Summary
Percutaneous coronary interventions of calcified coronary lesions are associated with worse clinical outcomes compared with noncalcified lesions and are still considered a technical challenge for interventional cardiologists. Rotational atherectomy (RA) can effectively optimize lesion preparation through plaque modification of heavily calcified coronary lesions. However, in conventional balloon angioplasty and bare metal stent eras, the use of RA was not associated with a significant improvement in restenosis and target lesion revascularization in patients with calcified lesions. Drug-eluting stents (DES) dramatically reduced the rates of restenosis and major adverse cardiac events. In the DES era, the need for RA is therefore questionable. Recently, some studies have reported clinical outcomes of patients with calcified lesions treated with DES and RA. In this article, we aim to critically review results from these randomized and observational clinical studies assessing the use of RA in the DES era.
1
Introduction
Coronary calcified lesions are associated with a higher procedural risk and worse clinical outcomes compared with noncalcified lesions . Appropriate plaque modification by rotational atherectomy (RA) allows safe and effective stent deployment. In the current era of percutaneous coronary intervention (PCI) with drug-eluting stents (DES), the use of RA is infrequent (3% to 5% of the procedures) . Although the potential synergy of both technologies is of interest, little scientific evidence exists regarding the merits and caveats of this combination in the current era. In this manuscript, we review the evidence for using RA and the scientific data regarding the combination of RA and DES in the treatment of calcified lesions.
2
Pathological characteristics of calcified lesions and implications for PCI
Coronary calcifications often occur in the intimal or medial layer of the arterial and increase the stiffness degree of the vessel . Although the correlation between calcification and plaque stability is controversial , the intimal and medial calcifications are clearly associated with atherosclerosis, which is characterized by inflammation, fibrosis, and lipid accumulation . A pathological analysis from cadavers revealed that 83% of the severely calcified coronary lesions contained extensive necrotic tissue with large numbers of cholesterol crystals, and 89% of the severely calcified coronary lesions had fibrofatty tissue with calcification .
The incidence of cardiovascular death or nonfatal myocardial infarction (MI) increases with higher coronary artery calcium scores . In the practice of PCI, calcified lesions often require high pressure expansion, which significantly increases the likelihood of dissection, perforation, and balloon rupture. The characteristic of high stiffness from calcification may lead to the failure of stent delivery and stent underexpansion. In addition, the advancement of DES across calcified plaque may cause polymer damage to the drug coating and inadequate drug diffusion to the vessel wall , which may increase the risk of stent thrombosis and restenosis. Compared with noncalcified lesions, calcified lesions have a higher risk of procedure failure and are associated with more major adverse myocardial events (MACE) during long-term follow-up. Thus, they remain a unique challenge for interventional cardiologists .
3
Basic principle and application progress of RA
To obtain optimal stent deployment, adequate lesion preparation is essential for patients with calcified lesions . Proposed as a device for lesion preparation, RA was first introduced in 1986 and has been used for over 25 years. Based on the principle of “differential cutting” and “orthogonal displacement of friction,” RA uses a rotating diamond shaped burr to pulverize the rigid calcified plaque, reduce the plaque burden, and modify the calcified lesion compliance . The luminal morphology of the lesions treated by RA is smooth, nonendothelialized, and completely different from those treated by balloon angioplasty, in which the increase in lumen diameter is achieved through squeezing plaque and stretching vessel . RA has been utilized in all main PCI eras: the balloon angioplasty era, the bare metal stents (BMS) era, and the DES era.
In the balloon angioplasty era, several clinical studies, including the Comparison of Balloon vs. Rotational Angioplasty (COBRA) study and the Excimer Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison (ERBAC) study, showed that the restenosis rate of lesions treated with RA was > 37% and similar to that with balloon angioplasty. During the BMS era, several studies demonstrated a higher procedural success rate and a trend toward lower restenosis in calcified lesions treated with RA prior to stenting vs. stenting without RA. Although there was a lower restenosis trend, the restenosis rate with RA prior to BMS remained as high at 20% to 30% .
In the DES era, neointimal formation was significantly inhibited, and the rates of restenosis and target lesion revascularization (TLR) were dramatically reduced in calcified and noncalcified lesions . In theory, the combined use of RA and DES in calcified lesions should be considered as a reasonable strategy, and as a result, some clinical studies were reported in the recent years. In this article, we will review these clinical studies and evaluate the utilization of RA in the DES era.
