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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.

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 < 0.0001; non‐ECMO vs. VA‐ECMO (weaned): 310 (277–327) days vs. 253 (208–299) days; P < 0.0001]. These results were still significant after multivariable adjustment with forced entry of predefined covariables. Conclusions Despite similar survival rates, VA‐ECMO due to PGD has a relevant life impact as defined by DAOH in the first year after HTX. As a more patient‐centred endpoint, DAOH may contribute to a more comprehensive assessment of outcome in HTX patients.

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 < 3 were associated with lower DAOH at 1 year [CKD: 280 (155–322) vs. 230 (0–219), P = 0.0286; pMCS: 294 (155–325) vs. 243 (0–293), P = 0.0004; INTERMACS 1: 218 (0–293) vs. INTERMACS 2: 264 (6–320) vs. INTERMACS 3: 299 (228–325) vs. INTERMACS 4: 313 (247–332), P ≤ 0.0001]. Intra‐operative additional implantation of a right ventricular assist device (RVAD) was also associated with lower DAOH [RVAD: 290 (160–325) vs. 174 (0–277), P ≤ 0.0001]. As post‐operative values that were associated with lower DAOH, dialysis and tracheotomy could be identified [dialysis: 300 (252–326) vs. 186 (0–300), P ≤ 0.0001; tracheotomy: 292 (139–325) vs. 168 (0–269), P ≤ 0.0001]. Multivariate analysis revealed that all of these factors besides pMCS were independently associated with DAOH. According to Kaplan–Meier analysis, only post‐operative dialysis was significantly associated with increased mortality at 1 year (survival: no dialysis 89.4% vs. dialysis 70.1%, hazard ratio: 0.56, 95% confidence interval: 0.33–0.94; P = 0.031). Conclusions The results of this study indicate that there can be a clear discrepancy between hard endpoints such as mortality and more patient‐centred outcomes reflecting life impact. DAOH may relevantly contribute to a more comprehensive selection process and outcome assessment in LVAD patients.

PurposeActivation of mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa)-channels is a crucial step for cardioprotection by preconditioning. Whether activation of these channels is involved in levosimendan-induced preconditioning is unknown. We investigated if cardioprotection by levosimendan requires activation of mBKCa-channels in the rat heart in vitro.MethodsIn a prospective blinded experimental laboratory investigation, hearts of male Wistar rats were randomized and placed on a Langendorff system, perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. All hearts were subjected to 33 min of global ischemia and 60 min of reperfusion. Before ischemia, hearts were perfused with different concentrations of levosimendan (0.03–1 μM) for determination of a dose-effect curve. In a second set of experiments, 0.3 μM levosimendan was administered in combination with the mBKCa-channel inhibitor paxilline (1 μM). Infarct size was determined by TTC staining.ResultsIn control, animal’s infarct size was 58 ± 7%. Levosimendan at a concentration of 0.3 μM reduced infarct size to 30 ± 7% (P < 0.05 vs. control). Higher concentrations with 1 μM levosimendan did not confer stronger protection. Paxilline completely blocked levosimendan-induced cardioprotection while paxilline alone had no effect on infarct size.ConclusionsThis study shows that activation of mBKCa-channels plays a pivotal role in levosimendan-induced preconditioning.

PurposeSmall and big conductance Ca2+-sensitive potassium (KCa) channels are involved in cardioprotective measures aiming at reducing myocardial reperfusion injury. For levosimendan, infarct size–reducing effects were shown. Whether activation of these channels is involved in levosimendan-induced postconditioning is unknown. We hypothesized that levosimendan exerts a concentration-dependent cardioprotective effect and that both types of Ca2+-sensitive potassium channels are involved.MethodsIn a prospective blinded experimental laboratory investigation, hearts of male Wistar rats were randomized and placed on a Langendorff system, perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. All hearts were subjected to 33 min of global ischemia and 60 min of reperfusion. At the onset of reperfusion, hearts were perfused with various concentrations of levosimendan (0.03–1 μM) in order to determine a concentration-response relationship. To elucidate the involvement of KCa-channels for the observed cardioprotection, in the second set of experiments, 0.3 μM levosimendan was administered in combination with the subtype-specific KCa-channel inhibitors paxilline (1 μM, big KCa-channel) and NS8593 (0.1 μM, small KCa-channel) respectively. Infarct size was determined by tetrazolium chloride (TTC) staining.ResultsInfarct size in controls was 60 ± 7% and 59 ± 6% respectively. Levosimendan at a concentration of 0.3 μM reduced infarct size to 30 ± 5% (P < 0.0001 vs. control). Higher concentrations of levosimendan did not induce a stronger effect. Paxilline but not NS8593 completely abolished levosimendan-induced cardioprotection while both substances alone had no effect on infarct size.ConclusionsCardioprotection by levosimendan-induced postconditioning shows a binary phenomenon, either ineffective or with maximal effect. The cardioprotective effect requires activation of big but not small KCa channels.

