Case Report. The patient was a 61-year-old Caucasian male with a past medical history of hypertension and coronary artery disease (with a history of stent placement to the circumflex artery 5 years ago). He was admitted to an outside hospital with acute inferior myocardial infarction and was treated with tissue plasminogen activator. Later, he was found to have multivessel coronary artery disease. His left anterior descending artery (LAD) had an 80% lesion after the first septal perforator involving the ostial second diagonal artery. His circumflex artery had 40% proximal and 90% distal stenosis in the mid-portion of a large obtuse marginal branch involving the ostium of his small main circumflex artery, which had multiple 95% tandem lesions. His right coronary (RCA) was a dominant vessel, with a 90% proximal stenosis followed by a second 99% stenosis in the mid-portion of the vessel, with intraluminal thrombus. In addition, there was a 60% bifurcation lesion involving the posterior descending and posterolateral branches. His ejection fraction on echocardiography was reported to be 50%, with inferobasal hypokinesia. The decision was made to revascularize him by staged percutaneous coronary intervention (PCI). His RCA was intervened upon first; the mid-RCA was stented using a Taxus™ (Boston Scientific Corp., Natick, Massachusetts) 3.0 x 32 mm stent inflated to 12 atmospheres, followed by proximal stent placement using a 3.0 x 12 mm Taxus stent that was inflated to 18 atmospheres, with excellent results. The distal RCA lesion was not treated. Two days later, the patient underwent PCI to his LAD. The LAD lesion was stented using a 3.0 x 16 mm stent inflated to 14 atmospheres. The ostial diagonal was stented via the T-stenting technique by using a second 2.75 x 32 mm Taxus stent inflated to 8 atmospheres. The patient was stable post procedure, and was discharged a few days later. He was pain-free for 2 days, but then developed recurrent chest pain, which brought him to our emergency room. His initial ECG revealed 1 mm ST-elevation in the lateral leads with reciprocal ST-depression in the inferior leads. The patient was treated with aspirin, heparin and eptifibatide in the emergency room and had stable vital signs. He was already on atorvastatin, aspirin and clopidogrel prior to admission and was adamant about his medication compliance. He was taken to the cardiac catheterization laboratory for urgent angiography which showed subacute stent thrombosis of the diagonal artery, with a normal appearance of the RCA (Figures 1 and 2). We were able to advance a PT2 (Boston Scientific) wire distal to the occlusion with initial inflation of a 2.0 x 15 mm Maverick™ balloon (Boston Scientific) which was inflated to 8 atmospheres. Next, a 2.75 x 9 mm Maverick balloon was advanced into the LAD and a 2.5 x 15 mm Maverick balloon into the ostial diagonal. Kissing balloon angioplasty was performed. The LAD balloon was inflated to 8 atmospheres and the diagonal balloon was inflated to 14 atmospheres using the pullback technique in order to avoid thrombus dislodgement into the LAD, with satisfactory results (Figures 3 and 4). The patient was pain-free at the end of the procedure and was treated with continuous intravenous infusion of eptifibatide and oral clopidogrel. In the early morning of the next day, the patient had recurrent persistent substernal chest pressure similar to his myocardial infarction pain, with no significant ECG changes. He was taken to the cardiac catheterization laboratory again and an angiogram revealed patent LAD, RCA and diagonal stents (Figure 5). The decision was made to intervene on the circumflex lesion due to persistent chest pain and high-grade flow obstructive lesions (Figure 6). Due to the small diameter of the main circumflex artery, the main circumflex was treated with a 2.25 x 15 mm Maverick balloon which was inflated to 8 atmospheres, followed by stenting at the site of the bifurcation in the large obtuse marginal branch using a 3.0 x 18 mm Cypher® stent (Cordis Corp., Miami, Florida) inflated to 16 atmospheres. This was followed by balloon angioplasty of the ostial main circumflex artery using a 2.25 x 15 mm Maverick balloon