Fully magnetically centrifugal left ventricular assist device and long-term outcomes: the ELEVATE registry.

BACKGROUND AND AIMS: HeartMate 3 (HM3) is a fully magnetically levitated continuous flow left ventricular assist device, which received CE marking in 2015. The ELEVATE Registry was initiated to collect real-world outcomes in patients treated with HM3 post-CE Mark approval. METHODS: A total of 540 subjects implanted at 26 centres between March 2015 and February 2017 were included in this registry. Of these, 463 received the device as a primary implant (primary implant cohort, PIC), 19 as a pump exchange (pump exchange cohort), and in 58 patients, only anonymized survival data were collected (anonymized cohort, AC). Patients in the PIC contributed to the baseline demographics, survival, adverse events, quality of life (QoL) (EuroQoL-5 Dimensions-5 Levels visual analogue scale), and functional capacity (6 min walk distance) assessments, while patients in the AC contributed only to survival. RESULTS: Primary implant cohort patients had a mean age of 56 years and were predominantly male (89%) with 48% ischaemic aetiology. The majority of subjects was designated bridge to transplant (66%) and had INTERMACS Profiles 1-3 (70%). At baseline, the subjects had poor functional capacity (104 ± 140 m) and impaired QoL (35 ± 19 points). The overall survival rate of the PIC was 63.3% and survival free of stroke was 58.1% at 5 years. Significant improvements in functional capacity and QoL were observed and maintained for 5 years (301 ± 131 m and 64 ± 20 points, respectively). CONCLUSIONS: Real-world data from the ELEVATE registry demonstrate an overall survival rate for primary implants of 63.3%. In the PIC, reductions in adverse events for patients in the extended follow-up and improved QoL and functional capacity were observed at 5 years in this patient population with advanced heart failure.

Disparities in donor heart acceptance between the USA and Europe: clinical implications.

BACKGROUND AND AIMS: Given limited evidence and lack of consensus on donor acceptance for heart transplant (HT), selection practices vary widely across HT centres in the USA. Similar variation likely exists on a broader scale-across countries and HT systems-but remains largely unexplored. This study characterized differences in heart donor populations and selection practices between the USA and Eurotransplant-a consortium of eight European countries-and their implications for system-wide outcomes. METHODS: Characteristics of adult reported heart donors and their utilization (the percentage of reported donors accepted for HT) were compared between Eurotransplant (n = 8714) and the USA (n = 60 882) from 2010 to 2020. Predictors of donor acceptance were identified using multivariable logistic regression. Additional analyses estimated the impact of achieving Eurotransplant-level utilization in the USA amongst donors of matched quality, using probability of acceptance as a marker of quality. RESULTS: Eurotransplant reported donors were older with more cardiovascular risk factors but with higher utilization than in the USA (70% vs. 44%). Donor age, smoking history, and diabetes mellitus predicted non-acceptance in the USA and, by a lesser magnitude, in Eurotransplant; donor obesity and hypertension predicted non-acceptance in the USA only. Achieving Eurotransplant-level utilization amongst the top 30%-50% of donors (by quality) would produce an additional 506-930 US HTs annually. CONCLUSIONS: Eurotransplant countries exhibit more liberal donor heart acceptance practices than the USA. Adopting similar acceptance practices could help alleviate the scarcity of donor hearts and reduce waitlist morbidity in the USA.

Intracerebral Hemorrhage in COVID-19 Patients with Pulmonary Failure: A Propensity Score-Matched Registry Study.

