ORIGINAL ARTICLES

Rheolytic Thrombectomy in Patients with ST-elevation Myocardial Infarction and Large Thrombus Burden: The Thoraxcenter Experienc

Georgios Sianos, MD, PhD, Michail I. Papafaklis, MD, Sofia Vaina, MD, Joost Daemen, MD, Carlos A. van Mieghem, MD, Ron T. Van Domburg, PhD, Lampros K. Michalis, MD, MRCP, Peter de Jaegere, MD, PhD, Patrick W. Serruys, MD, PhD
Georgios Sianos, MD, PhD, Michail I. Papafaklis, MD, Sofia Vaina, MD, Joost Daemen, MD, Carlos A. van Mieghem, MD, Ron T. Van Domburg, PhD, Lampros K. Michalis, MD, MRCP, Peter de Jaegere, MD, PhD, Patrick W. Serruys, MD, PhD

 

Primary percutaneous coronary intervention (PCI) is superior to thrombolysis in patients with ST-elevation myocardial infarction (STEMI), even when the latter is administered shortly after the onset of symptoms.1 Furthermore, stenting has ameliorated the outcome of patients with STEMI in comparison to balloon angioplasty,2 while there are promising results reported from the first published data regarding the use of drug-eluting stents (DES) in STEMI.3,4 The use of pharmacological agents, mainly glycoprotein (GP) IIb/IIIa receptor inhibitors, during primary PCI improved immediate and long-term outcomes.5,6
The presence of intracoronary thrombus is associated with adverse procedural complications such as distal embolization and no reflow, and worse clinical outcome compared to nonthrombus-containing lesions in acute coronary syndromes (ACS).7,8 Mechanical treatment of thrombotic lesions by means of thrombectomy and distal or proximal protection devices has been proposed to prevent the complications caused by thrombus and improve the outcome after a primary PCI. Initial reports showed promising results, but the randomized trials failed to demonstrate any beneficial effect of routine use of thrombectomy and distal protections devices on myocardial reperfusion or the clinical outcome during STEMI.9–12
There are no available data reporting on the selective use of rheolytic thrombectomy (RT) based on thrombus burden in patients undergoing primary PCI for STEMI. In the current report, the experience at Erasmus Medical Center is described regarding the use of RT in patients with large thrombus burden (LTB) who underwent primary PCI for STEMI.

Methods

Patients and procedure. From April 2002, when DES were introduced, until December 2004, 900 consecutive patients presented with STEMI; 266 had LTB. All patients underwent PCI (primary or rescue) within 12 hours after the onset of chest pain. PCI was performed according to standard clinical practice. The choice of stenting technique, the use of RT (the only thrombectomy or aspiration system used in our institution) and the peri-procedural pharmacological treatment was upon the operator’s discretion. All patients received dual anti-platelet therapy; aspirin 325 mg/day indefinitely and clopidogrel 75 mg/day for 1 month after balloon angioplasty or bare metal stent implantation and for 3 and 6 months after sirolimus- and paclitaxel-eluting stent implantation, respectively.
Clinical follow-up. Information regarding baseline clinical characteristics, procedural details and in-hospital events was obtained from electronic databases maintained at Erasmus Medical Center. Post-discharge survival status was obtained from the Municipal Civil Registry. A questionnaire was mailed to all living patients focusing on re-hospitalization and major adverse cardiac events (MACE). Referring cardiologists, general practitioners and patients were contacted when necessary for additional information. Written consent was obtained from all living patients. Definitions. Thrombus burden was graded as previously reported.13 According to that classification, large thrombus burden was defined as definite presence of thrombus with the greatest dimension ≥ 2 vessel diameters by visual assessment. Patients with occluded vessels at presentation were reclassified to a thrombus category after some flow restoration either with guidewire crossing or predilation with 1.5-mm balloon. TIMI flow14 and myocardial blush15 were graded as previously reported. No reflow was defined as reduced antegrade flow (TIMI flow grade < 2) in the absence of occlusion at the treatment site or evidence of distal embolization. Distal embolization was defined as migration of a filling defect to distally occlude the target vessel or one of its branches, or a new abrupt cut-off of the distal vessel/branch. MACE were defined as death, non-fatal myocardial infarction (MI) and target vessel revascularization (TVR). Myocardial infarction was defined as a rise in the creatinine kinase level to more than twice the upper normal limit with an increased creatinine kinase-MB. TVR was defined as a re-intervention in the infarct-related artery.
Statistics. Baseline characteristics were compared using the chi-square test or Fisher’s exact test when appropriate for categorical variables (presented as counts and percentages) and the unpaired t-test for continuous variables (presented as their mean ± standard deviation). Cumulative event rates were estimated using the Kaplan-Meier method and differences between groups assessed with the use of the log-rank test of significance. Multivariate Cox regression analysis was used for identifying the independent predictors of MACE. All tests were two-tailed and p-values less than 0.05 were considered significant. The SPSS statistical software package (version 12.0 for Windows, SPSS Inc. Chicago, Illinois) was used for the analysis.

