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Orbital Atherectomy for the Treatment of Long (≥25–40 mm) Severely Calcified Coronary Lesions: ORBIT II Sub-Analysis
CARREV-01789; No of Pages 7 Cardiovascular Revascularization Medicine xxx (xxxx) xxx
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Cardiovascular Revascularization Medicine
Orbital atherectomy for the treatment of long (≥25–40 mm) severely calcified coronary lesions: ORBIT II sub-analysis Gautam Kumar a,⁎, Eric Youngyoon Shin a, Rajesh Sachdeva a, Evan Shlofmitz b, Ann N. Behrens c, Brad J. Martinsen c, Jeffrey W. Chambers d a
Division of Cardiology, Emory University and Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, USA Department of Clinical and Scientific Affairs, Cardiovascular Systems, Inc., St. Paul, MN, USA d Metropolitan Heart and Vascular Institute, Mercy Hospital, Minneapolis, MN, USA b c
a r t i c l e
i n f o
Article history: Received 17 September 2019 Received in revised form 17 December 2019 Accepted 23 December 2019 Available online xxxx Keywords: Atherectomy Calcification Percutaneous coronary intervention Long lesions
a b s t r a c t Background: Orbital atherectomy (OA) is an effective method of lesion preparation of severely calcified vessels prior to stent deployment. Long calcified lesions may lead to higher risk of post-procedural complications, yet the optimal treatment strategy has not been established. In this study we sought to determine the safety and efficacy of OA in patients with long (≥25–40 mm) calcified target lesions. Methods: ORBIT II was a single-arm trial that enrolled 443 patients at 49 U.S. sites. De novo, severely calcified coronary lesions were treated with OA prior to stenting. Patients treated with the OA device were stratified into two groups according to target lesion length as visually estimated by the investigator: those with short (b25 mm; N = 314) vs. long (≥25–40 mm; N = 118) lesions. Lesions N40 mm were excluded per protocol. The primary endpoint was the 3-year major adverse cardiac event (MACE) rate, defined as a composite of cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR). Results: The 3-year MACE rates in patients with short (b25 mm) vs. long (≥25–40 mm) lesions were 21.1% vs. 29.9% respectively (p = 0.055). The rate of cardiac death (6.5% vs. 7.8%, p = 0.592) and TVR (8.5% vs. 13.7%, p = 0.153) did not significantly differ. The rate of MI (CK-MB N 3× ULN) at 3 years was significantly higher in patients with long (≥25–40 mm) lesions (9.0% vs. 17.0%, p = 0.024), with the majority occurring in-hospital (7.0% vs. 13.6%, p = 0.037). Conclusions: Patients with long (≥25–40 mm) calcified target lesions had similar outcomes in terms of MACE at 3 years despite higher rates of MI, which mostly occurred in-hospital. Using the more contemporary SCAI definition of MI, there was no significant difference in rates of MI between the short (b25 mm) and long (≥25–40 mm) groups. Further studies are warranted to determine how OA compares to focal force balloon angioplasty, rotational atherectomy and other novel treatment options for long severely calcified lesions. Summary for annotated table of contents: Percutaneous coronary intervention of long calcified lesions is inherently more complex and higher risk and may require more intensive lesion preparation. This sub-analysis of ORBIT II revealed that orbital atherectomy treatment of longer (≥25–40 mm) lesions was associated with a higher rate of MACE at 30 days, but not at 3 years. This difference, however, was driven primarily by a higher in-hospital non-Q-wave MI rate; using the more contemporary SCAI definition of MI, there was no significant difference in rates of MI between the short (b25 mm) and long (≥25–40 mm) groups. Published by Elsevier Inc.
Abbreviations: BMS, bare metal stent; CABG, coronary artery bypass graft; CK-MB, creatine kinase-myocardial band; CSI, Cardiovascular Systems, Inc.; DES, drug eluting stent; eGFR, estimated glomerular filtration rate; IVUS, intravascular ultrasound; LAD, left anterior descending artery; LCX, left circumflex artery; MACE, major adverse cardiac events; MI, myocardial infarction; MLD, minimal luminal diameter; OA, orbital atherectomy; OAS, orbital atherectomy system; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; RCA, right coronary artery; RVD, reference vessel diameter; SCAI, Society for Cardiovascular Angiography and Interventions; TLR, target lesion revascularization; TVR, target vessel revascularization; ULN, upper limit of normal. ⁎ Corresponding author at: Division of Cardiology, Emory University and Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA 30033, USA. E-mail addresses: [email protected] (G. Kumar), [email protected] (E.Y. Shin), [email protected] (R. Sachdeva), [email protected] (A.N. Behrens), [email protected] (B.J. Martinsen), [email protected] (J.W. Chambers).
https://doi.org/10.1016/j.carrev.2019.12.027 1553-8389/Published by Elsevier Inc.
Please cite this article as: G. Kumar, E.Y. Shin, R. Sachdeva, et al., Orbital atherectomy for the treatment of long (≥25–40mm) severely calcified coronary lesions: ORBIT ..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.12.027
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G. Kumar et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx
1. Introduction
2.3. Study device
Significant coronary artery calcifications affect N70% of all target lesions, when studied by intravascular ultrasound (IVUS) [1]. Arterial calcium poses a significant barrier to successful percutaneous coronary intervention (PCI) both in terms of technical difficulty as well as postprocedural complications [2–5]. The ORBIT II trial demonstrated that orbital atherectomy (OA) (Diamondback 360®, Cardiovascular Systems, Inc. [CSI], St. Paul, MN) is safe and effective in the pretreatment of calcified lesions for enabling successful stent deployment without eliciting undue risk of major adverse cardiac events (MACE) at either 30 days or 3 years following the index procedure [6,7]. In this study, we sought to perform a subgroup analysis of the ORBIT II trial with specific focus on longer (≥25–40 mm) lesions, as there is currently limited published data regarding use of OA in this subgroup. PCI of longer target lesions is known to be associated with worse clinical outcomes, likely due to extensive manipulation and injury to the arterial luminal wall causing exaggerated neointimal hyperplasia [8–10]. Operators may thus be understandably cautious in approaching these longer lesions with OA due to the potential for longer treatment time and the possible increase in embolic material. In the ORBIT II study, the myocardial infarction (MI) rate was 2.0% using the Society for Cardiovascular Angiography and Interventions (SCAI) definition of clinically relevant MI after PCI [11,12]; however, outcomes were not reported specifically for long lesions. Therefore, we evaluated procedural outcomes and MACE for up to 3 years in this clinically challenging but important subgroup.
The coronary orbital atherectomy system (OAS) modifies calcified plaque to facilitate stent delivery and to help optimize stent expansion in severely calcified arteries. The mechanism of action is differential sanding of coronary calcification: the diamond-coated crown's orbital diameter expands radially via centrifugal force and provides proximal and distal sanding to modify the plaque, increasing the lumen size and vessel compliance. As the crown is moved through the lesion, an increase in time in contact with the lesion, rotational speed, or number of passes allows for an increase in luminal gain. The healthy elastic tissue flexes away from the crown, minimizing damage to the vessel wall. The elliptical orbit allows blood and micro-particulate to flow past the crown and be dispersed, lowering the risk of thermal injury [18]. The orbital atherectomy device is designed to track and spin only over the ViperWire (CSI). Continual infusion of saline and ViperSlide lubricant (CSI) is critical for safe OAS operation; the ViperSlide lubricant is required for cooling and lubricating the orbital atherectomy device during use to reduce the risk of overheating.
2. Methods 2.1. Study design and population
2.4. Study procedure One target lesion was treated per patient. Investigators were required to implant an FDA-approved stent after performing orbital atherectomy and were not allowed to use thrombectomy, embolic protection devices, brachytherapy, or cutting balloons. Pre-dilatation after atherectomy and post-dilatation after stenting was left to the discretion of the operator. Quantitative coronary angiography (QCA) was not required for Investigator-reported angiographic data points. 2.5. Study endpoints
The study design of ORBIT II has been previously described [6]. It was a prospective, non-blinded, single-arm study conducted in 49 U.S. centers that enrolled 443 patients with severely calcified coronary lesions undergoing PCI between May 25, 2010, and November 26, 2012. The trial conformed to good clinical practice and the applicable U.S. Code of Federal Regulations. Each site received approval from its respective institutional review board and all subjects signed informed consent. The ORBIT II key inclusion criteria were: (1) target vessel reference diameter ≥2.5 mm and ≤4.0 mm with a stenosis ≥70% and b100% or a stenosis ≥50% and b70% with evidence of clinical ischemia via either positive stress test, fractional flow reserve value ≤0.8, or IVUS minimum lumen area ≤4.0 mm2; (2) target lesion length ≤40 mm; and (3) evidence of severe calcium at the lesion site based on the angiographic presence of radio-opacities noted without cardiac motion prior to contrast injection, involving both sides of the arterial wall in at least one location, total length of calcium of ≥15 mm and extending partially into the target lesion; or presence of ≥270° of calcium at one cross section via IVUS. The exclusion criteria included: (1) the target vessel had a stent from a previous PCI unless the stent was on a different branch than the target lesion and was implanted N30 days prior with no higher than 30% in-stent restenosis; (2) recent MI, defined as creatine kinase N1 times upper limit of normal (ULN) within 30 days before the index procedure; and (3) chronic renal failure unless on hemodialysis, or a serum creatinine level N2.5 mg/dl; and evidence of current left ventricular ejection fraction ≤25%.
