Heart transplantation in the era of corona virus disease 2019: Impact of the pandemic on donors, recipients and outcome.

INTRODUCTION: Since March 2020, the COVID-19 pandemic has tremendously impacted health care all around the globe. We analyzed the impact of the pandemic on donors, recipients, and outcome of heart transplantation (HTx). METHODS: Between 2010 and early 2022, a total of n = 235 patients underwent HTx in our department. Patients were assigned to the study groups regarding the date of the performed HTx. Group 1 (09/2010 to 02/2020): n = 160, Group 2 (03/2020 to 02/2022): n = 75. RESULTS: Since the pandemic, the etiology of heart failure in the recipients has shifted from dilated (Group 1: 53.8%, Group 2: 32.0%) to ischemic cardiomyopathy (Group 1: 39.4%, Group 2: 50.7%, p < .01). The percentage of high urgency status of the recipients dropped from 50.0% to 36.0% (p = .05), and the use of left ventricular assist (LVAD) support from 56.9% to just 37.3% (p < .01). Meanwhile, the waiting time for the recipients also decreased by about 40% (p = .05). Since the pandemic, donors were 2- times more likely to have been previously resuscitated (Group 1: 21.3%, Group 2: 45.3% (p < .01), and drug abuse increased by more than 3-times (p < .01), indicating acceptance of more marginal donors. Surprisingly, the incidence of postoperative severe primary graft dysfunction requiring extracorporeal life support decreased from 33.1% to 19.4% (p = .04) since the pandemic. CONCLUSION: The COVID-19 pandemic affected both donors and recipients of HTX but not the postoperative outcome. Donors nowadays are more likely to suffer from ischemic heart disease and are less likely to be on the high-urgency waitlist and on LVAD support. Simultaneously, an increasing number of marginal donors are accepted, leading to shorter waiting times.

Use of Organs for Heart Transplantation after Rescue Allocation: Comparison of Outcome with Regular Allocated High Urgent Recipients.

BACKGROUND: The number of patients waiting for heart transplantation (HTx) is exceeding the number of actual transplants. Subsequently, waiting times are increasing. One possible solution may be an increased acceptance of organs after rescue allocation. These organs had been rejected by at least three consecutive transplant centers due to medical reasons. METHODS: Between October 2010 and July 2019, a total of 139 patients underwent HTx in our department. Seventy (50.4%) of the 139 patients were transplanted with high urgency (HU) status and regular allocation (HU group); the remaining received organs without HU listing after rescue allocation (elective group, n = 69). RESULTS: Donor parameters were comparable between the groups. Thirty-day mortality was comparable between HU patients (11.4%) and rescue allocation (12.1%). Primary graft dysfunction with extracorporeal life support occurred in 26.9% of the elective group with rescue allocated organs, which was not inferior to the regular allocated organs (HU group: 35.7%). No significant differences were observed regarding the incidence of common perioperative complications as well as morbidity and mortality during 1-year follow-up. CONCLUSIONS: Our data support the use of hearts after rescue allocation for elective transplantation of patients without HU status. We could show that patients with rescue allocated organs showed no significant disadvantages in the early perioperative morbidity and mortality as well at 1-year follow-up.

Extracorporeal Membrane Oxygenation after Heart Transplantation: Impact of Type of Cannulation.

BACKGROUND: Primary graft dysfunction (PGD) is a common cause of early death after heart transplantation (htx). The use of extracorporeal life support (ECLS) after htx has increased during the last years. It is still discussed controversially whether peripheral cannulation is favorable compared to central cannulation. We aimed to compare both cannulation techniques. METHODS: Ninety patients underwent htx in our department between 2010 and 2017. Twenty-five patients were treated with ECLS due to PGD (10 central extracorporeal membrane oxygenator [cECMO] and 15 peripheral extracorporeal membrane oxygenator [pECMO] cannulation). Pre- and intraoperative parameters were comparable between both groups. RESULTS: Thirty-day mortality was comparable between the ECLS-groups (cECMO: 30%; pECMO: 40%, p = 0.691). Survival at 1 year (n = 18) was 40 and 30.8% for cECMO and pECMO, respectively. The incidence of postoperative renal failure, stroke, limb ischemia, and infection was comparable between both groups. We also did not find significant differences in duration of mechanical ventilation, intensive care unit stay, or in-hospital stay. The incidence of bleeding complications was also similar (cECMO: 60%; pECMO: 67%). Potential differences in support duration in pECMO group (10.4 ± 9.3 vs. 5.7 ± 4.7 days, p = 0.110) did not reach statistical significance. CONCLUSIONS: In patients supported for PGD, peripheral and central cannulation strategies are safe and feasible for prolonged venoarterial ECMO support. There was no increase in bleeding after central implantation. With regard to the potential complications of a pECMO, we think that aortic cannulation with tunneling of the cannula and closure of the chest could be a good option in patients with PGD after htx.

