Intravascular lithotripsy as a treatment option for recalcitrant in-stent restenosis in symptomatic patients with chronic iliofemoral venous obstruction

Abstract

Reinterventions after stenting for chronic iliofemoral venous obstruction have an incidence of approximately 20% to 40% in the literature. The most common reason for this tends to be in-stent restenosis (ISR). Although angioplasty historically has been the modality used to treat this problem, at times ISR can be robust and associated with calcium deposits, leading to an inadequate outcome. Although newer debulking devices like the RevCore can be helpful, sometimes even these devices are not adequate given their inability to secure a foothold on the fibrotic tissue to enable its removal. Using an intravascular lithotripsy catheter (12 mm) helps to soften the fibrotic tissue and fracture the calcium deposits, thus enabling angioplasty or a debulking device (if needed) to be successful. This case series outlines the author’s experience with three patients with recalcitrant ISR who benefited from using an intravascular lithotripsy catheter that enabled prolonged symptom improvement and stent patency over a follow-up of 19 months. However, the use of such a catheter for the treatment of venous ISR represents an off-label use of the device.

The last two decades have witnessed the evolution of stenting to become the first line of treatment for symptomatic patients with chronic iliofemoral venous obstruction (CIVO) who have failed conservative therapy.1, 2, 3, 4, 5, 6 With this increased use of stenting comes the need for reintervention for stent failure. The latter can be in the form of in-stent restenosis (ISR), stent compression, a combination of the two, or stent occlusion.^6,7 With ISR, in patients presenting with recurrent symptoms impairing their quality of life, historically treatment has been angioplasty with a balloon of a rated caliber equal to the stent diameter (isodilation); if that does not succeed in restoring an adequate flow channel, then with an even larger caliber balloon (hyperdilation).^7,8 There is a group of patients in whom this is not successful; for them, laser ablation of ISR (Spectranetics Corp, Colorado Springs, CO) followed by angioplasty⁹ or more recently use of a debulking device (ClotTriever¹⁰ or RevCore,¹¹ Inari Medical, Irvine, CA) may be helpful.^10,11 However, there is a small cohort of patients in whom these measures may not be successful owing to the firmness of the fibrotic tissue that constitutes the ISR, calcium deposits, or both. In these situations, this author has found the use of an intravascular lithotripsy catheter to be helpful. The experience with three patients in whom angioplasty was unsuccessful initially but was successful after the use of a 12-mm intravascular lithotripsy balloon catheter (Shockwave Medical, Santa Clara, CA) and consequent hyperdilation is recounted. Adequate flow channel luminal areas were restored in all three patients who continue to do well from a symptom relief and stent patency standpoint at 19 months after the intervention. However, it must be noted that the use of such a catheter for treatment of venous ISR represents an off-label use of the device. Permission was obtained from the patients to publish this case series.

Case reports

Patient 1

A 53-year-old Caucasian woman with a history of cardiac arrhythmia and rheumatoid arthritis who presented with pain (visual analog scale [VAS] pain score of 8/10), swelling and cramping of the right leg (Clinical, Etiological, Anatomical, Pathological [CEAP] clinical class 3, and a Venous Clinical Severity Score [VCSS] of 9) and had failed conservative therapy. Symptoms started in the setting of a right total knee arthroplasty. In light of her quality-of-life-impairing symptoms, she underwent right iliofemoral venous stenting under general anesthesia. Stenting was carried out using a combination of Wallstents and a Z stent across the iliocaval confluence to overcome the choke point effect following the diagnosis of a multifocal nonthrombotic iliac vein lesion (NIVL) on intravascular ultrasound (IVUS) examination. After the procedure, she was started on apixaban 5 mg twice daily for stent protection. She had good symptom relief after the procedure that was maintained alongside a patent stent for more than 5 years of follow-up, at which point she developed a recurrence of previously noted symptoms (VCSS of 9). Duplex ultrasound (DUS) examinations revealed ISR across the stent column with a maximum of 46% in the external iliac vein. A plan was made to pursue reintervention, starting with an IVUS interrogation of her stent column to confirm the diagnosis.

Patient 2

A 58-year-old Caucasian woman with a history of hyperlipidemia, Crohn's disease, and gastroesophageal reflux disease who underwent left iliofemoral venous stenting for swelling, heaviness, tightness, and pain (VAS pain score of 6/10) in the lower extremity (CEAP clinical class 3 and VCSS of 8). Stenting was with the use of a Wallstent-Z stent combination after a diagnosis of a combination of NIVL and post-thrombotic obstruction on IVUS. Although she did well after the procedure with improvement in symptoms, she underwent three reinterventions for recurrent symptoms over 7 years. All these reinterventions were for ISR, which was treated with angioplasty alone. However, 6 months after her last reintervention, she developed yet another recurrence of quality-of-life-impairing symptoms (VCSS of 7). DUS examination revealed ISR across the entirety of the stent with a maximum of 72% in the external iliac vein. To this point, she had been on apixaban 5 mg twice daily for stent protection, but was switched to dabigatran 150 mg twice daily given the ISR build-ups. A plan was formulated for IVUS interrogation with the intent to treat.