Procedural success was defined as angiographically successful stent delivery with residual stenosis b50% without in-hospital major adverse cardiac event (MACE), where MACE is defined as the composite of cardiac death, MI, or target vessel revascularization (TVR). MI was defined as creatine kinase-myocardial band (CK-MB) N3 times ULN with or without new pathological Q-wave. TVR was defined as repeat revascularization of the target vessel (inclusive of the target lesion) after completion of the index procedure. The rate of MI was also calculated using the SCAI definition of clinically relevant MI after PCI [12]. An independent clinical events committee adjudicated adverse events and severe angiographic complications including persistent slow flow/no reflow and abrupt closure; dissections and perforations were reported by the angiographic core lab (Cleveland Clinic Foundation, Cleveland, Ohio). Additionally, final minimal luminal diameter (MLD) and percent stenosis were determined by the angiographic core lab using computerassisted quantitative coronary angiography (QCA) software with an automated edge-detection system (PIE Medical Imaging, The Netherlands). All images were acquired immediately post nitroglycerin administration. An image of the contrast-filled catheter tip was necessary for calibration. To generate reference vessel diameter (RVD) measurements, segments immediately adjacent to the treated vessel area (one proximal and one distal, each within 5 mm of the treated area) were manually chosen and measured with the QCA software. The program calculated all segment statistics based on the frame's calibration factor. The QCA procedure was repeated for the matching orthogonal view.
2.2. Study population
2.6. Statistical analysis
Subjects treated with the OA device were stratified according to target lesion length as visually estimated by the investigator: short (b25 mm; N = 314) and long (≥25–40 mm; N = 118). The definition of long lesion as ≥25 mm was chosen based on other published studies that used a similar definition [13–17].
Continuous variables are expressed as mean ± standard deviation and categorical variables are presented as proportions. Wilcoxon rank sum test and Fisher's exact test were used to compare continuous and categorical variables, respectively. The Kaplan–Meier method was used to construct survival curves for the time-to-event variables;
Please cite this article as: G. Kumar, E.Y. Shin, R. Sachdeva, et al., Orbital atherectomy for the treatment of long (≥25–40mm) severely calcified coronary lesions: ORBIT ..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.12.027
G. Kumar et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx
event rates were compared using the Cox proportional hazards model. A p-value b 0.05 was considered statistically significant. Statistical analyses were performed with either SAS Software System (SAS Institute Inc., Cary, NC, USA) or R (R Core Team 2014).
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8.4%, p = 0.002) in the long (≥25–40 mm) group. Long (≥25–40 mm) lesions also had longer total length of calcium (26.2 ± 15.5 mm vs. 34.1 ± 13.1 mm, p b 0.001) (Table 2). 3.3. Procedural results
3. Results 3.1. Patient demographics and clinical history There were no significant differences in baseline demographics between the patients with short (b25 mm) vs. long (≥25–40 mm) target lesions (Table 1). Clinical characteristics such as medical history of cardiovascular risk factors, atherosclerotic cardiovascular disease, angina, PCI, coronary artery bypass grafting (CABG), and heart failure were similar between groups (Table 1). 3.2. Lesion characteristics As compared with short (b25 mm) lesions, long (≥25–40 mm) lesions less commonly affected the left circumflex artery (LCX) (16.9% vs. 8.5%, p = 0.032), and more commonly involved the right coronary artery (RCA) (25.2% vs. 40.7%, p = 0.002). Pre-procedure MLD was smaller (0.5 ± 0.3 mm vs. 0.4 ± 0.3 mm, p = 0.001) and preprocedure percent stenosis was more severe (83.4 ± 9.0% vs. 86.5 ± Table 1 Population demographics and baseline clinical characteristics.
Age (years) Male Ethnicity Caucasian Black or African American Asian Hispanic or Latino Native American Other BMI eGFR (ml/min/1.73 m2) Smoking No, never Yes, current Yes, former History of diabetes mellitus History of dyslipidemia History of hypertension History of stroke/TIA History of MI History of angina For subjects with history of angina, type Stable Unstable History of PCI History of CABG LVEF (%) NYHA classification of heart failure No history of heart failure Class I Class II Class III Class IV
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
p-Value
71.6 ± 9.9 199 (63.4)
71.3 ± 10.0 79 (66.9)
0.6925 0.5015 0.7375
277 (88.2) 17 (5.4) 7 (2.2) 9 (2.9) 1 (0.3) 3 (1.0) 29.2 ± 5.8 76.3 ± 26.2 (N = 312)
105 (89.0) 6 (5.1) 1 (0.8) 6 (5.1) 0 (0.0) 0 (0.0) 29.7 ± 5.9 74.0 ± 26.6
105 (33.4) 47 (15.0) 162 (51.6) 112 (35.7) 292/313 (93.3) 288 (91.7) 26/313 (8.3) 68/311 (21.9) 243 (77.4)
39 (33.1) 23 (19.5) 56 (47.5) 43 (36.4) 106 (89.8) 107 (90.7) 13 (11.0) 26/116 (22.4) 96 (81.4)
155 (63.8) 88 (36.2) 145/311 (46.6) 45 (14.3) 56.6 ± 9.5 (N = 309) N = 312
62 (64.6) 34 (35.4) 53/117 (45.3) 19 (16.1) 56.5 ± 9.8 (N = 117) N = 117
22 (7.1) 183 (58.7) 106 (34.0) 1 (0.3) 0 (0.0)
5 (4.3) 61 (52.1) 50 (42.7) 1 (0.9) 0 (0.0)
Compared with short (b25 mm) lesions, long (≥25–40 mm) lesions required more total OAS device run time (60.3 ± 36.8 s vs. 84.2 ± 60.2 s, p = 0.0002) and longer average OAS individual device run time (19.1 ± 5.7 s vs. 20.5 ± 5.3 s, p = 0.039). There was no significant difference in post-OAS MLD or post-OAS residual stenosis (Table 3). There were more post-OAS stents used per subject in the long (≥25– 40 mm) lesion group (1.1 ± 0.4 vs. 1.6 ± 0.7, p b 0.0001) and higher stent maximum deployment pressure (13.6 ± 3.1 atm vs. 14.3 ± 3.2 atm, p = 0.032), but no difference in percentage of drug eluting stents (DES) used or post-stent residual stenosis. Long (≥25–40 mm) lesions were associated with longer total procedure time (49.6 ± 26.9 min vs. 57.6 ± 33.5 min, p = 0.033), longer total fluoroscopy time (16.5 ± 10.1 min vs. 21.3 ± 15.1 min, p = 0.0005), and increased total contrast volume (166.3 ± 81.4 ml vs. 189.1 ± 91.6 ml, p = 0.017). There was no difference in final procedure MLD or final procedure stenosis. Procedural success was achieved in 91.7% and 83.9% in the short (b25 mm) and long (≥25–40 mm) groups, respectively (p = 0.022). Although rates of in-hospital cardiac death or TVR did not differ, the long (≥25–40 mm) group had a higher rate of in-hospital MACE (8.0% vs. 15.3%, p = 0.03) due to a significantly higher rate of in-hospital nonQ-wave MI (CK-MB N 3× ULN) (7.0% vs. 13.6%, p = 0.037) (Table 4). The rate of severe angiographic complications was higher in the long (≥25–40 mm) group (4.8% vs. 11.9%, p = 0.016). The incidence of perforation, persistent slow flow/no reflow, and abrupt closure were similar in both groups; the severe dissection rate trended higher in the long (≥25–40 mm) group (1.9% vs. 5.9%, p = 0.051) (Table 5). 3.4. 30-day and 3-year MACE
0.4719 0.6392 0.5058
0.9106 0.2285 0.7034 0.4510 0.8962 0.4312 1.0000
0.8285 0.6501 0.8447 0.2306
Values are n (%) or mean ± standard deviation (SD); BMI = body mass index; CABG = coronary artery bypass graft; CCS = Canadian Cardiovascular Society; eGFR = estimated glomerular filtration rate; LAD = left anterior descending artery; LCX = left circumflex artery; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association; PCI = percutaneous coronary intervention; RCA = right coronary artery; TIA = transient ischemic attack.
