Recurrent Coronary Restenosis in Takayasu Arteritis

Abstract

Background

Coronary involvement in Takayasu arteritis is uncommon but associated with high rates of in-stent restenosis and challenging revascularization.

Case Summary

A 22-year-old woman with Takayasu arteritis and congenital antithrombin III deficiency presented with non–ST-segment elevation myocardial infarction due to severe ostial right coronary artery in-stent restenosis after multiple prior percutaneous interventions. Intravascular ultrasound confirmed significant neointimal hyperplasia. A stent-sparing strategy using excimer laser coronary atherectomy, cutting balloon angioplasty, and paclitaxel drug-coated balloon under intravascular ultrasound guidance was performed with bivalirudin anticoagulation. Final angiography demonstrated TIMI 3 flow with significant luminal gain.

Discussion

Recurrent restenosis in Takayasu arteritis represents a major therapeutic challenge. This case highlights the role of multimodal, stent-avoidant strategies and individualized anticoagulation in complex inflammatory vasculopathy with concomitant thrombophilia.

Take-Home Messages

Recurrent in-stent restenosis in Takayasu arteritis reflects ongoing vascular inflammation and requires strategies beyond repeat stenting. A stent-sparing, intravascular imaging–guided approach using laser atherectomy and drug-coated balloon can effectively treat refractory restenosis while minimizing additional stent burden.

Graphical Abstract

History of Presentation

A 22-year-old woman presented with a 4-day history of progressively worsening substernal chest pressure rated 8 of 10 in intensity. The pain was nonradiating and associated with exertional limitation. She had been scheduled for elective percutaneous coronary intervention (PCI) due to known recurrent in-stent restenosis but presented earlier due to symptom progression. On presentation, she was hemodynamically stable with a blood pressure of 106/57 mm Hg and oxygen saturation of 97% on room air. Physical examination was unremarkable.

Past Medical History

Her past medical history was significant for Takayasu arteritis treated with methotrexate, infliximab, and prednisone. She had congenital antithrombin III deficiency, diagnosed at birth in the setting of a strong paternal family history of the disorder, with no prior thrombotic events to date, and documented clopidogrel resistance. Her cardiac history began at age 14 years with an inferior ST-elevation myocardial infarction requiring drug-eluting stent placement in the proximal right coronary artery (RCA) with a 3.0 × 15-mm Xience Alpine drug-eluting stent. Intravascular ultrasound at that initial procedure demonstrated good stent apposition, full expansion, and adequate coverage of the RCA ostium. This was followed by recurrent in-stent restenosis requiring balloon angioplasty the same year. At age 20, she underwent placement of a second overlapping drug-eluting stent. At age 21, she underwent intravascular ultrasound–guided angioplasty with a drug-coated balloon for recurrent restenosis.

Differential Diagnosis

The differential diagnosis included in-stent restenosis, stent thrombosis, progression of coronary vasculitis, coronary vasospasm, and nonatherosclerotic coronary obstruction related to Takayasu arteritis.

Investigations

Left ventricular systolic function with an ejection fraction of 55% to 60% and hypokinesis of the basal inferolateral wall. Coronary angiography performed via femoral access demonstrated severe ostial in-stent restenosis of the RCA as shown in Figure 1A. Intravascular ultrasound further characterized the lesion and revealed significant neointimal hyperplasia with good expansion of the previously placed stents. The minimum luminal area was 4.45 mm² within the proximal stented segment, and the lumen area at the ostium of the RCA measured 4.62 mm², as shown in Figure 2A.

Figure 1.

Coronary Angiography of the Right Coronary Artery

Arrows indicate the ostial segment of the right coronary artery: (A) the site of severe in-stent restenosis before intervention, and (B) the same segment after multimodal percutaneous coronary intervention, demonstrating restored luminal patency with TIMI 3 flow.

Figure 2.

