© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12653
Echocardiography
Intracardiac Mass as Initial Cardiac Manifestation of Behçet’s Disease: Think before You Cut David Leibowitz, M.D.,* Maya Korem, M.D.,* Dan M. Livovsky, M.D.,* Hagit Peleg, M.D.,* Tova Chajek-Shaul, M.D.,* and Nurith Hiller, M.D.† *Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; and †Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Behçet’s disease (BD) is a chronic multisystemic inflammatory disorder. Cardiac abnormalities including intracardiac thrombi have been described in up to 16% of cases. The clinical presentation of cardiac complications in BD may include fever, dyspnea, chest pain, hemoptysis, and edema. We present 2 cases of patients who underwent surgical excision of intracardiac masses thought to be intracardiac malignancies. Further pathological and clinical evaluation established intracardiac inflammatory masses due to BD as the final diagnosis. As intracardiac masses may be the presenting manifestation of BD, it is crucial for echocardiographers to consider BD in the differential diagnosis. A careful history and physical exam looking for signs and symptoms of BD is critical before considering surgical excision of unexplained intracardiac masses. If the final diagnosis is BD anti-inflammatory therapy should be considered the basis of treatment. (Echocardiography 2014;31:E243–E246) Key words: Behçet’s disease, intracardiac thrombus, echocardiography Behçet’s disease (BD) is a chronic multisystemic inflammatory disorder. Cardiac abnormalities including intracardiac thrombi have been described in up to 16% of cases of BD with a mortality rate as high as 20%.1 The clinical manifestations of cardiac complications in BD may include fever, dyspnea, chest pain, hemoptysis, and edema and these patients are frequently referred for chest imaging as part of their initial clinical evaluation. As the following cases illustrate it is crucial for cardiac imagers to consider BD in the differential diagnosis of patients with intracardiac masses. Case 1: A 35-year-old male patient of Arab origin, presented with high fever, night sweats, headache, and oral ulcers. Blood tests were significant for an elevated erythrocyte sedimentation rate (ESR). CT angiography (CTA) (GE Lightspeed, Milwaukee, WI, USA) of the chest revealed a hypodense mass measuring 22 9 31 9 43 mm attached to the right ventricular (RV) wall (Fig. 1A and B). Echocardiography (Vivid 7, GE Healthcare, Horten, Norway) confirmed the finding of a large echogenic mass with a broad attachment to the RV free wall near the apex (Fig. 1C). RV function Address for correspondence and reprint requests: David Leibowitz, M.D., Coronary Care Unit, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240, Israel. Fax: 972-2-5817360; E-mail: [email protected]
was normal. Given the suspicion of a cardiac tumor the patient underwent surgical excision of the mass. On histopathology a large blood clot with a polymorphonuclear infiltrate involving the adjacent myocardium was revealed. The patient was empirically treated with antibiotics and warfarin. Repeat echocardiography 3 weeks later revealed recurrence of the RV mass. Antibiotics were stopped and high-dose steroids and azathioprine started for a presumptive diagnosis of BD. This treatment resulted in rapid resolution of symptoms and normalization of the ESR. Follow-up echocardiography after 3 months showed marked diminution of the RV mass (Fig. 1D). Case 2: A 9-year-old boy of Moroccan Jewish descent presented with fever of 3-week duration. His medical history was significant for a 3-year history of recurrent fever and oral ulcers. ESR and C-reactive protein were 120 mm/h and 110 mg/L, respectively. Echocardiography (Vivid 7) showed a 2 9 2 cm mass attached to the RV free wall adjacent to the subvalvular apparatus of the tricuspid valve with normal RV function (Fig. 2C). On chest CTA a 30 9 42 9 30 mm hypodense homogeneous softtissue density mass attached to the RV free wall was demonstrated (Fig. 2A and B). A cardiac tumor was suspected and the patient underwent surgical resection of the mass. Pathologic examination revealed an organizing E243
Leibowitz, et al.
