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Introduction: Since the 2018 change in the US adult heart allocation policy, more patients are bridged-to-transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization., Methods: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant., Results: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra-aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno-arterial extra-corporeal membrane oxygenation group (n = 9)-p = .039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p = .044), were more likely to be sensitized at baseline - 3 of 9 (33.3%) compared to 2 out of 32 (6.3%) (p = .028) and received more transfusions with red blood cells (6 (66.6%) vs. 8 (25%), p = .02) and platelets (6 (66.6%) vs. 5 (15.6%), p = .002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p = .57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS-p = .028., Conclusions: Our findings suggest that patients bridged-to-transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Despite advances in medical therapy for patients with stage C heart failure (HF), survival for patients with advanced HF is <20% at 5 years. Durable left ventricular assist device (dLVAD) support is an important treatment option for patients with advanced HF. Innovations in dLVAD technology have reduced the risk of several adverse events, including pump thrombosis, stroke, and bleeding. Average patient survival is now similar to that of heart transplantation at 2 years, with 5-year dLVAD survival now approaching 60%. Unfortunately, greater adoption of dLVAD therapy has not been realized due to delayed referral of patients to advanced HF centers, insufficient clinician knowledge of contemporary dLVAD outcomes (including gains in quality of life), and deprioritization of patients with dLVAD support waiting for heart transplantation. Despite these challenges, novel devices are on the horizon of clinical investigation, offering smaller size, permitting less invasive surgical implantation, and eliminating the percutaneous lead for power supply., Competing Interests: Funding Support and Author Disclosures Dr Tedford has consulting relationships with Medtronic, Abbott, Aria CV Inc, Acceleron/Merck, Alleviant, CareDx, Cytokinetics, Itamar, Edwards Lifesciences, Eidos Therapeutics, Lexicon Pharmaceuticals, and Gradient; is a national principal investigator for the RIGHT-FLOW clinical trial (Edwards Lifesciences); has been a steering committee member for Merck, Edwards, and Abbott; is a research advisory board member for Abiomed; and has done hemodynamic core laboratory work for Merck. Dr Leacche has been a consultant for Abbott and Abiomed. Dr Drakos has been a consultant for Pfizer and Abbott; and receives research support from Novartis, the National Institutes of Health, the American Heart Association, Department of Veterans Affairs, and Treadwell Foundation. Dr Cowger is a paid speaker and receives research-related travel funds (2017) from Abbott; is a paid member of the medical advisory board and steering committee for Tendyne and Cephea valves; is a publication committee member for HeartMate 3 clinical trial; and receives institutional support for clinical trials on HeartMate 3 and Tendyne; is a paid speaker for Medtronic, study steering committee member, and national Principal Investigator (2017-present) for DT-PAS and Apogee trials; is on the advisory board, and has received institutional support for clinical trials from Medtronic; is an advisory board member and steering committee member for the Aortix pilot and pivotal trial (2018-present) for Procyrion; has stock options in the Aortix device; is an unpaid steering committee member for the Cordella device used in the Proactive trial (2019-present); has been a speaker for fellow education activities in 2021, 2022, and 2023 for Zoll (etc); has been a steering committee member for ALIVE trial and speaker/educator for BioVentrix; is a steering committee member for Nuwellis for the Restor-HF trial; is a Data Safety Monitoring Board member for BiVACOR; has been a consultant for CorWave; is a Data Safety Monitoring Board Member for Excor Inc; is deputy editor with MCS focus for the Journal of Heart and Lung Transplantation; and is a member of leadership team for STS Intermacs. Dr Pagani has been a noncompensated ad hoc scientific advisor for Abbott, CH Biomedical, FineHeart, and Medtronic; has been a noncompensated medical monitor for Abiomed; is a member of the Data Safety Monitoring Board for Carmat and the National Heart, Lung, and Blood Institute PumpKIN Study; receives grant funding from the NHLBI and the Agency for Healthcare Research and Quality; and receives partial salary support from Blue Cross/Blue Shield of Michigan as Associate Director of the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative. Dr Lorts is a consultant, paid speaker, and PI of research study for Abbott; has received a research grant from Medtronic; has been a speaker, served on the medical advisory board, and has received a research grant from Abiomed; has received a research grant from SynCardia; has been a consultant for Bayer; has been a principal investigator of the Berlin Excor Active Trial; has received a research grant and has been a consultant for Berlin Heart; and has served on the medical advisory board for Optum., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Intra-aortic balloon pump (IABP) utilization has significantly outpaced other Status 2 eligibility criteria for heart transplant. The risk of waitlist mortality of IABP-supported patients relative to other Status 2 listed patients has not been described., Methods: We performed a retrospective analysis of all adult patients listed Status 2 for heart transplantation under the current U.S. allocation policy, using data from the United Network for Organ Sharing. Patients listed status 1 and status 3 for high-dose inotropes were included for reference. Mortality and waitlist decompensation were modeled as a function of time-varying status in cause-specific Cox survival models., Results: We identified 3638 Status 2 listings, of whom 1676 (46%) were Status 2 due to IABP. Relative to patients supported with IABP, status 2 patients with ventricular tachycardia/fibrillation [VT/VF] (HR 4.0, p < .001), right-or-biventricular assist device configurations (HR 2.3, p = .002), or temporary surgical left ventricular assist devices [LVAD] (HR 2.6, p = .003) had greater risk of waitlist mortality and decompensation. Other Status 2 subgroups had mortality comparable to IABP Status 2. Risk of waitlist mortality and decompensation for IABP Status 2 was similar to Status 3 patients listed for high-dose inotropes (HR 1.2, p = .27) and lower than Status 1 patients (HR 0.7, p = .002)., Conclusions: Waitlist mortality varies significantly by Status 2 eligibility criteria and is highest among patients listed for VT/VF, right-or-biVAD configurations, or temporary surgical LVADs. IABP-supported patients were among those with the lowest Status 2 waitlist mortality risk and comparable to Status 3 inotrope-supported patients., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Donor heart scarcity remains the fundamental barrier to increased transplant access. We examined whether 2018 United Network for Organ Sharing (UNOS) policy changes have had an impact on donor heart acceptance rates., Methods and Results: We performed an interrupted time series analysis in UNOS to evaluate for abrupt changes in donor heart-acceptance rates associated with the new policy. All adult donor offers were evaluated between 2015 and 2021 (n = 66,654 donors). Donor volumes and transplants increased during this period, but the donor acceptance rate declined significantly from 31% in quarter 3 of 2018 to 26% acceptance in quarter 3 of 2021 (slope change -0.4% per quarter; P < 0.001). We identified 2 trends associated with this decline: (1) a growing number of donors with high-risk features, and (2) decreased acceptance of donors with certain high-risk features in the new allocation system., Conclusions: Heart transplant volumes have increased in recent years as a result of increased donor volumes, but donor heart acceptance rates began decreasing under the current allocation system. Changes in the donor pool and acceptance patterns for certain donor-risk features may explain this shift and warrant further evaluation to maximize donor heart use., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed "responders"). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown., Methods: To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders., Results: These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions., Conclusions: This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) may be complicated by heart failure. Management of advanced heart failure in this context is challenging., Methods: We reviewed our center's experience with advanced heart failure therapies in patients with ARVC. Three rapidly deteriorating patients with ARVC with biventricular heart failure were found. Their management and outcomes are presented. Data on ventricular fibrosis were available in 2 of them and are also included., Results: The first patient underwent initially successful paracorporeal pulsatile biventricular assist device (BiVAD) implantation. However, a large ischemic stroke occurred 2 weeks later, and the patient died after 2 months. The second patient underwent urgent BiVAD implantation after extracorporeal membrane oxygenation support because of cardiogenic shock, but his course was complicated by multiorgan failure due to systemic infection and the patient died. The last patient, being at Interagency Registry for Mechanically Assisted Circulatory Support 3-4 profile, underwent heart transplant with uneventful recovery. Extensive fibrosis was present in both ventricles of 2 patients undergoing pathology examination., Conclusions: Patients with ARVC and advanced biventricular heart failure are characterized by extensive ventricular fibrosis and considerable risk, but data on their management are limited. Biventricular circulatory support is associated with suboptimal outcomes, and prioritization for heart transplant seems preferable., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The 2018 U.S. heart allocation system offers an accelerated pathway for heart transplantation to the most urgent patients., Objectives: This study sought to determine whether the new allocation system resulted in lower likelihood of candidate recovery., Methods: Adult patients waitlisted for heart transplantation with temporary mechanical circulatory support at the time of initial listing between 2010 and 2020 in the United Network for Organ Sharing registry were included. Competing events of heart transplantation, waitlist death or delisting for deteriorating condition, and delisting for improved condition (candidate recovery) were analyzed in the new vs old heart allocation system., Results: A total of 688 patients were waitlisted with venoarterial extracorporeal membrane oxygenation or a surgical nondischargeable biventricular assist device (status 1 or old 1A). Overall, 2,237 patients were waitlisted with an intra-aortic balloon pump, a percutaneous left ventricular assist device (LVAD), or a surgical nondischargeable LVAD (status 2 or old 1A). Patients waitlisted with venoarterial extracorporeal membrane oxygenation or a nondischargeable biventricular assist device had significantly shorter median waitlist times (5 vs 31 days), higher incidence for cardiac transplantation (81.5% vs 43.0%), and lower incidence of candidate recovery (1.5% vs 7.9%) in the new vs old heart allocation system (all P < 0.05). Patients waitlisted with an intra-aortic balloon pump or percutaneous or a nondischargeable LVAD also had significantly shorter median waitlist times (8 vs 35 days), higher incidence of transplantation (88.9% vs 64.9%), and lower incidence of candidate recovery (0.2% vs 1.6%) in the new vs old heart allocation system (all P < 0.05)., Conclusions: Current practice of the new allocation system may not offer select temporary mechanical circulatory support patients the opportunity and adequate time to recover to the point of waitlist removal. Further research will determine which patients would benefit from urgent transplantation vs recovery strategy., Competing Interests: Funding Support and Author Disclosures Dr Topkara has been supported by NIH K08 HL146964. Dr Sayer has received consulting fees from Abbott Laboratories. Dr Clerkin has been supported by NIH K23 HL148528. Dr Wever-Pinzon has been supported by NIH K23 HL150322. Dr Burkhoff has received institutional educational grant support from Abiomed; and has received consulting fees from CardioDyme Inc and from Abbott Laboratories unrelated to mechanical circulatory assist. Dr Uriel has received consulting fees from Leviticus and LiveMetric. Dr Drakos is supported by the American Heart Association Heart Failure Strategically Focused Research Network (16SFRN29020000), NIH R01 HL135121, NIH R01 HL132067, Merit Review Award I01 CX0002291 (U.S. Department of Veterans Affairs), and Nora Eccles Treadwell Foundation. All other 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.)

