Abstract
Background
Giant coronary artery aneurysms (CAAs), defined as aneurysms exceeding 20 mm, are rare vascular anomalies with potentially life-threatening complications such as thrombosis, embolization, and rupture. CCAs are typically linked to atherosclerosis and vasculitis, and their occurrence in Castleman disease (CD), a rare lymphoproliferative disorder, is exceedingly rare.
Case Summary
A 68-year-old man presented with a large right atrial mass on echocardiography, later identified on coronary computed tomography angiography and cardiac magnetic resonance imaging as a giant right coronary artery aneurysm with thrombus.
Discussion
This case highlights a rare presentation of a giant CAA associated with CD and the potential role of interleukin-6 (IL-6) in aneurysm pathogenesis in CD. Additionally, this case underscores the importance of multimodal imaging in diagnosis and management. Further research is needed to explore the link between IL-6 dysregulation in CD and vascular abnormalities.
Take-Home Messages
CD may contribute to vascular abnormalities via IL-6-mediated inflammation. Multimodal imaging is essential for diagnosing giant CAAs and guiding appropriate intervention.
Key Words: advanced cardiac imaging, Castleman disease, giant coronary artery aneurysm, interleukin-6
Visual Summary
Visual Summary.
Timeline Illustration From Presentation to Diagnosis
History of Presentation
A 68-year-old man with a past medical history of hypertension and new extensive mediastinal lymphadenopathy on recent imaging presented to urgent care with a 2-day history of elevated resting heart rates at home ranging from 100 to 110 beats/min. He denied chest pain or dyspnea at the time of presentation. Physical examination was unremarkable. Initial electrocardiogram (ECG) showed sinus tachycardia, and he underwent transthoracic echocardiography. The echocardiogram revealed a large fluid-filled mass adjacent to the right atrium measuring 6.2 cm × 7.3 cm and an anteriorly located moderate pericardial effusion. Based on these findings, he was sent to the emergency department for expedited evaluation.
Take-Home Messages
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Elevated IL-6 levels in CD may contribute to vascular complications, including aneurysm formation, by promoting inflammation, MMP production, and vascular wall weakening. Understanding the role of IL-6 in CD can help in recognizing potential cardiovascular risks.
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Although CAAs in CD are rare, clinicians should consider the possibility of vascular involvement in patients with CD, particularly patients with symptoms suggestive of cardiovascular complications. Awareness of this rare association can aid in timely diagnosis and management.
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Accurate diagnosis of giant CAAs requires a comprehensive imaging approach. Techniques such as echocardiography, CT angiography, and CMR are essential for distinguishing CAAs from other cardiac masses and evaluating their size, structure, and complications.
Differential Diagnosis
The initial differential diagnosis of the right atrial mass included primary or metastatic cardiac tumor, giant coronary artery aneurysm (CAA), cardiac thrombus, and pericardial cyst or abscess.
Investigations
On hospital admission, his laboratory tests showed a high-sensitivity troponin elevation to 2,007, and his ECG showed Q waves in the inferior leads (II, III, aVF) and ST-segment depressions in the anterior precordial leads (V1-V3). He underwent coronary computed tomography (CT) angiography, which revealed a 6.2-cm mass in the right atrium with surrounding thrombus. Cardiac magnetic resonance (CMR) was subsequently performed, confirming that the mass was a mid-right coronary artery (RCA) aneurysm with a laminal thrombus measuring 5.7 × 5.2 × 5.1 cm, compressing both the right atrium and the right ventricle.
Management (Medical/Interventions)
Anticoagulation with heparin infusion was initiated, and coronary angiography was performed, showing minimal coronary artery disease in the left anterior descending and left circumflex arteries, along with contrast filling portions of the RCA aneurysm and left-to-right collateral flow to the distal RCA. The patient was referred to a tertiary care center for advanced intervention, including possible coronary artery bypass graft. Shortly after transfer, he experienced sustained ventricular fibrillation, requiring defibrillation. Repeat ECG subsequently showed inferior ST-segment elevations. He underwent an emergent coronary artery bypass graft with a saphenous vein graft placed to the distal RCA.
Outcome and Follow-Up
The postoperative course was complicated by right ventricular failure with intact left ventricular function with eventual stabilization and discharge to home. Pathology results from one of the mediastinal lymph nodes sampled during surgery showed an increased presence of IgG4-positive plasma cells and morphologic features consistent with Castleman disease (CD). Given the diagnosis of CD, he was referred to hematology for further management and consideration of interleukin (IL)-6 targeted therapy.
