The Challenge of Thrombus- Containing Lesions in 2009: An innovative solution for STEMI PCI to improve outcomes

Case 5 in a 5-part series

Thrombus-containing lesions remain a clear and present danger for today’s interventionalists in the accomplishment of successful percutaneous coronary intervention (PCI) procedures. Sianos et al1 demonstrated that patients with a large thrombus burden versus small thrombus burden in ST-elevation myocardial infarction (STEMI) treated with drug-eluting stents (DES) leads to higher acute failure (8.2%) and higher cardiac major adverse cardiac events (MACE) at two years. It has also been demonstrated that vein graft PCI with high thrombus burden increases the likelihood of procedural cardiac MACE and has a 10% death rate.2 There are many clinical scenarios where thrombus-containing lesions are identified, including STEMI, the majority of NSTEMI, aged degenerated vein grafts and stent thrombosis. Undoubtedly, increased procedural complications arise due to distal embolization, slow flow/no reflow and the higher likelihood of late stent thrombosis, especially with DES. One major challenge with thrombus-containing lesions is that our current detection system, angiography, is a poor tool for thrombus identification. Okamatsu et al studied 57 NSTEMI patients and found that thrombus was visible 18% of the time; however, in those same lesions, angioscopy showed thrombus presence 86% of the time.4 Not seeing thrombus does not allow us to ignore that in most cases, thrombus is present and must be addressed in order to ensure a successful outcome. Over three decades ago, De Wood et al showed that 90% of patients with MI had total coronary occlusion at angiography associated with acute thrombosis.5 Thus, making a pre-emptive strike in addressing the underlying thrombus burden may reduce many incidences of slow flow and no reflow or poor myocardial blush grade (MBG) during PCI procedures in these patients. Ito et al6 showed that patients with TIMI-2 flow after PCI showed substantial no reflow after angioplasty. Even with TIMI-3 flow, 16% of patients had no reflow. Despite our best efforts in addressing these complicated procedures, adverse outcomes are sometimes still inevitable with current standard of care modalities. Currently, in the U.S., our usual standard of care is to use extraction catheters, rheolytic thrombectomy or distal protection devices in conjunction with intravenous (IV) administration of glycoprotein (GP) IIb/IIIa inhibitors. This strategy is frequently flawed, due to failure of extraction catheters, embolization from rheolytic thrombectomy and the inability of IV administration of GP IIb/IIIa inhibitors to penetrate a heavy thrombus burden core. Furthermore, mechanical modalities such as distal filters fail to address thrombus that may form in the myocardial bed or was previously embolized during the plaque rupture. Additionally, the current focus on door-to-balloon time has left us with a tremendous dilemma regarding thrombus-containing lesions. In the quest of meeting the shortest door-to-balloon time possible, our focus has shifted away from preserving muscle through myocardial perfusion to focusing only on epicardial flow. Racing against the current 90-minute guideline in our rush to re-establish flow, we may actually be causing further damage downstream by embolizing the debris into the myocardial bed. Epicardial reperfusion is not synonymous with myocardial reperfusion, and myocardial damage is not terminated immediately, even with successful PCI. We have resolved one problem only to create a far worse one, since the death rate after an acute MI approaches 10%, and the incidence of cardiac failure after an acute MI is almost 25%.3 What is a responsible endovascular team to do? Recognizing the challenges of thrombus-containing lesions, we propose the consideration of different parameters for measuring success, by incorporating best practices to include a mechanical and pharmacological approach, in order to ensure the best case outcome. Guidelines for measuring progress should not only include TIMI-3 flow, but should also include myocardial blush scores, reduction in time to complete ST-segment resolution, and preserving left ventricular (LV) function. As described in prior publications in this journal, we present a patient with ST-elevation MI with large thrombus burden. Case Report The patient is a 58-year-old female who was admitted from the emergency room with acute anterolateral wall myocardial infarction. The