Abstract
Background
While rare, primary cardiac tumors, especially angiosarcomas, have a high mortality rate and are difficult to diagnose due to vague symptoms and limited visibility on transthoracic echocardiogram.
Case Summary
A 47-year-old patient was treated for acute pericarditis with transient resolution of a pericardial effusion but persistent dyspnea, chest pain, fatigue, and elevated inflammatory markers. Six months after the initial presentation, they developed tamponade, had hemorrhagic shock, and passed away due to right atrial rupture from an infiltrative tumor. Pathology demonstrated primary cardiac angiosarcoma.
Discussion
This case illustrates the diagnostic challenges and consequences of a cardiac tumor which was not apparent on serial echocardiograms.
Take-Home Messages
Primary cardiac malignancy should be considered in the setting of recurrent pericardial effusion with systemic symptoms and persistently elevated inflammatory markers. Echocardiogram has shown low sensitivity for cardiac tumors in the setting of effusion; advanced imaging modalities can facilitate early detection and intervention.
Key words: cardiac neoplasm, cardiac tamponade, cardiac tumor, pericardial effusion, pericarditis, primary cardiac angiosarcoma
Visual Summary
History of Presentation
A 47-year-old nonbinary patient assigned female at birth presented to our medical center in October 2024 with progressive dyspnea, orthopnea, and lower-extremity edema.
Six months prior (May 2024), the patient had been diagnosed with sepsis and acute pericarditis after presenting with presyncope, chest pain, nausea, and hypotension to 80 mm Hg systolic with sinus tachycardia to 120 beats/min. Labs revealed leukocytosis (white blood cell count [WBC] 17 × 103/μL; range 3.8-11.8), elevated lactic acid (3.2 mmol/L; range 0.5-1.9), and elevated C-reactive protein (CRP 1.8 mg/dL; range 0.0-1.0). High-sensitivity troponin was 8 ng/L and 10 ng/L on repeat (range <5). B-type natriuretic peptide was 39 pg/mL (range <100). A transthoracic echocardiogram (TTE) showed a moderate circumferential pericardial effusion measuring 1.25 cm (Figure 1A), and computed tomography (CT) chest angiography showed diffuse pulmonary nodules (Figure 1B). The patient was treated with intravenous antibiotics and colchicine.
Figure 1.
Initial Imaging at Presentation Showing Pericardial Effusion and Pulmonary Nodules
(A) Transthoracic echocardiogram during the first admission in May 2024 demonstrating a moderate pericardial effusion measuring 1.25 cm in the parasternal long-axis view. (B) Computed tomography chest angiography obtained in May 2024 demonstrating diffuse scattered pulmonary nodules throughout both lungs.
The patient was managed as an outpatient with a 3-month course (June-August 2024) of colchicine with high-dose nonsteroidal anti-inflammatory drugs (Ibuprofen 600 TID × 2 weeks followed by taper of 200 mg each week until off) but reported only mild symptom improvement with treatment. While outpatient, they had serial lab testing showing mild leukocytosis (WBC 10.6 × 103/μL; range 4.2-10.0) and persistently elevated inflammatory markers including CRP (22.8 mg/dL; range <0.8) and erythrocyte sedimentation rate (63 mm/h; range <25). Testing for HIV and respiratory viruses was negative except for low-positive Coccidioides IgM. Chest CT in June also showed decreased scattered bilateral pulmonary nodules, and given this improvement and the lack of known malignancy or receipt of cancer-directed therapies, they were favored to represent a resolving infectious process by the radiologist (Figure 2A). Serial TTE in July 2024 demonstrated complete resolution of the pericardial effusion (Figure 2B). An autoimmune evaluation was unremarkable.
Figure 2.
