Intravascular Ultrasound-Guided High-Pressure Balloon Predilatation for Optimal Drug-Eluting Stent Deployment in Restenosis of

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J INVASIVE CARDIOL 2008;20:E139-E145

After both its acute and long-term usage proved to be highly effective, drug-eluting stent (DES) implantation, although off-label, became a preferred intervention for inbare metal stent restenosis (BMS ISR).^1–3 However, lesion recurrence within the first year after BMS ISR restenting with DES occurs in up to 25% of cases, with potential for late restenosis as well.^4–6 At the same time, increasing attention has been paid recently to the higher rate of in-stent thrombosis after routine DES implantation.⁷ It has been argued that it is the off-label use of DES stenting that could be one of the likely explanations of the phenomenon.⁸ Accordingly, it has been shown that the regular use of DES for BMS ISR treatment, compared to other indications, is of a higher risk of subsequent in-stent thrombosis.^9,10 Intravascular ultrasound (IVUS)-based studies have shown that stent underexpansion is the most frequent mechanism of in-DES thrombosis (minimal stent cross-sectional area of < 5.0 mm²).¹¹ Also, lesion recurrence after DES implantation, for either de novo or BMS ISR lesions, is mostly the result of DES underexpansion.^12,13 Interestingly, this is in accordance with the angiographic model of in-DES renarrowing (apple core lesions).^14,15 When preparing for a restenting procedure, it is important to know that the initial BMS underexpansion initiates and certainly adds to lesion recurrence in almost 25% of BMS ISR cases.^16,17 One should also know that reexpansion of a previously implanted stent is the leading mechanism of acute luminal gain during angioplasty of BMS ISR.^18,19
We report a case of a patient with ISR of a BMS implanted 7 years earlier, in whom preprocedural IVUS clarified initial stent expansion. As a result, high-pressure balloon predilatation with an angiographically-oversized balloon was applied just prior to the planned DES deployment. Subsequent IVUS verified expansion of the stents.^10,20

Case Report
A 57-year-old hypertensive male with hyperlipidemia, who 7 years earlier underwent elective implantation of a 3.0 x 18 mm BMS in the mid segment of his left circumflex artery (LCx), underwent cardiac catheterization due to chest pain recurrence and concomitant positive exercise test results.

In addition to insignificant stenosis of the proximal left anterior descending artery (LAD), coronary angiography revealed the presence of a moderate degree of neointimal hyperplasia (NIH) that was limited to the stent length only in the mid segment of the large-dominant LCx. The adjacent proximal vessel segment had no apparent stenosis, unlike the distal one, which was slightly narrowed. The previously-implanted BMS appeared to be well expanded. Relevant quantitative measurements were performed with a computer-assisted automated edge-detection algorithm (Trex^™ QCA system, Trex Medical Corp., Copiague, New York) and their results are shown in Figure 1.
Complementary IVUS examination (Galaxy^™, Atlantis SR Pro 40 Mhz catheter, Boston Scientific Corp, Natick, Massachusetts), with the pullback done through the distal, mid and proximal LCx segments revealed the following:
• a large artery with a 3.5 mm distal lumen reference (Figure 2A);
• a significant (minimal lumen cross-sectional area of 2.4 mm²) fibrocalcified lesion located just after the marginal branch takeoff (Figure 2B);
• diffuse and fibrocalcified NIH restricted to the length of the severely underexpanded BMS (stent minimal cross-sectional area of 4.7 / 4.8 mm²), with a large amount of calcified persistent plaque (Figures 2 C–E).
The angiographic and, mostly, IVUS results demonstrating diffuse ISR in BMS implanted 7 years earlier prompted the decision to perform immediate percutaneous coronary intervention (PCI). IVUS-guided high-pressure plain balloon predilatation prior to planned DES stent implantation was chosen as the interventional strategy due to the following target lesion characteristics: 1) underexpansion of the 3.0 mm BMS, which was implanted in the artery of a half-size larger distal luminal reference; 2) a significant amount of chronic calcified plaque; and 3) diffuse fibrocalcified NIH.

The LCx was engaged using a 7 Fr Amplatz guiding catheter, and a 0.014 inch Balance Middleweight wire (Guidant Corp., Santa Clara, California) was passed distally, both providing extra support. Next, a 3.5 x 20 mm semicompliant SeQuent PTCA^® balloon (B. Braun Medical, Inc., Bethlehem, Pennsylvania) was inflated at the lesion site, along with balloon predilatation of the entire length of the previouslyimplanted BMS. The exact location of BMS, which was clearly identified by IVUS, allowed the SeQuent markers to be positioned exactly within the length of the selected target (within the posterolateral and marginal branches). Next, 2 high-pressure (16 and 20 atm) balloon inflations were performed (Figure 3). It is worth noting that a gradual increase in the inflation pressure was applied, with intentional short pauses at 2, 4 and 6 atm. In our opinion, it may have helped that we secured firm balloon engagement within the target lesion, thus preventing the balloon from being squeezed into the adjacent vessel segments. Control angiography performed just after aggressive balloon predilatation demonstrated diffuse vessel spasm propagating from the distal lesion located just after the marginal branch takeoff. Poor blood flow to the distal LCx was also noticed (Figure 4A). Low-pressure (6 atm) SeQuent inflation at the site of the vessel spasm restored TIMI 3 blood flow (Figure 4 B and C). Another IVUS followed (Figure 5), confirming successful correction of the BMS expansion and creation of a space large enough for a DES one-half size larger. Neither coronary dissection nor plaque shift were observed at the site of the earlier vessel spasm (Figure 5 A and B). Based on the pre- and intraprocedural IVUS measurements, a 3.5 x 24 mm Taxus^® Express2^™ paclitaxel-eluting coronary stent (Boston Scientific) was selected. The stent was positioned in the mid-LCx segment, extending from the posterolateral branch takeoff and covering the 5 mm long distal lesion located just after the marginal branch takeoff. The stent was then inflated to 18 atm.

