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Background: Circulatory support with a catheter-based microaxial flow pump (mAFP) plays a major role in the treatment of severe cardiogenic shock. In most patients who fail to recover while on temporary mechanical circulatory support (tMCS) and who are not eligible for heart transplantation, durable left ventricular assist device (dLVAD) implantation is usually considered a reliable option. This study aimed to describe the outcome of dLVAD therapy following mAFP support and to identify predictors of mortality. Methods: This was a retrospective analysis of data from a multicenter registry on patients who underwent dLVAD implantation following tMCS with a mAFP between January 2017 and October 2022 (n = 332) from 19 European centers. Results: Patients were supported with an Impella 5.5 (n = 92), 5.0 (n = 153) or CP (n = 87) and were transitioned to a HeartWare HVAD (n = 128) or Heartmate 3 (n = 204) during the same period. One hundred and twenty-five patients (39.2%) also required extracorporeal life support before and/or during mAFP therapy. The 30-day and 1-year survival were 87.8% and 71.1%, respectively. The following risk factors for 1-year mortality were identified: age (odds ratio [OR], 1.02), specifically age over 55 years (OR, 1.09), body mass index >30 kg/m2 (OR, 2.2), female sex (OR for male sex, 0.43), elevated total bilirubin (OR, 1.12), and low platelet count (OR, 0.996). Conclusions: Based on the identified risk factors, a risk score for estimating 1-year mortality was calculated to optimize patient selection for dLVAD implantation.

Abstract Aims This study aimed to compare the changes in the left ventricle (LV) and right ventricle (RV) geometry and performance after the implantation of HeartMate II (HMII) and HeartMate 3 (HM3). In addition, we investigated whether the echocardiographic parameters LV sphericity index (LVSI) and the novel pressure‐dimension index (PDI) can predict post‐operative right ventricular failure (RVF). Methods and results Between 2012 and 2020, 46 patients [HMII (n = 22) and HM3 (n = 24)] met the study's criteria and had echocardiography tests pre‐operatively, 6 and 12 months post‐operatively. The LVSI and PDI were calculated together with the standard LV and RV echocardiographic parameters. The mean follow‐up was 24 ± 7 months. In both groups, the LV end‐diastolic diameter (LVEDD) significantly decreased 12 months post‐operatively compared with the pre‐operative values (HMII: 6.4 ± 1.4 cm vs. 5.7 ± 0.9 cm, P = 0.040; HM3: 6.7 ± 1.3 cm vs. 5.5 ± 0.9 cm, P

Abstract Background Surgical aortic valve replacement (SAVR) is an established therapy for severe calcific aortic stenosis. Enhanced recovery after cardiac surgery (ERACS) protocols have been shown to improve outcomes for elective cardiac procedures. The COVID-19 pandemic prompted early extubation post-elective surgeries to preserve critical care resources. Aim of this study To investigate the effects of extubating patients within 6 h post-elective SAVR on hospital and ICU length of stay, mortality rates, ICU readmissions, and postoperative pneumonia. Study Design and methods The retrospective analysis at the University Hospital Aachen, Germany, includes data from 2017 to 2022 and compares a total of 73 elective SAVR patients. Among these, 23 patients were extubated within 6 h (EXT group), while 50 patients remained intubated for over 6 h (INT group). Results The INT group experienced longer postoperative ventilation, needed more vasopressor support, had a higher incidence of postoperative pneumonia, and longer ICU length of stay. No significant differences were noted in overall hospital length of stay, mortality, or ICU readmission rates between the groups. Conclusion This study demonstrates that early extubation in high-risk, multimorbid surgical aortic valve replacement patients is safe, and is associated with a reduction of pneumonia rates, and with shorter ICU and hospital length of stays, reinforcing the benefits of ERACS protocols, especially critical during the COVID-19 pandemic to optimize intensive care use.

AimsChronic kidney disease (CKD) is a risk factor for the development of cardiovascular diseases, e.g., atherosclerosis and calcific aortic valve disease, leading inevitably to valve replacement surgery. CKD patients with bioprosthetic cardiovascular grafts, in turn, have a higher risk of premature graft degeneration. Peroxisome proliferator-activated receptor gamma (PPARγ) activation by pioglitazone has cardio-renal protective properties, and research using a heterotopic valve implantation model has shown anti-degenerative effects of PPARγ activation on bioprosthetic valved grafts (BVG) in rats. The present work aims to analyze a potential protective effect of pioglitazone treatment on BVG in an adenine-induced rat model of CKD.Methods and ResultsBVG of Sprague Dawley rats were heterotopically implanted in Wistar rats in an infrarenal position for 4 and 8 weeks. Animals were distributed into three groups for each time point: 1) control group receiving standard chow, 2) CKD group receiving 0.25% adenine and 3) CKD + pioglitazone group (300 mg per kg of 0.25% adenine chow). BVG function was analyzed by echocardiography. Plasma analytes were determined and explanted grafts were analyzed by semi-quantitative real-time PCR, Western blot analysis, histology and immunohistology.PPARγ activation significantly reduced CKD-induced calcification of aortic and valvular segments of BVG by 44% and 53%, respectively. Pioglitazone treatment significantly also reduced CKD-induced intima hyperplasia by 60%. Plasma analysis revealed significantly attenuated potassium and phosphate levels after pioglitazone treatment. Moreover, PPARγ activation led to significantly decreased interleukin-6 gene expression (by 57%) in BVG compared to CKD animals. Pioglitazone treatment leads to functional improvement of BVG.ConclusionThis study broadens the understanding of the potential value of PPARγ activation in cardio-renal diseases and delineates pioglitazone treatment as a valuable option to prevent bioprosthetic graft failure in CKD. Further mechanistic studies, e.g., using small molecules activating PPARγ signaling pathways, are necessary for the evaluation of involved mechanisms. Additionally, the translation into pre-clinical studies using large animals is intended as the next research project.

Abstract Background Left ventricular assist devices (LVAD) are an established treatment for end-stage left ventricular heart failure. Parameters are needed to identify the most appropriate patients for LVADs. This study aimed to evaluate pectoral muscle mass and density as prognostic parameters. Methods This single-center study included all patients with LVAD implantation between January 2010 and October 2017 and a preoperative chest CT scan. Pectoral muscle mass was assessed using the Pectoralis Muscle Index (PMI, surface area indexed to height, cm2/m2) and pectoral muscle density by Hounsfield Units (HU). Overall mortality was analyzed with Kaplan–Meier survival analysis and 1-year and 3-year mortality with receiver operating characteristic (ROC) curves and Cox regression models. Results 57 patients (89.5% male, mean age 57.8 years) were included. 64.9% of patients had end-stage left ventricular failure due to ischemic heart disease and 35.1% due to dilated cardiomyopathy. 49.2% of patients had preoperative INTERMACS profile of 1 or 2 and 33.3% received mechanical circulatory support prior to LVAD implantation. Total mean PMI was 4.7 cm2/m2 (± 1.6), overall HU of the major pectoral muscle was 39.0 (± 14.9) and of the minor pectoral muscle 37.1 (± 16.6). Mean follow-up was 2.8 years (± 0.2). Mortality rates were 37.5% at 1 year and 48.0% at 3 years. Neither PMI nor HU were significantly associated with overall mortality at 1-year or 3-year. Conclusions The results of our study do not confirm the association between higher pectoral muscle mass and better survival after LVAD implantation previously described in the literature.

