Intracardiac Masses I-Mass Study Single Center Experience Within 12 Years


 Objective : The aim of this cross-sectional, retrospective, descriptive study was to review and classify cardiac masses systematically and to determine their frequencies.Methods : The medical records of 64,862 consecutive patients were investigated within 12 years. Every patient with a cardiac mass imaged by transthoracic echocardiography (TTE) and confirmed with an advanced imaging modality such as transesophageal echocardiography (TEE), computed tomography (CT) and / or cardiac magnetic resonance imaging (CMR) was included. Acute coronary syndromes triggering thrombus formation, vegetations, intracardiac device and catheter related thrombi were excluded.Results : Data demonstrated 127 (0.195 %) intracardiac masses consisting of 33 (0.050 %) primary benign, 3 (0.004 %) primary malignant, 20 (0.030 %) secondary tumors, 3 (0.004 %) hydatid cysts and 68 (0.104 %) thrombi respectively. The majority of primary cardiac tumors were benign (91.67 %), predominantly myxomas (78.79 %), and the less malignant (8.33 %). Secondary cardiac tumors were common than the primary malignant tumors (20:3), with male dominancy (55 %), lymphoma and lung cancers were the most frequent. Intracardiac thrombi was the majority of the cardiac masses, thrombi accompanying malignancies were in the first range (n=17, 25%), followed by autoimmune diseases (n=13, 19.12 %) and ischemic heart disease with low ejection fraction (n=12, 17.65 %).Conclusion: This retrospective analysis identified 127 patients with cardiac masses. The majority of benign tumors were myxoma, the most common tumors that metastasized to the heart were lymphoma and lung cancers, and the thrombi associated with malignancies and autoimmune diseases were the most frequent.


Introduction
Cardiac masses include primary and secondary tumors, cysts, thrombi, and vegetations. The studies published to date include either autopsy data 1 , clinical features and treatment options in speci c groups of cardiac masses 2-6 , imaging modalities 5,[7][8][9] , or global reviews [10][11][12][13][14][15] and case reports. The incidence rates of cardiac masses differ between studies and autopsy series. No study addressing cardiac masses of the heart cavity collectively including tumors, cysts and thrombi has yet been reported. The aim of this cross-sectional, retrospective, descriptive study was to determine the frequencies of intracardiac masses consisting of primary and secondary tumors, cysts and thrombi in hospitalized and out-patients referred to the echocardiography laboratory within twelve years.

Methods
To identify patients with cardiac masses, we retrospectively reviewed the medical records of 64,862 patients referred to the echocardiography laboratory between 2006 -2017. Every patient with a suspected cardiac mass imaged by two and/or three dimensional (2D -3D) transthoracic echocardiography (TTE) and con rmed with an advanced imaging modality such as transesophageal echocardiography (TEE), computed tomography (CT) and / or cardiac magnetic resonance imaging (CMR) was included. Patients with a history of acute myocardial infarction within six months and left ventricular apical thrombus, left atrial appendage thrombus revealed by TEE before cardioversion for atrial brillation, cardiac masses associated with mechanical or bio-prosthetic valves, vegetations of proven infective endocarditis and intracardiac device and / or catheter / lead induced thrombi were excluded, de-novo thrombi were evaluated.
Data collection and evaluation was started at the beginning of 2018, and completed by the end of 2019.
Echocardiographic examinations were performed using Vivid 7 Dimension (GE Vingmed Ultrasound AS, Horten, Norway) and iE33 xMatrix -DS ultrasound imaging system (Philips Ultrasound, Bothell, WA). The rst step examination for all patients with a de nite mass in the heart, including the aortic and pulmonary roots was 2D and/or 3D TTE and TEE with standard views performed according to the guidelines 16, 17 . The anatomical localization of the mass, mobility, echogenicity, tissue properties, pedicle, if present, relation to adjacent cardiac structures, invasions and extensions, effects on blood ow and valve functions were examined and recorded and the patient was referred to CT and / or CMR before the appropriate treatment decision.

