Intracoronary Coagulative Nightmare During Recanalization of a Recent Total Occlusion of the Left Anterior Descending Artery

Case Report. A 43-year-old man with hypertension, stress and family history for coronary artery disease presented at the Emergency Department one hour after the onset of chest pain with an acute anterolateral wall myocardial infarction (MI), for which he was treated with a full dose of abciximab (ReoPro, Eli Lilly and Company, Indianapolis, Indiana) and 50 mg of recombinant TPA bolus (Reteplase,Centocor, Inc., Malvern, Pennsylvania), heparin (PTT between 60 and 90), aspirin, intravenous nitroglycerin, and lidocaine. In approximately 30 minutes, the pain was relieved and the ST-segment elevation resolved with appearance of Q waves in leads V1–3. The peak CK was 1,580 IU/L with an MB fraction of 165 IU. Diagnostic coronary angiography, performed on day 4 for recurrence of pain, revealed a total occlusion of the proximal left anterior descending artery (LAD) with an apparent huge thrombus with distal LAD filling from the right coronary artery (RCA) (Figure 1). The left ventriculogram showed apical akinesia with mild anterior hypokinesia. Because of the huge thrombotic burden of the lesion, it was safer to submit the patient to a one-week course of subcutaneous enoxaparin (Aventis Pharmaceuticals, Bridgewater, New Jersey) 1 mg/Kg bid, coupled with aspirin 320 mg and ticlopidine 500 mg per day. During this treatment, there was no drop in platelet count, and the antithrombin level was within the normal limits. At the control angiography, the proximal LAD was still occluded. Patient management. We elected to proceed with recanalization of the LAD. Heparin (100 IU/Kg) and aspirin (500 mg) were administered intravenously; after cannulation of the femoral artery, eptifibatide (Integrilin, Cor Therapeutics, Inc., San Francisco, California) one half of the bolus was administered intracoronary after the left coronary ostium was cannulated with a 6 French extra backup 3.5 (XB 3.5, Cordis Corporation) guiding catheter. The lesion was crossed with an intermediate guidewire (Guidant Corporation, Temecula, California) with no opacification of the distal vessel; therefore, a 1.5/20 mm U-pass balloon (Cordis Corporation) was passed through, inflated at 6 bars, and then withdrawn. At control angiography, the distal vessel was recanalized with a TIMI I flow through the small channel created by the tiny balloon, but some cobblestone-like radiolucent images appeared in proximal LAD and left main stem (Figure 2). It was thought that thrombus was pulled back by the withdrawal of the balloon. At this time, the patient complained of some chest discomfort, with mild ST-segment elevation in the anterior leads, with a stable hemodynamic condition. The ACT was 289 seconds. The remaining half bolus of eptifibatide, aspirin (500 mg), and additional 3,000 IU of heparin were immediately administered intracoronary, together with a full intravenous dose infusion of eptifibatide. At the same time, the left circumflex (LCX) was wired and brisk intracoronary injections of saline were repeatedly given. This caused some migration of thrombi and reduction of flow along the intermediate branch, ostial LCX, diagonal, and LAD, with subsequent total occlusion of the LAD. After about 20 minutes, as there was no satisfactory resolution of the intracoronary thrombosis, an additional intracoronary half bolus of eptifibatide, coupled with 10 mg of recombinant TPA, were administered. Also, recombinant TPA (25 mg) were given intravenously over one hour. After about 30 more minutes, all thrombi cleared up, but the LAD remained closed as at start. An intracoronary bolus of 250 micrograms of nitroglycerin was given and the vessel reopened, showing a critical mid-proximal discrete LAD stenosis with some remaining thrombi. After wiring of the diagonal branch, a Carbostent (3.0 x 15 mm) (Sorin Corporation, Saluggia, Italy) was implanted at prox-mid LAD at 10 bars, and another 3.5 x 9 mm more proximally because of further appearance of some thrombi (Figure 3), with a final overexpansion inside the two stents at 16 bars. This resulted in an excellent angiographic result with a TIMI III flow along all the left coronary tree (Figure 4). The final ACT was 375 seconds. A critical stenosis of the mid diagonal (Figure 4) was left untreated because of fear of causing more thrombus formation. The patient was continued on eptifibatide, heparin (16,000 IU), and intravenous nitroglycerin for the following 24 hours. The CK rose to 316 IU/L (normal value David Ramsdale, MD Consultant Cardiologist, The Cardiothoracic Centre Liverpool, United Kingdom The correct time to attempt percutaneous coronary intervention (PCI) in this young man with an acute anterior MI was immediately after admission. This would probably avoid the difficulties that ensued due to the organization of the intracoronary thrombus that was occluding (or possibly reoccluding) the LAD. Assuming that primary PCI was not available, then the correct time to perform coronary angiography was as soon as possible after admission and treatment, so that revascularization