The aim of this study was to evaluate the prognostic value of osteopontin (OPN) as a marker for left ventricular (LV) hypertrophy and its reversibility after surgical aortic valve replacement (SAVR). Echocardiographic data and OPN plasma levels of 149 consecutive patients undergoing SAVR were obtained preoperatively and 3 months postoperatively. OPN was measured by Quantikine Human OPN immunoassay. There was a significant correlation between higher OPN plasma levels and lower LV-mass regression. In patients receiving SAVR combined with coronary artery bypass grafting, high OPN plasma levels were also an indicator for eccentric hypertrophy phenotype. OPN may be a useful indicator for LV hypertrophy phenotype and could have a prognostic value to estimate LV-mass regression after SAVR.

Background: The number of patients waiting for heart transplantation (HTX) is increasing. Optimizing the use of all available donor hearts is crucial. While mortality seems not to be affected by donor cardiopulmonary resuscitation (CPR), the impact of donor CPR on days alive and out of hospital (DAOH) is unclear. Methods: This retrospective study included adults who underwent HTX at the University Hospital Duesseldorf, Germany from 2010–2020. Main exposure was donor-CPR. Secondary exposure was the length of CPR. The primary endpoint was DAOH at one year. Results: A total of 187 patients were screened and 171 patients remained for statistical analysis. One-year mortality was 18.7%. The median DAOH at one year was 295 days (interquartile range 206–322 days). Forty-two patients (24.6%) received donor-CPR hearts. The median length of CPR was 15 (9–21) minutes. There was no significant difference in DAOH between patients with donor-CPR hearts versus patients with no-CPR hearts (CPR: 291 days (211–318 days) vs. no-CPR: 295 days (215–324 days); p = 0.619). Multivariate linear regression revealed that there was no association between length of CPR and DAOH (unstandardized coefficients B: −0.06, standard error: 0.81, 95% CI −1.65–1.53, p = 0.943). Conclusions: Donor CPR status and length of CPR are not associated with reduced DAOH at one year after HTX.

Acute kidney injury (AKI), requiring renal replacement therapy (RRT). is a serious complication after orthotopic heart transplantation (HTX). In patients with preexisting impaired renal function, postoperative AKI is unsurprising. However, even in patients with preserved renal function, AKI requiring RRT is frequent. Therefore, this study aimed to identify risk factors associated with postoperative AKI requiring RRT after HTX in this sub-cohort. This retrospective cohort study included patients ≥ 18 years of age with preserved renal function (defined as preoperative glomerular filtration rate ≥ 60 mL/min) who underwent HTX between 2010 and 2021. In total, 107 patients were included in the analysis (mean age 52 ± 12 years, 78.5% male, 45.8% AKI requiring RRT). Based on univariate logistic regression, use of extracorporeal membrane oxygenation, postoperative infection, levosimendan therapy, duration of norepinephrine (NE) therapy and maximum daily increase in tacrolimus plasma levels were chosen to be included into multivariate analysis. Duration of NE therapy and maximum daily increase in tacrolimus plasma levels remained as independent significant risk factors (NE: OR 1.01, 95%CI: 1.00–1.02, p = 0.005; increase in tacrolimus plasma level: OR 1.18, 95%CI: 1.01–1.37, p = 0.036). In conclusion, this study identified long NE therapy and maximum daily increase in tacrolimus plasma levels as risk factors for AKI requiring RRT in HTX patients with preserved renal function.

Background: Angiogenesis-angiostasis balance and leukocyte recruitment are influenced by different concentrations of distinct chemokines. Objective: To investigate the relative contribution of angiogenic and angiostatic CXC chemokines to the pathogenesis of idiopathic pulmonary fibrosis (IPF) and granulomatous lung diseases, we examined the in vitro production of an angiogenic chemokine (IL-8), and 2 angiostatic chemokines (IP-10 and MIG) by alveolar macrophages. Methods: Alveolar macrophages from 16 patients with granulomatous lung diseases [8 with sarcoidosis, 8 with extrinsic allergic alveolitis (EAA)], 16 patients with IPF, and 8 control subjects were cultured for 24 h. IL-8, IL-18, IP-10 and MIG in the culture supernatants were measured by a fluorescent bead-based multiplex technique. Results: In IPF patients, IL-8 was increased and correlated with bronchoalveolar lavage (BAL) neutrophils, whereas the levels of IP-10 and MIG were normal. In sarcoidosis and EAA patients, IL-8, IP-10, and MIG were all increased and IP-10 and MIG correlated with IL-18, a Th1 cytokine, and the percentage and number of BAL lymphocytes. Conclusions: The difference in the expression of CXC chemokines and a Th1 cytokine may contribute to the different immunopathogenesis, clinical course and responsiveness to treatment of these diseases.