patient was given aspirin 325 mg, IV heparin and 600 mg of clopidogrel, and was emergently brought to the cardiac catheterization laboratory. On initial diagnostic angiography, subtotal occlusion of the left anterior descending (LAD) with dye stain suggestive of significant thrombus burden and total occlusion of left circumflex (LCX) were observed (Figures 1–2). The right coronary artery had 75% stenosis in the proximal segment and LV ejection fraction (LVEF) was 45% by visual estimate on the left ventriculogram. Because of the patient’s multi-vessel coronary disease and severe angina, along with high risk for PCI procedure, an 8Fr intra-aortic balloon pump (IABP) (Datascope, Inc., Mahwah, NJ) was inserted in a prophylactic fashion. An 8Fr VL3.5 guiding catheter (Abbott Vascular, Redwood City, CA) was chosen to engage the left main coronary artery. We were able to easily cross the subtotal occlusion of the LAD with an 0.014-inch BMW Universal wire (Abbott Vascular). Subsequently, a 2.0 mm x 20 mm ClearWay RX catheter (Atrium Medical Corp., Hudson, NH) was placed just proximal to the lesion and 10.2 cc of abciximab bolus administered (Figure 3). This resulted in a reduction of thrombus burden and normalization of flow in the LAD (Figure 4). We then did balloon angioplasty and stented the LAD using three Taxus DES (Boston Scientific, Natick, MA). The same ClearWay catheter was reinserted into the LAD and intra-coronary (IC) adenosine 80 mcg was administered (Figure 5). Final LAD angiography revealed TIMI grade three and MBG 3 (Figure 6). At this point, spontaneous recanalization of the LCX was also seen with TIMI grade one flow in that vessel (Figure 7). It was thought that the LCX occlusion was also acute and we proceeded with recanalization of that vessel. It was treated using two Taxus DES and one bare-metal Vision stent (Abbott Vascular), resulting in TIMI grade three and MBG three (Figures 8-9). The next day, the patient’s IABP was removed and she was discharged three days later without any complications. The patient was brought back six weeks later for PCI of the RCA, which was carried out successfully with one DES. All of the left coronary system stents were found to be widely patent. The patient was again seen in follow up six months later. She remained asymptomatic with a LVEF of 50% by echocardiography. Discussion The above-mentioned strategy in a clinical case stems from multiple studies with IC abciximab as well as in vitro demonstrations of the de-thrombotic effects of abciximab in higher concentrations. By utilizing the novel technology of the ClearWay Rx infusion catheter, we can achieve high local concentration of abciximab IC. The ClearWay Rx therapeutic infusion catheter allows 500 times the systemic concentration of abciximab locally with its unique property of occlusion, containment and selective local infusion. This has resulted in many more of our thrombotic patients consistently leaving the lab with a blush score and TIMI score of three. By improving microvascular circulation, one can decrease infarct size and increase survival. Certainly, local drug delivery was in fashion approximately ten years ago, with local lytic therapy leading the way as a promising modality. Unfortunately, the bleeding risk proved too great to show a clinical benefit. Our drugs have evolved over the last decade to provide significant cardio-protective benefits while reducing bleeding complications, and we would be remiss not to try to maximize these benefits by considering a novel method of delivery to consistently achieve the best outcome. Critics have argued that they can achieve similar results using guide catheters or end hole catheters for IC delivery. In the past, it was our routine practice to use end hole catheters to inject drugs IC. This resulted in wire loss, and further, proved a challenge in preventing the introduction of air embolus. Especially in the left system, drug delivered via guide catheter remains undesirable, since the bifurcation of the LAD and LCX will result in significant drug loss into the non-infarct-related artery. The ClearWay Rx is a monorail, highly trackable, low-profile device that is very easy to use without the loss of the wire. Further, it promotes almost no risk of air embolism with appropriate device preparation. In some cases, high enough receptor occupancy (80% or greater is required for complete thrombus dis-aggregation7) can be achieved utilizing current drug delivery modalities to dissolve acute clot. But, what about vein