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Abstract Aims Cancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy. CTRCD most frequently appears in patients with cardiovascular risk factors (CVR) or known cardiovascular disease. However, limited data exist on incidence and course of anthracycline-induced CTRCD in patients without preexisting risk factors. We therefore aimed to longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease (NCT03940625). Methods and results We enrolled 59 women with primary breast cancer and scheduled anthracycline-based therapy, but without CVR or preexisting cardiovascular disease. We conducted a longitudinal assessment before, immediately and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping. Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3% immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation, two of them were symptomatic. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired. Conclusion In every single patient anthracyclines induce a decline of myocardial contractility, even among patients without pre-existing risk factors for CTRCD. Our data suggest to thoroughly evaluate whether this may lead to an increased risk of future cardiovascular events. Graphical Abstract Reduced myocardial contractility in low-risk patients receiving anthracycline-based cancer therapy. This study included 59 otherwise healthy women with primary breast cancer undergoing anthracycline-based chemotherapy. CMR was performed at baseline, directly and 12 months after cancer therapy. A decline in left ventricular function was observed in every single patient accompanied by transient edema. More than 50% were diagnosed with cancer therapy related cardiovascular dysfunction. LVEF: left ventricular function, CTRCD: cancer therapy related cardiovascular dysfunction, GLS = Global longitudinal strain, hs-TnT = high sensitive Troponin T, NT-pro BNP = NT-pro brain natriuretic peptide

Abstract Background About 20–40% of people with Heart failure (HF) suffer from some depression, which is 4–5% greater than the overall population. This depression can lead to undesirable outcomes, including elevated mortality rate and frequent hospitalization. Purpose The current study aims to evaluate the impact of cognitive behavioural therapy (CBT) on self-care and the symptoms of depression and anxiety in HF patients. Methods We searched PubMed, Web of Science (WOS), Scopus, and Cochrane Library till 15 October 2022. All relevant randomized controlled trials (RCTs) were included. The data were extracted and pooled using Review Manager software (RevMan 5.4). Continuous data were pooled as mean difference and 95% confidence interval (CI). Results Our search retrieved 1146 records, and 7 studies (611 patients) were finally included. We assessed the Beck Depression Inventory-II (BDI-II) as the primary outcome of the study. Hamilton Rating Scale for Depression (HRSD-17), Change in Beck Anxiety Inventory, Kansas City Cardiomyopathy Questionnaire (KCCQ), and Self-Care of Heart Failure Index (SCHFI) were also assessed as secondary outcomes. With CBT, BDI-II showed a significant reduction after 4 to 6 months follow-up (MD = -4.87, 95% CI: [-8.06; -1.69], P = 0.003) as well as 8 to 9 months follow-up (MD = -5.71, 95% CI: [-8.95; -2.46], P = 0.0006). But no significant difference was shown with 3 months follow-up (M.D=-4.34; 95%CI: [-10.70; 2.03], P = 0.18). Conclusions CBT has long-term (4–9 months) significant favorable outcomes decreasing anxiety and depression compared to non-CBT groups. No significant short-term (less than 3 months) impact on HF patients’ self-care, depression, or anxiety were shown.

Abstract Aims A causal link between non‐ischaemic heart failure (HF) and humoral autoimmunity against G‐protein‐coupled receptors (GPCR) remains unclear except for Chagas' cardiomyopathy. Uncertainty arises from ambiguous reports on incidences of GPCR autoantibodies, spurious correlations of autoantibody levels with disease activity, and lack of standardization and validation of measuring procedures for putatively cardio‐pathogenic GPCR autoantibodies. Here, we use validated and certified immune assays presenting native receptors as binding targets. We compared candidate GPCR autoantibody species between HF patients and healthy controls and tested associations of serum autoantibody levels with serological, haemodynamic, metabolic, and functional parameters in HF. Methods Ninety‐five non‐ischaemic HF patients undergoing transcatheter endomyocardial biopsy and 60 healthy controls were included. GPCR autoantibodies were determined in serum by IgG binding to native receptors or a cyclic peptide (for β1AR autoantibodies). In patients, cardiac function, volumes, and myocardial structural properties were assessed by cardiac magnetic resonance imaging; right heart catheterization served for determination of cardiac haemodynamics; endomyocardial biopsies were used for histological assessment of cardiomyopathy and determination of cardiac mitochondrial oxidative function by high‐resolution respirometry. Results Autoantibodies against β1 adrenergic (β1AR), M5‐muscarinic (M5AR), and angiotensin II type 2 receptors (AT2R) were increased in HF (all P

