The effect of increasing operator experience on procedure-related characteristics in patients undergoing carotid artery stenting

Abstract

Objectives

To evaluate the efficacy and safety of carotid artery stenting for the treatment of severe carotid artery disease in our department and to investigate the effect of increasing operator experience on perioperative and procedure-related characteristics.

Methods

From January 2007 to February 2015 200 patients underwent 207 endovascular procedures for carotid artery stenosis. Of all, 113 arteries (56.5%) were symptomatic. Significant changes across time were calculated with the use of Change Point analysis using bootstrap and mean squared error estimates.

Results

The technical success was 98.6% (204/207 cases). Thirty-day neurological events included stroke in four patients (2%) and transient ischemic attack in two (1%). None of the patients died during the first 30 days. The most significant change of radiation duration occurred after the 33rd patient with a decrease from 25.31 min to 12.31 min, while for the total operative time that change occurred between the 31st and 33rd patient where mean operation time decreased from 88.89 min to 49.22 min. The most significant change of contrast media used occurred at the 40th patient with a decrease from 91.58 ml to 62 ml. During a mean follow-up period of 42 ± 20.02 months none of the patients experienced any cerebrovascular event. There was one case of significant recurrent stenosis, which was successfully treated by endovascular means.

Conclusions

Endovascular treatment of carotid artery stenosis performed in a single center with the use of a cerebral protection device seems to consist a safe therapeutic choice with acceptable results, within the referenced benchmarks proposed in the latest guidelines. Certain perioperative parameters such as the amount of contrast media used, the fluoroscopy and operation time, seem to decline overtime indicating increasing operator’s experience. A number of performed cases above 40 was related to the significant decrease of those parameters and may represent the learning curve of the procedure.

Keywords

Operator experience carotid artery stenting

Introduction

Atherosclerotic stenosis of the carotid artery is a major cause of ischemic stroke in the western world.¹ Carotid endarterectomy (CEA) has been used as a tool for stroke prevention for many decades. The beneficial role of CEA in preventing strokes, mostly for symptomatic and to a lesser extent for asymptomatic patients, has been highlighted in all current guidelines.² In the era of less invasive procedures carotid artery stenting (CAS) has emerged as an evolving alternative technique that may even be used as first-line treatment in high-risk patients.³ Randomized controlled trials comparing CEA and CAS have produced diverging results which may be at least partially explained by heterogeneity in patient’s cohort, endpoint definition, and operator experience.^3–6

Despite the continuous debate on the best treatment choice for carotid artery stenosis the use of endovascular therapy has intensely increased worldwide. CAS has shown an improvement over time to reduce the rate of perioperative and 30-day neurological events, a fact which may be attributed to the better patient selection, endovascular devices’ development and growing operator experience.^7,8 The performance of this procedure by experienced interventionists may also potentially further improve the results, though this is a point still under investigation as several reports still provide conflicting estimations.⁹

The aim of the present study was to analyze all CAS procedures performed at our institution between 2007 and 2015 with respect to efficacy, safety, and mid-term outcome and to investigate the effect of increasing operator experience on perioperative and procedure-related characteristics.

Materials and methods

All patients who underwent endovascular treatment for internal carotid artery (ICA) stenosis in our institution from the initiation of the CAS program in January 2007 until February 2015 were included. Symptomatic patients included those with previous transient ischemic attacks (TIA) or strokes ipsilateral to the carotid lesion within the last six months. The degree of stenosis was evaluated by color duplex ultrasound imaging according to established criteria and confirmed by computed tomography angiography (CTA) of the aortic arch and intracranial and extracranial arteries.¹⁰

Eligibility criteria for revascularization with CAS were determined on the basis of symptomatic stenosis over 70% or asymptomatic stenosis over 80% and the presence of significant medical co-morbidities. CAS was contraindicated in case of total ICA occlusion, the presence of free-floating thrombus, severe chronic kidney disease (estimated glomerular filtration rate (e-GFR) <30 ml/min) or contraindications against the use of dual antiplatelet therapy for at least four weeks. All patients signed an informed consent prior to the intervention and the study was approved by the institutional ethics committee.

Technique

All patients were put on dual anti-platelet therapy (acetylsalicylic acid (100 mg per day) and clopidogrel (75 mg per day)) at least three days prior to intervention.