inflated to 12 atmospheres, with satisfactory results in the circumflex artery and excellent results in the large obtuse marginal branch (Figure 7). The patient was pain-free postprocedure, but suffered from intermittent atrial flutter which partiality responded to intravenous metoprolol. He remained stable with mild pleuritic chest pain and was started on warfarin, together with heparin in addition to 75 mg of clopidogrel twice a day and aspirin. Three days later the patient was scheduled to be discharged and his CPK, which was initially peaked to 1,792, normalized. He had a transient increase of his baseline creatinine from 1.3 to 2.0, with recovery to 1.4 on the day of his planned cardioversion and discharge. His CBC was stable throughout his stay with stable platelet counts of over 300,000. In the early morning of the planned discharge day, he suffered from severe substernal chest pressure with marked ST-elevation in the entire anterior and lateral leads (Figure 8). Shortly after his ST-elevation, he developed ventricular fibrillation, which degenerated to electromechanical dissociation. Cardiopulmonary resuscitation (CPR) was started immediately. A bedside echocardiogram was urgently performed while transferring the patient to the cardiac catheterization laboratory. The echocardiogram revealed mild effusion, with no signs of ventricular rupture. He was treated with atropine, epinephrine, right ventricular pacing and pericardiocentesis, with no response. Finally, once the patient was under continuous CPR, he was transferred to the cardiac catheterization laboratory and an angiogram was performed which revealed total thrombotic occlusions of the LAD, diagonal and circumflex stents (Figure 9). The patient remained in electro- mechanical dissociation and expired after 60 minutes of CPR. Discussion. It is well known that subacute stent thrombosis has a very high mortality rate.1 The frequency rate of stent thrombosis is similar between DES and bare-metal stents (BMS). Stent thrombosis occurs in less than 1% of patients, even if multiple DES are used.2,3 However, the rate of subacute stent thrombosis significantly increases in high-risk patients. Predictors of increased risk of stent thrombosis include thrombus-containing lesions, stent underexpansion, increasing stent length, emergent stent placement, dissections, tissue prolapse, acute myocardial infarction and bifurcation lesions.4–9 Due to the high mortality rate, every effort should be undertaken to reduce this complication. In the era of DES, the number of multivessel and complex coronary stenting is rising. In comparison to coronary artery bypass surgery (CABG), multivessel coronary stenting has been associated with an increased risk of repeat revascularization or mortality in the majority of the trials in a non-drug-eluting stent era.10–15 However, DES have been found to be safe with similar morbidity and mortality rates compared to CABG in patients with multivessel coronary artery disease (ARTS II trial). It is important to note that high-risk patients such as those with acute ST-elevation MI or depressed left ventricular function were excluded in the majority of these trials, and that the timing between each coronary vessel intervention has not been clarified. Therefore, the results of these trials can not be extrapolated to the patients with acute ST elevation myocardial infarction. It is not unusual for a patient presenting with an acute myocardial infarction to have other significant lesions requiring intervention. There are no studies available to evaluate the safety of staged coronary intervention shortly after the primary stenting of acute ST-elevation infarct-related artery. One small randomized trial found that multi-vessel stenting done in the setting of one procedure was as safe as staged procedure.16 However, this trial excluded patients with acute ST elevation myocardial infarction. We have presented a fatal case of simultaneous stent closure of two DES after multivessel stenting which was performed to treat acute ST-elevation MI and subsequent unstable coronary syndrome shortly after stenting of the ST-elevation-related coronary artery. There is only one case report on the