Successful Heart Transplantation after Cardiopulmonary Resuscitation of Donors.

BACKGROUND: Heart transplantation (HTx) is the best therapy for end-stage heart failure. Unfortunately, death on the waiting list remains a problem. Decreasing the number of rejected organs could increase the donor pool. METHODS: A total of 144 patients underwent HTx at our department between 2010 and 2019. Of them, 27 patients received organs of donors with cardiopulmonary resuscitation (CPR) prior to organ donation (donor CPR) and were compared with patients who received organs without CPR (control; n = 117). RESULTS: We did not observe any disadvantage in the outcome of the donor CPR group compared with the control group. Postoperative morbidity and 1-year survival (control: 72%; donor CPR: 82%; p = 0.35) did not show any differences. We found no impact of the CPR time as well as the duration between CPR and organ donation, but we found an improved survival rate for donors suffering from anoxic brain injury compared with cerebral injury (p = 0.04). CONCLUSIONS: Donor organs should not be rejected for HTx due to resuscitation prior to donation. The need for CPR does not affect the graft function after HTx in both short- and mid-term outcomes. We encourage the use of these organs to increase the donor pool and preserve good results.

Chronic stable heart failure model in ovine species.

Establishing a chronic heart failure (HF) model is challenging, particularly in the ovine model. The aim of this study was to establish a reproducible model of HF in an ovine model. Seventeen sheep were operated using the left thoracotomy approach. Chronic HF was induced through ligation of the diagonal and marginal branches only. Perioperative hemodynamic and echocardiographic parameters were compared. A total of (3 ± 1) coronary ligations were used. Thirteen animals survived the procedure and were followed up for (15 ± 5) days. The mean arterial pressure, heart rate (HR), mean pulmonary artery pressure (mPAP), central venous pressure, and cardiac output at baseline and prior to animal sacrifice was (75 ± 14 mmHg) and (68 ± 16 mmHg) P = .261; (72 ± 9 bpm), (100 ± 28 bpm) P = .01; (15 ± 4 mmHg) and (18 ± 5 mmHg) P = .034; (10 ± 6 mmHg) and (8 ± 4 mmHg) P = .326; (3.4 ± 1 L/min) and (3.9 ± 1 L/min) P = .286, respectively. The LVEF at baseline and prior to animal sacrifice was (63 ± 13%) and (43 ± 6%) P = .012. Twelve surviving animals were supported with LVAD in a follow-up procedure. Chronic stable HF in sheep was successively established. Clinical symptoms and drastic increase in the mPAP and HR as well as echo findings were the most sensitive parameters of HF. This reproducible ovine model has proven to be highly promising for research regarding HF.

Heart transplantation in patients with ventricular assist devices: Impacts of the implantation technique and support duration.

BACKGROUND: Orthotopic heart transplantation (HTx) is the gold standard treatment for patients with terminal heart failure. As donor organs are limited, patients are often on ventricular assist device (VAD) support before receiving HTx. We aimed to compare the outcome after HTx in patients with and without preoperative VADs as well as in patients who underwent different VAD implantation techniques. METHODS: A total of 126 patients underwent HTx at our department between 2010 and 2019 and were retrospectively analyzed. While 47 patients underwent primary transplantation (No VAD), 79 were on VAD support. The preoperative and intraoperative parameters were comparable between the two groups. RESULTS: VAD support significantly increased the HTx operation time (<0.0001), cardiopulmonary bypass time (P < .01), and warm ischemia time (P = .04). The ventilation time (P = .02), intensive care unit (ICU) stay (P = .01), and hospital stay (P = .02) were also significantly longer in VAD patients than in No VAD patients. Minimally invasive VAD implantation significantly reduced the requirement for perioperative blood transfusion (P = .01) and rethoracotomy (P = .01). Nonetheless, survival analyses did not show significant differences between the groups, but there was a trend of better results for the primary transplantation patients (30-day survival: No VAD = 91.1%, VAD = 86.1%; n.s.). CONCLUSIONS: We observed significantly worse perioperative parameters in patients who underwent transplantation after the implantation of a VAD compared to those who underwent primary transplantation. Minimally invasive VAD implantation without full sternotomy decreased complications during the subsequent HTx. In patients who are dependent on temporary VAD support as a bridge to transplantation, we believe that minimally invasive implantation should be performed if possible.

