Selective Strategy for Thrombus Management in STEMI Interventions

Percutaneous coronary intervention (PCI) has become the standard of care for STEMI procedures, while those for distal embolization and no-reflow remain challenging.^1,2 Distal embolization is angiographically evident in 15% of patients undergoing primary PCI and is associated with decreased angiographic success, reduced myocardial blush grade (MBG), less ST-segment elevation resolution (STR), larger enzymatic infarct size, lower-left ventricular ejection fraction (LVEF) at discharge, and increased risk of death.^2,3

Mechanical adjunctive devices are classified into two categories: thrombectomy and aspiration catheters; and distal protection wires, filters or balloons.

Thrombus is associated with lower procedural success; increased abrupt vessel closure, death, myocardial infarction (MI), and incidence of emergency bypass surgery.^4–6 The SINCERE (Single INdividual Community Experience Registry) database, has helped develop a thrombus management strategy in ST-elevated myocardial infarction (STEMI) interventions.⁷

Methods

Patients. The SINCERE database is an ongoing, prospective database of all primary PCI for STEMI performed by a single, experienced interventional cardiologist which began in January 2005.⁸ To date, it includes over 600 STEMI interventions performed at 5 South Florida community, non-teaching hospitals, all of which have significant procedural volume and on-site cardiac surgery back-up.

Procedure. Short-D2B-Time STEMI interventions. In every STEMI intervention, full coronary anatomy was obtained. A quick assessment of the non-infarct vessel with a diagnostic catheter — taking two orthogonal views of the left coronary and a single LAO view of the right coronary artery — was usually performed. The guiding catheter was used to treat the culprit lesion. The procedure always finalized performing left ventriculography. The STEMI intervention was focused solely on the culprit lesion; all non-critical lesions were left alone, except in patients in cardiogenic shock.

A successful STEMI intervention required that 4 parameters be met — relief of chest pain, STR, thrombolysis in myocardial infarction (TIMI-3), and myocardial perfusion Grade 3. First, optimal stent deployment was confirmed; then the guidewire was removed; finally, 300 µg of intracoronary nitroprusside are delivered in increments of 50 µg through a non-side hole guiding catheter. Hypotension caused by nitroprusside was managed by phenylephrine (Neosynephrine, 100 µg IV bolus).

Bivalirudin was the anticoagulant of choice. For patients who have received unfractionated heparin, activated clotting time intervals were followed and the heparin switched to bivalirudin. This was used as a bolus and an intravenous drip continued for 2 hours after the procedure. Abciximab was employed in the presence of large thrombus burden, for residual thrombus, side-branch involvement, and if results were inadequate.

Guiding catheters of 6 F were generally employed. In rare circumstances, this catheter was exchanged for the 7 F Export Aspiration thrombectomy catheter (Medtronic, Inc., Minneapolis, Minnesota) or ThromCat (Kensey Nash Corporation, Exton, Pennsylvania). Technical management with a rapid to-and-fro spinning movement of the wire advanced it through the thrombus and virtually traced the course of the occluded vessel as it was advanced. For additional safety during device exchanges, the tips of these wires were doubled. DES were used for proximal left anterior descending lesions, diabetics, small vessels, long lesions, saphenous vein grafts and in-stent restenosis. Disposition was constantly assessed.

Finally, the clopidogrel test was performed. It screened the patient’s ability to take long-term anti-coagulants. It assessed coagulation history, bleeding history, future surgical procedures and financial capability.

Mehta strategy. In over 450 short D2B STEMI interventions in the SINCERE database, the Sianos classification was used as an angiographic assessment tool in the STEMI interventions.^7,9 Additionally, we implemented the Mehta strategy as the thrombus management approach for all primary PCI performed. The Mehta strategy is defined as “a selective strategy for thrombus management in STEMI interventions based upon the thrombus grade, with direct stenting recommended for low-grade thrombus, thrombo-aspiration for moderate thrombus, and rheolytic thrombectomy for high-grade thrombus (depending upon suitable anatomy). For unsuitable anatomy or unavailability of rheolytic thrombectomy, a strategy of dethrombosis with intracoronary abciximab via the Clearway catheter is an acceptable approach.” (Table 1)

Results

A total of 600 patients at 5 community hospitals underwent primary PCI for STEMI in the last 6 years and were included in the SINCERE database. Table 2 gives an overview of the demographic and clinical characteristics of the patients included in the SINCERE database. At the time of angiography, identification of the culprit lesion demonstrated the following distribution: left main coronary artery (LMCA) 2.5%, left anterior descending artery (LAD) 39.1%, left circumflex (LCX) 13.2%, right coronary artery (RCA) 42.6% (Table 3). A small proportion of patients had prior coronary bypass surgery, and 2.6% of the total population underwent intervention of a saphenous vein bypass graft. On initial angiography, the culprit vessel was found to have totally occluded culprit lesions with distal TIMI 0 flow in the majority of patients (59%).

