Abstract
Light chain cardiac amyloidosis (AL-CA) is a severe and progressively infiltrative disease caused by the deposition of misfolded monoclonal immunoglobulin light chains in the myocardial extracellular space. It is associated with poor prognosis and typically presents as diastolic heart failure, arrhythmias, and atrial appendage thrombosis. We report a case of light chain cardiac amyloidosis with bilateral atrial appendage thrombosis. The patient died from refractory heart failure four months after diagnosis.
Introduction
Light chain cardiac amyloidosis (AL-CA) is a systemic disease caused by the deposition of monoclonal immunoglobulin light chains produced by abnormal plasma cells into myocardial tissue (). It was first identified in the mid-20th century as a cardiac manifestation of systemic amyloidosis. With the advancement of histopathology and immunohistochemistry techniques, its pathogenesis has become increasingly clear. AL-CA progresses rapidly and has an extremely poor prognosis. Among all types of amyloidosis with cardiac involvement, AL-CA is associated with the most severe outcomes. Without timely treatment, the median survival after the onset of heart failure is often less than six months (). In recent years, the development of highly sensitive assays, bone marrow protein screening, and cardiac MRI has improved early detection. Furthermore, chemotherapy regimens based on bortezomib have significantly improved outcomes for some patients. However, early recognition and intervention remain critical to improving overall prognosis.
Case presentation
A 70-year-old woman was admitted with a one-year history of progressive exertional dyspnea and chest tightness, which had worsened over the preceding month and was accompanied by recurrent syncope.
One year prior to admission, the patient developed intermittent exertional chest tightness and shortness of breath, relieved by rest. One month before presentation, she experienced a sudden syncopal episode preceded by transient visual loss, with spontaneous recovery after approximately five minutes. No convulsions or incontinence were reported. Over the subsequent weeks, her symptoms progressed, with worsening dyspnea and paroxysmal nocturnal dyspnea. She was admitted for further evaluation of suspected cardiac disease.
The patient had a history of type 2 diabetes mellitus and a prior ischemic stroke. There was no history of atrial fibrillation, smoking, or alcohol consumption.
On admission, her blood pressure was 91/58 mmHg, and her heart rate was irregular at 72 beats per minute. Physical examination revealed bilateral basal lung rales and mild bilateral lower extremity edema. Cardiac auscultation demonstrated muffled heart sounds without murmurs.
Electrocardiography showed atrial flutter with variable atrioventricular conduction, low QRS voltage in the limb leads, and QS waves in the precordial leads (V1–V6) (Figure 1). Transthoracic echocardiography revealed biatrial enlargement, mild mitral and tricuspid regurgitation, preserved left ventricular ejection fraction (58%), mild thickening of the interventricular septum and posterior wall, and a small pericardial effusion.
Figure 1
Cardiac magnetic resonance imaging demonstrated diffuse late gadolinium enhancement involving both atrial and ventricular walls, including the interatrial septum, consistent with cardiac amyloidosis. Transmural enhancement at the left ventricular apex was also observed, initially raising suspicion of prior myocardial infarction (Figure 2).
Figure 2
Coronary computed tomography angiography revealed moderate (65%–69%) stenosis of the proximal left anterior descending artery and identified thrombi in both the right and left atrial appendages, along with pericardial and pleural effusions (Figure 3).
Figure 3
Holter monitoring documented atrial flutter with frequent ectopic beats and multiple prolonged RR intervals (> 2 s), with the longest pause lasting 4.8 s during syncopal episodes, confirming a cardiogenic etiology.
Laboratory testing showed markedly elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels (4,775 pg/mL). Serum and urine immunofixation electrophoresis demonstrated monoclonal lambda (λ) light chains. Serum free light chain analysis revealed a λ concentration of 12,166.78 mg/dL, with a κ/λ ratio of 0.003.
Histopathological examination of abdominal subcutaneous fat biopsy showed amyloid deposition (Figures 4C, D). Bone marrow biopsy demonstrated clonal plasma cell proliferation (Figures 4A, B).
Figure 4
Given the presence of recurrent syncope associated with prolonged RR intervals, a permanent VVI pacemaker was implanted. Anticoagulation therapy with rivaroxaban [(20 mg once daily)] was initiated after the detection of intracardiac thrombi. In addition, guideline-directed medical therapy for heart failure was administered, including metoprolol, empagliflozin, torasemide, and spironolactone. After treatment, NT-proBNP decreased to 3,646 pg/mL, and symptoms significantly improved, with no recurrence of syncope during hospitalization.