Abstract Background Over the past decades, international guidelines for cardiopulmonary resuscitation (CPR) have changed the recommendation for alternative routes for drug administration. Until now, evidence for the substantial superiority of one route with respect to treatment outcome after CPR has been lacking. The present study compares the effects of intravenous (IV), intraosseous (IO) and endotracheal (ET) adrenaline application during CPR in out-of-hospital cardiac arrest (OHCA) on clinical outcomes within the database of the German Resuscitation Registry (GRR). Methods This registry analysis was based on the GRR cohort of 212,228 OHCA patients between 1989 and 2020. Inclusion criteria were: OHCA, application of adrenaline, and out-of-hospital CPR. Excluded from the study were patients younger than 18 years, those who had trauma or bleeding as suspected causes of cardiac arrest, and incomplete data sets. The clinical endpoint was hospital discharge with good neurological outcome [cerebral performance category (CPC) 1/2]. Four routes of adrenaline administration were compared: IV, IO, IO + IV, ET + IV. Group comparisons were done using matched-pair analysis and binary logistic regression. Results In matched-pair group comparisons of the primary clinical outcome hospital discharge with CPC 1/2, the IV group (n = 2416) showed better results compared to IO (n = 1208), [odds ratio (OR): 2.43, 95% confidence interval (CI): 1.54–3.84, p

Abstract Aims Absolute treatment effects—i.e. numbers needed to treat (NNTs)—of novel antidiabetic drugs for cardiovascular outcomes have not been comprehensively evaluated. We aimed to perform a meta‐analysis of digitalized individual patient outcomes to display and compare absolute treatment effects. Methods and results Individual patient time‐to‐event information from Kaplan–Meier plots of cardiovascular mortality (CM) and/or hospitalization for heart failure (HHF) endpoints from cardiovascular outcome trials (CVOTs) evaluating dipeptidyl peptidase‐4 (DPP‐4) inhibitors, glucagon‐like peptide‐1 (GLP‐1) receptor agonists, and sodium glucose transporter 2 (SGLT2) inhibitors vs. placebo were digitalized using WebPlotDigitizer 4.2 and the R code of Guyot et al.; Weibull regression models were generated, validated, and used to estimate NNT for individual trials; random‐effects meta‐analysis generated Meta‐NNT with 95% confidence intervals. Sixteen CVOTs reported time‐to‐event information (14 in primary diabetes and 2 in primary heart failure populations). Thirteen studies including 96 860 patients were meta‐analysed for CM: At the median follow‐up of 30 months, Meta‐NNTs were 178 (64 to ∞ to −223) for DPP‐4 inhibitors, 261 (158 to 745) for GLP‐1 receptor agonists, and 118 (68 to 435) for SGLT2 inhibitors. Ten studies including 96 128 patients were meta‐analysed for HHF: At the median follow‐up of 29 months, estimated Meta‐NNTs were −644 (229 to ∞ to −134) for DPP‐4 inhibitors, 441 (184 to ∞ to −1100) for GLP‐1 receptor agonists, and 126 (91 to 208) for SGLT2 inhibitors. SGLT2 inhibitors were especially effective for HHF in primary heart failure populations [Meta‐NNT 25 (19 to 39)] vs. primary diabetes populations [Meta‐NNT 233 (167 to 385)] at 16 months of follow‐up. Conclusions We found only modest treatment benefits of GLP‐1 receptor agonists and SGLT2 inhibitors for CM and HHF in primary type 2 diabetes mellitus populations. In primary heart failure populations, SGLT2 inhibitor benefits were substantial and comparable in efficacy to established heart failure medication.

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.

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

Background: The recommended chronic kidney disease (CKD) first-line diagnostic test is based on the creatinine-derived (estimated) glomerular filtration rate (eGFR). Cystatin C use may provide a better assessment. Methods: We compared creatinine- and cystatin C-derived eGFR determination as the first-line diagnostic test for 112 hospital patients aged > 60 years (median = 76 years). The patients were judged to not have CKD (no-CKD group) according to the first-line diagnostic recommendations (n = 61, eGFR (CKD Epidemiology Collaboration (CKD-EPI)) ≥ 60 mL/min/1.73 m2, total urine protein < 150 mg/g creatinine, urinary red/white blood cells not increased) or classified to be at risk for kidney insufficiency due to aortic valve dysfunction (at-risk group; n = 51). The accuracy of the eGFR values was evaluated retrospectively with the final case diagnoses. Results: The eGFR (Caucasian, Asian, pediatric, and adult formula (CAPA)) was found to be linearly correlated to the eGFR (CKD-EPI) (R2 = 0.5, slope = 0.69, p < 0.0001). In 93/112 (>80%) cases, the eGFR (CAPA) yielded lower values (on average ≈−20%). In 55/112 (49%) cases, the cystatin C-derived CKD stage was lower. CKD reclassification from no-CKD to a kidney-insufficient state (i.e., CKD1/2 to CKD3a/b or 4) or reclassification to a more severe kidney insufficiency (i.e., CKD3a → 3b/4 or 3b → 4) was found in 41/112 (37%) cases. A worse CKD classification (no-CKD → kidney-insufficient) based on the eGFR (CAPA) was plausible in 30% of cases in light of the final case diagnoses. Conclusion: In elderly patients (>60 years), renal function appears to be systematically overestimated by the creatinine-based eGFR (CKD-EPI), indicating that, for this group, the cystatin C-based eGFR (CAPA) should be used as the first-line diagnostic test.