BACKGROUND: Hypercoagulability in Coronavirus Disease 2019 (COVID-19) causes deep vein thrombosis and pulmonary embolism necessitating systemic anticoagulation. Case reports of intracerebral hemorrhages in ventilated COVID-19 patients warrant precaution. It is unclear, however, if COVID-19 patients with acute respiratory distress syndrome (ARDS) with or without veno-venous extracorporeal membrane oxygenation therapy (VV-ECMO) have more intracerebral hemorrhages (ICH) compared to other ARDS patients. METHODS: We conducted a retrospective observational single-center study enrolling all patients with ARDS from 01/2018 to 05/2020. PCR-positive SARS-CoV-2 patients with ARDS were allocated to the COVID-19 group. Propensity score matching was performed for age, VV-ECMO, and bleeding risk. RESULTS: A total of 163 patients with moderate or severe ARDS were identified, 47 (28.8%) in the COVID-19 group, and 116 (71.2%) in the non-COVID-19 group. In 63/163 cases (38.7%), VV-ECMO therapy was required. The ICU survival was 52.8%. COVID-19 patients were older, more often male, and exhibited a lower SOFA score, but the groups showed similar rates of VV-ECMO therapy. Treatments with antiplatelet agents (p = 0.043) and therapeutic anticoagulation (p = 0.028) were significantly more frequent in the COVID-19 patients. ICH was detected in 22 patients (13.5%) with no statistical difference between the groups (11.2 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.21). Propensity score matching confirmed similar rates of ICH in both groups (12.8 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.57), thus leveling out possible confounders. CONCLUSIONS: Intracerebral hemorrhage was detected in every tenth patient with ARDS. Despite statistically higher rates of antiplatelet therapy and therapeutic anticoagulation in COVID-19 patients, we found a similar rate of ICH in patients with ARDS due to COVID-19 compared to other causes of ARDS.

Two-year outcome after implantation of a full magnetically levitated left ventricular assist device: results from the ELEVATE Registry.

AIMS: The ELEVATE Registry was designed to study long-term outcomes with the Heartmate 3 (HM3), a fully magnetically levitated centrifugal ventricular assist device, in a real-world population following CE-mark approval. METHODS AND RESULTS: A total of 540 patients, implanted in Europe and the Middle East were followed in ELEVATE. The registry included 463 patients receiving the HM3 as primary implant (Primary Implant Cohort), 19 patients underwent a pump upgrade from another device (Pump Exchange Cohort) and 58 patients who had experienced an outcome before having the possibility to sign the Informed Consent, for which only outcome data were collected (Anonymized Cohort). Data collection included demographics, survival, adverse events, EQ-5D Visual Analog Score quality of life (EQ-5D VAS QOL) questionnaire, and 6-min walk distance (6MWD). Mean age was 55.6 ± 11.7 years (89% male, 48% ischaemic cardiomyopathy). Seventy per cent of patients were in INTERMACS Profile 1-3 and 12.7% were on temporary mechanical circulatory support. Primary Implant Cohort survival was 83% after 2 years. In the Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Primary Implant Cohort, strokes were observed in 10.2%, gastrointestinal bleedings in 9.7%, pump thrombosis in 1.5%, and outflow graft twists in 3.5%. Heartmate 3 implantation resulted in a significant and sustained improvement of functional capacity and QOL. CONCLUSION: In a real-world population, cohort implanted with the HM3 left ventricular assist device we demonstrate good long-term survival, sustained improvement of functional capacity, and low rates of adverse events (including pump thrombosis). CLINICALTRIALS.GOV IDENTIFIER: NCT02497950.

Heart re-transplantation in Eurotransplant.

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation.

The endogenous thrombin potential in patients with left ventricular assist device or heart transplant.