There was a significant difference in 30-day MACE following revascularization of short (b25 mm) and long (≥25–40 mm) lesions (8.3% vs. 16.1%, p = 0.024). Compared to short (b25 mm) target lesions, treatment of long (≥25–40 mm) target lesions led to a significantly higher rate of MI (7.6% vs. 15.3%, p = 0.024), although there was no difference in rates of cardiac death or TVR (Table 6, Fig. 1A–D). The MACE rates at 1 and 2 years were similar in both groups (1 year: 15.5% vs. 20.3%, p = 0.208; 2 years: 17.8% vs. 25.5%, p = 0.078). At 3 years, the rates of MACE following revascularization of short (b25 mm) target lesions compared to long (≥25–40 mm) lesions were not significantly different (21.1% vs. 29.9%, p = 0.055), nor were individual components of cardiac death (6.5% vs. 7.8%, p = 0.592) and TVR (8.5% vs. 13.7%, p = 0.153). However, there was a significantly increased rate of MI in the long (≥25–40 mm) group (9.0% vs. 17.0%, p = 0.024) (Table 6, Fig. 1A–D). 4. Discussion Our findings suggest that orbital atherectomy for long (≥25–40 mm) lesions is feasible and the 3-year MACE outcome is comparable to those of short (b25 mm) lesions. In this ORBIT II subgroup analysis, the rates of severe dissection and perforation were numerically higher in the long (≥25–40 mm) group (1.9% vs. 5.9%, p = 0.051 and 1.3% vs. 3.4%, p = 0.222, respectively) and the composite severe angiographic complication rate was significantly higher (4.8% vs. 11.9%, p = 0.016). While not statistically significant, in comparison to short (b25 mm) target lesions the rate of MACE at 3 years was numerically higher in long (≥25–40 mm) lesions (21.1% vs. 29.9%, p = 0.055). The similar rates of MACE at follow-up are consistent with two published coronary atherectomy long lesion studies. In a contemporary multi-center registry of 458
Please cite this article as: G. Kumar, E.Y. Shin, R. Sachdeva, et al., Orbital atherectomy for the treatment of long (≥25–40mm) severely calcified coronary lesions: ORBIT ..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.12.027
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Table 2 Vessel and lesion characteristics.
Target lesion vessel LAD LCX Left main RCA Ramus Pre-procedure target lesion length⁎ (mm) Pre-procedure average RVD⁎ (mm) Pre-procedure MLD⁎ (mm) Pre-procedure percent stenosis⁎ Subjects with calcification determined by angiography only Total length of calcium (including segmented)⁎ (mm) Subjects with calcium visible on both sides of the vessel⁎ Subjects with calcification determined by IVUS Maximum degree of calcium via IVUS (°)
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
167 (53.2) 53 (16.9) 10 (3.2) 79 (25.2) 5 (1.6) 14.3 ± 4.7 3.1 ± 0.4 0.5 ± 0.3 83.4 ± 9.0 286 (91.1) 26.2 ± 15.5 286 (100) 28 (8.9) 294.1 ± 35.5
58 (49.2) 10 (8.5) 0 (0.0) 48 (40.7) 2 (1.7) 31.2 ± 4.9 3.1 ± 0.4 0.4 ± 0.3 86.5 ± 8.4 111 (94.1) 34.1 ± 13.1 111 (100) 7 (5.9) 298.6 ± 42.3
p-Value 0.0030 0.5168 0.0316 0.0684 0.0020 1.0000 b0.0001 0.6416 0.0014 0.0024 0.4285 b0.0001 0.4285 0.6540
Values are n (%) or mean ± standard deviation; IVUS = intravascular ultrasound; LAD = left anterior descending artery; LCX = left circumflex artery; MLD = minimal luminal diameter; RCA = right coronary artery; RVD = reference vessel diameter. ⁎ Visually estimated by the investigator.
patients who underwent OA treatment, long stent length (≥50 mm) was associated with similar major adverse cardiac and cerebrovascular events (MACCE) at 1 year compared to shorter stent length (b50 mm) (14.2% vs 11.5%, p = 0.40) [19]. Similarly, in a post-hoc analysis of the ROTATE registry which included patients undergoing rotational atherectomy, the MACE rate at follow-up (mean: 27.6 ± 22.9 months) did not differ in the longer lesion group (≥25 mm, 28.3%) and shorter lesion group (b25 mm, 28.0%) [13]. In this ORBIT II sub-analysis, the numerically higher rate of 3-year MACE in the long (≥25–40 mm) lesion group was driven primarily by a significantly higher rate of MI (9.0% vs. 17.0%, p = 0.024). Most of these MI events were non-Q-wave MIs and occurred in-hospital (7.0% vs. 13.6%, p = 0.037). Using the contemporary clinically relevant SCAI MI definition [12], there was a trend of increased acute MI in the long (≥25–40 mm) group (1.3% vs. 4.2%, p = 0.067). The observation of higher in-hospital non-Q-wave MI in the long (≥25–40 mm) group could partly be explained by the need for longer procedural times
required to achieve satisfactory post-PCI MLD as compared to shorter lesions. The cumulative effect of longer OAS run times, higher stent deployment pressures, increased number of stents placed, increased calcified particulate that needs to be cleared through the microvasculature and more contrast use per lesion likely lead to an increased chance of biochemical evidence of MI. Although prior investigators have shown that longer lesion length is associated with higher rates of MACE compared to shorter lesions, postprocedural event free survival has not been studied specifically in subjects who have concomitant heavily calcified target lesions. Despite the high risk nature of these lesions, in the ORBIT II study the MACE rate following OA at 2 years (25.5%) is numerically lower than the rate of MACE at 2 years in all subjects with calcified vessels (short or long) undergoing rotational atherectomy (29.4%) [20]. In the rotational atherectomy arm of the ROTAXUS trial, the mean lesion length was 20.6 ± 9.3 mm as compared to 31.2 ± 4.9 mm in the ORBIT II long lesion group [21]. In the more contemporary PREPARE-CALC study which
Table 3 Final overall procedural results.
OAS devices used per subject OAS speed(s) used (rpm) Low only (80,000) Low and high (80,000/120,000) High only (120,000) Total device run time (s) Average individual device run time (s) Post-OAS MLD⁎ (mm) Post-OAS residual stenosis⁎ (%) Subjects treated with post-OAS/pre-stent balloon dilations Post-OAS/pre-stent balloons used per subject Maximum inflation pressure (atm) Time at maximum pressure (s) Subjects with stent placed Post-OAS stents used per subject Types of stents used in study BMS Covered DES Maximum stent deployment pressure (atm) Post-stent residual stenosis⁎ (%) Total procedure time (min) Total fluoroscopy time (min) Total volume of contrast used (ml) Final procedure MLD† (mm) Final procedure stenosis† (%)
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
1.1 ± 0.2
1.1 ± 0.2
65 (20.7) 233 (74.2) 16 (5.1) 60.3 ± 36.8 (N = 313) 19.1 ± 5.7 (N = 312) 1.3 ± 0.6 58.6 ± 17.1 121 (38.5) 1.3 ± 0.6 11.3 ± 3.6 26.0 ± 23.6 311 (99.0) 1.1 ± 0.4
28 (23.7) 84 (71.2) 6 (5.1) 84.2 ± 60.2 20.5 ± 5.3 1.2 ± 0.5 59.0 ± 18.2 56 (47.5) 1.7 ± 1.0 13.4 ± 4.2 (N = 55) 30.7 ± 25.3 (N = 54) 116 (98.3) 1.6 ± 0.7
39/346 (11.3) 0 (0) 307/346 (88.7) 13.6 ± 3.1 (N = 311) 5.1 ± 9.7 (N = 311) 49.6 ± 26.9 16.5 ± 10.1 (N = 310) 166.3 ± 81.4 (N = 313) 2.9 ± 0.5 (N = 304) 4.1 ± 13.0 (N = 313)
20/190 (10.5) 2/190 (1.1) 168/190 (88.4) 14.3 ± 3.2 (N = 114) 7.7 ± 16.0 (N = 115) 57.6 ± 33.5 (N = 117) 21.3 ± 15.1 189.1 ± 91.6 (N = 117) 2.8 ± 0.5 (N = 113) 5.0 ± 16.3
p-Value 0.7029 0.7819
0.0002 0.0386 0.5892 0.8869 0.1003 0.0013 0.0027 0.1418 0.6173 b0.0001 0.2088
0.0323 0.4688 0.0325 0.0005 0.0165 0.2489 0.6277
Values are n (%) or mean ± standard deviation; BMS = bare metal stent; DES = drug eluting stent; MLD = minimal luminal diameter; OAS = orbital atherectomy system. ⁎ Visually estimated by the investigator. † As reported by the Angiographic Core Laboratory.
