Direct Stenting in Angiographically Apparent Thrombus-Containing Lesions

Although once considered to be a contraindication, accumulating data regarding stenting in thrombogenic milieu [acute myocardial infarction (AMI), unstable angina pectoris] in the presence of angiographically apparent thrombus reveal promising results with very low acute and subacute thrombosis rates.1–4 Obtaining TIMI 3 flow with percutaneous coronary intervention (PCI) was associated with a better prognosis in AMI.5 The GUSTO trial demonstrated a worse clinical outcome in cases where TIMI 3 flow could not be obtained.6 Primary angioplasty and thrombolytic therapy are the major treatment modalities for rapid and complete reperfusion in patients with acute ST-segment elevation MI. Mechanical disruption of thrombus with angioplasty was shown to have advantages compared to thrombolytic therapy.7,8 However, percutaneous transluminal coronary angioplasty (PTCA)-related major complications occur in patients with unstable angina, likely because of the plaque fissuring and thrombus that are frequently present. Abrupt closure (no re-flow) at the angioplasty site occurs in 11–50% of patients who undergo balloon angioplasty in the setting of AMI.9,10 Primary thrombus propagation may be more important when dilation is performed in the setting of pre-existing thrombus.11 No re-flow after percutaneous interventions may limit the procedural success. Infarct-related artery (IRA) occlusion and dissections are the major complications after PTCA in AMI leading to impaired clinical sequel.12 However, stenting may improve the blood flow in this thrombogenic milieu by overcoming these potential complications. Direct stenting (stenting without balloon predilation) is a novel approach in the percutaneous treatment of coronary artery lesions. Direct stenting may decrease the incidence of trauma, dissection and distal embolization, leading to a better outcome.13–16 However, data regarding these potential benefits of direct stenting in thrombus containing lesions are scarce. The aim of this study was to evaluate the impact of direct stenting, a novel PCI technique, on the angiographic results in the setting of angiographically apparent thrombus-containing lesions. METHODS Study population. We reviewed our institutional interventional database from February 1998 through February 2001 at Gazi University Hospital and identified all patients who had undergone PCI. Out of 837 PCIs performed during this period, we identified 188 patients (22.5%) in whom direct stenting was applied. Out of these 180 patients, we identified 30 patients (33% with unstable angina pectoris, 67% with AMI) in whom stenting was performed in the presence of angiographically apparent thrombus. Only the cases with definite but not probable thrombus were evaluated. Fifty-three patients with definite intracoronary thrombus were identified who had undergone conventional stenting during this period. The reason for conventional stenting in these patients was the lack of distal opacification (TIMI 0 flow) after guidewire passage in 26 patients, severe proximal tortuosity in 5 patients, ostial location of the lesion in 2 patients and operator preference in 20 patients. Clinical outcomes. Total creatine kinase (CK) and creatine kinase MB fraction (CK-MB) were measured before angioplasty and at 8 and 16 hours post-angioplasty. An electrocardiogram was obtained before angioplasty, immediately following angioplasty, if chest pain recurred and the following morning. MI was defined as an elevation of CK to > 3 times normal associated with elevation of CK-MB. Q-wave MI was diagnosed in the presence of new Q-waves in 2 contiguous leads. In-hospital death (due to any cause), recurrent MI, target vessel reintervention and coronary artery bypass operation were also noted. Angiographic evaluation. Angiograms were reviewed and graded by two independent film readers, who were unaware of the study purpose, to assess TIMI flow grades.17 Contrast flow through the epicardial artery was graded using the standard TIMI trial flow scale of 0–3. “No re-flow” was defined as an acute impairment of blood flow to TIMI 0–1 after successful dilation. “Slow flow” was defined as TIMI 2 flow. Angiographic success was defined as TIMI flow grade >= 2. Slow flow or no re-flow phenomena were treated with intracoronary nitroglycerin (200 µg) followed by intracoronary verapamil (150–250 µg). Thrombus was defined as a discrete, intraluminal-filling defect with defined borders, largely separated from the adjacent wall, with or without contrast staining. The vessel size, presenting percent stenosis and post-stenting percent stenosis were determined with the use of quantitative coronary angiography (QCA). Lesion characteristics and post-procedure angiographic characteristics, such as dissections, persistence of thrombus, sidebranch occlusion and TIMI flow grades, were recorded. QCA was performed with the use of an automatic edge detection system (General Electric DLX Angiographic Systems, GE Medical Systems Europe, Sedex, France). Coronary occlusion was assigned a value of 0 mm for minimal lumen diameter and 100% for percent diameter stenosis. Multi-vessel disease was defined as at least one major