Background: The Heartmate 3 (HM 3) is a left ventricular assist device featuring less shear stress, milder acquired von Willebrand syndrome, and fewer bleeding incidences than its predecessor the Heartmate II (HM II). The novel surface coating of the HM 3 suggests less contact activation of plasmatic coagulation. We hypothesized that patients with HM 3 exhibit fewer aberrations in their thrombin potential than patients with HM II. We compared these results with the thrombin potential of patients with heart transplantation (HTX). Methods: Thrombin generation in plasma samples of patients with HM II (n = 16), HM 3 (n = 20), and HTX (n = 13) was analyzed 3 days after implantation/transplantation and after long-term support (3-24 months) with HM II (n = 16) or HM 3 (n = 12) using calibrated automated thrombography. Heparin in postoperative samples was antagonized with polybrene. Results: Three days postoperatively HM II patients exhibited a lower endogenous thrombin potential (ETP) than HM 3 and HTX patients (HM II: 947 ± 291 nM*min; HM 3: 1231 ± 176 nM*min; HTX: 1376 ± 162 nM*min, p < 0.001) and a lower velocity index of thrombin generation (HM II: 18.74 ± 10.90 nM/min; HM 3: 32.41 ± 9.51 nM/min; HTX: 37.65 ± 9.41 nM/min, p < 0.01). Subtle differences in the thrombin generation profiles remained in HM II and HM 3 patients under long-term support (Velocity Index: HM II: 38.70 ± 28.46 nM/min; HM 3: 73.32 ± 32.83 nM/min, p < 0.05). Prothrombin fragments 1 + 2 were higher in HM II than in HM 3 patients (HM II: 377.7 ± 208.4 pM; HM 3: 202.1 ± 87.7 pM, p < 0.05) and correlated inversely with the ETP (r = -0.584, p < 0.05). Conclusion: We observed a more aberrant thrombin generation in HM II than in HM 3 despite comparable anticoagulation and routine parameters. A trend toward lower values was still observable in HM 3 compared to HTX patients. Calibrated automated thrombography may be a good tool to monitor the coagulation state of these patients and guide anticoagulation in the future.

Efficacy of levosimendan infusion in patients undergoing a left ventricular assist device implant in a propensity score matched analysis of the EUROMACS registry-the Euro LEVO-LVAD study.

OBJECTIVES: Early right-sided heart failure (RHF) was seen in 22% of recipients of a left ventricular assist device (LVAD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). However, the optimal treatment of post-LVAD RHF is not well known. Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure. We sought to evaluate the efficacy of levosimendan on post-LVAD RHF and 30-day and 1-year mortality. METHODS: The EUROMACS Registry was used to identify adults with mainstream continuous-flow LVAD implants who were treated with preoperative levosimendan compared to a propensity matched control cohort. RESULTS: In total, 3661 patients received mainstream LVAD, of which 399 (11%) were treated with levosimendan pre-LVAD. Patients given levosimendan had a higher EUROMACS RHF score [4 (2- 5.5) vs 2 (2- 4); P < 0.001], received more right ventricular assist devices (RVAD) [32 (8%) vs 178 (5.5%); P = 0.038] and stayed longer in the intensive care unit post-LVAD implant [19 (8-35) vs 11(5-25); P < 0.001]. Yet, there was no significant difference in the rate of RHF, 30-day, or 1-year mortality. Also, in the matched cohort (357 patients taking levosimendan compared to an average of 622 controls across 20 imputations), we found no evidence for a difference in postoperative severe RHF, RVAD implant rate, length of stay in the intensive care unit or 30-day and 1-year mortality. CONCLUSIONS: In this analysis of the EUROMACS registry, we found no evidence for an association between levosimendan and early RHF or death, albeit patients taking levosimendan had much higher risk profiles. For a definitive conclusion, a multicentre, randomized study is warranted.

Outcomes in patients with cardiac amyloidosis undergoing heart transplantation: the eurotransplant experience.

BACKGROUND: When advanced heart failure occurs in cardiac amyloidosis, prognosis is poor. In this setting heart transplantation (HTX) is a treatment option for selected patients. We here present the results of post-transplantation outcomes in cardiac amyloidosis within the Eurotransplant area, investigating possible predictors of survival. METHODS: Of 115 patients undergoing HTX due to cardiac amyloidosis in the Eurotransplant region between November 1987 and May 2020, detailed assessment prior to transplantation was available in 85 patients. The present study was conducted in a retrospective approach. Primary endpoint was mortality after HTX. Baseline variables were entered in a Cox proportional hazards model with the primary endpoint as a dependent variable. RESULTS: Median overall survival following HTX was 6.3 years in the overall collective and the subgroup. Univariate Cox proportional hazards model revealed a significant relationship between overall survival and the transplantation period (2008 to 2020 vs 1987 to 2007; median survival 9.7 years vs 1.8 years, hazard ratio 0.45, p = 0.01). Further predictors were albumin concentration (hazard ratio 0.92, p < 0.001), and systolic blood pressure (hazard ratio 0.96, p < 0.001). The transplant period as well as albumin concentration remained significant independent predictors in the AL sub cohort in a multivariate Cox proportional hazards model. CONCLUSIONS: HTX is a viable treatment option for patients at an advanced stage of cardiac amyloidosis as overall survival after transplantation has improved in the modern age. Patients at a very advanced stage of the disease, indicated by low serum albumin and blood pressure, show worse outcomes following HTX. Optimal timing and careful patient selection may therefore be particularly important to further improve post-HTX survival in amyloidosis patients.

