Cutting Balloon Angioplasty: To Cut is to Cure?<br />

The Cutting Balloon is an interventional device with 3–4 sharp microtome metal blades mounted longitudinally on the balloon surface. The microsurgical blades on the cutting balloon allow a more controlled dissection with lower inflation pressures within the coronary lesion compared to conventional balloon angioplasty. Cutting balloon angioplasty (CBA) is approved by the Food and Drug Administration for the treatment of “resistant” coronary lesions, and small studies have demonstrated some potential benefit for its application in small vessels, ostial lesions, calcified lesions and bifurcation lesions, although large, randomized head-to-head clinical trials versus balloon angioplasty and other devices are lacking. The increasing use of intracoronary stents has resulted in the introduction of an especially problematic form of restenosis, in-stent restenosis (ISR), in contemporary interventional practice. Due to the potential for minimizing intimal injury, reducing the proliferative neointimal response, achieving a greater post-procedural minimal luminal diameter, and decreasing slippage due to “watermelon seeding”, CBA has been studied to determine its efficacy for the treatment of in-stent restenosis. However, the impact of CBA in combination with vascular brachytherapy (VBT) for the treatment of ISR has not been well established. The theoretical advantage of combining CBA and VBT over conventional percutaneous transluminal coronary angioplasty (PTCA) and VBT includes the potential to avoid geographic miss by limiting the mismatch between the injured and irradiated arterial segments. CBA in de novo coronary lesions. The Global Randomized Trial was the largest multicenter trial comparing CBA with PTCA. The study enrolled 1,238 patients with 1,385 de novo type A or B stenoses in native coronary vessels. Preliminary results showed that there was no significant difference between CBA and PTCA at 6-month follow-up in angiographic and clinical results. The primary endpoint of angiographic restenosis at 6 months was similar for CBA compared to PTCA (31.4% versus 30.4%, respectively), and the secondary endpoints of target lesion revascularization and major adverse cardiac events (MACE) at 9 months were not statistically significant. The authors concluded that although CBA was equivalent in safety and efficacy endpoints to PTCA, it did not appear superior for the general population of coronary intervention patients. A small, randomized trial involving 71 patients compared the immediate and 6-month follow-up angiographic and clinical outcomes of CBA and conventional balloon angioplasty in small vessels (less than 3 mm in diameter). CBA had a similar success rate in smaller vessels but with fewer bail-out procedures, and a lower 6-month angiographic restenosis rate compared to PTCA (27% versus 47%, respectively; p CBA for in-stent restenosis. A matched study by Adamian et al. specifically addressed whether CBA had advantages over other modalities in the treatment of ISR. A total of 648 ISR lesions were divided into four groups according to the treatment strategy: CBA, rotational atherectomy, additional stenting and balloon PTCA. Following the matching process, a total of 258 lesions were entered into the analysis. Baseline clinical and angiographic characteristics were similar among the groups. Acute lumen gain was significantly higher in the stent group (2.12 ± 0.7 mm), whereas in the CBA group the gain was similar to that achieved following rotational atherectomy and following PTCA (1.70 ± 0.6 mm versus 1.79 ±0.5 mm and 1.56 ± 0.7 mm, respectively; p = NS). The lumen loss at follow-up was lower for CBA versus either rotational atherectomy or stenting (0.63 ± 0.6 mm versus 1.30 ± 0.8 mm and 1.36 ± 0.8 mm, respectively; p CBA in combination with vascular brachytherapy. The impact of CBA in combination with VBT for the treatment of ISR compared with conventional PTCA and VBT is a subject of ongoing study. We recently reported data from our institution which showed that the strategy of CBA and VBT using Sr-90 for ISR was associated with similar procedural and clinical outcomes compared to PTCA and VBT. In this study, the baseline demographics, angiographic characteristics and clinical outcomes of 102 consecutive patients with ISR treated either with CBA and VBT (n = 45) or with conventional PTCA and VBT (n = 57) were compared. The combined endpoint was the occurrence of MACE, which was defined as a composite of death, myocardial infarction (MI) or target vessel revascularization (TVR) at 6 months. The CBA + VBT Group had a shorter mean lesion length (14.3 ± 6.5 mm versus 21.1 ± 15.7 mm; p = 0.009), and greater utilization of glycoprotein IIb/IIIa inhibitors during the procedure (48.9% versus 26.3%; p = 0.02) compared to the PTCA + VBT Group. There were no significant differences in the baseline demographics, angiographic and procedural results, or subsequent MACE at 6 months between the two groups. Thus, this retrospective study did not demonstrate an advantage of CBA and VBT over routine PTCA and VBT. Current study. The study by Orford et al. in this issue of the Journal of Invasive Cardiology provides further insight into the various issues surrounding the use of CBA in a broad population of patients, but particularly for the treatment of ISR in combination with VBT. See Orford et al. on pages 720–724 The study consisted of 103 procedures involving 114 lesions performed at the Mayo Clinic. ISR was the most common indication for CBA, and the majority were also treated with VBT. The authors concluded that the strategy of CBA was feasible and safe and was associated with a low incidence of procedural complications and in-hospital adverse cardiac events when used primarily for ISR. Although this study demonstrated encouraging results for CBA, the authors emphasized several caveats. This was a retrospective study, and as a result, case selection and operator bias may