non-culprit vessel with more than 50% stenosis. Angioplasty procedure. PCI was performed after obtaining 2 orthogonal views of the thrombus-containing lesion. Procedural success was defined as successful deployment of the stent without any adverse cardiac events and angiographic success as a residual diameter stenosis 12 atmospheres). Stent to artery ratio was 1.1:1. Direct stenting was accomplished with the delivery balloon with a high-pressure single inflation. Post-dilation was not performed in any patients. In cases where the basal blood flow was TIMI 0–1, the patients were stented directly if TIMI 2–3 flow was achieved after guidewire crossing. During the procedure, an intravenous bolus dose of 10,000 units of standard heparin was given to maintain an activated clotting time > 300 seconds and continued for 6–24 hours. Standard heparin was replaced with enoxaparin (1 mg/12 hours for 72 hours) in addition to ticlopidine (250 mg twice daily for 30 days) and aspirin (300 mg indefinitely). RESULTS The study population consisted of 30 patients with a mean age of 57 ± 12 years who presented with acute coronary syndrome. There were 17 men and 13 women. Out of these 30 patients, twenty presented with AMI (14 primary, 6 rescue angioplasty) and 10 with unstable angina. Sixteen patients (53%) were on intravenous heparin (mean, 14 ± 6 hours) before the procedure. The remaining 14 patients (47%) had 10,000 units of intravenous heparin bolus just prior to the procedure (primary PTCA). The majority of patients had a baseline TIMI 2–3 flow (80%). Of the 6 patients (20%) who had TIMI 0–1 flow at baseline, four achieved a TIMI 2 flow immediately after crossing the lesion with a 0.014´´ guidewire. Although the remaining 2 patients had TIMI 1 flow after guidewire crossing, as distal opacification beyond the stenosis was obtained we performed direct stenting. Direct stenting was successful in all patients. Examples of the cases are depicted in Figures 1 and 2. There was no “no re-flow”, with a final TIMI 3 flow rate of 93.3%. In one patient with TIMI 2 flow after stenting, TIMI 3 flow was obtained after intracoronary verapamil. Two patients (6.7%) had TIMI 2 flow. There was no difference in the pre-procedural preparation of these 2 patients with final TIMI 2 flow. One was on intravenous heparin for 8 hours before the procedure and the other was taken to the laboratory for rescue PTCA 2 hours after t-PA with ongoing heparin infusion. Despite intracoronary nitroglycerin and verapamil, TIMI 3 flow could not be achieved in these patients (6.7%). Longer duration (24 hours) of intravenous heparin and nitroglycerin was given to these patients after the procedure. We implanted a second stent in 4 patients (13%) because of the persistence of thrombus at the stent edge and because of a distal edge dissection in 1 patient. Total occlusion of the vessel by the delivery system was observed in 5 patients (17%) when the stent was delivered to the lesion for implantation. However, there was no stent loss or imprecise stent placement. Only 1 patient out of 30 (4.8%) developed a distal dissection, requiring deployment of one additional stent. Post-procedural CK-MB levels peaked dramatically in the first 24 hours in patients with primary and rescue angioplasty procedures. However, in only 1 patient in the unstable angina pectoris group, an MB rise of Hospital outcome. There were no in-hospital deaths, repeat interventions or coronary artery bypass graft surgeries (CABG). However, two patients underwent mitral valve replacement due to severe mitral regurgitation. Eight patients with recurrent ischemia had control angiography; stents were found to be patent in all patients. Two patients experienced recurrent MI (6.6%). Late clinical follow-up. A complete 30-day clinical follow-up was completed in 25 patients (83%). One patient had elective CABG. Event-free survival at 30 days in the remaining 24 patients was 96%. Eight patients had repeat coronary angiogram at 30 days because of recurrent pain; all stents were found to be patent. However, a 6-month follow-up evaluation could only be obtained in 20 patients (66%). Of these 20 patients, six had control angiogram and 5 had patent stents. The remaining patient (5%) had a repeat intervention due to restenosis. DISCUSSION Angiographically apparent intracoronary thrombus has been documented to be a strong correlate of acute coronary occlusion during PTCA.18 Local activation of platelets and coagulation factors, as well as the liberation of clot-bound thrombin due to mechanical disruption of thrombus after balloon dilation, have been reported to be the responsible mechanisms.19,20 Balloon dilation of diffusely diseased saphenous vein grafts carries a major risk of abrupt closure or distal coronary embolization, likely due in part to the frequent presence of thrombus within these degenerated vessels.21 Often, dissection and thrombus formation coexist because of stasis and the exposure of intimal and medial surfaces resulting from dissection, which are potent activators of the thrombotic cascade. The extensive use of stents in the treatment of coronary artery disease has led cardiologists to simplify the procedure by introducing the concept of stenting