Intravascular Ultrasound Evaluation of the Ostial Right Coronary Artery Lesion

(A) Pre-intervention intravascular ultrasound demonstrating significant neointimal hyperplasia within the previously deployed stent, with a minimum lumen area of 4.62 mm² at the RCA ostium and 4.45 mm² within the proximal stented segment. (B) Postintervention intravascular ultrasound demonstrating improved stent expansion and luminal gain following laser atherectomy and drug-coated balloon angioplasty, with lumen area increasing to 6.30 mm² at the RCA ostium and 5.64 mm² within the proximal stented segment.

Management

Given the presence of antithrombin III deficiency, procedural anticoagulation was achieved using bivalirudin. A multimodal PCI strategy was performed. We elected to proceed with lesion preparation using excimer laser coronary atherectomy (ELCA) for debulking of resistant diffuse neointimal tissue with rapid recurrence following recent drug-coated balloon angioplasty. Using a 0.9-mm ELCA catheter, we started with a fluence of 45 mJ/mm² and a repetition rate of 25 Hz, then escalated to a high-energy setting with a fluence of 80 mJ/mm² and a repetition rate of 25 Hz. Lasing was performed with continuous saline flush. Contrast-enhanced ELCA was not performed given the absence of significant stent underexpansion or calcified disease. ELCA was followed by cutting balloon angioplasty using a 3.0 × 10-mm balloon inflated to 18 atm. High-pressure dilation was then performed with a 3.25 × 12-mm noncompliant balloon inflated to 20 atm to optimize stent expansion. After adequate lesion preparation, a 3.5 × 15-mm paclitaxel drug-coated balloon was deployed at 6 atm to deliver antiproliferative therapy while avoiding additional stent implantation. Repeat intravascular ultrasound demonstrated improved luminal dimensions with appropriate modification of the neointima and improved stent expansion.

Outcome and Follow-Up

Final angiography demonstrated resolution of the ostial stenosis with restoration of normal vessel caliber and TIMI flow grade 3 as shown in Figure 1B. Postintervention intravascular ultrasound confirmed significant luminal gain with the minimum luminal area increasing to 5.64 mm² within the proximal stented segment and the lumen area at the RCA ostium increasing to 6.30 mm², as shown in Figure 2B. The patient tolerated the procedure without complications. Postprocedurally, anticoagulation was managed with an argatroban infusion as a bridge to warfarin therapy. She was discharged on a tailored antithrombotic regimen consisting of short-duration dual antiplatelet therapy followed by ticagrelor and long-term warfarin. Long-term oral anticoagulation with a vitamin K antagonist was instituted as primary prophylaxis, given her congenital antithrombin III deficiency in combination with active inflammatory vasculopathy, recurrent in-stent restenosis, and a high-risk coronary substrate; she has had no prior thrombotic events. Direct oral anticoagulants were avoided because antithrombin III deficiency is associated with reduced predictability of their effect and because of the absence of robust data in this population.

Discussion

Takayasu arteritis is a rare, large-vessel vasculitis that predominantly affects women younger than 40 and produces granulomatous inflammation of the aorta and its proximal branches.¹ Coronary involvement occurs in approximately 10% to 30% of patients and is a major determinant of morbidity, with the ostia and proximal segments affected in 75% to 85% of cases with coronary lesions.1, 2, 3, 4, 5 This ostial predilection reflects extension of the aortitis into the coronary root with fibrotic contraction of the media and adventitia, rather than typical atherosclerosis.³

Revascularization in Takayasu arteritis is challenging because of high rates of failure.^6,7 Compared with coronary artery bypass grafting (CABG), PCI carries substantially higher restenosis and repeat-revascularization rates, with reported restenosis rates as high as 63% vs 25% for CABG and an approximately 5-fold higher need for repeat revascularization after PCI.^1,2,8 Desai et al⁹ described a 16-year-old female athlete with ostial Takayasu disease who, after PCI, suffered cardiac arrest from in-stent restenosis and required mechanical circulatory support and CABG,⁹ underscoring the precarious nature of stenting in young patients with Takayasu arteritis, in whom the inflammatory substrate and potential for stent protrusion into the aorta can promote thrombosis and neointimal hyperplasia.⁹

Despite the favorable patency of CABG, PCI remains a common initial approach for single-vessel disease or when surgical risk is elevated.² In our patient, recurrence after multiple drug-eluting stent procedures was rapid and aggressive, and although drug-eluting stents may offer some local anti-inflammatory benefit, their efficacy in Takayasu arteritis remains debated.³ The combination of ELCA and a drug-coated balloon was therefore selected as a stent-sparing salvage strategy intended to debulk resistant neointima and deliver antiproliferative therapy without adding another metal scaffold.