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 Background Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) acts as a transcriptional coactivator and regulates mitochondrial function. Various isoforms are generated by alternative splicing and differentially regulated promoters. In the heart, total PGC-1α deficiency knockout leads to dilatative cardiomyopathy, but knowledge on the complexity of cardiac isoform expression of PGC-1α remains sparse. Thus, this study aims to generate a reliable dataset on cardiac isoform expression pattern by long-read mRNA sequencing, followed by investigation of differential regulation of PGC-1α isoforms under metabolic and ischemic stress, using high-fat-high-sucrose-diet-induced obesity and a murine model of myocardial infarction. Results Murine (C57Bl/6J) or human heart tissue (obtained during LVAD-surgery) was used for long-read mRNA sequencing, resulting in full-length transcriptomes including 58,000 mRNA isoforms with 99% sequence accuracy. Automatic bioinformatic analysis as well as manual similarity search against exonic sequences leads to identification of putative coding PGC-1α isoforms, validated by PCR and Sanger sequencing. Thereby, 12 novel transcripts generated by hitherto unknown splicing events were detected. In addition, we postulate a novel promoter with homologous and strongly conserved sequence in human heart. High-fat diet as well as ischemia/reperfusion (I/R) injury transiently reduced cardiac expression of PGC-1α isoforms, with the most pronounced effect in the infarcted area. Recovery of PGC-1α-isoform expression was even more decelerated when I/R was performed in diet-induced obese mice. Conclusions We deciphered for the first time a complete full-length transcriptome of the murine and human heart, identifying novel putative PGC-1α coding transcripts including a novel promoter. These transcripts are differentially regulated in I/R and obesity suggesting transcriptional regulation and alternative splicing that may modulate PGC-1α function in the injured and metabolically challenged heart.

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 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 This multicentre study investigated the association of periprocedural changes in the levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) with clinical outcomes after transcatheter edge‐to‐edge mitral valve repair (TMVR). Methods and results Patients were retrospectively analysed who underwent TMVR with the MitraClip system (Abbott Vascular, Santa Clara, CA, USA) and had available sequential NT‐proBNP testing at baseline and 2 months after TMVR. Periprocedural changes in NT‐proBNP following TMVR were assessed as the percent change in NT‐proBNP between baseline and the 2 month follow‐up, and the significant reduction in NT‐proBNP was defined as a decrease of >30% in the follow‐up NT‐proBNP compared with the pre‐procedural NT‐proBNP level. Primary outcome was defined as a composite outcome consisting of all‐cause mortality and hospitalization due to heart failure from 2 months to 2 years after TMVR. Additionally, we identified the cut‐off value of pre‐procedural NT‐proBNP to predict the composite outcome using a receiver operating characteristic analysis (cut‐off: 2485 pg/mL). Of 485 patients undergoing TMVR (age: 76.2 ± 9.2 years, female: 42.1%, secondary mitral regurgitation: 67.2%), 150 patients (30.9%) had the significant reduction in NT‐proBNP (>30%) following the procedure. Patients with the NT‐proBNP reduction had a lower incidence of the composite outcome, compared with those without the reduction in NT‐proBNP (31.4% vs. 40.2%; log‐rank P = 0.03). The significant reduction in NT‐proBNP was also associated with a lower risk of the composite outcome [adjusted hazard ratio (HR): 0.67; 95% confidence interval (CI): 0.45–0.97; P = 0.04], independently of pre‐procedural NT‐proBNP levels and other clinical parameters. The percent change in NT‐proBNP was associated with a linear trend of the incidence of the composite outcome (adjusted HR per 10% decrease: 0.96; 95% CI: 0.94–0.98; P 2485 pg/mL) was associated with the increased risk of the composite outcome (adjusted HR: 1.50; 95% CI: 1.03–2.17; P = 0.03); however, patients with a higher pre‐procedural NT‐proBNP who achieved the significant reduction in NT‐proBNP had a similar risk of the composite outcome to those with a lower pre‐procedural NT‐proBNP. Conclusions Changes in sequential NT‐proBNP measurements were associated with clinical outcomes within 2 years after TMVR. The assessment of NT‐proBNP dynamics may be valuable to assess the residual risk for patients undergoing TMVR and could assist with post‐procedural management after TMVR.

