Takayasu arteritis (TA) is a chronic inflammatory disease of unknown etiology that affects large blood vessels, mainly the aorta and its main branches and the pulmonary and coronary vessels.1 Its rarity means that monitoring of disease activity and the best therapeutic approach are a challenge. When associated with acute coronary syndromes (ACS), the best interventional treatment has not been established. The results in case series of treatment by percutaneous transluminal coronary angioplasty (PTCA) and/or coronary artery bypass grafting (CABG) are inconsistent.1 Against this background, we describe the baseline characteristics, clinical manifestations, angiographic findings, treatment and long-term outcome of patients with TA and ACS.

We retrospectively analyzed eight patients with TA and ACS (unstable angina or myocardial infarction [MI]) between 2004 and 2010. The diagnosis of TA was based on the 1990 criteria of the American College of Rheumatology (age at disease onset <40 years, difference in blood pressure between limbs >10 mmHg, bruit over aorta, arteriogram abnormality on arteriography, Doppler ultrasound or computed tomography (CT) angiography.1

All patients with typical chest pain were immediately classified as having ACS and stratified according to clinical presentation. Those with atypical pain and/or equivalent ischemic symptoms, such as dyspnea, were managed on the basis of a chest pain protocol, remaining under observation for 12hours with ECG and testing of markers of myocardial necrosis (troponin and CK-MB) every three hours. Those with ST-segment depression on the ECG and/or positive myocardial necrosis markers were diagnosed with ACS and thus included in the study. The three cases with typical chest pain had normal ECG and myocardial necrosis markers, while the other five, with atypical pain and/or dyspnea, had ECG alterations or positive necrosis markers.

The following data were obtained: age, gender, clinical and electrocardiographic manifestations, Killip class, risk factors for ACS, markers of myocardial necrosis (CK-MB and troponin), creatinine clearance, left ventricular ejection fraction, inflammatory markers (C-reactive protein and erythrocyte sedimentation rate [ESR]), medication during hospital stay, angiographic findings, treatment (medical, percutaneous or surgical) and long-term outcome.

Data were also acquired on anatomical arterial lesions detected by conventional and/or CT angiography. Stenosis of ≥70% was considered significant in both systemic and coronary vessels.

In cases of PTCA, the type of stent (bare-metal or drug-eluting) was recorded, as were types of arterial or venous grafts used in CABG.

Statistical data were expressed as percentages and absolute values.

All eight patients were women, median age 49 years. The baseline characteristics of the population are described in Table 1. The most common clinical presentation was unstable angina, in 75% of cases; the ECG was normal in 62.5% of cases (Table 2).

The vessels most affected were the subclavian and renal arteries in 62.5% of cases, followed by the carotid arteries and aorta in 50% and the iliac arteries in 25%. Of the coronary arteries, the segments most affected were the left main and the right coronary artery in 62.5% of cases, followed by the left anterior descending and circumflex arteries in 25% of patients. In one case (12.5%) no obstructive coronary lesions were detected. Ostial lesions were observed in 75% of patients. There were three cases (37.5%) of three-vessel disease and two (25%) of two-vessel disease (Table 3).

Three patients were treated by CABG, three by PTCA (two with bare-metal stents and one with a drug-eluting stent), and two were treated medically. In-hospital mortality was 25% and there were no deaths during a mean follow-up of 30 months. One patient treated by CABG presented stable angina without needing reintervention and one case treated by PTCA with a bare-metal stent underwent reintervention due to unstable angina (Table 4).