Please cite this article as: G. Kumar, E.Y. Shin, R. Sachdeva, et al., Orbital atherectomy for the treatment of long (≥25–40mm) severely calcified coronary lesions: ORBIT ..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.12.027
G. Kumar et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx Table 4 Procedural success rates.
Procedural success Stent delivered Residual stenosis b50% In hospital MACE Cardiac death MI Non-Q-wave Q-wave Target vessel revascularization SCAI MI
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Table 6 Cumulative MACE rates (as estimated by Kaplan-Meier). Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
p-Value
288 (91.7) 311 (99.0) 312 (99.4) 25 (8.0) 1 (0.3) 23 (7.3) 22 (7.0) 1 (0.3) 2 (0.6)
99 (83.9) 114 (96.6) 115 (97.5) 18 (15.3) 0 (0.0) 18 (15.3) 16 (13.6) 2 (1.7) 1 (0.8)
0.0218 0.0922 0.1282 0.0302 1.0000 0.0163 0.0371 0.1824 1.0000
4 (1.3)
5 (4.2)
0.0672
Values in n (%); MACE = major adverse cardiac events; MI = myocardial infarction; SCAI = Society for Cardiovascular Angiography and Interventions.
used a new generation ultrathin (60 μm) strut biodegradable polymer Sirolimus-eluting stent (Orsiro, Biotronik AG, Bülach, Switzerland), the mean lesion length and total stent length per lesion were longer respectively at 29.81 ± 15.23 mm and 35.63 ± 15.69 mm in the rotational atherectomy arm (n = 100). The 9-month target vessel failure (TVF) rate was extremely low at 6% [22]; longer term follow-up is awaited. In the ROTAXUS trial, thermal injury due to rotational atherectomy resulting in exaggerated neointimal proliferation was thought to have contributed to increased late lumen loss despite higher initial acute gain. However, in the PREPARE-CALC trial, use of contemporary stents appears to have attenuated this effect. The higher rates of in-hospital MI (CK-MB N 3× ULN) observed following OAS assisted PCI in long lesions can perhaps be mitigated by techniques that may reduce collateral injury to the target vessel during lesion preparation. Of note, there was very limited use of intravascular imaging for assessment of calcification prior to OAS usage in this study, with b10% of all subjects undergoing IVUS. IVUS and optical coherence tomography (OCT) are invaluable tools in complex lesion treatment as these modalities can aid decision making during PCI by allowing for assessment of calcium depth prior to OAS, and ensure adequate vessel preparation, sizing of vessel, and verification of stent coverage post-OAS. Intravascular imaging guidance is consistent with best practices for OAS, and its use is known to reduce MACE following PCI, even in severely calcified vessels [18,23–25]. There may also have been a “learning curve” for orbital atherectomy as the ORBIT II trial represents initial OA use. For example, in the more contemporary OAS registry that included three centers in the United States performing this procedure routinely, the severe dissection (2.6%) and perforation (1.9%) rates reported for the long stent group (≥50 mm) were lower than the rates reported in the ORBIT II long (≥25–40 mm) lesion group [19].
4.1. Study limitations This was a post-hoc sub-analysis of ORBIT II—a non-randomized trial that lacked a control arm. The original trial was not powered to compare efficacy or safety of OAS in patients with varying lengths of target
30-day MACE Cardiac death Myocardial infarction Non-Q-wave Q-wave TVR TVR (non-TLR) TLR 1-year MACE Cardiac death Myocardial infarction Non-Q-wave Q-wave TVR TVR (non-TLR) TLR 2-year MACE Cardiac death Myocardial infarction Non-Q-wave Q-wave TVR TVR (non-TLR) TLR 3-year MACE Cardiac death Myocardial infarction Non-Q-wave Q-wave TVR TVR (non-TLR) TLR
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
p-Value
26 (8.3) 1 (0.3) 24 (7.6)
19 (16.1) 0 (0.0) 18 (15.3)
0.0235 0.9979 0.0237
22 (7.0) 2 (0.6) 3 (1.0) 1 (0.3) 2 (0.6) 48 (15.5) 10 (3.3) 27 (8.6)
16 (13.6) 2 (1.7) 2 (1.7) 1 (0.9) 1 (0.8) 24 (20.3) 4 (3.4) 19 (16.1)
0.0421 0.3261 0.5284 0.4875 0.8158 0.2082 0.9277 0.0311
25 (8.0) 2 (0.6) 16 (5.3) 2 (0.6) 16 (5.3) 55 (17.8) 12 (4.0) 27 (8.6)
17 (14.4) 2 (1.7) 7 (6.1) 4 (3.5) 3 (2.6) 30 (25.5) 8 (6.9) 20 (17.0)
0.0547 0.3261 0.7467 0.0535 0.2565 0.0780 0.2213 0.0181
25 (8.0) 2 (0.6) 21 (7.0) 4 (1.4) 19 (6.3) 64 (21.1) 19 (6.5) 28 (9.0)
18 (15.3) 2 (1.7) 11 (9.8) 5 (4.4) 6 (5.3) 35 (29.9) 9 (7.8) 20 (17.0)
0.0326 0.3261 0.3788 0.0714 0.6710 0.0547 0.5915 0.0240
25 (8.0) 3 (1.0) 25 (8.5) 6 (2.1) 21 (7.1)
18 (15.3) 2 (1.7) 15 (13.7) 6 (5.5) 10 (9.3)
0.0326 0.5285 0.1530 0.0875 0.5818
Values in n (%); MACE, major adverse cardiac event; TLR, target lesion revascularization; TVR, target vessel revascularization.
lesions. Furthermore, except for final MLD and final percent residual stenosis, angiographic measurements, including lesion length, were reported by the Investigator and not validated by the core laboratory.
5. Conclusions Long lesions are inherently more complex and higher risk, requiring more intensive lesion preparation. This sub-analysis of ORBIT II revealed that orbital atherectomy treatment of long (≥25–40 mm) lesions was associated with a higher rate of MACE at 30 days, but not at 3 years. This difference, however, was driven primarily by a higher in-hospital non-Q-wave MI rate; using the more clinically relevant SCAI definition of MI, there was no significant difference in rates of acute MI between the short (b25 mm) and long (≥25–40 mm) groups. Further studies are warranted to determine how OAS compares to focal force balloon angioplasty, rotational atherectomy and other novel treatment options for long severely calcified lesions.
Table 5 Severe angiographic complications.
Subjects with severe angiographic complications Severe dissection (types C, D, E, and F) Perforation Persistent slow flow/no reflow Abrupt closure
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
p-Value
15 (4.8) 6 (1.9) 4 (1.3) 2 (0.6) 5 (1.6)
14 (11.9) 7 (5.9) 4 (3.4) 1 (0.8) 3 (2.5)
0.0157 0.0512 0.2223 1.0000 0.4556
Values are n (%).
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Fig. 1. Time-to-event curves through 3 years. Cumulative event rates through 3 years in ORBIT II patients with short (25 mm) versus long (≥25–40 mm) target lesions — (A) major adverse cardiac events (MACE), (B) myocardial infarction, (C) target vessel revascularization, (D) cardiac death.
Funding sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Cardiovascular Systems, Inc. sponsored the ORBIT II study. Declaration of competing interest Brad Martinsen and Ann Behrens are employed by and own stock in CSI. Jeffrey Chambers receives consulting fees from CSI. Gautam Kumar, Eric Youngyoon Shin, Rajesh Sachdeva, and Evan Shlofmitz have no relevant conflict of interest to disclose. References [1] Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Chuang YC, et al. Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation 1995;91:1959–65. [2] Généreux P, Madhavan MV, Mintz GS, Maehara A, Palmerini T, Lasalle L, et al. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes: pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trials. J Am Coll Cardiol 2014;63:1845–54. [3] Lee MS, Yang T, Lasala J, Cox D. Impact of coronary artery calcification in percutaneous coronary intervention with paclitaxel-eluting stents: two-year clinical outcomes of paclitaxel-eluting stents in patients from the ARRIVE program. Catheter Cardiovasc Interv 2016;88:891–7.
