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Introduction: Donation after circulatory death (DCD) donors are becoming an important source of organs for heart-transplantation (HT), but there are limited data regarding their use in multiorgan-HT., Methods: Between January 2020 and June 2023, we identified 87 adult multiorgan-HTs performed using DCD-donors [77 heart-kidney, 6 heart-lung, 4 heart-liver] and 1494 multiorgan-HTs using donation after brain death (DBD) donors (1141 heart-kidney, 165 heart-lung, 188 heart-liver) in UNOS. For heart-kidney transplantations (the most common multiorgan-HT combination from DCD-donors), we also compared donor/recipient characteristics, and early outcomes, including 6-month mortality using Kaplan-Meier (KM) and Cox hazards-ratio (Cox-HR)., Results: Use of DCD-donors for multiorgan-HTs in the United States increased from 1% in January to June 2020 to 12% in January-June 2023 (p < 0.001); but there was a wide variation across UNOS regions and center volumes. Compared to recipients of DBD heart-kidney transplantations, recipients of DCD heart-kidney transplantations were less likely to be of UNOS Status 1/2 at transplant (35.06% vs. 69.59%) and had lower inotrope use (22.08% vs. 43.30%), lower IABP use (2.60% vs. 26.29%), but higher durable CF-LVAD use (19.48% vs. 12.97%), all p < 0.01. Compared to DBD-donors, DCD-donors used for heart-kidney transplantations were younger [28(22-34) vs. 32(25-39) years, p = 0.004]. Recipients of heart-kidney transplantations from DCD-donors and DBD-donors had similar 6-month survival using both KM analysis, and unadjusted and adjusted Cox-HR models, including in propensity matched cohorts. Rates of PGF and in-hospital outcomes were also similar., Conclusions: Use of DCD-donors for multiorgan-HTs has increased rapidly in the United States and early outcomes of DCD heart-kidney transplantations are promising., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Orthotopic heart transplant is the gold standard therapeutic intervention for patients with end-stage heart failure. Conventionally, heart transplant has relied on donation after brain death for organ recovery. Donation after circulatory death (DCD) is the donation of the heart after confirming that circulatory function has irreversibly ceased. DCD-orthotopic heart transplant differs from donation after brain death-orthotopic heart transplant in ways that carry implications for widespread adoption, including differences in organ recovery, storage and ethical considerations surrounding normothermic regional perfusion with DCD. Despite these differences, DCD has shown promising early outcomes, augmenting the donor pool and allowing more individuals to benefit from orthotopic heart transplant. This review aims to present the current state and future trajectory of DCD-heart transplant, examine key differences between DCD and donation after brain death, including clinical experiences and innovations in methodologies, and address the ongoing ethical challenges surrounding the new frontier in heart transplant with DCD donors., Competing Interests: Dr Jorde is a consultant for Abbott. Dr Goldstein is a consultant for Abbott Inc and a consultant and speaker for Abiomed Inc.

Background: The HeartMate 3 (HM 3; Abbott) left ventricular assist device (LVAD) has improved hemocompatibility-related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from substance accumulation between the outflow graft and its bend relief. We sought to evaluate the prevalence, course, and clinical implications of eOGO in an international study., Methods: A multicenter retrospective analysis of HM 3 LVADs implanted between November 2014 and April 2021 (n = 2108) was conducted across 17 cardiac centers in 8 countries. We defined eOGO as obstruction >25% in the cross-sectional area in imaging (percutaneous angiography, computed tomography, or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcomes (death, transplantation, or device exchange) were analyzed for eOGO cases., Results: Of 2108 patients, 62 were diagnosed with eOGO at a median LVAD support duration of 953 (interquartile range, 600-1267) days. The prevalence of eOGO was 3.0% and the incidence at 1, 2, 3, 4, and 5 years of support was 0.6%, 2.8%, 4.0%, 5.2%, and 9.1%, respectively. Of 62 patients, 9 were observed, 27 underwent surgical revision, 15 underwent percutaneous stent implantation, 8 received a heart transplant, and 2 died before intervention. One patient underwent surgical revision and later stent implantation. The mortality with therapeutic intervention was 9/53 (17.0%)., Conclusions: Although uncommon, HM 3 LVAD-supported patients might develop eOGO with an increasing incidence after 1 year of support. Although engineering efforts to reduce this complication are under way, clinicians must maintain a focus on early detection and remain vigilant., (Copyright © 2022 The American Association for Thoracic Surgery. All rights reserved.)