Final IVUS (Figure 6) confirmed that optimal acute results were achieved, including:
• coverage of the entire length of the target lesion, with stenting of the distal segment and uncompressed takeoff of the large posterolateral artery;
• adequate and uniform DES expansion (in-stent minimal cross-sectional area of 8.6 mm² which was almost equal to the lumen dimension of 9.0 mm² at the distal reference segment);
• ruling out outflow disease (Figures 6 A and G). Optimal angiographic and IVUS results were achieved. The patient experienced no ischemia on exercise testing and was discharged home angina-free.

Discussion
The preferred strategy of DES deployment at the site of BMS ISR is unknown.²¹ Several studies have shown that appropriate DES expansion is crucial for an uneventful long-term outcome.^11–13 Also, it is important to realize that in almost 20–25% of BMS ISR lesions, the previously-implanted stent is already severely underexpanded.¹⁷ Moreover, acute lumen gain during plain balloon angioplasty of BMS ISR is mainly (56–66%) dependent on reexpansion of the previouslyimplanted stent.^18,19 It is also well known that angiography has a limited ability to reliably assess stent expansion. Therefore, in the case presented here, serial IVUS evaluations were performed as an integral part of the BMS ISR restenting procedure.^10,20 Preprocedural IVUS revealed that the BMS implanted previously was severely underexpanded and allowed for precise assessment of the target lesion length and, most importantly, verified the size of the distal reference segment. Consequently, high-pressure (≥ 12 atm) predilatation using a conventional, optimally-sized balloon (a half-size larger than both the BMS diameter and distal reference segment measured with quantitative coronary angiography [QCA]) emerged as the strategy of choice.^19,22,23 The BMS was successfully reexpanded to double its initial dimension. Next, IVUS measurements guided DES sizing; a selected stent appeared a half-size larger than both the BMS diameter and distal reference segment as assessed by QCA. Of note, the previously-implanted BMS was 3.0 mm in size, but was able to be safely dilated to 3.5 mm.
Our intention was to avoid DES postdilatation since it could have a negative impact on the polymer structure and might lead to lesion recurrence.^24,25 We also believe that it is easier to achieve optimal restenting results with aggressive predilatation rather than “fine-tuning” postdilatation (Figure 7).²¹

Some operators believe that optimal BMS ISR restenting requires implantation of the DES “directly” or, if necessary, to precede it with nonaggressive (atraumatic) predilatation.^3,26–28 This approach helps to avoid geographic miss and is thought to prevent diffuse neointimal hyperplasia, which is believed to result from excessive vessel wall barotrauma. As for the harmful effects of geographic miss, we have shown previously that it is only the edge injury within the source dose fall-off that results in recurrent renarrowing after beta-radiation for BMS ISR, while the overt injury within the nonirradiated margin is clinically benign.²⁹ Furthermore, it has been shown that balloon squeezing into the adjacent vessel segments, which frequently results in geographic miss, has no impact on late outcomes of conventional BMS ISR angioplasty.³⁰ At the same time, it is our experience that the use of particular types of balloons (e.g., FX miniRAIL^® RX, Guidant) or, as presented here, slow and gradual balloon inflations with a short pause within the range of 2–6 atm, helps engage the balloon more firmly within the target, thus minimizing the risk of the “water-sledge” phenomenon. Cutting balloons decrease the incidence of balloon squeezing, but their mechanism of action during BMS ISR angioplasty relies on neointimal redistribution rather than stent reexpansion.^31,32 In regard to the concern that aggressive predilatation might incite diffuse instent tissue regrowth, it seems to be unfounded in light of the ARTIST trial results.³³ In this randomized study, atraumatic balloon angioplasty of BMS ISR neither minimized subsequently- measured neointima, nor allowed it to accumulate, as the stent dimension increased only minimally. Contrary to this, Sakamoto et al have shown that aggressive angioplasty of BMS ISR with a maximum inflation pressure of 14.3 ± 0.4 atm and a balloon-to-artery ratio of 1.33 ± 0.35 (balloon size determined by IVUS) resulted in a BMS cross-sectional area reexpansion of 2.9 mm², which led to superior long-term outcomes.³⁴ Finally, the prime interventional principle that “bigger is better” turned out to be equally true for this subgroup of in-stent restenotic lesions.³⁵ Again, we strongly recommend avoiding direct DES implantation at the site of BMS ISR (Figures 8 and 9).
The patient whose case is presented here was absolutely free of any cardiac complaints at 8-month follow up and adamantly refused to undergo control angiography. For this reason, we have shown the long-term results of another similar procedure during which the high-pressure balloon predilatation was successfully applied prior to BMS ISR restenting with DES (Figure 10).
In conclusion, aggressive balloon predilatation with parallel IVUS guidance is necessary when off-label DES stenting for diffuse in-bare metal stent restenosis is planned.

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