Interval Imaging Demonstrating Resolution of Pericardial Effusion and Decrease in Pulmonary Nodules
(A) Computed tomography chest obtained during outpatient care in July 2024 showing an interval decrease in the size of previously identified scattered bilateral pulmonary nodules. (B) Transthoracic echocardiogram obtained in July 2024 demonstrating complete resolution of previously observed pericardial effusion.
Past Medical History
Attention-deficit/hyperactivity disorder, insomnia, generalized anxiety disorder, class III obesity, prediabetes, and uterine fibroids status post total hysterectomy.
Differential Diagnosis
Ongoing acute pericarditis vs recurrent pericarditis was considered along with right- and/or left-sided heart failure. The etiology of the pericarditis was unclear, and the differential included infectious, idiopathic, drug-induced, myocardial ischemia, autoimmune, and neoplastic. There was concern for cardiac tamponade.
Investigations
During the October 2024 admission, the patient was found to be tachycardic with low-voltage precordial leads on ECG. They continued to exhibit leukocytosis (WBC 11.3 × 103/μL; range 4.2-10.0) and elevated CRP (2.8 mg/dL, range <0.8). The initial high-sensitivity troponin was 9 ng/L (range <5) and was unchanged on repeat. B-type natriuretic peptide was 81 pg/mL (range <100). On examination, there was pulsus paradoxus >10 mm Hg. Chest x-ray showed markedly enlarged cardiac silhouette (Figure 3A), and TTE demonstrated a large pericardial effusion anterior to the right ventricle measuring 3 cm with fibrinous material (Figure 3B, Video 1). TTE also showed new findings suggestive of tamponade, including septal bounce, diastolic inversion of the right ventricular wall, and decreased respiratory variation of the inferior vena cava. No masses could be appreciated on TTE.
Figure 3.
Readmission Imaging Demonstrating Recurrent Pericardial Effusion With Tamponade Physiology
(A) Chest radiograph obtained during the October 2024 admission showing marked enlargement of the cardiac silhouette. (B) Transthoracic echocardiogram obtained in October 2024 showing a large pericardial effusion anterior to the right ventricle measuring approximately 3 cm with fibrinous material. Echocardiographic findings were consistent with tamponade physiology.
Management
Due to evidence of tamponade, the patient underwent urgent pericardiocentesis via the subxiphoid approach with drain placement, performed under anesthesia. Opening pressure was 40 to 50 mm Hg, and 1,500 mL of bloody fluid was removed. However, TTE showed interval enlargement of the anterior pericardial effusion to approximately 6.5 cm with signs of ongoing severe cardiac tamponade, concerning hemopericardium (Video 2).
Outcome and Follow-Up
The patient underwent emergent surgery, which revealed a large right-atrial-wall defect and tumor burden in the intrapericardial space. Surgery was complicated by hemorrhagic shock and death due to erosion of the right atrial free wall by an infiltrative mass. Postmortem pathological examination revealed angiosarcoma originating from the right atrium with invasion of the pericardium (Figure 4) and numerous metastatic nodules in the pleura and lung parenchyma bilaterally (Figure 5). A timeline of events and take-home messages are presented in visual summary.
Figure 4.
Pathologic Findings of Right Atrial Angiosarcoma
(A) Histopathologic examination of the resected tumor demonstrating a vasoformative spindle cell neoplasm infiltrating the pericardium (upper right; hematoxylin and eosin stain). (B) Immunohistochemical staining showing strong expression of the endothelial cell marker E26 transformation specific-related gene (ERG) in the neoplastic cells. (C) Gross photograph of the postmortem explanted heart demonstrating residual sarcoma in the right atrium (arrow) surrounding the atrial patch (arrowhead).
Figure 5.
Pulmonary Metastases from Cardiac Angiosarcoma
(A) Gross photographs of lung specimens obtained at postmortem examination demonstrating multiple subpleural and intraparenchymal metastatic nodules (arrowheads) involving all pulmonary lobes. (B) Histopathologic examination of subpleural pulmonary nodules showing metastatic angiosarcoma invading the pulmonary parenchyma and obliterating a large intrapulmonary vessel (hematoxylin and eosin stain).
