Aims Heart transplantation (HTx) represents optimal care for advanced heart failure. Left ventricular assist devices (LVADs) are often needed as a bridge‐to‐transplant (BTT) therapy to support patients during the wait for a donor organ. Prolonged support increases the risk for LVAD complications that may affect the outcome after HTx. Methods and results A total of 342 patients undergoing HTx after LVAD as BTT in a 10‐year period in two German high‐volume HTx centres were retrospectively analysed. While 73 patients were transplanted without LVAD complications and with regular waiting list status (T, n = 73), the remaining 269 patients were transplanted with high urgency status (HU) and further divided with regard to the observed leading LVAD complications (infection: HU1, n = 91; thrombosis: HU2, n = 32; stroke: HU3, n = 38; right heart failure: HU4, n = 41; arrhythmia: HU5, n = 23; bleeding: HU6, n = 18; device malfunction: HU7, n = 26). Postoperative hospitalization was prolonged in patients with LVAD complications. Analyses of perioperative morbidity revealed no differences regarding primary graft dysfunction, renal failure, and neurological events except postoperative infections. Short‐term survival, as well as Kaplan–Meier survival analysis, indicated comparable results between the different study groups without disadvantages for patients with LVAD complications. Conclusions Left ventricular assist device therapy can impair the outcome after HTx. However, the occurrence of LVAD complications may not impact on outcome after HTx. Thus, we cannot support the prioritization or discrimination of HTx candidates according to distinct mechanical circulatory support‐associated complications. Future allocation strategies have to respect that device‐related complications may define urgency but do not impact on the outcome after HTx.
Calcific aortic valve disease (CAVD) is a frequent cardiac pathology in the aging society. Although valvular interstitial cells (VICs) seem to play a crucial role, mechanisms of CAVD are not fully understood. Development of tissue-engineered cellular models by 3D-bioprinting may help to further investigate underlying mechanisms of CAVD. VIC were isolated from ovine aortic valves and cultured in Dulbecco’s modified Eagle’s Medium (DMEM). VIC of passages six to ten were dissolved in a hydrogel consisting of 2% alginate and 8% gelatin with a concentration of 2 × 106 VIC ml−1. Cell-free and VIC-laden hydrogels were printed with an extrusion-based 3D-bioprinter (3D-Bioplotter® Developer Series, EnvisionTec, Gladbeck, Germany), cross-linked and incubated for up to 28 d. Accuracy and durability of scaffolds was examined by microscopy and cell viability was tested by cell counting kit-8 assay and live/dead staining. 3D-bioprinting of scaffolds was most accurate with a printing pressure of P < 400 hPa, nozzle speed of v < 20 mm s−1, hydrogel temperature of TH = 37 °C and platform temperature of TP = 5 °C in a 90° parallel line as well as in a honeycomb pattern. Dissolving the hydrogel components in DMEM increased VIC viability on day 21 by 2.5-fold compared to regular 0.5% saline-based hydrogels (p < 0.01). Examination at day 7 revealed dividing and proliferating cells. After 21 d the entire printed scaffolds were filled with proliferating cells. Live/dead cell viability/cytotoxicity staining confirmed beneficial effects of DMEM-based cell-laden VIC hydrogel scaffolds even 28 d after printing. By using low pressure printing methods, we were able to successfully culture cell-laden 3D-bioprinted VIC scaffolds for up to 28 d. Using DMEM-based hydrogels can significantly improve the long-term cell viability and overcome printing-related cell damage. Therefore, future applications 3D-bioprinting of VIC might enable the development of novel tissue engineered cellular 3D-models to examine mechanisms involved in initiation and progression of CAVD.
15 September 2021 in Immunity, Inflammation and Disease
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 < .01). During the first year, a total of 18 patients developed CMV‐DNAemia (D+/R−: 31.6%, D−/R+: 31.9%, D−/R−: 3.4%, D+/R+: 11.1%, p = .03).Conclusions: Seropositive recipients carry an important risk for CMV‐DNAemia. However, we did not observe differences in perioperative morbidity and mortality regarding CMV matching, which might be related to regularly administer prophylactic virostatics and additional CMV‐IVIG for risk constellations. For high‐risk constellation, long‐term application of CMV‐IVIG during the first year after transplant may be beneficial.
Despite the critical feature of heparin-induced thrombocytopenia (HIT) for patients on mechanical circulatory support, reports on its incidence and outcome are still scarce. Thus, we report on clinical features of HIT in patients under Impella 5.0 or 5.5 (Abiomed Inc., Danvers, MA, USA) (Impella 5+) support for acute cardiogenic shock (CS) by focusing on observed thrombotic events. Between November 2018 and December 2020, a total of 56 consecutive patients were enrolled in a single-center retrospective study. A total of 21 patients (37.5%) were tested for HIT, and 6 (10.7%) proved positive for HIT at 10.5 ± 2.89 days after the first heparin administration during current admission. Interestingly, thrombocyte counts dropped under Impella support in all groups (all cases, no HIT test, and HIT negative group: p < 0.001, HIT-positive group: p = 0.001). All HIT-positive patients were switched from heparin to argatroban. HIT-associated thrombotic events were observed in two cases resulting in Impella dysfunction due to pump thrombosis (n = 1) and left ventricular (LV) thrombus formation (n = 1). Under large Impella support, the prevalence of HIT was relatively high. Further, thrombocytopenia does not deliver a high specificity in the setting of Impella 5+ support. Considering HIT manifestation, a routine HIT test may be considered to avoid critical thrombotic adverse events.
Background and Aim of the Study Iron deficiency (ID), a common malnutrition, has been linked to impaired prognosis in patients with congestive heart failure. It remains unclear whether ID also affects the outcome after elective cardiac surgery. Methods A total of 378 consecutive patients undergoing either coronary artery bypass grafting (CABG) or surgical aortic valve replacement (SAVR) were prospectively enrolled, and blood samples were taken before surgery for analysis of iron metabolism. Incidence of major adverse cardiovascular and cerebrovascular events (MACCE) was defined as the primary endpoint of the study. Results ID (ferritin < 100 ng/ml or ferritin = 100–299 ng/ml and transferrin saturation < 20%) was common in cardiac surgery patients (ID, n = 265, 70%) and related to significant decreased preoperative hemoglobin values (ID: 13.6 ± 1.6 g/dl, Non‐ID: 14.3 ± 1.5 g/dl, p < 0.01). We did not observe any differences in the postoperative outcome of the two groups. The incidence of MACCE was 4.9% in patients with ID and 8.8% in Non‐ID (p = 0.16). In‐hospital mortality (ID: 1.9%, Non‐ID: 4.4%, p = 0.17) and stroke (ID: 1.1%, Non‐ID: 1.8%, p = 0.64) were also not altered by ID. In addition, intensive care unit and hospital stay, perioperative blood transfusions as well as perioperative morbidities, such as acute kidney injury, low cardiac output syndrome, major bleeding complication, and sternal wound infections were comparable in patients with and without ID. Conclusions The majority of patients undergoing elective CABG or SAVR suffer from ID; however, we found no significant differences in regard to MACCE and postoperative morbidity between ID and non‐ID patients.
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 (RY) or >60 years (RO)) and donor age (≤50 years (DY) or >50 years (DO). A total of n = 201 patients were included (DY/RY, n = 91; DO/RY, n = 38; DY/RO, n = 41; DO/RO, 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 DO/RO group (56.0%) compared to the other groups (DY/RY: 86.1%, DY/RO: 78.8%, DO/RY: 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.