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.

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.

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.

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.

Towards a cardiac allocation score: a retrospective calculation for 73 patients from a German transplant center.

BACKGROUND: Due to a growing discrepancy between the transplant waiting list and decreasing numbers of available donor hearts, cardiac transplantation rates in Germany have been declining in the past years. Currently, patients on the waiting list are prioritized by medical urgency and waiting time and therefore a majority of all cardiac transplants is performed in very ill patients. Recently, a different allocation algorithm was proposed that included predicted post-transplant survival as a parameter for organ allocation. So far, little data exists on how such a "Cardiac Allocation Score" (CAS) relates to our current transplant patient population and on how such a change in organ allocation could change clinical practice. METHODS: We calculated a theoretical retrospective Cardiac Allocation Score for 73 patients recruited and transplanted at our medium-volume center in Germany based on a hypothetical scoring algorithm recently published by Eurotransplant. RESULTS: Overall, 37 patients (50.7%) were transplanted on high urgency status (HU), 27 (37%) were being supported by a VAD at time of transplant. 57 (78.1%) were male. We found a relatively normal distribution of the hypothetical CAS with a median of 32.91 and a mean of 31.95 +/-10.02. Overall, CAS-Scores were lower than previously described for a Eurotransplant patient cohort of high urgency patients, but there was a significant overlap in score values between patients on HU and T status. CAS-values of VAD-supported patients were lower than in patients without mechanical support. The IMPACT-score as part of the CAS was used for prediction of post-transplant survival and seems suitable to predict outcome in our patient population. CONCLUSION: In a retrospective analysis, the recently proposed Cardiac Allocation Score seems to show a normal distribution of priority values in our patient cohort. The IMPACT-score predicted outcome after transplantation and could serve as part of the CAS-algorithm to predict post-transplant survival in this single center real-world scenario. Implementation of the CAS could significantly change organ allocation practice, including a potential prioritization of current T-status patients over HU-status patients.

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.

Does listing for heart transplant for longer than 30 days before ventricular assist device implantation influence utilization of psychotherapeutic support and outcome?

OBJECTIVES: Previous studies indicate that patients with mechanical ventricular assist devices (VADs) experience high psychosocial and emotional distress. Listing for transplant may trigger psychosocial adjustment to the transplantation as an upcoming critical life-event. We hypothesized that patients could profit from this adaptation when implantation of a VAD becomes necessary. METHODS: We arbitrarily chose a cut-off at 30 days after being put on the heart transplantation (HTX) waiting list. Eighteen patients were listed for HTX for >30 days (referred to as 'listed') and 26 for shorter periods or not at all ('non-listed'). Survival, the occurrence of mental disorders, the number of contacts of the patient with the psychologist and times spent on psychotherapeutic support for both patient groups and for their families were analysed. RESULTS: Survival after VAD implantation (observation time) and mental disorders were comparable for listed and non-listed patients. Mental disorders were developed in 80% of all patients irrespective of the listing group. The utilization of supportive psychotherapy did not differ between the listed and the non-listed group with regard to the number of contacts and to the time needed for individual therapy. Moreover, the number of families who requested support did not differ between the groups nor did the time spent on family therapy. However, the number of contacts and the time for individual psychotherapeutic support correlated with the observation time, whereas the time spent on family therapy did not. In contrast, family therapy correlated inversely with age. In addition, we compared bridge-to-transplantation patients with destination therapy patients. There were no differences in the occurrence of mental disorders, the number of contacts or in the time expenses for individual and for family therapy, neither for all patients nor after stratification for listing. CONCLUSIONS: Our data indicate that listing for HTX for >30 days before VAD implantation does not reduce the utilization of psychotherapeutic support by VAD patients. We assume that structured emotional and psychosocial support by the interdisciplinary VAD team, including professional supportive psychotherapy, is indispensable for successful coping of VAD patients and their families.

Established markers of renal and hepatic failure are not appropriate to predict mortality in the acute stage before extracorporeal life support implantation.