Discussion
Primary cardiac tumors have a reported prevalence of 0.001% to 0.03%.1, 2, 3 About 25% of primary cardiac tumors are malignant, with the majority being sarcomas, including angiosarcoma and intimal sarcoma.1, 2, 3, 4 Angiosarcomas are the most common type of primary cardiac sarcoma.5 They are associated with a poor prognosis, with a median survival of 6 to 25 months, with a median survival of 7 months (interquartile range 1-19 months) and a 1-year survival rate of 40.7%.3,5 Primary cardiac angiosarcoma (PCA) occurs at a mean age of 47.2 years with equal sex distribution.3,5 Distant metastases are present in 76% at diagnosis.6 Given the paucity of data on PCA, with most literature consisting of single case reports or case series, no guidelines exist for diagnosis or management.1,3,4
This report describes a case of a 47-year-old nonbinary patient assigned female at birth who initially presented in May 2024 with severe, sudden onset of chest pain, progressive dyspnea, and presyncope and was found to have severe sepsis. On evaluation, there was a pericardial effusion without evidence of cardiac mass or tamponade. The only other findings were elevated CRP and the presence of pulmonary nodules (Figure 1B), initially presumed infectious, which regressed with antibiotic and colchicine therapy (Figure 2A). However, autopsy later revealed these nodules represented metastatic disease.
In a retrospective review of 48 patients with PCA, the most common presenting symptom was dyspnea.1,3,6 Other symptoms include chest discomfort, palpitations, cough, syncope, and pericardial effusion.1,3,4,6,7 PCA often originates in the right atrium and typically fills the right atrium before infiltrating the pericardium, tricuspid valve, right ventricle, and right coronary artery. Clinical features may mimic benign causes of pericarditis, and diagnosis is often delayed due to low suspicion of this rare tumor.2,4,7,8
Echocardiogram is the first-line imaging modality for identifying cardiac masses, and the majority are found incidentally.9 PCA may appear on echocardiogram as a lobulated, heterogenous mass with areas of hemorrhage or necrosis.9 Ultrasound-enhancing microbubble contrast agents may also be used to assess perfusion enhancement, a marker of vascularity.9 Differences in perfusion can distinguish between highly vascular, malignant tumors and benign tumors (such as myxoma).7, 8, 9
TTE is limited in obese patients and those with chronic lung disease.7 In addition, TTE may have a low sensitivity for detecting cardiac tumors in the setting of a pericardial effusion.6 In one series of 17 cases of PCA from a single center, TTE had a sensitivity of 75% and was nondiagnostic for 2 patients (17%) with cardiac tamponade.6 Our patient's body habitus, pericardial effusion, and the PCA's broad-based attachment likely contributed to the PCA's elusiveness on imaging. Although the pericardial effusion resolved transiently, the patient was persistently symptomatic. A pericardial effusion of unclear origin (especially if hemorrhagic) should be monitored until resolution to exclude rare but deadly etiologies.6 Further imaging should be considered for recurrent or persistent pericarditis associated with effusions, abnormal enhancements on contrast TTE, and in patients with inexplicable arrhythmia, persistent symptoms, and/or inflammatory markers.4,6,7,9,10 CRP typically normalizes within 1 to 2 weeks after the initiation of therapy for acute pericarditis, and persistent elevation after 1 week of therapy is associated with a higher risk of recurrence (hazard ratio 2.4).10 High CRP levels are common with malignant effusions and often treatment-resistant, meaning CRP may not normalize unless the underlying cancer is effectively treated. If CRP remains high, it may indicate persistent tumor activity, infection, or ongoing pericardial inflammation.10 This patient's persistently elevated inflammatory markers could have prompted the authors to pursue advanced imaging, but it was not considered given the patient presented with a concern for tamponade.
