Search

Background: Degenerative aortic valve disease (DAVD) is a multifactorial process. We developed an animal model to analyze the isolated, local effect of reactive oxygen species (ROS) on its pathophysiology., Methods: We utilized a photodynamic reaction (PDR) as a source of ROS in the aortic valve by aiming a laser at the aortic valve for 60 min after the administration of a photosensitizer 24 h prior. ROS, laser, and sham groups ( n = 7 each) for every observation period (t = 0; t = 8 d; t = 84 d; t = 168 d) were established. The amount of ROS generation; morphological changes; inflammatory, immune, and apoptotic reactions; and hemodynamic changes in the aortic valves were assessed using appropriate histological, immunohistological, immunohistochemical, and echocardiographic methods., Results: The ROS group displayed an increased amount of ROS ( p < 0.01) and increased inflammatory activation of the endothelium ( p < 0.05) at t = 0. In the ROS group, aortic valves were calcified ( p < 0.05) and the transvalvular gradient was increased ( p < 0.01) at t = 168 d., Conclusion: The small animal model employed here may serve as a platform for analyzing ROS's isolated role in the DAVD context.

Background/Objectives : Coronary artery bypass surgery (CABG) with multiple arterial grafting (MAG) has shown potential to improve patient survival compared to single arterial bypass grafting. Whether this superiority in survival also exists in diabetics is uncertain. We therefore aimed to compare short and long-term outcomes of MAG in diabetic versus non-diabetic patients. Methods : In this retrospective study, we investigated short- and long-term clinical outcomes of diabetic ( n = 256) and non-diabetic ( n = 800) patients undergoing CABG with MAG between January 1999 and December 2019 at our institution. Results : Diabetics had a significantly higher EuroScore II (1.37 ± 2.4 vs. 0.88 ± 1.58, p < 0.0001) and underwent significantly less bilateral internal thoracic artery (BITA) grafting (51.95% vs. 67.75%; p < 0.0001) compared to non-diabetics. The incidence of postoperative adverse events, such as pneumonia, stroke, and sepsis, did not differ between the two groups. However, diabetics suffered significantly more often from post-cardiotomy cardiogenic shock, renal failure requiring dialysis, and sternal wound infections over the entire follow-up period. Non-diabetics had a significantly higher median survival time of 19.6 years compared to 14.54 years found in diabetic patients ( p < 0.0001). Conclusions : Among patients undergoing MAG, diabetic individuals were found to have a significantly lower overall median survival. This emphasizes the importance of diabetes as a risk factor in choosing individual surgical strategies.

Background : Aortic valve infective endocarditis (AV-IE) and mitral valve infective endocarditis (MV-IE) are often grouped together as one entity: left-sided endocarditis. However, there are significant differences between the valves in terms of anatomy, physiology, pressure, and calcification tendency. This study aimed to compare AV-IE and MV-IE in terms of patient characteristics, pathogen profiles, postoperative outcomes, and predictors of mortality. Methods : We retrospectively analyzed data from 3899 patients operated on for isolated AV-IE or MV-IE in six German cardiac surgery centers between 1994 and 2018. Univariable and multivariable analyses were performed to analyze the risk factors for 30 day and 1 year mortality. A Log-rank test was used to test for differences in long-term mortality. Results : Patients with MV-IE were more likely to be female (41.1% vs. 20.3%.; p < 0.001). Vegetation was detected more frequently in the MV-IE group (66.6% vs. 57.1%; p < 0.001). Accordingly, the rates of cerebral embolic events (25.4% vs. 17.7%; p < 0.001) and stroke (28.2% vs. 19.3%; p < 0.001) were higher in the MV-IE group. Staphylococci had a higher prevalence in the MV-IE group (50.2% vs. 36.4%; p < 0.001). Patients with MV-IE had comparable 30 day mortality (16.7% vs. 14.6%; p = 0.095) but significantly higher 1 year mortality (35.3% vs. 29.0%; p < 0.001) than those with AV-IE. Kaplan-Meier survival analysis showed significantly lower long-term survival in patients with MV-IE (log-rank p < 0.001). Conclusions : Due to the relevant differences between MV-IE and AV-IE, it might be useful to provide individualized, valve-specific guideline recommendations rather than general recommendations for left-sided IE.

