Abstract
Background
Ischemic stroke and disability caused by carotid artery stenosis have always been worldwide problems. At present, carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS) have been commonly used to treat carotid artery stenosis. Recently, transcarotid artery revascularization (TCAR) seems to be another option.
Methods
We searched PubMed and Embase to find literatures comparing TCAR with TFCAS and CEA. The primary outcomes were stroke, myocardial infarction (MI), transient ischemic attack (TIA), death, cranial nerve injure (CNI), and operative time. Secondary outcomes were stroke, death, MI in the elderly; cost; radiation; and entry site complication.
Results
Initial search of the literature included 165 articles, of which 12 studies were chosen in the end. These studies demonstrated high technical success rate of TCAR. Patients who received TCAR had lower risks of death, stroke/death and less radiation exposure compared to TFCAS. In meta analysis, the risk of stroke was significantly lower in TCAR group than TFCAS (OR 0.63; 95%CI 0.47–0.85). And there was no significant difference in TIA and MI. TCAR was associated with shorter operative time, lower risk of CNI and less blood loss compared to CEA. In older patients, the effect of TCAR was significantly better than that of TFCAS.
Conclusion
TCAR is associated with a lower risk of perioperative stroke compared to TFCAS. TCAR is also associated with shorter operative time, lower risk of CNI and less blood loss compared to CEA. TCAR may be a promising treatment option besides TFCAS and CEA.
Keywords: Carotid artery stenosis, carotid endarterectomy, carotid artery stenting, transcarotid artery revascularization, TCAR
Introduction
Stroke is one of the main causes of death and disability throughout the world, about 25% of stroke can be attributed to atherosclerotic carotid artery disease. 1 Timely and correct treatment of carotid artery disease is an important part of stroke prevention.2,3
Besides the best medical treatment (BMT), carotid artery revascularization including carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS) was recommended for the treatment of carotid artery stenosis. CEA and TFCAS are both currently performed for asymptomatic patients with carotid stenosis more than 75% and symptomatic patients with carotid stenosis more than 50%. 4 The CEA has long been thought to be the gold standard of the treatment, 5 but TFCAS has become an alternative to CEA due to its less invasive merit.5–7 However, both CEA and TFCAS have limitations.4,5 Recently, transcarotid artery revascularization (TCAR) with cerebral flow reversal seems to be an emerging option. 8 In this review, we compared the procedure-related outcomes of TCAR with TFCAS and CEA based on literatures published.
Methods
This systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). Literature search was updated last on June, 2021 in PubMed and Embase. The following search terms were used: carotid stenosis, carotid artery revascularization, transcarotid artery revascularization, TCAR, carotid artery stenting, CAS, carotid endarterectomy, and CEA.
The eligibility criteria included any English publication comparing TCAR with CEA and TFCAS. Only atherosclerotic stenotic carotid disease and restenosis after CEA were considered, with exclusion of procedures performed for nonatherosclerotic pathogeneses, review, study data coming from the same project and single-arm studies of TCAR. Only articles published after 2004, when the technique was first described, were considered.
Three authors (H.W., Z.W., M.L.) reviewed study eligibility and quality independently. Disagreements were resolved by consensus. The quality of each study was assessed based on well established criteria for non-randomised studies regarding selection, comparability and outcomes (Newcastle - Ottawa scale). 9
The primary outcomes were stroke, myocardial infarction (MI), transient ischemic attack (TIA), death, cranial nerve injure (CNI) and operative time. Secondary outcomes included stroke, death, MI in the elderly; cost; radiation; and entry site complication.
Meta analysis was conducted using Review Manager (RevMan, version 5.3. Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration, 2012). According to the data collected, we generated odds ratios (ORs) and 95% confidence intervals (CIs) of outcomes. The software produced forest plots and provided inconsistency (I2) statistics to evaluate the heterogeneity of the included studies.
Results
In total, the literature search included 165 studies according to the inclusion/exclusion criteria and 44 of them were reviewed in full text. Finally, twelve clinical studies were included (Figure 1). These studies provided the outcomes of a total of 18,300 patients who received TCAR (Table 1–3), and nine studies reported demographic information. Details of quality assessment of the studies were shown in Table 4.
Figure 1.
PRISMA flow diagram.
Table 1.