The majority of the patients in the database (96%) received bivalirudin as the anti-coagulant of choice (Table 4). Initially, a small percentage of patients initially received UFH and were subsequently switched to bivalirudin. A glycoprotein (GP) IIb/IIIa inhibitor was used in 29.8% of patients, the majority of whom were also on combination therapy with bivalirudin. In the majority of cases, GP IIb/IIIa agents were started upstream before primary PCI. The predominant GP IIb/IIIa agent used was abciximab, accounting for 27.1% of cases in which GP IIb/IIIas were administered. Abciximab was employed in the presence of large thrombus burden, for residual thrombus, side-branch involvement and if the result is inadequate (due to incomplete thrombus resolution or not achieving all 4 parameters of successful recanalization: relief of chest pain, ST-segment resolution, TIMI 3 flow and myocardial perfusion Grade 3). Eptifibatide was used in the remaining patients, who were treated with a GP IIb/IIIa agent. Review of procedural characteristics is demonstrated in Table 5.

Although stenting was performed in the majority of patients, 3.5% of patients underwent angioplasty alone, for a variety of reasons, including elimination of thrombus with thrombectomy alone, small target vessel or inability to pass the stent. Direct stenting without pre-dilation was achieved in 21.7% of patients overall. For the entire database, beginning about 6 years ago, of those patients who underwent stenting, drug-eluting stents (DES) were used. The choice of DES was distributed among the following: 151 (31.3%) for paclitaxel-eluting Taxus (Boston Scientific, Natick, Massachusetts) and 66 (13.2%) for sirolimus-eluting Cypher (Cordis Corp., Miami, Florida); 33 (7.1%) Endeavor (Medtronic, Minneapolis, Minnesota), 123 (25.1%) Xience V (Abbott Vascular, Santa Clara, California), and 104 (22.3%) Promus (Abbott Vascular and Boston Scientific) (Table 6).

Bare-metal stents (BMS) were used in 305 of the lesions. Non-culprit lesion angioplasty and/or stenting was performed in a minority of cases (12.9%) due to high-grade lesions with impending closure or ECG changes in the respective territory of involved myocardium. Two patients (0.3%) were referred for emergent coronary artery bypass graft (CABG) surgery. The majority of procedures (96.4%) were successful, based on relief of chest pain, >70% ST-segment resolution, TIMI-3 flow and myocardial perfusion grade 3 (Table 7).

We measured D2B time as the time from arrival to the time of reestablishing TIMI-3 flow in the culprit artery. For the SINCERE database as a whole, the median D2B time was 71 minutes, with 88.2% of procedures having D2B times of cases in 50-case intervals, there is definite improvement over the course of the study. Whereas for the first 50 cases the median D2B was 120 minutes, with less than a quarter of patients having DTB

A review of safety concerns demonstrated that the rate of complications or MACE was extremely low (Table 9). There were no severe bleeding episodes, intracranial, or lethal bleeding episodes. There were no cerebrovascular events, either hemorrhagic or ischemic. Although serial cardiac enzymes in the post-PCI period were not routinely recorded, clinical re-infarction was low, with sub-acute stent thrombosis and abrupt closure occurring in 2 patients (0.3%). Reviewing the three cases of sub-acute stent thrombosis, all occurred within 48 hours, and 1 was deemed the result of an undersized stent, while the other 2 were due to large residual thrombus load. The rate of overall in-hospital death was 2.8%.

Discussion

Thrombus is a sensitive, dynamic process which demands accurate classification and compulsive management. Optimal angiographic visualization of thrombus is the first step; thrombus is labile and its grading is better done after crossing the thrombotic lesion with the guidewire. Often, there is no change in thrombus grade, but thrombus grade 5 most commonly is downsized after wire passage.

The TIMI thrombus grade classifies the thrombus based on angiography. Clinical experience recommends against the use of balloon angioplasty, as they cause distal embolization and myocardial necrosis.