Primary graft dysfunction (PGD) after cardiac transplantation is a devastating complication with increasing frequency lately in the setting of donation after circulatory death (DCD). Severe PGD is commonly treated with extracorporeal membrane oxygenation (ECMO) using central or peripheral cannulation. We retrospectively reviewed the outcomes of PGD after cardiac transplantation requiring ECMO support at our center from 2015 to 2020, focused on our now preferential approach using peripheral cannulation without a priori venting. During the study period, 255 patients underwent heart transplantation at our center and 26 (10.2%) of them required ECMO for PGD. Of 24 patients cannulated peripherally 19 (79%) were alive at 30 days and 17 (71%) 1 year after transplant; two additional patients underwent central ECMO cannulation due to unfavorable size of femoral vessels and concern for limb ischemia. Successful decannulation with full graft function recovery occurred in 22 of 24 (92%) patients cannulated peripherally. Six of them had an indwelling intra-aortic balloon pump placed before the transplantation. None of the other 18 patients received a ventricular vent. In conclusion, the use of an a priori peripheral and ventless ECMO approach in patients with PGD after heart transplant is an effective strategy associated with high rates of graft recovery and survival., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Background: There is a paucity of data on heart transplantation (HT) using COVID-19 donors., Objectives: This study investigated COVID-19 donor use, donor and recipient characteristics, and early post-HT outcomes., Methods: Between May 2020 and June 2022, study investigators identified 27,862 donors in the United Network for Organ Sharing, with 60,699 COVID-19 nucleic acid amplification testing (NAT) performed before procurement and with available organ disposition. Donors were considered "COVID-19 donors" if they were NAT positive at any time during terminal hospitalization. These donors were subclassified as "active COVID-19" (aCOV) donors if they were NAT positive within 2 days of organ procurement, or "recently resolved COVID-19" (rrCOV) donors if they were NAT positive initially but became NAT negative before procurement. Donors with NAT-positive status >2 days before procurement were considered aCOV unless there was evidence of a subsequent NAT-negative result ≥48 hours after the last NAT-positive result. HT outcomes were compared., Results: During the study period, 1,445 "COVID-19 donors" (COVID-19 NAT positive) were identified; 1,017 of these were aCOV, and 428 were rrCOV. Overall, 309 HTs used COVID-19 donors, and 239 adult HTs from COVID-19 donors (150 aCOV, 89 rrCOV) met study criteria. Compared with non-COV, COVID-19 donors used for adult HT were younger and mostly male (∼80%). Compared with HTs from non-COV donors, recipients of HTs from aCOV donors had increased mortality at 6 months (Cox HR: 1.74; 95% CI: 1.02-2.96; P = 0.043) and 1 year (Cox HR: 1.98; 95% CI: 1.22-3.22; P = 0.006). Recipients of HTs from rrCOV and non-COV donors had similar 6-month and 1-year mortality. Results were similar in propensity-matched cohorts., Conclusions: In this early analysis, although HTs from aCOV donors had increased mortality at 6 months and 1 year, HTs from rrCOV donors had survival similar to that seen in recipients of HTs from non-COV donors. Continued evaluation and a more nuanced approach to this donor pool are needed., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited., Methods: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation., Results: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation., Conclusions: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after left ventricular assist device (LVAD) implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve 1-year survival and increase the likelihood of RV AMCS weaning., Methods: A multicenter retrospective database of 826 consecutive patients who received a HeartMate II or HVAD between January 2007 and December 2016 was analyzed. We identified 91 patients who had early RV AMCS on index admission. Cox proportional-hazards model was constructed to identify predictors of 1-year mortality post-RV AMCS implantation and competing risk modeling identified RV AMCS weaning predictors., Results: There were 91 of 826 patients (11%) who required RV AMCS after CF-LVAD implantation with 51 (56%) receiving a concomitant RV AMCS and 40 (44%) implanted with a postoperative RV AMCS during their ICU stay; 48 (53%) patients were weaned from RV AMCS support. Concomitant RV AMCS with CF-LVAD insertion was associated with lower mortality (HR 0.45 [95% CI 0.26-0.80], p = 0.01) in multivariable model (which included age, BMI, angiotensin-converting enzyme inhibitor use, and heart transplantation as a time-varying covariate). In the multivariate competing risk analysis, a TPG < 12 (SHR 2.19 [95% CI 1.02-4.70], p = 0.04) and concomitant RV AMCS insertion (SHR 3.35 [95% CI 1.73-6.48], p < 0.001) were associated with a successful wean., Conclusions: In patients with RVF after LVAD implantation, concomitant RV AMCS insertion at the time of LVAD was associated with improved 1-year survival and increased chances of RV support weaning compared to postoperative insertion., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: A shortage of donation after brain death (DBD) donors for heart transplantation (HT) persists. Recent improvements in organ procurement from donation after circulatory death (DCD) donors and promising early results of DCD-HTs from Europe and Australia have renewed interest in DCD-HT., Objectives: The current study evaluated donor and recipient characteristics, early outcomes, and potential impact of adult DCD-HT in the United States., Methods: The United Network for Organ Sharing registry was used to identify and compare adult DCD donors based on their use for HT between January 2020 and February 2021. Adult DCD-HTs with available post-HT outcomes data were compared with contemporary adult DBD-HTs during study period using Cox-regression analysis and propensity-matching., Results: Of the 3,611 adult DCD donors referred during the study period, 136 were used for HT. DCD donors used for HT were younger (median age 29 years), and most were male (90%), and blood type O (79%). On comparing DCD-HT (n = 127) and DBD-HT (n = 2,961) meeting study criteria and with available data on post-HT outcomes, there was no significant difference in 30-day or 6-month mortality, primary graft failure up to 30 days, or other outcomes including in-hospital stroke, pacemaker insertion, hemodialysis, and post-HT length of hospital stay. Results were similar in propensity matched DCD-HT and DBD-HT cohorts. The number of potential adult DCD donors referred has increased substantially (n = 871 in 2010 to n = 3,045 in 2020), and the authors estimated that widespread adoption of DCD-HT could lead to approximately 300 additional adult HTs in the United States annually., Conclusions: This preliminary analysis of adult DCD-HTs from the United States showed favorable early outcomes and suggested a potential for substantial increase in adult HT volumes with use of DCD donors., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The trends and outcomes of multiorgan heart-transplantation (HT) using hepatitis C virus (HCV) donors in the contemporary era are sparsely known. Using UNOS registry, 1322 adult multiorgan-HTs (n = 986 heart-kidney, n = 155 heart-lung, n = 181 heart-liver) between August-2015 and August-2020 were identified, of which 109 were performed using HCV-donors (n = 77 HCV nucleic-acid-amplification testing [NAT] positive irrespective of antibody status [HCV-viremic]; and n = 32 HCV Ab+/NAT-[HCV antibody + nonviremic]). The percentage of HCV-donors used for multiorgan-HT increased from 0% in 2015 to 14% in 2020 (p < 0.001), but there was wide variation across UNOS regions and center volumes. Recipients of multiorgan heart-kidney transplants from HCV-donors (n = 90) and HCV-naïve (HCV Ab-/NAT-) donors (n = 896) had similar 1-year survival using unadjusted and adjusted Cox-proportional hazards-regression models including in propensity-score matched cohorts. Post-HT rates of cardiac-allograft-vasculopathy (5.4% vs 5.8%) and chronic-dialysis (7.3% vs 4.9%) at 1-year were also similar. Use of HCV-donors (HCV-viremic, HCV Ab+ nonviremic) for multiorgan-HT has increased significantly. Encouraging 1-year outcomes in heart-kidney recipients from HCV-donors should support further expansion of heart-kidney transplantation using HCV-donors., Competing Interests: Disclosure statement The authors have no conflicts of interest to declare., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The optimal duration and frequency of routine surveillance endomyocardial biopsy (EMB) have been questioned in the current era of heart transplantation (HT), where the advances in immunosuppression and donor selection strategies have led to a decline in acute allograft rejection. We investigated the utility of routine EMB beyond 6 months post-HT. A single-center retrospective review was performed on 2963 EMBs from 220 HT recipients over 10 years. Each EMB was categorized into protocol or symptom-triggered biopsy and reviewed for rejection. Heart transplant recipients with ≥2 known risk factors for rejection were designated as an elevated risk group. The majority of rejections occurred within 3 months following HT. The yield of routine protocol EMBs was significantly lower than symptom-triggered EMBs, not only during the first 6 months post-HT (1.6% vs. 33.3%, P < .0001), but more so during the 6-12 months (0.1% vs 83.0%, P < .0001). A similar pattern was observed in heart transplant recipients at both elevated and standard risk for rejection. In conclusion, EMB was found to be a low-yield screening modality for rejection beyond 6 months post-HT., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: There is a lack of evidence to guide appropriate donor sizing in recipients with moderate pulmonary hypertension (pHTN) awaiting heart transplantation (HTx). It is common practice to oversize donor hearts for such recipients to prevent post-operative right ventricular failure. Therefore, our objective was to determine if oversizing in pre-transplant moderate pHTN provides a survival advantage., Methods: The United Network for Organ Sharing database was analyzed to include HTx recipients from 1994 to 2016. Recipients were considered as having moderate pHTN if the pulmonary vascular resistance (PVR) was 2.5 to 5 Wood units (WU) or transpulmonary gradient (TPG) was 10 to 18 mm Hg. Heart size mismatch was determined using the predicted heart mass equations. A size mismatch of ≥15% in either direction was considered undersized or oversized, respectively. Ninety-day and 1-year survival were analyzed based on size matching via univariate and Cox regression analysis. Propensity matching was performed to specifically evaluate the effect of donor sex among male transplant recipients., Results: Among 29,441 HTx recipients, 10,666 had moderate pHTN by PVR criteria and 12,624 HTx patients had moderate pHTN according to TPG criteria. Among patients with a PVR of 2.5 to 5 WU, oversizing was not associated with lower mortality compared with matched hearts at 90 days (7.6% vs 7.4%; p = 0.75) and 1 year (12.1% vs 11.3%; p = 0.26). Conversely, undersizing the donor was associated with a higher 90-day (10.6% vs 7.6% vs 7.4%; p < 0.01) and 1-year (15.3% vs 12.1% vs 11.3%; p < 0.01) mortality than recipients receiving oversized or matched hearts, respectively. On Cox regression analysis, there was no benefit with oversizing at 90 days (hazard ratio [HR] 0.88; p = 0.23) and 1 year (HR 0.99; p = 0.90), whereas undersizing was associated with higher 90-day (HR 1.32; p = 0.02) and 1-year mortality (HR 1.23; p = 0.03) compared to size-matched controls. Among patients with moderate pHTN based on TPG of 10 to 18 mm Hg, neither undersizing nor oversizing was predictive of mortality at 90 days and 1 year according to Cox regression analysis. Propensity matching revealed that female-to-male transplantation had similar 1-year mortality to male-to-male transplantation, and there was no advantage to oversizing female donors for male recipients., Conclusions: In this registry-based analysis, there was no benefit to oversizing donors for cardiac transplant recipients with moderate pHTN. Elimination of this restriction could increase the donor pool and reduce wait times for such recipients., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The impact of different types of regional wall motion abnormalities (RWMAs), including the Takotsubo syndrome-like (TTS-like) phenotype, on posttransplant outcomes when using donor hearts with transient left ventricular systolic dysfunction (LVSD) is unknown. We evaluated the prevalence, clinical characteristics, and prognostic association of different RWMAs including TTS-like hypokinesis and posttransplant outcomes when using donor hearts with transient LVSD., Methods: From all adult (≥18 years) heart transplants in United Network of Organ Sharing between January 2007 and September 2015, we identified 472 donor hearts with improving or transient LVSD, defined as left ventricular ejection fraction ≤ 40% on initial transthoracic echocardiogram (TTE) that improved to ≥50% on follow-up TTE during donor evaluation. These improved LVSD donors were then subdivided into 3 groups based on RWMAs on the initial TTE, TTS-like (49, 10.38%), non-TTS RWMAs (74, 15.68%), and diffuse global hypokinesis (349, 73.94%), and compared for baseline characteristics and posttransplant outcomes with follow up until June 2018., Results: Donors with TTS-like LVSD were older and more likely to be female. The type of RWMA on initial TTE (including TTS-like) of transient LVSD donor hearts was not associated with 1-year or 5-year posttransplant mortality. Posttransplant functional status scores of recipients (at 1 year) and donor left ventricular ejection fraction (at median follow-up of 3.6 years) improved in all 3 subgroups. Rates of stroke or pacemaker predischarge were also similar., Conclusions: In the largest analysis of transplanted donor hearts with transient LVSD, 1 in 4 had RWMAs on the initial TTE, but this was not associated with adverse posttransplant outcomes. Donor hearts with initial LVSD should be pursued irrespective of TTS-like hypokinesis or other RWMAs., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Ischemic tolerance of donor hearts has a major impact on the efficiency in utilization and clinical outcomes. Molecular events during storage may influence the severity of ischemic injury., Methods: RNA sequencing was used to study the transcriptional profile of the human left ventricle (LV, n=4) and right ventricle (RV, n=4) after 0, 4, and 8 hours of cold storage in histidine-tryptophan-ketoglutarate preservation solution. Gene set enrichment analysis and gene ontology analysis was used to examine transcriptomic changes with cold storage. Terminal deoxynucleotidyl transferase 2´-Deoxyuridine, 5´-Triphosphate nick end labeling and p65 staining was used to examine for cell death and NFκB activation, respectively., Results: The LV showed activation of genes related to inflammation and allograft rejection but downregulation of oxidative phosphorylation and fatty acid metabolism pathway genes. In contrast, inflammation-related genes were down-regulated in the RV and while oxidative phosphorylation genes were activated. These transcriptomic changes were most significant at the 8 hours with much lower differences observed between 0 and 4 hours. RNA velocity estimates corroborated the finding that immune-related genes were activated in the LV but not in the RV during storage. With increasing preservation duration, the LV showed an increase in nuclear translocation of NFκB (p65), whereas the RV showed increased cell death close to the endocardium especially at 8 hours., Conclusions: Our results demonstrated that the LV and RV of human donor hearts have distinct responses to cold ischemic storage. Transcriptomic changes related to inflammation, oxidative phosphorylation, and fatty acid metabolism pathways as well as cell death and NFκB activation were most pronounced after 8 hours of storage.

