Carotid artery stenting with intravascular lithotripsy for calcific carotid stenosis: A systematic literature review

Abstract

Background

Endovascular techniques such as stenting, endarterectomy, and transcarotid arterial revascularization are common therapeutic options in the management of carotid artery stenosis; however, they involve a risk of major complications (e.g. in-hospital transient ischemic attack or ischemic stroke). The application of shock wave therapy in the form of intravascular lithotripsy has been increasingly explored among patients with calcified arterial lesions. To the best of our knowledge, the diverse applications of intravascular lithotripsy have been documented in the context of peripheral artery disease, coronary artery disease, and transcarotid arterial revascularization; however, limited research has been conducted on other domains of endovascular management. In this systematic review, we aimed to elucidate the complication profile and document the safety of off-label intravascular lithotripsy prior to carotid artery stenting for calcific carotid artery stenosis.

Methods

A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, in which the databases of PubMed, CINAHL, Embase, and Scopus were searched to identify all cases of reported carotid artery stenosis treated with intravascular lithotripsy in conjunction with carotid artery stenting.

Results

Of the 711 initially identified articles, 7 were selected because they met the study criteria. Finally, 11 patients aged 56–82 years were included in our review. The prevalence of preoperative stenosis ranged from 60% to 95%; postoperative vessel patency was described in all cases. In the postoperative period, one patient experienced transient right eye blindness secondary to central retinal artery occlusion and another patient sustained a left hemispheric transient ischemic attack.

Conclusion

We explored the application of intravascular lithotripsy in carotid artery stenting procedures, in which success in improving lumen patency has been documented. Although postoperative complications such as transient ischemic attack have been reported, all patients exhibited good clinical outcomes, with no new permanent deficits being observed. Our findings cautiously recommend the use of intravascular lithotripsy as an adjunct to carotid artery stenting in the management of calcific carotid stenosis as a safe therapeutic option in selected patients. However, further research on this subject is warranted.

Introduction

According to a 2020 report, approximately 28% of the world’s population aged 30–79 years had an abnormal carotid intima-media thickness of ≥1.0 mm, 21% of individuals had carotid plaque, and 1.5% had carotid artery stenosis. This equated to 58 million people living with carotid artery stenosis. ¹ If left unmanaged, this pathology may lead to adverse health outcomes, including acute ischemic stroke and transient ischemic attack. ² Conventionally, this pathology is managed with carotid artery stenting (CAS) or endarterectomy, although stenting has been associated with a higher risk of periprocedural stroke or death. ³ CAS is a popular alternative to endarterectomy; however, CAS requires a much longer learning curve and may incur a higher risk of periprocedural complication/death rates early in a surgeon’s experience. ⁴ Therefore, it is paramount to explore novel options to reduce the risk of poor outcomes while optimizing the probability of technical success of CAS operations.

Shockwave lithotripsy (intravascular lithotripsy (IVL)) was first utilized in urology for renal calculi disintegration; however, based on recent literature, IVL has also been used in coronary stent placement and endovascular management of multilevel calcified peripheral artery disease (PAD).^5–8 In this limited systematic literature review, we aimed to document the application, safety, and complication profile of off-label IVL in conjunction with CAS procedures.

Methods

A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. ⁹ The databases of PubMed, CINAHL, Embase, and Scopus were searched on 1 May 2024 for all English language articles published in any year, using the following search terms: ((carotid artery stenting) OR (CAS) OR (carotid)) AND ((shock wave) OR (shockwave) OR (intravascular lithotripsy)).

Articles were then screened by title and/or abstract by two independent reviewers based on proper inclusion and exclusion criteria. All original research articles that detailed cases or case series of patients diagnosed with internal carotid artery (ICA) or common carotid artery (CCA) stenosis who received IVL prior to CAS or received IVL following the placement of an under-expanded stent were included. Articles were excluded if they were review papers, abstracts published from academic conferences, letters to the editor, non-human animal models, or published in a language other than English. After being imported into EndNote^TM 20 and removing duplicates, all articles were screened for inclusion via Rayyan, a web-based screening tool. ¹⁰

Following initial screening, full-text review was conducted by the same two reviewers. The following metrics were extracted: (a) sample size; (b) sex; (c) age; (d) side of femoral or radial access (if reported); (e) side of ICA or CCA stenosis; (f) size of lithotripsy balloon; (g) regimen of IVL treatment; (h) preoperative stenosis/postoperative lumen diameter; (i) type of stent employed; and (j) miscellaneous notes regarding any reported clinical presenting symptoms, postoperative complications, and postoperative outcomes. The details of the screening process are presented in Figure 1.

Figure 1.

Flowchart demonstrating the systematic review process according to the PRISMA 2020 guidelines. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Results

Patient demographics and characteristics of surgical interventions

Seven articles published between 2020 and 2022 involving 11 patients were identified for this review.^11–17 These articles consisted of case reports and case series of patients who had undergone CAS and intravascular lithotripsy. Three patients were female and six were male (patient sex was not reported in two cases). Patient ages ranged from 56 to 82 years. Six patients presented with left carotid artery stenosis, and five had lesions on the right. Vascular access was femoral in six, radial in two, and not specified in three cases.

