinical Utilization
Uri Rosenschein
Israel Institute of Technology, Haifa, Israel
INTRODUCTION
During the 1980s I was in training in cardiology while the revolution in coronary interventions was happening. Coronary revascularization frenzy was all over the literature, with a wide array of technologies (e.g., laser, drillers) and energies (e.g., thermal, optical).
One day I read a manuscript on the cavitron ultrasound surgical aspirator (CUSA) system, a surgical system using high-power low-frequency ultrasound to dissect internal mammary arteries for bypass surgery. The authors observed a varying susceptibility of tissue to ultrasound ablation that made the CUSA system an effective tool: the artery was resistant to ultrasound and the fat around the artery was sensitive to ultrasound ablation. The gradient in sensitivity to ultrasound ablation suggested that ultrasound might be ideal for intravascular interventions in which the artery has to be preserved, if the right technology to deliver ultrasound were developed. That CUSA manuscript started my quest for the use of ultrasound for thrombolysis.
INHERENT SELECTIVITY
The acoustic spectrum, not unlike the electromagnetic spectrum, must be analyzed with attention to frequency and power. Both parameters determine the physical behavior of the acoustic energy. With time we have learned that the spectrum of ultrasonic energy can be separated arbitrarily into two major zones:
1. a high-frequency low-power ultrasound zone (2.5-7 MHz), which is commonly used for diagnostic imaging (i.e.
echocardiography), where high-power energy is attenuated to heat;
2. a low-frequency high-power (LFHP) ultrasound zone, where acoustic energy is translated to the cavitation effect, which
has been used for decades as a laboratory tool to ablate tissue.
When applied in liquid medium, LFHP ultrasound generates microbubbles (cavitations) during the negative phase of the acoustic cycle. As pressure falls below the vapor pressure of the tissue the microbubbles undergo rapid expansion and later collapse during the positive phase of the ultrasound wave. As these bubbles implode, local intense shock waves lead to various phenomena including depolymerization and tissue ablation.
As suggested by the historical CUSA experience, tissue characteristics are important determinates of the sensitivity to the ablative effect of LFHP ultrasound. In our early works we observed that the rates of ablation of thrombi were w20 times higher than those of aorta samples [1,2]. The differences in ablation rates were accompanied by lower elasticity in the thrombus group than in the aortic wall group, by 3 orders of magnitude. The different ablation rates of the aortic wall and thrombus could have been predicted by extrapolation data obtained when using a hydroxyproline gelatin model to study the relationship of LFHP ultrasound ablation to elasticity. Experiments with hydroxyproline gelatin indicate the presence of
Cardiovascular Thrombus. https://doi.org/10.1016/B978-0-12-812615-8.00020-X
Copyright © 2018 Elsevier Inc. All rights reserved.
303
304 Cardiovascular Thrombus
https://t.me/med1917
a very strong negative correlation between elasticity and LFHP ultrasound ablation. Thus, the susceptibility of biologic tissues to ultrasonic disruption is inversely related to their elasticity; the higher the elasticity the higher the resistance to ultrasound ablation. Further, LFHP ultrasound ablation of thrombi was evident only above the cavitation threshold and its rate correlated with the level of ultrasound power. These principles underlie the observation of tissue selectivity to ultrasound ablation. This corresponds well with clinical observations that tissues containing a heavy matrix of collagen and elastin (e.g., arterial wall bladder or heart valves) are resistant to ultrasound. Tissues without elastic support, such as thrombi, fat, or calcic deposits, are easily disrupted by LFHP ultrasound.
FIRST-GENERATION DEVICE
In my mind by that time, LFHP ultrasound was the Holy Grail of energy for catheter-based interventions, but with no technologies to harness the energy. During my fellowship I teamed up with an engineer and we embarked upon an effort to develop a catheter-based, LFHP ultrasound system. The use of the long wavelength of LFHP ultrasound determines the need for an external transducer attached to a catheter, which will act as a waveguide. The development of a catheter-based therapeutic ultrasound delivery system had signicant challenges, including coupling ultrasound wavelength with the catheter length, energy dissipation, heat generation, optimal material, and exibility.