Importance: Left ventricular assist devices (LVADs) are well established in the treatment of advanced heart failure, but it is unclear whether outcomes are different based on the intended goal of therapy in patients who are eligible vs ineligible for heart transplant., Objective: To determine whether clinical outcomes in the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) trial differed by preoperative categories of bridge to transplant (BTT) or bridge to transplant candidacy (BTC) vs destination therapy (DT)., Design, Setting, and Participants: This study was a prespecified secondary analysis of the MOMENTUM 3 trial, a multicenter randomized clinical trial comparing the magnetically levitated centrifugal-flow HeartMate 3 (HM3) LVAD to the axial-flow HeartMate II (HMII) pump. It was conducted in 69 centers with expertise in managing patients with advanced heart failure in the United States. Patients with advanced heart failure were randomized to an LVAD, irrespective of the intended goal of therapy (BTT/BTC or DT)., Main Outcomes and Measures: The primary end point was survival free of disabling stroke or reoperation to remove or replace a malfunctioning device at 2 years. Secondary end points included adverse events, functional status, and quality of life., Results: Of the 1020 patients with implants (515 with HM3 devices [50.5%] and 505 with HMII devices [49.5%]), 396 (38.8%) were in the BTT/BTC group (mean [SD] age, 55 [12] years; 310 men [78.3%]) and 624 (61.2%) in the DT group (mean [SD] age, 63 [12] years; 513 men [82.2%]). Of the patients initially deemed as transplant ineligible, 84 of 624 patients (13.5%) underwent heart transplant within 2 years of LVAD implant. In the primary end point analysis, HM3 use was superior to HMII use in patients in the BTT/BTC group (76.8% vs 67.3% for survival free of disabling stroke and reoperation; hazard ratio, 0.62 [95% CI, 0.40-0.94]; log-rank P = .02) and patients in the DT group (73.2% vs 58.7%; hazard ratio, 0.61 [95% CI, 0.46-0.81]; log-rank P < .001). For patients in both BTT/BTC and DT groups, there were not significantly different reductions in rates of pump thrombosis, stroke, and gastrointestinal bleeding with HM3 use relative to HMII use. Improvements in quality of life and functional capacity for either pump were not significantly different regardless of preimplant strategy., Conclusions and Relevance: In this trial, the superior treatment effect of HM3 over HMII was similar for patients in the BTT/BTC or DT groups. It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure., Trial Registration: ClinicalTrials.gov identifier: NCT02224755.

