Accelerated allograft vasculopathy in cardiac transplant recipients occurs commonly five or more years after transplantation and limits patient survival.1,2 Unlike native atherosclerosis, this peculiar vasculopathy has a diffuse pattern of coronary involvement and most commonly determines heart failure or sudden death.3 This challenging condition requires a careful diagnostic approach based on noninvasive detection of ischemia, routine angiography and, often, intravascular ultrasound.4,5 Once diagnosed, revascularization strategies have been advocated for focal stenoses as well as diffusely diseased vessels using a wide armamentarium of coronary devices, including stents, atherectomy, brachytherapy and laser.6,7 Percutaneous coronary revascularization (PCI) in patients with allograft vasculopathy occurs most often after angiographic detection of asymptomatic disease, or because of clinical angina, heart failure or silent ischemia, as reported by Schnetzler et al.8 In their series, these authors describe only 1 patient treated with PCI because of ST-elevation acute myocardial infarction, corresponding to a frequency of primary PCI in allograft vasculopathy of 8 We report a case of PCI in a heart transplant recipient presenting with high-risk ST-elevation acute myocardial infarction. To our knowledge, this is the first case in which abciximab was used as a facilitation strategy before stenting. Case Report. A 69-year-old male with a history of orthotopic cardiac transplantation successfully performed in 1995 for ischemic cardiomyopathy, came to our observation because of chest pain of 2-hour duration. On physical examination, the patient was in moderate distress, had an audible third heart sound, a 3/6 apical holosystolic murmur and diffuse pulmonary rales. His blood pressure was 110/85 mmHg. A 12-lead electrocardiogram showed sinus tachycardia, right bundle branch block with left axis deviation, and a 4 mm ST-segment elevation in leads V1–V5. His Thrombolysis in Myocardial Infarction (TIMI) risk score was 6. Two-dimensional echocardiography showed a moderately dilated left ventricle, akinesia of the anterior septal wall, the anterior wall and the apex of left ventricle, with an estimated left ventricular ejection fraction of 30%. Doppler examination showed moderate mitral and tricuspid regurgitation. Primary PCI was deemed indicated for this high-risk patient. Emergency coronary angiography showed a totally occluded (TIMI flow 0) left anterior descending coronary artery (Figure 1) in the mid segment; the right posterior descending coronary artery was chronically occluded with ipsilateral collateral circulation; the left circumflex had a mild proximal lesion. Before catheterization, the patient received 500 mg acetylsalicylic acid intravenously; heparin was given as an initial bolus of 70 U/Kg, and additional boluses were administered during the procedure to achieve an activated clotting time between 200–300 seconds. Based on angiographic findings, an abciximab bolus was administered (0.25 mg/Kg), and the infusion started (0.125 µg/Kg per minute) according to the usual protocol. A 0.014 floppy guidewire was advanced through the occlusion and placed distally. At this point, TIMI flow 2 was achieved. A 3.0 x 18 mm Zeta Multilink stent (Guidant Corp., Indianapolis, Indiana) was implanted without predilatation at a pressure of 14 atmospheres. The final angiographic result was good, with TIMI 3 flow (Figure 2). The door-to-balloon time was 65 minutes. After PCI, a > 50% reduction in ST-segment elevation was observed. Intra-aortic balloon counterpulsation was started at the end of the procedure and continued for the next 48 hours. Immediately after the procedure, the patient received 300 mg clopidrogel. Heparin was continued for 2 days after the procedure; the patient was routinely treated with aspirin (325 mg/day indefinitely), and clopidrogel (75 mg/day) for 3 months. Creatine kinase (CK) reached a peak value of 1,725 U/L (normal reference: Discussion ST-elevation acute myocardial infarction in transplant recipients is exceedingly rare;8–10 in particular, typical chest pain with rapid admission to a catheterization laboratory is unusual due to frequent absence of symptoms in these patients as a consequence of cardiac denervation.11,12 In the original series published by Stanford University, the diagnosis of acute myocardial infarction was missed in as many as 60% of patients.3 Thus, it is not surprising that angiographic anatomy has rarely been obtained in the acute phase of infarction, and that PCI has been performed even more rarely.13 ST-elevation acute myocardial infarction in transplant recipients is not only rare and difficult to diagnose, but also carries a severe prognosis. In the same series, in-hospital mortality was as high as 32% with medical therapy alone, while half of the survivors required retransplantation within 6 months.3 Thus, all available diagnostic and therapeutic strategies must be optimized in these patients. To our knowledge, the present case is the first reported use of abciximab in ST-elevation acute myocardial infarction in the setting of allograft vasculopathy. Recent guidelines of the European Society of Cardiology for PCI recommend abciximab treatment as an established indication in ST-elevation acute myocardial infarction.14 Potential advantages of this treatment include improved microvascular perfusion,15 reduced embolization,16 less procedural complications,17 increased coronary blood flow15 and reduced reocclusion.18 These effects have been shown to translate into decreased mortality and need for repeat revascularization.19 The question arises as to whether these beneficial effects of abciximab can be extended to this exceedingly rare clinical situation. Fiane et al. reported that abciximab effectively inhibits platelet function in animal models of xenograft recipient.20 However, little is known about the pathologic process of acute coronary occlusion in allograft vasculopathy, especially regarding the amount and characteristics of thrombus formation and platelet activation. Pathologic examination of allograft recipients incurring sudden death or cardiogenic shock have shown an acute thrombotic occlusion superimposed on a diseased vessel wall,21 somewhat similar to what occurs in patients with native atherosclerotic disease. Moreover, it has been observed that the fibrinolytic system after heart transplantation is impaired because of prolonged steroid treatment,22 thus creating a prothrombotic environment. Biopsy specimens obtained from recipients of cardiac allografts showed depletion of tissue plasminogen activator in arteriolar smooth muscle cells and elevated levels of t-PA and plasminogen activator inhibitor.23 Although most of these characteristics would also suggest systemic thrombolysis as a reasonable option in this setting,10 an overwhelming amount of evidence now supports primary PCI as the best reperfusion strategy in ST-elevation acute myocardial infarction, particularly in high-risk patients when the door-to-balloon time is less than 90 minutes.24 According to current evidence, abciximab should be administered as soon as possible, since the effects on dethrombosis and early vessel reopening favorably impact outcomes.25 However, other operators use abciximab only in the catheterization laboratory.19 In our case, abciximab administration was deferred until the patient’s coronary anatomy was assessed due to the anticipated uncertainties concerning the feasibility of PCI in the event that diffuse vasculopathy was found. Safety issues should also be considered when using abciximab in a transplant recipient, especially because a wide variety of drugs are known to interfere with cyclosporine; however, no such interference has been found with abciximab in a web-based search, and no known increased risk of bleeding has been described in transplant recipients. In conclusion, emergency department physicians in primary and secondary referral hospitals should be alert to the fact that transplant patients may suffer an acute myocardial infarction with or without the characteristic chest pain. This report suggests that primary PCI can be successfully performed in these high-risk patients and that a revascularization strategy based on abciximab pretreatment can be effectively pursued.
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