All procedures were performed by the same senior operator (MM) and the same surgical and anesthesiology team following the same protocol. The procedures were performed under local anesthesia without sedation in an operation theatre with the presence of an anesthesiologist. During the procedure unfractionated heparin was administered (50 IU to 100 IU per kg body weight) to achieve an activated clotting time of 250–300 s. Access to the lesion was performed via the femoral artery using an 8F guiding catheter, finally positioned in the mid part of the common carotid artery. All procedures were attempted to be performed using cerebral protection devices. Following the placement of the protection device, the stent was deployed and post-dilation performed with a balloon of 5 to 5.5 mm in diameter. In case pre-dilatation was needed, a 2.5–3.5 mm diameter balloon was used. The choice of stent was at the discretion of the surgeon (tapering, open or closed cell design) and there was a preference of close-cell design for symptomatic lesions, according to the anatomy as well. Stenting was intended in every procedure and stent position typically extended from the common to the internal carotid, crossing the origin of the external carotid artery. Before retrieval of the protection device, final biplane angiogram of the stented lesion as well as intracranial views was obtained. Technical success was defined by the coverage of the carotid lesion with a stent in the presence of a residual stenosis <30% and normal flow. During the CAS-procedure, all patients were monitored neurologically as well as for vital parameters under the care of the anesthesiological team. After the procedure patients continued to receive dual anti-platelet therapy for at least one month and continued on single antiplatelet agent thereafter.

Outcome

All patients underwent neurological examination by a neurologist prior to and after the endovascular procedure as well as before hospital discharge. TIA was defined as a new focal, retinal or hemispheric event that persisted for less than 24 h. Minor stroke was defined as focal neurological deficit lasting more than 24 h with Ranking score <2 and National Institutes of Health (NIH) Stroke Score <4, while major stroke was diagnosed in the presence of a Ranking score >3 or NIH score >15.¹¹

Clinical and duplex ultrasound follow-up visits to our outpatient clinic were routinely scheduled at 1, 6, and 12 months after the index procedure and yearly thereafter. Restenosis was diagnosed in the presence of a >50% luminal narrowing as assessed by flow velocities using color duplex ultrasonography.¹¹ Stenosis was classified as: not significant (0–49% stenosis), moderate (50–69%), severe (70–99%), or occlusion (100%).

Statistical analysis

Data are expressed as mean ± standard deviation, except for non-Gaussian parameters, which are presented as median (range). Categorical data are represented by number (n) and percentage (%). Statistical analyses were performed using SPSS 20.0 statistics software (SPSS Inc, Chicago, IL). A p value of <0.05 was considered as statistically significant. Significant changes across time were calculated with the use of Change Point analysis using bootstrap and mean squared error (MSE) estimates. Change point analyzer v2.3 was used for that part of the analysis.

Results

During the study period, 207 CAS procedures were performed in 200 patients (mean age 70.5 ± 8.7 years, 81.5% male). The demographic and clinical data of the patients treated are summarized in Table 1. In all lesions the pathology was primary stenosis. Symptomatic stenoses were treated in 113 lesions (56.5%). Patients with symptomatic stenosis were more likely to suffer from diabetes (p = 0.02) and to have a history of smoking (p = 0.004), (Table 2). Symptoms included TIA in 63 (55.7%), stroke in 35 (31%) and Amaurosis fungax in 15 (13.3%) patients.

Table 1.

Patient and lesion characteristics.

	n (%)
Patient characteristics
Male gender	163 (81.5)
Age (years)	70.5 ± 8.7
Risk factors
Hypertension	128 (64)
Hyperlipidemia	135 (67.5)
Diabetes	42 (21)
CAD	74 (37)
COPD	58 (29)
Smoking	69 (34.5)
Lesion characteristics
Side
Left ICA	91 (44)
Right ICA	116 (56)
Symptomatic lesions
Stroke	35 (31)
TIA	63 (55.7)
Amaurosis fungax	15 (13.3)

CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; ICA: internal carotid artery; TIA: transient ischemic attack.

Table 2.

Patients’ characteristics according to the presence of symptoms.

	Symptomatic n = 113	Asymptomatic n = 87	p
Male gender	89 (78.8)	68 (78.2)	0.49
Age (years)	69.9 ± 8.6	71.1 ± 8.8	0.42
Risk factors
Hypertension	72 (63.7)	55 (63.2)	0.44
Hyperlipidemia	75 (66.4)	60 (69)	0.45
Diabetes	28 (24.8)	11 (12.6)	0.02
CAD	42 (37.2)	30 (34.5)	0.37
COPD	32 (28.3)	26 (29.9)	0.47
Smoking	50 (44.2)	19 (21.8)	0.004
Days of stay	2 (2–6)	2 (2–4)	0.78
Cerebrovascular events
Stroke	4	0	0.132
TIA	1	1	0.71
Stent design
Open cell	55	72
Closed cell	62	18	<0.001
Hybrid cell	2	2

CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; TIA: transient ischemic attack.