Double tunnel technique for the LVAD driveline: improved management regarding driveline infections.

A driveline exit site infection is a serious and common complication in long-term left ventricular assist device (LVAD) support. To reduce the incidence and severity of late driveline infections, we modified our surgical technique (double tunnel), and compared it to the conventional short and straight driveline tunnel technique (conventional). We analyzed 43 consecutive patients (37 HeartMate II; 6 Ventrassist) regarding late onset driveline exit site infections after using the surgical driveline tunnel technique after successful LVAD implantation. Of these 43 patients, 11 were treated with the conventional short and straight driveline tunnel technique (conventional), while 32 patients were treated with the modified long subfascial, C-shaped technique (double tunnel). We observed slightly fewer superficial driveline exit site infections in the double tunnel group, even though the difference was not statistically significant (0.638 vs. 1.148 infections/1,000 patient-days; P = 0.22). There were also insignificantly fewer surgical interventions because of exit site infections in the double tunnel group (0.159 vs. 0.581 revisions/1,000 patient-days; P = 0.18). The double tunnel technique offers more surgical options in the case of driveline exit site infections. Due to the long subfascial tunnel, the infected site can be separated from the new driveline exit site, and vacuum-assisted closure therapy can be applied to the infected area. In conclusion, we recommend using the double tunnel driveline technique because of the low infection rate and better treatment options in the case of driveline exit site infection.

Ex-Vivo Preservation with the Organ Care System in High Risk Heart Transplantation.

OBJECTIVE: Ex vivo organ perfusion is an advanced preservation technique that allows graft assessment and extended ex situ intervals. We hypothesized that its properties might be especially beneficial for high-risk recipients and/or donors with extended criteria. METHODS: We reviewed the outcomes of 119 consecutive heart transplant patients, which were divided into two groups: A (OCS) vs. B (conventional). Ex vivo organ perfusion was performed using the Organ Care System (OCS). Indications for OCS-usage were expected ischemic time of >4 h or >2 h plus given extended donor criteria. RESULTS: Both groups included mostly redo cases (A: 89.7% vs. B: 78.4%; p = 0.121). Incidences of donors with previous cardiac arrest (%) (A: 32.4 vs. B: 22.2; p < 0.05) or LV-hypertrophy (%) (A: 19.1 vs. B: 8.3; p = 0.119) were also increased in Group A. Ex situ time (min) was significantly longer in Group A (A: 381 (74) vs. B: 228 (43); p < 0.05). Ventilation time (days) (A: 10.0 (19.9) vs. B: 24.3 (43.2); p = 0.057), postoperative need for ECLS (%) (A: 25.0 vs. B: 39.2; p = 0.112) and postoperative dialysis (chronic) (%) (A: 4.4 vs. B: 27.5; p < 0.001) were numerically better in the OCS group, without any difference in the occurrence of early graft rejection. The 30-d-survival (A: 92.4% vs. B: 90.2%; p = 0.745) and mid-term survival were statistically not different between both groups. CONCLUSIONS: OCS heart allowed safe transplantation of surgically complex recipients with excellent one-year outcomes, despite long preservation times and unfavourable donor characteristics. Furthermore, we observed trends towards decreased ventilation times and fewer ECLS treatments. In times of reduced organ availability and increasing recipient complexity, OCS heart is a valuable instrument that enables otherwise infeasible allocations and contributes to increase surgical safety.

