Case presentation

A 45-year-old man presented to the emergency department with severe substernal chest pain of 2.5 hours duration. In the emergency department, the initial ECG showed sinus rhythm at a rate of 71 bpm with ST segment elevation in leads II, III, aVF, and V4 to V6. A “STEMI-Alert” was initiated to facilitate rapid coordination of reperfusion therapy.

The patient had a past history of atypical chest pain, hyperlipidemia, and gout. He worked as a self-employed artist; he denied tobacco abuse but smoked marijuana daily. He took no prescription medications. His physical examination was unremarkable, and laboratory studies found an initial troponin of 0.03 ng/mL, normal blood count and renal function, and marked lipid abnormalities (HDL 48 and LDL 213 mg/dL). Initial treatment began in the emergency room with aspirin (325 mg), clopidogrel (600 mg), and unfractionated heparin intravenous bolus (60 U/kg). He was referred for an emergency catheterization.

Cardiac catheterization

An ACT was measured and additional heparin administered to achieve an ACT between 250 and 300 seconds. Based on the ECG, the right coronary artery was the suspected infarct artery and was engaged first using a 6 French JR4 guiding catheter. Right coronary angiography revealed occlusion of the distal vessel, with retained contrast at the occlusion site (Figure 8-1 and Video 8-1). Eptifibatide was administered (two boluses, each of 180 mcg per kg, and an infusion of 2.0 mcg/kg per minute for 14 hours). The operator crossed the occlusion with a 0.014 inch floppy-tipped guidewire and TIMI-3 flow was restored after balloon dilatation with a 2.5 mm diameter by 15 mm long, compliant balloon. Following this, a 3.0 mm diameter by 23 mm long bare-metal stent was selected based on visual determination of the proximal and distal reference segments (Figure 8-2 and Video 8-2). A bare-metal stent was selected due to uncertainty about future medication compliance. The stent was positioned across the narrowed arterial segment and deployed at 14 atmospheres of pressure. The operator achieved a satisfactory angiographic result (Figure 8-3 and Video 8-3); intravascular ultrasound was not used.

FIGURE 8-1 Initial angiogram of the right coronary artery in the LAO cranial view showing the acute occlusion of the distal right coronary.

FIGURE 8-2 Placement of a bare-metal stent in the right coronary artery in the LAO cranial view following balloon angioplasty.

FIGURE 8-3 Final image of the right coronary artery in the LAO cranial view showing an excellent angiographic result in the distal right coronary artery. The more distal lesion was not significant in additional views.

Following stenting of the right coronary artery, the left coronary, imaged in standard views, showed minimal coronary atherosclerosis. A biplane left ventriculogram showed inferior and inferolateral hypokinesis with a preserved global ejection fraction estimated at 55%. The patient remained hemodynamically stable throughout the procedure. The vascular access sheath was removed with manual compression after 4 hours when the ACT was measured at less than 180 secs but while the eptifibatide infusion was continuing. He was treated during “off hours” with a door-to-balloon time of 64 minutes.

Postprocedural course

The patient recovered uneventfully, with his troponin level rising to 69 ng/mL. He was enrolled in cardiac rehabilitation and counseled regarding lifestyle modification, diet, weight loss, physical activity, and smoking (tobacco and marijuana) avoidance. He was discharged on the third hospital day and prescribed full-dose aspirin, clopidogrel, simvastatin, ezetimibe, lisinopril, and metoprolol. The importance of medical compliance, especially with aspirin and clopidogrel, was emphasized to the patient.

Three months later, the patient again presented to the emergency department after suffering chest pains for 5 hours. The initial ECG demonstrated 3 to 4 mm ST elevations in leads 2, 3, and aVF with Q waves in those leads. The patient had not kept his previous medical follow-up appointments and admitted to stopping all of his medications after running out of prescriptions 3 weeks prior to the current presentation. Again, he was promptly treated in the emergency department with aspirin (325 mg), clopidogrel (600 mg), and unfractionated heparin (60 U/kg) and brought emergently to the cardiac catheterization laboratory. Right coronary angiography confirmed the suspected occlusion at the site of the previously-placed bare-metal stent (Figure 8-4 and Video 8-4). Adjunctive pharmacology consisted of therapeutic levels of unfractionated heparin along with eptifibatide double bolus and infusion. The operator crossed the occluded stent with a conventional, 0.014 inch floppy-tipped guidewire, taking great care to avoid passing the wire behind stent struts. Similar to the first event, TIMI-3 flow was promptly restored after balloon dilatation with a 2.5 diameter by 15 mm long, compliant balloon (Figure 8-5 and Video 8-5). The operator chose to further expand the stent with a 3.0 mm diameter by 20 mm long, noncompliant balloon inflated to 18 atmospheres of pressure. Angiography confirmed the lack of any distal embolization and an acceptable angiographic result (Figure 8-6). Hemostasis was achieved with a closure device and the patient was transferred to the coronary care unit. Again, the patient was treated during “off hours” with a door-to-balloon time of 74 minutes.

FIGURE 8-4 Angiogram of the right coronary artery obtained during the second admission showing the acute occlusion of the distal right coronary at the site of the prior bare-metal stent placed 3 months earlier (late stent thrombosis). The occlusion site is clearly within the prior stent. The patient had stopped all of his medications due to cost and noncompliance.

FIGURE 8-5 After careful wire placement in the distal right coronary artery, a balloon is inflated within the prior stent.

