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Case summary

A 57-year-old male with past medical history of coronary artery disease, status post two DES implantations (sirolimus-eluting stent, 3.0×18 and 3.0×15 mm) to the right coronary artery (RCA) 4 years ago and hyperlipidemia, was transferred from an outside facility with an inferior wall ST-segment elevation myocardial infarction (STEMI). The patient underwent a routine screening colonoscopy earlier that day. Five days ago, he was taken off aspirin and clopidogrel as a routine measure precolonoscopy. The patient denied any recent exertional symptoms and had been in his usual state of health. He had a normal stress test several months ago. He had an unremarkable colonoscopy and no biopsies were taken. During recovery from the anesthesia, the patient started experiencing chest pain with pressure radiating to his shoulders associated with some shortness of breath. He had no nausea, vomiting but appeared pale and diaphoretic. He was immediately transferred to the emergency room where a 12-lead EKG showed normal sinus rhythm with acute ST-segment elevations in leads II, III, and aVF with reciprocal changes in leads I and AVL, V1 through V3. Due to bad weather, he could not be medflighted and the nearest mobile intensive care unit was at least 60 min away. It was hence decided to proceed with fibrinolytic therapy after all contraindications were excluded. The patient was given 10 U of reteplase over 2 min followed by another 10 U at 30 min apart. Following reteplase, his chest pain resolved and there was near complete resolution of ST elevation at 90 min. The patient stayed hemodynamically and electrically stable throughout. He was then transferred to our university hospital for further management. A transthoracic echocardiogram was done which showed a left ventricular ejection fraction of 50% with moderate hypokinesis of the inferior myocardium.

A coronary angiogram showed normal left main coronary artery and nonobstructive disease in the left anterior descending and circumflex arteries. RCA was a very large dominant vessel with a patent stent in the distal segment and TIMI 3 flow throughout the vessel. The mid RCA had a patent stent, but just proximal to this stent there was a 40–50% stenosis ( Fig. 1 ). Left ventricular angiogram showed an ejection fraction of 55–60%. The left ventricular end-diastolic pressure was 15 mmHg. The inferobasal and mid inferior walls were hypokinetic.

Patent stent in mid-distal RCA with good flow.

The patient was started on optimal medical therapy including dual antiplatelets (ASA 325 mg qid and clopidogrel 75 mg qid), beta-blocker, ACE inhibitor, and statin. He did remarkably well throughout the hospitalization without any adverse events and was discharged 3 days later. The patient was seen 3 weeks later in the clinic and he was totally asymptomatic. He underwent an exercise treadmill test and he walked for >9 min without any symptoms.

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Comment

Very late ST (>1 year) has emerged as a well-recognized complication of DES. In observational studies, the risk of late stent thrombosis (LST) continues to be reported at a constant rate (0.6%/year; significantly higher with DES) up to at least 4 years after stenting . It is now well established that delayed healing (i.e., lack of complete endothelialization) is the primary pathologic substrate underlying these events and that >50% of stent struts in humans are not covered by the endothelium up to 24 months after DES placement . DES thrombosis leads to complete vessel occlusion with a high thrombus burden. The inciting event and pathophysiology are distinct from plaque rupture and ensuing thrombosis. However, the final common pathway is the same, i.e., thrombosis. Its occurrence is expected to increase with the number of stent—in particular (DES)—implantation procedures done worldwide. Clinical consequences of ST are generally catastrophic, including short-term mortality rates of up to 20% to 25% and major myocardial infarction (MI) in 60% to 70% of cases and 6-month mortality rates, among survivors of ST, of up to 20% to 25% . The presentation of ST is very often a STEMI . Repeat percutaneous coronary intervention (PCI) is the commonly adopted treatment in the ST setting. However, few scientific data are available on procedural and midterm comparison of STEMI due to ST vs. de novo STEMI.

Chechi et al. compared outcomes and procedural success rates from 92 patients with STEMI due to ST with 98 patients with de novo STEMI. All patients underwent primary PCI. Patients with ST had a lower likelihood of successful reperfusion (odds ratio 6.8, P =.004), higher distal embolization rates, and higher rates of in-hospital major adverse cardiovascular events (MACE). Patients in the ST group had a higher in-hospital MACE rate (25.6% vs. 9.2%, P =.003), with higher mortality, reinfarction, and target vessel revascularization rates but not stroke rate, which was similar between the two groups (17.4% vs. 7.1%, P =.03; 8.1% vs. 1%, P =.02; 9.3% vs. 2%, P =.009; 0% vs. 1%, P =.3, respectively).

Primary PCI is considered the therapy of choice for STEMI. There are, however, numerous limitations with logistics being the major one. It is now well established that in patients with total ischemic time (from onset of chest pain) <1 h, fibrinolytic therapy has the same success rate and clinical outcomes as compared to PCI . The absolute risk reduction in death, reinfarction, and stroke conferred by primary PCI over fibrinolysis is lost if the PCI-related time delay (door-to-balloon time−door-to-needle time) is >1 h. Hence when a substantial delay in initiating primary PCI is anticipated, reperfusion therapy with fibrinolytic agents should be strongly considered . This would be all the more important in the setting of an ST given the several-fold higher adverse outcome rates.

One important issue pertains to establishing the precise diagnosis of ST, especially late and very late ST. Diagnosing late or very late ST may be particularly challenging as events could occur secondary to restenosis and target lesion revascularization, especially if an additional or different stent is implanted at that time . Given this challenge, the Academic Research Consortium (ARC) has formulated consensus definitions for DES study end points . Accordingly, ST is defined as definite (confirmation of thrombus either at angiography, autopsy, or thrombectomy), probable (any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of ST and in the absence of any other obvious cause), or possible (clinical definition of possible ST is considered to have occurred with any unexplained death from 30 days after intracoronary stenting until end of trial follow-up). Our patient met the criteria for both definite and probable ST per ARC criteria. Moreover, the ARC recommends the combination of adjudicated definite and probable ST to best characterize very late ST. It should be noted that the ARC definitions require evidence of a clinical event and do not include silent late occlusions as manifestations of ST.

Sciahbasi et al. recently reported four cases of successful fibrinolytic therapy for ST. All cases had a very short symptom-to-treatment time (<50 min). Bowater et al. also presented a case of successful thrombolysis with tenecteplast and adjunctive glycoprotein IIb/IIIa inhibitor for subacute ST. Similarly, our patient received fibrinolytic therapy within 30 min of onset of chest pain and had near complete ST-segment resolution at 90 min.

Taken together, these cases demonstrate the feasibility, safety, and efficacy of fibrinolytic therapy for LST without the need for further mechanical intervention. It is very important to appreciate that success (immediate and long-term) of fibrinolytic therapy is largely contingent on symptom-to-treatment time.