Sianos et al demonstrated the importance of thrombus burden in clinical outcomes in ACS.⁹ Compared to small thrombus burden (Grades 0–3), large intracoronary thrombus burden (Grade 4) was an independent predictor of mortality and MACE.

The TAPAS trial compared manual aspiration in STEMI patients with conventional primary PCI.¹⁹ The aspiration arm demonstrated a lower percentage of MBG 0 or 1 (17.1% versus 26.3% p 20 Dudek et al found improvements in thrombectomy pretreatment with respect to STR and LVEF at 3 months compared to PCI with stent implantation alone (60.3 ± 9.2% versus 55.3 ± 14.7%, non-specific).²¹ In De Luca’s study, 26.8% developed LV dilation (p = 0.006).²² Aspiration catheters and thrombectomy before primary PCI are not associated with greater reperfusion success, reduced infarct size, STR or major cardiac adverse event (MACE).^17,23,24

Ali et al failed to demonstrate significant improvements in MBG or STR in the thrombectomy group.¹⁷ In this group the final infarct size was larger, TIMI-3 was lower and 30-day MACE was higher.

The EMERALD Trial compared results post-PCI with and without prior distal protection and aspiration.²⁵ Researchers found similar STR between the groups (63.3% versus 61.9%), in the infarct size (12.0% versus 9.5%; p = 0.15), and in MACE at 6 months (10.0% versus 11.0%).

De Luca et al found that patients treated with adjunctive devices before primary PCI were associated with a better TIMI-3 flow, MBG, and decreased distal embolization. No mortality benefit was associated with the adjunctive treatment groups.²⁶ Bavry et al found significant improvement in TIMI-3 flow and STR in the adjunctive devices.²⁷ Burzotta found similar rates of early mortality between the adjunctive treatment groups and conventional groups.²⁸

With fastidious adherence to the Mehta classification, the SINCERE database has been populated with excellent procedural and clinical success.^7,8

If the thrombus is small (Grades 0–1), direct angioplasty and stenting may be sufficient (Figure 1). Moderate thrombus burden, Grades 2–3, warrants pretreatment with an aspiration catheter (Figure 2). Passes with the aspiration catheters should be made throughout the entire length of thrombus until there is no angiographic evidence of it; often just two passes is sufficient. The aspiration catheters are not perfect monorail devices and attention should be paid to the tip of the guide-wire as these catheters advance. Reducing the imaging magnification will also prevent adverse results. Thrombus will often clog the aspiration holes, halting aspiration. Before abandoning them as unsuccessful, remove the catheter, flush it profusely, and reuse. In rare situations, the aspiration catheter will drag the tail of a long thread thrombus that may get dislodged.

Larger thrombus burden (Grades 4–5) are challenging, and thrombectomy may be justified (Figures 3 and 4). The rheolytic thrombectomy device is effective for debulking voluminous thrombi. Thrombus is aspirated and extracted after high velocity water jets create a vacuum.¹⁴ Compared to stenting alone, rheolytic thrombectomy may be successful in improving epicardial flow, frame count, MBG and infarct size.^15,16

The new catheters (4 Fr thrombectomy catheter) track well. Thrombectomy should be performed through the length of thrombus. The rheolytic thrombectomy is invaluable in managing organized thrombus in late-presenting patients. In SINCERE, rheolytic thrombectomy was successful in several procedures in which aspiration thrombectomy catheters were unsuccessful in aspirating such dense, organized thrombus.

The Mehta classification provides a selective strategy for thrombus management, based upon the thrombus grade. This methodology contradicts that thrombus can be managed by a single modality irrespective of the thrombus grade, as in the TAPAS Trial. Organized and dense thrombus in late-presenting STEMI patients can be extremely difficult cases and their management — from crossing the impenetrable lesions to debulking them, requires considerable skills, and often mechanical thrombectomy.

The TAPAS and the AiMI Trials¹⁷ were constrained with a single strategy for all-comers without volumetric adjustments for thrombus burden. This drawback has been partially corrected in the JetStent Trial.¹⁸ The INFUSE-AMI Trial is planned to utilize the Atrium Clearway catheter (Atrium Medical, Hudson, New Hampshire) as a single therapy for managing thrombus without its grading or having a selective methodology.¹⁹ The mechanism of debulking thrombus with a de-thrombotic pharmacological agent delivered through a novel catheter is very attractive. We reserve it as an alternative to situations — usually anatomically challenging ones — unfavorable for rheolytic thrombectomy.

