Multivessel Epicardial Coronary Artery Thrombosis after Heart Transplantation

Introduction: Although cardiac allograft vasculopathy (CAV) remains one of the leading causes of graft failure after heart transplantation (HTx), simultaneous thrombosis of multiple epicardial coronary arteries (CA) is an uncommon finding. Case Report: A 43-year-old male patient with non-ischemic dilated cardiomyopathy underwent successful HTx in 2019. The first two years after HTx were uneventful, surveillance endomyocardial biopsies (EMB) did not reveal any rejection episodes, coronary CTA revealed only minimal non-calcified CA plaques. The patient was admitted to hospital due to fever and chest pain in 2021. Immunosuppressive therapy consisted of tacrolimus, mycophenolate-mofetil and methylprednisolone. ECG verified sinus rhythm. Laboratory test revealed elevated hsTroponin T, NT-proBNP and CRP levels. Cytomegalovirus, SARS-CoV-2-virus and hemoculture testing was negative. Several high-titre donor-specific HLA class I and II antibodies (DSAs;including complement-binding DQ7) could have been detected since 2020. Echocardiography confirmed mildly decreased left ventricular systolic function and apical hypokinesis. EMB verified mild cellular and antibody-mediated rejection (ABMR) according to ISHLT grading criteria. Cardiac MRI revealed inferobasal and apical myocardial infarction (MI);thus, an urgent coronary angiography was performed. This confirmed thrombotic occlusions in all three main epicardial CAs and in first diagonal CA. As revascularization was not feasible, antithrombotic therapy with acetylsalicylic acid, clopidogrel and enoxaparin was started for secondary prevention. Tests for immune system disorders, thrombophilia and cancer were negative. Patient suddenly died ten days after admission. Necropsy revealed intimal proliferation in all three main epicardial CAs, endothelitis, thrombosis, chronic pericoronary fat inflammation, fat necrosis, and subacute MI. CA vasculitis owing to persistent high-titre DSAs, chronic ABMR and acute cellular and antibody-mediated rejection led to multivessel CA thrombosis and acute multiple MI. ABMR after HTx may be underdiagnosed with traditional pathological methods. Pathologies affecting coronary vasculature of HTx patients with DSAs, unique manifestations of CAV lesions and occlusive thrombosis of non-stenotic, non-atherosclerotic lesions should be emphasized.Copyright © 2023

Effect of Seroconversion after SARS-CoV-2 Vaccination on the Severity of COVID-19 Disease in Heart Transplant Recipients

Heart transplant (HTX) recipients are prone to develop serious symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their vaccination is often ineffective. In this high-volume single center study, we aimed to examine the seroconversion rates achieved with various types and doses of SARS-CoV-2 vaccines and assessed factors influencing vaccine immunogenicity and predictors of severe SARS-CoV-2 infection. 229 HTX recipients were enrolled at a university clinic. Type of the first two doses of vaccine included mRNA, vector and inactivated vaccines as well. We carried out analyses on seroconversion after the second and third doses of vaccination and on severity of coronavirus disease 2019 (COVID-19). Anti-SARS-CoV-2 IgG levels were measured with Elecsys immunoassay (Roche). Effect of the first two vaccine doses was studied on patients who did not suffer SARS-CoV-2 infection before antibody measurement (n=175). Seroconversion after the third vaccine was analysed among seronegative patients after two doses (n=53). Predictors for severe infection defined as pneumonia, hospitalization or death was assessed in all HTX recipients who had COVID-19 (n=92). Logistic regression was applied for further analyses. 62% of the recipients became seropositive after the second vaccination. Longer time between HTX and vaccination (OR: 2.35, 95% CI: 1.28 - 4.49, p=0.007) and mRNA type of vaccine (OR: 4.83, 95% CI: 1.33 - 17.5, p=0.012) were predictors of seroconversion. 58% of the non-responsive patients became seropositive after receiving the third vaccine. Male sex increased the chance of IgG production after the third dose (OR: 5.65, 95% CI: 1.61 - 22.7, p=0.009). Clinical course of SARS-CoV-2 infection was severe in 32%. Of all parameters assessed, only seropositivity was proven to have a protective effect against severe infection (OR: 0.12, 95% CI: 0.02 - 0.64, p=0.019). Longer time since HTX, mRNA vaccine type and male sex promoted seroconversion after SARS-CoV-2 vaccination in HTX recipients. Seropositivity was proven to be protective against severe SARS-CoV-2 infection in single center cohort. Routine screening of HTX patients for anti-SARS-COV-2 antibodies may help to identify patients at risk for severe infection requiring addtional measures of anti-SARS-CoV-2 protection. [ FROM AUTHOR] Copyright of Journal of Heart & Lung Transplantation is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Newly diagnosed chronic lymphocytic leukemia during symptomatic COVID-19: Case reports

Patients with malignant diseases have high risk of severe or critical forms of COVID-19. Chronic lymphocytic leukemia (CLL) can dysregulate both the adaptive and innate immune response. CLL-related immune dysfunctions may involve Tand B cells, the phagocytic cells and the complement system. SARS-CoV-2 infection also affects the function of the immune system, causing mainly the depletion of CD4+ and CD8+ T cells. When these diseases meet, the weakening of the immune system could help to avoid the fatal overreaction of the immune and inflammatory response. In our cases CLL manifested during a severe COVID-19 pneumonia. A 43-year-old man with IDDM was admitted to hospital in February with bilateral COVID pneumonia. He was transferred to hematology due to a vertebra CT showing signs of malignancy. He had 17.2 G/L WBC, 62.9% lymphocyte, 33% pathological B cells. The diagnosis of CD38+ B-CLL with two subclones was made. He had no paraproteinaemia but high levels of IgM and IgG type antibody against SARS-CoV-2 S protein. The other case is a 53-year-old man, hospitalized in March with severe COVID pneumonia. Signs of B-CLL was found (WBC 123 G/L, lymphocyte 91%, hemoglobin 107 g/L). Flow cytometric assay showed 82% pathological B cells with the diagnosis of CD38-B-CLL. The IgH gene rearrangement was positive. He had 1.2 g/L IgG kappa type monoclonal paraprotein. These two patients being in Rai 0-1 stage recovered after COVID pneumonia without shifting into a critical state in intensive care unit. The long-term follow-up of patients with CLL that manifested during symptomatic COVID-19 may further improve our knowledge about the immune system being attacked from several pathways.