Intensive Care Resources and 60-Day Survival of Critically-Ill COVID-19 Patients.

BACKGROUND: Germany reported sufficient intensive care unit (ICU) resources throughout the first wave of coronavirus disease 2019 (COVID-19). The treatment of critically ill COVID-19 patients without rationing may improve the outcome. We therefore analyzed ICU resources allocated to COVID-19 patients with respiratory failure and their outcomes. METHODS: Retrospectively, we enrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-positive patients with respiratory failure from 03/08/2020 to 04/08/2020 and followed until 05/28/2020 in the university hospital of Freiburg, Germany. RESULTS: In the defined interval, 34 COVID-19 patients were admitted to the ICU with median age of 67±13 (31-86) years. Six of 34 (17.6%) were female. All patients suffered from moderate or severe acute respiratory distress syndrome (ARDS), 91.2% of the patients were intubated and 23.5% required extracorporeal membrane oxygenation (ECMO). Proning was performed in 67.6%, renal replacement therapy (RRT) was required in 35.3%. Ninety-six percent required more than 20 nursing hours per day. Mean ICU stay was 21±19 (1-81) days. Sixty-day survival of critically ill COVID-19 patients was 50.0% (17/34). Causes of death were multi-organ failure (52.9%), refractory ARDS (17.6%) and intracerebral hemorrhage (17.6%). CONCLUSIONS: Treatment of critically ill COVID-19 patients is protracted and resource-intense. In a context without resources shortage, 50% of COVID-19 with respiratory failure survived up to 60 days.

COVID-19 among heart transplant recipients in Germany: a multicenter survey.

AIMS: Heart transplantation may represent a particular risk factor for severe coronavirus infectious disease 2019 (COVID-19) due to chronic immunosuppression and frequent comorbidities. We conducted a nation-wide survey of all heart transplant centers in Germany presenting the clinical characteristics of heart transplant recipients with COVID-19 during the first months of the pandemic in Germany. METHODS AND RESULTS: A multicenter survey of all heart transplant centers in Germany evaluating the current status of COVID-19 among adult heart transplant recipients was performed. A total of 21 heart transplant patients with COVID-19 was reported to the transplant centers during the first months of the pandemic in Germany. Mean patient age was 58.6 ± 12.3 years and 81.0% were male. Comorbidities included arterial hypertension (71.4%), dyslipidemia (71.4%), diabetes mellitus (33.3%), chronic kidney failure requiring dialysis (28.6%) and chronic-obstructive lung disease/asthma (19.0%). Most patients received an immunosuppressive drug regimen consisting of a calcineurin inhibitor (71.4%), mycophenolate mofetil (85.7%) and steroids (71.4%). Eight of 21 patients (38.1%) displayed a severe course needing invasive mechanical ventilation. Those patients showed a high mortality (87.5%) which was associated with right ventricular dysfunction (62.5% vs. 7.7%; p = 0.014), arrhythmias (50.0% vs. none; p = 0.012), and thromboembolic events (50.0% vs. none; p = 0.012). Elevated high-sensitivity cardiac troponin T- and N-terminal prohormone of brain natriuretic peptide were significantly associated with the severe form of COVID-19 (p = 0.017 and p < 0.001, respectively). CONCLUSION: Severe course of COVID-19 was frequent in heart transplanted patients. High mortality was associated with right ventricular dysfunction, arrhythmias, thromboembolic events, and markedly elevated cardiac biomarkers.

Does the heart transplant have a future?