Background: Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival rates after implantation of durable ventricular assist device (dVAD). We aimed to characterize post-dVAD adverse event burden and survival rates in patients requiring pre-operative TCS., Method: We analyzed 13,511 adults (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] Profiles 1-3) with continuous-flow dVADs in International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support (2013-2017) according to the need for pre-operative TCS (n = 5,632) vs no TCS (n = 7,879). Of these, 726 (5.4%) had biventricular assist devices (BiVAD). Furthermore, we compared prevalent rates (events/100 patient-months) of bleeding, device-related infection, hemorrhagic and ischemic cerebrovascular accidents (hemorrhagic cerebral vascular accident [hCVA], and ischemic cerebral vascular accident [iCVA]) in early (<3 months) and late (≥3 months) post-operative periods., Results: TCS included extracorporeal membrane oxygenation (ECMO) (n = 1,138), intra-aortic balloon pump (IABP) (n = 3,901), and other TCS (n = 593). Within 3 post-operative months, there were more major bleeding and cerebrovascular accidents (CVAs) in patients with pre-operative ECMO (events/100 patient-months rates: bleeding = 19, hCVA = 1.6, iCVA = 2.8) or IABP (bleeding = 17.3, hCVA = 1.5, iCVA = 1.5) vs no TCS (bleeding = 13.2, hCVA = 1.1, iCVA = 1.2, all p < 0.05). After 3 months, adverse events were lower and similar in all groups. Patients with ECMO had the worst short- and long-term survival rates. Patients with BiVAD had the worst survival rate regardless of need for pre-operative TCS. CVA and multiorgan failures were the common causes of death for patients with TCS and patients without TCS., Conclusions: Patients requiring TCS before dVAD had a sicker phenotype and higher rates of early post-operative adverse events than patients without TCS. ECMO was associated with very high early ischemic stroke, bleeding, and mortality. The extreme CS phenotype needing ECMO warrants a higher-level profile status, such as INTERMACS "0.", (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Hepatitis C virus (HCV) donors should be categorized as HCV-viremic (antibody [Ab] negative or positive/Nucleic Acid testing [NAT] positive) or HCV Ab + nonviremic (Ab + /NAT - ). Whereas recipients of hearts from HCV-viremic donors will develop viremia but can be cured of HCV shortly after transplant with direct-acting antivirals (DAAs), recipients of hearts from HCV Ab + nonviremic donors are highly unlikely to become viremic or require DAAs. Given this important difference in risk, we assessed the utilization trends and post-heart-transplantation outcomes of HCV-naive (Ab - /NAT - ), HCV-viremic, and HCV Ab + nonviremic donor hearts., Methods: A total of 26,572 adult donors (≥18 years) with information on HCV Ab and NAT status were identified in the United Network for Organ Sharing registry between August 2015 and June 2018 for utilization rates. Adult heart transplant recipients of these donors were compared for primary graft failure (PGF) at 90 days and 1-year recipient survival., Results: A total of 96 HCV Ab + nonviremic and 135 HCV-viremic adult donor hearts were transplanted during the study period. The utilization rates of both HCV Ab + nonviremic (1.4%-23.4%) and HCV-viremic (0.7%-25.4%) donor hearts increased significantly approaching HCV-naive rates (29.04%). There was no significant difference in rates of PGF and 1-year survival between recipients in the 3 donor HCV groups. We also used (1:3) propensity score matching and found similar 1-year survival in different donor HCV groups (HCV-naive vs HCV Ab + nonviremic, p = 0.59, and HCV-naive vs HCV-viremic, p = 0.98)., Conclusions: Recipients of HCV-viremic and HCV Ab + nonviremic donor hearts had equivalent risk of PGF and 1-year mortality compared with recipients of HCV-naive donor hearts. Although only HCV-viremic organs require DAAs and the risk of coronary artery vasculopathy after treated HCV infection has not been defined, the utilization rates of both HCV Ab + nonviremic and HCV-viremic adult donor hearts have increased at an equal pace now approaching HCV-naive rates., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Human immunodeficiency virus-positive (HIV+) patients are not routinely offered heart transplantation (HT) due to lack of adequate outcomes data. Between January 2004 and March 2017, we identified 41 adult (≥18 years) HT recipients with known HIV+ serostatus at the time of transplant in UNOS and evaluated post-HT outcomes. Overall, Kaplan-Meier (KM) estimates of survival at 1 and 5 years were 85.9% and 77.3%, respectively, with no significant difference in bridge-to-transplant ventricular-assist device (BTT-VAD, n = 22) and no-BTT-VAD (n = 19). KM estimates of cardiac allograft vasculopathy (CAV) and malignancy at 5 years were 32% and 19%, respectively. Using propensity scores, 41 HIV+ HT recipients were matched to 41 HIV- HT recipients for idiopathic dilated-cardiomyopathy; and there was no significant difference in post-HT survival up to 5 years. Furthermore, only 24 centers in the United States had performed HIV+ HT during the study period, indicating that >80% of HT centers in the United States had not performed any HIV+ HT. In a cohort representative of the current status of HIV+ HTs in the United States, we found that the posttransplant survival was excellent and rates of CAV and malignancy were comparable to the overall HT population. These results should encourage greater number of centers to offer HT to suitable HIV+ candidates and help reduce unequal access to HT for HIV+ patients., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Hepatitis C (HCV) donors are rarely used for cardiac transplantation due to historically poor outcomes. In 2015, nucleic acid testing (NAT) for viral load was added to the routine work-up of organ donors, allowing for the distinction between subjects who remain viremic (HCV Ab + /NAT + ) and those who have cleared HCV and are no longer viremic (HCV Ab + /NAT - ). The American Society of Transplantation recently recommended that HCV Ab + /NAT - donors be considered non-infectious and safe for transplantation. We present our initial experience with such donors., Methods: All patients were counseled regarding donor HCV antibody (Ab) and NAT. Transplant recipients were tested post-transplant at 1 week and at 1, 3, and 6 months for HCV seropositivity and viremia. We also analyzed the UNOS database to determine the potential impact of widespread acceptance of HCV Ab + /NAT - organs., Results: Fourteen HCV Ab ‒ subjects received hearts from HCV Ab + /NAT - donors in 2017. Over a median follow-up of 256 (192 to 377) days, 3 patients developed a reactive HCV Ab, yet none had a detectable HCV viral load during prospective monitoring at any time. Analysis of the UNOS database for the calendar year 2016 revealed that only 7 (3%) of 220 HCV Ab + /NAT - donors were accepted for heart transplantation., Conclusions: We have demonstrated the feasibility of utilizing HCV Ab + /NAT - donors for cardiac transplantation without recipient infection. A small percentage of recipients developed HCV Ab without evidence of viremia, possibly consistent with a biological false reactive test, as has been seen in other settings. Large-scale validation of our data may have a significant impact on transplantation rates., (Copyright © 2018 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular assist device (LVAD) recipients undergoing heart transplantation have increased bleeding risk. We compared conventional warfarin reversal with fresh frozen plasma vs 4-factor prothrombin complex concentrate (PCC) and the effect on transfusion requirements, blood bank costs, and clinical outcomes., Methods: A retrospective review identified 60 consecutive LVAD recipients undergoing heart transplantation divided into two groups: 30 (no PCC) received fresh frozen plasma and 30 (PCC) received PCC. Patient characteristics, intraoperative and postoperative transfusion requirements, short-term clinical outcomes, and blood bank costs were compared. PCC association with transfusion requirements was assessed by multivariate linear regression., Results: Patients who received PCC were younger (50 ± 11 vs 57 ± 13 years, p = 0.02), fewer had ischemic cardiomyopathy (23% vs 60%, p = 0.01), had more than one prior sternotomy (7% vs 30%, p = 0.04), and had higher preoperative hemoglobin (11.8 ± 1.8 vs 10.4 ± 1.8 g/dL, p = 0.01). The PCC group had a significantly shorter bypass time (185 vs 217 minutes, p = 0.01), received less fresh frozen plasma (2 vs 5 units, p = 0.03), cryoprecipitate (0 vs 2 units, p = 0.05), and total blood products (9 vs 13.5 units, p = 0.03) intraoperatively, and was less likely to require delayed sternal closure (3% vs 23%, p = 0.05). On multivariate linear regression, PCC was significantly associated with decreased intraoperative transfusion (β = -6.09, p = 0.02). There was no difference in thromboembolic events or in-hospital death. Total blood bank costs were $4,949 for PCC and $3,677 for no PCC (p = 0.01)., Conclusions: Although more costly, PCC reduced transfusion requirements and delayed sternal closure in heart transplant recipients bridged with LVAD, justifying its use over traditional warfarin reversal., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Gastrointestinal bleeding (GIB) is a major complication of continuous flow left ventricular assist device (CF LVAD) therapy. The precise pathophysiology of CF LVAD-related bleeding remains poorly understood, and the effect of pump removal at the time of transplantation on actual bleeding frequency has not previously been studied. A single-center retrospective review was conducted on patients who received CF LVAD and subsequently developed GIB. Baseline demographics and markers of pulsatility (aortic valve opening and the HeartMate II [HM2] pulse index) were compared between those with and without GIB. In those patients who had GIB and proceeded to heart transplantation, the frequency and etiology of recurrent GIB post-transplant was assessed. A total of 88 GIBs occurred in 54 of 214 patients who received CF LVAD implantation (25%, 0.36 events per patient-year). Median time to first bleeding was 65 (interquartile range [IQR]: 37-229) days, and arteriovenous malformation (AVM) was the etiology in 36% of all episodes. On multivariate analysis, age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.01-1.09; p = 0.006) and HM2 pulse index (OR: 0.57; 95% CI: 0.35-0.90; p = 0.017) were significantly associated with GIB. There were 28 patients who had at least one GIB event during LVAD support and proceeded to transplant. None of these patients had recurrent bleeding after heart transplantation. This is the first documentation that transplantation effectively eliminates CF LVAD-related GIB. Current guidelines recommending prioritization for transplant for patients who develop recurrent GIB after CF LVAD are justified.