OBJECTIVES: End-organ function, especially of the kidney and liver, actual inflammation and acid-base balance affect the outcome in extracorporeal life support (ECLS) patients. However, the often unexpected necessity of ECLS implies that information on patients is scarce. Even established global scores are not always useful in the rapid decision process for ECLS. Therefore, we evaluated laboratory parameters for kidney or liver function and for inflammation and acid-base balance with regard to outcome. METHODS: The retrospective analysis includes 69 consecutive adult patients with veno-arterial ECLS. Laboratory markers for function of kidney (creatinine, urea) and liver (total bilirubin in plasma, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase) as well as for inflammation (C-reactive protein, leucocyte counts) and acid-base balance (pH, lactate) were acquired within 24 h before ECLS implantation. RESULTS: A total of 38 patients (55%) could be weaned or bridged. Bridged patients were switched to ventricular assist devices, n=10, or total artificial hearts, n=2, and one patient underwent heart transplantation. Overall, 26 ECLS patients (38%) survived for >4 weeks. Thirty-one patients (45%) died on ECLS. About three out of four patients presented with impaired renal or hepatic performance, approximately two-thirds with signs of increased inflammatory state, and more than a half with deranged acid-base balance. Neither signs of hepatic or renal failure nor of inflammation or impaired acid-base balance allowed a prediction of survival in these patients. The outcome did also not depend on indication for ECLS implantation. However, there was a significant correlation between the patients' age and mortality (P=0.006). CONCLUSIONS: Our data indicate that renal and hepatic insufficiency, increased inflammatory state and deranged acid-base balance as determined by pre-operative laboratory data are not associated with poor outcome of ECLS. Further, survival is not related to indications for ECLS. In a number of patients, ECLS allows for successful bridging to other treatment options.

Effects of donor pre-treatment with dopamine on survival after heart transplantation: a cohort study of heart transplant recipients nested in a randomized controlled multicenter trial.

OBJECTIVES: We determined the outcome of cardiac allografts from multiorgan donors enrolled in a randomized trial of donor pre-treatment with dopamine. BACKGROUND: Treatment of the brain-dead donor with low-dose dopamine improves immediate graft function after kidney transplantation. METHODS: A cohort study of 93 heart transplants from 21 European centers was undertaken between March 2004 and August 2007. We assessed post-transplant left ventricular function (LVF), requirement of a left ventricular assist device (LVAD) or biventricular assist device (BVAD), need for hemofiltration, acute rejection, and survival of recipients of a dopamine-treated versus untreated graft. RESULTS: Donor dopamine was associated with improved survival 3 years after transplantation (87.0% vs. 67.8%, p = 0.03). Fewer recipients of a pre-treated graft required hemofiltration after transplant (21.7% vs. 40.4%, p = 0.05). Impaired LVF (15.2% vs. 21.3%, p = 0.59), requirement of a LVAD (4.4% vs. 10.6%, p = 0.44), and biopsy-proven acute rejection (19.6% vs. 14.9%, p = 0.59) were not statistically different between groups. Post-transplant impaired LVF (hazard ratio [HR]: 4.95; 95% confidence interval [CI]: 2.08 to 11.79; p < 0.001), requirement of LVAD (HR: 6.65; 95% CI: 2.40 to 18.45; p < 0.001), and hemofiltration (HR: 2.83; 95% CI: 1.20 to 6.69; p = 0.02) were predictive of death. The survival benefit remained (HR: 0.33; 95% CI: 0.12 to 0.89; p = 0.03) after adjustment for various risks affecting mortality, including pre-transplant LVAD/BVAD, inotropic support, and impaired kidney function. CONCLUSIONS: Treatment of brain-dead donors with dopamine of 4 µg/kg/min will not harm cardiac allografts but appears to improve the clinical course of the heart allograft recipient. (Prospective Randomized Trial to Evaluate the Efficacy of Donor Preconditioning With Dopamine on Initial Graft Function After Kidney Transplantation; NCT00115115).

Acquired Von Willebrand syndrome is an early-onset problem in ventricular assist device patients.