Studies included in this review.
| Study | Design | Proc | Age-y | Males | Symptomatic patients |
|---|---|---|---|---|---|
| Conway, 2020 | Retrospective | TFCAS(1917) TCAR(1619) |
68.8 ± 9.5 72.7 ± 9.1 |
68.3% 66.2% |
38.8% 56.6% |
| Schermerhorn, 2019 | Prospective | TFCAS(3286) TCAR(3286) |
69.7 ± 9.7 73.1 ± 9.4 |
64.9% 63.7% |
64.8% 49.4% |
| Lin, 2005 | Prospective | TFCAS(24) TCAR(31) |
NA NA |
NA NA |
54.2% 58.1% |
| Liang, 2020 |
Retrospective | TFCAS(463) TCAR(463) |
69.9 ± 9.4 70.2 ± 9.7 |
65.2% 62.4% |
65% 67% |
| Cui, 2021 | Prospective | CEA(NA) TCAR(NA) |
NA NA |
NA NA |
NA NA |
| Yee, 2020 | Retrospective | CEA(342) TCAR(109) |
67.8 ± 10.5 70.7 ± 9.2 |
62.3% 83.5% |
55.8% 48.6% |
| Schermerhorn, 2020 |
Retrospective | CEA(10,797) TCAR(1182) |
71（64–77） 74（66–79） |
NA NA |
27% 32% |
| Kashyap, 2019 | Retrospective | CEA(292) TCAR(292) |
70.9 ± 8.5 71.1 ± 8.7 |
63% 65.8% |
36.3% 35.3% |
| Jayarajan, 2019 |
Retrospective | CEA(44) TCAR(46) |
NA NA |
NA NA |
36.4% 45.7% |
| Plessers, 2016 | Retrospective | CEA(10) TFCAS(8) TCAR(16) |
65.7 ± 4.3 62.4 ± 9.9 71.3 ± 9.5 |
60% 62.5% 81.2% |
NA NA NA |
| Malas, 2020 | Retrospective | CEA(53,869) TCAR(8104) |
71 (65–77) 74 (67–80) |
NA NA |
29·8% 23·8% |
| Dakour-Arid, 2020 |
Retrospective | CEA(61,650) TFCAS(10,381) TCAR(3152) |
71 (65–77) 70 (63–77) 74 (67–80) |
60.7% 65.6% 64.2% |
28.9% 53.8% 39.1% |
Table 2.
Perioperative outcomes of TFCAS vs. TCAR.
| Study | TFCAS
a
(n = ) |
TCAR
b
(n = ) |
Periprocedural results (within 30 days) |
|---|---|---|---|
| Conway, 2020 | 1917 | 1619 | No significant difference in Stroke, MI, TIA, and TIA/Stroke/death. Significantly lower risk of death after TCAR (0.1% vs 1.1%; P < 0.0025). |
| Schermerhorn, 2019 |
3286 | 3286 | No significant difference in TIA, MI. Significantly lower risk of stroke/death after TCAR (1.9% vs. 3.7%, P < 0.001). Significantly lower risk of death after TCAR (0.8% vs. 1.5%, P = 0.007). Significantly lower risk of technical failure after TCAR (0.5% vs. 1.2%, P = 0.007). |
| Lin,2005 | 24 | 31 | No significant difference in technical failure. |
TFCAS = transfemoral carotid artery stenting; bTCAR = transcarotid artery revascularization
Table 3.
Perioperative outcomes of TCAR vs. CEA.
| Study | TCAR a (n = ) | CEA b (n = ) | Outcomes |
|---|---|---|---|
| Yee, 2020 |
109 | 342 | No significant difference in LOS, CNI, Stroke, MI, and Death.(Perioperative) Significantly shorter operative time after TCAR (73min vs 144min, P < 0.0 1). Significantly shorter reverse-flow/clamp time after TCAR (15 vs 55 min, P < 0.01). Significantly estimated less blood loss after TCAR (44.4 vs 102.2 mL, P < 0.01). |
| Schermerhorn, 2020 |
1182 | 10,797 | No significant difference in Stroke, MI, Death, Stroke/death, and Stroke/death/MI. Significantly lower risk of CNI after TCAR (0.6% vs 1.8%; P < 0.001). Significantly lower risk of have a postoperative LOS >1 day after TCAR (27% vs 30%; P = 0.046). Significantly shorter operative time after TCAR (78 ± 33 vs 111 ± 43 min; P <.001). |
| Kashyap, 2019 |
292 | 292 | No significant difference in Stroke, MI, Death, Stroke/death, and Stroke/death/MI. Significantly lower risk of CNI after TCAR (0.3% vs 3.1%; P = 0.01). Significantly shorter operative time after TCAR (75minutes vs 109minutes; P <0.01). |
| Jayaraja, 2019 |
46 | 44 | No significant difference in LOS, and Stroke/death/MI. Significantly shorter operative time after TCAR (83 vs 137 min; P <.001). |
| Plessers, 2016 |
16 | 10 | No significant difference in CNI. |
| Malas, 2020 |
8104 | 53,869 | No significant difference in Stroke, Death, Stroke/Death, and Stroke/death/MI. Significantly lower risk of MI and CNI after TCAR.(0.5% vs. 0.9%, P = 0.005; 0.4% vs. 2.7%, P < 0.001). Significantly shorter operative time after TCAR (83 vs 137 min; P <.001). |
TCAR = transcarotid artery revascularization; bCEA = carotid endarterectomy. LOS, length of stay.