[4] Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med 2004;164:1285–92. https://doi.org/10.1001/archinte.164.12.1285. [5] Mosseri M, Satler LF, Pichard AD, Waksman R. Impact of vessel calcification on outcomes after coronary stenting. Cardiovasc Revasc Med 2005;6:147–53. [6] Chambers JW, Feldman RL, Himmelstein SI, Bhatheja R, Villa AE, Strickman NE, et al. Pivotal trial to evaluate the safety and efficacy of the orbital atherectomy system in treating de novo, severely calcified coronary lesions (ORBIT II). JACC Cardiovasc Interv 2014;7:510–8. [7] Lee M, Généreux P, Shlofmitz R, Phillipson D, Anose BM, Martinsen BJ, et al. Orbital atherectomy for treating de novo, severely calcified coronary lesions: 3-year results of the pivotal ORBIT II trial. Cardiovasc Revasc Med 2017;18:261–4. https://doi.org/ 10.1016/j.carrev.2017.01.011. [8] Claessen BE, Smits PC, Kereiakes DJ, Parise H, Fahy M, Kedhi E, et al. Impact of lesion length and vessel size on clinical outcomes after percutaneous coronary intervention with everolimus- versus paclitaxel-eluting stents pooled analysis from the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) and COMPARE (second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice) randomized trials. JACC Cardiovasc Interv 2011;4:1209–15. https://doi.org/10.1016/j.jcin.2011.07.016. [9] Habara S, Mitsudo K, Goto T, Kadota K, Fujii S, Yamamoto H, et al. The impact of lesion length and vessel size on outcomes after sirolimus-eluting stent implantation for in-stent restenosis. Heart Br Card Soc 2008;94:1162–5. https://doi.org/10.1136/ hrt.2007.128595. [10] Kastrati A, Elezi S, Dirschinger J, Hadamitzky M, Neumann FJ, Schömig A. Influence of lesion length on restenosis after coronary stent placement. Am J Cardiol 1999;83: 1617–22. https://doi.org/10.1016/s0002-9149(99)00165-4. [11] Généreux P, Lee AC, Kim CY, Lee M, Shlofmitz R, Moses JW, et al. Orbital atherectomy for treating de novo severely calcified coronary narrowing (1-year results from the pivotal ORBIT II trial). Am J Cardiol 2015;115:1685–90. https://doi.org/10.1016/j. amjcard.2015.03.009. [12] Moussa ID, Klein LW, Shah B, Mehran R, Mack MJ, Brilakis ES, et al. Consideration of a new definition of clinically relevant myocardial infarction after coronary
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[20] de Waha S, Allali A, Büttner H-J, Toelg R, Geist V, Neumann F-J, et al. Rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: two-year clinical outcome of the randomized ROTAXUS trial. Catheter Cardiovasc Interv 2016;87:691–700. [21] Abdel-Wahab M, Richardt G, Joachim Büttner H, Toelg R, Geist V, Meinertz T, et al. Highspeed rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: the randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease) trial. JACC Cardiovasc Interv 2013;6:10–9. https://doi.org/10.1016/j.jcin.2012.07.017. [22] Abdel-Wahab M, Toelg R, Byrne RA, Geist V, El-Mawardy M, Allali A, et al. Highspeed rotational atherectomy versus modified balloons prior to drug-eluting stent implantation in severely calcified coronary lesions. Circ Cardiovasc Interv 2018;11: e007415. https://doi.org/10.1161/CIRCINTERVENTIONS.118.007415. [23] Desai R, Mirza O, Martinsen BJ, Kumar G. Plaque modification of severely calcified coronary lesions via orbital atherectomy: single-center observations from a complex Veterans Affairs cohort. Health Sci Rep 2018;1:e99. https://doi.org/10.1002/hsr2.99. [24] Witzenbichler B, Maehara A, Weisz G, Neumann F-J, Rinaldi MJ, Metzger DC, et al. Relationship between intravascular ultrasound guidance and clinical outcomes after drug-eluting stents: the assessment of dual antiplatelet therapy with drugeluting stents (ADAPT-DES) study. Circulation 2014;129:463–70. https://doi.org/ 10.1161/CIRCULATIONAHA.113.003942. [25] Shlofmitz E, Martinsen B, Lee M, Généreux P, Behrens A, Kumar G, et al. Utilizing intravascular ultrasound imaging prior to treatment of severely calcified coronary lesions with orbital atherectomy: an ORBIT II sub-analysis. J Interv Cardiol 2017;30: 570–6. https://doi.org/10.1111/joic.12423.
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Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Orbital atherectomy for the treatment of long (≥25–40 mm) severely calcified coronary lesions: ORBIT II sub-analysis Gautam Kumar a,⁎, Eric Youngyoon Shin a, Rajesh Sachdeva a, Evan Shlofmitz b, Ann N. Behrens c, Brad J. Martinsen c, Jeffrey W. Chambers d a
Division of Cardiology, Emory University and Atlanta Veterans Affairs Medical Center, Atlanta, GA, USA Section of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC, USA Department of Clinical and Scientific Affairs, Cardiovascular Systems, Inc., St. Paul, MN, USA d Metropolitan Heart and Vascular Institute, Mercy Hospital, Minneapolis, MN, USA b c
a r t i c l e
i n f o
Article history: Received 17 September 2019 Received in revised form 17 December 2019 Accepted 23 December 2019 Available online xxxx Keywords: Atherectomy Calcification Percutaneous coronary intervention Long lesions
a b s t r a c t Background: Orbital atherectomy (OA) is an effective method of lesion preparation of severely calcified vessels prior to stent deployment. Long calcified lesions may lead to higher risk of post-procedural complications, yet the optimal treatment strategy has not been established. In this study we sought to determine the safety and efficacy of OA in patients with long (≥25–40 mm) calcified target lesions. Methods: ORBIT II was a single-arm trial that enrolled 443 patients at 49 U.S. sites. De novo, severely calcified coronary lesions were treated with OA prior to stenting. Patients treated with the OA device were stratified into two groups according to target lesion length as visually estimated by the investigator: those with short (b25 mm; N = 314) vs. long (≥25–40 mm; N = 118) lesions. Lesions N40 mm were excluded per protocol. The primary endpoint was the 3-year major adverse cardiac event (MACE) rate, defined as a composite of cardiac death, myocardial infarction (MI), and target vessel revascularization (TVR). Results: The 3-year MACE rates in patients with short (b25 mm) vs. long (≥25–40 mm) lesions were 21.1% vs. 29.9% respectively (p = 0.055). The rate of cardiac death (6.5% vs. 7.8%, p = 0.592) and TVR (8.5% vs. 13.7%, p = 0.153) did not significantly differ. The rate of MI (CK-MB N 3× ULN) at 3 years was significantly higher in patients with long (≥25–40 mm) lesions (9.0% vs. 17.0%, p = 0.024), with the majority occurring in-hospital (7.0% vs. 13.6%, p = 0.037). Conclusions: Patients with long (≥25–40 mm) calcified target lesions had similar outcomes in terms of MACE at 3 years despite higher rates of MI, which mostly occurred in-hospital. Using the more contemporary SCAI definition of MI, there was no significant difference in rates of MI between the short (b25 mm) and long (≥25–40 mm) groups. Further studies are warranted to determine how OA compares to focal force balloon angioplasty, rotational atherectomy and other novel treatment options for long severely calcified lesions. Summary for annotated table of contents: Percutaneous coronary intervention of long calcified lesions is inherently more complex and higher risk and may require more intensive lesion preparation. This sub-analysis of ORBIT II revealed that orbital atherectomy treatment of longer (≥25–40 mm) lesions was associated with a higher rate of MACE at 30 days, but not at 3 years. This difference, however, was driven primarily by a higher in-hospital non-Q-wave MI rate; using the more contemporary SCAI definition of MI, there was no significant difference in rates of MI between the short (b25 mm) and long (≥25–40 mm) groups. Published by Elsevier Inc.
Abbreviations: BMS, bare metal stent; CABG, coronary artery bypass graft; CK-MB, creatine kinase-myocardial band; CSI, Cardiovascular Systems, Inc.; DES, drug eluting stent; eGFR, estimated glomerular filtration rate; IVUS, intravascular ultrasound; LAD, left anterior descending artery; LCX, left circumflex artery; MACE, major adverse cardiac events; MI, myocardial infarction; MLD, minimal luminal diameter; OA, orbital atherectomy; OAS, orbital atherectomy system; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; RCA, right coronary artery; RVD, reference vessel diameter; SCAI, Society for Cardiovascular Angiography and Interventions; TLR, target lesion revascularization; TVR, target vessel revascularization; ULN, upper limit of normal. ⁎ Corresponding author at: Division of Cardiology, Emory University and Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA 30033, USA. E-mail addresses: [email protected] (G. Kumar), [email protected] (E.Y. Shin), [email protected] (R. Sachdeva), [email protected] (A.N. Behrens), [email protected] (B.J. Martinsen), [email protected] (J.W. Chambers).
https://doi.org/10.1016/j.carrev.2019.12.027 1553-8389/Published by Elsevier Inc.
Please cite this article as: G. Kumar, E.Y. Shin, R. Sachdeva, et al., Orbital atherectomy for the treatment of long (≥25–40mm) severely calcified coronary lesions: ORBIT ..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.12.027
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1. Introduction
2.3. Study device
Significant coronary artery calcifications affect N70% of all target lesions, when studied by intravascular ultrasound (IVUS) [1]. Arterial calcium poses a significant barrier to successful percutaneous coronary intervention (PCI) both in terms of technical difficulty as well as postprocedural complications [2–5]. The ORBIT II trial demonstrated that orbital atherectomy (OA) (Diamondback 360®, Cardiovascular Systems, Inc. [CSI], St. Paul, MN) is safe and effective in the pretreatment of calcified lesions for enabling successful stent deployment without eliciting undue risk of major adverse cardiac events (MACE) at either 30 days or 3 years following the index procedure [6,7]. In this study, we sought to perform a subgroup analysis of the ORBIT II trial with specific focus on longer (≥25–40 mm) lesions, as there is currently limited published data regarding use of OA in this subgroup. PCI of longer target lesions is known to be associated with worse clinical outcomes, likely due to extensive manipulation and injury to the arterial luminal wall causing exaggerated neointimal hyperplasia [8–10]. Operators may thus be understandably cautious in approaching these longer lesions with OA due to the potential for longer treatment time and the possible increase in embolic material. In the ORBIT II study, the myocardial infarction (MI) rate was 2.0% using the Society for Cardiovascular Angiography and Interventions (SCAI) definition of clinically relevant MI after PCI [11,12]; however, outcomes were not reported specifically for long lesions. Therefore, we evaluated procedural outcomes and MACE for up to 3 years in this clinically challenging but important subgroup.