This study was performed to determine if organ selection practices for heart utilization by Region 9 transplant programs were optimal, and to identify opportunities to increase local organ recovery. A retrospective review of de-identified region-wide donor data January 1, 2010 through December 31, 2013 was performed. Over the study period 537 heart donors were identified, of which 321 (60%) were transplanted. Two hundred-sixteen consented hearts were not used; 190 of these were not recovered, and 26 were recovered but not transplanted. Of these, 245/321 (76%) hearts were transplanted at one of 5 regional programs, 15 (5%) were transplanted out of region as primary offers, and 61 (19%) were turned down in region and exported. Of the 61 exported hearts, 43 were turned down in region for donor-related "quality" codes (UNOS 830, 833-837) by at least one program, the remaining 18 hearts were turned down for non-"quality" reasons, primarily histocompatibility and size. Only 5/43 exported were turned down for "quality" reasons by all regional programs offered the organ. A review of consented, not recovered donor offers suggested an additional 28 organs were possibly appropriate for transplant. Our review of regional turn-downs suggests transplant centers could potentially identify additional usable organs without compromising short-term outcomes., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: This study sought to determine outcomes of adult recipients of early adolescent (EA) (10 to 14 years) donor hearts., Background: Despite a shortage of donor organs, EA donor hearts (not used for pediatric patients) are seldom used for adults because of theoretical concerns for lack of hormonal activation and changes in left ventricular mass. Nonetheless, the outcomes of adult transplantation using EA donor hearts are not clearly established., Methods: All adult (≥18 years of age) heart transplant recipients in the United Network for Organ Sharing database between April 1994 and September 2015 were eligible for this analysis. Recipients of EA donor hearts were compared with recipients of donor hearts from the usual adult age group (ages 18 to 55 years). Main outcomes were all-cause mortality and cardiac allograft vasculopathy up to 5 years, and primary graft failure up to 90 days post-transplant. Propensity score analysis was used to identify a cohort of recipients with similar baseline characteristics., Results: Of the 35,054 eligible adult recipients, 1,123 received hearts from EA donors and 33,931 from usual-age adult donors. With the use of propensity score matching, 944 recipients of EA donor hearts were matched to 944 recipients of usual-age adult donor hearts. There was no difference in 30-day, 1-year, 3-year, and 5-year recipient survival or primary graft failure rates in the 2 groups using both Cox hazards ratio and Kaplan-Meier analysis. Of note, adult patients who received EA donor hearts had a trend toward less cardiac allograft vasculopathy (Cox hazard ratio, 0.80; 95% confidence interval: 0.62 to 1.01; p = 0.07)., Conclusions: In this largest analysis to date, we found strong evidence that EA donor hearts, not used for pediatric patients, can be safely transplanted in appropriate adult patients and have good outcomes. This finding should help increase the use of EA donor hearts., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular systolic dysfunction (LVSD) accounts for almost 25% of nonacceptance of potential donor hearts. Previous smaller, single-center studies showed that LVSD following brain death may be transient, and such hearts can be successfully resuscitated with resolution of LVSD, then transplanted., Objectives: This study evaluated outcomes of donor hearts with LVSD on initial transthoracic echocardiogram (TTE) that resolved during donor management., Methods: We reviewed echocardiograms of all cardiac donors in the United Network of Organ Sharing database that were transplanted from January 1, 2007, to September 30, 2015, and identified 472 donor hearts with LVSD (left ventricular ejection fraction [LVEF] ≤40%) on initial TTE that resolved (LVEF ≥50%) during donor management on a subsequent TTE. These patients comprised the improved donor LVEF group. These were compared with donor hearts with normal LVEF (LVEF ≥55%) on the initial TTE for recipient mortality, cardiac allograft vasculopathy (CAV), and primary graft failure (PGF)., Results: There was no significant difference in recipient mortality at 30 days, 1 year, 3 years, and 5 years of follow-up, nor any difference in rates of PGF at 90 days and CAV at 5 years between recipients of donor hearts with improved LVEF and recipients of donor hearts with initially normal LVEF. Post-transplant length of stay was also similar between the 2 groups. Using propensity scores, 461 transplants in the improved-donor LVEF group were matched to 461 transplants in the normal-donor LVEF group. There was no significant difference in PGF at 90 days or recipient mortality after up to 5 years of follow-up., Conclusions: In the largest analysis of donor hearts with transient LVSD, we found that such hearts can be successfully resuscitated and transplanted without increasing recipient mortality, CAV, or PGF. These results underscore the importance of appropriate donor management and should help to increase utilization of donor hearts with transient LVSD., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Despite a limited supply of organs, only 1 in 3 potential donor hearts is accepted for transplantation. Elevated donor troponin levels have generally been considered a contraindication to heart transplantation; however, the data supporting this practice are limited., Methods and Results: We identified 10 943 adult (≥18 years) heart transplant recipients in the United Network of Organ Sharing (UNOS) database with preserved donor left ventricular ejection fraction (≥50%) and where peak donor troponin I values were available. When analyzed as a continuous variable, there was no association between peak donor troponin levels and recipient mortality up to 1 year follow-up in unadjusted (hazards ratio, 0.999; 95% confidence interval, 0.997-1.002; P=0.856) and adjusted Cox models (hazards ratio, 1.000; 95% confidence interval, 0.997-1.002; P=0.950). Next, we divided the entire cohort into 3 groups based on donor troponin I values: <1 ng/mL (n=7812), 1 to 10 ng/mL (n=2770), and >10 ng/mL (n=361). Using unadjusted and adjusted Cox models and Kaplan-Meier analysis, there was no significant difference in recipient mortality at 30 days, 1 year, 3 years, or 5 years between the 3 groups. Similarly, cardiac allograft vasculopathy up to 5 years and primary graft failure up to 30 days of follow-up post transplant did not differ between the 3 donor troponin groups. The median length of hospital stay post transplant was also similar across groups., Conclusions: Elevated donor troponin I levels in the setting of preserved left ventricular ejection fraction were not associated with intermediate-term mortality, cardiac allograft vasculopathy, or primary graft failure rates in hearts accepted for transplantation. This finding could help expand the donor pool., (© 2016 American Heart Association, Inc.)