TA mainly affects women (90% of cases) aged between 10 and 40 years. In the literature some form of coronary disease is reported in 6–30% of patients with TA.1–4 Its pathogenesis is not fully understood; it is thought to result from chronic autoimmune inflammation of the large arteries, although other factors, including infectious agents and genetic predisposition, may also be involved. The disease develops in two stages: an initial phase characterized by elevation of inflammatory markers, followed by a chronic phase with vascular damage.3

It is not known exactly when coronary lesions appear. Most studies show a correlation between ACS and elevated inflammatory markers such as C-reactive protein and ESR.1 However, some case reports have shown no direct relationship between active inflammation and coronary symptoms.5 In our series, elevated C-reactive protein was observed in 50% of patients and elevated ESR in 87%, suggesting that the latter is more strongly associated with ACS in patients with TA.

Clinical manifestations range from stable angina to MI, and must be promptly diagnosed in order to begin immunosuppressive therapy together with appropriate cardiological treatment, which will improve prognosis.4 The few case reports in the literature indicate that myocardial ischemia is one of the main causes of death in TA, with mortality of up to 50% at five years.3 Only three patients in our series (37.5%) had typical chest pain, while five (62.5%) had no ECG alterations suggesting acute ischemia. Only two patients (25%) were diagnosed with MI, most being categorized as having unstable angina. In-hospital mortality was 25%, in both cases due to cardiogenic shock. There were no deaths during a mean follow-up of 30 months, in contrast to the mortality reported in the literature, although the small sample size makes comparisons difficult. The high in-hospital mortality may have been due to the severity of cases with ostial lesions in the left main coronary artery. The low long-term mortality may be partly due to better control of TA-related inflammation following ACS.

Ostial lesions in the right and left coronary arteries are the most common findings, in 87.5% of TA cases with coronary involvement. In these diseased vessels, luminal narrowing is caused by extension of intimal proliferation and contraction of the fibrotic media and adventitia from the ascending aorta. Ostial involvement was found in 75% of our patients, in agreement with the literature. However, lesions may also occur in more distal segments, the chronic inflammation found in TA accelerating the development of atherosclerosis, as seen in 50% of the patients in our series.4 Diagnosis is usually based on clinical features and cine coronary angiography, although recent studies have demonstrated excellent results with CT angiography in TA.4

Implantation of bare-metal stents in patients with TA is followed by restenosis in up to 78% of cases. In the few reports of drug-eluting stents being used in this population, short- and long-term restenosis rates are also high, casting doubt on their effectiveness in these patients. Some authors suggest that drug-eluting stents are only useful as a bridge while immunosuppression is optimized and until CABG can be performed.2,4,6,7 Yokota et al.,4 reported the case of a 52-year-old woman who underwent PTCA of the left anterior descending artery four times using drug-eluting stents. Restenosis occurred three times, the problem only being overcome after the fourth intervention; the authors considered that vessel patency was preserved due to the addition of steroid therapy at that time.4,8 In our series in-stent restenosis occurred in one of two cases even with only mild inflammatory activity, further fueling the debate over which type of stent to use in these patients. Once again, the small study population severely limits the ability to establish correlations between stent use and outcome.

The best type of graft for CABG has yet to be established for these patients, and the presence of ostial lesions of the aorta and possible involvement of the subclavian arteries makes the decision more complex. Unlike most CABG procedures, saphenous vein grafts are generally used in TA patients, except in cases of severe aortic calcification. Survival with saphenous vein-to-left anterior descending artery grafting is 80% at 10 years, with event-free survival of 77%. Internal mammary in-situ grafts are not totally contraindicated but should be avoided, and if used should be preceded by imaging studies of the subclavian arteries to ensure their patency.1,9 In two cases in our series in which left internal mammary artery in-situ grafts were used, the patients were still asymptomatic after 20 months. Only one saphenous vein graft lesion was detected, which did not require reintervention.

Coronary involvement in TA is rare but extremely serious due to the complexity of the lesions. Knowledge of patients’ clinical, ECG, angiographic and hemodynamic characteristics is essential to decide on the best form of treatment, but this is still the subject of debate given the paucity of cases reported. In our study, patients who survived the acute phase and were discharged home had good long-term outcomes.

The authors have no conflicts of interest to declare.