The rst-generation LFHP ultrasonic device [3,4] was an experimental device capable of guiding LFHP ultrasound into the arterial system in a relatively exible delivery system. The device consisted of a 30-cm exible solid ultrasound transmission wire, 1 mm in diameter, attached at its proximal end to a piezoelectric element vibrating at 20 kHz. The device was powered by an external off-the-shelf generator (Sonier, Model 250, Branson Ultrasonic Corp.). The ultrasound energy was transformed into longitudinal vibrations of the ultrasound wire that guides the energy into the arterial system. The ultrasound generator was operat ed in the pulsed mode with a 30% duty cycle (pulse width 300 ms, period 1000 ms) to guarantee resonance capture of the ultrasound wires longitudinal resonant mode. Temperature rise in the ultrasound wire did not exceed 10
To elucidate the mechanism of action of the ultrasound ablative effects, the production of cavitations by the LFHP ultrasonic device was studied in an arterial phantom. To determine the cavitation threshold (i.e., the Lowe power level at which cavitations are produced), the production of cavitations was studied at different ultrasound intensity output settings. Cavitations were identied using standard ultrasound imaging as highly echogenic microbubbles [4]. At 12 W, a conically shaped eld of cavitations could be observed from the distal tip of the ultrasound wire that reached a maximal distance of 20 mm and a maximal radius of 17 mm.
In vitro, the ultrasonic device effectively disrupted fatty plaques and thrombi. Fatty plaques were signicantly more susceptible to ultrasound than complicated plaques. Histologic studies of solicited arterial segments indicate that the device disrupts atherosclerotic plaques with only minimal damage to the adjacent arterial wall [3].
In vitro, the device achieved dramatic thrombus liquefaction [3]: the weight of the residual solid thrombi was reduced by ultrasound (2 min application) by 75% of the thrombus that was liqueed. In the control group, mechanical penetration of the thrombi with the catheter without ultrasound reduced the weight of the solid thrombus by only 16%. Studies of the supernatant from the liqueed thrombi revealed the presence of multiple brin fragments, a high level of brin degradation products, and no morphologic damage to the red blood cells (under microscopic examination). The supernatants of the disrupted thrombi did not recoagulate. Thus, we hypothesized that the cavitation effect depolymerized the brin matrix, effecting ultrasound brinolysis(Fig. 20.1).
Later, we studied the effects of ultrasound thrombolysis in an in vivo model of a thrombus-rich lesion: in thrombotically occluded canine femora arteries [3]. We found a striking reduction in clot mass after sonication for only 2 min compared with mechanical penetration (dottering). The signicant high degree of recanalization was achieved in all the sonicated arteries with no damage to the arterial wall.
Hartnell et al. [5] studied the effect of coronary ultrasound thrombolysis using our system in an in vitro apparatus simulating the geometrical conguration and physical environment of intracoronary thrombus. They demonstrated that ultrasound can induce very efcient thrombus ablation, with the majority of debris being of subcapillary size. Muller et al.
[6] studied further the potential risk of embolization by ultrasound-lysed clots in vivo. They measured the coronary ow
and myocardial perfusion at baseline, after intracoronary injection of ultrasound-lysed clot and after intracoronary injection of control mechanically ablated clots. Following injection of ultrasound-lysed clots, a signicant increase in myocardial perfusion was observed. However, after injection of the mechanically ablated clot debris, a signicant reduction in ow was observed.
Thus, the data of the experimental studies suggest efcient thrombolysis with LFHP ultrasound and low risk of distal embolization.
To understand the effects of LFHP ultrasound on human arterial pathology and the limitations of in vivo models, ultrasound was applied using our system intraoperatively on totally occluded peripheral arteries during femoral popliteal
C.