Changing the Standard of Care in STEMI PCI

Combining mechanical reperfusion and pharmacologic therapy to improve myocardial perfusion

Primary percutaneous coronary intervention (PCI) to restore coronary blood flow is the current standard of care for ST-elevation myocardial infarction (STEMI) PCI. Centers for Medicare & Medicaid Services (CMS)/The Joint Commission have established a door-to-balloon time of less than 90 minutes as one of the core performance measure to motivate clinicians and hospitals to adhere to this important class IA recommendation of 2004 American College of Cardiology (ACC)/ American Heart Association (AHA) and 2005 Society for Cardiovascular Angiography and Interventions (SCAI) PCI guidelines. Now additional resources are utilized by hospitals and clinicians to achieve this goal. There are certain parameters utilized for assessment of success in primary PCI which include TIMI flow, myocardial blush grades and ST-segment resolution.1,2,3 A recently published trial, Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS)4, demonstrated that patients that did not achieve a myocardial blush grade of at least 3 had a 5-fold higher rate of death at 30 days. One-year data, recently released, substantiates this trend.5 Moreover, a recently published study reported up to a 40% chance of “no reflow” or inadequate tissue perfusion in patients undergoing primary PCI for STEMI.6 It seems that the whole country is focused on door-to-balloon time, when in reality, it may be advantageous to consider door-to-myocardial perfusion time. According to the AHA/ACC guidelines, an ideal reperfusion strategy in patients with acute myocardial infarction (AMI) should not only restore flow in the occluded artery, but should attempt to reduce microvascular damage and improve reperfusion of the infarcted myocardium. One of the current existing limitations is operators’ lack of experience in assessing myocardial blush grades (MBG) on a routine basis. We have provided a brief guideline on how to assess MBG (Table 1). The TAPAS study demonstrated that use of aspiration catheters improves outcome in primary STEMI PCI. Even though aspiration catheter thrombectomy is successful in restoring the flow, it is often incomplete in removing the full degree of thrombus, specifically emboli that have traveled down to the myocardium. In TAPAS, patients did receive intravenous (IV) abciximab unless contraindicated. Despite aspiration thrombectomy and use of IV abciximab in the TAPAS study, only 45% of patients had blush grades of 3. Hence, refocusing the strategy from door-to-balloon time to door-to-reperfusion time may prove advantageous to myocardial salvage. Thiele et al7 recently published a randomized trial suggesting that the use of intra-coronary (IC) abciximab is emerging as an important adjunct to the current treatment algorithm for STEMI PCI. Their study concluded that IC abciximab acts as powerful thrombolytic agent in high concentrations, “which may facilitate the diffusion of the antibody to platelets inside the flow-limiting thrombus, thus resulting in improved dissolution of thrombi and microemboli at the ruptured plaque and further downstream in the microcirculation.” In this study, patients receiving IC abciximab had lower infarct sizes when compared to patients receiving IV abciximab as measured by MRI. Moreover, the trend towards improved TIMI flow and blush grade was also noted in the IC abciximab arm compared to the IV abciximab arm; however, the study was not powered to assess the absolute change in these parameters. Herein, we will propose a new strategy utilizing aspiration/thrombectomy, combined with pharmacologic intervention, which has delivered promising results (improvement in myocardial blush grades and reduction in infarct size) in our practice. We have provided the algorithm that we routinely use for our STEMI PCI cases (Table 2). This strategy is currently being tested in several clinical trials, such as CRYSTAL AMI, COCTAIL and INFUSE AMI. In a series looking at a total of five cases (the first one published in this issue of Cath Lab Digest), we will demonstrate the use of the ClearWay™ Therapeutic infusion balloon (Atrium Medical Corporation, Hudson, NH) delivering IC abciximab and IC nitroprusside/adenosine combined with mechanical or aspiration thrombectomy in patients undergoing primary PCI for STEMI. Before describing the first case, let’s look at why delivery of IC abciximab in a high concentration locally may have substantial advantages over IV or IC guide catheter-delivered abciximab. Recently, there has been a significant amount of research investigating the intra-coronary (IC) delivery of specific drugs as compared to IV injections. This research has shown that when specific compounds are delivered locally, they provide different pharmacokinetic properties, above their usual mechanism of action.8,9 In vitro studies have demonstrated that IC glycoprotein IIb/IIIa inhibitors, in high concentration, virtually disaggregate fresh thrombus and also enable non-antithrombotic effects such as lytic properties and anti-inflammatory effects to be expressed.10 IC injection via guide or end hole catheter does attempt to deliver the drug as close to the infarct site as possible. However, this approach has some shortcomings. When a drug is delivered down the guide catheter, it will be diverted through all of the bifurcations before it reaches the culprit lesion. Some drug may reach the target destination and will be certainly in a higher concentration than through IV delivery. However, the drug will quickly be diluted into the bloodstream within a couple of heartbeats and soon reach lower IV concentrations. ClearWay is a low-profile, rapid-exchange therapeutic infusion catheter and is indicated for localized perfusion of various diagnostic and therapeutic agents into the coronary and peripheral vasculature. The ClearWay therapeutic infusion catheter enables local drug delivery to reach approximately a 500-fold greater drug concentration versus systemic delivery. The catheter’s novel OCI (occlusion, containment and infusion) therapeutics platform occludes flow temporarily. While the flow is occluded, the thrombus is contained and the drug is infused, maximizing the drug bioavailability at the site and enabling an enhanced therapeutic effect. In addition to IC delivery of abciximab, we also employ the strategy of either adenosine or sodium nitroprusside delivery via ClearWay prior to stent implantation in STEMI PCI, especially in the presence of high thrombus burden lesions. It is our observation that some degree of microembolization is inevitable in these type of lesions, despite successful aspiration thrombectomy and IC abciximab. Vasodilators such as adenosine and sodium nitroprusside might have a role in improving microvascular function and reduction of the no-reflow phenomenon.11,12 Following is case one of five, with the remaining four cases to be published in the next four issues of Cath Lab Digest. Case One: Acute Anterior Wall AMI Complicated by Cardiac Arrest and Cardiogenic Shock History The patient is a 38-year-old female who presented to the emergency department 1.5 hours after onset of chest pain. Electrocardiogram (EKG) documented ST-segment changes suggestive of an anterior ST-elevation myocardial infarction (STEMI). The patient was given chewable aspirin, nitroglycerin, and intravenous (IV) heparin. As she was being counseled on the recommendation for emergency cardiac catheterization, she went into ventricular fibrillation. She was cardioverted 360 Jules x 4. The patient was intubated and 300 mg IV amiodarone was administered. IV pressors were started to treat hypotension. Despite IV pressors, the patient’s systolic blood pressure (BP) was in the range of 80. The patient was taken emergently to cardiac catheterization for primary percutaneous coronary intervention (PCI). On arrival to the cath lab, an intra-aortic balloon pump (IABP) was placed from the left femoral approach to treat refractory hypotension. Diagnostic angiography demonstrated patent left main, left circumflex (LCX) and right coronary artery (RCA) with total occlusion of the proximal left anterior descending artery (LAD). Procedure A 7-French (Fr) guide was placed, and a 0.014” Balance Middle Weight (BMW) wire (Abbott Vascular, Santa Clara, CA) was placed through total occlusion. A Diver aspiration catheter (ev3, Plymouth, MN) was used for thrombectomy. After the Diver aspiration catheter, there was no improvement in the flow. The patient then arrested and was cardioverted. Conclusion Post procedure left ventriculography showed hypokinesis of anterior wall. The patient had an uneventful recovery with hospital discharge 4 days post admission. In this case, use of abciximab via ClearWay instantly resolved the thrombus burden and saved this patient’s life by establishing TIMI-3 flow in the infarct-related artery and also resolving slow flow in the LCX. Future studies, such as CRYSTAL AMI, COCTAIL and INFUSE AMI (Dr. Rajesh Dave is the CRYSTAL AMI Principal Investigator, Dr. Francesco Prati is the Principal Investigator of COCTAIL, Dr. Gregg Stone and Dr. C. Michael Gibson are the Co-Principal Investigators of INFUSE AMI), will provide greater insight into this concept. We have seen very encouraging results in over 130 cases with the ClearWay catheter and local delivery of IC abciximab. We will be providing similar cases in the next four issues of Cath Lab Digest to demonstrate the effectiveness of this strategy and provide further technical pearls to improve outcomes in STEMI PCI. Rajesh M. Dave, MD, can be contacted at rdintervention@yahoo.com