could be performed by PCI if the LAD was severely stenosed or still occluded. At day four, when the LAD is shown to be occluded by thrombus, there is little point in hoping that a one-week course of subcutaneous heparin will reopen this vessel in the absence of any anterograde flow. Generally, the longer the vessel is left closed, the more organized the occluding thrombus becomes, and the more difficult it is to clear. The retraction of organized thrombus into the proximal LAD, LCX, intermediate and left main coronary arteries is an unusual but realistic risk during PTCA, in such vessels loaded with intracoronary thrombus. However, in the situation that the operators found themselves, the best treatment would be to attempt thrombectomy using either the Angiojet™ or the X-Sizer™ device. Most of the thrombus within the LAD could then be removed mechanically, as could any thrombus that had been accidentally withdrawn into the more proximal coronary circulation. Any residual thrombus could be lysed by intracoronary r-tPA (5 mg boluses down the left coronary artery via the guiding catheter every five minutes (up to 50 mg) usually will suffice). If the vessel then looks clear of thrombus and distal coronary flow looks good, IV heparin over the next 24 hours should be continued (ACT 200 seconds). If residual thrombus appears to exist or distal coronary flow appears suboptimal, then abciximab should be given (intracoronary bolus followed by a 12-hour IV infusion). However, in this situation, it is essential to carefully monitor the hematological and clotting indices and observe for any signs of bleeding if serious hemorrhagic complications are to be avoided. If thrombectomy devices were not available, then it would be important to establish anterograde flow down the LAD by using a larger diameter balloon catheter and dilating and stenting any significantly obstructing lesion within it before using intracoronary r-tPA etc. as described above to remove intracoronary thrombus and effectively restore distal coronary artery perfusion. Jeffrey A. Werner, MD, FACC Vice President, Cardiovascular Services Mercy Health Systems of Northwest Arkansas Rogers, Arkansas The reader has the benefit of seeing the results of waiting one week from the time of presentation of the initial infarction and a repeat angiogram demonstrating a persistently occluded vessel and persistent thrombus. This period of time, of course, “closes” the therapeutic window for treatment of the acute event and converts the purpose of attempted recanalization of the vessel to the hope of a better long-term outcome with an open artery. The patient is very fortunate, as this patient was apparently clinically fairly stable during this period, and the cardiac enzyme elevations seem more modest than would be expected given the complete proximal LAD occlusion and the wall motion abnormalities described. Therefore, it is, in my view, likely that the true original occlusion of the LAD may in fact have occurred some time earlier, perhaps “silently.” That said, in general, the cause of persistent thrombus (if a systemic thrombogenic syndrome or state is excluded), is either ongoing active plaque rupture (not likely but possible, based on the clinical picture), or more likely, a mechanical lesion downstream. In addition, the longer the vessel is occluded, the more likely capillary flow is to become compromised either due to absent flow or more actively due to microemboli and/or small vessel vasospasm. In fact, the lack of response to ReoPro and 50 mg/ms of TPA initially also speaks to a more complicated problem than just transient occlusive thrombus. Although there are many reasons to perform coronary angiography in the setting of an acute or recent MI, once the anatomy is revealed, an acute or even “semi-acute” thrombus is, in my view, an indication for attempted intervention. If heparin, TPA, aspirin and ReoPro were not effective in restoring some antegrade flow, there is little reason to wait any longer. In fact, one of the dreaded complications of acute intervention in the acute setting, namely, the pulling back of thrombus into the left main coronary or producing showers of emboli, occurred anyhow a week later. My approach to any proximally occluded vessel is to attempt to get some visualization of the distal vessel as soon as possible. I agree with the use of a small balloon for initial dilatations; however, if this does not result in immediate visualization of the distal anatomy, my practice is to advance the balloon a distance down the vessel and then to remove the wire and inject contrast into the distal lumen of the balloon. This assures, first of all, that I am in the true lumen and gives me some idea of how extensive the vessel is. In addition, one or more additional lesions can sometimes be demonstrated downstream that become the target subsequent dilatations. I will usually then administer a coronary vasodilator at this time to try to relieve distal vasospasm and encourage some antegrade flow. Following the replacement of the wire and anchoring in a more distal location in the visualized vessel, dilatations are then carried out