Abstract Incidence of SARS‐CoV‐2 remains high in the population. Consequently, an increasing percentage of reported organ donors are also SARS‐CoV‐2 positive. Although donors may not have experienced COVID‐19‐related symptoms, there is a chance of unnoticed cardiovascular effects associated with this disease. Therefore, SARS‐CoV‐2 donor grafts have been regularly rejected for heart transplantation (HTx) for a long time. We hereby present three consecutive patients receiving grafts from SARS‐CoV‐2 positive donors (defined by the PCR cycle threshold value

Abstract Background Cytomegalovirus (CMV) infections after heart transplantation (HTx) can cause cardiac allograft vasculopathy. Consequently, monitoring and prophylaxis for cytomegalovirus deoxyribonucleic acid (CMV‐DNAemia) within the first weeks after HTx is recommended. Methods All patients who underwent HTx between September 2010 and 2021 surviving the first 90 days (n = 196) were retrospectively reviewed. The patients were divided on the prevalence of CMV‐DNAemia during the first postoperative year after the end of the prophylaxis. A total of n = 35 (20.1%) developed CMV‐DNAemia (CMV group) and were compared to patients without CMV‐DNAemia (controls, n = 139). The remaining patients (n = 22) were excluded due to incomplete data. Results Positive donors and negative recipients (D+/R−) and negative donors and positive recipients (D−/R+) serology was significantly increased and D−/R− decreased in the CMV group (p

Abstract Background Acute aortic dissection type A (AADA) is associated with high perioperative morbidity and mortality. A novel non-covered hybrid prosthesis (AMDS, CryoLife, Kennesaw, USA) can be easily implanted to stabilize the true lumen. However, the role of AMDS for patients requiring additional aortic root surgery has not been described. Methods Between 2010 and 2020 a total of n = 370 patients underwent surgery for AADA in our department. Of those, n = 120 underwent treatment for aortic root in addition to proximal arch replacement without resection of the aorta beyond the innominate artery (Control, n = 111) and were compared to patients who received additional AMDS implantation (AMDS, n = 9). Results Aortic valve repair was performed in 48.6% (Control) and in 55.6% of AMDS patients. Cardiopulmonary bypass (Control: 248 ± 76 min, AMDS: 313 ± 53 min, P

Abstract The number of patients waiting for heart transplantation (HTX) is increasing. Thus, identification of outcome-relevant factors is crucial. This study aimed to identify perioperative factors associated with days alive and out of hospital (DAOH)—a patient-centered outcome to quantify life impact—after HTX. This retrospective cohort study screened 187 patients who underwent HTX at university hospital Duesseldorf, Germany from September 2010 to December 2020. The primary endpoint was DAOH at 1 year. Risk factors for mortality after HTX were assessed in univariate analysis. Variables with significant association were entered into multivariable quantile regression. In total, 175 patients were included into analysis. Median DAOH at 1 year was 295 (223–322) days. In univariate analysis the following variables were associated with reduced DAOH: recipient or donor diabetes pre-HTX, renal replacement therapy (RRT), VA-ECMO therapy, recipient body mass index, recipient estimated glomerular filtration rate (eGFR) and postoperative duration of mechanical ventilation. After adjustment, mechanical ventilation, RRT, eGFR and recipient diabetes showed significant independent association with DAOH. This study identified risk factors associated with reduced DAOH at 1-year after HTX. These findings might complement existing data for outcome of patients undergoing HTX.

Abstract Patients undergoing heart transplantation (HTx) with active infection of left ventricular assist devices (LVAD) are at high risk for postoperative infections. Between 2021 and 2022, five (P1–P5) of a total of n = 44 patients underwent HTx in our department while suffering from LVAD infection. Postoperatively, patients received adjuvant IgM‐enriched human intravenous immunoglobulin (IGM‐IVIG), consisting of 76% IgG, 12% IgM, and 12% IgA as a novel approach to prevent infective complications. While in P1, P2, and P4, LVAD driveline infection was known before HTx; in P3 and P5, abscess of device pocket was found incidentally during HTx. After a single dose of IGM‐IVIG, all patients showed adequate rise in serum immunoglobulins. In the postoperative course, no patient developed infective complications. All patients were successfully discharged and in good condition at the last follow‐up. Therefore, IGM‐IVIG seems to be an effective adjuvant treatment for patients undergoing HTx with LVAD infections.

Introduction: Left ventricular assist device (LVAD) implantation is a common therapy for end-stage heart failure. Heart failure patients often present with atrial fibrillation (AF). The purpose of this study was to evaluate the influence of preoperative AF as well as vascular complications on outcome in LVAD patients. Methods: Between 01/2010 and 12/2017, 168 patients (141 male) with end-stage heart failure underwent LVAD implantation at a single center. Patient outcome was retrospectively studied by using the Kaplan-Meier method for analyzing crude survival as well as Cox regression for analyzing risk factors. Results: Sixty-two patients suffered from preoperative atrial fibrillation at LVAD implantation. Mean age was 56.8±11.9 years (range: 22–79) and 141 (84%) were male. Postoperative vascular or visceral surgical management due to malperfusion was needed in 27 patients (16.1%) and did not correlate with postoperative mortality (P=0.121, HR=1.587, CI=0.885–2.845). Patients with preoperative AF had a worse outcome in the Kaplan-Meier analysis (P=0.069). In contrast, cox regression showed that postoperative AF could not to be considered to be an independent predictor of mortality in this study group. Conclusion: Our data suggest that preoperative AF may be a potential predictor of mortality and impaired long-term outcome in LVAD patients. In contrast, preoperative ECLS and vascular or visceral surgery after LVAD implantation did not represent limiting factors with regard to mortality after LVAD implantation.

Background Neurologic events during primary stay in heart transplant (HTx) recipients may be associated with reduced outcome and survival, which we aim to explore with the current study. Methods and Results We screened and included all patients undergoing HTx in our center between September 2010 and December 2022 (n=268) and checked for the occurrence of neurologic events within their index stay. Neurologic events were defined as ischemic stroke, hemorrhage, hypoxic ischemic injury, or acute symptomatic neurologic dysfunction without central nervous system injury. The cohort was then divided into recipients with (n=33) and without (n=235) neurologic events after HTx. Using a multivariable Cox regression model, the association of neurologic events after HTx and survival was assessed. Recipients with neurologic events displayed a longer intensive care unit stay (30 versus 16 days; P=0.009), longer mechanical ventilation (192 versus 48 hours; P

Abstract Aim The quality of the donor heart is known to have a crucial effect on outcome after heart transplantation (HTx). Although leading to brain death in the end, the initial cause of death of the donor and its potential influences on organ quality are heterogeneous. However, it is still controversial to which extent the donor cause of death is associated with outcome or survival post‐HTx. Methods and results We included all patients undergoing HTx in our centre between September 2010 and June 2021 (n = 218). Recipients were divided in five groups related to their donor cause of death: intracerebral bleeding (‘ICB’, n = 95, 44%), traumatic brain injury (‘trauma’, n = 54, 25%), hypoxic brain damage (‘hypoxic’, n = 34, 16%), cerebrovascular (‘vascular’, n = 15, 7%), or other cause (n = 20, 9%). Baseline characteristics, perioperative parameters, and survival after 30 and 90 days as well as 5 years after transplantation were collected. Results Intracerebral bleeding in donors compared with traumatic brain injury is associated with higher probability of need for ECLS post‐HTx (35% vs. 19%, P = 0.04) and significantly reduced survival up to 5 years post‐HTx (i.e. 1 year survival: 61% vs. 95%, P

Abstract Aims Implantation of left ventricular assist devices (LVADs) as a bridge to transplant or as destination therapy is increasing. The selection of suitable patients and outcome assessment belong to the key challenges. Mortality has traditionally been a focus of research in this field, but literature on quality of life is very limited. This study aimed to identify perioperative factors influencing patients' life as measured by days alive and out of hospital (DAOH) in the first year after LVAD implantation. Methods and results This retrospective single‐centre cohort study screened 227 patients who underwent LVAD implantation at the University Hospital Duesseldorf, Germany, between 2010 and 2020. First, the influence of 10 prespecified variables on DAOH was investigated by univariate analysis. Second, multivariate quantile regression was conducted including all factors with significant influence on DAOH in the univariate model. Additionally, the impact of all variables on 1 year mortality was investigated using Kaplan–Meier curves to oppose DAOH and mortality. In total, 221 patients were included into analysis. As pre‐operative factors, chronic kidney disease (CKD), pre‐operative mechanical circulatory support (pMCS), and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) stadium

