Coronary Vasculitis in Takayasu’s: A Case Report and Review of the Literature on Optimal Surgical Intervention

Abstract

Takayasu’s arteritis (TAK) is a rare, large-vessel vasculitis that typically involves the aorta and its major branches. Patients may experience coronary involvement, most commonly the left main coronary ostia. Patients with coronary artery occlusion often require emergent revascularization; however, there is debate regarding the optimal timing and type of surgical intervention in the setting of TAK. Herein we describe a 32-year-old female presenting with non-ST elevation myocardial infarction (NSTEMI) who underwent percutaneous intervention (PCI) with drug-eluting stent (DES) placement and was subsequently diagnosed with TAK. A 32-year-old female presented to the emergency department with chest pressure and dyspnea. Her electrocardiogram findings and troponin elevation were consistent with NSTEMI and she underwent coronary angiography with DES placement. During angiography, aortic insufficiency was noted. Transesophageal echocardiogram confirmed intimal thickening of the aortic root with aortic regurgitation. She was diagnosed with TAK, started on high-dose steroids, and transferred to a tertiary care center for rheumatology consultation. This patient’s clinical course raised several questions regarding surgical intervention in TAK. The optimal timing of surgery and preferred approach (endovascular intervention vs coronary artery bypass grafting [CABG]) were specifically critiqued. While endovascular intervention (PCI with angioplasty or stent) is typically less invasive than CABG, it may be associated with a higher risk of postsurgical re-stenosis and studies are conflicting regarding the optimal approach. Further research is necessary to determine the long-term efficacy and safety of these interventions, as well as their timing in the overall management plan.

Introduction

Takayasu’s arteritis (TAK) is a rare, systemic large-vessel vasculitis that mainly affects the aorta and its major branches. It most commonly presents in young women under the age of 40 years old and those of Asian heritage. ¹ Up to one-third of patients with TAK experience coronary artery involvement, commonly presenting with occlusion of the left main coronary ostia. ² Patients who present with acute coronary artery occlusion often require emergent revascularization; however, there is debate over the optimal surgical intervention, especially during acute vasculitis. Previous studies have shown that endovascular intervention such as percutaneous intervention with drug-eluting stent (PCI with DES) may result in greater rates of restenosis compared to coronary artery bypass grafting (CABG). ³ However, coronary bypass is a much more invasive procedure with a longer recovery time, and is typically performed in patients with multivessel disease or following multiple episodes of restenosis with stents. We present a case of a 32-year-old female who presented with a non-ST elevation myocardial infarction (NSTEMI) in the setting of a 95% ostial stenosis of the left main coronary artery. She underwent PCI with DES placement in the acute setting and was subsequently diagnosed with TAK.

Case Presentation

A 32-year-old female with no prior cardiac history presented to a community hospital emergency department with central chest pressure, dyspnea, and diaphoresis. An EKG was significant for diffuse ST segment depressions with ST elevations in augmented vector right (aVR). A high-sensitivity troponin was elevated to 27 670 (reference range for female sex <14.9), concerning for NSTEMI (Figure 1). She underwent urgent coronary angiography which confirmed a 95% ostial stenosis of the left main coronary artery (Figure 2). Aortic insufficiency was noted on angiography, prompting additional evaluation with a transesophageal echocardiogram. This showed intimal thickening of the aortic root extending into the ascending aorta with moderate-to-severe aortic regurgitation, consistent with aortitis (Figure 3). A DES was placed given the ostial location of the lesion, borderline hemodynamic instability, and EKG changes concerning for acute ischemia with associated heart failure.

Figure 1.

Electrocardiogram: ST segment depressions in the inferior and anterolateral leads representing diffuse ischemia.

Figure 2.

Coronary angiogram showing severe ostial left main stenosis.

Figure 3.

TEE showing dilated aortic root with thickened aortic wall and moderate-to-severe aortic regurgitation (arrow). TEE, transesophageal echocardiogram.

Infectious workup including syphilis, HIV, hepatitis, and blood cultures were negative. Urine toxicology screen was positive for cannabinoids, but negative for cocaine. Inflammatory markers were elevated with an ESR of 42 mm/h (1-20 mm/h), and C-reactive protein of 30 mg/L (<10 mg/L). C3 was marginally elevated (171 mg/dL, 82-167 mg/dL) with a normal C4 (31 mg/dL, 12-38 mg/dL). Cryoglobulins, rheumatoid factor, antinuclear antibody (ANA), and antineutrophilic cytoplasmic antibody (ANCA) panel were negative.