ELCA delivers ultraviolet energy that, through localized heating and photoacoustic shock waves, disrupts the targeted substrate. Contemporary use of ELCA is largely reserved for challenging anatomies such as heavily calcified undilatable lesions and diffuse in-stent restenosis, where it ablates neointimal hyperplasia with high procedural success and a low complication rate compared with balloon angioplasty alone.¹⁰ Comparative data against rotational atherectomy in bare-metal stent restenosis show similar postprocedural luminal dimensions, although volumetric analysis suggests rotational atherectomy may achieve greater neointimal reduction; in underexpanded stents, ELCA carries an increased risk of perforation and no-reflow.¹⁰ In our patient, the original 3.0 × 15-mm Xience Alpine stent had been well-apposed and fully expanded at index deployment, making strut ablation by rotational atherectomy unnecessary; the target was the recurrent fibrotic neointima, for which ELCA followed by cutting balloon angioplasty offered a tailored debulking approach.

The efficacy of drug-coated balloon angioplasty depends on the quantity of antiproliferative drug transferred to the vessel wall, which is enhanced by controlled microinjury that exposes deeper tissue planes; optimal lesion preparation is therefore a key determinant of procedural success.¹¹ In this patient, sequential ELCA, cutting balloon, and high-pressure noncompliant balloon dilation were chosen to maximize neointimal modification and facilitate paclitaxel transfer from the subsequent drug-coated balloon.

Critically, the success of any revascularization in Takayasu arteritis is heavily dependent on the control of systemic inflammation. Active disease at the time of intervention is a strong predictor of restenosis and major adverse cardiac events.^1,2 Guidelines recommend that elective revascularization be delayed until remission is achieved, typically through corticosteroids and steroid-sparing agents such as methotrexate or infliximab.² Our patient was on a robust immunosuppressive regimen including infliximab and methotrexate, yet still developed restenosis, highlighting the refractory nature of the disease in some individuals. Furthermore, the presence of antithrombin III deficiency necessitated a complex anticoagulation strategy with warfarin and ticagrelor, balancing the risks of stent thrombosis against the hazards of bleeding, a complication noted in patients with Takayasu arteritis even without congenital thrombophilia.

Visual Summary.

Timeline Summarizing the Patient's Coronary Artery Disease Progression and Sequential Revascularization Procedures

DCB = drug-coated balloon; IVUS = intravascular ultrasound; STEMI = ST-elevation myocardial infarction.

Conclusions

This case illustrates the complexity of managing recurrent in-stent restenosis in young patients with Takayasu arteritis, particularly when standard therapeutic options are limited by previous stent layers and concurrent thrombophilia. The rapid recurrence of stenosis following standard therapies in this patient necessitated an aggressive multimodal approach. The successful use of ELCA to debulk neointimal tissue, followed by drug-coated balloon angioplasty, provided an effective solution that restored luminal patency without the placement of further stents. This strategy offers a viable alternative for refractory restenosis in complex inflammatory vasculopathies, although close surveillance and aggressive control of systemic inflammation remain paramount.

Equipment List

The procedure utilized a 0.9-mm ELCA catheter, a 3.0 × 10-mm Wolverine cutting balloon, a 3.25 × 12-mm NC EMERGE noncompliant balloon, and a 3.5 × 15-mm Agent paclitaxel drug-coated balloon.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Take-Home Messages

• •Recurrent in-stent restenosis in Takayasu arteritis reflects ongoing vascular inflammation and requires strategies beyond repeat stenting.
• •A stent-sparing, intravascular imaging–guided approach using laser atherectomy and drug-coated balloon can effectively treat refractory restenosis while minimizing additional stent burden.