Purpose of Review: Allograft vasculopathy is the leading cause of late allograft loss following solid organ transplantation. Ischemia reperfusion injury and donor-specific antibody-induced complement activation confer heightened risk for allograft vasculopathy via numerous innate immune mechanisms, including MyD88, high-mobility group box 1 (HMGB1), and complement-induced noncanonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling., Recent Findings: The role of MyD88, a signal adaptor downstream of the Toll-like receptors (TLR), has been defined in an experimental heart transplant model, which demonstrated that recipient MyD88 enhanced allograft vasculopathy. Importantly, triggering receptor on myeloid receptor 1, a MyD88 amplifying signal, was present in rejecting human cardiac transplant biopsies and enhanced the development of allograft vasculopathy in mice. HMGB1, a nuclear protein that activates Toll-like receptors, also enhanced the development of allograft vasculopathy. Complement activation elicits assembly of membrane attack complexes on endothelial cells which activate noncanonical NF-κB signaling, a novel complement effector pathway that induces proinflammatory genes and potentiates endothelial cell-mediated alloimmune T-cell activation, processes which enhance allograft vasculopathy., Summary: Innate immune mediators, including HMGB1, MyD88, and noncanonical NF-κB signaling via complement activation contribute to allograft vasculopathy. These pathways represent potential therapeutic targets to reduce allograft vasculopathy after solid organ transplantation.

Objectives: The study sought to characterize patterns in the HeartWare (HeartWare Inc., Framingham, Massachusetts) ventricular assist device (HVAD) log files associated with successful medical treatment of device thrombosis., Background: Device thrombosis is a serious adverse event for mechanical circulatory support devices and is often preceded by increased power consumption. Log files of the pump power are easily accessible on the bedside monitor of HVAD patients and may allow early diagnosis of device thrombosis. Furthermore, analysis of the log files may be able to predict the success rate of thrombolysis or the need for pump exchange., Methods: The log files of 15 ADVANCE trial patients (algorithm derivation cohort) with 16 pump thrombus events treated with tissue plasminogen activator (tPA) were assessed for changes in the absolute and rate of increase in power consumption. Successful thrombolysis was defined as a clinical resolution of pump thrombus including normalization of power consumption and improvement in biochemical markers of hemolysis. Significant differences in log file patterns between successful and unsuccessful thrombolysis treatments were verified in 43 patients with 53 pump thrombus events implanted outside of clinical trials (validation cohort)., Results: The overall success rate of tPA therapy was 57%. Successful treatments had significantly lower measures of percent of expected power (130.9% vs. 196.1%, p = 0.016) and rate of increase in power (0.61 vs. 2.87, p < 0.0001). Medical therapy was successful in 77.7% of the algorithm development cohort and 81.3% of the validation cohort when the rate of power increase and percent of expected power values were <1.25% and 200%, respectively., Conclusions: Log file parameters can potentially predict the likelihood of successful tPA treatments and if validated prospectively, could substantially alter the approach to thrombus management., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Rationale: Early graft inflammation enhances both acute and chronic rejection of heart transplants, but it is unclear how this inflammation is initiated., Objective: To identify specific inflammatory modulators and determine their underlying molecular mechanisms after cardiac transplantation., Methods and Results: We used a murine heterotopic cardiac transplant model to identify inflammatory modulators of early graft inflammation. Unbiased mass spectrometric analysis of cardiac tissue before and ≤72 hours after transplantation revealed that 22 proteins including haptoglobin, a known antioxidant, are significantly upregulated in our grafts. Through the use of haptoglobin-deficient mice, we show that 80% of haptoglobin-deficient recipients treated with perioperative administration of the costimulatory blocking agent CTLA4 immunoglobulin exhibited >100-day survival of full major histocompatibility complex mismatched allografts, whereas all similarly treated wild-type recipients rejected their transplants by 21 days after transplantation. We found that haptoglobin modifies the intra-allograft inflammatory milieu by enhancing levels of the inflammatory cytokine interleukin-6 and the chemokine MIP-2 (macrophage inflammatory protein 2) but impair levels of the immunosuppressive cytokine interleukin-10. Haptoglobin also enhances dendritic cell graft recruitment and augments antidonor T-cell responses. Moreover, we confirmed that the protein is present in human cardiac allograft specimens undergoing acute graft rejection., Conclusions: Our findings provide new insights into the mechanisms of inflammation after cardiac transplantation and suggest that, in contrast to its prior reported antioxidant function in vascular inflammation, haptoglobin is an enhancer of inflammation after cardiac transplantation. Haptoglobin may also be a key component in other sterile inflammatory conditions., (© 2015 American Heart Association, Inc.)

