Orbital Atherectomy of Severely Calcified Unprotected Left Main Coronary Artery Disease: One-Year Outcomes

Abstract: Objective. We assessed the 1-year outcomes of patients who underwent orbital atherectomy for severely calcified unprotected left main coronary artery (ULMCA) disease. Background. The standard of care for ULMCA is coronary artery bypass graft surgery. Percutaneous coronary intervention (PCI) is a reasonable option for the treatment for ULMCA disease, especially in patients who are not good candidates for surgical revascularization. Coronary artery calcification is associated with worse clinical outcomes in patients who undergo PCI. Modification of severely calcified plaque with orbital atherectomy facilitates stent delivery and expansion. Data on intermediate outcomes of patients with ULMCA disease who undergo orbital atherectomy are unknown. Methods. We retrospectively evaluated 62 patients who underwent PCI with orbital atherectomy for ULMCA disease. The primary endpoint was the major cardiac and cerebrovascular event (MACCE) rate, which was the composite of cardiac death, myocardial infarction, target-lesion revascularization, and stroke at 1 year. Results. Distal bifurcation disease was present in 71.0%, and a single-stent strategy was used in 90.5%. No patients experienced coronary perforation or no-reflow. Two patients experienced coronary dissection (3.2%). One patient experienced BARC-2 bleeding (1.6%). At 1 year, the MACCE rate was 11.3%, with cardiac death occurring in 1.6%, myocardial infarction in 8.1%, and target-lesion revascularization in 4.8%. Non-cardiac death occurred in 4.8%. No patient experienced stroke or stent thrombosis. Conclusion. Orbital atherectomy is an acceptable treatment option for patients with severely calcified ULMCA disease, especially if patients are deemed too high risk for surgical revascularization. 

J INVASIVE CARDIOL 2018;30(7):270-274.

Key words: coronary calcium, unprotected left main coronary artery disease, ULMCA, orbital atherectomy

Unprotected left main coronary artery (ULMCA) disease is associated with increased morbidity and mortality due to the large territory of jeopardized myocardium that it supplies. Patients with high SYNTAX score (>32) who underwent percutaneous coronary intervention (PCI) for ULMCA disease had worse clinical outcomes, including a higher mortality rate.¹ In the EXCEL trial, patients with SYNTAX scores ≤32 had similar rates of the composite of death, myocardial infarction, and stroke at 3 years compared with coronary artery bypass grafting (CABG).² Coronary artery calcification increases the SYNTAX score and may have resulted in the exclusion of many of these patients in the EXCEL trial.³ PCI of severely calcified coronary lesions is technically challenging, as it impedes stent delivery and optimal stent expansion and apposition, increasing the risk of ischemic complications.^4,5 

In the ORBIT II trial, orbital atherectomy (Cardiovascular Systems, Inc [CSI]) was safe and effective for the treatment of severe coronary artery calcification including protected left main lesions.^6-9 However, patients with ULMCA disease were excluded from the trial. We report the 1-year clinical outcomes in patients with severely calcified ULMCA disease treated with orbital atherectomy. 

Methods

In this retrospective analysis, a total of 64 patients with severely calcified ULMCA disease underwent orbital atherectomy followed by stenting between May 2014 to October 2016 at three centers (UCLA Medical Center in Los Angeles, California, St. Francis Hospital in Roslyn, New York, and North Shore University Hospital in Manhasset, New York). Severe coronary artery calcification was defined as the presence of radiopacities on fluoroscopy involving both sides of the arterial wall or by the presence of >270° arc of calcium on intravascular ultrasound. The operator performed PCI with orbital atherectomy rather than CABG for several reasons, including prohibitive surgical risk and patient preference. The institutional review board at each site approved the review of the data.

The mechanism of action of orbital atherectomy involves differential sanding, in which healthy elastic tissue flexes away from the 30 micron diamond-coated crown to minimize damage to the vessel. Another mechanism of action involves centrifugal force, whereby the crown achieves 360° contact with the vessel. Increasing the speed from 80,000 rpm (low speed) to 120,000 rpm (high speed), or decreasing the rate of crown advancement, increases the orbit diameter due to lateral expansion of the crown, allowing the operator to treat multiple vessel diameters with one crown through a 6 Fr sheath. The crown spins over the ViperWire (CSI) as the ViperSlide lubricant (CSI) is infused through the device. 

