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Aims One of the most important complications of heart transplantation is organ rejection, which is diagnosed on endomyocardial biopsies by pathologists. Computer-based systems could assist in the diagnostic process and potentially improve reproducibility. Here, we evaluated the feasibility of using deep learning in predicting the degree of cellular rejection from pathology slides as defined by the International Society for Heart and Lung Transplantation (ISHLT) grading system. Methods and results We collected 1079 histopathology slides from 325 patients from three transplant centres in Germany. We trained an attention-based deep neural network to predict rejection in the primary cohort and evaluated its performance using cross-validation and by deploying it to three cohorts. For binary prediction (rejection yes/no), the mean area under the receiver operating curve (AUROC) was 0.849 in the cross-validated experiment and 0.734, 0.729, and 0.716 in external validation cohorts. For a prediction of the ISHLT grade (0R, 1R, 2/3R), AUROCs were 0.835, 0.633, and 0.905 in the cross-validated experiment and 0.764, 0.597, and 0.913; 0.631, 0.633, and 0.682; and 0.722, 0.601, and 0.805 in the validation cohorts, respectively. The predictions of the artificial intelligence model were interpretable by human experts and highlighted plausible morphological patterns. Conclusion We conclude that artificial intelligence can detect patterns of cellular transplant rejection in routine pathology, even when trained on small cohorts.

Background Use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in elderly patients is controversial because of presumed poor outcome. Our primary aim was to determine the influence of advanced age on short- and long-term outcome; the secondary aim was to analyze risk factors for impaired outcome. Methods Between January 2006 and June 2020, 645 patients underwent VA-ECMO implantation in our department. The patients were categorized into four groups

Background The outcome after veno-venous extracorporeal membrane oxygenation in elderly patients is supposed to be unsatisfactory. Our primary aim was to determine the influence of advanced age on short- and long-term outcomes; the secondary aim was to analyze risk factors for impaired outcomes. Methods Between January 2006 and June 2020, 755 patients received V-V ECMO support at our department. Patients were grouped according to age (18–49.9, 50–59.9, 60–69.9, ≥70 years old), and then retrospectively analyzed for short- and long-term outcomes. Risk factors for in-hospital mortality and death during follow-up were assessed using multivariate regression analysis. Results Duration of V-V ECMO support was comparable between all groups median (8–10 days, p = 0.256). Likewise, the weaning rate was comparable in all age groups 68.2%–76.5%; (p = 0.354), but in-hospital mortality was significantly climbing with increasing age (

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 The 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 ACE inhibitors or angiotensin 1-receptor blockers (ACEi/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 qPCR in atrial biopsies of 81 patients undergoing coronary artery bypass grafting and we compared 62 patients that received ACEi/ARB versus 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 from 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 heart 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, hemodynamic factors seem to be equally important for regulation of cardiac ACE2 mRNA expression. This article is protected by copyright. All rights reserved.

Background Weaning failure from cardiopulmonary bypass, postoperative low cardiac output (LCO), and cardiopulmonary resuscitation (CPR) are common scenarios preceding extracorporeal life support (ECLS) implantation after cardiac surgery. The impact of these scenarios on short- and long-term outcome are not well described. Methods Between March 2006 and December 2018, 261 patients received ECLS support after cardiac surgery. Data of patients with weaning failure (NW), postoperative LCO, and CPR leading to ECLS implantation were retrospectively analyzed regarding outcome. Risk factors for outcome after postcardiotomy ECLS were assessed by uni- or multivariate regression analysis. Results Median duration of extracorporeal support was 5.5 ± 8.5 days. Overall mortality on ECLS was 39.1%. Scenario analysis revealed weaning failure from cardiopulmonary bypass in 40.6%, postoperative LCO in 24.5%, and postoperative CPR in 34.9% leading to initiation of ECLS. Most common cause of death was refractory LCO (25.3%). Overall follow-up survival was 23.7%. Survival after weaning and during follow-up in all subgroups was 9.2% (CPR), 5.0% (LCO), and 9.6% (NW), respectively. Uni- or multivariate regression analysis revealed age, aortic surgery, and vasopressor medication level on day 1 as risk for death on support, as well as postoperative renal failure, and body mass index (BMI) as risk factors for death during follow-up. Conclusion Mortality after postcardiotomy ECLS is high. Overall, outcome after CPR, NW, weaning failure and LCO is comparable. Postoperative resuscitation does not negatively affect outcome after postcardiotomy ECLS. Neurological status of ECLS survivors is good.