All procedures were accomplished under local anesthesia, while in all patients access was achieved through the femoral artery. Successful recanalization of treated vessel was obtained in 204 cases (98.6%). There were three technical failures. In one patient we were unable to deploy the embolic protection device (EPD) proximal to the lesion due to severe ICA kinking, while in another patient common carotid artery catheterization was failed due to the presence of hostile aortic arch. The third patient had a nearly occluded ICA characterized by an echoluscent, irregular plaque and we were not able to cross the lesion. All three patients were converted on site to CEA under general anesthesia with a good clinical result.

The type of the stent and EPD used are shown in Table 3. EPDs were applied in all technically successful procedures. The vast majority (98.5%) included filter devices, while balloon occlusion devices were used only in three patients. The lesions were pre-dilated in 37 cases (18.1%) and post-dilated with a balloon in all procedures. Stents were applied in all lesions. One stent per procedure was used in 197 lesions (96.6%), while in seven lesions the use of two stents was necessary, due to long carotid lesions (4 cases), or extensive jumping of the first stent (3 cases). Stents with an open cell design were deployed in 118 patients, while closed cell stents in 86 patients. Symptomatic patients were more likely to receive a stent of closed cell design (p < 0.001).

Table 3.

Procedural characteristics.

	n (%)
Type of stent
Acculink (Abbott)	94 (44.5)
X-act (Abbott)	40 (18.9)
Exponent (Medtronic)	21 (10.1)
Adapt (Boston)	33 (15.6)
Protégé (Covidien)	12 (5.7)
Wallstent (Boston)	7 (3.3)
Crystalloo Id(Invatec, Medtronic)	4 (1.9)
Type of EPD
Accunet (Abbott)	81 (39.7)
Emboshield (Abbott)	54 (26.5)
Interceptor+ (Medtronic)	29 (14.2)
Filterwire (Boston)	37 (18.1)
Moma (Invatec, Medtronic)	3 (1.5)

EPD: embolic protection device.

Median fluoroscopy time was 9 (interquartile range 7-15) min (Figure 1). The table of significant changes (Table 4) shows that these occur after the 33rd patient with a decrease in fluoroscopy time values from 25.31 min to 12.31 min. The 100% confidence interval for this estimation shows that this change happens at the 33rd patient and this was very well defined. Another change in mean values occurs at about the 49th patient but with a large confidence interval for the 41st patient to the 62nd where fluoroscopy time values decrease from 12.31 min to 8.95 min. The third change occurs at the 173rd patient but it is with a very large confidence interval to be leading to any useful conclusion.

Figure 1.

Plot showing the duration of fluoroscopy applied in each case in chronological order.

Table 4.

Table for significant changes in fluoroscopy time.

Patients	Confidence interval	Conf. level	From (min)	To (min)	Level
33	(33,34)	100%	25.312	12.31	1
49	(41,62)	100%	12.312	8.95	2
173	(66,173)	90%	8.956	4.75	6

min: minutes; confidence level for candidate changes = 50%, confidence level for inclusion in table = 90%; confidence interval = 95%; bootstraps = 1000; Without replacements, MSE estimates.

Median contrast volume used was 44 ml (interquartile range (IQR) 30-70 ml) (Figure 2). The table of significant changes shows that these occur after the 7th patient with a decrease in contrast values from 146.67 ml to 121.43 ml (Table 5). The 99% confidence interval for this estimation is the 7th, 8th or 9th patient. Another change in mean values occurs for the 21st patient (20th to 22nd) where contrast values decrease from 121.43 ml to 91.58 ml. This change is more clearly stated and perfectly defined (confidence interval (CI): 100%) between the 20th and 22nd patient. The clearest of all changes occurs at the 40th patient with a decrease from 91.58 ml to 62 ml. This is characterized as a “level one” change since the 100% CI is 40–40. A final change occurs from 63 ml to 35.27 ml at the 55th (55th–58th) patient.

Figure 2.

Plot showing the amount of contrast media used in each case in chronological order.

Table 5.

Table for significant changes for contrast media.