Figure 1. A. Contrast-enhanced CT of the chest at the level of the heart revealing a large filling defect in the right ventricle (arrow). B. Sagittal reconstruction demonstrating the filling defect in the right ventricle (arrow). C. Transthoracic echocardiography in magnified four-chamber view demonstrating an echo density attached to the RV free wall near the apex (arrow). D. Followup apical four-chamber view showing minimal residual mass in the RV (arrow). RV = right ventricle.
mural thrombus with mixed inflammatory infiltrate consisting of lymphocytes, histiocytes, plasma cells, neutrophils, and eosinophils. During hospitalization the patient had recurrent episodes of superficial thrombophlebitis and the diagnosis of BD was considered. Treatment with high-dose steroids was started, with marked symptomatic improvement and reduction in ESR. Follow-up echocardiography 1 month after discharge demonstrated resolution of the RV mass (Fig. 2D). Discussion: The differential diagnosis of intracardiac masses is broad and includes benign and malignant primary cardiac tumors, metastatic tumors, thrombus, vegetations, iatrogenic material, and normal variants. The diagnosis of an inflammatory mass E244
related to BD should be considered as well prior to referral for invasive procedures. BD is a multisystem disorder affecting subjects from the Mediterranean, Middle East, and Far East regions. It classically presents with recurrent oral and genital ulcerations as well as ocular and skin lesions but may present with systemic pathology. While BD has a genetic component, the exact pathophysiology remains unclear. Neither of our patients had a family history consistent with BD. There have been multiple reports in the medical literature of intracardiac masses in patients with BD.2 While in most previous reports the thrombi involved the right side of the heart, left ventricular, and left atrial involvement have been described as well.3,4 The presence of RV thrombus is frequently associated with inflammatory involvement and aneurysmatic dilatation of
Intracardiac Mass in Behcet’s Disease
Figure 2. A. Contrast-enhanced CT of the chest in axial plan showing a large hypodense filling defect in the right ventricle (arrow). B. Sagittal CT image demonstrating the same findings (arrow). C. Transthoracic echocardiography in parasternal longaxis view demonstrating an echo density in the RV attached to the chordae of the tricuspid valve (arrow). D. Repeat echo in apical four-chamber view showing resolution of the RV mass. RV = right ventricle.
the pulmonary vessels.5 The high incidence of pulmonary thrombosis associated with cardiac thrombi in BD presumably represents in situ thrombosis secondary to pulmonary vasculitis, reflecting systemic involvement of the inflammatory process. Pathologic studies of underlying myocardium in patients undergoing surgical resection of intracardiac thrombi have shown variable results with some reports showing normal myocardium, others with inflammatory infiltrate and others with endomyocardial fibrosis.6 Appropriate therapy for intracardiac thrombi in BD has not been adequately defined. One of our 2 patients who underwent surgical excision had immediate recurrence of the intracardiac mass implying that surgery should be avoided in these patients. Several previous reports have doc-
umented resolution of these thrombi with immunosuppressive therapy alone or in combination with anticoagulation and pulmonary or systemic emboli appear to be rare.7,8 In most cases, antiinflammatory treatment appears to be sufficient particularly given the risks of anticoagulation in those patients, many of whom suffer from pulmonary artery aneurysms. Permanent anticoagulation in this condition is not supported by the available literature. Given its accessibility and ease of imaging echocardiography has been the traditional modality utilized in the evaluation of intracardiac masses. Features of the findings such as location, mobility, and homogeneity can help in the differential diagnosis. Real time three-dimensional echo may offer incremental value as well9 E245
Leibowitz, et al.
Cardiac CT and MRI are being increasingly utilized in this clinical setting given their high contrast resolution, multiplanar capability, and imaging of noncardiac structures (Figs. 1A and B, 2A and B). Tissue characterization particularly by MRI may also help clarify the diagnosis.10 PET-CT may be used as well when malignancy is suspected. An integrated multimodality approach together with the clinical scenario can lead to the diagnosis of BD. In summary, intracardiac thrombi may be the presenting manifestation of BD which should always be considered in the differential diagnosis of unexplained intracardiac masses. A careful medical history and physical exam looking for signs and symptoms of BD is critical before considering surgical excision and is routinely performed in our hospital in young patients with unexplained intracardiac masses. If the final diagnosis is BD anti-inflammatory therapy should be considered the basis of treatment. References 1. Wechsler B, Du LT, Kieffer E: Cardiovascular manifestations of Behcet’s disease. Ann Med Interne 1999;150:542–554.