TCTMD website reporting a similar occurrence of simultaneous stent closure in the LAD and the RCA.17 This complication has not been reported prior to the DES era. Ours is the second reported case of this deadly complication. Our patient had no documented hypercoagulable state and a normal platelet count when this fatal complication occurred, and was maximally anticoagulated by treatment with eptifibatide, clopidogrel, aspirin and intravenous heparin. As a cause of simultaneous stent closure in our patient, we can not exclude a hypercoagulable state,18 aspirin or clopidogrel19–22 resistance which are known risk factors for acute stent thrombosis. The patient underwent stent placement in his proximal circumflex artery 5 years earlier without any complications, suggesting that he had not been prone to stent thrombosis in the past. The cause of this fatal event remains unknown. Our patient had many high-risk characteristics for subacute stent thrombosis such as stenting of two bifurcation lesions, acute coronary syndrome, ST-elevation myocardial infarction, long stents and thrombus-containing lesions. However, the case report by Garcia et al17 on the TCTMD website did not feature any high-risk features, suggesting that another mechanism related to DES is responsible for this deadly complication. Similar complications have never been reported with BMS. This suggests that DES may play an important role in the pathogenesis of this complication. Late hypersensitivity reaction with fatal late stent thrombosis has been reported in patients treated with sirolimus-eluting23 and paclitaxel-eluting24 stents. Localized hypersensitivity vacuities were found in response to Cypher coronary stent placement, resulting in late stent thrombosis.23 However, in our patient, 2 different DES stents were used (Taxus in the LAD and Cypher in the circumflex artery), suggesting that this event was not specific to one drug. Both lesions in this patient were bifurcation lesions, which are known to be associated with a higher rate of subacute stent thrombosis.7,8 Low-pressure balloon inflation has been one of the risk factors for acute stent closure,6 explaining the initial diagonal stent thrombosis in our patient, but not the stent closure in the LAD or circumflex arteries. The finding in the ECG that showed ST-elevation in all leads before the occurrence of cardiac arrest, suggests that multiple stent thrombosis was the triggering event and was not secondary to prolonged CPR after the occurrence of cardiac arrest. We believe that clinicians should be aware of this major deadly complication of PCI which has only been reported since the arrival of DES, but has only been published thus far in one case report on the TCTMD website. Most interventional cardiologists are not aware of this deadly complication. Our patient, together with another reported case, suggests that this complication is more common than a single isolated case and is most likely directly related to DES. It is extremely important that clinicians be aware of these situations. Staged multivessel complex procedures in a very short period of time are now very common with the use of DES. We believe that this approach should be discouraged in stable patients, particularly after ST-elevation MI or in the presence of bifurcation lesions, and a longer period of time should elapse before a second artery is treated. The best timing for stent placement in a second artery has not been studied and is controversial. As discussed earlier, the occurrence of late stent thrombosis suggests that endothelialization can be delayed 3 to 6 months beyond the recommended dual antiplatelet therapy. In the case reported on the TCTMD website,17 simultaneous stent thrombosis occurred 8 hours after the intervention, and in our case, after 3 days. This suggests that this phenomenon may occur early after intervention. However, due to the fatal nature of this complication, the late occurrence of this phenomenon is difficult to document and the timing for the second artery intervention remains controversial. We suggest that in a stable patient, a longer waiting period before the second intervention might decrease the risk of this fatal complication, and the length of the waiting period should be individualized based on the acuity and severity of the patient’s symptoms.