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 In-hospital cardiac arrest (IHCA) is associated with poor outcomes. There are currently no standards for cardiac arrest teams in terms of member composition and task allocation. Here we aimed to compare two different cardiac arrest team concepts to cover IHCA management in terms of survival and neurological outcomes. This prospective study enrolled 412 patients with IHCA from general medical wards. From May 2014 to April 2016, 228 patients were directly transferred to the intensive care unit (ICU) for ongoing resuscitation. In the ICU, resuscitation was extended to advanced cardiac life support (ACLS) (Load-and-Go [LaG] group). By May 2016, a dedicated cardiac arrest team provided by the ICU provided ACLS in the ward. After return of spontaneous circulation (ROSC), the patients (n = 184) were transferred to the ICU (Stay-and-Treat [SaT] group). Overall, baseline characteristics, aetiologies, and characteristics of cardiac arrest were similar between groups. The time to endotracheal intubation was longer in the LaG group than in the SaT group (6 [5, 8] min versus 4 [2, 5] min, p = 0.001). In the LaG group, 96% of the patients were transferred to the ICU regardless of ROSC achievement. In the SaT group, 83% of patients were transferred to the ICU (p = 0.001). Survival to discharge did not differ between the LaG (33%) and the SaT (35%) groups (p = 0.758). Ultimately, 22% of patients in the LaG group versus 21% in the SaT group were discharged with good neurological outcomes (p = 0.857). In conclusion, we demonstrated that the cardiac arrest team concepts for the management of IHCA did not differ in terms of survival and neurological outcomes. However, a dedicated (intensive care) cardiac arrest team could take some load off the ICU.

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.

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

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.

BackgroundThe implantation depth (ID) is a critical condition for optimal hemodynamic and clinical outcomes in transcatheter aortic valve replacement (TAVR). The recently recommended cusp-overlap technique (COT) offers optimized fluoroscopic projections facilitating a precise ID. This single-center observational study aimed to investigate short-term clinical performance, safety, and efficacy outcomes in patients undergoing TAVR with self-expandable prostheses and application of COT in a real-world setting.Materials and methodsFrom September 2020 to April 2021, a total of 170 patients underwent TAVR with self-expandable devices and the application of COT, while 589 patients were treated from January 2016 to August 2020 with a conventional three-cusp coplanar view approach. The final ID and 30-day outcomes were compared after 1:1 propensity score matching, resulting in 150 patients in both cohorts.ResultsThe mean ID was significantly reduced in the COT cohort (−4.2 ± 2.7 vs. −4.9 ± 2.3 mm; p = 0.007) with an improvement of ID symmetry of less than 2 mm difference below the annular plane (47.3 vs. 57.3%; p = 0.083). The rate of new permanent pacemaker implantation (PPI) following TAVR was effectively reduced (8.0 vs. 16.8%; p = 0.028). While the fluoroscopy time decreased (18.4 ± 7.6 vs. 19.8 ± 7.6 min; p = 0.023), the dose area product increased in the COT group (4951 ± 3662 vs. 3875 ± 2775 Gy × cm2; p = 0.005). Patients implanted with COT had a shorter length of in-hospital stay (8.4 ± 4.0 vs. 10.3 ± 6.7 days; p = 0.007).ConclusionTranscatheter aortic valve replacement using the cusp-overlap deployment technique is associated with an optimized implantation depth, leading to fewer permanent conduction disturbances. However, our in-depth analysis showed for the first time an increase of radiation dose due to extreme angulations of the gantry to obtain the cusp-overlap view.

BackgroundTranscatheter tricuspid valve repair (TTVr) is routinely performed under general anesthesia (GA). This study aimed to investigate whether TTVr procedures can be performed effectively and safely without GA but using deep sedation (DS).MethodsWe performed a retrospective analysis of 104 patients from three centers who underwent TTVr between 2020 and 2021. The primary performance endpoints were technical success and severity of TR assessed at the time of discharge. The safety outcome was a composite of in-hospital complications, including occurrence of death, conversion to surgery, major adverse cardiac and cerebrovascular events, major vascular complications, or occurrence of pneumonia.ResultsSixty-four procedures were performed in GA and 40 procedures were performed in DS. The groups did not differ in age, EuroScore II, TR severity, ventricular function, or hemodynamic parameters. Technical success was achieved in 92.5% of the patients in the DS group and in 93.6% of the patients in the GA group (p = 0.805). In none of the patients intraprocedural conversion from DS to GA was required. There was no difference in total duration of the procedure, and number of devices implanted. The degree of TR was ≤2+ in 77.5% of the patients in the DS group and in 74.2% of the patients in the GA group (p = 0.705). The composite safety endpoint did not differ between the groups (2.5 vs. 6.3%, p = 0.384). The total duration of hospital stay was shorter in patients who underwent TTVr in DS compared to those who underwent TTVr in GA (6 [5, 9] days vs. 8 [6, 11] days; p = 0.011).ConclusionPerforming TTVr in DS was effective with similar procedural results, and was safe with similar low complication rates compared to GA.

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.