One patient presented with a history of radical neck surgery, hypertension, hyperlipidemia, coronary artery disease, and three episodes of right hemispheric TIA; another presented with a history of throat cancer, radiation therapy, hypertension, hyperlipidemia, and PAD. ¹¹ In addition, a patient received transcarotid artery revascularization 8 months prior, presenting with asymptomatic in-stent stenosis. Another patient with a history of hypertension, diabetes, hyperlipidemia, and chronic obstructive pulmonary disease presented with decompensated heart failure secondary to cardiomyopathy. ¹² A patient presented with TIA (right fugax amaurosis) and a history of multiple episodes of frontoparietal cerebral ischemia, ¹³ and another presented with a left hemispheric ischemic stroke. ¹⁴

One series (Case et al. ¹¹ ) included five patients in total; two of them underwent CAS. Of the three patients reported by Mehta and Wooster, ¹² one was excluded having received transcarotid arterial revascularization (Table 1).

Table 1.

Summary of CAS following lithotripsy.

Author, year	Case number (sex)	Age (years)	Lithotripsy balloon (mm)	Number of rounds	Number of pulses	Pressure level (atm)	Stent size (mm) and type ‡
Vadala et al. 2020 13	1 (F)	76	4 × 12	2	5	4–6	7 × 30 carotid wall stent, Boston Scientific
	2 (M)	72	4 × 12	1	7	4	9 × 30 carotid wall stent, Boston Scientific
Case et al. 2020 11	3 (M)	72	6 × 60	6	*	*	7–10 × 40 nitinol self-expanding stent, Abbott Vascular
	4 (M)	56	7 × 60	1	*	*	10 × 40 & 10 × 30 Cordis
Mehta and Wooster 2022 12	5 (F)	82	5 × 60	3	*	6–10	*
	6 (F)	60	5 × 60	2	*	4–6	10 × 31 self-expanding metal stent, Boston Scientific
Misztal et al. 2021 14	7 (M)	82	4 × 40	5	20	2–6	7 × 40 self-expanding metal stent, Boston Scientific
Kang and Wilson 2022 15	8 (M)	77	4 × 12	1	40	4–10	10–8 × 40 & 10 × 30 XACT stents, Abbott Vascular
Kiron et al. 2021 16	9 (M)	75	4 × 12	3	*	4	8–6 × 40 XACT self-expanding Nitinol stent, Abbott Vascular
Singh et al. 2022 17	10 (*)	*	4 × 40	*	*	*	Two 8 × 36 carotid wallstents, Boston Scientific
	11 (*)	*	3.5 × 40	*	*	*	8 × 36 carotid wallstent, Boston Scientific

^*Not reported.

^†Experienced stenosis of the common carotid artery.

^‡Manufacturing companies are as follows: Boston Scientific, Marlborough, MA, USA; Abbott, Chicago, IL, USA; Cordis, Miami Lakes, FL, USA.

CAS: carotid artery stenting; atm: atmosphere; M: male; F: female; L: left; R: right.

Patient outcomes

Preoperative stenosis was reported in seven patients, and its prevalence ranged from 60% to 95%. The postoperative lumen diameter was reported as 4.5 mm in case 1, with decreased percentages of stenosis in cases 3, 6, and 8. The postoperative lumen diameter was not reported in the other cases, although vessel patency was noted in all cases postoperatively (Table 2).^{11,13,14,16,17}

Table 2.

Summary of preoperative stenosis, postoperative lumen diameter, and medical therapy.

Author, year	Case number (sex)	† Preoperative stenosis	† Postoperative lumen diameter	Medical therapy
Vadala et al. 2020 13	1 (F)	“extremely calcified tight stenosis”	4.5 mm	*
	2 (M)	“tight calcified stenosis” “large load of calcium and an almost circumferential distribution”	“good angiographic result was obtained” “final IVUS confirmed good stent expansion and apposition to the vessel wall”	*
Case et al. 2020 11	3 (M)	90%	“final angiogram showing excellent dilatation and no significant residual stenosis”	*
	4 (M)	60%–79%	“angiography showed significant improvement in angiographic flow through LCCA”	*
Mehta and Wooster 2022 12	5 (F)	70%	30%	Aspirin, clopidogrel, and atorvastatin
	6 (F)	>70%	<30%	Aspirin, statin (unspecified), and clopidogrel
Misztal et al. 2021 14	7 (M)	“extremely calcified tight stenosis” “extensive calcific plaque”	“final angiography demonstrated good apposition of the stent and confirmed patency of the left ICA”	*
Kang and Wilson 2022 15	8 (M)	90%	10%	*
Kiron et al. 2021 16	9 (M)	“critical stenosis of the right ICA with 180% arc of calcium causing eccentric stenosis”	“minimal residual stenosis”	Aspirin, clopidogrel, and apixaban
Singh et al. 2022 17	10 (*)	80%	“post-procedure angiogram showed proper expansion of the carotid stents and unimpeded flow”	Ticagrelor and apixaban
	11 (*)	95%	“post-procedure angiogram showed proper expansion of the carotid stents and unimpeded flow”	Aspirin and ticagrelor

^*Not reported.

