SUBMITTED 27 DEC 21 1 REVISIONS REQ. 27 FEB & 22 MAY 22; REVISIONS RECD. 19 APR & 27 MAY 22 2 ACCEPTED 16 JUN 22 3 ONLINE-FIRST: AUGUST 2022 4 DOI: https://doi.org/10.18295/squmj.8.2022.051 5 6 Para-cardiac Inflammatory Mass Compressing the Heart 7 A possible association with COVID-19 8 Ahmad Mirdamadi,1 Amir M.M. Sadeghi,2 Mohsen M.M. Sadeghi,3 Majid 9 Rabani,4 *Shakiba Hassanzadeh5 10 11 1Department of Cardiology, Medical School, Islamic Azad University, Najafabad Branch, 12 Isfahan, Iran; 2Department of Cardiovascular Surgery, Isfahan University of Medical Sciences, 13 Isfahan, Iran; 3Department of Cardiac Surgery, Chamran Heart Center, Isfahan University of 14 Medical Sciences, Isfahan, Iran; 4Cardiac Ward, Khanevadeh Hospital, Isfahan, Iran; 5Division 15 of Pathology, Nickan Research Institute, Isfahan, Iran 16 *Corresponding Author’s e-mail: shak.hassanzadeh@gmail.com 17 18 Abstract 19 Infection with the SARS-CoV-2 virus causes coronavirus disease 2019 (COVID-19). COVID-19 20 usually affects the lungs but may also involve other organs such as the heart. We report a case of 21 a para-cardiac mass in a previously healthy 45-year-old man who developed persistent dyspnea 22 following SARS-CoV-2 infection. The patient underwent cardiac surgery since the mass was 23 attached to the pericardium and was causing constrictive pericarditis. The pathology report 24 indicated an inflammatory pattern for the mass. Based on our knowledge there has been no 25 previous report of developing a para-cardiac inflammatory mass after SARS-CoV-2 infection. In 26 conclusion, we would like to increase awareness regarding the possibility of developing a para-27 cardiac inflammatory mass following COVID-19. 28 Keywords: SARS-CoV-2; Pericarditis; Constrictive pericarditis; COVID-19; Cardiac tumor; 29 Mediastinal tumor 30 mailto:shak.hassanzadeh@gmail.com 31 Introduction 32 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is caused by the SARS-CoV-2 33 virus. The most common clinical manifestations of SARS-CoV-2 infection are respiratory 34 symptoms; however, this infection may also involve other organs such as the heart and kidneys.1 35 Some of the most common cardiac complications following coronavirus disease 2019 (COVID-36 19) include myocarditis, pericardial effusion and tamponade, myocardial infarction (MI), 37 arrhythmias, acute heart failure (HF) with cardiogenic shock, and pericarditis. Most of these 38 patients have shortness of breath and chest pain.1 On the other hand, primary cardiac tumors are 39 very rare and have an incidence of 0.001%–0.03% on autopsy findings and about 90% of them 40 are benign.2 In addition, 6 to 10% of primary cardiac tumors are primary pericardial masses 41 which are also usually benign. The clinical signs and symptoms of pericardial masses include 42 dyspnea, edema, pleural effusion, orthopnea, pericardial effusion, or murmur.3 We report a case 43 of a previously healthy 45-year-old male who developed persistent dyspnea and edema following 44 his recovery from SARS-CoV-2 infection. Cardiac evaluation revealed a para-cardiac mass 45 (attached to the pericardium) and constrictive pericarditis for which he underwent cardiac 46 surgery. The mass was removed and pathological evaluation reported an inflammatory mass. 47 This study follows the principles of the Declaration of Helsinki. Ethics approval from an 48 International Review Board was not applicable. Informed consent was obtained from the patient 49 for the publication of the information and images. 