Patients	Confidence interval	Conf. level	From (ml)	To (ml)	Level
7	(7.9)	99%	146.67	121.43	3
21	(20,22)	100%	121.43	91.58	2
40	(40,40)	100%	91.579	62	1
55	(55,58)	100%	62	35.27	4

Confidence level for candidate changes = 50%; confidence level for inclusion in table = 90%; confidence interval = 95%; bootstraps = 1000, without replacements, MSE estimates.

Median total operation time was 45 min (interquartile range 20–180 min) (Figure 3). As shown from the table of significant changes (Table 6), of the six changes the most clearly defined is the one between the 31rd and 33rd patient where mean operation time decreases from 88.89 min to 49.22 min. Smaller changes occur before that and the one at the 22nd to 24th patient is well defined and shows a decrease from 106.67 min to 88.89 min. All other changes observed are rather vaguely defined as to the number of patients that establishes them.

Figure 3.

Plot showing the duration of the procedure in each case in chronological order.

Table 6.

Table for significant changes for total operation time.

Patients	Confidence interval	Conf. level	From (min)	To (min)	Level
13	(8,14)	98%	139.17	106.67	4
22	(22,24)	100%	106.67	88.89	3
31	(31.33)	100%	88.89	49.22	1
91	(63,95)	98%	49.22	37.25	7
111	(101,154)	96%	37.25	44.46	5
155	(146,155)	100%	44.46	26.25	2

min: minutes; confidence level for candidate changes = 50%; confidence level for inclusion in table = 90%; confidence interval = 95%; bootstraps = 1000, Without replacements, MSE estimates.

During the 30-day postoperative period, four patients, all symptomatic, suffered an ipsilateral stroke, yielding a periprocedural stroke rate of 2%. All these strokes were minor and none of them became disabling through the hospitalization period. Two (1%) patients, one symptomatic and one asymptomatic, suffered a TIA, while in two other patients cognitive dysfunction was observed after the operation that completely resolved after 1–3 days. All the cerebrovascular events occurred after the completion of the procedure. The events occurred in various patients (39th, 46th, 59th, 95th, 112th, 169th) and no temporal relationship was evident. No significant correlation between the cerebrovascular event occurrence and the presence of symptoms was found (stroke, p = 0.104; TIA, p = 0.607). Also, no significant relation was shown between the cerebrovascular event occurrence and the type of stent (stroke, p = 0.405; TIA, p = 0.624). There were no deaths or myocardial infarction within 30 days. Median hospital in-stay was two days.

During a follow-up period spanning an average of 42 ± 20 months 24 patients (12%) were lost to follow-up. All had completed the first year of follow-up, and 14 had completed ≥2 years before they were considered lost to follow-up. The latest recorded data for these patients were used for the analysis. None of the patients suffered any cerebrovascular event during the follow-up period. There was only one restenosis observed at two years post-operatively, in a patient suffering from asymptomatic disease. It was an in-stent restenosis in the mid portion of the stent that was progressed in >90% after two more years. This patient was successfully treated by CAS again, using a balloon expandable short stent this time.

Discussion

CAS constitutes a minimally invasive procedure currently indicated in the treatment of those patients in whom surgery is contraindicated.² Although randomized trials could not establish its equivalence and non-inferiority to CEA, CAS is rapidly evolving and been increasingly performed around the world.¹² Numerous inclusion and exclusion criteria defining the eligibility of the participating patients in the randomized trials have raised concerns whether their results could be extrapolated to the daily practice. Results of CAS on single center basis are quite promising, showing high feasibility and very low rates of cerebrovascular events.^13,14 The results of the present series show that CAS in patients treated in a single center can be performed safely and with mid-term outcome comparable to CEA. In the present series, the procedure proved feasible yielding a technical success rate of nearly 98%. This rate is comparable with those reported in the literature varying between 95% and 100%.¹⁵ Interestingly the two out of three cases of failure due to technical difficulties were in the first 30 procedures of this series. After that only one technical failure in 150 procedures was noted, probably reflecting the growing institution’s experience.

The overall stroke rate of CAS within our population was 2%, while none of the patients died. This rate is lower than those reported in the randomized controlled trials (RCTs) and below the referenced benchmark of 3% recommended in the European guidelines.^3–6,16 All strokes occurred in symptomatic patients, though this difference have not reached a statistical significance, probably due to the relatively small number of patients and events. Larger studies often report symptomatic patients to have worse outcomes.¹⁷ Furthermore during the perioperative period two patients suffered from cognitive dysfunction, expressed mostly as short-term memory loss. Maggio et al reported that peri-procedural brain microembolic load found with brain MR impacts negatively on cognitive functions, independently from the influence of patients-related variables.¹⁸ In both of our patients however this dysfunction completely resolved after one and three days, while no findings of postoperative new white matter lesions in the brain CT were evident.