Standard techniques were used for PCI using a transfemoral or transradial approach. Patients were treated with dual-antiplatelet therapy (DAPT). Antithrombotic therapy included either intravenous heparin to maintain the activated clotting time >250 seconds or bivalirudin. Temporary pacemaker insertion and/or intravascular imaging were at the operator’s discretion. Intracoronary nitroglycerin (100-200 µg) was administered to decrease the risk of vasospasm. Each pass was limited to ≤25 seconds. 

Patients continued DAPT for at least 1 month if bare-metal stents were used and for 1 year if drug-eluting stents were used. Patients were treated with cardioprotective medications, including beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and statins, unless contraindicated. 

The primary endpoint was a composite of major adverse cardiac and cerebrovascular event (MACCE) rate, defined as cardiac death, myocardial infarction, stroke, and target-lesion revascularization at 1 year. Death was considered cardiac in origin unless a non-cardiac origin was documented. Myocardial infarction was defined as recurrent symptoms with new ST-segment elevation or re-elevation of cardiac markers to at least twice the upper limit of normal. Target-lesion revascularization was defined as repeat revascularization of the target lesion because of restenosis within the stent or in the 5 mm distal or proximal segments. Stroke was defined as focal loss of neurological function caused by an ischemic or hemorrhagic event that was confirmed by computed tomography or magnetic resonance imaging. Stent thrombosis was defined in accordance with the Academic Research Consortium.¹⁰Bleeding was defined by the Bleeding Academic Research Consortium (BARC) criteria.¹¹Procedural success was defined as residual stenosis ≤30% and Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 without death, or coronary revascularization during the first 24 hours. Medical records were reviewed to obtain patient data, which were recorded into a central PCI database. 

Statistical analysis. Categorical variables are presented as number and percentage, and continuous variables are presented as mean ± standard deviation. Statistical analysis was performed with SAS software system (SAS Institute, Inc).

Results

The mean patient age was 76.2 ± 9.0 years, and nearly two-thirds (61.5%) were male (Table 1). Nearly one-quarter (24.2%) had left ventricular systolic dysfunction. The vast majority of cases (79.0%) were for acute coronary syndrome. 

Distal bifurcation disease was present in 71.0%, and a single-stent strategy was used for most cases (Table 2). A hemodynamic support device was used in 17.7% of patients. 

Procedural success rate was 100%. No patients experienced coronary perforation or no-reflow (Table 3). Two patients experienced coronary dissection (3.2%). One patient experienced BARC-2 bleeding (1.6%). 

At 1 month, 1 patient experienced MACCE (1.6%), due to myocardial infarction (Table 4). No patient experienced cardiac death, target lesion revascularization, stroke, and stent thrombosis. At 1 year, the MACCE rate was 11.3%. The incidence of cardiac death was 1.6%, myocardial infarction was 8.1%, and target-lesion revascularization was 4.8%. Non-cardiac death occurred in 4.8%. No patient experienced stroke or stent thrombosis. 

Discussion

Our results demonstrate the safety and clinical efficacy of orbital atherectomy for this high-risk subset of patients, including those who were considered poor candidates for surgical revascularization. No patients experienced perforation or no-reflow. The primary endpoint was acceptable, with a low rate of target-lesion revascularization. 

It is vital to the success of PCI to identify the presence of severe coronary calcification, which increases the complexity of PCI. Severe coronary artery calcification may be difficult to diagnose. Intravascular imaging, including intravascular ultrasound and optical coherence tomography, can accurately detect the presence of severe coronary artery calcification and assess stent expansion and apposition. Inability to fully dilate and expand the stent can increase the risk of restenosis and stent thrombosis. Adjunctive treatment with coronary atherectomy modifies the calcified plaque, which facilitates stent delivery and expansion. Attempting to predilate a resistant lesion at high inflation pressure may be unsuccessful or lead to dissection at the junction of the calcified and non-calcified tissues with a strategy that does not incorporate lesion preparation with atherectomy in these lesions.¹² Overall, PCI without atherectomy in heavily calcified lesions may potentially increase procedural time if multiple balloons (including scoring and non-compliant balloons) and “mother and child” catheters such as GuideLiner (Vascular Solutions) or Guidezilla guide extension catheters (Boston Scientific) are needed. Lesion preparation with orbital atherectomy was projected to be cost effective for patients who undergo PCI for severely calcified lesions.¹³ If a dissection occurs, atherectomy is no longer an option for the operator, which lowers the procedural success rate. The patient may develop acute coronary ischemia, leading to hemodynamic and electrical instability, especially given the large myocardial territory the ULMCA supplies. Thus, modification of calcified plaque may actually reduce the length of stay in the hospital, readmission rates, and long-term adverse clinical events. 