The coronary orbital atherectomy system (OAS) modifies calcified plaque to facilitate stent delivery and to help optimize stent expansion in severely calcified arteries. The mechanism of action is differential sanding of coronary calcification: the diamond-coated crown's orbital diameter expands radially via centrifugal force and provides proximal and distal sanding to modify the plaque, increasing the lumen size and vessel compliance. As the crown is moved through the lesion, an increase in time in contact with the lesion, rotational speed, or number of passes allows for an increase in luminal gain. The healthy elastic tissue flexes away from the crown, minimizing damage to the vessel wall. The elliptical orbit allows blood and micro-particulate to flow past the crown and be dispersed, lowering the risk of thermal injury [18]. The orbital atherectomy device is designed to track and spin only over the ViperWire (CSI). Continual infusion of saline and ViperSlide lubricant (CSI) is critical for safe OAS operation; the ViperSlide lubricant is required for cooling and lubricating the orbital atherectomy device during use to reduce the risk of overheating.
2. Methods 2.1. Study design and population
2.4. Study procedure One target lesion was treated per patient. Investigators were required to implant an FDA-approved stent after performing orbital atherectomy and were not allowed to use thrombectomy, embolic protection devices, brachytherapy, or cutting balloons. Pre-dilatation after atherectomy and post-dilatation after stenting was left to the discretion of the operator. Quantitative coronary angiography (QCA) was not required for Investigator-reported angiographic data points. 2.5. Study endpoints
The study design of ORBIT II has been previously described [6]. It was a prospective, non-blinded, single-arm study conducted in 49 U.S. centers that enrolled 443 patients with severely calcified coronary lesions undergoing PCI between May 25, 2010, and November 26, 2012. The trial conformed to good clinical practice and the applicable U.S. Code of Federal Regulations. Each site received approval from its respective institutional review board and all subjects signed informed consent. The ORBIT II key inclusion criteria were: (1) target vessel reference diameter ≥2.5 mm and ≤4.0 mm with a stenosis ≥70% and b100% or a stenosis ≥50% and b70% with evidence of clinical ischemia via either positive stress test, fractional flow reserve value ≤0.8, or IVUS minimum lumen area ≤4.0 mm2; (2) target lesion length ≤40 mm; and (3) evidence of severe calcium at the lesion site based on the angiographic presence of radio-opacities noted without cardiac motion prior to contrast injection, involving both sides of the arterial wall in at least one location, total length of calcium of ≥15 mm and extending partially into the target lesion; or presence of ≥270° of calcium at one cross section via IVUS. The exclusion criteria included: (1) the target vessel had a stent from a previous PCI unless the stent was on a different branch than the target lesion and was implanted N30 days prior with no higher than 30% in-stent restenosis; (2) recent MI, defined as creatine kinase N1 times upper limit of normal (ULN) within 30 days before the index procedure; and (3) chronic renal failure unless on hemodialysis, or a serum creatinine level N2.5 mg/dl; and evidence of current left ventricular ejection fraction ≤25%.
Procedural success was defined as angiographically successful stent delivery with residual stenosis b50% without in-hospital major adverse cardiac event (MACE), where MACE is defined as the composite of cardiac death, MI, or target vessel revascularization (TVR). MI was defined as creatine kinase-myocardial band (CK-MB) N3 times ULN with or without new pathological Q-wave. TVR was defined as repeat revascularization of the target vessel (inclusive of the target lesion) after completion of the index procedure. The rate of MI was also calculated using the SCAI definition of clinically relevant MI after PCI [12]. An independent clinical events committee adjudicated adverse events and severe angiographic complications including persistent slow flow/no reflow and abrupt closure; dissections and perforations were reported by the angiographic core lab (Cleveland Clinic Foundation, Cleveland, Ohio). Additionally, final minimal luminal diameter (MLD) and percent stenosis were determined by the angiographic core lab using computerassisted quantitative coronary angiography (QCA) software with an automated edge-detection system (PIE Medical Imaging, The Netherlands). All images were acquired immediately post nitroglycerin administration. An image of the contrast-filled catheter tip was necessary for calibration. To generate reference vessel diameter (RVD) measurements, segments immediately adjacent to the treated vessel area (one proximal and one distal, each within 5 mm of the treated area) were manually chosen and measured with the QCA software. The program calculated all segment statistics based on the frame's calibration factor. The QCA procedure was repeated for the matching orthogonal view.
2.2. Study population
2.6. Statistical analysis
Subjects treated with the OA device were stratified according to target lesion length as visually estimated by the investigator: short (b25 mm; N = 314) and long (≥25–40 mm; N = 118). The definition of long lesion as ≥25 mm was chosen based on other published studies that used a similar definition [13–17].
Continuous variables are expressed as mean ± standard deviation and categorical variables are presented as proportions. Wilcoxon rank sum test and Fisher's exact test were used to compare continuous and categorical variables, respectively. The Kaplan–Meier method was used to construct survival curves for the time-to-event variables;
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event rates were compared using the Cox proportional hazards model. A p-value b 0.05 was considered statistically significant. Statistical analyses were performed with either SAS Software System (SAS Institute Inc., Cary, NC, USA) or R (R Core Team 2014).
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8.4%, p = 0.002) in the long (≥25–40 mm) group. Long (≥25–40 mm) lesions also had longer total length of calcium (26.2 ± 15.5 mm vs. 34.1 ± 13.1 mm, p b 0.001) (Table 2). 3.3. Procedural results
3. Results 3.1. Patient demographics and clinical history There were no significant differences in baseline demographics between the patients with short (b25 mm) vs. long (≥25–40 mm) target lesions (Table 1). Clinical characteristics such as medical history of cardiovascular risk factors, atherosclerotic cardiovascular disease, angina, PCI, coronary artery bypass grafting (CABG), and heart failure were similar between groups (Table 1). 3.2. Lesion characteristics As compared with short (b25 mm) lesions, long (≥25–40 mm) lesions less commonly affected the left circumflex artery (LCX) (16.9% vs. 8.5%, p = 0.032), and more commonly involved the right coronary artery (RCA) (25.2% vs. 40.7%, p = 0.002). Pre-procedure MLD was smaller (0.5 ± 0.3 mm vs. 0.4 ± 0.3 mm, p = 0.001) and preprocedure percent stenosis was more severe (83.4 ± 9.0% vs. 86.5 ± Table 1 Population demographics and baseline clinical characteristics.
Age (years) Male Ethnicity Caucasian Black or African American Asian Hispanic or Latino Native American Other BMI eGFR (ml/min/1.73 m2) Smoking No, never Yes, current Yes, former History of diabetes mellitus History of dyslipidemia History of hypertension History of stroke/TIA History of MI History of angina For subjects with history of angina, type Stable Unstable History of PCI History of CABG LVEF (%) NYHA classification of heart failure No history of heart failure Class I Class II Class III Class IV
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
p-Value
71.6 ± 9.9 199 (63.4)
71.3 ± 10.0 79 (66.9)
0.6925 0.5015 0.7375
277 (88.2) 17 (5.4) 7 (2.2) 9 (2.9) 1 (0.3) 3 (1.0) 29.2 ± 5.8 76.3 ± 26.2 (N = 312)
105 (89.0) 6 (5.1) 1 (0.8) 6 (5.1) 0 (0.0) 0 (0.0) 29.7 ± 5.9 74.0 ± 26.6
105 (33.4) 47 (15.0) 162 (51.6) 112 (35.7) 292/313 (93.3) 288 (91.7) 26/313 (8.3) 68/311 (21.9) 243 (77.4)
39 (33.1) 23 (19.5) 56 (47.5) 43 (36.4) 106 (89.8) 107 (90.7) 13 (11.0) 26/116 (22.4) 96 (81.4)
155 (63.8) 88 (36.2) 145/311 (46.6) 45 (14.3) 56.6 ± 9.5 (N = 309) N = 312
62 (64.6) 34 (35.4) 53/117 (45.3) 19 (16.1) 56.5 ± 9.8 (N = 117) N = 117
22 (7.1) 183 (58.7) 106 (34.0) 1 (0.3) 0 (0.0)
5 (4.3) 61 (52.1) 50 (42.7) 1 (0.9) 0 (0.0)
Compared with short (b25 mm) lesions, long (≥25–40 mm) lesions required more total OAS device run time (60.3 ± 36.8 s vs. 84.2 ± 60.2 s, p = 0.0002) and longer average OAS individual device run time (19.1 ± 5.7 s vs. 20.5 ± 5.3 s, p = 0.039). There was no significant difference in post-OAS MLD or post-OAS residual stenosis (Table 3). There were more post-OAS stents used per subject in the long (≥25– 40 mm) lesion group (1.1 ± 0.4 vs. 1.6 ± 0.7, p b 0.0001) and higher stent maximum deployment pressure (13.6 ± 3.1 atm vs. 14.3 ± 3.2 atm, p = 0.032), but no difference in percentage of drug eluting stents (DES) used or post-stent residual stenosis. Long (≥25–40 mm) lesions were associated with longer total procedure time (49.6 ± 26.9 min vs. 57.6 ± 33.5 min, p = 0.033), longer total fluoroscopy time (16.5 ± 10.1 min vs. 21.3 ± 15.1 min, p = 0.0005), and increased total contrast volume (166.3 ± 81.4 ml vs. 189.1 ± 91.6 ml, p = 0.017). There was no difference in final procedure MLD or final procedure stenosis. Procedural success was achieved in 91.7% and 83.9% in the short (b25 mm) and long (≥25–40 mm) groups, respectively (p = 0.022). Although rates of in-hospital cardiac death or TVR did not differ, the long (≥25–40 mm) group had a higher rate of in-hospital MACE (8.0% vs. 15.3%, p = 0.03) due to a significantly higher rate of in-hospital nonQ-wave MI (CK-MB N 3× ULN) (7.0% vs. 13.6%, p = 0.037) (Table 4). The rate of severe angiographic complications was higher in the long (≥25–40 mm) group (4.8% vs. 11.9%, p = 0.016). The incidence of perforation, persistent slow flow/no reflow, and abrupt closure were similar in both groups; the severe dissection rate trended higher in the long (≥25–40 mm) group (1.9% vs. 5.9%, p = 0.051) (Table 5). 3.4. 30-day and 3-year MACE
0.4719 0.6392 0.5058
0.9106 0.2285 0.7034 0.4510 0.8962 0.4312 1.0000
0.8285 0.6501 0.8447 0.2306
Values are n (%) or mean ± standard deviation (SD); BMI = body mass index; CABG = coronary artery bypass graft; CCS = Canadian Cardiovascular Society; eGFR = estimated glomerular filtration rate; LAD = left anterior descending artery; LCX = left circumflex artery; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association; PCI = percutaneous coronary intervention; RCA = right coronary artery; TIA = transient ischemic attack.