Table 4.
Quality of included studies per Ottawa-Newcastle criteria.
| Study | Selection a | Comparability a | Outcomes a |
|---|---|---|---|
| Conway, 2020 | 3 | 2 | 2 |
| Schermerhorn,2019 | 4 | 2 | 3 |
| Lin, 2005 | 1 | 1 | 1 |
| Liang, 2020 | 3 | 2 | 3 |
| Cui, 2021 | 2 | 1 | 1 |
| Yee, 2020 | 3 | 2 | 3 |
| Schermerhorn,2020 | 3 | 2 | 2 |
| Kashyap, 2019 | 4 | 2 | 3 |
| Jayarajan, 2019 | 4 | 1 | 3 |
| Plessers, 2016 | 4 | 2 | 2 |
| Malas, 2020 | 4 | 2 | 3 |
| Dakour-Arid, 2020 | 2 | 2 | 3 |
Selection score: 0–4; comparability score: 0–2; outcomes score: 0–3; maximum total score: 9.
Nine studies reported early outcomes. Three studies compared the perioperative results of TFCAS with TCAR. Six studies reported the results of CEA and TCAR. For patients receiving TFCAS, the mean age was 69.4 years and 66.1% of them were male (data from 2 studies). For patients who received CEA, the mean age was 69.8 years (data from 5 studies) and 62.6% of them were males (data from 3 studies). For patients who received TCAR, the mean age was 80.6 years (data from 7 studies) and 65.0% of them were males (data from 5 studies).
Perioperative outcomes
Several previous researches on TCAR and TFCAS showed there was no significant difference in TIA and MI (Table 2), 10–12 but there was a lower risk of death and stroke/death after TCAR. And the procedure failure rates were inconsistent.
As for the perioperative outcomes of TCAR and TFCAS, the risk of stroke was significantly lower in TCAR group (OR 0.63; 95%CI 0.47–0.85) (Figure 2A). There was no significant difference in the risks of death (OR 0.27; 95%CI 0.06–1.29), TIA (OR 0.73; 95%CI 0.48–1.12), MI (OR 1.07; 95%CI 0.51–2.24) and technical failure (OR 0.59; 95%CI 0.29–1.21) (Figure 2B, 2C, 2D, 2E). With regard to heterogeneity, data for death showed I2 value >70%, indicating significant heterogeneity. These results were consistent in the sensitivity analysis that exclude low-quality studies.
Figure 2.
Forest plot showing the perioperative event rates of TCAR and TFCAS. (A) Stroke; (B) Death; (C) TIA; (D) MI; (E) Technical failure. Abbreviations: TCAR = Transcarotid Artery Revascularization, TFCAS = Transfemoral Carotid Artery Stenting, TIA = Transient Ischemic Attack, MI = Myocardial Infarction.
Several previous researches showed that TCAR was associated with shorter operative time, lower risk of CNI and less blood loss compared to CEA. But there was no difference in MI, stroke, death and stroke/death/MI rates in the perioperative period (Table 3).13–18
There was a significantly lower rate of CNI in TCAR group compared to that of CEA group (OR 0.26; 95%CI 0.17–0.39) (Figure 3A), but there was no significant difference in the risks of stroke (OR 1.07; 95%CI 0.83–1.37), death (OR 1.72; 95%CI 0.82–3.62), MI (OR 0.91; 95%CI 0.36–2.29), stroke/death (OR 1.05; 95%CI 0.83–1.33) and stroke/death/MI (OR 0.95; 95%CI 0.78–1.16) (Figure 3B, 3C, 3D, 3E, 3F).
Figure 3.
Forest plot showing the perioperative event rates of TCAR and CEA. (A) CNI; (B) Stroke; (C) Death; (D) MI; (E) Stroke/Death; (F) Stroke/Death/MI. Abbreviations: TCAR = Transcarotid Artery Revascularization, CEA = Carotid Endarterectomy, CNI = Cranial Nerve Injury, MI = Myocardial Infarction.
With regard to heterogeneity, data for MI showed I2 values >70%, indicating significant heterogeneity.