Abstract Thromboembolism is frequent in infective endocarditis (IE). However, the optimal antithrombotic regimen in IE is unknown. Staphylococcus aureus (SA) is the leading cause of IE. First studies emphasize increased platelet reactivity by SA. In this pilot study, we hypothesized that platelet reactivity is increased in patients with SA− IE, which could be abrogated by antiplatelet medication. We conducted a prospective, observatory, single-center cohort study in 114 patients with IE, with four cohorts: (1) SA coagulase positive IE without aspirin (ASA) medication, (2) coagulase negative IE without ASA, (3) SA coagulase positive IE with ASA, (4) coagulase negative IE with ASA. Platelet function was measured by Multiplate electrode aggregometry, blood clotting by ROTEM thromboelastometry. Bleeding events were assessed according to TIMI classification. In ASA-naïve patients, aggregation with ADP was increased with coag. pos. IE (coagulase negative: 39.47 ± 4.13 AUC vs. coagulase positive: 59.46 ± 8.19 AUC, p = 0.0219). This was abrogated with ASA medication (coagulase negative: 42.4 ± 4.67 AUC vs. coagulase positive: 45.11 ± 6.063 AUC p = 0.7824). Aspirin did not increase bleeding in SA positive patients. However, in SA negative patients with aspirin, red blood cell transfusions were enhanced. SA coagulase positive IE is associated with increased platelet reactivity. This could be abrogated by aspirin without increased bleeding risk. The results of this pilot study suggest that ASA might be beneficial in SA coagulase positive IE. This needs to be confirmed in clinical trials.

Abstract Aims Primary graft dysfunction (PGD) is a feared complication after heart transplantation (HTX). HTX patients frequently receive veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) until graft recovery. Long‐term mortality of patients weaned from VA‐ECMO after HTX is comparable with non‐ECMO patients. However, impact on quality of life is unknown. This study investigated days alive and out of hospital (DAOH) as patient‐centred outcome in HTX patients at 1 year after surgery. Methods and results This retrospective single‐centre cohort study included patients who underwent HTX at the University Hospital Düsseldorf, Germany, from 2010 to 2020. Main exposure was VA‐ECMO due to PGD. VA‐ECMO and non‐VA‐ECMO patients were compared regarding the primary endpoint DAOH at 1 year after HTX. Subgroup analysis for patients weaned from VA‐ECMO was performed. In total, 144 patients were included into analysis; 1 year mortality was significantly lower in non‐ECMO patients [non‐ECMO 14.3% (14/98) vs. VA‐ECMO 34.8% (16/46), adjusted hazard ratio: 0.32, 95% confidence interval: 0.15–0.74; P = 0.002]. Mortality did not differ significantly between patients weaned from VA‐ECMO and non‐ECMO patients [non‐ECMO 14.3% (14/98) vs. VA‐ECMO (weaned) 18.9% (7/37), adjusted hazard ratio: 0.72, 95% confidence interval: 0.27–1.90; P = 0.48]. DAOH were significantly higher in non‐ECMO patients compared with VA‐ECMO patients and patients weaned from VA‐ECMO [non‐ECMO vs. VA‐ECMO: median 310 (inter‐quartile range 277–327) days vs. 243 (0–288) days; P

Abstract Aims Donor heart shortage leads to increasing use of left ventricular assist device (LVAD) as bridge‐to‐transplant or destination therapy. Prolonged LVAD support is associated with aortic valve insufficiency, representing a relevant clinical problem in LVAD patients. Nevertheless, the impact of LVAD support on inflammation, remodelling, and chondro‐osteogenic differentiation of the aortic valve is still not clearly understood. The aim of the study is to evaluate the impact of LVAD support on structural and molecular alterations of the aortic valve. Methods and results During heart transplantation, aortic valves of 63 heart failure patients without (n = 22) and with LVAD support (n = 41) were collected and used for analysis. Data on clinical course as well as echocardiographic data were analysed. Calcification and markers of remodelling, chondro‐osteogenic differentiation, and inflammation were evaluated by computed tomography, by mRNA analysis and by histology and immunohistochemistry. Expression of inflammation markers of the LVAD group was analysed with regard to levels of C‐reactive protein and driveline infections. Calcium accumulation and mRNA expression of determined markers were correlated with duration of LVAD support. Data were also analysed relating to aortic valve opening and aortic valve insufficiency. There was no difference in the frequency of cardiovascular risk factors or comorbidities between the patient groups. Expression of matrix metalloproteinase‐9 (P = 0.007), alpha‐smooth muscle actin (P = 0.045), and osteopontin (P = 0.003) were up‐regulated in aortic valves of LVAD patients. Histological appearance of the aortic valve was similar in patients with or without LVAD, and computed tomography‐based analysis not yet revealed significant difference in tissue calcification. Expression of interferon gamma (P = 0.004), interleukin‐1 beta (P

Abstract The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasing, but mortality remains high. Early assessment of prognosis is challenging and valid markers are lacking. This study aimed to investigate Neutrophil–Lymphocyte Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Procalcitonin (PCT) for early assessment of prognosis in patients undergoing VA-ECMO. This retrospective single-center cohort study included 344 consecutive patients ≥ 18 years who underwent VA-ECMO due to cardiogenic shock. Main exposures were NLR, PLR and PCT measured within 24 h after VA-ECMO initiation. The primary endpoint was all-cause in-hospital mortality. In total, 92 patients were included into final analysis (71.7% male, age 57 ± 14 years). In-hospital mortality rate was 48.9%. Receiver operating characteristics (ROC) curve revealed an area under the curve (AUC) of 0.65 [95% confidence interval (CI) 0.53–0.76] for NLR. The AUCs of PLR and PCT were 0.47 [95%CI 0.35–0.59] and 0.54 [95%CI 0.42–0.66], respectively. Binary logistic regression showed an adjusted odds ratio of 3.32 [95%CI 1.13–9.76] for NLR, 1.0 [95%CI 0.998–1.002] for PLR and 1.02 [95%CI 0.99–1.05] for PCT. NLR is independently associated with in-hospital mortality in patients undergoing VA-ECMO. However, discriminative ability is weak. PLR and PCT seem not to be suitable for this purpose.

Abstract Objective Cytomegalovirus (CMV) infections are correlated with complications following heart transplantation (HTx) and impaired outcome. The impact of a serologic mismatch between donor and recipient and the necessity of prophylactic virostatic medication is still a matter of concern. Methods We retrospectively reviewed all patients that underwent HTx between 2010 and 2020 in our department. The recipients (n = 176) could be categorized into four risk groups depending on their serologic CMV matching (D+/R− = donor CMV‐IgG positive and recipient CMV‐IgG negative, n = 32; D−/R+, n = 51; D−/R−, n = 35; D+/R+, n = 58). All patients followed the same protocol of CMV prophylaxis with application of ganciclovir/valganciclovir and intravenous CMV hyperimmune globulin. RESULTS Incidence of postoperative morbidity such as primary graft dysfunction, neurological events, infections, and graft rejection were comparable between all groups (p > .05). However, the incidence of postoperative acute kidney injury with hemodialysis was by trend increased in the D−/R+ group (72.0%) compared to the other groups. In‐hospital CMV‐DNAemia was observed in serologic positive recipients only (D+/R−: 0.0%, D−/R+: 25.0%, D−/R−: 0.0%, D+/R+: 13.3%, p

