Takayasu's arteritis causing coronary stenosis with myocardial ischemia, severe aortic regurgitation, and pericarditis

Abstract

Takayasu's Arteritis (TA) is a rare, chronic large-vessel vasculitis that can lead to severe cardiac complications and life-threatening outcomes. Early diagnosis is essential for improving patient prognosis, but its nonspecific clinical presentation and laboratory findings often cause delays. We present a 34-year-old woman with a history of heart murmur who presented with chest pain but no additional symptoms. Imaging revealed aortic regurgitation, ventricular septal defect, myocardial ischemia, pericarditis, aortic wall thickening, and multivessel stenoses, leading to a diagnosis of Takayasu's Arteritis, treated with coronary bypass and aortic tube graft surgery. Takayasu's Arteritis should be included in the differential diagnosis of patients presenting with atypical clinical features and cardiac involvement, particularly in cases with valvular disease. This case highlights the essential role of multimodal imaging in the detection and management of TA.

Graphical Abstract

Introduction

Takayasu's Arteritis is a rare chronic, idiopathic, large-vessel vasculitis primarily affecting the aorta, its major branches, the pulmonary artery, and the coronary arteries. It affects predominantly young women under 40 years old but can be observed in adults of any age [1]. It has a heterogeneous global distribution, with higher incidence rates observed in Asian populations, with an annual incidence of 0.4 to 2.6 cases per million [2].

Although its exact etiology and pathogenesis remain unclear, complex genetic factors, including HLA-B*52, immune response regulators, and proinflammatory cytokines, play a significant role [4].

Histologically, TA is characterized by granulomatous panarteritis caused by infiltration of the arterial wall by T and B lymphocytes, macrophages, and multinucleated giant cells [1].

Clinical manifestations can vary widely, depending on the topography of arterial lesions, ranging from asymptomatic disease to absent pulses to catastrophic cardiac failure, with cardiac or neurological complications being the most common causes of death [1]. The nonspecific clinical presentation and laboratory findings (elevated CRP and ESR) can lead to a delayed diagnosis. Given its high morbidity and mortality, early diagnosis is crucial for improving outcomes.

We hereby present a case of a young female patient diagnosed with Type IIb TA showing multiple vessel involvement.

Case presentation

A 34-year-old Spanish woman who presented with chest pain, initially misdiagnosed as anxiety, was referred to the cardiology department due to a cardiac murmur. Physical examination revealed bilateral cervical systolic, apical systolic, and left parasternal diastolic murmurs. She had no history of hypertension, diabetes, dyslipidemia, or other comorbidities, including autoimmune or inflammatory diseases.

The differential diagnosis included myocardial infarction, vasculitis, coronary artery disease, valvular heart disease, myopericarditis.

The echocardiogram revealed severe aortic regurgitation (AR), mild left ventricular (LV) dilation, and a left ventricular ejection fraction at the lower limit of normality.

Laboratory tests revealed elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels.

Cardiac MRI demonstrated severe AR, with a regurgitation fraction of 40% observed in the 4D flow sequence (Fig. 1 and Video 1), small perimembranous ventricular septal defect from the left ventricular outflow tract to the subvalvular region of the tricuspid valve (of small caliber and low-velocity predominance during diastole) (QP/QS = 1.16) (Fig. 2 and Video 2), mild pulmonary (9%), tricuspid (10%), and mitral (5%-10%) insufficiencies, LV dilatation, prominent left atrium, and global hypokinesis (ejection fraction 44%) (Video 3). Late gadolinium enhancement (LGE) sequence (Fig. 3) revealed a focus of transmural enhancement in the basal lateral segment of the LV, suggestive of ischemic necrosis, and diffuse enhancement of the pericardium and left pleura, indicative of inflammation (Fig. 3).

Fig. 1.

4D flow sequence. Severe aortic regurgitation. Wide diastolic reverse flow jet from the aortic root with velocity-based color coding and vectors indicating flow direction (arrow).

Fig. 2.

4D flow sequence. Perimembranous septal defect. Small jet from the aortic root to the right ventricular outflow tract (asterisk).

Fig. 3.

Late gadolinium enhancement MRI sequence. Transmural enhancement in the basal lateral segment of the left ventricle, suggesting an ischemic lesion (asterisk). Diffuse enhancement of the pericardium and left pleura (arrows).