Results

Follow-up information was obtained in all 266 patients with LTB; 75 patients (28.2%) underwent RT. Baseline characteristics were comparable between the two groups (Table 1).
The majority of the patients in both groups underwent primary PCI and received GP IIb/IIIa receptor inhibitors. The incidence of cardiogenic shock was comparable in both groups, (13.1% in the non-RT group vs. 9.3% in RT group; p = 0.4). Distal protection devices were infrequently used. The patients in RT had a higher rate of temporary pacemaker use (84% vs. 8.4%; p < 0.001) and direct stenting (70.7% vs. 42.9%; p < 0.001), while drug-eluting stents tended to be implanted more often in the non-RT group (86.9% vs. 78.7%; p = 0.09).
Procedural and in-hospital outcome. The RT group had better procedural and in-hospital outcomes compared to the non-RT group (Table 2).
Two-year outcome. There were 73 patients in the RT group and 170 in the non-RT group who were discharged alive. In these patients, there were 4 (5.5%) deaths in the RT group and 12 (7.1%) deaths in the non-RT group at a mean follow-up period of 18.6 ± 7.2 months. Consequently, there were 69 and 158 survivors in the 2 groups who had no difference in the mean follow-up interval (19.1 vs. 18.4 months respectively; p = 0.45). Seventeen (10%) patients in the non-RT and 3 (4.1%) in the RT group experienced a non-fatal repeat MI (p = 0.13), while 23 (13.5%) patients and none (0%), respectively, underwent repeat TVR (p < 0.001).
The 2-year cumulative survival was higher in the RT group (92% vs. 82.7%; p = 0.051; Figure 1A). Furthermore, the RT group had significantly better 2-year cumulative death/MI-free and MACE-free survival rates compared to the non-RT group (87.7% vs. 74%; p = 0.017 and 87.7% vs. 69.9%; p = 0.004, respectively; Figures 1B and 1C). The independent predictors of MACE are presented in Table 3.

Discussion

The Erasmus Medical Center experience regarding the use of RT in patients with STEMI and LTB treated with PCI is reported here. In this high-risk population, RT improves the procedural angiographic outcome and the in-hospital clinical outcome. Furthermore, patients undergoing RT have a significantly lower mortality and MACE rate at 2 years.
Angiographically evident thrombus has been associated with failure to achieve final TIMI 3 flow, reduced myocardial blush and increased incidence of distal embolization, all contributing to adverse clinical outcome.15–18 Furthermore, persistent thrombus after administration of tirofiban (Aggrastat®, Merck & Co., Inc., Whitehouse Station, New Jersey) results in a 2.4-fold increase in 30-day mortality and MI rate in patients with ACS.19 In this population, RT significantly increased TIMI 3 flow and blush grade 3 translated to improved clinical outcome.
No difference in the incidence of distal embolization or no reflow were observed. In all RT cases, after crossing the thrombotic lesion with the RT catheter, pull-back thrombectomy was performed and might have contributed to distal embolization. In cases of STEMI, in which the thrombus is fresh and fragile, forward thrombectomy with activation of the RT catheter before crossing the thrombotic lesion might be preferable and should be further explored. Moreover, the significantly higher incidence of very large thrombus (greatest length > 4 vessel diameters) in the RT group (64% vs. 33.5%; p < 0.001), indicative that thrombectomy is selectively used in patients with very large thrombus burden, might have also contributed to the comparable incidence of distal embolization and no reflow between the two groups.
The administration of GP IIb/IIIa receptor inhibitors during PCI in thrombus containing lesions improves the short- and long-term survival (reduction of 1.8% in mortality at 3 years).20 In a recent meta-analysis the administration of abciximab in patients undergoing primary PCI was associated with significant reduction in 30-day mortality and MI rate and a further significant benefit in mid-term mortality.6 In the Erasmus Medical Center population, the administration of GP IIb/IIIa inhibitors was at the discretion of the operator and approximately 70% of the patients received this adjunctive treatment. Their administration was comparable between the patients with or without RT indicating the additional benefit of using RT in this group of patients.
Intuitively, thrombus extraction before PCI in STEMI patients should be effective. The X-Sizer® (ev3, Inc., Plymouth, Minnesota),10,21,22 excimer laser23 and various simple manual aspiration thrombectomy catheters24–27 demonstrated promising results in the treatment of acute MI with improvement shown in surrogate endpoints such as resolution of ST-elevation, but all failed to demonstrate any benefit in hard clinical endpoints. In the majority of these trials, presence or extent of thrombus burden was not taken into account.
RT was first described in 1992 with first human application in 1993 and first use in coronary vasculature in 1995.28 After safety and effectiveness studies, RT has shown positive outcomes in thrombus-containing lesions when compared with intracoronary thrombolysis.29,30 More recently, it was proven superior to standard treatment in acute MI patients regarding optimal perfusion endpoints such as final TIMI frame count, ST-segment resolution and infarct size.31
However, the recent randomized AiMI trial investigating the routine use of RT during STEMI failed to show any benefit.12 The primary endpoint of final infarct size at 14 to 28 days was higher in the thrombectomy group (12.5% vs. 9.8%; p < 0.02) as well as the secondary endpoint of 30-day MACE (6.7% vs. 1.7%; p < 0.01), mainly due to higher mortality in the RT group (4.6% vs. 0.8%; p < 0.02). This is in contrast to our results where a benefit in in-hospital and 2-year mortality was observed. The most rational explanation is the very low prevalence of large thrombus burden, just 10% in AiMI, which favors the approach of preferentially using RT in patients with large thrombus burden.