Abstract Aims Acute cellular rejection (ACR) following heart transplantation (HTX) is associated with long‐term graft loss and increased mortality. Disturbed mitochondrial bioenergetics have been identified as pathophysiological drivers in heart failure, but their role in ACR remains unclear. We aimed to prove functional disturbances of myocardial bioenergetics in human heart transplant recipients with mild ACR by assessing myocardial mitochondrial respiration using high‐resolution respirometry, digital image analysis of myocardial inflammatory cell infiltration, and clinical assessment of HTX patients. We hypothesized that (i) mild ACR is associated with impaired myocardial mitochondrial respiration and (ii) myocardial inflammation, systemic oxidative stress, and myocardial oedema relate to impaired mitochondrial respiration and myocardial dysfunction. Methods and results We classified 35 HTX recipients undergoing endomyocardial biopsy according International Society for Heart and Lung Transplantation criteria to have no (0R) or mild (1R) ACR. Additionally, we quantified immune cell infiltration by immunohistochemistry and digital image analysis. We analysed mitochondrial substrate utilization in myocardial fibres by high‐resolution respirometry and performed cardiovascular magnetic resonance (CMR). ACR (1R) was diagnosed in 12 patients (34%), while the remaining 23 patients revealed no signs of ACR (0R). Underlying cardiomyopathies (dilated cardiomyopathy 50% vs. 65%; P = 0.77), comorbidities (type 2 diabetes mellitus: 50% vs. 35%, P = 0.57; chronic kidney disease stage 5: 8% vs. 9%, P > 0.99; arterial hypertension: 59% vs. 30%, P = 0.35), medications (tacrolimus: 100% vs. 91%, P = 0.54; mycophenolate mofetil: 92% vs. 91%, P > 0.99; prednisolone: 92% vs. 96%, P > 0.99) and time post‐transplantation (21.5 ± 26.0 months vs. 29.4 ± 26.4 months, P = 0.40) were similar between groups. Mitochondrial respiration was reduced by 40% in ACR (1R) compared with ACR (0R) (77.8 ± 23.0 vs. 128.0 ± 33.0; P 14 CD3+‐lymphocytes/mm2 (100% sensitivity, 82% specificity; P

Abstract Aims Extracorporeal life support (ECLS) represents a popular treatment option for therapy‐refractory circulatory failure and substantially increases survival. However, comprehensive follow‐up (FU) data beyond short‐term survival are mostly lacking. Here, we analyse functional recovery and quality of life of longer‐term survivors. Methods and results Between 2011 and 2016, a total of n = 246 consecutive patients were treated with ECLS for therapy‐refractory circulatory failure in our centre. Out of those, 99 patients (40.2%) survived the first 30 days and were retrospectively analysed. Fifty‐eight patients (23.6%) were still alive after a mean FU of 32.4 ± 16.8 months. All surviving patients were invited to a prospective, comprehensive clinical FU assessment, which was completed by 39 patients (67.2% of survivors). Despite high incidence of early functional impairments, FU assessment revealed a high degree of organ and functional recovery with more than 70% of patients presenting with New York Heart Association class ≤ II, 100% free of haemodialysis, 100% free of moderate or severe neurological disability, 71.8% free of moderate or severe depression, and 84.4% of patients reporting to be caring for themselves without need for assistance. Conclusions Patients surviving the first 30 days of ECLS therapy for circulatory failure without severe adverse events have a quite favourable outcome in terms of subsequent survival as well as functional recovery, showing the potential of ECLS therapy for patients to recover. Patients can recover even after long periods of mechanically support and regain physical and mental health to participate in their former daily life and work.

Abstract Adequate immune response to vaccination remains a challenge in patients after solid organ transplantation. We report a case of a 61‐year‐old male patient who received a left ventricular assist device as a bridge to transplant therapy. Three months before transplantation, he suffered mild SARS‐CoV‐2 infection and was successfully discharged thereafter. Eight days before his successful heart transplantation, he received mRNA BNT 162b2 vaccination. Immediately after transplantation, we detected sufficient rise of nucleocapsid and spike antibodies despite immune suppression therapy. We suspect potential booster effects of the previous SARS‐CoV‐2 infection giving rise to adequate immune response following single vaccination.

Abstract Aims Pre‐operative or post‐operative heart failure (HF) and cardiogenic shock of various natures frequently remain refractory to conservative treatment and require mechanical circulatory support. We report our clinical experience with large Impella systems (5.0 or 5.5; i.e. Impella 5+) (Abiomed Inc., Boston, USA) and evaluate the parameters that determined patient outcome. Methods and results The initial 50 cases of Impella 5+ implanted for acute HF between November 2018 and August 2020 at a single centre were enrolled in this study. Data, including preoperative characteristics, perioperative clinical course information, and post‐operative outcomes, were retrospectively collected from the hospital data management and quality assurance system. Descriptive and univariate analyses were performed. Among the 49 patients in this study, 28 (56.0%) survived in the first 30 days post‐operatively, and 3 died of non‐cardiac reasons later. In‐hospital mortality was significantly higher in patients with biventricular failure [P

Abstract Aims Percutaneous left ventricular assist devices (pVADs) are used to haemodynamically stabilize patients with cardiogenic shock (CS) caused by acute myocardial infarction (AMI). One out of every two patients has a non‐ischaemic cause of CS, and these patients differ profoundly from patients with AMI‐related CS. We assessed the usefulness of pVAD support for patients with non‐ischaemic CS. Methods and results We analysed 106 patients with CS and Impella® support between 2015 and 2018. CS was non‐ischaemic in 36 patients and AMI‐related in 70 patients. Compared with the AMI group, those in the non‐ischaemic group were significantly younger [median age 62 (50.8, 70.8) years vs. 68 (58.0, 75.5) years, P = 0.007] and had more patients with severely reduced left ventricular function (94% vs. 79%, P = 0.035) and worse glomerular filtration rate [45 (27, 57) mL/min vs. 60 (44, 78) mL/min]. Propensity score matching yielded 31 patients with non‐ischaemic CS and 31 patients with AMI‐related CS, without a difference in baseline laboratory values or comorbidities. In both groups, pVAD support was performed along with haemodynamic stabilization, reduction of catecholamines and normalization of lactate levels. In 7 days, systolic blood pressure increased from 91 (80, 101) mmHg at baseline to 100 (100, 120) mmHg in the non‐ischaemic CS group (P = 0.001) and 89 (80, 100) mmHg at baseline to 112 (100, 128) mmHg in the AMI‐related CS group (P = 0.001). Moreover, in 7 days, the need of catecholamines (calculated as vasoactive‐inotropic score) decreased from 32.0 (11.1, 47.0) at baseline to 5.3 (0, 16.1) in the non‐ischaemic group (P = 0.001) and from 35.2 (18.11, 67.0) to zero (0, 0) in the AMI‐related CS group (P = 0.001). Lactate level decreased from 3.8 (2.8, 5.9) mmol/L at baseline to 1.0 (0.8, 2.1) mmol/L (P = 0.001) in the non‐ischaemic CS group and from 3.8 (2.6, 6.5) mmol/L to 1.2 (1.0, 2.0) mmol/L in the AMI‐related group (P = 0.001). In the non‐ischaemic CS group, eight patients (25.8%) were upgraded to veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) or long‐term mechanical circulatory support. Two of these upgraded patients received heart transplantation. In the AMI group, eight patients (25.8%) were upgraded to VA‐ECMO or long‐term mechanical circulatory support. Ninety‐day survival did not significantly differ between the groups (non‐ischaemic CS group 48.4%, AMI‐related CS group 45.2%, P = 0.799). Conclusions pVAD support is useful for haemodynamic stabilization of patients with non‐ischaemic CS and is valuable as a bridge to patients' recovery or long‐term left ventricular support and heart transplantation.