The patient was subsequently started on high-dose corticosteroids (1 mg/kg prednisone; 60 mg daily) given the concern for vasculitis and no signs of active infection. The next day, she developed discordant blood pressures between her left and right upper extremities. Vascular duplex ultrasound revealed severe narrowing of the left subclavian artery with retrograde flow within the left vertebral artery consistent with subclavian steal syndrome. The patient was subsequently transferred to a tertiary care center for rheumatology consultation. Left subclavian stenosis consistent with vasculitis was confirmed on magnetic resonance imaging (magnetic resonance angiography [MRA]; Figure 4). She was diagnosed with TAK based upon the presence of imaging-confirmed vasculitis in the setting of elevated inflammatory markers.

Figure 4.

MRA neck showing severe stenosis of the proximal left subclavian (arrow).

During the hospitalization, the patient’s chest pain resolved and blood pressure stabilized. She was continued on 60 mg of prednisone daily until outpatient follow-up with rheumatology. At her first outpatient visit 3 weeks later, she remained asymptomatic, with normalized inflammatory markers and was started on a gradual prednisone taper from 60 to 20 mg daily over the following 2 months. In addition, infliximab was initiated (5 mg/kg every 5 weeks) as steroid sparing therapy. An echocardiogram at 8 months post-initial admission showed an improvement in ejection fraction to 65%. She has been monitored closely by cardiology and cardiothoracic surgery given the moderate-to-severe aortic insufficiency, and will likely require a mechanical aortic valve replacement or Ross procedure in the future given the degree of insufficiency.

Discussion

TAK is a systemic, large-vessel vasculitis that typically affects young women ages 20 to 40 years old. Coronary involvement in TAK occurs in 10% to 30% of cases, commonly involving the left main coronary ostia, as seen in our patient. An older review in 1991 described 63 TAK patients with 92 coronary lesions; 66 (73%) involved the coronary ostia of either the left main or right main coronary arteries. ⁴ The second most common location included nonostial proximal aspects of the major coronary arteries (18.5% of lesions). ⁴ A systemic review in 2020 confirmed that the coronary ostia is still the most common location of coronary involvement. In this review, approximately 30% of lesions were found in the right coronary artery, 30% in the left main coronary, 25% in the left anterior descending, 10% in the circumflex, and <1% in the posterior descending artery. ⁵

Classification criteria from the American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) were updated in 2022. Absolute requirements for the diagnosis of TAK include an age of onset prior to the age of 60 years old, and evidence of vasculitis on imaging. ⁶ Notably, the preferred imaging modality is magnetic resonance imaging given its ability to identify mural inflammation and changes to vessel lumens. ⁷ Additional clinical features in the classification criteria include female sex, angina, extremity claudication, vascular bruit, reduction in pulse in the upper extremity, carotid artery tenderness and/or reduced pulse, systolic blood pressure difference greater than 20 mmHg between limbs, and number and location of affected vascular territories. The clinical and imaging features in our patient resulted in a score of 7, satisfying the classification requirements for TAK (score ≥5 is needed).

Our patient’s clinical course raised several pertinent questions regarding surgical intervention in TAK. The optimal timing of surgery and preferred approach were specifically critiqued. A review from 2023 suggests that patients with active inflammation should receive immunosuppression prior to revascularization, except in emergent cases where surgical intervention cannot be delayed. ⁸ Notably, the 2021 ACR/Vasculitis Foundation Guidelines for the Management of TAK underscore coronary artery involvement with risk for impending infarction as a scenario that may warrant immediate surgical intervention. ⁹ These guidelines also recommend the use of high-dose glucocorticoids in the periprocedural period in patients with active disease. The data which support these recommendations primarily arises from retrospective cohort studies. Fields et al described surgical outcomes among 251 patients with TAK in the Mayo Clinic registry between 1975 and 2002. ¹⁰ Forty-two patients (17%) required surgical intervention in this mostly prebiologic cohort, but only one was for coronary artery disease. Thirteen patients had active disease at the time of surgical intervention. This group was more likely to require subsequent revision surgery and more likely to develop symptomatic disease at another site. Zheng et al described clinical outcomes in 46 patients with TAK undergoing cardiovascular surgery (4 with coronary intervention) between 2010 and 2015. ¹¹ Disease activity was strongly associated with postoperative complications, which occurred in all 8 patients (100%) with active vasculitis, but only 4 of 38 patients with inactive disease (10.5%; P < .001). Similarly, only 4% of patients with a preoperative CRP <5 mg/L suffered postoperative complications, compared to 63% of patients with preoperative CRP values ≥5 mg/L. Finally, preoperative immunosuppression was associated with fewer surgical complications (4% of patients) than patients not on therapy at the time of surgery (50% of patients).