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 V1 (PTFV1) has been associated with atrial cardiomyopathy, but this association is poorly understood. We investigated PTFV1 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 PTFV1 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. PTFV1 was assessed as the product of negative P‐wave amplitude and duration in lead V1 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 PTFV1. In patients with acute myocardial infarction, left atrial (LA) strain was significantly reduced in the subgroup with an abnormal PTFV1 (LA reservoir strain: 32.28 ± 12.86% vs. 22.75 ± 13.94%, P = 0.018; LA conduit strain: 18.87 ± 10.34% vs. 10.17 ± 8.26%, P = 0.004). Abnormal PTFV1 showed a negative correlation with LA conduit strain independent from clinical covariates (coefficient B: −7.336, 95% confidence interval −13.577 to −1.095, P = 0.022). CaMKII activity was significantly increased from (normalized to CaMKII expression) 0.87 ± 0.17 to 1.46 ± 0.15 in patients with an abnormal PTFV1 (P = 0.047). This increase in patients with an abnormal PTFV1 was independent from clinical covariates (coefficient B: 0.542, 95% confidence interval 0.057 to 1.027, P = 0.031). Atrial fibrosis was significantly lower with 12.32 ± 1.63% in patients with an abnormal PTFV1 (vs. 20.50 ± 2.09%, P = 0.006), suggesting PTFV1 to be a marker for electrical but not structural remodelling. Conclusions Abnormal PTFV1 is an independent predictor for impaired atrial function and for electrical but not for structural remodelling. PTFV1 may be a promising tool to evaluate patients for atrial cardiomyopathy and for risk of atrial fibrillation.

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 nation-wide 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 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.

The concept of minimized cardiopulmonary bypass targets at reduction of adverse effects triggered by extracorporeal circulation. In this study, benefits of minimized bypass in CABG were evaluated under particular consideration of patient body mass index and surgeon impact. From 2004 to 2014, 5164 patients underwent coronary bypass surgery (CABG). Conventional cardiopulmonary bypass (CCPB) was used in 2376 patients, minimized cardiopulmonary bypass (MCPB) in 2788 cases. Multivariate regression models were used in the entire cohort and in a propensity score-matched subgroup after expert CABG to figure out clinical differences such as mortality, postoperative renal function, and thromboembolic events. Overall mortality was 1.5% (n = 41) in the MCPB group and 3.5% (n = 82) in CCPB patients (p

The use of minimized cardiopulmonary bypass support to reduce the side effects of extracorporeal circulation is still contradictorily discussed. This study compares perfusion operated by conventional (CCPB) and minimized (MCPB) cardiopulmonary bypass support during coronary artery bypass grafting (CABG). This study includes the data of 5164 patients treated at our department between 2004 and 2014. Tissue perfusion during cardiopulmonary bypass support and cardiac arrest was assessed by means of body mass index, hemodilution, blood pressure with corresponding pump flow and venous oxygen saturation, serum lactate, and serum pH. Hemodilution was more pronounced after CCPB: hemoglobin had dropped to 4.47 ± 0.142 g/dL after CCPB and to 2.77 ± 0.148 g/dL after MCPB (P = 0.0022). Despite the higher pump flow in conventional circuits (4.86-4.95 L/min vs. 4.1-4.18 L/min), mean blood pressure was higher during minimized bypass support (53 ± 10 vs. 56 ± 13 mm Hg [aortic clamping], 57 ± 9 vs. 61 ± 12 mm Hg [34°C], 55 ± 9 vs.59 ± 11 mm Hg [aortic clamp removal], P 0.0001) at all time points. Venous oxygen saturation remained on comparable levels of70% during both conventional and minimized cardiopulmonary bypass support. The increase in serum lactate was more pronounced after CCPB (8.98 ± 1.28 vs. 3.66 ± 1.25 mg/dL, P = 0.0079), corresponding to a decrease in serum pH to acidotic levels (7.33 ± 0.06 vs. 7.35 ± 0.06, P 0.0001). These effects were evident in all BMI ranges. Minimized cardiopulmonary bypass support provides efficient perfusion in all BMI ranges and is thus equivalent to conventional circuits.

Background: Less invasive procedures have replaced open surgical treatment in many cardiovascular disorders. During these interventions, iatrogenic cardiac perforation may ensue, which is a severe complication and requires immediate diagnostic assessment and treatment. Methods: From March 2011 to April 2016, all patients referred to the Dept. of Cardio-thoracic Surgery with the diagnosis of iatrogenic perforation of myocardial wall or great vessels were included into the retrospective study. Complications during transapical transcutaneous aortic valve replacements (TAVR) procedures and percutaneous coronary intervention (PCI) were excluded from analysis. Symptoms, therapeutic strategy, intraoperative findings, and outcome were evaluated. Results: Forty-four patients suffered from myocardial wall or vessel perforation. Most common site of perforation were right (n=26; 59.1%) and left (n=8; 18.2%) ventricle. Other structures were involved in ten cases (22.7%). Open surgical treatment was required in 27 cases (61.4%). Mortality after left and right ventricular laceration was 75.0% and 11.5%, respectively. Most common cause of death was cardiocirculatory failure (n=5). Conclusions: Iatrogenic perforation of myocardial wall or central vessels during percutaneous interventional procedures is a rare but life-threatening complication. Despite immediate treatment efforts, mortality is high, particularly after left ventricular laceration.