Diabetes and its major key determinants insulin resistance and hyperglycemia are known risk factors for calcific aortic valve disease (CAVD). The processes leading to molecular and structural alterations of the aortic valve are yet not fully understood. In previous studies, we could show that valvular interstitial cells (VIC) display canonical elements of classical insulin signaling and develop insulin resistance upon hyperinsulinemia and hyperglycemia accompanied by impaired glucose metabolism. Analyses of cultured VIC and aortic valve tissue revealed extracellular matrix remodeling and degenerative processes. Since PI3K signaling through mammalian target of rapamycin (mTOR) is involved in fibrotic processes of the heart, we aim at further functional investigation of this particular Akt-downstream signaling pathway in the context of diabetes-induced CAVD. Primary cultures of VIC were treated with hyperinsulinemia and hyperglycemia. Phosphorylation of mTOR(Ser2448) was determined by Western blot analysis after acute insulin stimulus. Inhibition of mTOR phosphorylation was performed by rapamycin. Phosphorylation of mTOR complex 1 (MTORC1) downstream substrates 4E-BP1(Thr37/46) and P70S6K(Thr389), and MTORC2 downstream substrate Akt(Ser473) as well as the PDK1-dependent phosphorylation of Akt(Thr308) was investigated. Markers for extracellular matrix remodeling, cell differentiation and degenerative changes were analyzed by Western blot analysis, semi-quantitative real-time PCR and colorimetric assays. Hyperinsulinemia and hyperglycemia lead to alterations of VIC activation, differentiation and matrix remodeling as well as to an abrogation of mTOR phosphorylation. Inhibition of mTOR signaling by rapamycin leads to a general downregulation of matrix molecules, but to an upregulation of α-smooth muscle actin expression and alkaline phosphatase activity. Comparison of expression patterns upon diabetic conditions and rapamycin treatment reveal a possible regulation of particular matrix components and key degeneration markers by MTORC1 downstream signaling. The present findings broaden the understanding of mitogenic signaling pathways in VIC triggered by hyperinsulinemia and hyperglycemia, supporting the quest for developing strategies of prevention and tailored treatment of CAVD in diabetic patients.

Objectives: Decellularized extracellular matrix (dECM) is increasingly used in a wide range of regenerative medicine applications and may also offer the potential to support injured myocardium. Here, we evaluated the myocardial gene expression pattern after myocardial infarction (MI) in a standardized rodent LAD-ligation model with and without ventricular stabilization with a customized, cardiac dECM-based scaffold (cdECM).Methods: MI was induced in male Wistar rats by standard LAD-ligation and confirmed 14 days post-intervention by echocardiographic parameters (FAS

Myat Soe Thet et al. published a letter [...]

To investigate the pathogenic mechanisms of calcified aortic valve disease (CAVD), it is necessary to develop a new three-dimensional model that contains valvular interstitial cells (VIC) and valvular endothelial cells (VEC). For this purpose, ovine aortic valves were processed to isolate VIC and VEC that were dissolved in an alginate/gelatin hydrogel. A 3D-bioprinter (3D-Bioplotter® Developer Series, EnvisionTec, Gladbeck, Germany) was used to print cell-laden tissue constructs containing VIC and VEC which were cultured for up to 21 days. The 3D-architecture, the composition of the culture medium, and the hydrogels were modified, and cell viability was assessed. The composition of the culture medium directly affected the cell viability of the multicellular tissue constructs. Co-culture of VIC and VEC with a mixture of 70% valvular interstitial cell and 30% valvular endothelial cell medium components reached the cell viability best tested with about 60% more living cells compared to pure valvular interstitial cell medium (p = 0.02). The tissue constructs retained comparable cell viability after 21 days (p = 0.90) with different 3D-architectures, including a “sandwich” and a “tube” design. Good long-term cell viability was confirmed even for thick multilayer multicellular tissue constructs. The 3D-bioprinting of multicellular tissue constructs with VEC and VIC is a successful new technique to design tissue constructs that mimic the structure of the native aortic valve for research applications of aortic valve pathologies.

Abstract Antibody‐mediated graft rejection caused by donor‐specific antibodies (DSA‐MR) remains a serious problem after heart transplantation (HTx). IgM‐enriched human intravenous immunoglobulin (IGM‐IVIG) consists of 76% IgG, 12% IgM, and 12% IgA and provides a new multifactorial approach for DSA‐MR. Between 2017 and 2020, four (P1–4) of 102 patients developed DSA‐MR after HTx in our department and were repetitively treated with IGM‐IVIG in combination with anti‐thymocyte globulin. While in P1 and P4, DSA‐MR occurred within the early post‐operative interval, P2 and P3 developed DSA‐MR approximately 1 year after transplantation. An impairment of ventricular function was observed in three of four patients. Furthermore, P1 and P4 suffered from malign ventricular arrhythmias. After the application of IGM‐IVIG, the ventricular function recovered, and all patients could be discharged from the hospital. As part of a multifactorial therapeutic approach, treatment with IGM‐IVIG seems to be a safe and effective strategy to address DSA‐MR.

Abstract Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) supports patients suffering from refractory cardiogenic shock. Thromboembolic complications (TeC) are common in VA-ECMO patients and are associated with increased morbidity and mortality. Valid markers to predict TeC in VA-ECMO patients are lacking. The present study investigated the predictive value of baseline Fibrinogen–Albumin-Ratio (FAR) for in-hospital TeC in patients undergoing VA-ECMO. This retrospective cohort study included patients who underwent VA-ECMO therapy due to cardiogenic shock at the University Hospital Duesseldorf, Germany between 2011 and 2018. Main exposure was baseline FAR measured at initiation of VA-ECMO therapy. The primary endpoint was the in-hospital incidence of TeC. In total, 344 patients were included into analysis (74.7% male, mean age 59 ± 14 years). The in-hospital incidence of TeC was 34%. Receiver operating characteristics (ROC) curve of FAR for in-hospital TeC revealed an area under the curve of 0.67 [95% confidence interval (CI) 0.61–0.74]. Youden index determined a cutoff of 130 for baseline FAR. Multivariate logistic regression revealed an adjusted odds-ratio of 3.72 [95% CI 2.26–6.14] for the association between FAR and TeC. Baseline FAR is independently associated with in-hospital TeC in patients undergoing VA-ECMO. Thus, FAR might contribute to the prediction of TeC in this cohort.

Despite the growing utilization of a large microaxial pump, i. e., Impella 5.0 or 5.5 (Abiomed Inc., Danvers, MA, USA) (Impella 5+) for patients with cardiogenic shock (CS), adverse events including the necessity of re-implantation have not been well discussed. In all 67 patients, in-hospital mortality was 52.2% (n = 35). Explantation of Impella 5+ was performed in 39 patients (58.2%), 22 of whom (32.8%) recovered under Impella 5+, and ten further patients (14.9%) survived after a successful transition to permanent mechanical circulatory support. Embolic events were considerable complications in each access. They occurred in the right arm after the removal of Impella 5+ via a subclavian artery (SA) (n = 3, 9.1%) or in the form of leg ischemia in patients with Impella 5+ via femoral artery (FA) (n = 2, 33.3%). Re-implantation was necessary for 10 patients (14.9%) due to 1) recurrent CS (n = 3), 2) pump thrombosis (n = 5), or 3) pump dislocation (n = 2), all of which were successfully performed via the same access route. In univariate analysis, FA access was a significant risk factor for Impella dysfunction compared to SA access (FA vs. SA, 42.9% vs. 9.8%, p < 0.05, odds ratio 6.88). No statistical difference of overall mortality was observed in patients with Impella 5+ re-implantation (n = 10) compared to patients with primary Impella 5+ support (n = 57) (80.0% (n = 8/10) vs. 47.4% (n = 27/57), p = 0.09). Our results suggested the acceptable clinical outcome of Impella 5+ despite a 15% re-implantation rate. Our observational data may merit further analysis of anticoagulation strategies, including risk stratification for embolic events.