without predilation, i.e., direct stenting. Several studies confirmed the safety and feasibility of the procedure with success rates greater than 90%.13,14,16 Besides reductions in procedure time, fluoroscopy time and procedural costs, balloon-induced dissections were also reported to be lower.13,14 Obtaining TIMI 3 flow is the ultimate goal after PCI. In a meta-analysis, TIMI 3 flow was found to be associated with significantly less mortality compared to all the other TIMI flow grades, including TIMI 2.22 Stenting was also shown to be superior to plain old balloon angioplasty (POBA) at improving coronary flow reserve (CFR).25 Edep et al. recently showed that coronary blood flow is increased after stenting compared to POBA in the setting of AMI as measured by the TIMI frame count method.23 In addition, Sasao et al. reported that primary stenting is superior to POBA in acute anterior MI for preventing myocardial injury and restoring left ventricular function. The authors speculated that primary stenting improves regional wall motion by improving the coronary vasodilator reserve.24 It has been shown that CFR is not commonly normalized after PTCA, although reports suggest that CFR may be normalized after stent implantation.25 We think that eliminating the balloon predilation not only avoids balloon-related complications, but also achieves an immediately larger luminal diameter and normalizes the CFR, resulting in a higher final TIMI 3 flow. Animal studies revealed that endothelial denudation is less in direct stenting cases compared to conventional stenting, which may mean less vascular wall trauma and thrombosis risk.15,26 In addition, Webb et al. reported lesser atheromatous embolic debris during intervention in saphenous vein grafts with direct stenting compared to conventional stenting, which may lead to the “no re-flow” phenomenon.16 The authors reported that stents reduced the dislodgement of the thrombus and embolization by entrapping friable material. TIMI flow grades after stenting in the present study are quite high, with the majority being TIMI 3 flow (93%). This difference could be due to lesser trauma compared to conventional stenting with balloon predilation leading to less flow impairment. Trapping of the thrombus with the stent might also be an important factor in protecting the flow. The trauma caused by balloon predilation might be responsible for a greater amount of distal embolization of the thrombi and debris. Although small numbers limit the conclusions of our study, there was no “no re-flow” case and only 2 slow flow (TIMI 2) cases. In the presence of thrombi, a stent may act as a jail for the thrombus and prevent distal propagation. However, the potential pitfalls of direct stenting should always be considered. Although stenosis severity was not reported to be an indicator of successful direct stenting,13 passing a stent through a severe undilated stenosis might be more traumatic. During stent implantation, flow through the vessel is impaired and we observed total occlusion in 5 patients which made precise stent placement difficult. One trick that helped prevent this complication was the storage of the vessel image on a monitor above the one we were working with as a road map and studying the anatomical landmarks in case the vessel was totally occluded. This was very helpful in our practice. However, direct stenting may not be an appropriate approach in all lesion subsets and requires distal opacification of the vessel for accurate assessment of lesion characteristics and stent choice. In the present study, four out of 6 patients with TIMI 0–1 flow achieved TIMI 2 flow immediately after guidewire crossing. Although the remaining 2 patients had TIMI 1 flow, we successfully performed direct stenting as distal opacification beyond the stenosis was obtained. Since the majority of acute coronary syndromes develop in lesions with Study limitations. This is a single-center, retrospective and non-randomized study with a small number of patients; its limitations should be kept in mind before interpreting the results. Randomized studies with larger patient populations should be conducted. A higher frequency of baseline TIMI 2–3 flow grades in our cohort might be effective in achieving a high procedural success. Operator discretion could have led to a selection bias depending on the basal flow status regarding the selected procedure. Another limitation is that routine angiography was not performed, and the frequency of angiographic restenosis is unknown. Conclusion. Stent implantation without balloon predilation seems to be safe with the new generation of low-profile stents and refined stent delivery systems. There was a high angiographic success rate in patients treated with direct stenting in highly thrombogenic milieu. Direct stenting in thrombus-containing lesions seems to be a safe and feasible approach in avoiding no re-flow. However, this is a single-center, retrospective study with a small number of patients, which limits the results. We believe that the benefits observed with direct stenting in this study should be compared to conventional stenting in the same setting with a randomized study.

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