Neither the EXCEL trial³ nor NOBLE trial¹⁴ reported the number of patients with severely calcified ULMCA disease or the number who underwent coronary atherectomy. Unlike these trials, our analysis included patients who were not candidates for surgical revascularization, including those with left ventricular dysfunction, cardiogenic shock, and limited life expectancy. 

Restenosis rates for severely calcified lesions are higher compared with non-calcified lesions.⁵ In our analysis, the 1-year rate of target-lesion revascularization was low (4.8%)despite the high prevalence of diabetes mellitus and distal bifurcation disease. This compares favorably to the 1-year rate of target-lesion revascularization in the ORBIT II trial (4.7%), which excluded patients with ULMCA disease.⁷ 

There is a paucity of data with coronary atherectomy in ULMCA disease. A total of 64 patients with ULMCA disease who underwent rotational atherectomy had a 30-day mortality rate of 3.1%.¹⁵ In the SYNTAX trial, patients who underwent surgical revascularization had a 30-day mortality rate of 2.0%.¹⁶

Orbital atherectomy has a theoretical advantage compared with rotational atherectomy due to its quick set-up, single-sized crown, and continuous flow during activation. Rotational atherectomy requires a nitrogen tank, a foot pedal to activate the burr, and calibration to adjust the desired burr speed. The size of the LMCA (approximately 4 mm) commonly requires a rotational atherectomy burr of at least 1.75 mm in size. Initial treatment of the LMCA with a 1.75 mm burr may be too large and aggressive, especially if the calcified plaque burden and percent stenosis is high, leading to larger liberated particle size with a higher risk of distal embolization and slow or no-reflow.^17,18 However, initial treatment with a smaller burr (1.25 or 1.5 mm) requires removal, detachment, reattachment of a larger burr, and readvancement to the lesion to achieve adequate plaque modification of the large diameter of the LMCA. In contrast, the 1.25 mm orbital atherectomy crown can be initiated at low speed followed by high speed with the touch of a button to achieve a lumen size similar to a 1.75 mm burr by advancing the orbital crown slowly (1-3 mm/sec).¹⁹ The elliptical orbit of the orbital atherectomy crown may decrease the likelihood of slow or no-reflow, as it allows blood and microparticles to flow around the crown. Perturbation of flow during ULMCA-PCI may increase the risk of hemodynamic and electrical instability due to the large area of myocardium that the ULMCA supplies. 

Our study included high-risk patients who would be excluded from clinical trials for ULMCA disease. Patients with cardiogenic shock requiring hemodynamic support device and respiratory failure on mechanical ventilation were included in our analysis. Despite this, the 1-year cardiac mortality rate was 1.6%. 

Only 1 patient in our analysis had a temporary pacemaker inserted prior to ULMCA atherectomy. None of the patients experienced significant bradycardia during orbital atherectomy. In a study of 50 patients who underwent orbital atherectomy for calcified ULMCA as well as non-ULMCA lesions, 4% of patients experienced a heart rate decreasing to <50 beats/min.²⁰ However, these episodes were transient and did not require emergent placement of a transvenous pacemaker. 

Study limitations. Our study was small, non-randomized, and retrospective, with intermediate-term follow-up. Comparison with surgical revascularization as well as rotational atherectomy for patients with this lesion subset was not available. A clinical events committee did not adjudicate endpoints. Quantitative coronary analysis was not performed in all patients. The degree of coronary calcification was not determined by an angiographic core laboratory. Periprocedural myocardial infarction was likely under-diagnosed, as cardiac biomarkers were not measured on all patients.

Conclusion

Orbital atherectomy is a safe and effective treatment option for patients with severely calcified ULMCA disease, especially if patients are deemed too high risk for surgical revascularization. No patients experienced perforation or no-reflow. A prospective randomized trial is needed to determine the ideal revascularization strategy for patients with severely calcified ULMCA disease. 

References

1.    Serruys PW, Morice MC, Kappetein AP, et al; SYNTAX Investigators. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360:961-972.