IntroductionAcute aortic dissection type A (AADA) is associated with high perioperative morbidity and mortality. A novel non-covered hybrid prosthesis (Ascyrus Medical Dissection Stent (AMDS) Hybrid Prosthesis, Cryolife/Jotec, Hechingen, Germany) can be easily implanted to stabilize the true lumen (TL), improve remodeling, and preserve organ perfusion. Although developed for implantation in aortic zone 0, occasionally, partial replacement of the aortic arch and further distal implantation of AMDS may appear favorable. Implantation of AMDS with anastomosis line beyond zone 0 has not been described yet.Materials and MethodsBetween 08/2019 and 12/2020, a total of n = 97 patients were treated due to AADA at a single University hospital. Of those, n = 28 received an AMDS hybrid prosthesis, of whom in eight patients, due to intraoperative finding the distal anastomosis line was placed distal to the brachiocephalic trunk. Three patients had AMDS implantation in zone I and four were treated by implantation of the prostheses in zone II, and one patient had the implantation performed in zone III. Clinical outcome and the development of a proportional area of TL and false lumen (FL) at defined levels of the thoracic aorta were analyzed.ResultsNone of the surviving patients (87.5%) showed signs of clinical malperfusion (i.e., stroke, spinal cord injury, and need for dialysis). A postoperative CT scan showed an open TL in all patients. The proportion of TL with respect to total aortic diameter (TL+FL) was postoperatively significantly higher in zone III (p = 0.016) and at the level of T11 (p = 0.009). The mean area of TL+FL was comparable between pre- and postoperative CT-scan (p = n.s.). One patient with preoperative resuscitation died of multiple organ failure on extracorporeal life support on postoperative day 3.ConclusionImplantation of AMDS can be safely performed in patients who need partial replacement of the aortic arch beyond zone 0. The advantages of the AMDS can be combined with those of the total arch repair (remodeling of the arch and prevention of TL collapse) without the possible disadvantages (risk of spinal cord injury).

BackgroundRepeat hospitalizations, complications, and psychosocial burdens are common in patients with left ventricular assist devices (LVAD). Specialist palliative care (sPC) involvement supports patients during decision-making until end-of-life. In the United States, guidelines recommend early specialist palliative care (esPC) involvement prior to implantation. Yet, data about sPC and esPC involvement in Europe are scarce.Materials and MethodsThis is a retrospective descriptive study of deceased LVAD patients who had received sPC during their LVAD-related admissions to two university hospitals in Duesseldorf, Germany and Basel, Switzerland from 2010 to 2021. The main objectives were to assess: To which extent have LVAD patients received sPC, how early is sPC involved? What are the characteristics of those, how did sPC take place and what are key challenges in end-of-life care?ResultsIn total, 288 patients were implanted with a LVAD, including 31 who received sPC (11%). Twenty-two deceased LVAD patients (19 male) with sPC were included. Mean patient age at the time of implantation was 67 (range 49–79) years. Thirteen patients (59%) received LVAD as destination therapy, eight patients (36%) were implanted as bridge to transplantation (BTT), and one as an emergency LVAD after cardiogenic shock (5%). None of the eight BTT patients received a heart transplantation before dying. Most (n = 13) patients lived with their family and mean Eastern Cooperative Oncology Group (ECOG) performance status was three. Mean time between LVAD implantation and first sPC contact was 1.71 years, with a range of first sPC contact from 49 days prior to implantation to more than 6 years after. Two patients received esPC before implantation. In Duesseldorf, mean time between first sPC contact and in-hospital death was 10.2 (1–42) days. In Basel, patients died 16 (0.7–44) months after first sPC contact, only one died on the external sPC unit. Based on thorough examination of two case reports, we describe key challenges of sPC in LVAD patients including the necessity for sPC expertise, ethical and communicative issues as well as the available resources in this setting.ConclusionDespite unequivocal recommendations for sPC in LVAD patients, the integration of sPC for these patients is yet not well established.

Abstract Aims Heart transplantation (HTx) represents optimal care for advanced heart failure. Left ventricular assist devices (LVADs) are often needed as a bridge‐to‐transplant (BTT) therapy to support patients during the wait for a donor organ. Prolonged support increases the risk for LVAD complications that may affect the outcome after HTx. Methods and results A total of 342 patients undergoing HTx after LVAD as BTT in a 10‐year period in two German high‐volume HTx centres were retrospectively analysed. While 73 patients were transplanted without LVAD complications and with regular waiting list status (T, n = 73), the remaining 269 patients were transplanted with high urgency status (HU) and further divided with regard to the observed leading LVAD complications (infection: HU1, n = 91; thrombosis: HU2, n = 32; stroke: HU3, n = 38; right heart failure: HU4, n = 41; arrhythmia: HU5, n = 23; bleeding: HU6, n = 18; device malfunction: HU7, n = 26). Postoperative hospitalization was prolonged in patients with LVAD complications. Analyses of perioperative morbidity revealed no differences regarding primary graft dysfunction, renal failure, and neurological events except postoperative infections. Short‐term survival, as well as Kaplan–Meier survival analysis, indicated comparable results between the different study groups without disadvantages for patients with LVAD complications. Conclusions Left ventricular assist device therapy can impair the outcome after HTx. However, the occurrence of LVAD complications may not impact on outcome after HTx. Thus, we cannot support the prioritization or discrimination of HTx candidates according to distinct mechanical circulatory support‐associated complications. Future allocation strategies have to respect that device‐related complications may define urgency but do not impact on the outcome after HTx.

Abstract Background Femoral cannulation for extracorporeal circulation (ECC) is a standard procedure for minimally invasive cardiac surgery (MICS) of the atrio-ventricular valves. Vascular pathologies may cause serious complications. Preoperative computed tomography-angiography (CT-A) of the aorta, axillary and iliac arteries was implemented at our department. Methods Between July 2017 and December 2018 all MICS were retrospectively reviewed (n = 143), and divided into 3 groups. Results In patients without CT (n = 45, 31.5%) ECC was applied via femoral arteries (91.1% right, 8.9% left). Vascular related complications (dissection, stroke, coronary and visceral ischemia, related in-hospital death) occurred in 3 patients (6.7%). In patients with non-contrast CT (n = 35, 24.5%) only femoral cannulation was applied (94.3% right) with complications in 4 patients (11.4%). CT-angiography (n = 63, 44.1%) identified 12 patients (19.0%) with vulnerable plaques, 7 patients (11.1%) with kinking of iliac vessels, 41 patients (65.1%) with multiple calcified plaques and 5 patients (7.9%) with small femoral artery diameter (d ≤ 6 mm). In 7 patients (11.1%) pathologic findings led to alternative cannulation via right axillary artery, additional 4 patients (6.3%) were cannulated via left femoral artery. Only 2 patients (3.2%) suffered from complications. Conclusions CT-A identifies vascular pathologies otherwise undetectable in routine preoperative preparation. A standardized imaging protocol may help to customize the operative strategy.

A patient with a left atrial appendage occlusion device underwent mitral valve replacement. Later, the patient developed a left atrial thrombosis with thromboembolic myocardial infarction caused by a dislocation of the occlusion device. Exclusion of the device and non–device-based appendage occlusion may have prevented the patient from experiencing postoperative complications (Level of Difficulty: Intermediate.).

Abstract As long‐term outcomes of congenital heart diseases improve, the probability of adult patients presenting for heart transplantation for late failure of congenitally corrected heart disease also increases. In patients with dextro‐transposition of the great arteries (d‐TGA) who were initially treated in the era of Mustard or Senning procedures and before Jatene procedure was introduced, progressive systemic right ventricular failure represents a problem in the very long‐term follow‐up. We report a rare case of heart transplantation as a third operation 36 years after Mustard procedure in a patient with d‐TGA experiencing late failure of the systemic right ventricle.