Background: Acute aortic dissection type A (AADA) is a surgical emergency with relevant mortality and morbidity despite improvements in current management protocols. Identifying patients at risk of a fatal outcome and controlling the factors associated with mortality remain of paramount importance., Methods: In this retrospective observational study, we reviewed the medical records of 117 patients with AADA, who were referred to our centre and operated on between 2005 and 2021. Preoperative, intraoperative, and postoperative variables were analysed and tested for their correlation with in-hospital mortality., Results: The overall survival rate was 83%. Preoperatively, factors associated with mortality were age ( p = 0.02), chronic hypertension ( p = 0.02), any grade of aortic valve stenosis in the patient's medical history ( p = 0.03), atrial fibrillation ( p = 0.04), and oral anticoagulation ( p = 0.04). Non-survivors had significantly longer operative times ( p = 0.002). During the postoperative phase, mortality was strongly associated with acute kidney injury (AKI) ( p < 0.001), acute heart failure ( p < 0.001), stroke ( p = 0.02), focal neurological deficits ( p = 0.02), and sepsis ( p = 0.001). In the multivariate regression analysis, the onset of postoperative focal neurological deficits was the best predictor of a fatal outcome after adjusting for ARDS (odds ratio: 5.8, 95%-CI: 1.2-41.7, p = 0.04)., Conclusions: In this retrospective analysis, atrial fibrillation, oral anticoagulation, hypertension, and age were significantly correlated with mortality. Postoperatively, acute kidney injury, acute heart failure, sepsis, and focal neurological deficits were correlated with in-hospital mortality, and focal neurological deficit has been identified as a significant predictor of fatal outcomes. Early detection and interdisciplinary management of at-risk patients remain crucial throughout the postoperative phase.

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.

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

Objective: Although the application of higher doses of norepinephrine (NE) in potential organ donors is a frequent reason for heart decline, its associations with outcomes after heart transplantation (HTx) are discussed controversially. Therefore, we aimed to explore donor NE support’s potential impact on outcomes in our single-center heart transplant cohort. Methods: All patients who had undergone HTx in our center between September 2010 and April 2022 (n = 241) were screened for eligibility. From those, all patients with complete data on donor NE support (n = 238) were included. Recipients were divided into three groups according to their donor NE support: without support (n = 26), with low support of 0.01−0.2 µg/kg/min (n = 132), and with high support of > 0.2 µg/kg/min (n = 80). Receiver operating characteristics (ROC) and Kaplan Meier analysis was used to investigate the association of donor NE support and mortality after heart transplantation. Recipient and donor variables, including peri- and postoperative characteristics, were reviewed and compared. Results: NE support in donors ranged between 0 and 2.94 µg/kg/min (median 0.13 µg/kg/min, IQR 0.05−0.26 µg/kg/min). No association between donor NE support and mortality after HTx was observed (AUC for overall survival 0.494). Neither Kaplan-Meier analysis in survival up to 5 years after transplantation (Log Rank p = 0.284) nor group comparisons showed significant differences between the groups. With few exceptions, baseline characteristics in recipients and donors were comparable between the groups. Regarding peri- and postoperative parameters, increasing donor NE support was associated with a longer duration of mechanical ventilation (68 h and 95 h vs. 47 h), longer postoperative IMC/ICU stay (14 vs. 15 vs. 19 days), and a higher need for mechanical life support post-HTx (26% and 39% vs. 12%). Conclusion: In this retrospective analysis, NE support in donors prior to heart transplantation was unrelated to differing survival after heart transplantation. However, higher doses of donor NE were associated with prolonged ventilation, longer duration on IMC/ICU, and a higher need for extracorporeal life support in recipients post-HTx.

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.

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.

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.

As society is ageing, an increasing prevalence of elderly heart failure patients will be expected. In order to increase the donor pool, acceptance of older donors might be a reasonable choice. All patients undergoing heart transplantation between 2010 and 2021 at a single department were retrospectively reviewed and divided into different study groups with regard to recipient (≤60 years (R Y ) or >60 years (R O )) and donor age (≤50 years (D Y ) or >50 years (D O ). A total of n = 201 patients were included (D Y /R Y , n = 91; D O /R Y , n = 38; D Y /R O , n = 41; D O /R O , n = 31). Neither incidence of severe primary graft dysfunction ( p = 0.64) nor adverse events, such as kidney failure ( p = 0.27), neurological complications ( p = 0.63), infections ( p = 0.21) or acute graft rejection ( p = 1.00), differed between the groups. However, one-year survival was impaired in the D O /R O group (56.0%) compared to the other groups (D Y /R Y : 86.1%, D Y /R O : 78.8%, D O /R Y : 74.2%, p = 0.02). Given the impaired one-year survival, acceptance of grafts from old donors for old recipients should be performed with caution and by experienced centres only. Nevertheless, because of the otherwise dismal prognosis of elderly heart failure patients, transplantation of patients may still improve the therapy outcome.