Contrast-enhanced CT was performed with a 4-MDCT scanner (Somatom Sensation 4, Siemens Medical
Solutions) and a helical CT scanner (Somatom Plus-S, Siemens Medical Solutions) to investigate the size, location, morphology and tissue characteristics. For right atrial (RA) and right ventricular (RV) masses, intravenous contrast injection was performed to obtain optimal images and low-dose noncontrast and delayed CT imaging was performed in distinguishing intracardiac thrombus from tumor.
CMR was performed with a 1.5T system (Symphony, Siemens Medical Solutions, Erlangen, Germany) with ECG triggering, tissue characterization with T1-and T2-weighted images. Cine images, T1-and T2weighted turbo spin echo, rst-pass perfusion were used in patients referred to CMR with a diagnosis of a cardiac mass and TI scout sequences mainly for the diagnosis of tumors.
The researchers were allowed to obtain data from the general archives of the imaging devices and the electronic archives of the hospital with the authority granted by the institution. Patients and/or public were not involved in the design. The study was approved by Istanbul Faculty of Medicine Ethics Committee (75486), and conforms the principles outlined in the Declaration of Helsinki.  One lipoma and one broma were also incidentally observed.  Figure 1).  Figure 2). The rhabdomysarcoma was a poly-lobulated, mobile mass originating from the posterior wall of the LV myocardium, completely lling the LV cavity and prolapsing into the LV out ow tract towards the aortic lumen, also in ltrating the right ventricle (RV) ( Fig.  2A-D), with desmin-positive histology (Fig. 2E, F). Both angiosarcomas were huge masses originating from right atrioventricular groove in ltrating RA wall and cavity and RV lateral wall and pericardium ( Fig.  2G-I), con rmed by histology (Fig. 2J), accompanied by pericardial effusion.