OBJECTIVE: Acquired Von Willebrand syndrome (AVWS) can contribute to bleeding complications in patients with ventricular assist devices (VADs). AVWS results from shear stress, which causes unfolding of the high-molecular-weight (HMW) multimers of Von Willebrand factor (VWF) with subsequent cleavage. Loss of the HMW multimers of VWF is the leading finding in AVWS. In consequence, binding of VWF to collagen and to platelets is impaired. The onset of AVWS after VAD implantation is not yet determined. We examined VAD patients for presence of an AVWS in the early, intermediate, and late phase after VAD implantation. METHODS: Patients with a biventricular Thoratec-PVAD(®) (BVAD, n = 6) or a left-ventricular HeartMateII(®) (HMII, n = 11) were analyzed prior to VAD implantation and after 1, 3, 14, 30, and 60 days. Diagnosis of AVWS based on VWF:ristocetin cofactor activity/VWF:VWF antigen (VWF:RCo/VWF:Ag), collagen-binding capacity:VWF antigen (VWF:CB/VWF:Ag), and multimeric analysis. In addition, we analyzed the number of bleeding episodes, which required surgical intervention. RESULTS: No patient had an AVWS prior to VAD implantation. An AVWS was identified already in the very early postoperative period, that is, in almost all patients on the first day and in all patients on the third day. The AVWS was also detected in the majority of patients in the further course. Nine of all 17 patients suffered bleeding complications and required a total of 25 interventions due to hemorrhages. Forty percent of re-interventions were carried out within the first 10 days after implantation; five of these were necessary within the first 24h. CONCLUSION: The AVWS is present already in the early postoperative phase after VAD implantation. Therefore, reduced shear stress has to be an important feature of newly developed assist devices in the future.

Supportive psychotherapy for patients with heart transplantation or ventricular assist devices.

OBJECTIVE: Both heart transplant (HTX) candidates and patients on ventricular assist device (VAD) support suffer from severe heart failure and have to fear life-threatening complications. For both patient groups, the importance of screening for and treatment of psychosocial problems and mental disorders to optimize compliance and survival has been acknowledged. We compared the use of psychotherapeutic support by patients with primary HTX, on VAD support, either on destination therapy or to be transplanted, and successfully bridged to transplant. In addition, we evaluated the use for supportive psychotherapy for the families of our patients and present two typical cases. METHODS: Patients with primary HTX (HTX(prim), n=16), with VAD on destination therapy (VAD(dest), n=15), with VAD waiting for transplant (VAD(htx), n=9), and patients who have been successfully bridged on VAD to transplant (HTX(vad), n=11) were analyzed during the preoperative and the in-hospital postoperative period. International Classification of Diseases (ICD 10) diagnoses, number of contacts with the psychologist, time expenses for individual interventions, family interventions, and concomitant communication were assessed. RESULTS: Adjustment disorders were the most prevalent disturbances. HTX(vad) patients needed more psychotherapeutic interventions and required more time for individual support than HTX(prim) patients. Partners and families of almost one-half of all patients made use of supportive psychotherapy; there were no differences between the groups with regard to the needed time. Further, the groups did not differ in the time expenses for concomitant communication with the psychologist. At the latest contact with the psychologist, three VAD(dest) patients did not need further psychotherapy at this time; also, one VAD patient waiting for transplant and two after primary HTX were psychosocially stable. CONCLUSION: Our data reflect the high emotional distress, especially of HTX(vad) patients. Our data suggest further that patients on VAD support experience psychosocial and emotional stress as severe as HTX candidates and recipients do. Patients on destination therapy and those who are waiting for transplantation do not differ in this regard. The high complexity of the psychosocial problems of VAD and HTX patients warrants professional psychotherapeutic support.

Reducing the ischemic time of donor hearts will decrease morbidity and costs of cardiac transplantations.

With liberalization of donor eligibility criteria, donor hearts are being harvested from remote locations, increasing ischemic times. The aim of this study was to examine the effect of total ischemic time (TIT) on length of stay in the intensive care unit (LOS in ICU) and its economic consequences. The study population included recipients without prior mechanical support undergoing heart transplantation between 1998 and 2008 at a single institution. The mean age of the 72 recipients (56 men, 16 women) was 50.6 years (range 15-68 years) and the mean donor age was 41.5 years (range 11-61 years). The median TIT was 181.2 min (range 107-243) and median LOS in ICU was 11.5 days (range 3-107 days). There was a statistically significant linear relationship between TIT and LOS in ICU r(72)=0.317, P=0.004. Each 5 min and 38 s of TIT equated to one more day in ICU. An ischemic time >180 min was associated with higher LOS in ICU, renal failure, and a more frequent use of nitric oxide in our cohort. For longer distance harvesting, the reduction of TIT by the fastest possible transport (learjet, helicopter) would have economic advantages with regards to the high cost of treatment in ICU.

Haemolysis in patients with ventricular assist devices: major differences between systems.

