Aims Immunocompromised patients have been excluded from studies of SARS-CoV-2 messenger RNA vaccines. The immune response to vaccines against other infectious agents has been shown to be blunted in such patients. We aimed to analyse the humoral and cellular response to prime-boost vaccination with the BNT162b2 vaccine (Pfizer-BioNTech) in cardiothoracic transplant recipients. Methods and results A total of 50 transplant patients [1–3 years post heart (42), lung (7), or heart–lung (1) transplant, mean age 55 ± 10 years] and a control group of 50 healthy staff members were included. Blood samples were analysed 21 days after the prime and the boosting dose, respectively, to quantify anti-SARS-CoV-2 spike protein (S) immunoglobulin titres (tested by Abbott, Euroimmun and RocheElecsys Immunoassays, each) and the functional inhibitory capacity of neutralizing antibodies (Genscript). To test for a specific T-cell response, heparinized whole blood was stimulated with SARS-CoV-2 specific peptides, covering domains of the viral spike, nucleocapsid and membrane protein, and the interferon-γ release was measured (QuantiFERON Monitor ELISA, Qiagen). The vast majority of transplant patients (90%) showed neither a detectable humoral nor a T-cell response three weeks after the completed two-dose BNT162b2 vaccination; these results are in sharp contrast to the robust immunogenicity seen in the control group: 98% exhibited seroconversion after the prime dose already, with a further significant increase of IgG titres after the booster dose (average > tenfold increase), a more than 90% inhibition capability of neutralizing antibodies as well as evidence of a T-cell responsiveness. Conclusions The findings of poor immune responses to a two-dose BNT162b2 vaccination in cardiothoracic transplant patients have a significant impact for organ transplant recipients specifically and possibly for immunocompromised patients in general. It urges for a review of future vaccine strategies in these patients.

Aims Heart transplantation may represent a particular risk factor for severe coronavirus infectious disease 2019 (COVID-19) due to chronic immunosuppression and frequent comorbidities. We conducted a nationwide survey of all heart transplant centers in Germany presenting the clinical characteristics of heart transplant recipients with COVID-19 during the first months of the pandemic in Germany. Methods and results A multicenter survey of all heart transplant centers in Germany evaluating the current status of COVID-19 among adult heart transplant recipients was performed. A total of 21 heart transplant patients with COVID-19 was reported to the transplant centers during the first months of the pandemic in Germany. Mean patient age was 58.6 ± 12.3 years and 81.0% were male. Comorbidities included arterial hypertension (71.4%), dyslipidemia (71.4%), diabetes mellitus (33.3%), chronic kidney failure requiring dialysis (28.6%) and chronic-obstructive lung disease/asthma (19.0%). Most patients received an immunosuppressive drug regimen consisting of a calcineurin inhibitor (71.4%), mycophenolate mofetil (85.7%) and steroids (71.4%). Eight of 21 patients (38.1%) displayed a severe course needing invasive mechanical ventilation. Those patients showed a high mortality (87.5%) which was associated with right ventricular dysfunction (62.5% vs. 7.7%; p = 0.014), arrhythmias (50.0% vs. none; p = 0.012), and thromboembolic events (50.0% vs. none; p = 0.012). Elevated high-sensitivity cardiac troponin T-and N-terminal prohormone of brain natriuretic peptide were significantly associated with the severe form of COVID-19 (p = 0.017 and p < 0.001, respectively). Conclusion Severe course of COVID-19 was frequent in heart transplanted patients. High mortality was associated with right ventricular dysfunction, arrhythmias, thromboembolic events, and markedly elevated cardiac biomarkers.

Aims There is a lack of diagnostic and therapeutic options for patients with atrial cardiomyopathy and paroxysmal atrial fibrillation. Interestingly, an abnormal P-wave terminal force in electrocardiogram lead V 1 (PTFV 1 ) has been associated with atrial cardiomyopathy, but this association is poorly understood. We investigated PTFV 1 as a marker for functional, electrical, and structural atrial remodelling. Methods and results Fifty-six patients with acute myocardial infarction and 13 kidney donors as control cohort prospectively underwent cardiac magnetic resonance imaging to evaluate the association between PTFV 1 and functional remodelling (atrial strain). To further investigate underlying pathomechanisms, right atrial appendage biopsies were collected from 32 patients undergoing elective coronary artery bypass grafting. PTFV 1 was assessed as the product of negative P-wave amplitude and duration in lead V 1 and defined as abnormal if ≥4000 ms*μV. Activity of cardiac Ca/calmodulin-dependent protein kinase II (CaMKII) was determined by a specific HDAC4 pull-down assay as a surrogate for electrical remodelling. Atrial fibrosis was quantified using Masson's trichrome staining as a measure for structural remodelling. Multivariate regression analyses were performed to account for potential confounders. A total of 16/56 (29%) of patients with acute myocardial infarction, 3/13 (23%) of kidney donors, and 15/32 (47%) of patients undergoing coronary artery bypass grafting showed an abnormal PTFV 1 . In patients with acute myocardial infarction, left atrial (LA) strain was significantly reduced in the subgroup with an abnormal

Aims Coronavirus disease 2019 (COVID‐19) is a widespread pandemic with an increased morbidity and mortality, especially for patients with cardiovascular diseases. Angiotensin‐converting enzyme 2 (ACE2) has been identified as necessary cell entry point for SARS‐CoV‐2. Previous animal studies have demonstrated an increased ACE2 expression following treatment with either angiotensin‐converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) that have led to a massive precariousness regarding the optimal cardiovascular therapy during this pandemic. Methods and results We have measured ACE2 mRNA expression using real‐time quantitative polymerase chain reaction in atrial biopsies of 81 patients undergoing coronary artery bypass grafting and we compared 62 patients that received ACEi/ARB vs. 19 patients that were not ACEi/ARB‐treated. We found atrial ACE2 mRNA expression to be significantly increased in patients treated with an ACEi or an ARB, independent of potential confounding comorbidities. Interestingly, the cardiac ACE2 mRNA expression correlated significantly with the expression in white blood cells of 22 patients encouraging further evaluation if the latter may be used as a surrogate for the former. Similarly, analysis of 18 ventricular biopsies revealed a significant and independent increase in ACE2 mRNA expression in patients with end‐stage heart failure that were treated with ACEi/ARB. On the other hand, cardiac unloading with a left ventricular assist device significantly reduced ventricular ACE2 mRNA expression. Conclusion Treatment with ACEi/ARB is independently associated with an increased myocardial ACE2 mRNA expression in patients with coronary artery disease and in patients with end‐stage heart failure. Further trials are needed to test whether this association is deleterious for patients with COVID‐19, or possibly protective. Nevertheless, haemodynamic factors seem to be equally important for regulation of cardiac ACE2 mRNA expression.

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