Heart failure has remained the leading cause of death globally for the last 15 years-and its prevalence will continue to rise. Fifty years ago, heart failure management was enriched by the possibility of a heart transplant. Despite impressive improvements in medical treatment for heart failure, a heart transplant remains the most effective long-lasting treatment for advanced heart failure in terms of mortality and quality of life. However, donor and recipient characteristics have changed dramatically in recent years, leading to more complex decision-making regarding organ acceptance and to more demanding operations and postoperative management. With improving pathophysiological understanding in the last decades, today's scientific interest still focuses on basic knowledge. How to retrieve and conserve organs to minimize ischaemic injury; how best to allocate them, considering the likelihood of success (developing a heart-allocation scoring system similar to that for lung allocation); how to match donor/recipient characteristics (ABO blood-group antigen compatibility versus incompatibility); and how to avoid graft failure, rejection and secondary morbidities such as malignomas and cardiac allograft vasculopathy after the heart transplant-all these factors remain fundamental challenges in today's transplant medicine. The use of ex vivo perfusion (e.g. via the Organ Care System®, TransMedics, Andover, MA, USA) may play an important role in this change. Remarkably, there are huge regional divergences in current transplant practices: Whereas the number of transplants continues to rise in most Eurotransplant countries and other major transplant networks, there are some countries in which transplant numbers are static or even dropping (as in Germany). This difference results in wide variations across different countries as to how advanced heart failure is treated using mechanical circulatory-assist devices.

Non-surgical bleeding in patients with ventricular assist devices could be explained by acquired von Willebrand disease.

OBJECTIVE: Outcomes after ventricular assist device (VAD) implantation have significantly improved during the last decade. However, bleeding episodes remain a serious complication of VAD support. This cannot be explained by the individual anticoagulation regimen alone in several cases, but may be symptomatic of acquired von Willebrand disease (VWD). The leading finding in acquired VWD (AVWD) is the loss of large multimers which results in diminished binding to collagen and to the platelets. We, therefore, analysed patients with two VAD types for laboratory parameters of VWD and compared them with patients after heart transplantation (HTX). MATERIALS AND METHODS: Seven patients with a HeartMate II left-ventricular assist device and five patients who received a Thoratec biventricular assist device were included in this study. Eight HTX recipients served as controls. Analysis included international normalized ratio (INR), partial thromboplastin time (PTT), platelet count, von Willebrand factor (VWF) antigen, collagen binding capacity, ristocetin cofactor activity, the ratios of the latter two to the VWF antigen and presence of large VWF multimers. RESULTS: The VAD and HTX groups did not differ with regard to age or time-point of analysis after surgery. INR and number of platelets were comparable in both groups, PTT was prolonged in VAD patients. Both VAD and HTX patients had elevated but comparable amounts of VWF antigen. However, large multimers were missing in all of 10 tested VAD patients. In contrast, five of six tested HTX recipients displayed normal multimer pattern. Indeed, collagen binding capacity and ristocetin cofactor activity (which measures binding of VWF to platelets) were lower in VAD patients compared to HTX recipients. Impaired coagulation associated with VADs was also reflected by the diminished ratios of collagen binding capacity and ristocetin cofactor activity to VWF antigen. A pathologic collagen binding ratio was found in all 10 tested VAD patients and one of the eight HTX patients, a reduced ristocetin cofactor activity ratio in 10 of 12 VAD and one of eight HTX patients. CONCLUSION: Non-surgical postoperative bleeding after VAD implantation could be explained by an AVWD. Several pharmacologic treatment options (tranexamic acid, desmopressin, VWF-factor VIII concentrate, recombinant factor VIIa) may arise from our data. Improved VAD design could prevent this problem in the future.

Platelet Secretion Defects and Acquired von Willebrand Syndrome in Patients With Ventricular Assist Devices.