While it is important to establish TIMI-3 flow, great attention should be towards achieving robust MPG. Intracoronary vasodilators are extremely useful in augmenting MPG. Intracoronary nitroprusside is safe, well-tolerated and superior to nitroglycerine for improving coronary blood flow and microvascular circulation.¹⁰ Its administration before balloon angioplasty may decrease rates of no-reflow, increase MBG and shorten procedure times. Early upstream anti-platelet pharmacology must be incorporated as well. Systemic inhibition of GPIIb/IIIa receptors with intravenous abciximab is an established therapy to improve coronary microcirculation and reduce MACE in MI as an adjunct to primary PCI.^11–13

Early discharge from the hospital, by day 3, is becoming routine after a successful STEMI intervention, short D2B times and restoration of LV function.

Limitations of the Mehta Strategy

1. Several catheterization laboratories are not equipped with mechanical thrombectomy devices (AngioJet, Medrad Interventional/Possis, Minneapolis, Minnesota). Operators are unfamiliar with their use, which can delay D2B. Abciximab via the Atrium Clearway catheter provides a good alternative.
2. The new rheolytic thrombectomy device narrowed our relative contraindications (
3. We recommend mechanical thrombectomy for large thrombus grade, but in some cases thrombo-aspiration can work (Figure 5). Excellent debulking is observed with aspiration catheters. We suspect this happens in patients who present early, with fresh, red, soft thrombi that are easily and completely aspirated with these catheters. This observation is contrary to our proposed hypothesis, yet this powerful observation is shared for its tremendous practical benefit. Incidentally, this is also a rare situation where we will use a low-profile balloon to verify that the guidewire is in the true lumen. We currently postulate thrombo-aspiration as a default strategy. The rationale is the aspiration catheters are user-friendly, relatively inexpensive and take less than a balloon catheter to prep and deploy. With this methodology, we grade thrombus nevertheless, then quickly make a pass with the aspiration catheter, and either persist with more thrombo-aspiration or advance to using mechanical thrombectomy.
4. In some cases, even with moderate thrombus burden, the dense, organized thrombus cannot be debulked with thrombo-aspiration (Figures 6a and 6b).
5. Several newer trials appear to validate our strategy with the appropriate presently available devices. Founded on extensive experience, we feel confident in our strategy for effective thrombus management for STEMI interventions; nevertheless, this strategy needs endorsement by clinical trials. A single individual experience, irrespective of its expertise, cannot substitute for data from large, randomized, clinical trials and/or established guidelines.
6. We have also explored possibilities of using a time-to-presentation based strategy for applying a thrombectomy device. This idea is akin to use of prehospital lysis, as in the CAPTIM Trial, where the cohorts of very early AMI patients benefit from early lysis.²⁹ This probably results from effective lysis of a fresh clot. Thrombo-aspiration is effective therapy for early presenters ( 6 hours). Calculating time-to-presentation is challenging. Many variables affect thrombus presentation in STEMI, and the heterogeneity of thrombus and of its over-simplification. Interventional management of soft, red, early thrombus is quite different than that of dense, organized thrombus.

Conclusion

Dedicated attention to thrombus cannot be underestimated in STEMI interventions. Mechanical adjunct devices are useful tools for PCI, especially in evading distal embolization. Thrombus-graded approach to using these devices, as in the SINCERE database, produces excellent clinical results. Even if perfection is obtained in the catheterization lab, patient education and legislation to streamline the STEMI procedure are still hurdles that must be overcome.

References

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Role of adjunctive thrombectomy and embolic protection devices in acute myocardial infarction: A comprehensive meta-analysis of randomized trials. Eur Heart J 2008;29(24):2989–3001. 28. Burzotta F, Testa L, Giannico F, et al. Adjunctive devices in primary or rescue PCI: A meta-analysis of randomized trials. Int J Cardiol 2008;123(3):313–321. 29. Steg PG, Bonnefoy E, Chabaud S, et al. Impact of time to treatment on mortality after prehospital fibrinolysis or primary angioplasty: Data from the CAPTIM randomized clinical trial. Circulation 2003;108(23):2851–2856. ———————————————————— From the University of Miami, Miami, Florida. Address for correspondence: Sameer Mehta, MD, Miller School of Medicine, University of Miami, 185 Shore Drive South, Miami, FL 33133. The authors report no conflicts of interest regarding the content herein. Note: This article was not subject to the Journal of Invasive Cardiology peer-review process.