Secondary malignant cardiac tumors
These patients were histologically proven primary noncardiac cancers referred for echocardiographic examination of cardiac functions before initiation of chemotheraphy while they were on follow up in other clinics. In most of the patients, echocardiographic examinations were suboptimal due to deteriorated general condition. Because of limited body motion and di culty to achieve standard echocardiographic imaging planes, CMR and / or CT were predominantly used for diagnosis.  Table 4, Figure 4). Two of three cases were published before 19,20 .  Table 5).
The thrombi developed in patients with cardiac diseases were mainly located in the left heart chambers; those with systolic dysfunction in the LV (n=16), hypertension and valvular heart disease accompanied by atrial brillation in the LA (n=8). All of the patients received anticoagulant treatment, ve patients were operated on.
Intracardiac thrombi of the patients associated with malignancies (n= 17) were predominantly located in the RA (n=11), RV was the secondary heart chamber (n=3). Malignancies accompanied by thrombi were; lung cancer (n=4) (Fig. 5 A, LA and 1 RV large thrombi, three of whom were operated. Two patients with deep vein thrombosis, due to trauma and tibia fracture in one and diabetic foot ulcer in the other had RV thrombi followed by pulmonary embolism, were treated medically, details can be viewed from Supplementary Primary tumors of the heart are rare, based upon the data of autopsy series, the frequency of primary cardiac tumors ranges from 0.001 % to 0.03 %, 10 % malignant, 90 % benign 1, 3, 12, 15 . The majority of benign tumors are myxomas followed by papillary broelastomas, and very rare broma and lipoma 15 .
In a report of 323 operated consecutive patients of primary cardiac tumors, 94 % were benign and 50 % were myxomas 12 . Primary malignant cardiac tumors are predominantly sarcomas; angiosarcoma and undifferentiated sarcomas are the most prevalent 4 . Although our series consisted of patients referred to the echocardiography laboratory in a university hospital, the frequencies of the primary benign and malignant tumors is in consistent with autopsy and surgery based data and literature.
Speci c cardiac tumors have a predilection for certain locations, 75-85 % of myxomas arise in the LA, 15-20 % from the right atrial septum, usually solitary, with a pedicle attached to the atrial septum at the border of the fossa ovalis membrane, and the remainder from a variety of sites 10,12,14 . A retrospective analysis of 194 myxomas operated within fty years have experienced that, the LA was the most common location and atria were signi cantly more involved than the ventricles 6 . In our series, in accordance with these previous statements, majority of the myxomas were located in the LA, less in the RA, most of them originating from fossa ovalis with a pedicle, and few sessile masses. Myxomas with atypical locations are rare in the literature 22 .
Papillary broelastomas are small benign endocardial papillomas, the second most common primary benign cardiac tumors that invariably develop on aortic and mitral valves, left ventricular endocardium and tricuspid valves, but may arise anywhere in the heart 12,14 . An analysis of 725 histopathologically con rmed papillary broelastomas have demonstrated that, 77 % of them originate on the valves, 23 % in the endocardial nonvalvular surface 2 . In the present study, broelastomas were located at the mitral lea ets and tricuspid valve chorda, incidentally no broelastomas in the aortic valve. The lipoma and broma of the heart are rare tumors, lipoma with a predilection for the epicardium or endocardium, broma invariably located in the ventricles 12,14 . In our series, the single lipoma was imaged at the LV posterior wall originating from the epicardium and broma at the ventricular basis of posterior mitral lea et, a rather atypical location.
Angiosarcomas account for approximately 37 -40 % of cardiac sarcomas and typically present in the right atrioventricular groove, with frequent involvement of the pericardium and RA wall, with short survival 23 . Rhabdomyosarcomas derived from striated muscle are distinctly rare, accounting for 0 % to 5 % of primary cardiac sarcomas and most cases appear in children with poor survival 23 . The two angiosarcoma and one rhabdomyosarcoma in our series were in full agreement with the literature in terms of frequency, localization, tumor characteristics and surveillance.
Although primary cardiac tumors are rare, the frequency of secondary metastatic tumors to the heart in autopsy studies is between 0.7 % -3.5 %, up to 9.1 % in patients with known malignancies 13,24,25 . Tumors can reach the heart via 4 pathways: hematogenous or lymphatic spread, transvenous or direct extension 13 . Spread by the hematogenous route generally gives rise to myocardial or endocardial metastases and is common with melanoma, lymphoma, and sarcoma, whereas spread by the lymphatic route will often result in pericardial and epicardial tumor involvement, as with many epithelial tumors such as lung and breast 13 . Certain tumors can extend into the inferior vena cava and grow into the RA via transvenous extension 13 . In the present study, cardiac metastases were diagnosed in 20 patients, when evaluated in terms of frequency; lymphoma, lung cancer and sarcoma were the majority of the secondary metastatic tumors, followed by breast cancer. Lymphoma metastases were remarkably in the LV suggesting hematogenous spread, whereas lung cancer metastases predominantly in RA suggesting transvenous extension, in fact, secondary cardiac tumors were mostly observed in the atria, most of them in the RA which supports the transvenous extension.
Cardiac echinococcosis is an uncommon disease, with an estimated prevalence ranging from 0.5 % to 2 % 26 . In published series, involvement of all sites of cardiac structures have been reported 19,27,28,29 .
Three intracardiac cysts in this study were hydatid cysts with myocardial involvement, which revealed the fact of our endemic character, incidentally no other cysts were encountered.
Thrombi are the most common intracardiac masses, located within the atria, and/or both ventricle cavities with an underlying cardiac disease or hypercoagulable state. Left ventricular thrombi usually occur in the setting of systolic dysfunction, with or without aneurysm formation in ischemic heart disease and dilated cardiomyopathy 15 . Thrombi in the absence of underlying cardiac disease are much less common 15 . Conditions such as acute coronary syndrome within 6 months, newly diagnosed atrial brillation, patients with prosthetic valves where thrombus formation is expected and device and catheter induced thrombi were excluded in our series. De-novo intracardiac thrombus was identi ed in 68 patients and the majority of intracardiac thrombi were associated with malignancies, followed by autoimmune diseases, ischemic heart disease with systolic dysfunction and low ejection fraction, hypertension associated with atrial brillation and valvular heart disease. It should be noted here that, the most frequent cause of cardiac thrombus in patients with autoimmune diseases was Behcet's disease which has a peculiar geographical distribution in our country. The majority of thrombi were in the RA and LV and the less in the LA. The RA thrombi predominantly were associated with malignancy and autoimmune diseases, whereas LV thrombi were detected in patients with LV systolic dysfunction and, LA with valvular heart disease, hypertension and atrial brillation.

Conclusion
Although cardiac masses are rare entities, they are being increasingly recognized in the current era by means of advanced imaging modalities. In the current analysis, we classi ed and presented various categories of cardiac masses systematically in relation to concomitant disease, symptoms and their locations in the heart chambers. The majority of benign tumors were myxoma, the most common secondary malignant tumors that metastasized to the heart were lymphoma and lung cancers, and the thrombi associated with malignancies and autoimmune diseases were the most frequent. This descriptive analysis may, therefore, contribute to appropriate diagnosis of patients with cardiac mass, which principally rely on correct recognition of the masses made generally based on their localizations and imaging characteristics.