Limitations

This is a retrospective analysis with all of the limitations arising from such an approach, especially for the determination of angiographic parameters such as blush scoring that require great discipline in angiographic documentation. Only the RT system was used and thus, the positive results observed cannot be generalized to other mechanical or manual thrombectomy systems.

Conclusions

Selective use of RT in patients with large thrombus burden during PCI for STEMI was associated with better procedural outcomes and in-hospital and mid-term MACE-free survival. Further randomized studies are necessary to confirm these results.

 

 

 

 

References

References

  1. Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: A meta-analysis. Circulation 2003;108:1809–1814.
  2. Grines CL, Cox DA, Stone GW, et al. Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent Primary Angioplasty in Myocardial Infarction Study Group. N Engl J Med 1999;341:1949–1956.
  3. Lemos PA, Saia F, Hofma SH, et al. Short- and long-term clinical benefit of sirolimus-eluting stents compared to conventional bare stents for patients with acute myocardial infarction. J Am Coll Cardiol 2004;43:704–708.
  4. Cheneau E, Rha SW, Kuchulakanti PK, et al. Impact of sirolimus-eluting stents on outcomes of patients treated for acute myocardial infarction by primary angioplasty. Catheter Cardiovasc Interv 2005;65:469–472.
  5. Yip HK, Wu CJ, Chang HW, et al. Impact of tirofiban on angiographic morphologic features of high-burden thrombus formation during direct percutaneous coronary intervention and short-term outcomes. Chest 2003;124:962–968.
  6. De Luca G, Suryapranata H, Stone GW, et al. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: A meta-analysis of randomized trials. JAMA 2005;293:1759–1765.
  7. White CJ, Ramee SR, Collins TJ, et al. Coronary thrombi increase PTCA risk. Angioscopy as a clinical tool. Circulation 1996;93:253–258.
  8. Singh M, Berger PB, Ting HH, et al. Influence of coronary thrombus on outcome of percutaneous coronary angioplasty in the current era (the Mayo Clinic experience). Am J Cardiol 2001;88:1091–1096.
  9. Stone GW, Webb J, Cox DA, et al. Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: A randomized controlled trial. JAMA 2005;293:1063–1072.
  10. Lefevre T, Garcia E, Reimers B, et al. X-sizer for thrombectomy in acute myocardial infarction improves ST-segment resolution: Results of the X-sizer in AMI for negligible embolization and optimal ST resolution (X AMINE ST) trial. J Am Coll Cardiol 2005;46:246–252.
  11. Harjai KJ, Grines C, Stone GW, et al. Frequency, determinants, and clinical implications of residual intracoronary thrombus following primary angioplasty for acute myocardial infarction. Am J Cardiol 2003;92:377–382.
  12. Ali A, Cox D, Dib N, et al. Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30 day results from a multicenter randomized study. J Am Coll Cardiol 2006 (In Press).
  13. Gibson CM, de Lemos JA, Murphy SA, et al. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: A TIMI 14 substudy. Circulation 2001;103:2550–2554.
  14. The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. TIMI Study Group. N Engl J Med 1985;312:932–936.
  15. van ‘t Hof AW, Liem A, Suryapranata H, et al. 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;97:2302–2306.
