Alternative Rota-Flush Solution for Patients With Severe Coronary Artery Calcification who Undergo Rotational Atherectomy

Abstract: We assessed the feasibility and safety of a rota-flush solution with 10,000 U of unfractionated heparin in 1 L of normal saline in patients who underwent rotational atherectomy. Background. Rotational atherectomy with the Rotablator (Boston Scientific) rotational atherectomy system is an effective way to modify severely calcified plaque. Potential complications include coronary spasm and slow-flow/no-flow. A pressured rota-flush solution is infused into the device to lubricate the drive shaft to minimize the risk of these complications as well as facilitate delivery of the device. RotaGlide lubricant (Boston Scientific), which decreases the friction between the drive shaft and RotaWire (Boston Scientific), is routinely added to the rota-flush solution. Antispasmotic agents including nitroglycerin and verapamil are commonly added to the rota-flush solution, but can lead to hemodynamic disturbances like hypotension and bradycardia. Methods. A total of 67 consecutive patients who underwent rotational atherectomy from July 2012 to June 2015 were included in this analysis. The primary endpoint was procedural success. Results. Procedural success was achieved in all patients. Significant hypotension occurred in 6%. No patients developed severe bradycardia requiring emergent insertion of a transvenous pacemaker. Major adverse cardiac and cerebral events occurred in 6.0%, all due to non-fatal myocardial infarction. Slow/no flow occurred in 7%, with subsequent resolution after intracoronary vasodilator therapy. Coronary spasm occurred in 4%. Stent thrombosis, perforation, flow-limiting dissection, and stent loss were not observed. Conclusion. A rota-flush solution with 10,000 U of unfractionated heparin in 1 L of normal saline is a reasonable alternative to the routinely used solution which includes the RotaGlide lubricant, nitroglycerin, and verapamil. 

J INVASIVE CARDIOL 2017;29(1):25-28. Epub 2016 June 15.

Key words: rotational atherectomy, calcification, coronary artery disease

Severe coronary artery calcification increases the complexity of percutaneous coronary intervention (PCI) due to increased difficulty in stent delivery and optimal stent expansion.¹ Severe coronary artery calcification is also associated with an increased risk of major adverse cardiac events including death, myocardial infarction (MI), and repeat revascularization.² Rotational atherectomy (RA) with the Rotablator (Boston Scientific) is a safe and effective coronary atherectomy method that facilitates stent delivery and stent expansion by modifying severely calcified plaque.³ A pressurized flush solution lubricates the drive shaft to reduce friction and prevent overheating, which can lead to an increase in viscosity, coronary vasospasm, and slow-flow/no-flow. The standard flush includes the RotaGlide lubricant (Boston Scientific) as well as vasodilators like nitroglycerin and verapamil. Hypotension can develop during RA due to ischemia as well as from the vasodilators in the rota-flush solution. Bradycardia can also develop from verapamil. Therefore, in lieu of the standard rota-flush solution, we currently use a solution containing 10,000 U unfractionated heparin in a 1 L bag of normal saline. We report the feasibility and safety of RA with this rota-flush solution for the treatment of severe coronary artery calcification. 

Methods

Study population. Data were collected on 67 consecutive patients who underwent RA from July 2012 to June 2015 at the UCLA Medical Center, Los Angeles, California. All patients had severely calcified lesions ≥70% stenosis and reference vessel diameters measuring ≥2.5 mm and ≤5.0 mm. The institutional review board approved the review of the data.

Procedures and medical treatment. Standard techniques were used to perform PCI either with transfemoral or transradial access. Dual-antiplatelet therapy was administered prior to RA. Unfractionated heparin was administered intravenously to achieve an activated clotting time >250 seconds. Fractional flow reserve measurement was routinely obtained for coronary lesions with 50%-70% stenosis. Operator discretion was used to insert a temporary pacemaker, administer intracoronary nitroglycerin, and choose either a drug-eluting or bare-metal stent.

The size of the RA burr chosen was based upon a burr to reference vessel diameter ratio of 1:2. Typically, a 6 Fr guiding catheter was used when the maximum burr size was 1.25 or 1.5 mm. A 7 Fr or 8 Fr guiding catheter was used when the maximum burr size was 1.75 mm or 2.0 mm. 

