key: cord-0708858-1liu8348 authors: Nakanishi, Yuki; Honda, Sakiko; Yamano, Michiyo; Kawasaki, Tatsuya; Yoshioka, Keiji title: Constrictive pericarditis after SARS-CoV-2 vaccination: A case report date: 2022-01-19 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2022.01.027 sha: 395f2cb4ab385487500e9c0ea3bb6fafd9994f32 doc_id: 708858 cord_uid: 1liu8348 Coronavirus disease 2019 (COVID-19) and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with cardiovascular complications. We report a case of right-sided heart failure due to constrictive pericarditis that developed after administration of messenger ribonucleic acid (mRNA) vaccines against SARS-CoV-2. A 70-year-old woman presented with body weight gain, peripheral edema, and dyspnea on effort, which developed over a period of one week after the second vaccine injection. The jugular venous pressure was high with a prominent y descent (Friedreich's sign) and paradoxical increase on inspiration (Kussmaul's sign). The results of IgM and IgG testing specific to SARS-CoV-2 spike and nucleocapsid proteins were consistent with mRNA vaccine-induced antibody, not COVID-19 infection. Echocardiography demonstrated pericardial thickening and septal bounce of the interventricular septum. Computed tomography also revealed pericardial thickening compared with the previous examination four months earlier. A diagnosis of right-sided heart failure due to constrictive pericarditis was confirmed based on pressure analysis during cardiac catheterization. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a wide range of cardiovascular complications such as myocarditis, heart failure, arrhythmias, and venous thromboembolism [Chang et al., 2021] . Although SARS-CoV-2 vaccination has been widely adopted to prevent the spread of COVID-19, vaccine-associated cardiovascular complications, such as myocarditis and pericarditis, have been reported [Bozkurt et al, 2021 ; Pepe et al., 2021] . We report a case of right-sided heart failure due to constrictive pericarditis that developed after the administration of messenger ribonucleic acid (mRNA) vaccines against SARS-CoV-2. A 70-year-old woman was referred to the Department of Cardiology of Matsushita Memorial Hospital because of body weight gain, peripheral edema, and dyspnea on effort. Nine weeks before the current evaluation, the patient received the first vaccine against SARS-CoV-2 with no side effects. The patient was in a normal state of health until approximately five weeks before presentation, when weight increase (i.e., from 40 kg to 50 kg) followed by dyspnea on effort developed over a period of one week after the second vaccination six weeks earlier. Oral diuretics were administered and her weight decreased to 44 kg. Neither pleural effusion nor cardiomegaly was noted on chest radiography. Two weeks later, her body weight decreased to 41 kg and edema almost disappeared, but her N-terminal pro-brain natriuretic peptide (BNP) level was 466 pg/mL (reference value, ≤55). She had a medical history of type 2 diabetes, hypertension, dyslipidemia, and pulmonary fibrosis. She was prescribed azosemide, carvedilol, pitavastatin, ezetimibe, insulin degludec, glimepiride, vildagliptin, and miglitol, none of which was changed for more than a year. The patient was a past smoker with a 28-pack-year history, did not drink or use illicit drugs, and had no known allergies. The patient had no antecedent trauma to the chest. Her father had myocardial infarction and diabetes. On examination, her blood pressure was 129/60 mmHg, pulse was 88 beats per minute, body temperature was 36.3°C, respiratory was 18 breaths per min, and oxygen saturation was 98% while breathing ambient air. The jugular venous pressure was high with a prominent y descent (Friedreich's sign) and paradoxical increase on inspiration (Kussmaul's sign). Cardiac auscultation was unremarkable; no knock sound was audible. There was mild pitting edema in the legs. Electrocardiography demonstrated a normal axis and no ST-T segment changes. Chest radiography revealed a cardiothoracic ratio of 38% with reduced opacity in both lung fields, findings unchanged from those obtained three months previously. The complete blood cell counts were normal, as were the results of renal and liver function tests, electrolyte balance, C-reactive protein level, and thyroid function test. The glycated hemoglobin level was 7.5% and BNP level was 58.5 pg/mL (reference value, ≤18.4). The troponin T was negative (reference value, ≤0.014). The results of IgM against SARS-CoV-2, IgG specific to SARS-CoV-2 spike protein, and IgG specific to SARS-CoV-2 nucleocapsid protein were negative, positive, and negative, respectively, being consistent with vaccine-induced antibody and not COVID-19 infection [Noda et al., 2021] . On echocardiography, pericardial thickening and septal bounce (i.e., movement of the interventricular septum to the left ventricle during inspiration) were observed ( Figure 1A) . The respiratory variation of the E wave of the mitral flow was 26% and respiratory variation of the tricuspid E wave was 18%. The remainder of the echocardiographic examination was unremarkable. Computed tomography (CT) of the chest without administration of contrast material revealed pericardial thickening compared with the examination four months earlier ( Figures 1B and 1C) . Although no evidence suggesting myocardial involvement was shown on cardiac magnetic resonance, adhesion of the thickened pericardium to the myocardium was suggested on cine images. No stenosis was found on coronary arteriography, but right heart catheterization demonstrated an increase in end-diastolic filling pressures with a steep y descent on right ventricular pressure tracing, and a prominent x and y descent on right atrial pressure tracing (Figures 1D and 1E) . The pulmonary artery pressure was 27/16 mmHg (mean 21 mmHg) and pulmonary capillary wedge pressure was 16 mmHg. A diagnosis of right-sided heart failure due to constrictive pericarditis was made. Additional evaluations were performed to clarify the etiology of constrictive pericarditis. For example, the interferon-gamma release assay was negative and there were no clinical, imaging, or laboratory data suggesting malignancy or autoimmune disease. Pericardiectomy was deferred considering her mild symptoms with oral diuretics. The patient has been doing for more than three months after the diagnosis, although mild dyspnea has persisted. The current patient developed right-sided heart failure due to constrictive pericarditis a week after the second SARS-CoV-2 mRNA vaccination. Based on her clinical course and imaging findings including changes in the pericardium on CT, which was performed in an interval of four months, we diagnosed her with a rare complication after SARS-CoV-2 vaccination. The patient has no known history of malignancy, tuberculosis, autoimmune disease, or prior cardiac surgery, which are common causes of constrictive pericarditis. Constrictive pericarditis may be a complication of acute pericarditis. In a series of 500 consecutive patients with a first episode of acute pericarditis, constrictive pericarditis developed in nine (1.8%), among whom only two had idiopathic or viral pericarditis (0.48%) [Imazio et al., 2011] . It is important to note that the follow-up period of the study was long at 6 years, ranging from 2 to 10 years, which is consistent with constrictive pericarditis being a late complication of chronic pericarditis. In our case, no pericardial effusion was observed on CT four months before the diagnosis of constrictive pericarditis, which made a diagnosis of chronic pericarditis less likely before this episode. Interestingly, constrictive pericarditis reportedly developed two weeks after the initial symptoms in a patient with COVID-19 days and 26 months before admission; 12 patients had symptoms for less than 3 months. Although no invasive procedures to establish a diagnosis of effusive-constrictive pericarditis (i.e., simultaneous measurement of intrapericardial and intracardiac pressures before and after pericardial drainage) were performed in our case, the possibility was less likely because neither asymptomatic status nor stable hemodynamics without invasive therapy can be observed in patients with effusive-constrictive pericarditis [Yacoub et al., 2021] . In conclusion, the current case highlights the importance of acknowledging the rare complication of constrictive pericarditis in association not only with COVID-19, but also with vaccines against SARS-CoV-2. 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