E246
2. Mogulkoc N, Burgess MI, Bishop PW: Intracardiac thrombus in Behcet’s disease: A systematic review. Chest 2000;118:479–487. 3. Madanat WY, Prokaeva TB, Kotelnikova GP, et al: Endocarditis with left atrial thrombus formation in Behcet’s disease mimicking myxoma. J Rheumatol 1993;20:1982– 1984. 4. Vanhaleweyk G, El-Ramahi KM, Hazmi M, et al: Right atrial, right ventricular and left ventricular thrombi in Behcet’s disease. Eur Heart J 1990;11:957–959. 5. El-Ramahi KM, Fawzy ME, Sieck JO, et al: Cardiac and pulmonary involvement in Behcet’s disease. Scand J Rheumatol 1991;20:373–376. 6. Matsumoto T, Uekusa T, Fukuda Y: Vasculo-Behcet’s disease: A pathologic study of eight cases. Hum Pathol 1991;22:45–51. 7. Dogan SM, Birdane A, Korkmaz C, et al: Right ventricular thrombus with Behcßet’s syndrome: Successful treatment with warfarin and immunosuppressive agents. Tex Heart Inst J 2007;34:360–362. 8. Le Thi Huong D, Dolmazon C, De Zuttere D, et al: Complete recovery of right intraventricular thrombus and pulmonary arteritis in Behcet’s disease. Br J Rheumatol 1997;36:130–132. 9. Zaragossa-Macias E, Chen MA, Gill EA: Real time threedimensional echocardiography evaluation of intracardiac masses. Echocardiography 2012;29:207–219. 10. Motwani M, Kidambi A, Herzog BA, et al: MR imaging of tumors and masses. Radiology 2013;268:26–42.
Echocardiography
Intracardiac Mass as Initial Cardiac Manifestation of Behçet’s Disease: Think before You Cut David Leibowitz, M.D.,* Maya Korem, M.D.,* Dan M. Livovsky, M.D.,* Hagit Peleg, M.D.,* Tova Chajek-Shaul, M.D.,* and Nurith Hiller, M.D.† *Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; and †Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Behçet’s disease (BD) is a chronic multisystemic inflammatory disorder. Cardiac abnormalities including intracardiac thrombi have been described in up to 16% of cases. The clinical presentation of cardiac complications in BD may include fever, dyspnea, chest pain, hemoptysis, and edema. We present 2 cases of patients who underwent surgical excision of intracardiac masses thought to be intracardiac malignancies. Further pathological and clinical evaluation established intracardiac inflammatory masses due to BD as the final diagnosis. As intracardiac masses may be the presenting manifestation of BD, it is crucial for echocardiographers to consider BD in the differential diagnosis. A careful history and physical exam looking for signs and symptoms of BD is critical before considering surgical excision of unexplained intracardiac masses. If the final diagnosis is BD anti-inflammatory therapy should be considered the basis of treatment. (Echocardiography 2014;31:E243–E246) Key words: Behçet’s disease, intracardiac thrombus, echocardiography Behçet’s disease (BD) is a chronic multisystemic inflammatory disorder. Cardiac abnormalities including intracardiac thrombi have been described in up to 16% of cases of BD with a mortality rate as high as 20%.1 The clinical manifestations of cardiac complications in BD may include fever, dyspnea, chest pain, hemoptysis, and edema and these patients are frequently referred for chest imaging as part of their initial clinical evaluation. As the following cases illustrate it is crucial for cardiac imagers to consider BD in the differential diagnosis of patients with intracardiac masses. Case 1: A 35-year-old male patient of Arab origin, presented with high fever, night sweats, headache, and oral ulcers. Blood tests were significant for an elevated erythrocyte sedimentation rate (ESR). CT angiography (CTA) (GE Lightspeed, Milwaukee, WI, USA) of the chest revealed a hypodense mass measuring 22 9 31 9 43 mm attached to the right ventricular (RV) wall (Fig. 1A and B). Echocardiography (Vivid 7, GE Healthcare, Horten, Norway) confirmed the finding of a large echogenic mass with a broad attachment to the RV free wall near the apex (Fig. 1C). RV function Address for correspondence and reprint requests: David Leibowitz, M.D., Coronary Care Unit, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240, Israel. Fax: 972-2-5817360; E-mail: [email protected]