Unveiling the mechanism of deformation-induced supersaturation.

A Cu-6at%Ag cast alloy was deformed by means of high-pressure torsion to different applied strain levels until a steady-state regime is reached. The continuous structural refinement is attended by the successive dissolution of the Ag precipitates in the Cu matrix. The results show that the Ag regions need to fall below a phase size of ~ 5 nm to fully dissolve. Atomistic calculations indicate that the final dissolution can be explained based on the enthalpy difference between the solid solution and layered systems which are in between the coherent and semi-coherent structure. These findings are supported by detailed microstructural investigations.

Accredited cardiac arrest centers facilitate eCPR and improve neurological outcome.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a frequent medical emergency with low survival rates even after a return of spontaneous circulation (ROSC). Growing evidence supports formation of dedicated teams in scenarios like cardiogenic shock to improve prognosis. Thus, the European Resuscitation Council (ERC) recommended introduction of Cardiac Arrest Centers (CAC) in their 2015 guidelines. Here, we aimed to elucidate the effects of newly introduced CACs in Germany regarding survival rate and neurological outcome. METHODS: A multicenter retrospective observational cohort study was performed at three university hospitals and outcomes after OHCA were compared before and after CAC accreditation. Primary outcomes were survival until discharge and favorable neurological status (CPC 1 or 2) at discharge. RESULTS: In total 784 patients (368 before and 416 after CAC accreditation) were analyzed. Rates of immediate percutaneous coronary intervention (40 vs. 52%, p = 0.01) and implementation of extracorporeal CPR (8 vs. 13%, p < 0.05) increased after CAC accreditation. Likelihood of favorable neurological status at discharge was higher after CAC accreditation (71 vs. 87%, p < 0.01), whereas overall survival remained similar (35 vs. 35%, p > 0.99). CONCLUSION: CAC accreditation is linked to higher rates of favorable neurological outcome and unchanged overall survival.

Anthracycline therapy induces an early decline of cardiac contractility in low-risk patients with breast cancer.

AIMS: Cancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy. CTRCD most frequently appears in patients with cardiovascular risk factors (CVR) or known cardiovascular disease. However, limited data exist on incidence and course of anthracycline-induced CTRCD in patients without preexisting risk factors. We therefore aimed to longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease (NCT03940625). METHODS AND RESULTS: We enrolled 59 women with primary breast cancer and scheduled anthracycline-based therapy, but without CVR or preexisting cardiovascular disease. We conducted a longitudinal assessment before, immediately and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping. Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3% immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation, two of them were symptomatic. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired. CONCLUSION: In every single patient anthracyclines induce a decline of myocardial contractility, even among patients without pre-existing risk factors for CTRCD. Our data suggest to thoroughly evaluate whether this may lead to an increased risk of future cardiovascular events.

Interstitial Segregation has the Potential to Mitigate Liquid Metal Embrittlement in Iron.

The embrittlement of metallic alloys by liquid metals leads to catastrophic material failure and severely impacts their structural integrity. The weakening of grain boundaries (GBs) by the ingress of liquid metal and preceding segregation in the solid are thought to promote early fracture. However, the potential of balancing between the segregation of cohesion-enhancing interstitial solutes and embrittling elements inducing GB de-cohesion is not understood. Here, the mechanisms of how boron segregation mitigates the detrimental effects of the prime embrittler, zinc, in a Σ5 [001] tilt GB in α-Fe (4 at.% Al) is unveiled. Zinc forms nanoscale segregation patterns inducing structurally and compositionally complex GB states. Ab initio simulations reveal that boron hinders zinc segregation and compensates for the zinc-induced loss in GB cohesion. The work sheds new light on how interstitial solutes intimately modify GBs, thereby opening pathways to use them as dopants for preventing disastrous material failure.

Lactate versus Phosphate as Biomarkers to Aid Mechanical Circulatory Support Decisions in Patients with Out-of-Hospital Cardiac Arrest and Return of Spontaneous Circulation.