Patient 3

A 40-year-old African American woman with a history of hypothyroidism and migraines underwent right iliofemoral venous stenting for pain (VAS pain score of 10/10) and swelling in the lower extremity (CEAP clinical class 3 and VCSS of 8). Stenting was carried out using a combination of an Abre stent (Medtronic, Minneapolis, MN) cranially and a Wallstent caudally for a diagnosis of multifocal NIVL on IVUS examination. After the procedure, she did well, with improvement of pain and swelling to the point they were no longer bothersome. However, approximately 18 months later, she developed a recurrence of the pain and swelling (VCSS of 7). DUS examination revealed ISR across the entirety of the stent with a maximum of 53% in the external iliac vein. She had been only on aspirin 81 mg, but was started on apixaban 2.5 mg twice daily and was scheduled for IVUS confirmation of the diagnosis and stent reintervention.

Technical aspects

Each patient was placed under general anesthesia in a supine position with preprocedural thromboprophylaxis in the form of enoxaparin (30 mg or 40 mg, based on body mass index) subcutaneously and bivalirudin (75 mg) intravenously. Access was obtained in the midthigh femoral vein under ultrasound guidance and an 11F access sheath was placed. A diagnostic ascending venogram was performed (Fig 1). This demonstrated a reduction in the flow channel luminal area across the stented segment in all three patients. IVUS interrogation (Visions PV .035 digital IVUS catheter, Philips, Amsterdam, the Netherlands) was then performed to confirm the diagnosis of stent malfunction. The presence of mild-to-severe ISR across the stent column was noted with additional calcification noted in patient 1 (Fig 2). Isodilation (angioplasty with a balloon equal to the rated diameter of the stent) was then carried out followed by hyperdilation (angioplasty with a balloon larger than the rated diameter of the stent) in each patient. Interval IVUS interrogation was used to determine the extent of luminal gain. If an adequate flow channel was not restored on IVUS examination (noted in all three patients), intravascular lithotripsy was used and focused on the areas of ISR after angioplasty. To facilitate this, an 0.035” glide wire was switched out to an 0.018” wire and a 12-mm lithotripsy balloon catheter was introduced to treat the previously determined areas. In total, 300 pulses were delivered in patients 1 and 2; only 210 pulses were used in patient 3 (Fig 3). IVUS interrogation was again performed (Fig 4) and repeat hyperdilation (Fig 5) was carried out in areas where additional luminal gain was necessary. The goal was to secure a minimal luminal area of 125 mm², 150 mm^2, and 200 mm² in the stented common femoral, external iliac, and common iliac segments, respectively. In all three patients, these flow channel luminal areas were attained on completion IVUS interrogation at the end of the procedure. Completion venogram demonstrated good inflow, flow through the stent column, and outflow without any flow restrictions in all three patients (Fig 6). The preprocedural antithrombotic regimen was restarted the evening of the procedure with all three patients discharged on the day of the procedure with plans for continued long-term follow-up. No complications were noted either periprocedurally or on subsequent follow-up visits.

Fig 1.

Venogram in patient 1 demonstrating severe in-stent restenosis (ISR) in the external iliac vein (red oval) with collateral (orange arrow).

Fig 2.

Intravascular ultrasound (IVUS) image depicting severe in-stent restenosis (ISR) in the external iliac venous segment. The hyperechoic areas (orange arrows) are areas of calcification within the area of fibrotic ISR.

Fig 3.

A lithotripsy balloon (12 mm) in place delivered pulses in the external iliac venous segment in the area of maximum residual in-stent restenosis (ISR) after hyperdilation.

Fig 4.

Intravascular ultrasound (IVUS) image demonstrating luminal gain post intravascular lithotripsy (note luminal area is still below the 150 mm² expected in the external iliac vein).

Fig 5.

Intravascular ultrasound (IVUS) image after repeat hyperdilation using a 20-mm angioplasty balloon demonstrating a final luminal area of 184 mm².

Fig 6.

A completion venogram demonstrated good filling of the stent and disappearance of the collateral.

After the procedure

All three patients experienced symptom improvement after intervention, with the VCSS improving from 9 to 4 in patient 1, from 7 to 4 in patient 2, and from 7 to 3 in patient 3. The stents were widely patent on DUS in all three patients. These improvements were sustained over 19 months of follow-up. All patients will continue to with lifelong follow-ups with regular DUS examinations alongside clinical visits.

Discussion

Femoroiliocaval stenting has replaced open surgery as the treatment of choice for patients presenting with quality-of-life-impairing symptoms of CIVO who have failed conservative therapy. With this intervention comes the need for reintervention in patients with recurrent symptoms. ISR represents the most common reason for such reintervention.^1,6 Although many techniques exist to treat this problem, none of them are always successful. One particular subgroup in this category is patients with significant fibrotic tissue with or without calcification, where the firmness of the tissue precludes the success of iso or hyperdilation and/or the use of debulking devices owing to the nature of orientation of the tissue. For the latter to be successful, the device has to be able to get purchase on the fibrotic tissue, which can then be cored out. However, this process, as noted before, is not uniformly successful. The use of a device to potentially soften the firm fibrotic ISR can help to enhance the success of these options. This is where the intravascular lithotripsy catheter comes in. Although the largest lithotripsy catheter (12 mm) is small for standard venous procedures, it is adequate for the special role it plays in cases of recalcitrant ISR. Here, the ISR is significant enough that it enables contact with the balloon and consequent treatment effect. That all three patients had successful outcomes without complications underscores the need to keep this tool in the arsenal of interventionalists who have to deal with failing iliofemoral venous stents in the setting of recurrent, quality-of-life-impairing symptoms.

Conclusions

Intravascular lithotripsy is an option for patients with recurrent symptoms of CIVO owing to ISR in whom other conventional methods are not successful. Although the technique is safe and effective, further study is required.

Funding

None.

Disclosures

None.