distal to proximal. Any antegrade flow that can be accomplished via these methods can result in some mobilization of the original visualized proximal thrombus. If this occurs, theoretically, the proximal thrombus burden is likely to be less, and the likelihood of pulling thrombus more proximally during balloon withdrawal also likely to be less. I recall two of my cases in the last several years in which more thrombus appeared to be present after the initial dilatations and in multiple vessels similar to this case. Each was in the setting of very active infarction and therefore, a likely increased thrombogenicity. In each case, I sought urgent cardiovascular surgical consultation fearing “spontaneous” left main coronary occlusion. In each case, the surgeon wisely deferred, pointing out that the risk of multiple native vessel embolization would not be lessened by a proximal bypass graft, and the risk going through a surgical procedure was probably higher. In each case, once antegrade flow was at least partly restored, constant infusions of a glycoprotein (GP) IIB/IIIA inhibitor and heparin, as well as an hour or two of watchful waiting, resulted in a clear pattern of thrombus dissolution that was confirmed the next day. The take-home lesson, in my view, is that if therapeutic doses of antiplatelet, antithrombin and/or thrombolytic medications are not effective in reducing thrombus size and restoring antegrade flow in a coronary vessel or vein graft, there are almost always one or more mechanical lesions together with some degree of distal coronary vasospasm present and these need to be addressed. In patients without an unusual clotting abnormality, using “super therapeutic” doses of multiple medications are more likely to be associated with a significant bleeding complication, which itself, could be life-threatening. Deepak L. Bhatt MD, FACC, FSCAI, FESC Director, Interventional Cardiology Fellowship Cardiac, Peripheral, and Carotid Intervention Cleveland Clinic Foundation, Cleveland, Ohio The authors faced a very challenging case and obtained a nice clinical and angiographic result. I would have favored initial treatment with primary PCI. This case is a good example of the limitations of thrombolysis, even when it appears initially successful or when it is administered relatively early after onset of symptoms (within one hour in this case). Understandably, there is a global movement towards PCI as part of the initial therapy for acute MI. Furthermore, if initial PCI were not performed, I still would not have left the artery occluded for 1 week. Indeed, the artery did remain occluded, showing the futility of a strategy of prolonged anticoagulation instead of revascularization in this situation. In the United States, I would have used clopidogrel instead of ticlopidine, with the plan for long-term therapy.¹ Additionally, I would have just continued the enoxaparin through PCI, instead of changing to unfractionated heparin. There are ample data now to support the use of enoxaparin in PCI.² I agree with the use of glycoprotein IIb/IIIa blockade in this high-risk case. I would have additionally considered use of an ACE-inhibitor as part of the discharge medication regimen in this patient with an anterior MI. This case illustrates nicely how thrombus remains the bane of interventional cardiology, a nightmare that often disrupts a good night’s sleep. While pharmacological modulation remains key to the management of intra-procedural thrombus, in this instance of a large pre-existing thrombus burden, I may have favored using an Angiojet to remove some of the visible thrombus prior to balloon angioplasty and stenting. This approach may minimize the occurrence of distal embolization and perhaps decrease the likelihood of retrograde embolization (that is, thrombus being dragged back from the LAD by the balloon into the left main and/or circumflex. While this sort of retrograde embolization is rare, with a large amount of thrombus located in a proximal part of the vessel, it is a definite concern. While currently available emboli protection devices would only help decrease distal embolization, embolectomy devices would additionally help prevent retrograde embolization. Indeed, marriage of emboli protection devices and embolectomy catheters may theoretically lead to optimal thrombus removal.^3–5 Infusion of a bolus of intracoronary lytic, for example 10 or 20 mg of tPA via the guide catheter or via a balloon placed just proximally to the thrombus (or via an infusion catheter), may have also been useful in dissolving this relatively fresh thrombus. Recently, direct intracoronary administration (as opposed to intravenous administration) of GP IIb/IIIa inhibitors has been proposed as an effective means to help dissolve thrombus.⁶ Concomitant administration of intracoronary vasodilators such as sodium nitroprusside, verapamil, and adenosine can also help the microcirculation better absorb some degree of distal embolization. Such a multi-pronged approach, incorporating advanced device technology and pharmacotherapy, may offer our best chance for dealing with an “intracoronary coagulative nightmare.”