ABSTRACT: Percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) caused by in-stent restenosis (ISR) is sometimes very difficult due to the presence of hard occlusive components that prevent wire passage. We report a case of CTO caused by ISR (ISR-CTO) in which the occlusion was crossed with the wire subintimally along the outside of the stent and was successfully re-stented. Subintimal tracking along the outside of the stent can be considered as another approach for PCI of ISR-CTO in cases where conventional approaches fail. J INVASIVE CARDIOL 2008;20:E129–E132

and after (B) the placement of several stents 1 year before the index procedure.

Figure 1. Images of the right coronary artery before (A)

       Percutaneous treatment of coronary chronic total occlusions (CTO) remains one of the major challenges in interventional cardiology. Although CTO in the form of in-stent restenosis (ISR-CTO) is relatively rare, with an incidence of 1.6% of stent procedures, it is associated with significant morbidity.¹ The paucity of published data on this rare population indicates that the low success rate of PCI is mostly due to difficulty in passing the guidewire across the occlusive stent lumen.^1,2 Thus far, there is no consensus on the best method to overcome the failure of wire passage in this patient subset. Among the various techniques for CTO intervention, the subintimal tracking and re-entry (STAR) technique, described by Colombo, is a unique method in which the operator subintimally advances a guidewire by blunt dissection and the guidewire eventually re-enters the true lumen at the distal site.³ In this report, we present a case in which ISR-CTO was opened by subintimal tracking along the outside of the stent.

A guidewire with the Progreat microcatheter was passed subintimally along the outside of the original stent and re-entered the distal true lumen (B–D).

A guidewire with the Progreat microcatheter was passed subintimally along the outside of the original stent and re-entered the distal true lumen (B–D).

Figure 2. A diagnostic image of the right coronary artery (RCA) shows focal in-stent restenosis at the proximal RCA and a totally occluded stent from the mid-to-distal RCA (A).

       Case Report. The patient was a 52-year-old male with exertional chest pain for 2 months. One year prior, he underwent coronary angiography, and CTO of the right coronary artery (RCA) was successfully treated with multiple stents. The stented segment was extremely long; it consisted of 3 Taxus^® stents (2.5 x 24 mm, 3.0 x 32 mm, 3.5 x 32 mm; Boston Scientific Corp., Natick, Massachusetts) and a 4.0 x 15 mm Lekton Motion stent (Biotronik, Lake Oswego, Oregon) from the distal-to-proximal RCA segment (Figure 1). His coronary risk factors were hypertension and smoking. The resting electrocardiogram was not specific, and echocardiographic examination showed mild concentric left ventricular hypertrophy with a normal ejection fraction. Diagnostic angiography demonstrated focal ISR at the proximal RCA (Lekton Motion Stent) and total stent occlusion from the mid-to-distal RCA (Taxus stents). The occluded segment was very long (57.6 mm by quantitative coronary angiography), and the distal RCA was collateralized through its conus branch (Figure 2A). A 6 Fr JR 3.5 guiding catheter (Cordis Corp., Miami Lakes, Florida) was used via the right femoral artery. First, the focal ISR of the proximal RCA was dilated with a 4.0 x 10 mm Kongou balloon (Terumo, Bangkok, Thailand), followed by an attempt to cross the ISR-CTO with the support of a Progreat microcatheter (Terumo). However, Whisper (Guidant Corp., Santa Clara, California), Miracle 6g, Miracle 12g and Conquest Pro (Asahi Intec, Nagoya, Japan) wires could not cross the lesion since they were only able to penetrate the occlusion up to a depth of approximately 15 mm. For stronger backup support, the guiding catheter was exchanged for a 7 Fr AL 1.0 (Cordis); Miracle 6g, 12g and Conquest Pro wires were then used again to cross the lesion. However, instead of entering the true lumen, the wire repeatedly penetrated the stent struts and passed along the subintimal space (Figures 2B and 2C). After several difficult wire manipulations along the outside of the stent, the Miracle 12g finally entered the distal true lumen and was subsequently exchanged for the soft wire (Figure 2D). After balloon dilatation using a 1.5 x 15 mm Ryujin balloon (Terumo), intravascular ultrasound (IVUS) confirmed that the wire crossed the occlusion through the subintimal space along the outside of the stent and re-entered the distal true lumen, as expected (Figure 3). Multiple dilatations were performed using 2.5 x 20 mm and 2.75 x 20 mm balloons to crush the original stents; then the entire occluded segment, including the proximal posterior descending artery, was re-stented with 3 Cypher^™ stents (2.5 x 33 mm, 3.0 x 33 mm, and 3.5 x 33 mm; Cordis). The final angiogram revealed excellent results (Figures 2E and F). Post-stenting IVUS images were also obtained (Figure 4). The patient was stable without elevation of enzymes and was discharged with a triple antiplatelet regimen of aspirin, clopidogrel and cilostazol 2 days after the procedure. A 5-month follow-up angiogram showed no restenosis (Figures 2G and H), and the patient remained stable with a continuous triple antiplatelet regimen during the 9 months of clinical follow up.

The final images of the RCA after placement of several Cypher™ stents (E–F).

The final images of the RCA after placement of several Cypher™ stents (E–F).

A guidewire with the Progreat microcatheter was passed subintimally along the outside of the original stent and re-entered the distal true lumen (B–D).