Transesophageal echocardiogram, cardiac magnetic resonance imaging (MRI), or positron emission tomography (PET) may be necessary to diagnose a cardiac tumor. Transesophageal echocardiogram has a sensitivity of 97% for identifying cardiac masses and can provide information on tumor location, size, and mobility.2 However, advanced imaging with MRI or PET may better characterize tissue composition.2 MRI can assess tumor morphology, structure, and invasive characteristics and thus can differentiate malignant from benign tumors. PET identifies the metabolic activity of tumors and metastases and has nearly 100% sensitivity for detecting myocardial or pericardial involvement.7 Cardiac CT may also be used to assess cardiac masses, but MRI is more sensitive.2,7,8,10
Angiosarcomas tend to have direct involvement with the pericardium, resulting in pericardial effusions. While pericardiocentesis may alleviate symptoms temporarily, cytology of the pericardial fluid is frequently unrevealing, and definitive diagnosis requires biopsy.9 In a case series of 17 patients with PCA, 29% presented with recurrent pericarditis or pericardial effusions, and 18% with cardiac tamponade.6 However, pericardial fluid cytology was negative in all 15 patients undergoing pericardiocentesis. As a result, diagnostic approaches have been proposed that allow treatment strategy to be guided by advanced cardiac imaging without the need for pericardiocentesis.7
Visual Summary.
Clinical Presentation, Diagnostic Evaluation, Imaging Findings, and Management From Initial Presentation Through Postmortem Diagnosis of Cardiac Angiosarcoma
AFAB = assigned female at birth; BNP = B-type natriuretic peptide; CRP = C-reactive protein; CT = computed tomography; ECG = electrocardiogram; ESR = erythrocyte sedimentation rate; TTE = transthoracic echocardiography.
Conclusions
Early PCA diagnosis remains limited due to its rarity, lack of specific symptoms, aggressive nature, and variable detection on first-line imaging (TTE). Multimodal cardiac imaging can aid in earlier diagnosis and management and thus facilitate better outcomes for patients with PCA.
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Take-Home Messages
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•
Cardiac malignancy should be considered in the setting of recurrent or persistent pericardial effusion and/or hemorrhagic effusion, lack of systemic symptom resolution with standard therapy, and/or persistently elevated inflammatory markers.
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•
Advanced imaging modalities such as transesophageal echocardiogram, cardiac magnetic resonance imaging, computed tomography, or positron emissions tomography can facilitate detection and intervention.
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
October 2024 Transthoracic Echocardiography (TTE) Concerning Cardiac Tamponade
October 2024 TTE demonstrated a large pericardial effusion anterior to the right ventricle measuring 3 cm with fibrinous material, with new findings suggestive of tamponade, including septal bounce, diastolic inversion of the right ventricular wall, and decreased respiratory variation of the inferior vena cava. No masses could be appreciated on TTE.
Interval Enlargement of Pericardial Effusion on Postpericardiocentesis Transthoracic Echocardiography (TTE)
Postpericardiocentesis TTE showed interval enlargement of the anterior pericardial effusion to approximately 6.5 cm with signs of ongoing severe cardiac tamponade, concerning hemopericardium.
References
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Associated Data
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Supplementary Materials
October 2024 Transthoracic Echocardiography (TTE) Concerning Cardiac Tamponade
October 2024 TTE demonstrated a large pericardial effusion anterior to the right ventricle measuring 3 cm with fibrinous material, with new findings suggestive of tamponade, including septal bounce, diastolic inversion of the right ventricular wall, and decreased respiratory variation of the inferior vena cava. No masses could be appreciated on TTE.
Interval Enlargement of Pericardial Effusion on Postpericardiocentesis Transthoracic Echocardiography (TTE)
Postpericardiocentesis TTE showed interval enlargement of the anterior pericardial effusion to approximately 6.5 cm with signs of ongoing severe cardiac tamponade, concerning hemopericardium.