1. Abstract Cardiac angiosarcomas are uncommon, primary malignant cardiac tumors, characterized by an aggressive local growth within the myocardial structures. The majority occur in the right atrium, and at the moment of diagnosis usually infiltrate into neighboring structures. Due to the lack of typical features in clinical presentation, the diagnosis of cardiac angiosarcoma is challenging. Initial clinical workup includes different imaging modalities [transthoracic (TTE) and transesophageal echocardiography (TEE), computed tomography (CT), cardiac magnetic resonance and/or positron emission tomography], but definite diagnosis can be made only with an endomyocardial biopsy (EMB), which is performed infrequently. Broad histological and immunohistochemical stainings of obtained tissue samples allow for precise tumor identification resulting in better risk stratification and targeted treatment options. However, there is still little experience with invasive in-vivo diagnosis of intracardiac masses.
Keywords: Cardiac tumor; Cardio-oncology; Heart failure; Histopathology
2. Introduction Primary malignant cardiac tumors are extremely uncommon (< 0.3% of cardiac tumors in postmortem studies) and are associated with poor prognosis [1, 2]. To increase the survival rate, an early and effective diagnostic process is necessary. Although noninvasive imaging modalities are useful, a definite diagnosis in the majority of cases requires histologic examination, which remains a gold standard. We report a patient with new-onset heart failure (HF), in which a 3D transesophageal echocardiography (TEE) - guided endomyocardial biopsy (EMB) confirmed the diagnosis of cardiac angiosarcoma within a few days. We present the following case in accordance with the CARE reporting checklist.
3. Case Presentation A 73-year-old female with arterial hypertension and no other relevant past medical history was admitted to hospital due to signs of HF de novo. On admission she presented shortness of breath upon exertion [New York Heart Association Class (NYHA) II]. The patient reported a 10 kg body weight loss within the previous month. She denied chest pain, palpitations or other relevant symptoms. On physical examination, her vital signs were as follows: hemoglobin saturation, 94% (Fraction of Inspired Oxygen (FiO2) 0.21); heart rate, 90 beats/min; blood pressure, 95/78 mmHg; and no fever. Systolic-diastolic murmur on cardiac auscultation; general peripheral oedema; signs of bilateral pleural effusion and liver enlargement were present. Laboratory studies showed the following abnormalities suggesting acute kidney injury and decompensation of HF: serum creatinine, 1.94 mg/dl; estimated glomerular filtration rate (eGFR), 25 ml/min/1,73 m2; urea, 110 mg/dl; N-terminal pro-brain natriuretic peptide, 2392 pg/ml (N: < 125 pg/ml); D-dimer, 7973 ng/ml (N < 500 ng/ml). The cancer biomarker was elevated: Ca 125, 290 U/ml (N: < 35 U/ml). A chest X-Ray showed fluid in both pleural cavities without signs of congestions. A standard 12-lead electrocardiogram showed a normal sinus rhythm and inverted T waves in leads I, II, aVL. A transthoracic echocardiography (TTE) revealed a large mass (90 x 73 mm) with heterogeneous echogenicity almost completely filling the cavity of the right atrium, infiltrating its wall and the visceral pericardium of the right ventricle and the apex of the heart (Figure 1 and 2). The presence of this large mass in the right atrium resulted in severe obstruction of the inflow from both venae cavae with a mean gradient difference of 7 mmHg (Figure 3). Additionally, a moderate amount of fluid around the heart with no compression upon cardiac walls (Figure 1) and fluid in the pleural cavities were observed. A TEE confirmed a large polycyclic tumor (80 x 66 mm) with heterogeneous echogenicity, attached to the wall of the right atrium and infiltrating the right atrium wall, superior vena cava and visceral pericardium. The tumor occupied the entire right atrium causing functional tricuspid stenosis, but without invading the tricuspid valve and inferior vena cava (Figure 4). Chest, abdomen, and pelvis contrast-enhanced computed tomography revealed a large polycyclic tumor (88 x 67 x 74 mm) with heterogeneous densities (moderately enhanced by contrast, most likely containing necrotic areas) covering most of the right atrium, the adjacent part of the pericardium and extending into the orifice of the superior vena cava; pericardial effusion; bilateral pleural effusions and osteolytic metastatic changes in the vertebral bodies of the spine without other primary tumors.