^†Documented qualitatively when quantitative data were not reported

M: male; F: female; L: left; R: right; ICA: internal carotid artery; IVUS: intravascular ultrasound; LCCA: left common carotid artery

The lithotripsy balloon size varied from 3.5 to 7 mm (Table 1) among the 11 patients. The number of ultrasound rounds ranged from one to six, with the number of pulses ranging from 5 to 40 and pressure level ranging from 2 to 10 atm (Table 1).

One patient experienced transient postoperative right eye blindness secondary to central retinal artery occlusion and was successfully treated with tissue plasminogen activator. ¹¹ Another patient developed a left hemispheric TIA on postoperative day 5 and subsequently recovered to his preexisting neurologic baseline without further complications. ¹⁴ No other neurologic events were observed in patients after the procedures. The occurrence of left hemispheric TIA and central retinal artery occlusion yielded a procedural complication rate of 18%.

Discussion

As demonstrated above, the off-label use of IVL in conjunction with CAS may incur similar complication rates to that of CAS alone, while facilitating access to circumferential calcified lesions that may not otherwise have been accessible for stenting. Complications in the postoperative period included transient blindness secondary to central retinal artery occlusion and acute left hemispheric TIA.^11,14 Altogether, the use of IVL together with CAS may be considered safe, as all patients recovered to their preexisting neurologic status.

Historically, shock wave lithotripsy therapy has been employed for disintegrating the gallbladder and renal calculi. Interestingly, ultrasound exposure can be categorized based on its thermal and mechanical effects on living tissue, with the mechanical aspect of shock waves providing clinical utility in the fragmentation of calcium-based lesions. ⁵ Although this technology is conventionally used in the field of urology, ultrasonic forces have also been observed to induce changes in the bones and soft tissue, which may be advantageous in certain medical fields such as orthopedics.

The use of lithotripsy in the treatment of calcified lower extremity arterial stenosis has been well documented. In 2020, Adams et al. demonstrated that IVL is increasingly used concomitantly with endovascular therapies for peripheral calcific lesions within the context of the Disrupt PAD III Study. ⁷ Complications were exceedingly rare, and no abrupt occlusion, distal embolization, or thrombotic events were described. In addition, an average of 3.4 mm was gained at the end of the procedure with a final mean residual stenosis of 23.6%. ⁷ Successful and favorable complication profiles have been documented following the use of IVL for peripheral calcification, which may be partially attributed to the natural route of blood flow to the distal extremities because calcified debris is carried away from critical anatomic structures. Conversely, IVL, in the context of carotid stenting, may present a less favorable complication profile because debris flow distally into the intracranial vasculature.

The use of IVL in coronary artery pathology has been reported. In 2019, the Disrupt CAD I Study was conceived, which exemplified the feasibility and safety of modifying heavily calcified atherosclerotic coronary plaques via IVL before stenting. ⁸ In addition, IVL has been used in the context of under-expanded coronary stents, in which high technical success with favorable complication rates has been reported. ⁶ Altogether, these findings highlight the potential role of endovascular ultrasound technology in disrupting highly calcified stenotic lesions. Given the level of safety observed in both coronary and extremity arterial lesions, IVL may be safe and well-tolerated in the context of CAS, especially in the setting of a highly scrutinized patient selection process.

In January 2023, the Centers for Medicare and Medicaid Services expanded coverage for percutaneous transluminal angioplasty concurrent with stenting to include patients with standard surgical risk. ¹⁸ Therefore, there could be an increase in the number of patients undergoing carotid stenting procedures who may benefit from this novel technology. However, further studies are necessary to determine the relationship between IVL and CAS success. These results may be corroborated by expanding the literature review to include non-English publications.

This literature review is susceptible to certain limitations, chiefly owing to the relatively small sample size with subsequent confounding and bias. In addition, bias was introduced by the accumulation of individual cases and case series because each body of literature contains its own inherent reporting bias; thus, a formal standardized study on this subject is warranted. Nonetheless, the present review provides an accurate distillation of the current English literature regarding IVL in association with CAS. As such, this review presents a meaningful contribution toward understanding the intersection of IVL, endovascular management of calcific carotid lesions, and patient outcomes.

Conclusion

In this systematic review, we explore the off-label application of IVL for CAS procedures, wherein success in improving lumen patency has been documented. Moreover, the novel use of this technology has demonstrated unique advantages, especially with respect to circumferential calcific lesions that may not be amenable to stenting. Although postoperative complications such as TIA have been reported, all patients experienced good clinical outcomes. Further study is required to document the complication rates of IVL in this high-risk patient population. Nevertheless, our findings cautiously suggest that IVL can be a safe adjunct to CAS in the management of calcific carotid stenosis in selected patients.