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Background. Severe calcification of the carotid artery has been reported as a contraindication to stenting because the calcium prevents complete expansion of the stent. Cutting balloon angioplasty (CBA) may facilitate carotid stenting of severely calcified lesions by altering plaque morphology. We report the first case series of using CBA to facilitate stenting of heavily calcified carotid arteries. Methods. From August 2004–December 2005, 178 patients underwent carotid artery stenting at Baptist Medical Center-Princeton in Birmingham, Alabama. Of these patients, 23 (13%) had heavily calcified arteries, as determined by angiography and form the basis of this report. Mean patient age was 75 ± 18 yrs and 70% were asymptomatic. All patients were high risk for carotid endarterectomy (CEA). Cerebral protection was used in all but one patient (96%), where severe tortuosity precluded delivery of the protection catheter. Results. Quantitative angiographic analysis revealed baseline stenosis of 86 ± 6%. Following pre-dilatation with a cutting balloon, approximately 1–2 mm less than the reference vessel diameter and subsequent carotid artery stenting, angiographic success was achieved in all lesions with a mean residual post-dilatation stenosis of 14 ± 9%. There were no perioperative neurological complications. One perioperative death occurred secondary to severe hemorrhage from the groin site and anemia associated with ventricular fibrillation. Conclusion. Our series demonstrates the feasibility of stenting heavily calcified carotid arteries with this new pre-dilatation strategy. This study broadens the population of high-risk patients suitable for carotid artery stenting. Key words: cutting balloon angioplasty, carotid stenosis, calcium

Introduction
The Stenting and Angioplasty with Protection In Patients at High Risk for Endarterectomy (SAPPHIRE) trial demonstrated that among patients with severe carotid artery stenosis and significant comorbid conditions, carotid stenting with the use of an embolic-protection device was not inferior to carotid endarterectomy.¹ Still, a small number of patients in this trial were considered unsuited for stenting, partially based upon unfavorable anatomic features, and were excluded from the randomized protocol. Heavy calcification of the carotid artery lesion has been reported as an important predictor of complications and a contraindication to stenting because the calcium can inhibit complete expansion of the stent despite aggressive post dilatation.^2,3 In coronary arteries, cutting balloon angioplasty (CBA) can facilitate stenting in heavily calcified lesions. We report the first case series of CBA used to facilitate stenting of heavily calcified carotid arteries.

Methods
Patients. Between August 2004 and December 2005, 178 patients underwent carotid stenting at Baptist Medical Center Princeton, Birmingham, Alabama. Patients were eligible if they had neurologic symptoms and >50% diameter carotid artery stenosis or no symptoms and >80% stenosis. Of these patients, 23 (13%) had heavily calcified carotid arteries and form the cohort of this study. Heavy calcification was determined by the primary operator (FM) subjectively by fluoroscopy and was not otherwise quantified.

Technique. The carotid stenting procedure was performed as previously described⁴ with the following exceptions. Prior to the procedure 50mg of diphenyhydramine IV was administered to the patient for light sedative effects. Each patient was given 180mcg/kg IV bolus of eptifibatide and 0.75mg/kg IV bolus of bivalirudin prior to the intervention. The bivalirudin was continued at 1.75 mg/kg/hr for the duration of the procedure. All patients received aspirin 325mg and clopidogrel 600mg. In all patients, prior to stent delivery, the carotid lesion was pre-dilated with a cutting balloon (Boston Scientific, Natick, Massachusetts) with a diameter approximately 1–2mm less than the reference vessel diameter (i.e., the diameter of the internal carotid artery just past the lesion). A 2mm coronary balloon was used to predilate six lesions to facilitate delivery of the cutting balloon. The cutting balloon size was selected visually according to lesion length and diameter, with sizes ranging from 3mm x 6mm to 6mm x 15mm (see Table 2). The cutting balloon was subsequently slowly inflated (1 atm/5 sec) to 6 atm or nominal size. The cutting balloon was not inflated above 10 atm. The balloon was then slowly deflated and withdrawn into the guiding catheter. Cerebral protection (RX Accunet n=21, Guidant Corp. Menlo Park, California)(FilterWire EZ, n=2, Boston Scientific, Natick, Massachusetts) was used in all but one case where extreme tortuosity precluded delivery of the cerebral protection device. Routine inspection of the filter basket was not performed, but no macroscopic debris was observed when inspecting. Various stents were utilized during the carotid artery stenting procedures, including the Rx Acculink (n=21; (18) 10mm x 40mm; (3) 10mm x 30mm) (Guidant Corp.), Dynalink (n=1; 10mm x 28mm) (Guidant Corp.), and Conformexx (n=1; 10mm x 40mm) (CR Bard; Murray Hill, New Jersey). Following stent deployment, the lesion was post-dilated with a standard (non-cutting) angioplasty balloon with a diameter approximately equal to the reference vessel diameter. The average time from placement of the carotid sheath to removal was 49 minutes (± 33 minutes).

Data collection and end points. Clinical, angiographic, and hemodynamic data were prospectively recorded by a physician and research nurse. The primary clinical endpoint was: any death, minor or major stroke, TIA, or myocardial infarction during the hospitalization. Minor cerebral strokes were defined as neurological deficits that lasted <7 days or that increased the NIH Stroke Scale by 3 or less. Major cerebral strokes were neurological deficits that lasted >7 days and that increased the NIH Stroke Scale score by 4 or more. A TIA was defined as a new neurological deficit that completely resolved within 24 hours. A diagnosis of myocardial infarction was made when there was documentation of new pathological Q waves (>0.04 sec) on electrocardiogram in conjunction with an elevation in creatine kinase greater than twice the normal value with a positive CK-MB fraction or elevated troponin. Angiographic success was defined as achieving < 30% residual stenosis of the target lesion after stenting.