INTRODUCTION: Implantation of a ventricular assist device (VAD) is a seminal therapeutic option for patients with terminal cardiac failure. However, haemolysis remains a clinically relevant adverse effect of several VAD types. Lysed erythrocytes release lactate dehydrogenase (LDH) and haemoglobin. Free haemoglobin in plasma is bound by haptoglobin with high affinity. The complex is internalised by monocytes/macrophages and degraded. Any more released free haemoglobin is captured by haemopexin. This complex also undergoes lysosomal degradation in various cells. Only now, the excessive free haemoglobin can be measured in plasma. Here, we investigated haemolysis in patients supported by different VAD types. METHODS: Five patients with an intracorporeal centrifugal left ventricular VAD (LVAD), 10 patients with an axial LVAD and seven patients with a paracorporeal biventricular assist device (BVAD) were analysed preoperatively and 3 days (3.0+/-0.4 days, early), 2 weeks (14+/-1 days, intermediate) and 2 months (62+/-5 days, later) after VAD implantation for haptoglobin, haemopexin, free haemoglobin in plasma, LDH, total haemoglobin, haematocrit and transfusion requirements. RESULTS: Patients with a centrifugal LVAD displayed normal haptoglobin and haemopexin, low free haemoglobin and moderately increased LDH. In comparison, axial LVADs were accompanied by lower haptoglobin and haemopexin and higher free haemoglobin and LDH values. In contrast, BVADs led to an almost complete loss of haptoglobin and haemopexin and to high levels of free haemoglobin and LDH at each analysed time point. CONCLUSIONS: While severe haemolysis accompanies BVAD support, erythrocyte damage is less pronounced in the axial LVAD examined and only slight in the intracorporeal centrifugal LVAD. Haemopexin, a scavenger of free haemoglobin, can be used, in combination with haptoglobin and free haemoglobin, to assess erythrocyte damage.

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.

Implantable left ventricular assist device for treatment of pulmonary hypertension in candidates for orthotopic heart transplantation-a preliminary study.

OBJECTIVES: Elevated pulmonary vascular resistance (PVR) unresponsive to pharmacological intervention is a major limitation in heart transplantation (HTX). The post-operative course of these patients is associated with an increased risk of life-threatening right heart failure. We evaluated the efficiency of an implantable left ventricular assist device (LVAD) to decrease PVR by unloading the left ventricle and to lower the risk of later orthotopic HTX. METHODS: Six patients with end-stage heart failure (NYHA class IV) and 'fixed' pulmonary hypertension (PVR 5.7+/-0.7, range 4.4-6.5 Wood units) were analyzed. Despite maximal pharmacological intervention at initial evaluation (oxygen inhalation, nitrates, alprostadil infusion) PVR could not be reduced to under 2.5 Wood units. Four patients received a TCI Heartmate, one patient a Novacor, and one patient a Jarvik 2000. RESULTS: All patients survived the LVAD implantation, four patients could be discharged from hospital. Cardiac index and pulmonary artery pressure values returned to normal during the early post-operative phase. After a mean support time of 191+/-86 days PVR had fallen to 2.0+/-1.2 (range 0.8-3.6) Wood units. All patients could be bridged to transplantation, one patient died 3 months after transplant, five patients are still alive after a mean follow-up of 16.2+/-10.5 months. CONCLUSIONS: Mechanical support using an implantable LVAD is a very efficient approach with an acceptable risk to treat severe pulmonary hypertension in end-stage heart failure patients before HTX. Adequate reduction of PVR can be expected within 3-6 months. Subsequent HTX is associated with a good outcome.

Successful treatment of pulmonary hypertension with inhaled nitric oxide after pulmonary embolectomy.

Inhaled nitric oxide is an agent known to reduce pulmonary vascular resistance and prevent right heart failure. Pulmonary embolism is frequently followed by right heart failure and cardiogenic shock. Although successful treatment of patients with right ventricular failure caused by pulmonary embolism has been reported, clinical use of inhaled nitric oxide as an adjunct to surgical treatment is not in widespread use. We present a case of a 69-year-old woman with massive pulmonary embolism followed by right ventricular failure. After emergency operation, weaning from ventilation was prolonged. Pulmonary hypertension was decreased with low-dose inhaled nitric oxide, although pulmonary gas exchange did not improve. The patient was weaned successfully from ventilation 52 hours after operation and recovered completely. In a follow-up examination after 9 months, the patient is in healthy constitution with good cardiopulmonary function.