FIGURE 8-6 Final angiogram of the right coronary artery in the LAO cranial view following repeat balloon angioplasty at high pressure for late stent thrombosis.

The patient remained asymptomatic throughout the admission. The serum troponin peaked at 6.6 ng/mL. The patient was advised to continue taking clopidogrel indefinitely for his late stent thrombosis. His medications were reinitiated as before and he was again strongly advised regarding lifestyle, medication, compliance, and follow-up.

Discussion

This patient presented initially with an acute ST-segment elevation myocardial infarction with chest pain of 2.5 hours duration. Consistent with modern practice, he was rapidly evaluated according to a prespecified protocol that activated the cardiac catheterization laboratory staff and an interventionalist for rapid reperfusion therapy with direct PCI. The goal of therapy is to achieve a “door-to-balloon time” of less than 90 minutes; in the present case, this was accomplished in 64 minutes. The patient was first treated in the emergency department according to prespecified protocols with aspirin 325 mg, clopidogrel 600 mg load, and unfractionated heparin (60 U/kg). The exact protocols vary between institutions. In our catheterization laboratory, we visualized the presumed infarct-related artery first using a guiding catheter, with the intent to treat rapidly with PCI if there was no doubt about the clinical story and infarct artery. Other laboratories might choose to image the noninfarct artery first to have a complete definition of the coronary anatomy. The advantage of the former approach is speed to reperfusion. The advantage of the latter is more complete information prior to a specific therapy being initiated. There is no consensus regarding this strategy.

The approach to PCI reperfusion has been a rapidly evolving field. There is increasingly compelling data to suggest that thrombus extraction with a simple aspiration catheter improves clinical outcomes prior to stenting for acute ST-elevation MI.¹ This was not done in our laboratory at the time this case occurred but has currently become the preferred approach, when technically feasible. Similarly the optimal adjunctive pharmacologic therapy is in a state of evolution. In this case, unfractionated heparin and eptifibatide were used, but other heparins and GP IIb/IIIa inhibitors are also appropriate. The HORIZON trial has established the role of bivalirudin without routine GP IIb/IIIa inhibitors in such cases.² Although early stent thrombosis was increased with bivalirudin, this was not significant at later time points and the reduction in bleeding with bivalirudin was associated with decreased mortality at 1 year in patients with STEMI. In a separate publication, the HORIZON’s investigators also established the role of drug-eluting stents in ST-elevation MI and showed significantly reduced angiographic evidence of restenosis and recurrent ischemia necessitating repeat revascularization procedures with no safety concerns apparent at 1 year with drug-eluting stents.³ The challenge of such cases is to establish the bleeding risk and patient compliance issues during the “fast-forward” environment of an acute PCI. In this case, there were concerns raised regarding compliance with medications and a bare-metal stent was selected.

This patient did well for 2 months, but then became noncompliant with his follow-up and stopped taking all his medications, including aspirin and clopidogrel. Predictably, he developed late stent thrombosis within 3 weeks. The role of aspirin and clopidogrel (dual antiplatelet therapy) in the prevention of late stent thrombosis is well established. Clopidogrel has replaced ticlopidine as the ADP-receptor blocker of choice due to its improved safety profile. However, there is a defined incidence of clopidogrel resistance which results from multiple factors including its complex pharmacology and need for conversion from a pro-drug to its active form. Stent thrombosis has been associated with clopidogrel resistance as measured by platelet aggregation studies and with bedside platelet monitoring. Newer agents such as prasugrel (Triton TIMI 38) and ticagrelor (PLATO) may have improved efficacy against stent thrombosis.⁴

Stent thrombosis complicates approximately 2% of coronary interventional procedures and is associated with significant morbidity and mortality and a high risk of myocardial infarction. Certain situations are known to have increased risk of stent thrombosis including unstable angina, diabetes mellitus, low ejection fraction, renal failure, small vessel diameter, long lesions (with multiple stents), bifurcation lesions, downstream poorly-functioning myocardium, residual uncovered dissection, poor distal runoff, and suboptimal final postprocedure lumen. Proper stent deployment with optimal sizing and avoidance of malapposition are important technical factors in avoiding stent thrombosis. Intravascular ultrasound may be helpful in defining risk factors for stent thrombosis, including improper sizing, stent malapposition, and edge dissections. Whether the “on label” use of drug-eluting stents treated with dual antiplatelet therapy results in increased late and very late thrombosis compared with bare-metal stents remains uncertain.⁵

In this case, the late stent thrombosis was treated with high-pressure balloon angioplasty alone. There is increasing evidence that placement of additional stents can result in still greater increases in recurrent stent thrombosis, so additional stents are typically avoided in these cases unless specifically indicated due to dissection or unacceptable angiographic result. Whether intravascular ultrasound can more precisely define therapy and diminish repeat episodes of stent thrombosis remains unproven.

In research trials, stent thrombosis is often classified using the ARC definition as definite, probable, or possible; and as early (0 to 30 days), late (31 to 360 days), or very late (over 360 days). The definition of definite stent thrombosis requires the presence of an acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion. Probable stent thrombosis includes unexplained deaths within 30 days after the procedure, or acute myocardial infarction involving the target-vessel territory without angiographic confirmation. Possible stent thrombosis also includes all unexplained deaths occurring at least 30 days after the procedure. Intervening target lesion revascularization is defined as any repeated percutaneous revascularization of the stented segment, including the 5-mm proximal and distal margins that preceded stent thrombosis.