AIMS: Identifying patients who may benefit from mechanical circulatory support (MCS) after out-of-hospital cardiac arrest (OHCA) and return of spontaneous circulation (ROSC) remains challenging; thus, a search for helpful biomarkers is warranted. We aimed to evaluate phosphate and lactate levels on admission regarding their associations with survival with and without MCS. METHODS: In 224 OHCA patients who achieved ROSC, the initial phosphate and lactate levels were investigated to discriminate in-hospital mortality by receiver operating characteristic (ROC) curves. According to the Youden Index (YI) from the respective ROC, the groups were risk stratified by both biomarkers, and 30-day mortality was analyzed in patients with and without MCS. RESULTS: Within the entire collective, MCS was not associated with a better chance of survival. Both phosphate and lactate level elevations showed good yet comparable discriminations to predict mortality (areas under the curve: 0.80 vs. 0.79, p = 0.74). In patients with initial phosphate values > 2.2 mmol/L (>YI), 30-day mortality within the MCS cohort was lower (HR 2.3, 95% CI: 1.4-3.7; p = 0.0037). In patients with lower phosphate levels and groups stratified by lactate, 30-day mortality was similar in patients with and without MCS. CONCLUSIONS: We found a significant association between survival and MCS therapy in patients with phosphate levels above 2.2 mmol/L (Youden Index), and a similar discrimination of patient overall survival by lactate and phosphate. Prospective studies should assess the possible independent prognostic value of phosphate and its clearance for MCS efficiency.

Receptor autoantibodies: Associations with cardiac markers, histology, and function in human non-ischaemic heart failure.

AIMS: A causal link between non-ischaemic heart failure (HF) and humoral autoimmunity against G-protein-coupled receptors (GPCR) remains unclear except for Chagas' cardiomyopathy. Uncertainty arises from ambiguous reports on incidences of GPCR autoantibodies, spurious correlations of autoantibody levels with disease activity, and lack of standardization and validation of measuring procedures for putatively cardio-pathogenic GPCR autoantibodies. Here, we use validated and certified immune assays presenting native receptors as binding targets. We compared candidate GPCR autoantibody species between HF patients and healthy controls and tested associations of serum autoantibody levels with serological, haemodynamic, metabolic, and functional parameters in HF. METHODS: Ninety-five non-ischaemic HF patients undergoing transcatheter endomyocardial biopsy and 60 healthy controls were included. GPCR autoantibodies were determined in serum by IgG binding to native receptors or a cyclic peptide (for ß1AR autoantibodies). In patients, cardiac function, volumes, and myocardial structural properties were assessed by cardiac magnetic resonance imaging; right heart catheterization served for determination of cardiac haemodynamics; endomyocardial biopsies were used for histological assessment of cardiomyopathy and determination of cardiac mitochondrial oxidative function by high-resolution respirometry. RESULTS: Autoantibodies against ß1 adrenergic (ß1 AR) , M5-muscarinic (M5AR), and angiotensin II type 2 receptors (AT2R) were increased in HF (all P < 0.001). Autoantibodies against α1 -adrenergic (α1 AR) and angiotensin II type 1 receptors (AT1R) were decreased in HF (all P < 0.001). Correlation of alterations of GPCR autoantibodies with markers of cardiac or systemic inflammation or cardiac damage, haemodynamics, myocardial histology, or left ventricular inflammation (judged by T2 mapping) were weak, even when corrected for total IgG. ß1 AR autoantibodies were related inversely to markers of left ventricular fibrosis indicated by T1 mapping (r = -0.362, P < 0.05) and global longitudinal strain (r = -0.323, P < 0.05). AT2R autoantibodies were associated with improved myocardial mitochondrial coupling as measured by high-resolution respirometry in myocardial biopsies (r = -0.352, P < 0.05). In insulin-resistant HF patients, AT2R autoantibodies were decreased (r = -.240, P < 0.05), and AT1R autoantibodies were increased (r = 0.212, P < 0.05). CONCLUSIONS: GPCR autoantibodies are markedly altered in HF. However, they are correlated poorly or even inversely to haemodynamic, metabolic, and functional markers of disease severity, myocardial histology, and myocardial mitochondrial efficiency. These observations do not hint towards a specific cardio-pathogenic role of GPCR autoantibodies and suggest that further investigations are required before specific therapies directed at GPCR autoantibodies can be clinically tested in non-ischaemic HF.

Probing the composition dependence of residual stress distribution in tungsten-titanium nanocrystalline thin films.

Nanocrystalline alloy thin films offer a variety of attractive properties, such as high hardness, strength and wear resistance. A disadvantage is the large residual stresses that result from their fabrication by deposition, and subsequent susceptibility to defects. Here, we use experimental and modelling methods to understand the impact of minority element concentration on residual stresses that emerge after deposition in a tungsten-titanium film with different titanium concentrations. We perform local residual stress measurements using micro-cantilever samples and employ machine learning for data extraction and stress prediction. The results are correlated with accompanying microstructure and elemental analysis as well as atomistic modelling. We discuss how titanium enrichment significantly affects the stress stored in the nanocrystalline thin film. These findings may be useful for designing stable nanocrystalline thin films.