Cardiac CT (Naeotom Alpha, Siemens Healthineers, Forchheim, Germany) revealed marked thickening of the aortic root, valvular plane, and proximal ascending aorta, severe irregularity and deformity of the arterial lumen (Fig. 4), critical stenosis of the left coronary ostium (Fig. 5) with distal recanalization of the left anterior descending, left circumflex, and left marginal arteries, small ventricular septal defect in the left ventricular outflow tract, signs of pericardial, anterior mediastinal, and descending aortic inflammation (Fig. 4) and slight dilation of the left ventricle. In the virtual noncontrast imaging, high attenuation of the pathological mural wall was evident (Fig. 4).

Fig. 4.

Angio-CT. Left: Irregular and thickened wall of the ascending aorta (arrows). Middle: Irregular and thickened wall of the aortic arch and descending aorta with involvement of mediastinal fat (arrows). Right: Spectral angio-CT. Virtual noncontrast longitudinal view of the aorta showing high attenuation of the aortic wall.

Fig. 5.

Coronary CT. Occlusion of the left main trunk in axial (red arrow) and 3D reconstruction views (white arrow).

Aortic angio-CT showed an occlusion at the origin of left carotid and subclavian arteries (Fig. 6) and severe stenosis of the brachiocephalic trunk immediately proximal to the bifurcation (Fig. 7), with preserved right carotid and vertebral arteries supplying flow to the circle of Willis and to the left subclavian artery (subclavian steal syndrome) (Fig. 7). The abdominal aorta and its branches were normal (Fig. 8).

Fig. 6.

Angio-CT. Occlusion at the origin of the left common carotid (white arrows) and left subclavian artery (red arrow).

Fig. 7.

Angio-CT. Left: Severe proximal stenosis of the brachiocephalic trunk (red arrow). Right: Subclavian steal syndrome. Slow reverse flow in the left vertebral artery (asterisk), secondary to proximal left subclavian occlusion (white arrow).

Fig. 8.

Angio-CT. Volumetric reconstruction showing the abdominal aorta and its branches as normal.

Coronary angiography confirmed complete occlusion of the left main trunk (Video 4 and Fig. 9) with recanalization of its branches through collateral arteries supplied by the right coronary artery.

Fig. 9.

Coronary angiography. Occlusion of the left main trunk (arrow) with filling of the anterior descending coronary artery by collateral vessels from the right coronary artery.

Based on these findings, our patient met the diagnostic criteria for Takayasu's arteritis (TA).

She initially received treatment with glucocorticoids and colchicine. Subsequently, surgical intervention involved replacing the aortic valve and root, ascending aorta, and brachiocephalic trunk with a tube graft. A saphenous vein bypass was performed to the obtuse marginal and left anterior descending arteries (Fig. 10), along with closure of the ventricular septal defect.

Fig. 10.

Postoperative angio-CT. Volumetric reconstruction showing a right brachiocephalic graft (arrow), occlusion of the origins of the left carotid and subclavian arteries (asterisk), and a double coronary bypass (arrowhead).

These treatments were chosen for their ability to address both the inflammation and the structural complications caused by TA, balancing the need for rapid immunosuppression with the necessity of surgical correction.

She clinically improved in response to treatment. The follow-up angio-CT revealed postsurgical changes, including the replacement of the aortic root, proximal aortic arch, and right brachiocephalic trunk with grafts and surgical clips for a double coronary bypass, without complications. A fluid collection with gas bubbles surrounded the ascending aorta and the right brachiocephalic trunk. A mild pericardial effusion and bilateral pleural effusions, predominantly on the left, with subsegmental bibasal pulmonary atelectasis and the path of a previous right thoracic drainage tube were also observed. Follow-up imaging with CT or MRI is recommended to monitor disease progression, stents or bypass vessels, and should continue lifelong to detect relapses with MRI.

Discussion

Based on our experience with this case, we emphasize that in complex cases, particularly when there is clinical-radiological discordance, it is essential to complement the study with various imaging techniques (ultrasound, MRI, CT) to ensure a comprehensive evaluation and rule out rare conditions, such as autoimmune vasculitis, as observed in this case.

As large-artery biopsies are challenging to perform, multimodal imaging -including echocardiography, cardiac CT, and cardiac MRI- is essential for TA diagnosis [1]. While digital subtraction angiography was previously the gold standard, it is invasive and only provides information on luminal changes, which are typically a late feature [3].

Multidetector CT angiography and MR angiography are noninvasive and depict both luminal and mural lesions in large vessels, thereby facilitating the early detection of vasculitis in TA [1]. Angiographic classification divides TA into 6 types. Type V is the most common. Our patient was a type IIb (ascending aorta, aortic arch and its branches, and thoracic descending aorta). Additionally, coronary and pulmonary artery involvement should be indicated as C (+) or P (+), respectively [1].