1. Gibson CM, Schömig A. Coronary and myocardial angiography: angiographic assessment of both epicardial and myocardial perfusion. Circulation 2004: 109:3096-3105.

2. Gibson CM, Cannon CP, Murphy SA, et al. Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction. Circulation 2002: 105(16):1909-1913.

3. van 't Hof AW, Liem A, Suryapranata H. 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):2302-2306

4. Svilaas T, Vlaar PJ, van der Horst IC, et al. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med 2008;358:557-567.

5. Vlaar PJ, Svilaas T, van der Horst IC, et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet 2008 Jun 7;371(9628):1915-1920.

6. Niccoli G, Giubilato S, Russo E. Plasma levels of thromboxane A2 on admission are associated with no-reflow after primary percutaneous coronary intervention. Eur Heart J 2008 Aug;29(15):1843-1850.

7. Thiele H, Schindler K, Friedenberger J, et al. Intracoronary compared with intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: the randomized Leipzig immediate percutaneous coronary intervention abciximab IV versus IC in ST-elevation myocardial infarction trial. Circulation 2008 Jul 1;118(1):49-57.

8. Collet JP, Montalescot G, Lesty C, et al. Disaggregation of in vitro preformed platelet-rich clots by abciximab increases fibrin exposure and promotes fibrinolysis. Arterioscler Thromb Vasc Biol 2001 Jan;21(1):142-148.

9. Romagnoli E, Burzotta F, Trani C, et al. Rationale for intracoronary administration of abciximab. J Thromb Thrombolysis 2007 Feb;23(1):57-63.

10. Moser M, Bertram U, Peter K, et al. Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates. J Cardiovasc Pharmacol 2003 Apr;41(4):586-592.

11. Hillegass WB, Dean NA, Liao L, et al. Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience. J Am Coll Cardiol 2001 Apr;37(5):1335-1343.

12. Assali AR, Sdringola S, Ghani M, et al. Intracoronary adenosine administered during percutaneous intervention in acute myocardial infarction and reduction in the incidence of “no reflow” phenomenon. Cathet Cardiovasc Interv 2000;51:27-31.