Aims: Identifying patients who may benefit from mechanical circulatory support (MCS) after out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC) remains challenging; thus, a search for helpful biomarkers is warranted. We aimed to evaluate phosphate and lactate levels on admission regarding their associations with survival with and without MCS. Methods: In 224 OHCA patients who achieved ROSC, the initial phosphate and lactate levels were investigated to discriminate in-hospital mortality by receiver operating characteristic (ROC) curves. According to the Youden Index (YI) from the respective ROC, the groups were risk stratified by both biomarkers, and 30-day mortality was analyzed in patients with and without MCS. Results: Within the entire collective, MCS was not associated with a better chance of survival. Both phosphate and lactate level elevations showed good yet comparable discriminations to predict mortality (areas under the curve: 0.80 vs. 0.79, p = 0.74). In patients with initial phosphate values > 2.2 mmol/L (>YI), 30-day mortality within the MCS cohort was lower (HR 2.3, 95% CI: 1.4–3.7; p = 0.0037). In patients with lower phosphate levels and groups stratified by lactate, 30-day mortality was similar in patients with and without MCS. Conclusions: We found a significant association between survival and MCS therapy in patients with phosphate levels above 2.2 mmol/L (Youden Index), and a similar discrimination of patient overall survival by lactate and phosphate. Prospective studies should assess the possible independent prognostic value of phosphate and its clearance for MCS efficiency.

Abstract Aims Percutaneous mitral valve repair (PMVR) has emerged as standard treatment in selected patients with clinically relevant mitral regurgitation (MR) and increased surgical risk. We aimed to evaluate the safety and clinical outcomes in nonagenarians undergoing PMVR. Methods and results Altogether, 493 patients with severe MR who were treated with PMVR were included in this open‐label prospective study and followed up for 2 years. We treated 25 patients with PMVR aged 90 years or above, 185 patients aged 80–89 years, and 283 patients aged

Objective: To evaluate the impact of severe tricuspid valve insufficiency (TVI) at the time of left ventricular assist device (LVAD) implantation on the hemodynamic and LVAD parameters in an acute ovine model. Methods: Stable heart failure (HF) was induced in 10 ovines through the application of 3 ± 1 coronary ligations. Once stable HF was obtained (after 15 ± 5 days), the animals were supported with an LVAD. Hemodynamic data and pump parameters were obtained and compared in 2 settings; first with LVAD in place after weaning from the cardiopulmonary bypass machine (no TVI condition) and second following the induction of severe TVI through resection of the tricuspid valve (TVI condition). Results: There were no statistically significant differences in the hemodynamic and pump parameters between TVI condition and no TVI conditions except for lower cardiac output in the TVI condition (2 [1.38-2.8] L/min vs 3.2 [1.55-3.7] L/min, P = .027) and the expected greater central venous pressure in the TVI condition (26 [24-31] mm Hg vs 15 [13-25] mm Hg, P = .020). A median pump flow of 2.8 (2.45-3.75) L/min versus 2.9 (2.75-3.8) L/min in the TVI condition and no TVI condition was documented (P = .160). Conclusions: Results from this acute animal study suggest that severe TVI in HF with preserved right ventricular function does not have significant impact on the LVAD pump parameters. The observed reduction in cardiac output may warrant further investigations, especially under loading conditions.

Background: Transcatheter aortic valve replacement is an evolving interventional therapy for patients with symptomatic severe aortic stenosis. Infolding (INF) as wrinkling along the valve frame is only seen in self-expandable transcatheter valves or surgical sutureless prostheses and is known to be a very rare event during delivery but probably underreported. Therefore, we aimed to (1) determine the frequency of events, (2) identify potential predictors of INF, and (3) evaluate the potential clinical impact of this adverse event. Methods: INF cases of 2 centers were retrospectively analyzed in an all-comer cohort of 1416 patients with older- and newer-generation self-expandable (SEV) devices. The underlying functional, anatomical, and procedural conditions were evaluated by univariate analysis. Results: INF+ was observed in 14 patients (1.0%) with the following valve size distribution: SEV-26: 14.3%, SEV-29: 28.6%, and SEV-34: 57.4%. Several dependent predictors of INF were pointed out, such as severe peripheral kinking, severe aortic calcification, resheathing maneuvers, valve-in-valve procedures, and the use of the largest valve size. INF+ patients showed a higher incidence of acute kidney injury (INF− vs. INF+: 12.3% vs. 35.7%; p = 0.008), of a new atrioventricular block (INF− vs. INF+: 14.8% vs. 42.9%; p = 0.003), and a higher need of permanent pacemaker implantation (INF− vs. INF+: 14.9% vs. 35.7%; p = 0.031). Conclusions: Identifying potential predictors of INF can probably influence the implantation strategy and improve safety algorithms and clinical outcomes. Even being a rare but potentially life-threatening and underreported event, safety rules must be established when expanding transcatheter aortic valve replacement treatment to younger patients.

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.