Background: Transplantation of a cardiac allograft from an infected donor risks transmission of disease to the immunocompromised recipient. Such organs are often not utilized despite little supporting evidence. We sought to evaluate outcomes following cardiac transplant with the use of an infected allograft., Methods: The UNOS/OPTN database was used to identify first time, adult heart transplant recipients from 1995 to 2009. Patients receiving allografts from blood culture positive donor (CPD) were compared to those who did not (NCPD)., Results: A total of 26,813 recipients were included. Nine hundred ninety-five (3.7%) received a heart from a CPD. Recipients of hearts from CPDs were more likely to be diabetic (24% vs. 20%, p = 0.01), hypertensive (42% vs. 38%, p = 0.02), status 1 (80% vs. 76%, p = 0.0021), have a BMI > 30 (19% vs. 16%, p = 0.001), on intra-aortic balloon pump (IABP) support (7% vs. 5%, p = 0.017), and worse functional status. Recipients with a CPD were more likely to be treated for a post-transplant infection (28% vs. 23%, p = 0.003) but not for an episode of rejection in the first year after transplantation (39% vs. 40%, p = 0.73). Receipt of a CPD allograft was not a multivariate predictor for mortality. CPD and NCPD survival was similar at one year (86% vs. 87%, p = 0.2585) and 15 years (34% vs. 36%, p = 0.0929)., Conclusion: Use of allografts from CPD has no influence on survival despite the fact that these recipients tend to have a higher acuity and more comorbidities at the time of transplantation. Utilization of a heart from a donor with a confirmed blood stream infection should be carefully considered., (© 2015 Wiley Periodicals, Inc.)

Background: With health care reform firmly on the horizon, it is critical to understand the costs associated with new technologies such as continuous-flow left ventricular assist device (CF-LVAD) compared with well established treatments such as heart transplantation (HT). Scarce data exist describing the costs of these 2 therapies after 1 year of support., Methods and Results: The study population consisted of 20 consecutive subjects who underwent implantation of a CF-LVAD and 20 consecutive subjects who underwent HT and survived ≥1 year. Comprehensive cost calculation included all direct and indirect costs from day of operation through 365 days and were inflation adjusted to 2010 US dollars. Hospital charges were converted to costs with the use of hospital-specific cost-to-charge ratios and were analyzed by time segment as well as cost center. The total 1-year cost was higher in the CF-LVAD group, although this difference did not reach statistical significance ($369,519 [interquartile range [IQR] $321,020-$520,395] vs $329,648 [IQR $278,924-$395,456]; P = .242). In both groups, the index admission constituted >50% of the total 1-year cost and the major drivers of expense by cost center were organ/device acquisition, room and board, and professional fees., Conclusions: Patients surviving to 1 year on CF-LVAD support accrued costs similar to those of HT recipients; however, the total cost, at more than one-third of a million dollars, remains high. Reduction in the postoperative length of stay offers an avenue for significant cost savings., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Persistent left superior vena cava (LSVC) is the most common congenital venous abnormality. With the increasing number of children who survive into adulthood with congenital heart malformations, the recognition of persistent LSVC among patients with advanced heart failure is likely to rise. We present two cases of orthotopic heart transplantation in the setting of LSVC successfully managed with biatrial and bicaval techniques., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Limited options exist for mechanical circulatory support as a bridge to transplantation in pediatric patients with advanced heart failure. This is particularly true when it comes to intracorporeal technologies. We describe the first reported experience with the use of the HVAD in the US as a successful bridge to transplantation in a 13-yr-old patient., (© 2012 John Wiley & Sons A/S.)

Background: Cardiac transplantation in many centers is programmatically limited to patients aged younger than 70 years. We investigated the trends and outcomes for cardiac transplantation in recipients aged 70 years and older in the United States., Methods: De-identified data were provided by United Network of Organ Sharing. Transplant recipients were grouped by age 60-69 years and 70 years and older. Univariate comparisons were performed using Student's t-test or the Pearson chi-square test. Survival was estimated using the Kaplan-Meier technique and compared with the log-rank test. Cox regression was used to determine predictors of death after transplant. Statistical significance was assigned to p < 0.05., Results: Between January 1, 1998, and June 15, 2010, 5,807 sexagenarians and 332 septuagenarians received allografts. The septuagenarian cohort had more men, less diabetes, was less likely to have a ventricular assist device, and more likely to be status II. Donors for septuagenarians were older and died more frequently from intracranial hemorrhage. Median unadjusted survival was 9.8 years for sexagenarians vs 8.5 years for septuagenarians (p = 0.003). There was no difference in the incidence of cerebrovascular accident, length of stay, or pacemaker need between groups. Septuagenarians were less likely to be treated for rejection the first year (p = 0.001). Age was a multivariate predictor of death (hazard ratio, 1.289; 95% confidence interval, 1.039-1.6; p = 0.021)., Conclusions: Selected septuagenarians with advanced heart failure can derive great benefit from cardiac transplantation, although survival is inferior to that of an immediately younger sexagenarian cohort. Most of the mortality risk is seen in the first year after transplantation. A reduced incidence of rejection was observed and warrants further study., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Prior retrospective studies have suggested that tacrolimus monotherapy is an option associated with excellent outcomes and reduced toxicities., Method: We conducted a prospective, randomized, 2-center study of tacrolimus combination therapy vs monotherapy. From April 16, 2004, to September 15, 2005, 58 adult heart transplant patients were studied. All received oral tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were then randomized to a group where mycophenolate was maintained (COMBO) or to a group where it was discontinued (MONO) 14 days post-transplant. Corticosteroids were rapidly withdrawn in both groups between 8 and 12 weeks., Result: The primary end point (mean 6-month International Society of Heart and Lung Transplantation biopsy score) was 0.44 +/- 0.04 in the MONO group and 0.60 +/- 0.05 in the COMBO group (p = 0.013, unpaired Student's t-test). The freedom from rejection grade of 2R or higher at 6 and 12 months was 93.3% with MONO and 92.9% with COMBO (p = NS)., Conclusion: Tacrolimus monotherapy appears to be safe and efficacious in heart transplant recipients and is not associated with excess rejection in the first year post-transplant. Further studies of this approach are warranted.