Purpose: We sought to develop and validate machine learning (ML) models to increase the predictive accuracy of mortality after heart transplantation (HT)., Methods and Results: We included adult HT recipients from the United Network for Organ Sharing (UNOS) database between 2010 and 2018 using solely pre-transplant variables. The study cohort comprised 18 625 patients (53 ± 13 years, 73% males) and was randomly split into a derivation and a validation cohort with a 3:1 ratio. At 1-year after HT, there were 2334 (12.5%) deaths. Out of a total of 134 pre-transplant variables, 39 were selected as highly predictive of 1-year mortality via feature selection algorithm and were used to train five ML models. AUC for the prediction of 1-year survival was .689, .642, .649, .637, .526 for the Adaboost, Logistic Regression, Decision Tree, Support Vector Machine, and K-nearest neighbor models, respectively, whereas the Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score had an AUC of .569. Local interpretable model-agnostic explanations (LIME) analysis was used in the best performing model to identify the relative impact of key predictors. ML models for 3- and 5-year survival as well as acute rejection were also developed in a secondary analysis and yielded AUCs of .629, .609, and .610 using 27, 31, and 91 selected variables respectively., Conclusion: Machine learning models showed good predictive accuracy of outcomes after heart transplantation., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The new heart allocation system in the United States prioritizes patients supported by temporary mechanical circulatory support (TMCS) devices over those with uncomplicated durable continuous-flow left ventricular assist devices (CF-LVADs), which may increase the number of patients bridged to transplant with TMCS. Limited data are available in guiding post-transplant outcomes with various TMCS devices. We sought to describe post-transplant outcome and identify clinical variables associated with post-transplant outcome in patients bridged to transplant with TMCS., Methods: Using data from the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, we included subjects who underwent transplantation between 2005 and 2016 with known use of mechanical circulatory support. Pre-transplant recipient, donor, and transplant-specific variables were abstracted. The primary outcome was patient survival at 1-year post-transplant. Outcomes of patients bridged to transplant with TMCS were compared with those of patients bridged with CF-LVADs. Cox regression analyses were performed to identify clinical variables associated with the outcomes., Results: There were 6,528 patients bridged to transplant with the following types of mechanical circulatory support: durable CF-LVADs (n = 6,206), extracorporeal membrane oxygenation (ECMO, n = 134), percutaneous temporary CF-LVADs (n = 75), surgically implanted temporary CF-LVADs (n = 38) or surgically implanted temporary BiVAD (n = 75). Bridging with ECMO (hazard ratio 3.79, 95% confidence interval [CI] 2.69-5.34, p < 0.001) or percutaneous temporary CF-LVADs (hazard ratio 1.83, 95% CI 1.09-3.08, p = 0.02) was independently associated with higher risk of mortality. Additional risk factors included older donor age, female/male donor-recipient match, older recipient age, higher recipient body mass index, higher recipient creatinine, and prolonged ischemic time., Conclusions: This analysis of a large international cohort of patients bridged to transplant with mechanical circulatory support identified ECMO and percutaneous temporary CF-LVADs as predictors of mortality after transplant, along with additional donor and recipient clinical characteristics. These findings may provide guidance to clinicians in decisions on mechanical circulatory support device selection, transplant eligibility, and timing of transplant., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac allograft vasculopathy (CAV) remains an important source of mortality after heart transplant. The aim of our study was to identify structural and microvasculature changes in severe CAV., Methods and Results: The study group included heart transplant recipients with severe CAV who underwent retransplantation (severe CAV, n=20). Control groups included time from transplant matched cardiac transplant recipients without CAV (transplant control, n=20), severe ischemic cardiomyopathy patients requiring left ventricular assist device implantation (ischemic control, n=18), and normal hearts donated for research (donor control, n=10). We collected baseline demographic information, echocardiography data, and performed histopathologic examination of myocardial microvasculature. Echocardiographic features of severe CAV included lack of eccentric remodeling and presence of significant diastolic dysfunction. In contrast, diastolic function was preserved in transplant control subjects. Histopathologic examination showed increased interstitial fibrosis among severe CAV, transplant controls, and ischemic control patients. Compared with transplant controls, severe CAV subjects had reduced capillary density and increased capillary wall thickness ( P<0.05)., Conclusions: Our results suggest that the marked diastolic dysfunction and resultant symptoms in patients with severe CAV may be secondary to the loss of microvasculature and remodeling of remaining microvessels rather than a consequence of interstitial fibrosis. The clinical significance and potential therapeutic implications of these unique microvasculature characteristics warrant further investigation.