  16. Yip HK, Chen MC, Chang HW, et al. Angiographic morphologic features of infarct-related arteries and timely reperfusion in acute myocardial infarction: predictors of slow-flow and no-reflow phenomenon. Chest 2002;122:1322–1332.
  17. Henriques JP, Zijlstra F, Ottervanger JP, et al. Incidence and clinical significance of distal embolization during primary angioplasty for acute myocardial infarction. Eur Heart J 2002;23:1112–1117.
  18. Fukuda D, Tanaka A, Shimada K, et al. Predicting angiographic distal embolization following percutaneous coronary intervention in patients with acute myocardial infarction. Am J Cardiol 2003;91:403–407.
  19. Zhao XQ, Theroux P, Snapinn SM, Sax FL. Intracoronary thrombus and platelet glycoprotein IIb/IIIa receptor blockade with tirofiban in unstable angina or non-Q-wave myocardial infarction. Angiographic results from the PRISM-PLUS trial (Platelet receptor inhibition for ischemic syndrome management in patients limited by unstable signs and symptoms). PRISM-PLUS Investigators. Circulation 1999;100:1609–1615.
  20. Anderson KM, Califf RM, Stone GW, et al. Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol 2001;37:2059–2065.
  21. Beran G, Lang I, Schreiber W, et al. Intracoronary thrombectomy with the X-sizer catheter system improves epicardial flow and accelerates ST-segment resolution in patients with acute coronary syndrome: a prospective, randomized, controlled study. Circulation 2002;105:2355–2360.
  22. Napodano M, Pasquetto G, Sacca S, et al. Intracoronary thrombectomy improves myocardial reperfusion in patients undergoing direct angioplasty for acute myocardial infarction. J Am Coll Cardiol 2003;42:1395–1402.
  23. Dahm JB, Topaz O, Woenckhaus C, et al. Laser-facilitated thrombectomy: a new therapeutic option for treatment of thrombus-laden coronary lesions. Catheter Cardiovasc Interv 2002;56:365–372.
  24. Dudek D, Mielecki W, Legutko J, et al. Percutaneous thrombectomy with the RESCUE system in acute myocardial infarction. Kardiol Pol 2004;61:523–533.
  25. Burzotta F, Trani C, Romagnoli E, et al. Manual thrombus-aspiration improves myocardial reperfusion: the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombus-aspiration in primary and rescue angioplasty (REMEDIA) trial. Evid Based Cardiovasc Med. 2005;9:309–313.
  26. De Luca L, Sardella G, Davidson CJ, et al. Impact of intracoronary aspiration thrombectomy during primary angioplasty on left ventricular remodeling in patients with anterior ST-elevation myocardial infarction. Heart. 2005 Oct 26; [Epub ahead of print].
  27. van Ommen V, Michels R, Heymen E, et al. Usefulness of the rescue PT catheter to remove fresh thrombus from coronary arteries and bypass grafts in acute myocardial infarction. Am J Cardiol. 2001;88:306–308.
  28. Drasler WJ, Jenson ML, Wilson GJ, et al. Rheolytic catheter for percutaneous removal of thrombus. Radiology 1992;182:263–267.
  29. Nakagawa Y, Matsuo S, Kimura T, et al. Thrombectomy with AngioJet catheter in native coronary arteries for patients with acute or recent myocardial infarction. Am J Cardiol 1999;83:994–999.
  30. Kuntz RE, Baim DS, Cohen DJ, et al. A trial comparing rheolytic thrombectomy with intracoronary urokinase for coronary and vein graft thrombus (the Vein Graft AngioJet Study [VeGAS 2]). Am J Cardiol 2002;89:326–330.
  31. Antoniucci D, Valenti R, Migliorini A, et al. Comparison of rheolytic thrombectomy before direct infarct artery stenting versus direct stenting alone in patients undergoing percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2004;93:1033–1035.