Background: Ventricular assist devices (VADs) are increasingly used to support critically ill heart failure patients awaiting transplantation. Previous work has focused on the Thoratec Heartmate VE device, use of which is associated with pre-formed antibody production. We reviewed our cumulative experience with the Worldheart Novacor VAD as a bridge to transplantation (BTT)., Methods: From January 1989 through October 2002, 39 patients required a VAD bridge, with 26 of 39 surviving to transplantation. Antibody levels were assessed by complement-dependent cytotoxicity assay at routine intervals and expressed as panel reactive antibody (PRA) levels. Post-transplant allograft rejection, coronary vasculopathy, and survival were compared between Novacor-supported patients and non-VAD transplant recipients., Results: PRA values did not significantly change after VAD implantation (12.4% +/- 11.2% vs 14.8% +/- 12.3%, p = 0.28). Survival for the BTT patients was 80.4%, 75.7%, 64.0%, 64.0%, and 64.0%, respectively, for 1, 3, 5, 7, and 10 years post-transplant, with similar results for non-BTT patients. The freedom from coronary vasculopathy was 90.2%, 90.2%, 72.2%, and 72.2%, respectively, at 1, 3, 5, and 7 years post-transplant., Conclusions: First, to our knowledge, this study is the first to examine the incidence of allosensitization after Novacor implant in detail. In contrast with previous results of work with other VAD systems, as assessed by PRA levels, Novacor patients did not become sensitized. Second, compared with 220 non-BTT patients who received transplants during a similar time frame, Novacor BTT patients had equivalent rejection profiles and survival. Finally, the incidence of transplant-associated coronary artery disease was lower than in previous reports.

Innate immunity represents the first line of defense against microbial invasion. Recent studies have determined that a group of germline-encoded receptors, termed Toll-like receptors (TLRs), are critical for recognizing foreign motifs on microbial organisms and initiating innate responses. An exciting area of research has recently linked activation of TLRs on antigen-presenting cells (APCs) to effective antigen presentation and activation of naive T cells. Most studies have shown that TLR-dependent immune function leads to T-helper 1 (TH1) immunity, although evidence also supports that TH2 immune responses may be initiated by TLR signaling in certain contexts. In either case, innate immune signaling via TLRs leads to a productive adaptive immune response. In contrast to studies in purely infectious models, emerging data from experimental and clinical studies have provided evidence that TLR immune function is important in acute allograft rejection. Specifically, MyD88, an important TLR signal adaptor, was found to be critical for the rejection of minor-mismatched skin allografts, and important for alloimmune priming and TH1 immunity against fully allogeneic skin grafts. Furthermore, a clinical study has shown that recipients with TLR 4 polymorphisms associated with endotoxin hyporesponsiveness manifest reduce acute lung allograft rejection. Collectively, these studies demonstrate that innate immunity is important for alloimmunity. Future therapeutic modalities that target innate rather than adaptive immune mechanisms represent a promising avenue for future studies in thoracic organ transplantation.

Toll-like receptors (TLRs) are innate immune receptors that are critical for recognizing conserved microbial motifs by inducing TH1 immunity. The majority of TLRs utilize the adaptor protein MyD88 for signal transduction, although other adaptors have been recently described. As the role of innate immunity in transplantation is unclear, we examined the importance of the MyD88 pathway in acute rejection of fully MHC-mismatched murine allografts and specifically investigated whether MyD88 signaling is important for DC (dendritic cell) function and TH1 alloimmune responses. Our results demonstrate that acute rejection of both fully allogeneic skin and cardiac allografts occurs in the absence of MyD88. However, priming of naïve recipient T cells by allogeneic DCs and TH1 immune responses were diminished in the absence of MyD88, although TH2 immunity remained intact. Thus, these results demonstrate that MyD88 signaling is important for DC function and TH1 responses during fully MHC-mismatched solid-organ transplantation, although graft rejection occurs independently of MyD88., (Copyright 2004 Blackwell Munksgaard)

Since the effects of bradycardia after cardiac transplantation are not known, we tested the hypothesis that perioperative bradycardia would lead to an increase in adverse outcomes after cardiac transplantation. We conducted a retrospective case control study with inclusion criterion of a heart rate (HR) less than 80 bpm during the 1st week after transplantation. Control patients were matched for gender, age and time since transplantation. We identified 34 patients as having perioperative bradycardia out of the 174 who underwent cardiac transplantation between 1994 and 1997. The results demonstrated no significant differences in donor ischemic times (180 vs. 183, p = 0.88), operative surgeon (p = 0.62) or pretransplant cardiac disease (p = 0.81) between groups. Bradycardic patients were more likely to be on pretransplant amiodarone (RR = 20.4, p < 0.001). Perioperative bradycardia did not lead to increases in cellular rejection (p = 0.72) or vasculopathy (p = 0.79). The patients prescribed pretransplant amiodarone (n = 14) had a trend toward delayed time to first rejection episode (31.0 vs. 15.5 days, median, p = 0.07). In conclusion, perioperative bradycardia does not increase adverse outcomes after cardiac transplantation and is associated with pretransplant use of amiodarone. Amiodarone may modify the recipients' immune response by delaying the occurrence of rejection.

A case study of 61-year-old female with a history of non-ischemic cardiomyopathy and left ventricular assist device implantation was admitted for pre-operative heart transplant optimization. it mentions laboratory values revealed elevated levels of lactate dehydrogenase despite being on therapeutic anticoagulation with warfarin. It also mentions recommendation of aggressive anticoagulation for asymptomatic patients.

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life. [ABSTRACT FROM AUTHOR]

Regional outcomes after implantation of continuous-flow left ventricular assist devices (LVADs) have not been described. We examined differences in patient selection, survival, and adverse events across 3 geographic regions of the world: the Americas, Asia-Pacific, and Europe. Using data from The International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support registry, all adult patients implanted with a continuous-flow LVADs were included in this International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support analysis (n = 15,560), of whom, 9,988 (64%) received axial-flow devices and 5,572 (36%) received centrifugal-flow devices. There were significant interregional differences in the rate of implantation of patients aged >70 years (Americas: 14%, Asia-Pacific: 1%, Europe: 5%; p < 0.0001), morbidly obese (Americas: 5%, Asia-Pacific: 1%, Europe: 1%; p < 0.0001), male (Americas: 79%, Asia-Pacific: 77%, Europe: 85%; p < 0.0001), and implanted as destination therapy (Americas: 48%, Asia-Pacific: 4%, Europe: 22%; p < 0.0001). The rates of centrifugal pump usage varied by region (Americas: 30%, Asia-Pacific: 34%, Eu: 74%; p < 0.0001). Survival rates varied by region and the type of pump flow, with survival at 12 and 48 months (axial flow vs centrifugal flow) being 82% vs 82% and 52% vs 53 in Americas; 92% vs 86% and 83% vs 74% in Asia-Pacific; and 80% vs 75% and 69% vs 53% in Europe, respectively (regional survival p < 0.0001). There are marked global differences in LVAD recipient characteristics, device utilization, and post-operative care. These heterogeneities along with differences in patient management and transplantation rates may impact long-term survival. Regional differences in adverse event incidence warrant further investigation. [ABSTRACT FROM AUTHOR]