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THIS IS AN OPEN ACCESS ARTICLE UNDER THE CC BY-NC-ND LICENSE (http://creativecommons.org/licenses/by-nc-nd/4.0/). CASE REPORT CLINICAL CASE Intraventricular Conundrum in a SARS-CoV-2–Positive Patient With Elevated Biomarkers of Myocardial Injury María L. Servato, MD,a,b Filipa X. Valente, MD,a,b Laura Gutiérrez García-Moreno, MD,a,b Guillem Casas, MD,a,b Rubén Fernández-Galera, MD,a,b Gemma Burcet, MD,c Gisela Teixidó-Tura, MD, PHD,a,b Hug Cuéllar Calabria, MD, PHD,c Ignacio Ferreira González, MD, PHD,a,d José F. Rodríguez-Palomares, MD, PHDa,b ABSTRACT We present a case of acute myocarditis with left ventricular dysfunction and intracavitary thrombosis in a 55-year-old man with severe acute respiratory syndrome coronavirus 2 infection (coronavirus disease 2019) who was admitted with bilateral atypical pneumonia. The patient was treated with anticoagulation and optimal heart failure therapy and had an improvement of left ventricular function and thrombus resolution. (Level of Difficulty: Intermediate.) (J Am Coll Cardiol Case Rep 2021;-:-–-) © 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc- nd/4.0/). A 55-year-old man who tested positive for se- vere acute respiratory coronavirus-2 (SARS-CoV-2) (the agent of coronavirus disease-2019 [COVID-19]) was admitted syndrome- pro–B-type natriuretic peptide (NT-proBNP) levels were unremarkable. Blood pressure 77 mm Hg, heart rate was 84 beats/min, body temper- ature was 36  C, and respiration rate was 24 breaths/ was 144/ to the intensive care unit of Vall d’Hebron University min. The patient required high- flow oxygen through Hospital, Barcelona, with a diagnosis of bilateral a nasal cannula (fraction of inspired oxygen [Fi O2] 1) atypical pneumonia (Figure 1). Blood tests demon- to maintain a peripheral oxygen saturation of 96%. strated leukopenia, elevated C-reactive protein of However, 3 days after hospitalization, D-dimer levels 12.35 mg/dl, and interleukin-6 levels of 1,946 pg/dl. increased significantly (up to 12,835 ng/ml), as did High- sensitivity troponin I, D-Dimer, and N-terminal troponin I and NT-proBNP levels (4,162 ng/l and 7,460 pg/ml, respectively). He had no cardiovascular LEARNING OBJECTIVES symptoms and was hemodynamically stable. A bedside echocardiogram showed a dilated left  To recognize cardiovascular complications ventricle with moderate systolic dysfunction (left ven- among COVID-19 patients. tricular [LV] ejection fraction [LVEF] of 35% to 40%),  To learn the role of multimodality imaging in global hypokinesia, and a huge multilobed, mobile, challenging cases. and hyperechogenic mass measuring 41  26 mm From the aDepartment of Cardiology, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Autonomous University of Barcelona, Barcelona, Spain; bCenter for Biomedical Investigation Cardiovascular Consortium, Madrid, Spain; cRadiology Ser- vice, Institute for Diagnostic Imaging, Vall d’Hebron University Hospital, Barcelona, Spain; and the dCenter for Biomedical Investigation Epidemiology and Public Health Consortium, Madrid, Spain. 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. Manuscript received October 16, 2020; revised manuscript received January 14, 2021, accepted January 22, 2021. ISSN 2666-0849 https://doi.org/10.1016/j.jaccas.2021.01.030 2 Servato et al. JACC: CASE REPORTS, VOL. -, NO. -, 2021 Intraventricular Conundrum in a SARS-CoV-2 Patient - 2021:-–- ABBREVIATIONS and attached to the apex. Right ventricular F I G U R E 1 Chest Radiograph on Admission AND ACRONYMS function was preserved (tricuspid annular plane systolic excursion of 22 mm and tis- CMR = cardiac magnetic sue Doppler systolic wave [S] of 12 cm/s), resonance and there was no valve disease (Figures 2A COVID-19 = coronavirus disease-2019 and 2B, Videos 1 and 2). With these FiO2 = fraction of inspired findings, anticoagulation with full-dose oxygen low-molecular-weight heparin and heart LV = left ventricular failure treatment (carvedilol and enalapril) LVEF = left ventricular ejection were started. fraction PAST MEDICAL HISTORY NT-proBNP = N-terminal pro– B-type natriuretic peptide SARS-CoV-2 = severe acute His past medical history included obesity respiratory syndrome- (body mass index, 31 kg/m 2) and obstructive coronavirus-2 sleep apnea syndrome requiring continuous positive airway pressure. He had no previous cardio- vascular disease. hyperintensity of the middle and apical anterior wall DIFFERENTIAL DIAGNOSIS (slow contrast washout). Overall, these findings are suggestive of diffuse myocardial edema, predomi- Given the patient’s clinical presentation with LV nantly in the anterior wall (Figures 5, 6A to 6C, and 7, dysfunction, the differential diagnosis included Videos 3 and 4). First-pass perfusion and early and ischemic cardiomyopathy, myocarditis, and decom- late gadolinium enhancement were performed, and pensation of a previously unknown cardiomyopathy. no intraventricular mass was observed, a finding that Because of the presence of a huge intraventricular suggested a thrombotic origin. Because 2 comple- mass, thrombus versus intracardiac tumor was mentary studies had demonstrated the absence of a proposed. mass, a second echocardiogram during hospitaliza- INVESTIGATIONS tion was not performed to reduce the risk of conta- gion for the sonographer, according to international An electrocardiogram showed a previously unknown recommendations (1). The patient did not experience left bundle branch block (Figure 3). At 6 and 7 days any symptoms or signs suggestive of peripheral after the echocardiogram and the start of anti- embolism. coagulation, cardiac computed tomography and car- MANAGEMENT diac magnetic resonance (CMR) were performed. Computed tomography showed no coronary lesions The patient required only high-flow oxygen (Fi O2 1) and a dilated left ventricle with moderate systolic with no requirements of ventilation or hemodynamic dysfunction (LVEF, 38%) (Figures 4A to 4D). No support. He was treated with ceftriaxone, azi- intracavitary mass was visualized. CMR revealed thromycin, hydroxychloroquine, lopinavir and rito- mildly increased diffuse wall thickness with an navir in combination, and tocilizumab, according to elevated myocardial signal intensity in the anterior the local protocol at the time. Anticoagulation with middle and apical wall in balanced steady-state free full-dose low-molecular-weight heparin was also precession cine sequences. In addition, short tau prescribed, as well as complete heart failure therapy. inversion recovery images showed mild hyper- intensity of the anterior wall, with a T 2 ratio of DISCUSSION myocardium to skeletal muscle of 2.6. Native T1 mapping was elevated overall (native T1 of 1,107 ms Severe acute respiratory syndrome associated with [reference values 950 to 1,050 ms]), as was the SARS-CoV-2 infection appears to affect the myocar- extracellular volume ( 29%). T 2 mapping sequences dium by different mechanisms (2): infection-related showed an elevated global T2 value of 62 ms (65 ms in myocarditis, hypoxemia, and/or ischemia, and it is the anterior and anteroseptal wall, 55 ms in the considered an important prognostic factor (3). More- inferior wall). Late gadolinium enhancement se- over, COVID-19 may be associated with a hypercoag- quences demonstrated no foci or areas of contrast ulable state. There is evidence of a high prevalence of uptake; nevertheless, there was a diffuse mild clinically relevant thrombosis, essentially pulmonary JACC: CASE REPORTS, VOL. -, NO. -, 2021 Servato et al. 3 - 2021:-–- Intraventricular Conundrum in a SARS-CoV-2 Patient F I G U R E 2 Bedside 2-Dimensional Echocardiography The images show a dilated left ventricle with a huge multilobed, mobile, and hyperechogenic mass attached to the apex (arrows). Left ventricle in (A) the apical 4 chamber view and (B) the apical 3-chamber view. F I G U R E 3 Electrocardiogram on Admission 4 Servato et al. JACC: CASE REPORTS, VOL. -, NO. -, 2021 Intraventricular Conundrum in a SARS-CoV-2 Patient - 2021:-–- F I G U R E 4 Coronary Computed Tomography Angiography The images show no coronary stenosis in (A) the right coronary artery, (B) the left anterior descending artery, and (C) the circumflex artery. (D) No evidence of left ventricular thrombus is noted. embolisms (16.7%), in patients with hypoxemic acute whereas the expansion of the extracellular space is respiratory failure (4). Furthermore, venous and supported by the finding of increased native T1 and arterial thromboembolisms are emerging as among T 2 mapping, as well as increased extracellular the most severe sequelae of the disease associated volume. with poorer outcomes (5). In addition, acute coronary Echocardiography is helpful in assessing cardiac syndromes are noted to occur after severe acute res- hemodynamics in the presence of chest pain, elec- piratory syndrome (6). trocardiographic changes, or biomarker elevation We report a case of myocarditis associated with COVID-19 with LV dysfunction and a large mobile LV F I G U R E 5 Balanced Steady-State Free Precession Cine thrombus in a young patient with no cardiovascular Images in the 2-Chamber View history. This thrombus could have resulted in severe complications without prompt diagnosis and treat- ment initiation. Because endomyocardial biopsy is not