As part of our institutional protocol all carotid stenting procedures were performed with the deployment of an EPD. The use of embolic protection consists currently an integral part of the procedure; though the choice of proximal or distal EPD has been debatable.¹⁵ In the vast majority of cases we used a distal filter given their ease of use. The lesion has to be crossed before filter deployment and in some cases even a pre-dilatation of the lesion may be needed. The application of a balloon occlusion device was performed only in three patients whose plaque morphology and luminal stenosis prohibited the crossing of the lesion without protection. These devices do not require lesion crossing, they can be applied in pre-occlusive lesions with significant thrombus and can be deployed from the beginning. However they require larger sheath while they may also compromise common carotid artery and aortic arch integrity. In a randomized trial of nearly 60 patients undergoing CAS, proximal balloon occlusion as compared with filter protection significantly reduced the embolic load to the brain.¹⁹ Larger studies are certainly needed to clarify the indications for each technique.

Another part of the procedure still under investigation is the use of open or closed cell stents. A small randomized trial reported non-superiority of either cell structure,²⁰ while a larger retrospective study reported a possible higher postoperative complication rate with the increase of free cell area of stents.²¹ A recent meta-analysis showed no significant differences in 30-day cerebrovascular complications between the open-cell and the closed-cell group.²² In our study most patients were treated with open cell stents. Symptomatic patients were more likely to receive a stent of closed cell design; though no correlation was found between the event occurrence and the stent type. Since there are no recommendations regarding the best option, our practice is mainly based on the clinical presentation of the patient, plaque characteristics as well as the presence of severe tortuosity of the ICA.

The performance of CAS by experienced operators is a subject thoroughly analyzed in the literature, though the number of procedures required per operator-center remains unspecified. It is widely accepted that the operator’s CAS volume is an important predictor of morbidity after carotid stenting procedures.²³ The European Society for Vascular Surgery (ESVS) guidelines suggest performance in high volume centers exceeding 30 cases per year with individual practitioners exceeding 15 cases annually.¹⁶ Carafiello et al. by reporting outcomes in 103 CAS patients found a statistically significant difference in cerebrovascular complication occurrence in the first 50 patients when compared to the last 53 pts.²⁴ Although in this study the division of the patients in two groups was empirical, a relation of the learning experience of the operators and the neurological complications was implied. More recently a pooled analysis of carotid stenting trialists collaboration concludes that CAS is safe to be performed by interventionists whose volume exceeds six cases per annum.²⁵ However the use of the periprocedural complication rates to define the number of interventions required to overcome the negative effects of the initial CAS learning phase seems problematic, considering the low event rates. This kind of analysis would require a huge number of patients from a single-center to reach an adequate statistical power.

The present single–center series includes all patients treated at our institution and therefore comprises a learning curve. Perioperative parameters such as radiation time, duration of the operation, and amount of contrast media used may serve as indicators of operator’s experience. Excess of fluoroscopy time and consequently the exposure dose during the procedure could cause hazards to the patient,¹⁸ while the excessive volume of contrast material is considered a risk factor and independent predictor of acute kidney injury.²⁶ Their decline overtime could potentially designate increased operator’s experience. In the present series the duration of fluoroscopy and radiation time significantly declined approximately after the 40th case and so did the dose of contrast media maintaining a specific range of values in the following. Considering these findings we may define the 40 cases as the learning curve of the procedure.

Long-term prevention from neurologic events constitutes the hallmark of effective carotid revascularization. During the follow-up period none of our patients sustained any cerebrovascular event. These results are in coherence with those reported in randomized studies that have demonstrated the same low mid-term stroke rate with no significant differences between CAS and CEA.^27,28

This study reports data from a single center and due to its retrospective nature lacks power to draw widely applicable conclusions. All procedures were performed by the same senior operator and the same surgical and anesthesiology team. We admit that this could have been a limitation in the present study since the result may reflect the learning curve of one operator, rather than the average (or median) learning curve of a group of operators. On the other side, such an analysis would have required data from a much larger CAS cohort that could not be easily provided from a single-center study. Furthermore the relatively limited number of patients does not allow subgroup analysis for detection of patient or lesion’s characteristics that may account for a different risk for cerebrovascular events.

Conclusion

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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