A 0.009˝ Rota-floppy wire (Boston Scientific) was used to traverse the lesion. However, for complex lesions, a work-horse wire was initially used to traverse the lesion followed by swapping out the wire with an over-the-wire balloon for the Rota-floppy wire. A pressure bag infused the rota-flush solution containing 10,000 U of unfractionated heparin in 1 L of normal saline in lieu of a solution containing the RotaGlide lubricant, nitroglycerin, and verapamil. After starting the rota-flush solution and advancing the burr on the wire prior to entering the Touhy Borst, the burr was activated primed at 150,000-170,000 rpm. The duration of each pass with the burr was ≤20 seconds. 

Patients were treated with dual-antiplatelet therapy for a minimum of 1 month for bare-metal stent and 1 year for drug-eluting stent as well as statin, beta-blocker, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, unless contraindicated. 

Study endpoints and clinical follow-up. The primary endpoint was procedural success, defined as residual stenosis ≤30% and Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 without death, emergency coronary artery bypass graft surgery and/or PCI, and stent loss during the first 24 hours. Secondary endpoints were severe hypotension (drop in systolic blood pressure ≥20 mm Hg) as well as severe bradycardia requiring emergent transvenous pacemaker insertion. Major adverse cardiac and cerebral events were defined as cardiac death, non-fatal MI, target-lesion revascularization, and stroke. Death was considered cardiac in origin unless a non-cardiac origin was documented. MI was defined as the development of ischemic symptoms and new ST-segment elevation or elevation of cardiac markers ≥2x the upper limit of normal. Target-lesion revascularization was defined as percutaneous or surgical revascularization of the target lesion for ischemia due to stenosis ≥50% of the luminal diameter anywhere within the stent or within the 5 mm borders proximal or distal to the stent. Stent thrombosis was defined according to the Academic Research Consortium definition.⁴

Medical records were used to obtain patient data and adverse clinical events. Data were entered into a dedicated PCI database. 

Statistical analysis. Continuous variables are expressed as mean and standard deviation. Categorical variables are expressed as percentages. Statistical analysis was performed with SAS version 9.1 (SAS Institute, Inc).

Results

Patient characteristics. The majority of the patients were male (69%), and 39% were diabetic (Table 1). Acute coronary syndrome was the indication for RA in 33% of patients. The target vessels treated included unprotected left main disease in 7% of patients (Table 2). The mean maximum burr size was 1.5 ± 0.1 mm, the mean number of burrs used was 1.3 ± 0.2, and the mean number of passes per case was 3.6 ± 1.2.

Clinical outcomes at 30 days. Procedural success was achieved in all 67 patients (Table 3). Four patients (6%) experienced significant hypotension requiring bolus of intravenous phenylephrine. Hemodynamic stability was achieved in 3 patients prior to leaving the cardiac catheterization laboratory. One patient required inotropic agents and emergent insertion of an intraaortic balloon pump. No patients developed severe bradycardia requiring emergent insertion of a transvenous pacemaker. The burr was successfully delivered to the target lesion and subsequently removed after atherectomy without loss of wire position in all patients. Major adverse cardiac and cerebral events occurred in 6.0%, all due to non-fatal MI. Cardiac death, target-lesion revascularization, and stroke did not occur. Slow-flow/no-flow occurred in 7%, all of whom had lesion length >30 mm, with subsequent resolution with intracoronary vasodilator therapy and achievement of TIMI grade 3 flow in all patients. Coronary spasm occurred in 4%, and resolved after administration of intracoronary nitroglycerin in all patients. Stent thrombosis, perforation, flow-limiting dissection, and stent loss were not observed. 

Discussion

The main finding of this study was that RA performed with 10,000 U of unfractionated heparin in 1 L of normal saline infused with a pressure bag was a safe and effective alternative to the conventional rota-flush solution that contains RotaGlide lubricant, nitroglycerin, and verapamil. The primary endpoint of procedural success was achieved in all patients with acceptable rates of severe hypotension, bradycardia slow-flow, and coronary spasm. 

In patients who underwent RA in the ROTAXUS trial, no patients experienced slow-flow/no-flow.⁵ In our analysis, 7% of patients experienced slow-flow/no-flow. A possible explanation for the higher rate of slow-flow/no-flow in our cohort was the absence of vasodilators in the rota-flush solution. Another explanation is that all patients who experienced slow-flow/no-flow had a lesion length >30 mm. RA is indicated in patients with native-vessel atherosclerotic coronary artery disease lesions <25 mm in length, whereas patients with lesions >25 mm who undergo RA are at a higher risk for adverse events.⁶ Atherectomy of long lesions may lead to distal embolization of atherosclerotic debris, which can lead to slow-flow/no-flow. In addition to the optimal rota-flush solution, techniques to potentially reduce the incidence of such complications include a short duration of each pass (<15-20 seconds), using a lower speed (<150,000 rpm), short repetitive movements (“pecking”) of the RotaLink advancer when engaging the lesion, resisting the urge to push the Advancer aggressively if the burr encounters resistance as demonstrated by deceleration of >5000 rpm or a change in the pitch of the spinning burr, and a strategy of starting with a small burr and escalating to a larger size if necessary. 