BACKGROUND: The number of implanted ventricular assist devices (VADs) has increased significantly recently. Bleeding, the most frequent complication, cannot be solely attributed to anticoagulation therapy. Acquired von Willebrand syndrome (AVWS) caused by increased shear stress is frequent in VAD patients and can increase the bleeding risk. The HeartMate III (HM III) is a novel left VAD featuring potential improvements over the HeartMate II. METHODS AND RESULTS: In this study, we investigated the prevalence and onset of AVWS in 198 VAD patients. To our knowledge, this is the largest cohort of VAD patients whose longitudinal data on AVWS have been collected. We also analyzed whether AVWS is less severe in HM III patients than in HeartMate II patients. Because platelet dysfunction can raise the bleeding risk, we investigated platelet function in a subset of patients. In total, 198 VAD patients and 60 patients with heart transplants as controls were included in this study. The ratio of von Willebrand factor collagen binding capacity to von Willebrand factor:antigen, multimer analyses, and platelet function (especially secretion of α- and δ-granules) were investigated. All 198 VAD patients developed AVWS. As soon as the VAD was explanted, the AVWS disappeared within hours. AVWS was less severe in the HM III patients than in the HeartMate II patients. The HM III patients had fewer bleeding symptoms. In addition, VAD patients exhibited a platelet α- and δ-granule secretion defect. CONCLUSIONS: AVWS develops in VAD patients and may increase the bleeding risk. The HM III device causes less severe AVWS. Platelet secretion defects should be investigated in VAD patients because they also raise the bleeding risk. CLINICAL TRIAL REGISTRATION: https://www.drks.de/drks_web. Unique identifier: DRKS00000649.

The clinical impact of donor-specific antibodies in heart transplantation.

Donor-specific antibodies (DSA) are integral to the development of antibody-mediated rejection (AMR). Chronic AMR is associated with high mortality and an increased risk for cardiac allograft vasculopathy (CAV). Anti-donor HLA antibodies are present in 3-11% of patients at the time of heart transplantation (HTx), with de novo DSA (predominantly anti-HLA class II) developing post-transplant in 10-30% of patients. DSA are associated with lower graft and patient survival after HTx, with one study suggesting a three-fold increase in mortality in patients who develop de novo DSA (dnDSA). DSA against anti-HLA class II, notably DQ, are at particularly high risk for graft loss. Although detection of DSA is not a criterion for pathologic diagnosis of AMR, circulating DSA are found in almost all cases of AMR. MFI thresholds of ~5000 for DSA against class I antibodies, 2000 against class II antibodies, or an overall cut-off of 5-6000 for any DSA, have been suggested as being predictive for AMR. There is no firm consensus on pre-transplant strategies to treat HLA antibodies, or for the elimination of antibodies after diagnosis of AMR. Minimizing the risk of dnDSA is rational but data on risk factors in HTx are limited. The effect of different immunosuppressive regimens is largely unexplored in HTx, but studies in kidney transplantation emphasize the importance of adherence and maintaining adequate immunosuppression. One study has suggested a reduced risk for dnDSA with rabbit antithymocyte globulin induction. Management of DSA pre- and post-HTx varies but typically most centers rely on a plasmapheresis or immunoadsorption, with or without rituximab and/or intravenous immunoglobulin. Based on the literature and a multi-center survey, an algorithm for a suggested surveillance and therapeutic strategy is provided.

Donor heart selection and outcomes: An analysis of over 2,000 cases.

BACKGROUND: Decision-making when offered a donor heart for transplantation is complex, and supportive data describing outcomes according to acceptance or non-acceptance choices are sparse. Our aim was to analyze donor heart acceptance decisions and associated outcomes at a single center, and after subsequent acceptance elsewhere. METHODS: This investigation was a retrospective analysis of data obtained from the University of Vienna Medical Center and Eurotransplant centers for the period 2001 to 2015. RESULTS: Our center accepted 31.8% (699 of 2,199) of donor hearts offered. Unlike other centers, the acceptance rate, with or without transplantation, did not increase over time. Of the donor hearts rejected by our center, 38.1% (572 of 1,500) were later accepted elsewhere. Acceptance rates were twice as high for donor hearts initially rejected for non-quality reasons (339 of 601, 56.4%) compared with initial rejection for quality reasons (233 of 899, 25.9%). Three-year patient survival rate was 79% at Vienna; for donor hearts initially rejected by Vienna for non-quality reasons or quality reasons, it was 73% and 63%, respectively (p < 0.001). Outcomes at other centers after transplantation of grafts rejected by Vienna varied according to the reason for rejection, with good 3-year survival rates for rejection due to positive virology (77%), high catecholamines (68%), long ischemic time (71%), or low ejection fraction (68%), but poor survival was observed for hearts rejected for hypernatremia (46%), cardiac arrest (21%), or valve pathology (50%). CONCLUSIONS: A less restrictive policy for accepting donor hearts at our center, particularly regarding rejection for non-quality reasons or for positive virology, high catecholamine levels, longer ischemic time, or low ejection fraction, could expand our donor pool while maintaining good outcomes.