Implantation techniques for orthotopic heart transplantation (HTx) have evolved over the centuries. Recently new approaches of modified bicaval techniques to minimize warm ischemia are gaining popularity in the literature. Between 2010 and 2022 n = 238 patients underwent HTx in our department. The recipients were retrospectively reviewed and divided regarding their anastomoses’ technique. Anastomoses were sutured either in biatrial (n = 37), bicaval (n = 191) or in a modified bicaval (n = 10) manner with suturing of the superior cava vein and A. pulmonalis anastomosis after removing the aortic cross-clamp during the reperfusion. Warm ischemia was 62 ± 11 min for biatrial, 66 ± 15 min for bicaval, but only 48 ± 10 min for modified bicaval technique (p < 0.001). The incidence of severe primary graft dysfunction (PGD) was comparable between biatrial (27.0%) and bicaval (28.8%) anastomoses. In contrast, in patients with modified bicaval technique PGD occurred only in a single patient (10.0%). The incidence of postoperative pacemaker implantation was 18.2% for biatrial compared to 3.0% for bicaval and 0.0% for modified bicaval technique (p = 0.01). The modified bicaval technique enables to decrease the crucial warm ischemia during HTx compared to both biatrial and regular bicaval techniques. Therefore, we strongly recommend bicaval anastomoses, ideally in a modified manner.

Objectives: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) may be cannulated using either central (cannulation of aorta) or peripheral (cannulation of femoral or axillary artery) access. The ideal cannulation approach for postcardiotomy cardiogenic shock (PCS) is still unknown. The aim of this study is to compare the outcome of patients with PCS who were supported with central vs. peripheral cannulation.Methods: This is a single-center retrospective data analysis including all VA-ECMO implantations for PCS from January 2011 to December 2017. The central and peripheral approaches were compared in terms of patient characteristics, intensive care unit (ICU) stay, hospitalization length, adverse event rates, and overall survival.Results: Eighty-six patients met the inclusion criteria. Twenty-eight patients (33%) were cannulated using the central approach, and 58 patients (67%) were cannulated using the peripheral approach. Forty-three patients (50%) received VA-ECMO in the operating room and 43 patients (50%) received VA-ECMO in the ICU. Central VA-ECMO group had higher EuroSCORE II (p = 0.007), longer cross-clamp time (p = 0.054), higher rate of open chest after the procedure (p < 0.001), and higher mortality rate (p = 0.02). After propensity score matching, 20 patients in each group were reanalyzed. In the matched groups, no statistically significant differences were observed in the baseline characteristics between the two groups except for a higher rate of open chests in the central ECMO group (p = 0.02). However, no significant differences were observed in the outcome and complications between the groups.Conclusions: This study showed that in postcardiotomy patients requiring VA-ECMO support, similar complication rates and outcome were observed regardless of the cannulation strategy.

Prolonged treatment of organ donors in the intensive care unit (ICU) may be associated with complications influencing the outcome after heart transplantation (HTx). We therefore aim to explore the potential impact of the donor length of stay (LOS) in the ICU on outcomes in our cohort. We included all patients undergoing HTx in our center between September 2010 and April 2022 (n = 241). Recipients were divided around the median into three groups regarding their donor LOS in the ICU: 0 to 3 days (≤50th percentile, n = 92), 4 to 7 days (50th–75th percentile, n = 80), and ≥8 days (≥75th percentile, n = 69). Donor LOS in the ICU ranged between 0 and 155 days (median 4, IQR 3–8 days). No association between the LOS in the ICU and survival after HTx was observed (AUC for overall survival 0.514). Neither the Kaplan–Meier survival analysis up to 5 years after HTx (Log-Rank p = 0.789) nor group comparisons showed significant differences. Baseline recipient characteristics were comparable between the groups, while the donor baselines differed in some parameters, such as less cardiopulmonary resuscitation prior to HTx in those with a prolonged LOS. However, regarding the recipients’ peri- and postoperative parameters, the groups did not differ in all of the assessed parameters. Thus, in this retrospective analysis, although the donors differed in baseline parameters, the donor LOS in the ICU was not associated with altered recipient survival or outcome after HTx.

Abstract Concomitant surgery on the aortic arch with hypothermic cardiac arrest in the setting of heart transplantation (HTX) is extremely rare. Herein, we report a case of combined HTX and proximal arch replacement at our institution.

Background Cardiac surgery using cardiopulmonary bypass (CPB) frequently provokes a systemic inflammatory response syndrome, which is triggered by TLR4 (Toll‐like receptor 4) and TNF‐α (tumor necrosis factor α) signaling. Here, we investigated whether the adiponectin receptor 1 and 2 agonist AdipoRon modulates CPB‐induced inflammation and cardiac dysfunction. Methods and Results Rats underwent CPB with deep hypothermic circulatory arrest and were finally weaned from the heart‐lung machine. Compared with vehicle, AdipoRon application attenuated the CPB‐induced impairment of mean arterial pressure following deep hypothermic circulatory arrest. During the weaning and postweaning phases, heart rate and mean arterial pressure in all AdipoRon animals (7 of 7) remained stable, while cardiac rhythm was irretrievably lost in 2 of 7 of the vehicle‐treated animals. The AdipoRon‐mediated improvements of cardiocirculatory parameters were accompanied by increased plasma levels of IL (interleukin) 10 and diminished concentrations of lactate and K+. In myocardial tissue, AdipoRon activated AMP‐activated protein kinase (AMPK) while attenuating CPB‐induced degradation of nuclear factor κB inhibitor α (IκBα), upregulation of TNF‐α, IL‐1β, CCL2 (C‐C chemokine ligand 2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inducible nitric oxide synthase. Correspondingly, in cultured cardiac myocytes, cardiac fibroblasts, and vascular endothelial cells, AdipoRon activated AMPK, upregulated IL‐10, and attenuated activation of nuclear factor κB, as well as upregulation of TNF‐α, IL‐1β, CCL2, NADPH oxidase, and inducible nitric oxide synthase induced by lipopolysaccharide or TNF‐α. In addition, the treatment of cardiac myocytes with the AMPK activator 5‐aminoimidazole‐4‐carboxamide 1‐β‐D‐ribofuranoside resulted in a similar inhibition of lipopolysaccharide‐ and TNF‐α–induced inflammatory cell phenotypes as for AdipoRon. Conclusions Our observations indicate that AdipoRon attenuates CPB‐induced inflammation and impairment of cardiac function through AMPK‐mediated inhibition of proinflammatory TLR4 and TNF‐α signaling in cardiac cells and upregulation of immunosuppressive IL‐10.

Epicardium-derived cells (EPDC) and atrial stromal cells (ASC) display cardio-regenerative potential, but the molecular details are still unexplored. Signals which induce activation, migration and differentiation of these cells are largely unknown. Here we have isolated rat ventricular EPDC and rat/human ASC and performed genetic and proteomic profiling. EPDC and ASC expressed epicardial/mesenchymal markers (WT-1, Tbx18, CD73, CD90, CD44, CD105), cardiac markers (Gata4, Tbx5, troponin T) and also contained phosphocreatine. We used cell surface biotinylation to isolate plasma membrane proteins of rEPDC and hASC, Nano-liquid chromatography with subsequent mass spectrometry and bioinformatics analysis identified 396 rat and 239 human plasma membrane proteins with 149 overlapping proteins. Functional GO-term analysis revealed several significantly enriched categories related to extracellular matrix (ECM), cell migration/differentiation, immunology or angiogenesis. We identified receptors for ephrin and growth factors (IGF, PDGF, EGF, anthrax toxin) known to be involved in cardiac repair and regeneration. Functional category enrichment identified clusters around integrins, PI3K/Akt-signaling and various cardiomyopathies. Our study indicates that EPDC and ASC have a similar molecular phenotype related to cardiac healing/regeneration. The cell surface proteome repository will help to further unravel the molecular details of their cardio-regenerative potential and their role in cardiac diseases.