was normal. Given the suspicion of a cardiac tumor the patient underwent surgical excision of the mass. On histopathology a large blood clot with a polymorphonuclear infiltrate involving the adjacent myocardium was revealed. The patient was empirically treated with antibiotics and warfarin. Repeat echocardiography 3 weeks later revealed recurrence of the RV mass. Antibiotics were stopped and high-dose steroids and azathioprine started for a presumptive diagnosis of BD. This treatment resulted in rapid resolution of symptoms and normalization of the ESR. Follow-up echocardiography after 3 months showed marked diminution of the RV mass (Fig. 1D). Case 2: A 9-year-old boy of Moroccan Jewish descent presented with fever of 3-week duration. His medical history was significant for a 3-year history of recurrent fever and oral ulcers. ESR and C-reactive protein were 120 mm/h and 110 mg/L, respectively. Echocardiography (Vivid 7) showed a 2 9 2 cm mass attached to the RV free wall adjacent to the subvalvular apparatus of the tricuspid valve with normal RV function (Fig. 2C). On chest CTA a 30 9 42 9 30 mm hypodense homogeneous softtissue density mass attached to the RV free wall was demonstrated (Fig. 2A and B). A cardiac tumor was suspected and the patient underwent surgical resection of the mass. Pathologic examination revealed an organizing E243
Leibowitz, et al.
Figure 1. A. Contrast-enhanced CT of the chest at the level of the heart revealing a large filling defect in the right ventricle (arrow). B. Sagittal reconstruction demonstrating the filling defect in the right ventricle (arrow). C. Transthoracic echocardiography in magnified four-chamber view demonstrating an echo density attached to the RV free wall near the apex (arrow). D. Followup apical four-chamber view showing minimal residual mass in the RV (arrow). RV = right ventricle.
mural thrombus with mixed inflammatory infiltrate consisting of lymphocytes, histiocytes, plasma cells, neutrophils, and eosinophils. During hospitalization the patient had recurrent episodes of superficial thrombophlebitis and the diagnosis of BD was considered. Treatment with high-dose steroids was started, with marked symptomatic improvement and reduction in ESR. Follow-up echocardiography 1 month after discharge demonstrated resolution of the RV mass (Fig. 2D). Discussion: The differential diagnosis of intracardiac masses is broad and includes benign and malignant primary cardiac tumors, metastatic tumors, thrombus, vegetations, iatrogenic material, and normal variants. The diagnosis of an inflammatory mass E244
related to BD should be considered as well prior to referral for invasive procedures. BD is a multisystem disorder affecting subjects from the Mediterranean, Middle East, and Far East regions. It classically presents with recurrent oral and genital ulcerations as well as ocular and skin lesions but may present with systemic pathology. While BD has a genetic component, the exact pathophysiology remains unclear. Neither of our patients had a family history consistent with BD. There have been multiple reports in the medical literature of intracardiac masses in patients with BD.2 While in most previous reports the thrombi involved the right side of the heart, left ventricular, and left atrial involvement have been described as well.3,4 The presence of RV thrombus is frequently associated with inflammatory involvement and aneurysmatic dilatation of
Intracardiac Mass in Behcet’s Disease
Figure 2. A. Contrast-enhanced CT of the chest in axial plan showing a large hypodense filling defect in the right ventricle (arrow). B. Sagittal CT image demonstrating the same findings (arrow). C. Transthoracic echocardiography in parasternal longaxis view demonstrating an echo density in the RV attached to the chordae of the tricuspid valve (arrow). D. Repeat echo in apical four-chamber view showing resolution of the RV mass. RV = right ventricle.