Outcomes comparison in the elderly
The advantages of TCAR became more obvious among the elderly. A recent study showed the risk of stroke/death was significantly lower in TCAR group compared to TFCAS (OR 0.35; 95%CI 0.20–0.62). And the risks of in-hospital stroke and stroke/death/MI were reduced by 72% and 76% in TCAR respectively. Moreover, the odds of stroke/death after TFCAS was doubled compared to TCAR at the age of 77, and it tripled at the age of 90. 19 These results showed that TCAR may be a safe choice in the elderly.
Cost comparison
A study showed TCAR was more expensive compared to CEA ($ 10,490.18 vs. $5093.62). The increased cost of TCAR was mainly due to the use of equipment and supplies ($6258 vs. $780). 16 Another study also showed a similar result. 20
Radiation and entry site complication comparison
Compared to TFCAS, TCAR was associated with a significantly shorter fluoroscopy time (5 min vs. 16minutes, P < 0.01) and a smaller amount of contrast (30mL vs. 80mL, P < 0.01).11,21 But TCAR was associated with a higher risk of entry site bleeding leading to interventional therapy (1.3% vs 0.8%, RR 1.63; 95% CI 1.02–2.61). 11
Discussion
Based on recent literatures, TCAR is a new technique compared to TFCAS and CEA, since it can be proceeded from the carotid access directly.22,23 It can also provide improved reversal of blood flow because of the shorter length and larger lumen diameter of the sheath. 21 However, the cost and entry site bleeding should be noted.
A study compared TCAR with TFCAS basing on the outcomes of new ischemic brain lesions on Magnetic Resonance Imaging (MRI) sequences. The result showed there were fewer new postprocedural ischemic infarcts in TCAR compared to TFCAS (12.9% vs 33.3%, P = 0.03). 24 The result of Diffusion-weighted Magnetic Resonance Imaging (DW-MRI) also showed TCAR and CEA had similar effects in reducing cerebral embolism.8,25 These researches showed TCAR can effectively reduce the risk of stroke.
There was no significant difference in neurologic events (stroke plus TIA) after CEA between the elderly and young counterparts, but the overall mortality rate was significantly higher in the elderly. 26 So age should be taken into consideration when selecting a therapeutic method.27–29 Given the better performance of TCAR in the elderly, TCAR may be a better choice in these patients.
One study showed the risk of CNI in TCAR group was significantly lower than that of in CEA because of the smaller surgical field, but the risk of death after TCAR was significantly higher. 8 It may be because patients who received TCAR tended to be older and more likely to be with fatal complications. 19 Moreover, patients undergoing TCAR may have higher degree of carotid stenosis, irradiation therapy history in the neck, reintervention for restenosis and history of ipsilateral neck dissection. 13,14,30
The duration of blood flow reversal during the operation did not affect the prognosis in TCAR. 31 The learning curve of TCAR was also shorter compared to TFCAS and CEA.15,32 In a retrospective analysis of 81 patients, only one patient experienced a slight change in the electroencephalographic (EEG) during TCAR due to hypotension. And the patient recovered when the blood pressure was raised. 33 Cerebral ischemia did not occur in most patients of TCAR group. 34 TCAR may also provide another safe alternative for patients with contralateral carotid artery occlusion (CCO). In a recent study including 5485 TCAR cases, there was no significant difference in the risks of neurological changes, in-hospital stroke/death, death, stroke, death/stroke/MI and the 30-day mortality in the patients with CCO compared to those without CCO. 35
TCAR has also been preliminarily proved to be safe in the treatment of carotid artery restenosis and carotid artery aneurysm.36,37 At present, TCAR provides a new option for the restenosis treatment after CEA and TFCAS. 38 Also, two case reports have demonstrated that TCAR could be used to treat carotid artery pseudoaneurysm and outcomes were satisfying.39,40
But there are also restrictions of TCAR. First, some anatomic variation may not suitable for TCAR. One study found that around 72% of the carotid arteries meet the TCAR's criteria.41,42 Second, high flow reversal intolerance may occur in some patients, but this can be solved after being familiar with this technique. 31,35,43
The meta-analysis also has some limitations. First, the lack of allocation concealment and randomization increased the risk of confusion and selection bias. Second, this relatively small number of published studies included in the analysis may decrease the strength of the conclusion. In addition, the absence of risk factors for the patients in each group was also a limitation.
Conclusion
TCAR is a minimally invasive surgery. It is also associated with lower risk of perioperative stroke compared to TFCAS. TCAR also has shorter operative time, a lower risk of CNI and less blood loss compared to CEA. So TCAR is a promising surgical technique and it may be widely used in the future.
Footnotes
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) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China, Key projects of medical science and technology in Henan Province, Health Science and Technology Innovation Fund for Distinguished Young Scholars of Henan Province, (grant number 81870369, SBGJ202002035, YXKC2021040)
ORCID iD: Haoliang Wu https://orcid.org/0000-0002-9019-1327
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