2.     Stone GW, Sabik JF, Serruys PW, et al; EXCEL Trial Investigators. Everolimus-eluting stents or bypass surgery for left main coronary artery disease. N Engl J Med. 2016;375:2223-2235.

3.     https://www.syntaxscore.com/calculator/start.htm

4.     Lee MS, Shah N. The impact and pathophysiologic consequences of coronary artery calcium deposition in percutaneous coronary interventions. J Invasive Cardiol. 2016;28:160-167. 

5.     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;88:891-897. 

6.    Chambers JW, Feldman RL, Himmelstein SI, 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;7:510-518.

7.    Généreux P, Lee AC, Kim CY, 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;115:1685-1690.

8.    Généreux P, Bettinger N, Redfors B, et al. Two-year outcomes after treatment of severely calcified coronary lesions with the orbital atherectomy system and the impact of stent types: insight from the ORBIT II trial. Catheter Cardiovasc Interv. 2016;88:369-377. 

9.    Lee MS, Shlofmitz E, Shlofmitz R, Sahni S, Martinsen B, Chambers J. Outcomes after orbital atherectomy of severely calcified left main lesions: analysis of the ORBIT II study. J Invasive Cardiol. 2016;28:364-369.

10.    Cutlip DE, Windecker S, Mehran R, et al. Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007;115:2344-2351.

11.     Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123:2736-2747.

12.     Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection after angioplasty: an observational study using intravascular ultrasound. Circulation. 1992;86:64-70.

13.     Chambers J, Généreux P, Lee A, et al. The potential cost-effectiveness of the Diamondback 360® Coronary Orbital Atherectomy System for treating de novo, severely calcified coronary lesions: an economic modeling approach. Ther Adv Cardiovasc Dis. 2016;10:74-85. 

14.     Mäkikallio T, Holm NR, Lindsay M, et al; NOBLE Study Investigators. Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial. Lancet. 2016;388:2743-2752.

15.     Yabushita H, Takagi K, Tahara S, et al. Impact of rotational atherectomy on heavily calcified, unprotected left main disease. Circ J. 2014;78:1867-1872. 

16.     Morice MC, Serruys PW, Kappetein AP, et al. Outcomes in patients with de novo left main disease treated with either percutaneous coronary intervention using paclitaxel-eluting stents or coronary artery bypass graft treatment in the synergy between percutaneous coronary intervention with TAXUS and cardiac surgery (SYNTAX) trial. Circulation. 2010;121:2645-2653.

17.     Kini A, Marmur JD, Duvvuri S, Dangas G, Choudhary S, Sharma SK. Rotational atherectomy: improved procedural outcome with evolution of technique and equipment. Single-center results of first 1,000 patients. Catheter Cardiovasc Interv. 1999;46:305-311. 

18.     Adams GL, Khanna PK, Staniloae CS, Abraham JP, Sparrow EM. Optimal techniques with the Diamondback 360° System achieve effective results for the treatment of peripheral arterial disease. J Cardiovasc Transl Res. 2011;4:220-229.

19.     Shlofmitz E, Martinsen BJ, Lee M, et al. Orbital atherectomy for the treatment of severely calcified coronary lesions: evidence, technique, and best practices. Expert Rev Med Devices. 2017;14:867-879.

20.     Lee MS, Nguyen H, Shlofmitz R. Incidence of bradycardia and outcomes of patients who underwent orbital atherectomy without temporary pacemaker. J Invasive Cardiol. 2017;29:59-62. 

From ¹UCLA Medical Center, Los Angeles, California; ²St. Francis Hospital, Roslyn, New York; ³Cardiovascular Research Foundation, New York, New York; ⁴Columbia University Medical Center, New York, New York; ⁵Seoul National University Medical Center, Seoul, South Korea. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Lee, E. Shlofmitz, and R. Shlofmitz report honoraria from Cardiovascular Systems, Inc. Dr Jeremias reports grant support and personal fees from Abbott Vascular and Philips Volcano; personal fees from Opsens. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted February 6, 2018, provisional acceptance given February 23, 2018, final version accepted March 5, 2018.

Address for correspondence: Dr Michael S. Lee, UCLA Medical Center, 100 Medical Plaza, Suite 630, Los Angeles, CA 90095. Email: mslee@mednet.ucla.edu