50 51 Case Report 52 A 45-year-old male came to our clinic complaining of persistent exertional dyspnea and edema 53 in 2021. The patient had a history of hospital admission been due to COVID-19 two months 54 earlier and his symptoms had developed following his SARS-CoV-2 infection. Based on the 55 medical records of his previous admission, the patient was a healthy and active individual with 56 no limiting conditions and there was no report of any thoracic lesions. Upon evaluation, a large 57 hypoechoic mass with a size of 9×3.1cm was observed on echocardiography, (Figure 1). The 58 report was suggestive of a possible extra pericardial inflammatory mass or a large hematoma 59 with central liquefaction over the right atrium (RA) and right ventricle (RV) that had 60 compressive effects. In addition, there was bilateral pleural effusion (PE) which was turbid with 61 possible exudative effusion. There was also a mild to moderate RV dysfunction as well as a 62 moderate left ventricular (LV) systolic dysfunction with normal LV size. LV ejection fraction 63 (LVEF) by Simpson’s mode was 45%. Based on the echocardiography result, although there was 64 no thickening or calcification of the pericardium, physiological constrictive pericarditis was 65 assumed to have occurred due to a mass. Therefore, the patient was referred to a cardiac surgeon 66 with the impression of a localized exudative para-cardiac mass or hematomata to remove the 67 mass, evaluate the pericardium, and drain the pleural effusion. A multi-slice high-resolution 68 computed tomography (HRCT) scan of the chest revealed bilateral mild pleural effusion. In 69 addition, there was patchy and ground-glass opacity in the right lower lobe (RLL) which was 70 suggestive of a sequel of his previously SARS-CoV-2 infection. Linear atelectasis was detected 71 in both the right and left upper lobes as well as the left lower lobe (LLL). The report also noted 72 minimal atelectasis with pericardial effusion (Figure 2). Evaluation with cardiac magnetic 73 resonance (CMR) confirmed the findings detected on echocardiography and CT scan. CT scan 74 and MRI images are shown in Figure 2. Consequently, based on the results of echocardiography, 75 CT scan, and CMR, a diagnosis of para-cardiac mass with compressive effects on the heart and 76 physiological constrictive pericarditis was established and the patient was scheduled for surgery. 77 Treatment with anti-inflammatory drugs (such as corticosteroids or interleukin-receptor 78 antagonist) to reduce the para-cardiac mass was not initiated before cardiac surgery. On 79 admission, his condition was good with unremarkable signs and normal physical examination. 80 The patient had no significant medical or family histories and did not use any medication. 81 Laboratory results and electrocardiography (ECG) were also normal. A summary of the patient’s 82 laboratory workup is shown in Table 1. A day after admission, the patient underwent open-heart 83 surgery with general anesthesia for two hours. Upon surgery, a median sternotomy was 84 performed and a large mass with the size of 10x4x3cm with severe adhesion to the RA and RV 85 was detected (Figure 3). Cardiopulmonary bypass (CPB) with an arterial cannula in the 86 ascending aorta was established and the venous return was achieved through the femoral vein. 87 With beating heart bypass surgery, the mass was completely excised by sharp and blunt 88 dissections. Subsequently, the patient was weaned from CPB without any difficulty. Chest 89 closure was performed with the placement of two drains (mediastinal and right pleural). There 90 were no signs of any complications during surgery. The patient was discharged from the hospital 91 four days later with stable vital signs and no evidence of post-surgical complications. The 92 macroscopic pathological evaluation of the mass revealed a 10×6×3.5cm mass with elastic 93 brown tissue and a soft cystic change at the center of the tissue. On microscopic evaluation, some 94 lesions had necrosis, neutrophilic infiltration, and foamy macrophages. In addition, some of the 95 fibrotic areas contained lymphocytic infiltration and lympho-plasma cells. However, there was 96 no evidence of malignancy or granuloma. The patient did not have any medical complaints on 97 his cardiology and cardiosurgery follow-up visits. 