recommended in patients with COVID-19 and suspected myocarditis (1), and given that the patient had a good evolution, a biopsy was not performed. Moreover, recent biopsy data revealed that T1 and T 2 increase in this population is related to myocarditis (lymphocytic infiltrates) (7). Although the presence of elevated troponin I is frequently seen in patients with myocarditis and is usually associated with myocyte necrosis, our pa- tient had elevated troponin but no late gadolinium enhancement. We believe that these findings can be explained by the marked myocardial inflammation and associated submillimetric and nonhomogeneous areas of necrosis (8). The lesser severity of myocardial Mildly increased wall thickness and higher myocardial signal injury also explains the overall improvement of intensity in the anterior middle and apical wall (arrowheads). myocardial systolic function during follow-up, JACC: CASE REPORTS, VOL. -, NO. -, 2021 Servato et al. 5 - 2021:-–- Intraventricular Conundrum in a SARS-CoV-2 Patient F I G U R E 6 Short Tau Inversion Recovery and Mapping Images (A) Short tau inversion recovery images in the short axis with mild hyperintensity of the anterior wall (arrowheads). (B) T1 mapping study shows an overall elevated native T1 value of 1,107 ms and an extracellular volume of 29%. (C) T2 mapping shows an elevated global T2 value of 62 ms (65 ms in the anterior and anteroseptal wall, 55 ms in the inferior wall). suggestive of myocardial injury, myopericarditis, or heart injury biomarkers, to establish a correct diag- fulminant myocarditis (9), and it should be planned nosis, guide management, and reduce complications. in patients with new onset of malignant ventricular To the best of our knowledge, no similar case has arrhythmias not associated with a prolonged QT in- been published. terval (10). As demonstrated in our case, echocardi- ography permitted accurate diagnosis and FOLLOW-UP management. We highlight the importance of echocardiography The patient was discharged in good clinical condi- in patients with SARS-CoV-2 infection and elevated tion. He is currently receiving the following F I G U R E 7 Late Gadolinium Enhancement Images Late gadolinium enhancement images in the 2-chamber (left) and mid–short-axis views (right) with no evidence of focal necrosis or fibrosis. Nevertheless, there is diffuse mild hyperintensity of the middle and apical anterior wall (arrows). 6 Servato et al. JACC: CASE REPORTS, VOL. -, NO. -, 2021 Intraventricular Conundrum in a SARS-CoV-2 Patient - 2021:-–- F I G U R E 8 Control Echocardiogram 2 Months After Discharge Showing Left Ventricular Function Improvement and the Absence of Intraventricular Thrombus Left ventricle in (A) the apical 4-chamber view and (B) the apical 3-chamber view. medications: carvedilol, 6.25 mg b.i.d.; enalapril, 5 normalization of T1 and T 2 values (Figures 9A and 9B, mg o.d.; and acenocoumarol. Two months after Videos 7 and 8). discharge, he is asymptomatic, and an echocardio- gram revealed improvements in contractility and CONCLUSIONS ventricular function (LVEF, 50%), as well as the absence of intracavitary thrombus (Figures 8A and 8B, This is a rare case of myocarditis with acute LV Videos 5 and 6). Moreover, control CMR showed a thrombosis and dysfunction in a young patient with F I G U R E 9 Control Cardiac Magnetic Resonance The images show normalization of (A) T1 and (B) T2 values. JACC: CASE REPORTS, VOL. -, NO. -, 2021 Servato et al. 7 - 2021:-–- Intraventricular Conundrum in a SARS-CoV-2 Patient SARS-CoV-2 pneumonia. The patient had a favorable clinical evolution under anticoagulation and heart ADDRESSES FOR CORRESPONDENCE: Dr. Jose F. failure treatment. We highlight the importance of Rodriguez-Palomares, Department of Cardiology,  Hospital Universitari Vall dHebron, Paseo Vall d’He- echocardiography in patients with SARS-CoV-2 infection and biomarker elevation suggestive of bron 119-129, 08035 Barcelona, Spain. E-mail: myocardial injury, to guide management and reduce jfrodriguezpalomares@gmail.com OR jfrodrig@ complications and mortality. vhebron.net. OR Dr. Ignacio Ferreira González, Department of Cardiology, Hospital Universitari Vall FUNDING SUPPORT AND AUTHOR DISCLOSURES  dHebron, Paseo Vall d’Hebron 119-129, 08035 Barce- lona, Spain. E-mail: nachoferreira@secardiologia.es The authors have reported that they have no relationships relevant to the contents of this paper to disclose. OR iferreir@vhebron.net. REFERENCES 1. The European Society for Cardiology. ESC guid- 5. Abou-Ismail M, Diamond A, Kapoor S, et al. The 9. Zeng JH, Liu YX, Yuan J, et al. 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