Acquired Von Willebrand syndrome in patients on long-term support with HeartMate II.

Objectives: Impaired binding of Von Willebrand factor (VWF) to platelets and to collagen due to acquired Von Willebrand syndrome (AVWS) is associated with support from a ventricular assist device (VAD) and can contribute to bleeding tendencies in patients with VADs. The onset of AVWS has been shown to occur immediately after VAD implantation. Our aim was to determine long-term data on AVWS in VAD patients. Methods: We analysed 278 data sets of 74 patients on HeartMate II (HMII) support for 3-80 months after implantation (11.2 ± 12.1, median 6.3 months.). Ristocetin cofactor activity (VWF:RCo), collagen binding capacity (VWF:CB), VWF antigen (VWF:Ag) and the ratios of VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag were determined. Further, the presence of high molecular weight (HMW) multimers of VWF was investigated. Results: Abnormally low values of VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag were found in 69% and 97% of blood samples, respectively. Only ten of 181 multimer analyses showed a normal pattern, and HMW multimers were present in both specimens in only one of the 74 patients. No significant changes in these parameters were observed over time. The VWF:CB/VWF:Ag ratio correlated with the multimer patterns, whereas the VWF:RCo/VWF:Ag ratio seemed to be less sensitive for AVWS. Conclusions: Our data indicate that AVWS is a typical phenomenon in patients with VAD support and that there are no time-dependent changes in these parameters apparent in most patients on long-term support with HMII.

Outcomes in HeartMate II Patients With No Antiplatelet Therapy: 2-Year Results From the European TRACE Study.

BACKGROUND: Current recommendations of antithrombotic therapy for HeartMate II (HMII) patients include the use of both an anticoagulant and an antiplatelet agent. Because bleeding is still the most frequent adverse event, the TRACE (STudy of Reduced Anti-Coagulation/Anti-platelet Therapy in Patients with the HeartMatE II) study was initiated to evaluate the incidence of adverse events in HMII patients on reduced antithrombotic (RT) therapy. METHODS: HMII patients (n = 101) from nine centers were enrolled in the European arm of TRACE and were managed on a single anticoagulant (vitamin K antagonist) with no antiplatelet agents. An analysis of bleeding and thrombotic adverse events from all 101 patients with 2-year follow-up after initiation of RT therapy is reported here. RESULTS: Median age was 56 years (range, 18 to 72 years), 93% were men, 70% had an Interagency Registry for Mechanically Assisted Circulatory Support profile 1 to 3, and 82% received the HMII as a bridge to transplantation. Ninety-two percent were placed on RT therapy as a center standard of care or due to physician preference and 6% as a response to bleeding. Median HMII support duration on RT therapy was 25 months (range, 1 to 93 months). Median international normalized ratio was 2.31 [quartile 1 to quartile 3: 2.07 to 2.60]. At 2 years, freedom from bleeding, ischemic stroke, hemorrhagic stroke, and pump thrombosis after initiation of RT therapy was 81% ± 6%, 96% ± 2%, 94% ± 3%, and 94% ± 3%, respectively. CONCLUSIONS: The 2-year analysis of the observational European TRACE study suggests that managing HMII patients with a vitamin K antagonist with a target international normalized ratio of 2.3 without antiplatelet therapy may help to reduce the incidence of major bleeding without increasing the risk of thromboembolic events, including ischemic stroke and pump thrombosis.