98 99 Informed consent was obtained from the patient for publication of this case report and any 100 accompanying images. 101 102 Discussion 103 There have been reports of cardiovascular complications and death or deterioration of pre-104 existing cardiac disorders following influenza infection.1 SARS-CoV-2 infection may also lead 105 to cardiovascular complications. Post-COVID-19 cardiac complications include myocarditis 106 (42.1%), pericardial effusion (15.8%), acute MI (15.8%), cardiac arrhythmias (10.5%), RV 107 mural thrombus with pulmonary embolism (5.3%), acute HF with cardiogenic shock (5.3%), 108 cardiac tamponade, Takotsubo cardiomyopathy, pericarditis, and myopericarditis.1 In addition, 109 the majority of symptoms of post-COVID-19 cardiac complications include shortness of breath 110 (52.6%), chest pain (36.8%), fever (26.3%), cough (26.3%), fatigue (10.5%), abnormal troponin 111 levels (68.4%), abnormal B-type natriuretic peptide (BNP) levels (42.1%), and ST-segment 112 elevation (52.6%).1 Different factors are involved in myocardial injury and the development of 113 cardiovascular complications of COVID-19 and include an increased hypercoagulable status, 114 systemic inflammatory response to a viral infection which may lead to increased metabolic 115 activity, angiotensin-converting enzyme 2 (ACE2) expression on cardiac cells (which act as a 116 receptor for the SARS-CoV2 virus leading to the invasion of the cardiac cells by the virus), and 117 direct viral injury of cardiac cells.1 118 119 On the other hand, around 90% of primary cardiac tumors are benign including myxoma (50%), 120 fibroelastoma (26%), fibroma (6%), lipoma (4%), inflammatory myofibroblastic tumors (IMTs) 121 (< than 5%), and other benign tumors.2 Primary pericardial masses are also usually benign and 122 constitute about 6% to 10% of primary cardiac tumors. These benign primary pericardial masses 123 include lipomas, pericardial cysts, and paragangliomas, and hemangiomas. In addition, 124 pericardial tumors are associated with some disorders such as Erdheim-Chester disease and 125 IgG4-related disease. The clinical signs and symptoms of pericardial masses include dyspnea, 126 edema, pleural effusion, orthopnea, pericardial effusion, or murmur.3 Inflammatory 127 pseudotumors of the pericardium are among the primary pericardial tumors that are benign. 128 Although the exact cause of inflammatory pseudotumors is unknown, these masses have been 129 reported to occur following surgery, trauma, IgG4-related sclerosing disease, or infection (with 130 bacteria such as Mycoplasma and Nocardia). In addition, some have argued that inflammatory 131 pseudotumors develop through a low-grade neoplastic process.4 Cardiac and pericardial tumors 132 are rare and to our knowledge, there have been no reports of SARS-CoV-2 infection inducing the 133 development of a cardiac or para-cardiac mass (that may present as a cardiac mass such as in our 134 case). We report a previously healthy 45-year-old male that developed persistent dyspnea and 135 edema following SARS-CoV-2 infection. He underwent cardiac surgery due to the presence of a 136 compressive mass with physiological constrictive pericarditis. The pericardium was intact and 137 the mass was removed. The pathology report indicated an inflammatory nature for the mass. 138 Confirmation of an association between the development of a para-cardiac inflammatory mass 139 and SARS-CoV-2 infection requires further investigation. 