grafts or patients that present outside of the four-hour window who have more organized clot? If the artery is occluded, guide catheter delivery will be incapable of penetrating clot, thus resulting in the drug taking the path of least resistance (typically down the aorta), and thus, not allowing its full dose to reach the distal myocardial bed. Certainly, with more organized clot burden, these modalities will likely prove unsuccessful, for the drug will potentially be incapable of penetrating the thrombotic core. In an occluded thrombotic vessel, positioning a ClearWay Rx catheter inside the thrombus increases the contact surface of abciximab into the thrombus perimeter, addressing residual clot left behind after mechanical extraction, and further, substantially increases the residence time of abciximab in the distal microcirculatory bed. These two features are essential if the de-thrombotic effect of abciximab is to be realized as evidence in ex-vivo studies. Concerns have also been expressed regarding the timing of drug delivery, and potential delay of IC delivery versus starting IV delivery at the beginning of the case. In a recent prospective study,8 17% of patients did not receive the IC bolus until after the procedure was completed, with no adverse effects. It is important to understand that the presence of abciximab molecules is not only important at the site of the thrombus, but also in the distal myocardial perfusion bed, in order to address residual thrombus after mechanical aspiration as well as thrombus that may have traveled or formed during PCI. A study conducted by Kloner et al9 showed that any agent successful in the reduction of infarct size should also reduce the incidence of no reflow. Thiele et al8 showed that infarct size was reduced significantly with IC delivery of abciximab as measured by contrast-enhanced magnetic resonance imaging (MRI). Of note, in this study, none of the patients who received IC abciximab had incidences of no reflow, and low incidences have also been observed in several other IC studies.8-11 This strategy has also consistently proven to be true in our own practice. Lastly, concerns have been expressed regarding possible bleeding from the addition of IV IIb/IIIa inhibitors. Most recently, presented HORIZON-AMI trial results showed mortality benefit in patients with bivalirudin alone in primary PCI procedures, mainly due to reduced bleeding.12 All of these factors suggest that a new strategy is essential to reduce upfront thrombus reduction to improve procedural success, and ensure more patients leave the lab with a higher MBG while keeping the bleeding risk to a minimum. In our clinical practice, IC abciximab delivered via the ClearWay Rx infusion catheter has shown substantial reduction in thrombus burden without increasing bleeding risk. We believe that the reduced bleeding risk seen with this strategy is primarily related to eliminating IV IIb/IIIa inhibitor maintenance infusions. A recently published retrospective analysis by Kini et al13 demonstrated no difference in the clinical outcome between IV bolus IIb/IIIa inhibitor versus bolus + infusion strategy. Moreover, recently presented data from the COCTAIL study (ClearWay catheter utilizing Optical Coherence Tomography to measure the impact of Abciximab intracoronary delivery on thrombus burden) at TCT 2008, by Dr. Francesco Prati, suggests significant reduction in the thrombus core by IC abciximab bolus delivery via the ClearWay Rx infusion catheter. (The thrombus core was generated by utilizing optical coherence tomography, a very sensitive and specific tool to evaluate IC thrombus burden.) Therefore, it is of paramount importance that the interventionalist understand the critical role of addressing thrombus during the PCI procedure to improve acute and late outcomes. Patients with both normal tissue level perfusion and a normal MBG have a lower risk of mortality. In the quest to improve door-to-balloon time, our focus may need to evolve to include myocardial reperfusion as the hallmark for restored blood flow. For complete reperfusion, success can not be declared until a significant reduction in thrombus burden results in the highest TIMI and blush score possible. The combination of mechanical reperfusion, coupled with the ClearWay catheter and abciximab, may result in a more consistent improvement in outcomes to improve myocardial reperfusion. Rajesh M. Dave, MD, can be contacted at rdintervention@yahoo.com

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