Background: Acute myocardial infarction-related cardiogenic shock (AMI-CS) still has high likelihood of in-hospital mortality. The only trial evidence currently available for the intra-aortic balloon pump showed no benefit of its routine use in AMI-CS. While a potential benefit of complete revascularisation has been suggested in urgent revascularisation, the CULPRIT-SHOCK trial demonstrated no benefit of multivessel compared to culprit-lesion only revascularisation in AMI-CS. However, mechanical circulatory support was only used in a minority of patients.Objectives: We hypothesised that more complete revascularisation facilitated by Impella support is related to lower mortality in AMI-CS patients.Methods: We analysed data from 202 consecutive Impella-treated AMI-CS patients at four European high-volume shock centres (age 66 ± 11 years, 83% male). Forty-seven percentage (n = 94) had cardiac arrest before Impella implantation. Revascularisation was categorised as incomplete if residual SYNTAX-score (rS) was >8.Results: Overall 30-day mortality was 47%. Mortality was higher when Impella was implanted post-PCI (Impella-post-PCI: 57%, Impella-pre-PCI: 38%, p = 0.0053) and if revascularisation was incomplete (rS ≤ 8: 37%, rS > 8: 56%, p = 0.0099). Patients with both pre-PCI Impella implantation and complete revascularisation had significantly lower mortality (33%) than those with incomplete revascularisation and implantation post PCI (72%, p < 0.001).Conclusions: Our retrospective analysis suggests that complete revascularisation supported by an Impella microaxial pump implanted prior to PCI is associated with lower mortality than incomplete revascularisation in patients with AMI-CS.

Background Optimizing risk stratification in patients undergoing transcatheter mitral valve repair is an ongoing challenge. The Mitral Regurgitation International Database (MIDA) score represents a user‐friendly mortality risk stratification tool that is validated on a large‐scale registry of patients with degenerative mitral regurgitation (MR). We here assessed the potential benefit of the MIDA risk score for patients with functional or degenerative MR undergoing transcatheter mitral valve repair. Methods and Results In total, 680 patients undergoing MitraClip implantation were stratified according to MIDA score tertiles into a low (0–7), intermediate (8–9), and a high (10–12) MIDA score group. MR was assessed in follow‐up echocardiograms in 416 patients at 323±169 days after transcatheter mitral valve repair. During 2‐year follow‐up, 8.2% (15/182) of patients with low, 21.3% (64/300) with intermediate, and 26.3% (52/198) with high MIDA score died (log‐rank test P

Background: In secondary MR, data on left ventricular (LV) remodeling after MitraClip procedure are rare, even this information may impact patient selection. This study investigated changes in LV structure and function by cardiovascular magnetic resonance (CMR) following MitraClip implantation for secondary mitral regurgitation (MR) in order to assess extent and predictors of LV reverse remodeling (LVRR). Methods and Results: Twenty-nine patients underwent CMR imaging prior to and six months after MitraClip procedure. LVRR was defined by a decrease of LV end-diastolic volume index (LVEDVi) > 15% compared to baseline. According to the definition of LVRR, 34% of patients displayed LVRR at follow-up CMR. Baseline LV stroke volume index (LVSVi), LV ejection fraction (LVEF), LV circumferential strain and MR volume at baseline were predictors of LVRR at follow-up. At second CMR, we detected an improvement in hemodynamic status as illustrated by an increase in effective LVSVi (28 ± 8 ml/m2 vs. 33 ± 8 ml/m2; p = 0.053) and cardiac index (2.0 ± 0.5 vs. 2.3 ± 0.5 l/min; p = 0.016), while LVEF and LV strain parameters did not change (p > 0.05). Improvements in effective LVSVi were associated with the decrease of MR volume (r = 0.509; p = 0.018) and MR fraction (r = 0.629; p = 0.002) by MitraClip. Conclusions: Together, MitraClip implantation is associated with LVRR in one third of patients. Baseline LV function and magnitude of MR are important predictors of LVRR. Improvement of hemodynamic status may be assessed by effective stroke volume index and correlates with the reduction of MR by MitraClip implantation, rather than an increase in LV contractility.

Heart failure: Energy metabolism reflects cardiac function The capacity of mitochondria in heart muscle cells to use oxygen to produce energy correlates with cardiac function. Julia Szendroedi at Heinrich-Heine University, Düsseldorf, Germany, and colleagues have established a technique to reliably evaluate mitochondrial energy metabolism in patients with or recovering from heart failure. They showed that the mitochondrial oxidative capacity of cells in the lower heart chambers (ventricles) was significantly higher than in the upper heart chambers (atria). Moreover, they found that mitochondrial oxidative capacity was reduced by 44% in heart muscle biopsies from patients with heart failure compared with biopsies from heart transplant recipients with normal ventricular function. Stimulating the respiration rate of mitochondria in ventricular heart cells could be a promising strategy for improving cardiac function.

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.