Postoperative high-sensitivity troponin T predicts 1-year mortality and days alive and out of hospital after orthotopic heart transplantation.

BACKGROUND: Orthotopic heart transplantation (HTX) is the gold standard to treat end-stage heart failure. Numerous risk stratification tools have been developed in the past years. However, their clinical utility is limited by their poor discriminative ability. High sensitivity troponin T (hsTnT) is the most specific biomarker to detect myocardial cell injury. However, its prognostic relevance after HTX is not fully elucidated. Thus, this study evaluated the predictive value of postoperative hsTnT for 1-year survival and days alive and out of hospital (DAOH) after HTX. METHODS: This retrospective cohort study included patients who underwent HTX at the University Hospital Duesseldorf, Germany between 2011 and 2021. The main exposure was hsTnT concentration at 48 h after HTX. The primary endpoints were mortality and DAOH within 1 year after surgery. Receiver operating characteristic (ROC) curve analysis, logistic regression model and linear regression with adjustment for risk index for mortality prediction after cardiac transplantation (IMPACT) were performed. RESULTS: Out of 231 patients screened, 212 were included into analysis (mean age 55 ± 11 years, 73% male). One-year mortality was 19.7% (40 patients) and median DAOH was 298 days (229-322). ROC analysis revealed strongest discrimination for mortality by hsTnT at 48 h after HTX [AUC = 0.79 95% CI 0.71-0.87]. According to Youden Index, the cutoff for hsTnT at 48 h and mortality was 1640 ng/l. After adjustment for IMPACT score multivariate logistic and linear regression showed independent associations between hsTnT and mortality/DAOH with odds ratio of 8.10 [95%CI 2.99-21.89] and unstandardized regression coefficient of -1.54 [95%CI -2.02 to -1.06], respectively. CONCLUSION: Postoperative hsTnT might be suitable as an early prognostic marker after HTX and is independently associated with 1-year mortality and poor DAOH.

Reply to Thet et al. Comment on "Oehler et al. Outcome and Midterm Survival after Heart Transplantation Is Independent from Donor Length of Stay in the Intensive Care Unit. Life 2022, 12, 1053".

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

Donor Noradrenaline Support Is Not Associated with Decreased Survival in Heart Transplant Recipients.

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.

Outcome and Midterm Survival after Heart Transplantation Is Independent from Donor Length of Stay in the Intensive Care Unit.

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.

Levosimendan for Treatment of Primary Graft Dysfunction After Heart Transplantation: Optimal Timing of Application.

OBJECTIVES: Primary graft dysfunction remains a serious problem after heart transplant. Pharmacological treatment with the calcium sensitizer levosimendan may be an additive treatment for primary graft dysfunction. MATERIALS AND METHODS: Patients undergoing heart transplant between 2010 and 2020 were retrospectively reviewed and divided depending on postoperative treatment with (n = 41) or without (n = 109) levosimendan. Recipients who received levosi mendan were further divided with regard to timing of levosimendan application (early group: started ≤48 hours posttransplant [n = 23]; late group: started >48 hours posttransplant [n = 18]). RESULTS: Patients who received levosimendan treatment displayed a remarkable incidence (87.8%) of postoperative primary graft dysfunction with need for venoarterial extracorporeal membrane oxygenation and therefore often presented with perioperative morbidity. Patient with early application of levosimendan showed significantly decreased duration of venoarterial extracorporeal membrane oxygenation support (5.1 ± 3.5 days vs 12.6 ± 9.3 days in those with late application; P < .01) and decreased mortality during venoarterial extracorporeal membrane oxygenation support (0.0% vs 33.3% in early vs late group; P < .01). In addition, compared with patients with late levosimendan application, patients with early application needed fewer blood transfusions (P < .05), had shorter ventilation times (279 ± 235 vs 428 ± 293 h; P = .03), and showed a trend of reduced incidence of postoperative renal failure (69.6% vs 94.4%; P = .06). Moreover, survival analyses indicated an increased survival for patients with early start of levosimendan therapy within the first 48 hours after heart transplant (P = .09). CONCLUSIONS: Pharmacotherapy with levosimendan may be a promising additive in the treatment of primary graft dysfunction after heart transplant. With administration of levosimendan within the first 48 hours posttransplant, rates of successful weaning from venoarterial extracorporeal membrane oxygenation and outcomes after heart transplant were shown to increase.