Several additional retrospective analyses described surgical outcomes in disease impacting the coronary arteries in TAK. Wang et al described clinical outcomes in 46 patients undergoing coronary revascularization (PCI or CABG) in the setting of TAK. ¹² Roughly one-third (15 of 46 patients) suffered a major adverse cardiac event (MACE; myocardial infarction, repeated revascularization, cardiac death) during follow-up. MACE was recorded in 52% of patients in the PCI group (13 of 25) and 9.5% of patients in the CABG group (2 of 21), which was a statistically significant difference. When stratified according to disease activity (stable or active), patients undergoing PCI during active TAK had the highest incidence of MACE, affecting nearly 80% of patients over a period of 8 to 10 years. Interestingly, in patients undergoing revascularization during stable or inactive TAK, there was no statistically significant difference in MACE between patients in the PCI and CABG groups. This finding suggests that some of the risks of subsequent complications following PCI may stem from its selective use in patients with higher baseline disease activity. Among patients with active TAK undergoing revascularization, the use of perioperative corticosteroids lowered the subsequent risk of MACE compared to those not treated with corticosteroids. A second cohort study was conducted in 2021 at the same institution in China as the Wang cohort. ³ This study described long-term outcomes in 51 TAK patients who underwent coronary revascularization with either PCI or CABG. Cardiovascular mortality was similar between groups across a median follow-up of 5 years (7.1% in PCI group vs 13% in CABG; P = .772). Restenosis was significantly higher among the PCI group (39.3% in PCI group vs 8.7% in CABG; P = .022). Together, these studies suggest inflammation in the active phase of TAK worsens procedural outcomes, while corticosteroid use in the perioperative setting improves outcomes. Overall, PCI appears to be associated with similar risk of future myocardial infarction, stroke, heart failure, and death in comparison to CABG, but with higher risk of subsequent revascularization. Given the retrospective nature of these studies, confounding bias may be present as patients with active, untreated new-onset TAK may be more likely to receive PCI compared to CABG in the acute setting.

Given the sparse data in the literature, in addition to the limitations inherent in retrospective analyses, ongoing debate regarding the optimal surgical intervention in TAK with coronary involvement remains. The studies by Wang and Huang suggest similar mortality rates between PCI and CABG, but 5-fold higher rates of revascularization following PCI. These findings are supported by several additional case series and case reports documenting multiple episodes of restenosis in TAK following PCI, with some patients eventually requiring CABG for definitive treatment.^8,13-15 Nonetheless, the use of PCI with DES has become more common in TAK, especially in those with single vessel disease. A recent study from India describes improved outcomes with PCI compared to other studies and may provide important insight into surgical intervention in TAK. This study included 942 patients with 2450 arterial lesions, numbers far greater than any previous study in this area. Coronary lesions had higher rates of restenosis and lower definitive success rates compared with other sites of vascular involvement. ¹⁶ At all sites, PCI use resulted in early success in restoring blood flow for arterial occlusions, but follow-up angiography often confirmed subsequent re-stenosis. This study describes the safety and efficacy of multiple repeated percutaneous interventions (which improved late success rates in obstructive lesions from 48.6% to 83.3% across a median follow-up of 3 years). Unfortunately, there are no randomized controlled trials investigating the optimal surgical intervention in TAK, and current literature comes from case reports, literature reviews, and retrospective studies. Additional research is needed to determine the optimal timing and surgical approach in patients with ischemic injury in TAK, but in the interim, some useful guidance for clinicians is reviewed below (Table 1).

Table 1.

Important Treatment Considerations for Newly Diagnosed TAK.

Important treatment considerations for newly diagnosed TAK affecting the coronary arteries
Initiate immunosuppressive therapy as soon as possible after diagnosis is confirmed
High-dose glucocorticoids are recommended in the periprocedure period for patients who require surgical intervention (endovascular or bypass)
In nonemergent scenarios affecting the limbs or other organs, progressive ischemia is typically addressed by escalation of immunosuppression prior to surgical intervention a
Endovascular intervention (PCI with angioplasty or stent) may be associated with a higher risk of postsurgical re-stenosis compared to CABG, but high-quality studies are lacking and further research is necessary to define the optimal surgical approach

Abbreviations: CABG, coronary artery bypass grafting; PCI, percutaneous intervention; TAK, Takayasu’s arteritis.

^aImmediate surgical intervention may be necessary in coronary artery involvement due to risk of progressive tissue infarction, as well as other sites where delay is thought to pose life- or organ-threatening risk.

Conclusion

We present a case of a 32-year-old female presenting with an acute NSTEMI in the setting of new onset TAK, who underwent PCI with DES in addition to treatment with corticosteroids. Expert guidelines suggest that patients with a high suspicion of TAK should be started on immunosuppression prior to surgical intervention, when possible, with exceptions in emergent scenarios as described in our case presentation. PCI with DES is a less-invasive procedure than CABG, but has been associated with higher rates of restenosis in the literature. In addition, coronary artery involvement tends to have lower definitive success rates compared to other sites of vascular involvement. Given the rarity of disease, randomized controlled trials comparing methods of surgical intervention are impossible. Additional research is needed to determine the optimal timing and surgical approach in patients with ischemic injury in TAK.