       Discussion. The treatment of CTO remains a therapeutic and technical challenge for interventional cardiologists. ISR–CTO is relatively rare, particularly in this era of drug-eluting stents (DES). However, its clinical impact is fairly significant. Most patients with ISR-CTO display recurrent stable angina at the time of repeat angiography (60%), while only a minority of these patients present with unstable syndrome.¹ This is directly related to the components of this new lesion: smooth muscle cells, collagen and extracellular matrix constitute a homogenous tissue that becomes a more fibrous structure with, at most, a small component of thrombus. Thus, although the previous stent may allow direct visualization of the anatomic course of the vessel, hard fibrous tissue can hinder correct wire advancement into the stent lumen and may cause wire penetration into the subintimal space through the stent struts.

Follow-up angiogram 5 months after reintervention (G–H).

Follow-up angiogram 5 months after reintervention (G–H).

       The Frontrunner blunt microdissection catheter (LuMend, Inc., Redwood City, California) can help this subset of patients because the original stent struts prevent the advancement of this catheter into the subintimal space.^4,5 However, since the Frontrunner catheter was not available in our country, we continued to manipulate the wire in the subintimal space; finally, we were able to pass the wire into the true lumen distal to the occlusion. To our knowledge, this successful procedure may be the first reported case in which PCI of ISR-CTO was done via a subintimal approach. Subintimal angioplasty was originally used in peripheral intervention,^6,7 and Colombo applied this technique to the coronary field by naming it the STAR technique. In Colombo’s series comprised of 31 patients, the STAR technique was predominantly applied in RCA (87%) lesions, and it achieved a relatively high complete angiographic success rate of 68%.³

(B). The IVUS catheter is placed in the subintimal space. The occluded original stent is seen at the 9–12 o’clock position

Figure 3. Intravascular ultrasound (IVUS) images from the posterior descending artery to the mid RCA after guidewire passage and predilatation. The IVUS catheter is placed in the distal true lumen. The posterolateral branch is seen at the 11 o’clock position (A). The IVUS catheter is placed in the subintimal space. The original stent is seen at the 3–4 o’clock position

       It is well known that the use of DES in the treatment of CTOs drastically reduces major adverse coronary events and restenosis compared with bare-metal stents (BMS).^8,9 When we considered which would be more appropriate — sirolimuseluting stents (SES; Cordis) or paclitaxel-eluting stents (PES; Boston Scientific)—to treat complex lesions in small-vessel disease,^10,11 long lesions,^12,13 in-stent restenosis^14,15 and CTOs,^16,17 we found that many, though not all, studies have shown SES to be better than PES in terms of angiographic and clinical outcomes. In our case, ISR-CTO occurred after PES placement for a native CTO lesion. However, no restenosis was observed at 5-month angiographic follow up of SES treatment for this ISR-CTO. This again suggests that stent type could have an impact on the late outcome of complex lesions. In Colombo’s series,³ the restenosis rate of subintimal angioplasty was relatively high (52.4%). However, considering that the majority of restenosis cases occurred in the BMS and partial angiographic success groups, the significant benefits of using DES for reducing restenosis in CTO intervention appears to be applied to the subintimal approach, as seen in our case.

(C). The IVUS catheter is now seen in the original stent lumen at the proximal portion of the occlusion site (D)

(C). The IVUS catheter is now seen in the original stent lumen at the proximal portion of the occlusion site (D)

       However, the disadvantages of this technique should not be disregarded. Wire handling, ballooning and stenting in the subintimal space or in the periadventitial layer in a more aggressive situation will certainly increase the risk of vessel perforation, which occurred in 10% of Colombo’s series.³ As mentioned in the IVUS finding, several large extraluminal hematomas were observed in our case (Figure 4). The subintimal space also appears to be highly thrombogenic due to the exposed collagen and tissue factor. Additionally, protracted stent length and an excessive use of stents could increase the risk of stent thrombosis.¹⁸ Thus, meticulous care should be taken to avoid stent thrombosis, which is why our patient remains on a triple antiplatelet regimen to this day.

The new stent is placed in the subintimal space. The crushed original stent is seen at the 3–5 o’clock position (double arrows), and an extraluminal hematoma is observed at the 12–2 o’clock position (single arrow) (B)

Figure 4. Final intravsacular images from the posterior descending artery to the mid RCA. The new stent is placed at the posterior descending artery. The posterolateral branch is emerging at the 11–12 o’clock position (A).

       Although ISR-CTO is a rare and challenging field with a low success rate, various techniques and devices can help treat this subset of patients, and the successful treatment of these patients may provide benefits similar to those obtained with successful PCI of native CTOs.¹⁹ In this case, we successfully recanalized an ISR-CTO by using the subintimal approach. This unique technique appears to be helpful, particularly since the occluded stent segment in our patient was difficult to cross by conventional approaches. However, considering the potential risks involved with this technique, it might be reasonable to reserve this method as a final option in the treatment of ISR-CTO.

The new stent is now placed in the original stent at the proximal portion of the occlusion site (D).

The new stent is placed in the subintimal space. The crushed original stent is seen at the 12–2 o’clock position (double arrow), and the extraluminal hematoma is observed at the 9–12 o’clock position (single arrow) (C)