Discussion
Giant CAAs, defined as aneurysms exceeding 20 mm in diameter, are exceedingly rare and most commonly arise secondary to coronary artery disease.1 However, they have also been linked to autoimmune or inflammatory conditions, such as vasculitides including Kawasaki disease and Takayasu arteritis.1 In our case, the patient presented with a lymphoproliferative disorder, CD. A direct association between CD and giant CAAs has not been established. There have been reports of vascular aneurysms and arteritis in patients with CD, although coronary involvement remains extremely rare.2, 3, 4
CD is a rare lymphoproliferative disorder that can manifest in 2 main forms: unicentric and multicentric. Unicentric CD typically involves a single lymph node or a single region of lymph nodes and is often asymptomatic or manifests with localized symptoms. Multicentric CD, on the other hand, involves multiple lymph node regions and is associated with systemic symptoms due to dysregulated cytokine activity, particularly IL-6. Multicentric CD can be further classified into HHV8-associated multicentric CD and idiopathic multicentric CD. HHV8-associated multicentric CD is often seen in immunocompromised patients, such as patients with human immunodeficiency virus, and is driven by IL-6 produced by the virus.5
Systemic disease in patients with multicentric CD is driven by dysregulated IL-6 activity that leads to systemic inflammation, manifesting as fever, fatigue, weight loss, night sweats, anemia, hypoalbuminemia, hepatosplenomegaly, and generalized lymphadenopathy. IL-6 plays a central pathogenic role by promoting B-cell and plasma cell proliferation, driving proinflammatory cascades, and impairing albumin synthesis, contributing to hypoalbuminemia and generalized edema. Multicentric CD often progresses to severe complications, including organ failure, infections, or lymphoma transformation if untreated.6 Therapeutic targeting of IL-6 has proven effective in managing CD. Tocilizumab, a humanized anti-IL-6 receptor antibody, and siltuximab, a novel anti-IL-6 monoclonal antibody, have shown significant efficacy in reducing systemic symptoms and stabilizing disease progression. These advancements underscore the critical role of IL-6 in CD pathophysiology and highlight the effectiveness of IL-6-directed therapies in altering the disease course.7
This cytokine has also been implicated as a key proinflammatory mediator in the pathogenesis of vascular diseases, and in fact elevated IL-6 levels are associated with increased cardiovascular risk, myocardial infarction, and mortality. Studies show that high IL-6 levels are closely linked to the development and progression of aortic and CAAs. Furthermore, IL-6 is upregulated in both thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). In experimental models, IL-6 knockout mice exhibited significantly smaller TAA sizes compared with wild-type mice, indicating a protective effect in aneurysm formation when IL-6 is absent. Pharmacologic inhibition of IL-6 with tocilizumab also significantly reduced TAA size, further confirming the involvement of IL-6. In the context of AAA, IL-6 is similarly upregulated and associated with increased signaling pathways that promote aneurysm growth and rupture.8 Moreover, IL-6 is actively secreted by aneurysmal tissues, and higher venous IL-6 concentrations observed in patients with AAA suggest that the aneurysm itself is a source of the cytokine.9
IL-6 signaling plays a central role in aneurysm development by activating cellular processes that contribute to vascular inflammation and wall weakening. It induces vascular inflammation by promoting the recruitment of inflammatory cells, such as macrophages and lymphocytes, to the arterial wall. This inflammation leads to the degradation of the extracellular matrix (ECM), weakening the vessel and predisposing it to aneurysm formation. IL-6 also enhances the production of matrix metalloproteinases (MMPs), enzymes that break down the ECM, further contributing to the structural weakening of the vessel. Inflammatory cells within the aneurysmal wall further secrete cytokines that stimulate the production of MMPs and induce a feedback loop within the vessel wall. This creates a vicious cycle where the activation of proteolytic enzymes leads to the release of more cytokines, perpetuating chronic inflammation and further ECM degradation.