140 141 Conclusion 142 We report the first reported case of a para-cardiac mass development following SARS-CoV-2 143 infection in a previously healthy 45-year-old man. 144 145 Author Contributions 146 AM, AMS, and MMMR, MR clinically managed the patient. The primary draft was conducted by 147 SH. AM, AMS, MMMR, and MR conducted the first edit. All authors have read and approved 148 the final manuscript. 149 150 References 151 1. Bhandari B, Neupane S, Khanal R, Lnu K, Wert Y, Komanduri S. COVID-19 pericarditis 152 mimicking an acute myocardial infarction: a case report and review of literature. J Community 153 Hosp Intern Med Perspect 2021; 11(3):315-21. https://doi.org/10.1080/20009666.2021.1896429. 154 https://doi.org/10.1080/20009666.2021.1896429 2. Deng MD, Han JY, Lin K, Tang H. Cardiac inflammatory myofibroblastic tumor in 155 interventricular septum: A rare case report. Medicine (Baltimore) 2018; 97(48):e13219. 156 https://doi.org/10.1097/md.0000000000013219. 157 3. Maleszewski JJ, Anavekar NS. Neoplastic Pericardial Disease. Cardiol Clin 2017; 35(4):589-158 600. https://doi.org/10.1016/j.ccl.2017.07.011. 159 4. Restrepo CS, Vargas D, Ocazionez D, Martínez-Jiménez S, Betancourt Cuellar SL, Gutierrez 160 FR. Primary pericardial tumors. Radiographics 2013; 33(6):1613-30. 161 https://doi.org/10.1148/rg.336135512. 162 163 Table 1. A summary of the patient’s laboratory workup before surgery. 164 Laboratory test Result Normal range WBC 109/L 8.77 Adult: 5-10 RBC 106/uL 4.27 (Low) Male: 4.7-6.1 Hb g/dl 11.5 (Low) Male: 13.2-16.2 HCT % 34.8 (Low) Male: 39-52 Neutrophil % 63.5 (High) 40-60 Lymphocyte % 28.8 20-40 Platelets 103/ml 469 (High) 150-450 PTT seconds 64 30-45 PT seconds 18.1 (High) 12-16.5 INR (ratio) 1.36 Ratio: 1.34 Blood group O positive - ESR (1hr) mm/hr 67 (High) <10 CRP mg/l 32.5 (High) Up to 6 Magnesium mg/dl 2.2 1.8-2.6 Hbs Ag (Index) Negative <1: Negative HCV Ab (Index) Non-reactive Non-reactive: <0.9 HIV (IFA) (Index) Non-reactive Negative: <0.25 Abbreviations: White blood cells (WBC), Red blood cells (RBC), Hemoglobin (Hb), 165 Hematocrit (HCT), PTT (Partial thromboplastin time), PT (Prothrombin time), INR 166 (international normalized ratio), ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), 167 https://doi.org/10.1097/md.0000000000013219 https://doi.org/10.1016/j.ccl.2017.07.011 https://doi.org/10.1148/rg.336135512 Hbs Ag (Hepatitis B virus surface antigen), HCV Ab (Hepatitis C virus antibody), HIV (human 168 immunodeficiency virus), and Indirect fluorescent antibody (IFA). 169 170 171 Figure 1. Echocardiography: A large hypoechoic mass (size: 9x3.1cm in size) suggestive of an 172 extra pericardial inflammatory mass or a large hematoma with central liquefaction over the right 173 atrium (RA) and right ventricle (RV) causing compressive effects. 174 175 176 Figure 2. A. Multi-slice high-resolution computed tomography (HRCT) scan of the chest 177 revealing bilateral mild pleural effusion; Patchy and ground-glass opacity in the right lower lobe 178 (RLL) [suggestive of a sequel of the patient’s previously COVID-19 infection]; Linear 179 atelectasis in both the right and left upper lobes as well as the left lower lobe (LLL); Minimal 180 atelectasis with pericardial effusion; Arrow showing the mass. B and C. MRI of the chest; 181 Arrows showing the mass (RV: Right Ventricle; LV: Left ventricle; PE; pleural effusion). 182 183 184 Figure 3. A. Image of the large mass (size of 10x4x3cm) that was excised upon surgery. B, C, 185 and D. Microscopic evaluation of the mass (some lesions had necrosis, neutrophilic infiltration, 186 and foamy macrophages; some of the fibrotic areas contained lymphocytic infiltration and 187 lympho-plasma cells. No evidence of malignancy or granuloma). 188