There was a significant difference in 30-day MACE following revascularization of short (b25 mm) and long (≥25–40 mm) lesions (8.3% vs. 16.1%, p = 0.024). Compared to short (b25 mm) target lesions, treatment of long (≥25–40 mm) target lesions led to a significantly higher rate of MI (7.6% vs. 15.3%, p = 0.024), although there was no difference in rates of cardiac death or TVR (Table 6, Fig. 1A–D). The MACE rates at 1 and 2 years were similar in both groups (1 year: 15.5% vs. 20.3%, p = 0.208; 2 years: 17.8% vs. 25.5%, p = 0.078). At 3 years, the rates of MACE following revascularization of short (b25 mm) target lesions compared to long (≥25–40 mm) lesions were not significantly different (21.1% vs. 29.9%, p = 0.055), nor were individual components of cardiac death (6.5% vs. 7.8%, p = 0.592) and TVR (8.5% vs. 13.7%, p = 0.153). However, there was a significantly increased rate of MI in the long (≥25–40 mm) group (9.0% vs. 17.0%, p = 0.024) (Table 6, Fig. 1A–D). 4. Discussion Our findings suggest that orbital atherectomy for long (≥25–40 mm) lesions is feasible and the 3-year MACE outcome is comparable to those of short (b25 mm) lesions. In this ORBIT II subgroup analysis, the rates of severe dissection and perforation were numerically higher in the long (≥25–40 mm) group (1.9% vs. 5.9%, p = 0.051 and 1.3% vs. 3.4%, p = 0.222, respectively) and the composite severe angiographic complication rate was significantly higher (4.8% vs. 11.9%, p = 0.016). While not statistically significant, in comparison to short (b25 mm) target lesions the rate of MACE at 3 years was numerically higher in long (≥25–40 mm) lesions (21.1% vs. 29.9%, p = 0.055). The similar rates of MACE at follow-up are consistent with two published coronary atherectomy long lesion studies. In a contemporary multi-center registry of 458
Please cite this article as: G. Kumar, E.Y. Shin, R. Sachdeva, et al., Orbital atherectomy for the treatment of long (≥25–40mm) severely calcified coronary lesions: ORBIT ..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.12.027
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Table 2 Vessel and lesion characteristics.
Target lesion vessel LAD LCX Left main RCA Ramus Pre-procedure target lesion length⁎ (mm) Pre-procedure average RVD⁎ (mm) Pre-procedure MLD⁎ (mm) Pre-procedure percent stenosis⁎ Subjects with calcification determined by angiography only Total length of calcium (including segmented)⁎ (mm) Subjects with calcium visible on both sides of the vessel⁎ Subjects with calcification determined by IVUS Maximum degree of calcium via IVUS (°)
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
167 (53.2) 53 (16.9) 10 (3.2) 79 (25.2) 5 (1.6) 14.3 ± 4.7 3.1 ± 0.4 0.5 ± 0.3 83.4 ± 9.0 286 (91.1) 26.2 ± 15.5 286 (100) 28 (8.9) 294.1 ± 35.5
58 (49.2) 10 (8.5) 0 (0.0) 48 (40.7) 2 (1.7) 31.2 ± 4.9 3.1 ± 0.4 0.4 ± 0.3 86.5 ± 8.4 111 (94.1) 34.1 ± 13.1 111 (100) 7 (5.9) 298.6 ± 42.3
p-Value 0.0030 0.5168 0.0316 0.0684 0.0020 1.0000 b0.0001 0.6416 0.0014 0.0024 0.4285 b0.0001 0.4285 0.6540
Values are n (%) or mean ± standard deviation; IVUS = intravascular ultrasound; LAD = left anterior descending artery; LCX = left circumflex artery; MLD = minimal luminal diameter; RCA = right coronary artery; RVD = reference vessel diameter. ⁎ Visually estimated by the investigator.
patients who underwent OA treatment, long stent length (≥50 mm) was associated with similar major adverse cardiac and cerebrovascular events (MACCE) at 1 year compared to shorter stent length (b50 mm) (14.2% vs 11.5%, p = 0.40) [19]. Similarly, in a post-hoc analysis of the ROTATE registry which included patients undergoing rotational atherectomy, the MACE rate at follow-up (mean: 27.6 ± 22.9 months) did not differ in the longer lesion group (≥25 mm, 28.3%) and shorter lesion group (b25 mm, 28.0%) [13]. In this ORBIT II sub-analysis, the numerically higher rate of 3-year MACE in the long (≥25–40 mm) lesion group was driven primarily by a significantly higher rate of MI (9.0% vs. 17.0%, p = 0.024). Most of these MI events were non-Q-wave MIs and occurred in-hospital (7.0% vs. 13.6%, p = 0.037). Using the contemporary clinically relevant SCAI MI definition [12], there was a trend of increased acute MI in the long (≥25–40 mm) group (1.3% vs. 4.2%, p = 0.067). The observation of higher in-hospital non-Q-wave MI in the long (≥25–40 mm) group could partly be explained by the need for longer procedural times
required to achieve satisfactory post-PCI MLD as compared to shorter lesions. The cumulative effect of longer OAS run times, higher stent deployment pressures, increased number of stents placed, increased calcified particulate that needs to be cleared through the microvasculature and more contrast use per lesion likely lead to an increased chance of biochemical evidence of MI. Although prior investigators have shown that longer lesion length is associated with higher rates of MACE compared to shorter lesions, postprocedural event free survival has not been studied specifically in subjects who have concomitant heavily calcified target lesions. Despite the high risk nature of these lesions, in the ORBIT II study the MACE rate following OA at 2 years (25.5%) is numerically lower than the rate of MACE at 2 years in all subjects with calcified vessels (short or long) undergoing rotational atherectomy (29.4%) [20]. In the rotational atherectomy arm of the ROTAXUS trial, the mean lesion length was 20.6 ± 9.3 mm as compared to 31.2 ± 4.9 mm in the ORBIT II long lesion group [21]. In the more contemporary PREPARE-CALC study which
Table 3 Final overall procedural results.
OAS devices used per subject OAS speed(s) used (rpm) Low only (80,000) Low and high (80,000/120,000) High only (120,000) Total device run time (s) Average individual device run time (s) Post-OAS MLD⁎ (mm) Post-OAS residual stenosis⁎ (%) Subjects treated with post-OAS/pre-stent balloon dilations Post-OAS/pre-stent balloons used per subject Maximum inflation pressure (atm) Time at maximum pressure (s) Subjects with stent placed Post-OAS stents used per subject Types of stents used in study BMS Covered DES Maximum stent deployment pressure (atm) Post-stent residual stenosis⁎ (%) Total procedure time (min) Total fluoroscopy time (min) Total volume of contrast used (ml) Final procedure MLD† (mm) Final procedure stenosis† (%)
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
1.1 ± 0.2
1.1 ± 0.2
65 (20.7) 233 (74.2) 16 (5.1) 60.3 ± 36.8 (N = 313) 19.1 ± 5.7 (N = 312) 1.3 ± 0.6 58.6 ± 17.1 121 (38.5) 1.3 ± 0.6 11.3 ± 3.6 26.0 ± 23.6 311 (99.0) 1.1 ± 0.4
28 (23.7) 84 (71.2) 6 (5.1) 84.2 ± 60.2 20.5 ± 5.3 1.2 ± 0.5 59.0 ± 18.2 56 (47.5) 1.7 ± 1.0 13.4 ± 4.2 (N = 55) 30.7 ± 25.3 (N = 54) 116 (98.3) 1.6 ± 0.7
39/346 (11.3) 0 (0) 307/346 (88.7) 13.6 ± 3.1 (N = 311) 5.1 ± 9.7 (N = 311) 49.6 ± 26.9 16.5 ± 10.1 (N = 310) 166.3 ± 81.4 (N = 313) 2.9 ± 0.5 (N = 304) 4.1 ± 13.0 (N = 313)
20/190 (10.5) 2/190 (1.1) 168/190 (88.4) 14.3 ± 3.2 (N = 114) 7.7 ± 16.0 (N = 115) 57.6 ± 33.5 (N = 117) 21.3 ± 15.1 189.1 ± 91.6 (N = 117) 2.8 ± 0.5 (N = 113) 5.0 ± 16.3
p-Value 0.7029 0.7819
0.0002 0.0386 0.5892 0.8869 0.1003 0.0013 0.0027 0.1418 0.6173 b0.0001 0.2088
0.0323 0.4688 0.0325 0.0005 0.0165 0.2489 0.6277
Values are n (%) or mean ± standard deviation; BMS = bare metal stent; DES = drug eluting stent; MLD = minimal luminal diameter; OAS = orbital atherectomy system. ⁎ Visually estimated by the investigator. † As reported by the Angiographic Core Laboratory.