Additionally, IL-6 exacerbates this process by destabilizing atherosclerotic plaques. It reduces collagen synthesis, a crucial structural component of the plaque, while increasing MMP activity, which destabilizes the plaque and increases the risk of rupture. This disruption of plaque stability can contribute to the development of aneurysms. Through its dual roles in both promoting ECM degradation and destabilizing atherosclerotic plaques, IL-6 leads to significant remodeling of the vascular wall that accelerates vascular wall weakening, aneurysm formation, and the potential for rupture.10
In summary, IL-6 plays a pivotal role in the pathogenesis of CD and in vascular inflammation and aneurysm formation. Parallel mechanisms may be present in Kawasaki disease and Takayasu arteritis, in which inflammatory-mediated vascular damage, endothelial dysfunction, and transmural infiltration contribute to aneurysm formation. Whereas previous reports have linked CD to systemic vasculitis and arterial aneurysms, coronary involvement remains extremely rare. The presence of an RCA aneurysm in this case raises the question of whether IL-6 dysregulation in CD may contribute to coronary aneurysm formation through mechanisms similar to those seen in other IL-6-driven vascular diseases. Further investigation through biopathologic studies are needed to determine whether a true link between CD and giant CAAs through an IL-6 mediated signaling pathway exists.
Lastly, multimodal cardiac imaging was essential for accurately differentiating this cardiac mass. In our case, initial echocardiography (Figures 1 and 2) demonstrated a large echolucent mass of unclear origin. CT angiography (Figure 3), coronary angiogram (Videos 1 and 2) and CMR (Figures 4 and 5) provided detailed three-dimensional visualization, confirming the diagnosis of a giant CAA with intraluminal thrombi. These imaging modalities also delineated the size and structure of the aneurysm and its compressive effects on adjacent cardiac structures. Coronary angiography was critical in confirming the coronary origin of the aneurysm, detecting thrombotic occlusion, and evaluating collateral artery formation. The integration of these imaging techniques highlights their complementary roles in diagnosing and managing rare vascular anomalies such as giant CAAs, emphasizing the importance of a comprehensive approach to delineate etiology and guide treatment strategies.
Figure 1.
Transthoracic Echocardiography
Subcostal view showing a large anteriorly located intracardiac mass of unknown etiology (red circle). LA = left atrium; LV = left ventricle; RV = right ventricle.
Figure 2.
Transthoracic Echocardiography
Apical 4-chamber view showing a large anteriorly located intracardiac mass of unknown etiology (red circle). The mass is incompletely characterized by transthoracic echocardiography alone. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.
Figure 3.
Nongated Computed Tomography Angiography of the Chest
Axial view showing the location of the mass (red arrow) in relation to other intrathoracic structures. LV = left ventricle; RA = right atrium.
Figure 4.
Cardiac Magnetic Resonance
Short axis view demonstrating the mass originating from the aortic root near the origin of the right coronary artery (red arrow). Ao = aortic; LV = left ventricle.
Figure 5.
Cardiac Magnetic Resonance
Phase-sensitive inversion recovery late gadolinium enhancement imaging demonstrating the coronary artery aneurysm (red arrow), along with layered thrombus and/or calcification (yellow arrows).
Conclusions
This case highlights the rare occurrence of a giant CAA (Figure 6) in a patient with CD, potentially linked to elevated IL-6 activity. The inflammatory pathways driven by IL-6 contribute to vascular pathology, including aneurysm formation and endothelial dysfunction, which may explain development of the aneurysm in this patient. The use of multimodal imaging was crucial for accurate diagnosis and management, underscoring its importance in rare vascular conditions. Further studies are needed to better understand the potential connection between CD and giant CAAs, particularly through IL-6-mediated mechanisms.
Figure 6.
Surgical Specimen
Intraoperative view of the giant right coronary artery aneurysm.
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
For supplemental videos, please see the online version of this paper.
Appendix
Coronary Angiogram
Contrast fills a giant coronary aneurysm and eventually washes out. Note that the coronary aneurysm is not fully opacified owing to its gigantic size.
Coronary Angiogram
The presence of left to right collaterals to the distal right coronary artery may suggest significant occlusion to the distal portion of the aneurysm.
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Associated Data
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Supplementary Materials
Coronary Angiogram
Contrast fills a giant coronary aneurysm and eventually washes out. Note that the coronary aneurysm is not fully opacified owing to its gigantic size.
Coronary Angiogram
The presence of left to right collaterals to the distal right coronary artery may suggest significant occlusion to the distal portion of the aneurysm.