Although a daratumumab-based CyBorD regimen was recommended to suppress monoclonal light chain production, the patient declined chemotherapy due to financial constraints.
After discharge, follow-up was conducted via telephone. At 2 months, the patient reported no recurrence of syncope or worsening heart failure symptoms. However, at 4 months, family members reported that the patient had discontinued all medications and subsequently died at home. Based on the clinical course, refractory heart failure was considered the most likely cause of death.
No repeat imaging was available during follow-up, as all follow-up assessments were conducted via telephone Table 1.
Table 1
| Time | Clinical Events |
|---|---|
| 1 year before admission | Progressive chest tightness and exertional dyspnea |
| 1 month before admission | Recurrent syncope |
| Admission | Diagnosis of AL cardiac amyloidosis with bilateral atrial appendage thrombosis |
| Hospitalization | Pacemaker implantation; initiation of rivaroxaban and heart failure therapy |
| Discharge | Symptom improvement; NT-proBNP decreased |
| 2 months follow-up | No recurrence of symptoms (telephone follow-up) |
| 4 months follow-up | Death at home after discontinuation of medication |
Timeline of clinical course.
Discussion
Light-chain cardiac amyloidosis (AL-CA) represents the most aggressive form of cardiac amyloidosis and is associated with rapid disease progression and poor prognosis. Among the more than 30 proteins known to form amyloid fibrils in vivo, monoclonal immunoglobulin light chains and transthyretin account for over 98% of cases with cardiac involvement (). This case is notable for the coexistence of advanced AL-CA with bilateral atrial appendage thrombosis, recurrent cardiogenic syncope, and rapid clinical deterioration, highlighting several important diagnostic and therapeutic challenges.
AL cardiac amyloidosis and diagnostic pitfalls
Cardiac involvement in AL amyloidosis results from extracellular deposition of misfolded immunoglobulin light chains, leading to restrictive cardiomyopathy, conduction disturbances, and heart failure. Among all amyloid subtypes, AL-CA carries the worst prognosis. According to the Mayo 2012 staging system, patients with stage III disease have a median survival of approximately one year, and survival may be significantly shorter in the absence of effective plasma cell–directed therapy ().
In recent years, noninvasive imaging modalities have transformed the diagnostic approach to cardiac amyloidosis. Cardiac magnetic resonance imaging (CMR) plays a central role, with diffuse late gadolinium enhancement (LGE), abnormal myocardial nulling, increased native T1 values, and expanded extracellular volume fraction serving as characteristic features (). Nuclear imaging with technetium-99m–labeled tracers (such as 99mTc-PYP or 99mTc-DPD) has become a standard diagnostic tool for transthyretin amyloid cardiomyopathy, although its sensitivity is limited in AL amyloidosis ().
In the present case, extensive LGE involving both atria and ventricles strongly supported the diagnosis of advanced cardiac amyloidosis, consistent with previously reported imaging patterns (). However, the presence of transmural enhancement at the left ventricular apex initially raised concern for prior myocardial infarction. Differentiating AL-CA from ischemic cardiomyopathy can be challenging, particularly in patients with coexisting coronary artery disease. Electrocardiographic findings such as low QRS voltage in the presence of increased ventricular wall thickness—the so-called “voltage-to-mass discrepancy”—are considered relatively specific for cardiac amyloidosis (, ). In this patient, coronary computed tomography angiography demonstrated only moderate stenosis of the proximal left anterior descending artery, which was insufficient to explain the extensive myocardial involvement. Taken together, multimodality imaging, laboratory findings, and histopathological confirmation favored amyloid infiltration rather than ischemic myocardial injury.
Atrial mechanical dysfunction and bilateral atrial appendage thrombosis
A notable and clinically significant feature of this case is the presence of thrombi in both the right and left atrial appendages. While atrial fibrillation and atrial flutter are well-recognized risk factors for atrial thrombosis, accumulating evidence suggests that thrombus formation in cardiac amyloidosis is not solely dependent on rhythm abnormalities. Previous studies have demonstrated that intracardiac thrombi may occur even in patients in sinus rhythm, likely due to atrial electromechanical dissociation ().
In AL-CA, amyloid infiltration of the atrial myocardium leads to structural remodeling, impaired contractility, endothelial dysfunction, and blood stasis, thereby creating a prothrombotic milieu. These pathophysiological changes predispose to thrombus formation independent of atrial rhythm. The occurrence of bilateral atrial appendage thrombosis is rare and likely reflects severe atrial mechanical failure and an advanced disease stage. In the present case, the coexistence of atrial flutter and extensive atrial involvement may have synergistically increased thrombotic risk.