4. Discussion Cardiac angiosarcomas are characterized by aggressive growth and early metastases. The diagnostic and therapeutic approach is very demanding because of the intracardiac localization of the tumor. Clinical presentation of cardiac angiosarcomas depends on their size, location, status of local infiltration and/or distant metastases, relation with other cardiac structures and potential signs of hemodynamic compromise. In the majority of cases, angiosarcomas are diagnosed when the disease is already advanced with evidence of metastases, and often with atypical signs of HF [3]. Therefore, an early diagnosis of angiosarcoma is crucial for therapeutic options and the patient’s prognosis. Comprehensive clinical and multimodality imaging (TTE and TEE, including 3D, contrast or intracardiac echocardiographic imaging; cardiac magnetic resonance (CMR); positron emission tomography (PET)) evaluation of cardiac tumors is fundamental to obtain a proper initial differential diagnosis [4,5,6,7]. In our case, an initial diagnosis of a malignant cardiac tumor was made by use of echocardiography, both TTE and TEE, followed by contrast-enhanced computed tomography, which revealed a huge, dense mass with areas of necrosis in the right atrium. Angiosarcomas are mostly immobile and broadbased with endocardial to myocardial growth [1]. CMR could be useful but in our patient a CMR was not performed because of kidney insufficiency. CMR findings in angiosarcomas include heterogeneous T1 and T2-weighted signal intensity and a heterogeneous contrast enhancement pattern [1]. A PET scan with the use of 18F-2-fluoro-2-deoxy-D-glucose (FDG) can reveal areas of high FDG uptake within the mass and evidence of metastatic disease [8,9]. Histopathology is necessary to reach the final diagnosis and plan subsequent clinical management in some types of cardiac masses [10]. The histopathological features of angiosarcomas are: a highly vascularized mass with myocardial infiltration and signs of pleomorphism, necrosis and mitosis, clearly indicating diagnosis [1]. EMB is still the only method allowing for a definite diagnosis, but it is not commonly performed, despite a very low complication rate (< 1%) [11,12,13]. EMB using broad histologic and immunohistochemical methods allows for the definition of the type of tumor, management of the treatment methods and better risk stratification. Echocardiography-, electroanatomic mapping- or in the future CMR-guided EMB, increases the accuracy and safety of the procedure [14]. Many echocardiographic modalities can be helpful during EBM, including intracardiac visualization [15,16]. In our case, TEE guidance allowed direct visualization of the tumor and bioptome position on its surface. We proved that biopsy forceps, when guided by TEE, are feasible for diagnosis of intracardiac tumors.
5. Ethical Statement The authors are accountable for all aspects of the work and ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was not obtained from the patient. Presented data do not allow for the subject to be identified.
References 1. Bussani R, Castrichini M, Restivo L, et al. Cardiac Tumors: Diagnosis, Prognosis, and Treatment. Curr Cardiol Rep. 2020; 22: 169.
2. Sultan I, Bianco V, Habertheuer A, Kilic A, Gleason TG, Michel EA, et al. Long-Term Outcomes of Primary Cardiac Malignancies: Multi-Institutional Results From the National Cancer Database. J Am Coll Cardiol. 2020; 75: 2338-2347.
3. Kupsky DF, Newman DB, Kumar G, Maleszewski JJ, Edwards WD, Klarich KW. Echocardiographic features of cardiac angiosarcomas: the Mayo Clinic experience (1976–2013). Echocardiography. 2016; 33: 186-92.
4. Donisan T, Balanescu DV, Lopez-Mattei JC, et al. In Search of a Less Invasive Approach to Cardiac Tumor Diagnosis: Multimodality Imaging Assessment and Biopsy. JACC Cardiovasc Imaging. 2018; 11: 1191-1195.
5. Buckley O, Madan R, Kwong R, et al. Cardiac Masses, Part 1: Imaging Strategies and Technical Considerations. American Journal of Roentgenology 2011; 197:5, W837-W841
6. Joshi M, Kumar S, Noshirwani A, Harky A. The Current Management of Cardiac Tumours: a Comprehensive Literature Review. Braz J Cardiovasc. Surg. 2020; 35: 770-780.
7. Chen Y, Li Y, Zhang N et al. Clinical and Imaging Features of Primary Cardiac Angiosarcoma. Diagnostics. 2020;10: 776; doi:10.3390/ diagnostics10100776
8. Krishnan T, Pettersson G, Mukherjee R, et al. Cardiac angiosarcoma: A diagnostic and therapeutic challenge. J Cardiol Cases. 2020; 22: 90-93.
9. Tymińska A, Ozierański K, Caforio ALP, et al. Emerging nuclear medicine modalities to improve diagnostic accuracy in myocarditis. Kardiol Pol. 2020; 78: 1297-1298.
10. Tyebally S, Chen D, Bhattacharyya Set al. Cardiac Tumors: JACC CardioOncology State-of-the-Art Review. JACC: CardioOncology. 2020; 2: 293-311
11. Caforio ALP, Pankuweit S, Arbustini E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013; 34: 2636-2648.
12. Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol 2007; 50: 1914-1931.
13. Aghdassi A, Gupta A. Endomyocardial Biopsy: Examining Indications and Trends in Use – More Native Heart Biopsies to Come? Cardiology 2019; 142: 102-104. doi: 10.1159/000494612
14. Toscano G, Gambino A, Bagozzi L, et al. Endomyocardial biopsy under echocardiographic monitoring. Multimed Man Cardiothorac Surg. 2016; 2016: mmw006.
Ewa Szczerba. Primary Cardiac Angiosarcoma Diagnosed by 3D Transesophageal Echocardiography Guided Endomyocardial Biopsy – Case Report. Annals of Clinical and Medical Case Reports 2021