Perioperative hemodynamic depression was defined as hypotension (systolic blood pressure [SBP] <90mmHg) or bradycardia (heart rate <60 beats/min), regardless of symptoms. Postoperatively, patients requiring continuous vasopressor agents to keep SBP>90, atropine for symptomatic bradycardia, or pacemaker implantation were considered to have persistent hemodynamic depression.

Statistical analysis. All values are expressed as mean ± standard deviation.

Results
Patient demographics. Patient characteristics are summarized in Table 1. From August 2004 to December 2005, 23 patients underwent stenting of their heavily calcified carotid artery lesions. The majority of the patients (70%) were asymptomatic and referred to us after duplex ultrasonography or angiography disclosed evidence of carotid occlusive disease. Among the symptomatic patients, three had a history of a stroke, while four presented with TIAs. All patients included in the study had evidence of high-risk clinical features as follows: age >80 (n=9; 39%); severe COPD (n=5; 22%); severe CAD (n=21; 91%); contralateral carotid occlusion (n=2; 9%); or recurrent stenosis after CEA (n=1; 4%).

Angiographic results. All patients had heavily calcified carotid lesions by fluoroscopy. Quantitative angiographic analysis of the lesions at baseline and at the conclusion of the procedure is shown in Table 2. Pre-dilatation with a small non-cutting angioplasty balloon was necessary in six patients (26%) to facilitate delivery of the cutting balloon. Nineteen patients had CBA with stenting of the RICA, while four patients had CBA with stenting of the LICA. Mean stenosis at baseline was 86% (± 6%). Mean residual stenosis was 14% following the procedure. All procedures were angiographically successful (Figure 1).

Hemodynamic changes. Periprocedural hemodynamic depression (HD) was noted in six patients (26%). Non-persistent HD included isolated bradycardia without hypotension in one patient (3%) and hypotension, not requiring vasoactive medications, in two patients (9%) during the procedure.

Persistent hemodynamic depression was noted in three procedures (13% of all cases and 50% of all HD patients). Hypotension requiring dopamine occurred during the procedure in one patient (4%) and after the procedure in two patients (9%). The dopamine was continued for a mean of 7 ± 5 hours.

Procedural outcomes. There were no perioperative strokes, TIAs, or myocardial infarctions. One perioperative death occurred secondary to severe hemorrhage from the groin site due to the inability to control the bleeding following removal of the 6 Fr sheath. This resulted in acute blood loss anemia causing ventricular fibrillation. No other deaths occurred. Long-term results were not evaluated.

Discussion
This series demonstrates the feasibility and clinical utility of using CBA to facilitate carotid stenting in heavily calcified lesions. While this study is not randomized, it is unlikely that these calcified lesions could have been successfully stented with the standard approach. In all likelihood, the stents would have failed to expand fully being limited by the rigidity of the calcified plaques. In our study, the atherotomes on the cutting balloon scored the lesion improving the compliance of the calcified plaque enabling better stent expansion.
CBA has been successfully employed for coronary intervention on heavily calcified lesions.^5,6 It has also been used as a predilatation strategy in carotid stenting,⁷ but not specifically on carotid lesions with extreme calcification.

Heavy calcification of the carotid artery has been reported as a major risk factor for complications following carotid artery stenting. A proposed new carotid artery stenosis management algorithm³ strongly emphasizes the risk associated with heavy calcification. Likewise, in the recent Carotid Revascularization with ev3 Arterial Technology Evolution (CREATE) trial it was noted that heavy calcification led to the inability to stent certain patients.⁸

Severe calcification not only prevents full expansion of the stent, but it also prolongs dilatation time and requires increased balloon inflation pressures. A recent retrospective study revealed that patients with heavy calcification are at significantly higher risk of developing persistent hemodynamic depression (HD) during carotid artery stenting, which has been associated with adverse outcomes.⁹ It was proposed that the heavy calcification facilitates transmission of inflation pressures to the carotid baroreceptors leading to HD.⁹ These data come from studies using standard angioplasty balloons to pre-dilate calcified carotid arteries.

Although HD occurred in 7 patients (30%) in our study, vasoactive medications were necessary in only 3 cases (13%) with more persistent hemodynamic changes. Gupta et al⁹ noted approximately 50% of their patients that developed persistent HD had heavily calcified plaques. The risk of peri-procedural hemodynamic depression appears lower with the use of the cutting balloon to pre-dilate the lesion.

Our results indicate that CBA prior to stenting heavily calcified carotid arteries may improve the outcomes associated with these difficult lesions. While one death occurred not specifically related to carotid dilatation, our results are encouraging since no strokes or TIAs were observed.

A limitation of this study was the qualitative, not quantitative assessment of plaque calcification. Intravascular ultrasound (IVUS) could have been used to quantify the calcium in these lesions, but that was not determined to be clinically necessary given that fluoroscopy is moderately sensitive for characterizing heavy calcification¹⁰ and data from prior studies had assessed calcification qualitatively.

While not randomized, our study suggests that CBA facilitates stenting of severely calcified carotid lesions and leads to good clinical outcomes. If confirmed by other studies or even a randomized comparison to non-cutting balloon pre-dilatation, this approach may become the standard for these difficult to treat lesions.