Anticoagulation strategy in AL-CA
In this patient, intracardiac thrombi were identified prior to the initiation of anticoagulation therapy, and anticoagulation with rivaroxaban (20 mg once daily) was subsequently initiated. However, follow-up imaging was not available to assess thrombus resolution. Therefore, the efficacy of direct oral anticoagulant (DOAC) therapy in this case cannot be determined, representing an inherent limitation.
Current guidelines emphasize that anticoagulation decisions in cardiac amyloidosis should not rely solely on the presence of atrial fibrillation. The 2021 European Society of Cardiology position statement recommends considering anticoagulation in high-risk patients with cardiac amyloidosis regardless of rhythm status (). Nevertheless, the optimal anticoagulation strategy in AL-CA remains uncertain. Whether DOACs provide equivalent efficacy to vitamin K antagonists in preventing or resolving intracardiac thrombi, particularly in advanced disease, remains controversial. The presence of extensive bilateral atrial appendage thrombosis at diagnosis in this case suggests a profoundly prothrombotic state and underscores the importance of early and individualized anticoagulation strategies.
Arrhythmia, syncope, and disease severity
Syncope in AL cardiac amyloidosis is a marker of advanced disease and is associated with poor prognosis. Potential mechanisms include severe conduction system disease, malignant ventricular arrhythmias, autonomic dysfunction, and electromechanical dissociation. In this case, prolonged RR intervals documented on Holter monitoring confirmed a cardiogenic cause of syncope, prompting permanent pacemaker implantation. Despite symptomatic improvement following pacing and optimized heart failure therapy, the occurrence of syncope reflected advanced myocardial infiltration and limited cardiac reserve.
Therapeutic limitations and rapid clinical deterioration
The cornerstone of treatment for AL amyloidosis is rapid suppression of monoclonal light chain production through plasma cell–directed therapy. The daratumumab-based CyBorD regimen has become first-line treatment, and the ANDROMEDA trial demonstrated significant improvements in hematologic and cardiac response rates as well as overall survival (). In addition, novel therapies targeting amyloid fibrils directly, such as CAEL-101, are currently under investigation and may further improve outcomes in the future (). Unfortunately, in this case, definitive anti–plasma cell therapy was not administered because of financial constraints. The patient ultimately discontinued all medications and died from refractory heart failure within four months of diagnosis. This outcome underscores the aggressive natural history of advanced AL-CA and highlights that supportive care alone is insufficient to alter disease progression.
Conclusion
This case highlights the severe thrombotic risk and rapid clinical deterioration associated with advanced AL cardiac amyloidosis. Bilateral atrial appendage thrombosis may occur even in the absence of atrial fibrillation, reflecting profound atrial mechanical dysfunction and electromechanical dissociation. Early recognition, timely initiation of anticoagulation, and access to disease-modifying therapy are critical to improving outcomes in this high-risk population.
Statements
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
Ethics statement
The requirement of ethical approval was waived by Ethics Committee of the Affiliated Hospital of Hebei University for the studies involving humans because Ethics Committee of the Affiliated Hospital of Hebei University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
WZ: Conceptualization, Investigation, Validation, Writing – original draft, Writing – review & editing. SJ: Writing – original draft, Writing – review & editing. HJ: Writing – original draft, Writing – review & editing. ZM: Writing – original draft, Writing – review & editing. XM: Investigation, Supervision, Writing – review & editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. Affiliated Hospital of Hebei University In-hospital Research Fund (2025Q17).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Summary
Keywords
bradyarrhythmia, cardiac amyloidosis, diastolic heart failure, electromechanical dissociation, syncope
Citation
Jia H, Jia S, Zhang W, Ma Z and Meng X (2026) Bilateral atrial appendage thrombosis in light chain cardiac amyloidosis: a case report. Front. Cardiovasc. Med. 13:1663802. doi: 10.3389/fcvm.2026.1663802
Received
10 July 2025
Revised
03 May 2026
Accepted
28 May 2026
Published
15 July 2026
Volume
13 - 2026
Edited by
Pietro Enea Lazzerini, University of Siena, Italy
Reviewed by
Kevin Shah, The University of Utah, United States
Illya Chaikovsky, National Academy of Sciences of Ukraine (NAN Ukraine), Ukraine
Updates
Copyright
© 2026 Jia, Jia, Zhang, Ma and Meng.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Haiyan Jia 706550155@qq.com Weifeng Zhang doctorweifeng@163.com
† These authors have contributed equally to this work
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.