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G. Kumar et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx Table 4 Procedural success rates.
Procedural success Stent delivered Residual stenosis b50% In hospital MACE Cardiac death MI Non-Q-wave Q-wave Target vessel revascularization SCAI MI
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Table 6 Cumulative MACE rates (as estimated by Kaplan-Meier). Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
p-Value
288 (91.7) 311 (99.0) 312 (99.4) 25 (8.0) 1 (0.3) 23 (7.3) 22 (7.0) 1 (0.3) 2 (0.6)
99 (83.9) 114 (96.6) 115 (97.5) 18 (15.3) 0 (0.0) 18 (15.3) 16 (13.6) 2 (1.7) 1 (0.8)
0.0218 0.0922 0.1282 0.0302 1.0000 0.0163 0.0371 0.1824 1.0000
4 (1.3)
5 (4.2)
0.0672
Values in n (%); MACE = major adverse cardiac events; MI = myocardial infarction; SCAI = Society for Cardiovascular Angiography and Interventions.
used a new generation ultrathin (60 μm) strut biodegradable polymer Sirolimus-eluting stent (Orsiro, Biotronik AG, Bülach, Switzerland), the mean lesion length and total stent length per lesion were longer respectively at 29.81 ± 15.23 mm and 35.63 ± 15.69 mm in the rotational atherectomy arm (n = 100). The 9-month target vessel failure (TVF) rate was extremely low at 6% [22]; longer term follow-up is awaited. In the ROTAXUS trial, thermal injury due to rotational atherectomy resulting in exaggerated neointimal proliferation was thought to have contributed to increased late lumen loss despite higher initial acute gain. However, in the PREPARE-CALC trial, use of contemporary stents appears to have attenuated this effect. The higher rates of in-hospital MI (CK-MB N 3× ULN) observed following OAS assisted PCI in long lesions can perhaps be mitigated by techniques that may reduce collateral injury to the target vessel during lesion preparation. Of note, there was very limited use of intravascular imaging for assessment of calcification prior to OAS usage in this study, with b10% of all subjects undergoing IVUS. IVUS and optical coherence tomography (OCT) are invaluable tools in complex lesion treatment as these modalities can aid decision making during PCI by allowing for assessment of calcium depth prior to OAS, and ensure adequate vessel preparation, sizing of vessel, and verification of stent coverage post-OAS. Intravascular imaging guidance is consistent with best practices for OAS, and its use is known to reduce MACE following PCI, even in severely calcified vessels [18,23–25]. There may also have been a “learning curve” for orbital atherectomy as the ORBIT II trial represents initial OA use. For example, in the more contemporary OAS registry that included three centers in the United States performing this procedure routinely, the severe dissection (2.6%) and perforation (1.9%) rates reported for the long stent group (≥50 mm) were lower than the rates reported in the ORBIT II long (≥25–40 mm) lesion group [19].
4.1. Study limitations This was a post-hoc sub-analysis of ORBIT II—a non-randomized trial that lacked a control arm. The original trial was not powered to compare efficacy or safety of OAS in patients with varying lengths of target
30-day MACE Cardiac death Myocardial infarction Non-Q-wave Q-wave TVR TVR (non-TLR) TLR 1-year MACE Cardiac death Myocardial infarction Non-Q-wave Q-wave TVR TVR (non-TLR) TLR 2-year MACE Cardiac death Myocardial infarction Non-Q-wave Q-wave TVR TVR (non-TLR) TLR 3-year MACE Cardiac death Myocardial infarction Non-Q-wave Q-wave TVR TVR (non-TLR) TLR
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
p-Value
26 (8.3) 1 (0.3) 24 (7.6)
19 (16.1) 0 (0.0) 18 (15.3)
0.0235 0.9979 0.0237
22 (7.0) 2 (0.6) 3 (1.0) 1 (0.3) 2 (0.6) 48 (15.5) 10 (3.3) 27 (8.6)
16 (13.6) 2 (1.7) 2 (1.7) 1 (0.9) 1 (0.8) 24 (20.3) 4 (3.4) 19 (16.1)
0.0421 0.3261 0.5284 0.4875 0.8158 0.2082 0.9277 0.0311
25 (8.0) 2 (0.6) 16 (5.3) 2 (0.6) 16 (5.3) 55 (17.8) 12 (4.0) 27 (8.6)
17 (14.4) 2 (1.7) 7 (6.1) 4 (3.5) 3 (2.6) 30 (25.5) 8 (6.9) 20 (17.0)
0.0547 0.3261 0.7467 0.0535 0.2565 0.0780 0.2213 0.0181
25 (8.0) 2 (0.6) 21 (7.0) 4 (1.4) 19 (6.3) 64 (21.1) 19 (6.5) 28 (9.0)
18 (15.3) 2 (1.7) 11 (9.8) 5 (4.4) 6 (5.3) 35 (29.9) 9 (7.8) 20 (17.0)
0.0326 0.3261 0.3788 0.0714 0.6710 0.0547 0.5915 0.0240
25 (8.0) 3 (1.0) 25 (8.5) 6 (2.1) 21 (7.1)
18 (15.3) 2 (1.7) 15 (13.7) 6 (5.5) 10 (9.3)
0.0326 0.5285 0.1530 0.0875 0.5818
Values in n (%); MACE, major adverse cardiac event; TLR, target lesion revascularization; TVR, target vessel revascularization.
lesions. Furthermore, except for final MLD and final percent residual stenosis, angiographic measurements, including lesion length, were reported by the Investigator and not validated by the core laboratory.
5. Conclusions Long lesions are inherently more complex and higher risk, requiring more intensive lesion preparation. This sub-analysis of ORBIT II revealed that orbital atherectomy treatment of long (≥25–40 mm) lesions was associated with a higher rate of MACE at 30 days, but not at 3 years. This difference, however, was driven primarily by a higher in-hospital non-Q-wave MI rate; using the more clinically relevant SCAI definition of MI, there was no significant difference in rates of acute MI between the short (b25 mm) and long (≥25–40 mm) groups. Further studies are warranted to determine how OAS compares to focal force balloon angioplasty, rotational atherectomy and other novel treatment options for long severely calcified lesions.
Table 5 Severe angiographic complications.
Subjects with severe angiographic complications Severe dissection (types C, D, E, and F) Perforation Persistent slow flow/no reflow Abrupt closure
Short (b25 mm) (N = 314)
Long (≥25–40 mm) (N = 118)
p-Value
15 (4.8) 6 (1.9) 4 (1.3) 2 (0.6) 5 (1.6)
14 (11.9) 7 (5.9) 4 (3.4) 1 (0.8) 3 (2.5)
0.0157 0.0512 0.2223 1.0000 0.4556
Values are n (%).
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Fig. 1. Time-to-event curves through 3 years. Cumulative event rates through 3 years in ORBIT II patients with short (25 mm) versus long (≥25–40 mm) target lesions — (A) major adverse cardiac events (MACE), (B) myocardial infarction, (C) target vessel revascularization, (D) cardiac death.
Funding sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Cardiovascular Systems, Inc. sponsored the ORBIT II study. Declaration of competing interest Brad Martinsen and Ann Behrens are employed by and own stock in CSI. Jeffrey Chambers receives consulting fees from CSI. Gautam Kumar, Eric Youngyoon Shin, Rajesh Sachdeva, and Evan Shlofmitz have no relevant conflict of interest to disclose. References [1] Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Chuang YC, et al. Patterns of calcification in coronary artery disease. A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation 1995;91:1959–65. [2] Généreux P, Madhavan MV, Mintz GS, Maehara A, Palmerini T, Lasalle L, et al. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes: pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trials. J Am Coll Cardiol 2014;63:1845–54. [3] Lee MS, Yang T, Lasala J, Cox D. Impact of coronary artery calcification in percutaneous coronary intervention with paclitaxel-eluting stents: two-year clinical outcomes of paclitaxel-eluting stents in patients from the ARRIVE program. Catheter Cardiovasc Interv 2016;88:891–7.
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Please cite this article as: G. Kumar, E.Y. Shin, R. Sachdeva, et al., Orbital atherectomy for the treatment of long (≥25–40mm) severely calcified coronary lesions: ORBIT ..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.12.027