1. Ong AT, Hoye A, Aoki J, et al. Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after bare-metal, sirolimus, or paclitaxel stent implantation. J Am Coll Cardiol 2005;45:947‚Äì53. 2. Moreno R, Fernandez C, Hernandez R, et al. Drug-eluting stent thrombosis: Results from a pooled analysis including 10 randomized studies. J Am Coll Cardiol 2005;45:954‚Äì959. 3. Iakovou I, Sangiorgi GM, Stankovic G, et al. Results and follow-up after implantation of four or more sirolimus-eluting stents in the same patient. Catheter Cardiovasc Interv 2005;64:436‚Äì439; Discussion pp440‚Äì441. 4. Cheneau E, Leborgne L, Mintz GS, et al. Predictors of subacute stent thrombosis: Results of a systematic intravascular ultrasound study. Circulation 2003;108:43‚Äì47. 5. Beohar N, Davidson CJ, Weigold G, et al. Predictors of long-term outcomes following direct percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2001;88:1103‚Äì1107. 6. Mak KH, Belli G, Ellis SG, Moliterno DJ. Subacute stent thrombosis: Evolving issues and current concepts. J Am Coll Cardiol 1996;27:494‚Äì503. 7. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126‚Äì2130. 8. Iakovou I, Colombo A. Two-stent techniques for the treatment of coronary bifurcations with drug-eluting stents. Hell J Cardiol 2005;46:188‚Äì198. 9. Biondi-Zoccai GG, Sangiorgi GM, Chieffo A, et al. Validation of predictors of intraprocedural stent thrombosis in the drug-eluting stent era. Am J Cardiol 2005;95:1466‚Äì1468. 10. Mercado N, Wijns W, Serruys PW, et al. One-year outcomes of coronary artery bypass graft surgery versus percutaneous coronary intervention with multiple stenting for multisystem disease: A meta-analysis of individual patient data from randomized clinical trials. J Thorac Cardiovasc Surg 2005;130:512‚Äì519. 11. Hannan EL, Racz MJ, Walford G, et al. Long-term outcomes of coronary-artery bypass grafting versus stent implantation. N Engl J Med 2005;352:2174‚Äì2183. 12. Malenka DJ, Leavitt BJ, Hearne MJ, et al. Comparing long-term survival of patients with multivessel coronary disease after CABG or PCI: Analysis of BARI-like patients in northern New England. Circulation 2005;112:I371‚Äì1376. 13. Villareal RP, Lee VV, Elayda MA, Wilson JM. Coronary artery bypass surgery versus coronary stenting: Risk-adjusted survival rates in 5,619 patients. Tex Heart Inst J 2002;29:3‚Äì9. 14. Rodriguez A, Rodriguez Alemparte M, Baldi J, et al. Coronary stenting versus coronary bypass surgery in patients with multiple vessel disease and significant proximal LAD stenosis: Results from the ERACI II study. Heart 2003;89:184‚Äì188. 15. Rodriguez AE, Baldi J, Fernandez Pereira C, et al. Five-year follow-up of the Argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II). J Am Coll Cardiol 2005;46:582‚Äì588. 16. Ijsselmuiden AJ, Ezechiels J, Westendorp IC, et al. Complete versus culprit vessel percutaneous coronary intervention in multivessel disease: A randomized comparison. Am Heart J 2004;148:467‚Äì474. 17. Garcia J, Robetson M, Casserly I. Acute Drug eluting stent Thrombosis of the LAD and RCA. TCTMD web site September 6, 2005. 18. Acar G, Dogan A, Altinbas A, Turker Y. Recurrent acute stent thrombosis associated with protein C and S deficiencies. Int J Cardiovasc Imaging 2006. 19. Berger PB. Resistance to antiplatelet drugs: Is it real or relevant? Catheter Cardiovasc Interv 2004;62:43‚Äì45. 20. Muller I, Besta F, Schulz C, et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 2003;89:783‚Äì787. 21. Steinhubl SR, Charnigo R, Moliterno DJ. Resistance to antiplatelet resistance is it justified? J Am Coll Cardiol 2005;45:1757‚Äì1758. 22. von Beckerath N, Taubert D, Pogatsa-Murray G, et al. A patient with stent thrombosis, clopidogrel-resistance and failure to metabolize clopidogrel to its active metabolite. Thromb Haemost 2005;93:789‚Äì791. 23. Virmani R, Guagliumi G, Farb A, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: Should we be cautious? Circulation 2004;109:701‚Äì705. 24. Liistro F, Colombo A. Late acute thrombosis after paclitaxel eluting stent implantation. Heart 2001;86:262‚Äì264.