Modified Ishikawa's criteria are the most commonly used for diagnosis [2]. In this case, the patient met 1 major criterion (left mid-subclavian artery lesion) and several minor criteria (High ESR, AR, left mid-common carotid lesion, brachiocephalic trunk lesion, descending aorta lesion, and coronary lesion).

Luminal stenosis is observed in 90% of patients, involving the abdominal and thoracic descending aorta in 60%, with the subclavian and common carotid arteries being the most commonly affected branches, typically in their proximal portions, followed by the renal arteries, as was seen in this patient. Collateral vessels may be observed in some cases, mitigating ischemic events. CT typically shows concentric mural thickening of the involved arteries, with transmural calcification in 27% of patients. However, in contrast to atherosclerosis, the arterial lumen remains uniform and smooth [3]. On precontrast CT, the mural thickening shows high attenuation compared with the lumen, whereas contrast-enhanced CT typically reveals a double-ring enhancement pattern [1], usually seen in the venous phase [1]. Less commonly, occlusion, ectasia, dissection, and aneurysms of the vessels may occur due to damage to the media layer [3].

Dilatation and aneurysms are usually observed in the ascending and abdominal aorta, respectively. Pulmonary involvement is seen in 63% of patients [1].

MRI offers several advantages over CT, such as greater sensitivity for detecting mural edema, which is diagnostic for aortitis [3,5]. However, it also has limitations, including difficulty in visualizing small branch vessels, suboptimal visualization of vascular calcification, and potential overestimation of the degree of vascular stenosis [3].

There is cardiac involvement in about 50% of patients, and it is the major cause of morbidity and mortality in TA [6,7]. It can present as pericarditis, myocarditis, coronary arteritis leading to myocardial ischemia, valvulopathy (most commonly aortic insufficiency, followed by mitral insufficiency), or intracavitary thrombosis [6,7].

This patient presented with a coronary artery occlusive lesion (which occurs in 44% of cases) and aortic regurgitation (occurring in up to 25% of TA patients) due to aortic root involvement [1,4]. The aortic subvalvular involvement also caused abnormal flow from left ventricle outflow tract to right ventricle.

Cardiac MR with 4D Flow sequence provides both qualitative and quantitative flow data (as aortic regurgitant fraction) and can depict anomalous flows like interventricular communication.

Cardiac MR late enhancement sequence is also important for distinguishing between myocardial inflammation, fibrosis, or ischemic sequelae, and detecting other cardiac conditions such as pericarditis [8]. The most common late gadolinium enhancement pattern in TA myocarditis is mid-myocardial (13.8%), followed by epicardial fibrosis (11.11%) [8].

TA is treated with immunosuppressors. Typically, corticosteroids are administered to induce remission, followed by the use of steroid-sparing drugs, with a remission rate of up to 60% [1,3]. Symptomatic stenoses or occlusions may require percutaneous transluminal treatment (angioplasty and stenting) or surgery. Surgical management is indicated for aneurysmal enlargement with risk of rupture, symptomatic severe aortic regurgitation, stenotic or occlusive lesions causing critical organ ischemia, and uncontrolled hypertension due to renal artery stenosis [1].

Although combined aortic valve and root replacement is more complex than isolated aortic valve replacement, it offers a better outcome in terms of late postoperative cardiac events [9]. Postsurgical complications such as restenosis, valve detachment, or anastomotic aneurysm formation commonly occur due to tissue fragility from inflammation. Therefore, to improve repair success rates, surgical intervention is often best delayed until inflammation has been sufficiently treated with immunosuppressive therapy [5]. The left coronary ostium is the most frequently affected, sometimes requiring coronary artery bypass grafting, usually performed with saphenous venous grafts [10].

Conclusions

Atypical clinical findings and multivessel or cardiac involvement, particularly valvular involvement, in a young patient should prompt the inclusion of vasculitis, including Takayasu's arteritis, in the differential diagnosis. Multimodal imaging techniques, including echocardiography, cardiac CT, and cardiac MRI, play a central role in the diagnostic approach.

Patient consent

I confirm that written, informed consent for the publication of her case was obtained from the patient.

Appendix. Supplementary materials

Video 1: 4D flow sequence. Severe aortic regurgitation: regurgitation jet.

Video 2: 4D flow sequence. Perimembranous septal defect: small jet from aortic root to right ventricular outflow tract.

Video 3: Short-axis CINE MRI. Global hypokinesia of the left ventricle.

Video 4: Coronary catheterization. Left ostial occlusion with collateral vessels from the right coronary artery supplying the left coronary territory.