Due to shortages of medical resources during the Coronavirus Disease 2019 (COVID-19) pandemic, an allocation algorithm for Transcatheter Aortic Valve Replacement (TAVR) was established. We investigated the impact on patient selection and procedural results. In total, 456 TAVR patients before (pre-COVID-19 group) and 456 TAVR patients after (COVID-19 group) the implementation of our allocation algorithm were compared. Concerning patient characteristics, the COVID-19 group revealed a higher rate of cardiac decompensations/cardiogenic shocks (10.5% vs. 1.3%; p < 0.001), severe angina pectoris (Canadian Cardiovascular Society (CCS) II, III and IV: 18.7% vs. 11.8%; p = 0.004), troponin elevation (>14 ng/L: 84.9% vs. 77%; p = 0.003) and reduced left ventricular ejection fraction (LVEF) (p = 0.006). Referring to procedural characteristics, more predilatations (46.3% vs. 35.1%; p = 0.001) and a longer procedural time (80.2 min (+/−29.4) vs. 66.9 min (+/−17.5); p < 0.001) were observed. The success rate was evenly high; no differences in safety parameters were reported. Examining the utilization of hospital resources, the COVID-19 group showed a shorter in-hospital stay (8.4 days (+/−5.9) vs. 9.5 days (+/−9.33); p = 0.041) and fewer TAVR patients were treated per month (39 (+/−4.55) vs. 46.11 (+/−7.57); p = 0.03). Our allocation algorithm supported prioritization of sicker patients with similar efficient and safe TAVR procedures. In-hospital stay could be shortened.

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14–39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty® (Pfizer-BioNTech) (n = 11), Vaxzevria® (AstraZenica) (n = 2) and Janssen® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4+ and CD8+ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4+ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.

AimsTo evaluate whether CMR-derived RV assessment can facilitate risk stratification among patients undergoing transcatheter mitral valve repair (TMVR).BackgroundIn patients undergoing TMVR, only limited data exist regarding the role of RV function. Previous studies assessed the impact of pre-procedural RV dysfunction stating that RV failure may be associated with increased cardiovascular mortality after the procedure.MethodsSixty-one patients underwent CMR, echocardiography and right heart catheterization prior TMVR. All-cause mortality and heart failure hospitalizations were assessed during 2-year follow-up.ResultsAccording to RV ejection fraction (RVEF) ConclusionIn patients undergoing TMVR, pre-existing RV dysfunction and RV dilatation are associated with reduced survival, in progressive additive fashion. The assessment of RV volumes and function by CMR may aid in risk stratification prior TMVR in these high-risk patients.

Objectives The aim of this study was to investigate the impact of acute left ventricular unloading by percutaneous left ventricular assist device on pulmonary congestion and pneumonia in patients with cardiogenic shock (CS).Methods In this retrospective study, we analysed patients with CS who received the Impella percutaneous left ventricular assist device (n=50) compared with those who received intra-aortic balloon pump (IABP) support (n=50). Pulmonary congestion was longitudinally assessed while on support by calculating characteristic findings on the chest X-ray using the Halperin score. The rate of pneumonia and early mortality were assessed as a secondary endpoint.Results The groups (Impella vs IABP) did not differ in terms of age, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology, Chronic Health Evaluation (APACHE) II score or serum lactate levels. Pulmonary congestion decreased in patient treated with Impella at each time point postimplantation. No change in congestion status was observed in patients supported with IABP. Multivariate analysis indicated Impella support as an independent predictor for pulmonary decongestion (OR 4.06, 95% CI 1.15 to 14.35, p=0.030). The rate of early pneumonia was lower in the Impella group compared with the IABP group (54% vs 74%, p=0.037). Failure of pulmonary decongestion during mechanical circulatory support independently predicted early pneumonia (OR 0.28, 95% CI 0.12 to 0.70, p=0.006).Conclusion Pulmonary decongestion may facilitate treatment of pneumonia in patients with CS. Left ventricular unloading by Impella device might support pulmonary decongestion, although a larger prospective trial in this patient population is required.

Background: In-hospital mortality in acute myocardial infarction-related cardiogenic shock (AMI-CS) remains high. The only adequately powered randomized trial showed no benefit of routine use of the intra-aortic balloon pump in AMI-CS. We compared individually predicted mortality using CardShock- and IABP-Shock II-scores in AMI-CS patients treated with an Impella microaxial pump, who met the IABP-Shock II-trials inclusion/exclusion criteria, to observed mortality on circulatory support in order to determine whether standardized use of an Impella microaxial flow-pump in AMI-CS is associated with lower than predicted mortality rates and whether timing of implantation or selecting patients based on predicted risk is meaningful.Methods and Results: We analyzed data from 166 consecutive Impella-treated AMI-CS patients meeting the inclusion/exclusion criteria of the IABP-Shock II-trial (age 64 ± 11 years). Thirty-nine percentage of 64 patients had been resuscitated before Impella implantation. Overall 30-day mortality was 42%. Mortality was higher in resuscitated patients (50 vs. 36%, p = 0.0452) and when Impella was implanted post-PCI (Impella-pre-PCI: 28%, Impella-post-PCI: 51%, p = 0.0039). While in both score systems there was no significant difference between predicted and observed overall 30-day mortality, predicted mortality was significantly higher than observed mortality on Impella support only for individuals with highest predicted risk based on CardShock score (predicted 77 vs. observed 51%, p = 0.025).Conclusions: Our retrospective analysis suggests that the use of the Impella microaxial pump may be effective in selected cases of high risk patients with AMI-CS.Condensed abstract: Mortality is high in acute myocardial infarction-related cardiogenic shock despite rapid revascularization. Haemodynamic support with an intraortic balloon pump does not reduce mortality. In this retrospective registry including 166 consecutive IABP-Shock II-eligible cardiogenic shock patients in four dedicated shock centers, observed mortality on circulatory support with an Impella was significantly lower than predicted in patients with highest mortality risk. Implantation prior to PCI in acute myocardial infarction-related cardiogenic shock seemed to be associated with lower mortality than implantation post PCI.