have accounted for some of the findings. Furthermore, whether similar results could have been demonstrated in the treatment of more complex lesions, such as bifurcating, ostial, calcified, tortuous or smaller vessels, is uncertain. In a small but not insignificant number of patients, the device could not be advanced to the site of the lesion, and one wonders whether the incidence of failed device delivery may have been even higher if patients with more high-risk coronary anatomy were enrolled. Although the study provides important information on the acute angiographic results and peri-procedural adverse events after CBA, assessment of long-term angiographic and clinical outcomes would have provided further insight into the efficacy of this device in current practice. Moreover, although CBA was used as the primary modality for ISR, a large number of patients (73%) required treatment with a second device, such as additional balloon angioplasty (39%) or stent placement (34%), raising doubts about the potential advantageous effects of CBA. Furthermore, it is unclear how many patients in this cohort required pre-dilation with a standard balloon prior to treatment with CBA. Thus, this study describes the peri-procedural outcomes of selected patients with mostly ISR who were treated with CBA, but it does not address the utility of this device for the treatment of more complex coronary anatomy or smaller vessels. The study highlights one of the major limitations of CBA, which is the need for adjunctive PTCA or stenting in the majority of patients, and leaves unanswered the important question of whether CBA is better or worse than plain old balloon angioplasty for the treatment of ISR, particularly in combination with VBT. Mechanisms of CBA and clinical implications. The lack of proven benefit with CBA in large clinical trials compared to standard balloon angioplasty is striking. For the treatment of ISR, previous studies have shown that additional stent expansion, neointimal tissue ablation and neointimal tissue extrusion through the stent struts are the main mechanisms of luminal gain using various interventional techniques. Additional stent expansion is the primary mechanism involved during conventional high-pressure PTCA, and from a mechanical perspective, this effect may be the most important factor for decreasing subsequent restenosis during treatment of ISR. This proposed mechanism has also been used as the explanation for why rotational atherectomy, which primarily results in neointimal tissue ablation without stent overexpansion, was not superior to PTCA for the treatment of ISR in the large, randomized ARTIST Trial. Similarly, for the treatment of ISR lesions prior to VBT, there appears to be no added utility of debulking devices in the reduction of restenosis compared to high-pressure PTCA. What is the primary mechanism of CBA during treatment of ISR lesions? Intravascular ultrasound analysis by Ahmed et al. demonstrated that luminal enlargement after treatment of ISR with CBA, unlike conventional PTCA, is due primarily to neointimal extrusion through the stent struts with some axial redistribution with very little additional stent expansion. The authors proposed that extrusion of the tissue through the stent is facilitated by the division of the neointima into smaller parts by the sharp microtomes of the balloon. Thus, although CBA theoretically results in less intimal injury and decreases geographic miss by decreasing the mismatch between the injured and irradiated arterial segments, the lack of significant additional stent expansion with CBA may be the reason why a reduction in long-term restenosis rates has not been demonstrated for CBA for the treatment of ISR, with or without VBT, compared to conventional PTCA. Therapeutic modalities for ISR targeted specifically at decreasing neointimal proliferation at the molecular level, such as intracoronary brachytherapy and drug-eluting stents, have been shown to be the most effective treatment options for lowering subsequent restenosis, and the incremental value of a mechanical interventional device such as CBA in this setting remains to be proven. In summary, although CBA has several theoretical advantages that make it particularly appealing for the treatment of coronary stenosis, the precise indications for the utilization of this device as well as the patient subsets who derive benefit from this approach are yet unidentified. Although several randomized clinical trials performed to date comparing CBA to conventional PTCA have shown that CBA is safe and feasible for both de novo coronary lesions and ISR, significant benefits in terms of decreased long-term MACE or angiographic restenosis have not been demonstrated, other than perhaps in smaller vessels. Furthermore, rare, serious complications have been reported with CBA. Whether newer-generation cutting balloon devices with smaller profiles or treatment with higher inflations might result in improved clinical and angiographic outcomes requires further study. The role of CBA in the era of drug-eluting stents is especially ambiguous. Other situations to consider CBA include those in which an increased restenosis rate is anticipated, such as bifurcation lesions and in combination with VBT for ISR. Clearly, further investigation is needed to evaluate the role of CBA in these and other specific scenarios, and to determine whether increased use of CBA would be a cost-effective strategy, resulting in greater or less need for additional interventional devices. In the absence of convincing data from large randomized trials demonstrating clear benefits, the widespread utilization of CBA for all “resistant” coronary lesions appears premature and cannot be defended. CBA may actually offer no clinically relevant advantage over plain old balloon angioplasty in either native vessels or for ISR despite its many theoretical advantages, and that may be, as Shakespeare so eloquently phrased it, “the most unkindest cut of all”.