the pulmonary vessels.5 The high incidence of pulmonary thrombosis associated with cardiac thrombi in BD presumably represents in situ thrombosis secondary to pulmonary vasculitis, reflecting systemic involvement of the inflammatory process. Pathologic studies of underlying myocardium in patients undergoing surgical resection of intracardiac thrombi have shown variable results with some reports showing normal myocardium, others with inflammatory infiltrate and others with endomyocardial fibrosis.6 Appropriate therapy for intracardiac thrombi in BD has not been adequately defined. One of our 2 patients who underwent surgical excision had immediate recurrence of the intracardiac mass implying that surgery should be avoided in these patients. Several previous reports have doc-
umented resolution of these thrombi with immunosuppressive therapy alone or in combination with anticoagulation and pulmonary or systemic emboli appear to be rare.7,8 In most cases, antiinflammatory treatment appears to be sufficient particularly given the risks of anticoagulation in those patients, many of whom suffer from pulmonary artery aneurysms. Permanent anticoagulation in this condition is not supported by the available literature. Given its accessibility and ease of imaging echocardiography has been the traditional modality utilized in the evaluation of intracardiac masses. Features of the findings such as location, mobility, and homogeneity can help in the differential diagnosis. Real time three-dimensional echo may offer incremental value as well9 E245
Leibowitz, et al.
Cardiac CT and MRI are being increasingly utilized in this clinical setting given their high contrast resolution, multiplanar capability, and imaging of noncardiac structures (Figs. 1A and B, 2A and B). Tissue characterization particularly by MRI may also help clarify the diagnosis.10 PET-CT may be used as well when malignancy is suspected. An integrated multimodality approach together with the clinical scenario can lead to the diagnosis of BD. In summary, intracardiac thrombi may be the presenting manifestation of BD which should always be considered in the differential diagnosis of unexplained intracardiac masses. A careful medical history and physical exam looking for signs and symptoms of BD is critical before considering surgical excision and is routinely performed in our hospital in young patients with unexplained intracardiac masses. If the final diagnosis is BD anti-inflammatory therapy should be considered the basis of treatment. References 1. Wechsler B, Du LT, Kieffer E: Cardiovascular manifestations of Behcet’s disease. Ann Med Interne 1999;150:542–554.
E246
2. Mogulkoc N, Burgess MI, Bishop PW: Intracardiac thrombus in Behcet’s disease: A systematic review. Chest 2000;118:479–487. 3. Madanat WY, Prokaeva TB, Kotelnikova GP, et al: Endocarditis with left atrial thrombus formation in Behcet’s disease mimicking myxoma. J Rheumatol 1993;20:1982– 1984. 4. Vanhaleweyk G, El-Ramahi KM, Hazmi M, et al: Right atrial, right ventricular and left ventricular thrombi in Behcet’s disease. Eur Heart J 1990;11:957–959. 5. El-Ramahi KM, Fawzy ME, Sieck JO, et al: Cardiac and pulmonary involvement in Behcet’s disease. Scand J Rheumatol 1991;20:373–376. 6. Matsumoto T, Uekusa T, Fukuda Y: Vasculo-Behcet’s disease: A pathologic study of eight cases. Hum Pathol 1991;22:45–51. 7. Dogan SM, Birdane A, Korkmaz C, et al: Right ventricular thrombus with Behcßet’s syndrome: Successful treatment with warfarin and immunosuppressive agents. Tex Heart Inst J 2007;34:360–362. 8. Le Thi Huong D, Dolmazon C, De Zuttere D, et al: Complete recovery of right intraventricular thrombus and pulmonary arteritis in Behcet’s disease. Br J Rheumatol 1997;36:130–132. 9. Zaragossa-Macias E, Chen MA, Gill EA: Real time threedimensional echocardiography evaluation of intracardiac masses. Echocardiography 2012;29:207–219. 10. Motwani M, Kidambi A, Herzog BA, et al: MR imaging of tumors and masses. Radiology 2013;268:26–42.