2
Pathological characteristics of calcified lesions and implications for PCI
Coronary calcifications often occur in the intimal or medial layer of the arterial and increase the stiffness degree of the vessel . Although the correlation between calcification and plaque stability is controversial , the intimal and medial calcifications are clearly associated with atherosclerosis, which is characterized by inflammation, fibrosis, and lipid accumulation . A pathological analysis from cadavers revealed that 83% of the severely calcified coronary lesions contained extensive necrotic tissue with large numbers of cholesterol crystals, and 89% of the severely calcified coronary lesions had fibrofatty tissue with calcification .
The incidence of cardiovascular death or nonfatal myocardial infarction (MI) increases with higher coronary artery calcium scores . In the practice of PCI, calcified lesions often require high pressure expansion, which significantly increases the likelihood of dissection, perforation, and balloon rupture. The characteristic of high stiffness from calcification may lead to the failure of stent delivery and stent underexpansion. In addition, the advancement of DES across calcified plaque may cause polymer damage to the drug coating and inadequate drug diffusion to the vessel wall , which may increase the risk of stent thrombosis and restenosis. Compared with noncalcified lesions, calcified lesions have a higher risk of procedure failure and are associated with more major adverse myocardial events (MACE) during long-term follow-up. Thus, they remain a unique challenge for interventional cardiologists .
3
Basic principle and application progress of RA
To obtain optimal stent deployment, adequate lesion preparation is essential for patients with calcified lesions . Proposed as a device for lesion preparation, RA was first introduced in 1986 and has been used for over 25 years. Based on the principle of “differential cutting” and “orthogonal displacement of friction,” RA uses a rotating diamond shaped burr to pulverize the rigid calcified plaque, reduce the plaque burden, and modify the calcified lesion compliance . The luminal morphology of the lesions treated by RA is smooth, nonendothelialized, and completely different from those treated by balloon angioplasty, in which the increase in lumen diameter is achieved through squeezing plaque and stretching vessel . RA has been utilized in all main PCI eras: the balloon angioplasty era, the bare metal stents (BMS) era, and the DES era.
In the balloon angioplasty era, several clinical studies, including the Comparison of Balloon vs. Rotational Angioplasty (COBRA) study and the Excimer Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison (ERBAC) study, showed that the restenosis rate of lesions treated with RA was > 37% and similar to that with balloon angioplasty. During the BMS era, several studies demonstrated a higher procedural success rate and a trend toward lower restenosis in calcified lesions treated with RA prior to stenting vs. stenting without RA. Although there was a lower restenosis trend, the restenosis rate with RA prior to BMS remained as high at 20% to 30% .
In the DES era, neointimal formation was significantly inhibited, and the rates of restenosis and target lesion revascularization (TLR) were dramatically reduced in calcified and noncalcified lesions . In theory, the combined use of RA and DES in calcified lesions should be considered as a reasonable strategy, and as a result, some clinical studies were reported in the recent years. In this article, we will review these clinical studies and evaluate the utilization of RA in the DES era.
4
Identification of studies
Previous reports written in English were searched in PubMed databases on March 31, 2014. The following search terms were used: drug-eluting stent, sirolimus, paclitaxel, zotarolimus, everolimus, and biolimus. In addition, the following terms were used to identify: rotational atherectomy, rotablation, rotablator. A total of 162 abstracts were initially identified and were further evaluated individually. To focus the present work on original randomized and observational studies, the following articles were excluded: reviews, case reports, letters. All full-text articles were then evaluated once more, and those articles were excluded if the number of reported cases was below fifty.
5
Clinical studies regarding RA and DES
5.1
Data from noncontrolled observational clinical studies
Noncontrolled, observational clinical studies regarding RA and DES are shown in Table 1 . In these studies , the rate of procedural and angiographic success was achieved in more than 92.5% of the cases. During the follow-up period of 14–49 months, MACE rates varied from 4.4% to 17.7%, mainly driven by TLR, which was less than 10% in most of the studies. Abdel-Wahab et al. reported the highest MACE rate (17.7%); however, the TLR rate (6.8%) and definite cardiac death rate (3.7%) were comparable to other studies, and noncardiac/unknown death accounted for 5.3%. Patients of these studies were particularly old and had complex lesions as well as more risk factors of cardiac events. Therefore, the long-term clinical outcomes were considered inspiring and demonstrated the feasibility and efficacy of RA associated with DES implantation in such a subset of the population.