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.

Serum levels of cytokines interleukin 1 beta ( IL-1β ) and interleukin 33 (IL-33) are highly abnormal in heart failure and remain elevated after mechanical circulatory support (MCS). However, local cytokine signaling induction remains elusive. Left (LV) and right ventricular (RV) myocardial tissue specimens of end-stage heart failure (HF) patients without ( n = 24) and with MCS ( n = 39; 594 ± 57 days) were analyzed for cytokine mRNA expression level of IL-1B , interleukin 1 receptor 1/2 ( IL-1R1/2 ), interleukin 1 receptor-like 1 ( IL-1RL1 ), IL-33 and interleukin-1 receptor accessory protein ( IL-1RaP ). MCS patients showed significantly elevated IL-1B expression levels (LV: 2.0 fold, p = 0.0058; RV: 3.3 fold, p < 0.0001). Moreover, IL-1R1 , IL-1RaP and IL-33 expression levels strongly correlated with each other. IL-1RL1 and IL-1R2 expression levels were significantly higher in RV myocardial tissue (RV/LV ratio IL-1R2 HF: 4.400 ± 1.359; MCS: 4.657 ± 0.655; IL-1RL1 HF: 3.697 ± 0.876; MCS: 4.529 ± 0.5839). In addition, IL1-RaP and IL-33 RV expression levels were significantly elevated in MCS. Furthermore, IL-33 expression correlates with C-reactive protein (CRP) plasma levels in HF, but not in MCS patients. Increased expression of IL-1B and altered correlation patterns of IL-1 receptors indicate enhanced IL-1β signaling in MCS patients. Correlation of IL-1 receptor expression with IL-33 may hint towards a link between both pathways. Moreover, diverging expression in LV and RV suggests specific regulation of local cytokine signaling.

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: It is current practice to perform concomitant coronary artery bypass grafting (CABG) in patients with infective endocarditis (IE) who have relevant coronary artery disease (CAD). However, CABG may add complexity to the operation. We aimed to investigate the impact of concomitant CABG on perioperative outcomes in patients undergoing surgery for IE., Methods: We retrospectively used data of surgically treated IE patients between 1994 and 2018 in six German cardiac surgery centers. We performed inverse probability weighting (IPW), multivariable adjustment, chi-square analysis, and Kaplan-Meier survival estimates., Results: CAD was reported in 1242/4917 (25%) patients. Among them, 527 received concomitant CABG. After adjustment for basal characteristics between CABG and no-CABG patients using IPW, concomitant CABG was associated with higher postoperative stroke (26% vs. 21%, p = 0.003) and a trend towards higher postoperative hemodialysis (29% vs. 25%, p = 0.052). Thirty-day mortality was similar in both groups (24% vs. 23%, p = 0.370). Multivariate Cox regression analysis after IPW showed that CABG was not associated with better long-term survival (HR: 1.00, 95% CI: 0.82-1.23, p = 0.998)., Conclusion: In endocarditis patients with CAD, adding CABG to valve surgery may be associated with a higher likelihood of postoperative stroke without adding long-term survival benefits. Therefore, in the absence of critical CAD, concomitant CABG may be omitted without impacting outcome. The results are limited due to a lack of data on the severity of CAD, and therefore there is a need for a randomized trial.

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.

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.

Extracorporeal life support (ECLS) is a promising therapeutic option for patients with refractory cardiogenic shock. However, as the mortality rate still remains high, there is a need for early outcome parameters reflecting therapy success or futility. Therefore, we investigated whether liver enzyme levels could serve as prognostic mortality markers for patients with ECLS. The present study is a retrospective single-center cohort study. Adult patients >18 years of age who received ECLS therapy between 2011 and 2018 were included. Bilirubin, glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic-transaminase (GPT) serum levels were analyzed at day 5 after the start of the ECLS therapy. The primary endpoint of this study was all-cause in-hospital mortality. A total of 438 patients received ECLS during the observation period. Based on the inclusion criteria, 298 patients were selected for the statistical analysis. The overall mortality rate was 42.6% ( n = 127). The area under the curve (AUC) in the receiver operating characteristic curve (ROC) for bilirubin on day 5 was 0.72 (95% confidence interval (CI): 0.66-0.78). Cox regression with multivariable adjustment revealed a significant association between bilirubin on day 5 and mortality, with a hazard ratio (HR) of 2.24 (95% CI: 1.53-3.30). Based on the results of this study, an increase in serum bilirubin on day 5 of ECLS therapy correlates independently with mortality.