Despite the critical feature of heparin-induced thrombocytopenia (HIT) for patients on mechanical circulatory support, reports on its incidence and outcome are still scarce. Thus, we report on clinical features of HIT in patients under Impella 5.0 or 5.5 (Abiomed Inc., Danvers, MA, USA) (Impella 5+) support for acute cardiogenic shock (CS) by focusing on observed thrombotic events. Between November 2018 and December 2020, a total of 56 consecutive patients were enrolled in a single-center retrospective study. A total of 21 patients (37.5%) were tested for HIT, and 6 (10.7%) proved positive for HIT at 10.5 ± 2.89 days after the first heparin administration during current admission. Interestingly, thrombocyte counts dropped under Impella support in all groups (all cases, no HIT test, and HIT negative group: p < 0.001, HIT-positive group: p = 0.001). All HIT-positive patients were switched from heparin to argatroban. HIT-associated thrombotic events were observed in two cases resulting in Impella dysfunction due to pump thrombosis (n = 1) and left ventricular (LV) thrombus formation (n = 1). Under large Impella support, the prevalence of HIT was relatively high. Further, thrombocytopenia does not deliver a high specificity in the setting of Impella 5+ support. Considering HIT manifestation, a routine HIT test may be considered to avoid critical thrombotic adverse events.

Background: We aimed to examine the anti-calcification and anti-inflammatory effects of pioglitazone as a PPAR-gamma agonist on bioprosthetic-valve-bearing aortic grafts in a rat model of diabetes mellitus (DM). Methods: DM was induced in male Wistar rats by high-fat diet with an intraperitoneal streptozotocin (STZ) injection. The experimental group received additional pioglitazone, and controls received normal chow without STZ (n = 20 each group). Cryopreserved aortic donor grafts including the aortic valve were analyzed after 4 weeks and 12 weeks in vivo for analysis of calcific bioprosthetic degeneration. Results: DM led to a significant media proliferation at 4 weeks. The additional administration of pioglitazone significantly increased circulating adiponectin levels and significantly reduced media thickness at 4 and 12 weeks, respectively (p = 0.0002 and p = 0.0107, respectively). Graft media calcification was highly significantly inhibited by pioglitazone after 12 weeks (p = 0.0079). Gene-expression analysis revealed a significant reduction in relevant chondro-osteogenic markers osteopontin and RUNX-2 by pioglitazone at 4 weeks. Conclusions: Under diabetic conditions, pioglitazone leads to elevated circulating levels of adiponectin and to an inhibition of bioprosthetic graft degeneration, including lower expression of chondro-osteogenic genes, decreased media proliferation, and inhibited graft calcification in a small-animal model of DM.

Type 2 diabetes mellitus (T2D) is one of the prominent risk factors for the development and progression of calcific aortic valve disease. Nevertheless, little is known about molecular mechanisms of how T2D affects aortic valve (AV) remodeling. In this study, the influence of hyperinsulinemia and hyperglycemia on degenerative processes in valvular tissue is analyzed in intact AV exposed to an either static or dynamic 3D environment, respectively. The complex native dynamic environment of AV is simulated using a software-governed bioreactor system with controlled pulsatile flow. Dynamic cultivation resulted in significantly stronger fibrosis in AV tissue compared to static cultivation, while hyperinsulinemia and hyperglycemia had no impact on fibrosis. The expression of key differentiation markers and proteoglycans were altered by diabetic conditions in an environment-dependent manner. Furthermore, hyperinsulinemia and hyperglycemia affect insulin-signaling pathways. Western blot analysis showed increased phosphorylation level of protein kinase B (AKT) after acute insulin stimulation, which was lost in AV under hyperinsulinemia, indicating acquired insulin resistance of the AV tissue in response to elevated insulin levels. These data underline a complex interplay of diabetic conditions on one hand and biomechanical 3D environment on the other hand that possesses an impact on AV tissue remodeling.

Background: Although, in theory, valve-sparing aortic root replacement (David procedure) is an ideal surgical option for acute aortic dissection type A (AADA) it is usually not regarded as the first-choice treatment due to the emergency setting and the relative complexity of the procedure. Here, we report the results of a consecutive, single-surgeon series of 45 AADA patients with the David procedure as first-choice treatment strategy.Methods and Results: Between September 2009 and July 2013 a total of 49 patients with AADA were consecutively operated by the same surgeon at our institution. The David procedure was the treatment of choice for the proximal aorta unless aortic valve pathology or critical preoperative patient status advocated against it. Median follow-up was 5.0 years (CI95%, 4.0–6.0). Out of the 45 patients included in this study the David procedure was performed in 28 patients (62.2%), while in 17 patients (37.8%) an alternative surgical strategy had to be pursued. Although X-clamping (168.5 ± 41.7 vs. 110.3 ± 51.1 min; p = 0.001), cardiopulmonary bypass (CPB) (245.0 ± 62.4 vs. 211.8 ± 123 min; p = 0.029) and total operation time (383.8 ± 88.5 vs. 312.8 ± 144.8; p = 0.047) were significantly longer in the David-group as compared to the non-David group, there was no difference in major complication rate as well as 30-day (17.9 vs. 23.5%; p = 0.645) and 5-year mortality (28.6 vs. 35.3%) between groups.Conclusions: This small series indicates that the David procedure may be safe and feasible as a primary surgical treatment strategy for AADA.

Calcific aortic valve disease is the most common valvular heart disease in industrialized countries. Pulsatile pressure, sheer and bending stress promote initiation and progression of aortic valve degeneration. The aim of this work is to establish an ex vivo model to study the therein involved processes. Ovine aortic roots bearing aortic valve leaflets were cultivated in an elaborated bioreactor system with pulsatile flow, physiological temperature, and controlled pressure and pH values. Standard and pro-degenerative treatment were studied regarding the impact on morphology, calcification, and gene expression. In particular, differentiation, matrix remodeling, and degeneration were also compared to a static cultivation model. Bioreactor cultivation led to shrinking and thickening of the valve leaflets compared to native leaflets while gross morphology and the presence of valvular interstitial cells were preserved. Degenerative conditions induced considerable leaflet calcification. In comparison to static cultivation, collagen gene expression was stable under bioreactor cultivation, whereas expression of hypoxia-related markers was increased. Osteopontin gene expression was differentially altered compared to protein expression, indicating an enhanced protein turnover. The present ex vivo model is an adequate and effective system to analyze aortic valve degeneration under controlled physiological conditions without the need of additional growth factors.

The hallmarks of calcific aortic valve disease (CAVD), an active and regulated process involving the creation of calcium nodules, lipoprotein accumulation, and chronic inflammation, are the significant changes that occur in the composition, organization, and mechanical properties of the extracellular matrix (ECM) of the aortic valve (AV). Most research regarding CAVD is based on experiments using two-dimensional (2D) cell culture or artificially created three-dimensional (3D) environments of valvular interstitial cells (VICs). Because the valvular ECM has a powerful influence in regulating pathological events, we developed an in vitro AV tissue culture model, which is more closely able to mimic natural conditions to study cellular responses underlying CAVD. AV leaflets, isolated from the hearts of 6–8-month-old sheep, were fixed with needles on silicon rubber rings to achieve passive tension and treated in vitro under pro-degenerative and pro-calcifying conditions. The degeneration of AV leaflets progressed over time, commencing with the first visible calcified domains after 14 d and winding up with the distinct formation of calcium nodules, heightened stiffness, and clear disruption of the ECM after 56 d. Both the expression of pro-degenerative genes and the myofibroblastic differentiation of VICs were altered in AV leaflets compared to that in VIC cultures. In this study, we have established an easily applicable, reproducible, and cost-effective in vitro AV tissue culture model to study pathological mechanisms underlying CAVD. The valvular ECM and realistic VIC–VEC interactions mimic natural conditions more closely than VIC cultures or 3D environments. The application of various culture conditions enables the examination of different pathological mechanisms underlying CAVD and could lead to a better understanding of the molecular mechanisms that lead to VIC degeneration and AS. Our model provides a valuable tool to study the complex pathobiology of CAVD and can be used to identify potential therapeutic targets for slowing disease progression.