Various “cocktails” for the rota-flush have been used to minimize the risk of RA complications like vasospasm. Typically, these include normal saline, unfractionated heparin, nitroglycerin, verapamil, and RotaGlide lubricant. The RotaGlide lubricant, which includes egg white phospholipids and olive oil, is a lipid-based emulsion that decreases the friction between the drive shaft and RotaWire. Despite not using RotaGlide as a part of the rota-flush solution, the adverse clinical event rates were acceptable. The incidence of coronary vasospasm was 4%, while significant hypotension occurred in 6%. The use of this rota-flush without RotaGlide is a reasonable and inexpensive alternative, especially if RotaGlide is not available and RA is required to modify calcified plaque to successfully perform PCI. For cost comparison, RotaGlide is approximately $80 while 10,000 U of unfractionated heparin is generally less than $5. The rota-flush that was used in our study may be a particularly attractive option in patients who are hypotensive or have severe left ventricular dysfunction and may not have the contractile reserve to tolerate a cocktail that includes vasodilators like nitroglycerin and verapamil, which can cause hypotension.

Although verapamil is a vasodilator to decrease the incidence of coronary spasm, it is also an atrioventricular nodal blocker. The addition of verapamil in the rota-flush can lead to severe bradycardia. Our rota-flush solution did not include verapamil and may be particularly attractive in patients who are bradycardic at baseline. No patients experienced severe bradycardia in our study. 

Despite the absence of the RotaGlide lubricant, the burr was delivered to the lesion without difficulty. After completion of RA, the burr was easily removed and the wire position was not lost. If exchanging and upsizing to a larger burr is required, meticulous management by constant wiping of the Rota Wire to remove the formation of grit from dried contrast and blood is recommended.

Study limitations. This study was non-randomized and conducted at a single center by a single operator. Comparison with patients who underwent RA with the conventional rota-flush solution was not performed. The number of patients was small and the duration of follow-up was short. The outcomes of our study need validation in a larger population of patients with longer-term follow-up. Periprocedural MI may have been underdiagnosed, as cardiac biomarkers were not routinely drawn on all patients. 

Conclusion 

The use of a rota-flush solution containing 10,000 U of unfractionated heparin in 1 L of normal saline is a feasible and reasonable alternative to the use of a rota-flush solution that contains RotaGlide and vasodilators like nitroglycerin and verapamil. It is inexpensive and may be particularly attractive in a patient with hypotension or severe left ventricular dysfunction. Patients with bradycardia at baseline are also good candidates for this rota-flush solution, which does not include an atrioventricular nodal blocker. Further studies are needed to determine the safety and efficacy of this treatment strategy compared with the standard rota-flush solution.

References

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2.     Lee MS, Yang T, La Sala 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 Jan 12 (Epub ahead of print).

3.     Levine GN, Bates ER, Blankenship JC, et al. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58:e44-e122.

4.     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.

5.     Abdel-Wahab M, Richardt G, Joachim Buttner H, et al. High-speed 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;6:10-19.

6.     Rotablator Rotational Atherectomy System: Indications, Safety, and Warnings. Accessed at https://www.bostonscientific.com/en-US/products/plaque-modification/rotablator-rotational-atherectomy-system/indications--safety-and-warnings1.html. Accessed on  April 23, 2016.

From the ¹Division of Cardiology, University of California, Los Angeles Medical Center, Los Angeles, California; ²Division of Cardiology, Dong-A University Medical Center, Busan, Korea; and ³Cardiovascular Center, Korea University Guro Hospital, Seoul, Korea.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lee reports speaker’s bureau fees from CSI. The remaining authors report no disclosures regarding the conflict herein.

Manuscript submitted April 18, 2016, final version accepted April 26, 2016.

Address for correspondence: Michael S. Lee, MD, Associate Professor of Medicine, 100 Medical Plaza Suite 630, Los Angeles, CA 90095. Email: mslee@mednet.ucla.edu