| Trial | Patient Number (N) | Burr/artery Bur size (mm) | Angiographic/ Procedure Success (%) | In-hospital MACE/Death (%) | MACE/TLR (%, FU) | ST (%) | Procedural events (%) |
|---|---|---|---|---|---|---|---|
| Furuichi et al.; 2009 | 95 | 0.58 ± 0.14 1.48 ± 0.18 | 99/95.8 | 3.2/0 | 15.8/9.5 14.7 mo | Late ST: 2.1: definite 2.1: probable | slow-flow: 1.0 perforation: 1.0 dissection: 2.0 |
| Mezilis et al.; 2010 | 150 | 0.6–0.7 1.25–2.2 | 98/98 | 0/0 | 11.3/2.2 3 y | N/A | N/A |
| Benezet et al.; 2011 | 102 | 0.56 ± 0.1 1.5 ± 0.2 | 99/97 | 2.9/0.9 | 12.7/8.8 15 mo | Early ST: 2.9: definite 1.9: probable | dissection: 2.9 |
| Dardas et al.; 2011 | 184 | ≤ 0.6–0.7 ≥ 1.25 | 97.3/97.3 | 0/0 | 14.9/2.8 49 mo | N/A | N/A |
| Jiang et al.; 2012 | 253 | 0.55 ± 0.08 1.5–1.75 | 100/98 | 2.0/0.8 | 4.4/3.2 3 y | N/A | perforation: 0.8 dissection: 1.2% slow-flow: 2.0 |
| Abdel-Wahab et al.; 2013 | 205 | 0.43–0.57 1.5–1.75 | 98.1/95.6 | 4.4/1.5 | 17.7/6.8 15 mo | 1.0 | slow-flow: 2.0 perforation: 1.0 |
| Chiang et al.; 2013 | 67 | 0.6 ± 0.1 1.60 ± 0.2 | 100/92.5 | 7.5/7.5 | 17.9/10.4 23.3 mo | 1.5 | N/A |
In previous studies, RA was more likely to cause vascular spasm, perforation, and transient vessel occlusions compared with balloon angioplasty before the DES era . However, complications correlated with RA were infrequent among the present studies in the DES era, including dissection (1.2% to 2.9%), slow flow/no flow (1.0% to 2%), and perforation (0.8% to 1.0%). In consideration of the difficulty in treating heavily coronary calcified lesions (HCCLs) with conventional devices and low occurrence of RA-related complications, RA remains an important tool in overcoming the challenge from HCCLs.
The occurrence of definite and probable stent thrombosis fluctuated significantly among the studies, from 1% to 4.8%. These rates are higher compared with those usually observed in noncalcified lesions . Heavily complex lesions and severe clinical presentation might contribute to this finding. In addition, the accuracy of stent-thrombosis occurrence may be affected by retrospective analysis and limited sample size of these clinical studies.
5.2
Data from controlled studies: RA and DES vs. DES alone
Despite inspiring outcomes in the combination of DES and RA, it was not clear whether the results were attributed to the combination of the two devices or were solely related to DES alone. In other words, are there differences between RA plus DES and DES alone?
Two clinical studies compared the outcomes in patients receiving DES with or without RA use. In the report from Clavijo et al. , despite a higher proportion of complex type C lesions in the sirolimus-eluting stent (SES) and RA group (48.1% vs. 30.4%, P = 0.001), no differences were found in clinical success rate (both > 98%), in-hospital and 6-month follow-up outcomes between the two groups. ROTAXUS study (Rotational Atherectomy Prior to TAXUS Stent Treatment for Complex Native Coronary Artery Disease) was a multicenter, prospective, randomized trial comparing the safety and efficacy of RA followed by paclitaxel-eluting stent (PES, n = 120) with PES alone (n = 120) in patients with complex calcified coronary lesions. With similar baseline characteristics, higher crossover rate was recorded in the PES group (12.5% vs. 4.2%, P = 0.02), which translated into higher strategy success rate in the PES and RA group (92.5% vs. 83.3%, P = 0.03). At 9 months, late lumen loss was greater in patients treated with PES and RA (0.44 ± 0.58 vs. 0.31 ± 0.52 mm, P = 0.04), while clinical outcomes were similar in both groups. The principal finding of the study was that the combination of PES and RA is not superior to PES alone in reducing late lumen loss at 9 months.
RA can ablate plaques, obtaining greater lumen diameter, but pays the price of greater lumen injury, which may result in more neointimal formation. Potential clinical significance in ROTAXUS study included: (1) RA can’t improve the anti-proliferative effect of DES; however, it remained to be an important tool to treat complex HCCLs and significantly improved the procedural success; (2) RA may be associated with greater neointimal hyperplasia and thus should be used as a default strategy for complex calcified lesions, such as HCCLs, un-crossable, or un-dilatable lesions.
5.3
Advantages of DES compared with BMS for HCCLs treated with RA
DESs have dramatically reduced the rates of restenosis, TLR, and MACE in different lesion types; however, whether DESs have superiority compared with BMS in calcified lesions treated with RA needs to be further clarified. Clinical studies regarding DES and RA vs. BMS and RA are shown in Table 2 .
