key: cord-0836199-sabn6ewq authors: Berg, Nicholas; Ilonze, Onyedika; Bajpai, Vatsal; Guglin, Maya; Rao, Roopa title: Acute Biventricular Heart Failure after COVID-19 Infection in Orthotropic Heart Transplant Patient date: 2021-03-19 journal: Transplant Proc DOI: 10.1016/j.transproceed.2021.03.013 sha: e916a870a7f42e3912ddab1c57bcdfe31de06919 doc_id: 836199 cord_uid: sabn6ewq The cardiac effects of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include myocarditis, takotsubo cardiomyopathy, pericardial effusion and cardioembolic events in the general population. Effects of SARS-CoV-2 in heart transplant patients is unclear. We describe a case of myocarditis in the transplanted heart that responded to methylprednisolone. Our patient is 66-year-old male with a history of an orthotropic heart transplant in 2013 and dystonic muscular dystrophy type 2 who presented with shortness of breath and fatigue and found to have biventricular systolic dysfunction. He was incidentally found to test positive for coronavirus disease 2019 (COVID-19) without having respiratory symptoms other than dyspnea on exertion. His other co-morbidities included recent diagnosis of prostate cancer, hypertension, chronic kidney disease stage 3. At presentation, his blood pressure was 128/94 mmHg, heart rate 108 beats per minute, respiratory rate was 24, temperature was 37 C, and his oxygen saturation was 97%. He also reported nausea at home and missed taking his immunosuppressive drugs two days prior to presentation. On admission, his troponin-I was 0.04 ng/ml on two blood draws, slightly elevated above the lab cutoff of 0.03, then down trended to 0.03. BNP was within normal limits at 47 pg/ml. His EKG showed diffuse T wave inversions, including new inversions in leads II, III, and V4-V6. His echocardiogram on presentation showed left ventricular ejection fraction (LVEF) of 37% and right ventricle that was dilated with at least moderately reduced systolic function, both changes from a normal echo five months prior. Due to history of shortness of breath SARS-CoV-2 was tested, which came back positive. Endomyocardial biopsy was done due to new biventricular failure in the setting of not taking immunosuppression medications. The endomyocardial biopsy showed no evidence of acute cellular rejection (Grade 0R) or antibody mediated rejection with negative immunofluorescence. There was subendocardial fibrosis and Quilty lesion. He was treated with high-dose steroids at 1g/day of methylprednisolone for 3 days for presumed rejection until the biopsy results were completed. Followup echocardiogram at the end of 3 days showed improvement of LVEF to 66% and grossly normal right ventricular function. Since the advent of SARS-CoV-2 from coronavirus-2019 infection, immunocompromised and solid organ transplant recipients have been recognized as a vulnerable population with potentially worse outcomes. Currently available data on presentation, management, and outcomes are limited to case reports and case series 1 . There is only one other case of cardiac allograft dysfunction reported in a patient with COVID-19 infection who had undergone heart and kidney transplantation 2 . The index patient underwent heart transplant 7 years ago with no significant rejection history and had no nosocomial COVID-19 exposure. Our patient had a very vague and non-specific presentation with fatigue, dyspnea on exertion but notably had no fever, anosmia or typical viral prodrome typically associated with SARS-CoV-2. The concomitant allograft dysfunction in the presence of a non-significant troponin elevation and no arrhythmia presented a diagnostic and therapeutic dilemma. The differential diagnosis included non-rejection mechanisms -myocarditis, or stress cardiomyopathy which has been described in COVID-19 disease, 3,4 cardiac allograft vasculopathy and possibly allograft rejection. The probability of transplant rejection was low since he was 7 years post-transplant and endomyocardial biopsy was negative for cellular and antibody-mediated rejection with normal filling pressures and cardiac output. He had a coronary angiogram 3 months prior to presentation that showed no coronary artery disease or cardiac allograft vasculopathy. The optimal management especially of immunosuppression would depend greatly on the leading differential diagnosis as treatment for rejection may be contradictory to that of a severe viral infection. The recent International Society for Heart and Lung Transplantation recommendations to centers treating cases of severe COVID-19 disease in cardiothoracic transplantation recipients advises reducing or holding the anti-metabolites 5 . He was treated with three days of high dose IV methylprednisolone and because our patient did not have any significant hypoxia, pneumonia or marker of severe inflammatory disease, we decided to continue his baseline immunosuppression with cyclosporine and azathioprine and maintain therapeutic levels. We postulate that without any specific evidence for rejection or myocarditis, the patient most likely experienced transient stress injury to the allograft from critical illness that resolved as his condition improved within 5 days of admission. Some additional proof of cardiac damage is revealed by a study involving cardiac magnetic resonance imaging (MRI) on patients after recovering from a PCR-diagnosed COVID19 infection. New data reveals that myocarditis may be present even in healthy, young patients with minimal symptoms. This is further supported by a study on 100 patients in Germany with one-third of them requiring hospitalization. 78% were shown to have cardiac involvement with 60 still showing inflammation on cardiac MRI. 6 Developing data also shows some cases of myocarditis in patients who contract the SARS-CoV-2 virus. The incidence of myocarditis in COVID patient is unknown, but there are numerous case reports and reviews. One such study took place in China involving 416 patients with 82 of them showing cardiac injury. These patients with cardiac involvement had a much higher mortality rate. These symptoms vary anywhere from mild with fatigue, dyspnea, chest pain, and palpitations to severe with patients presenting in cardiogenic shock or sudden death due to arrythmias. 7 Overall, the early data from China suggested the myocardial injury was fairly common with an estimated incidence of 7-23% of reported cases. 1, 8, 9 Our case adds to the growing body of literature documenting the potential cardiotoxic effects of the suggesting that the cytokine storm might affect disease severity. 9 (Chen) Zheng et al. proposed that the mechanism of injury might be related to angiotensin-converting enzyme 2 (ACE2); which is widely expressed not only in the lungs but also in the cardiovascular system, so ACE2-related signaling pathways might also have a role in heart injury. 10 ACE2 is a membrane-bound aminopeptidase that has been identified as a functional receptor for coronaviruses. SARS-CoV-2 infection is triggered by the spike protein of the virus binding to ACE2, which is highly expressed in the heart and lungs resulting in ARDS and fulminant myocarditis. In a less-adopted hypothesis, several authors have speculated that SARS-CoV-2-induced severe acute respiratory distress syndrome (ARDS) results in persistent hypoxemia leading to myocardial cell damage. 11 Great interest is invested in the care for immunosuppressed patients infected with COVID-19. Studies are beginning to provide data to guide treatment for these patients with organ transplants and how to adjust the medications used. Two studies in particular, the COVID-LT and SETH, suggest that certain immunosuppressants may be protective and that complete pause of these drugs may be unwise. 12, 13 In the COVID-LT study, there was a mortality reduction in patients who continued taking calcineurin inhibitors. The SETH study showed a trend toward reduced severity of COVID-19 pneumonia in patients taking tacrolimus, but it was not statistically significant. 12, 13 Both studies demonstrated that stopping immunosuppressive therapies had no survival benefit. This data supports continued use of immune modulating medications in patients with solid organ transplants despite concerns for severe viral infections in these patients. This case demonstrates the importance of further investigation into the effects of the SARS-CoV-2 virus on the human body, especially the cardiovascular system. The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. COVID-19 and Myocarditis: What Do We Know So Far? 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