Background. High CHA2DS2-VASC and HAS-BLED scores are linked to increased mortality in structural and nonstructural cardiovascular interventions irrespective of the presence of atrial fibrillation (AF) or oral anticoagulation. We aimed to use the aforementioned scores to quantify the risk of 30-day mortality, major vascular and bleeding events (MVASC/BARC), and cerebrovascular insults (CVI) in patients undergoing different access routes in transcatheter aortic valve replacement (TAVR). Methods. Out of 1329 patients, 980 transfemoral (TF) TAVR (73.7%) and 349 transapical (TA) TAVR (26.3%) were included. CHA2DS2-VASC, HAS-BLED, and combined “CHADS-BLED” scores were calculated and compared to the predictive value of the established EuroSCORE and STS score. Results. In all-comers TF TAVR patients, the applied risk models showed only poor association with 30-day mortality while, in patients with concomitant AF, a strong association was observed using the combined CHADS-BLED score (c-index: 0.83; 95% CI: 0.76–0.91; p

Endothelial microparticles (EMPs) are markers of endothelial injury and activation. The role of EMPs in arterial hypertension is not well understood and EMPs are increased both in arterial hypertension and coronary artery disease (CAD). The data presented here show EMPs as defined by CD31+/41−, CD62e+, and CD144+ surface markers and vascular hemodynamic parameters including office and central blood pressure, heart rate, aortic augmentation index, pulse wave velocity, flow-mediated dilation, nitroglycerin-mediated dilation, brachial artery diameter, hyperemic wall shear stress, and laser Doppler perfusion of the cutaneous microcirculation of normotensives and hypertensives with and without CAD.

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.

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.

Abstract Background While most patients recover from suspected acute myocarditis (sAMC) some develop progressive disease with 5-year mortality up to 20%. Recently, parametric Cardiovascular Magnetic Resonance (CMR) approaches, quantifying native T1 and T2 relaxation time, have demonstrated the ability to increase diagnostic accuracy. However, prognostic implications of T2 values in this cohort are unknown. The purpose of the study was to investigate the prognostic relevance of elevated CMR T2 values in patients with sAMC. Methods and Results We carried out a prospective study in 46 patients with sAMC defined by current ESC recommendations. A combined endpoint was defined by the occurrence of at least one major adverse cardiac event (MACE) and hospitalisation for heart failure. Event rate was 24% (n = 11) for 1-year-MACE and hospitalisation. A follow-up after 11 ± 7 months was performed in 98% of the patients. Global T2 values were significantly increased at acute stage of disease compared to controls and decreased over time. During acute disease, elevated global T2 time (odds ratio 6.3, p 80 ms (odds ratio 4.9, p

The safety and efficacy of deep sedation (DS) in MitraClip® procedures have been shown previously. However, clinical experience demonstrates that in some patients DS is difficult to achieve. We hypothesize that some patient characteristics can predict difficult DS.We prospectively analysed 69 patients undergoing MitraClip® procedures using DS. Application of DS was graded as simple (group 1) or difficult (group 2) depending on a cumulative score based on one point for each of the following criteria: decrease in oxygen saturation, retention of carbon dioxide, disruptive body movements, and the need for catecholamines. Patients with one point or less were classified as group 1, and patients with two or more points were classified as group 2.In 58 of 69 patients (84.1%), the performance of DS was simple, while in 11 patients (15.9%), DS was difficult to achieve. Patients with difficult DS were characterized by a higher body mass index (33.7 ± 6.0 kg/m2 vs. 26.1 ± 4.1; p = 0.001), younger age (67 ± 13 years vs. 75 ± 13 years; p = 0.044), and reduced left ventricular ejection fraction (36% ± 10 vs. 45% ± 14; p = 0.051) and presented more often with an obstructive sleep apnoea syndrome (6.9% vs. 45.5%; p = 0.003). In the multivariate analysis, body mass index was an independent predictor of difficult DS. Using a body mass index of 31 kg/m2 as a cut-off value, the sensitivity of predicting difficult DS was 73%, and the specificity was 88%. Using a body mass index of 35 kg/m2 as a cut-off value, the specificity increased to 97%, with a sensitivity of 36%.In patients with a higher body mass index who undergo MitraClip® procedures, DS might be difficult to perform.