Background: Current organ allocation policy and the rapid growth of mechanical support favor heart transplant (HT) candidates on left ventricular assist devices. HT candidates with hypertrophic cardiomyopathy (HCM) are usually not left ventricular assist device candidates and may have a disadvantage compared with dilated forms of cardiomyopathy., Methods and Results: Adult HT candidates registered in the Scientific Registry of Transplant Recipients database between 1999 and 2016 were included. HCM candidates were compared with ischemic cardiomyopathy (ICM) and non-ICM patients. Two eras were defined on the basis of the approval date of the first continuous-flow left ventricular assist device for bridge-to-transplant in the United States (2008). Patients outcomes were evaluated while on the waitlist and after HT. The proportion of patients with HCM listed for HT increased by 44% in era 2 compared with era 1. Waitlist mortality in patients with ICM (15.5%-8.7%) and non-ICM (14.2%-8.2%) declined across eras, but minimal decline was observed in HCM patients (11.7%-9.6%; P =0.06). In era 2, the 12-month rate of HT in HCM (64.8%) was comparable to that of ICM (60.9%) and non-ICM (62.7%) patients ( P =0.06). Post-transplant survival in HCM patients was the most favorable in the most recent era (1 year: 91.6% and 5 years: 82.5%; P <0.05 for all comparisons)., Conclusions: The number of patients with HCM in need of HT is increasing. Although post-transplant survival in HCM is excellent, waitlist mortality is substantial and with minimal decline in the most recent era, despite the frequent use of listing status upgrade by exception in this patient cohort. Different strategies to improve the performance of the organ allocation system in patients with HCM are needed., (© 2018 American Heart Association, Inc.)

Background: Survival beyond 1 year after heart transplantation has remained without significant improvement for the last 2 decades. A more individualized approach to post-transplant care could result in a reduction of long-term mortality. Although recipient age has been associated with an increased incidence of certain post-transplant morbidities, its effect on cause-specific mortality has not been established., Methods: We analyzed overall and cause-specific mortality of heart transplant recipients registered in the International Society for Heart and Lung Transplantation Registry between 1995 and 2011. Patients were grouped by recipient age: 18 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥ 70 years. Multivariable regression models were used to examine the association between recipient age and leading causes of post-transplant mortality. We also compared immunosuppression (IS) use among the different recipient age groups., Results: There were 52,995 recipients (78% male; median age [5th, 95th percentile]: 54 [27, 66] years). Survival through 10 years after transplant was lower in heart transplant recipients in the 2 more advanced age groups: 49% for 60 to 69 years and 36% for ≥ 70 years (p < 0.01 for pairwise comparisons with remaining groups). The risk of death caused by acute rejection (hazard ratio [HR], 4.11; p < 0.01), cardiac allograft vasculopathy (HR, 2.85; p < 0.01), and graft failure (HR, 2.29; p < 0.01) was highest in the youngest recipients (18-29 years) compared with the reference group (50-59 years). However, the risk of death caused by infection (HR, 2.10; p < 0.01) and malignancy (HR, 2.23; p < 0.01) was highest in older recipients (≥ 70 years). Similarly, the risk of death caused by renal failure was lower in younger recipients than in the reference group (HR, 0.53; p < 0.01 for 18-49 years vs 50-59 years). The use of induction IS was similar among the different recipient age groups, and differences in maintenance IS were not clinically important., Conclusions: Causes of death in this large cohort of heart transplant recipients varied significantly with recipient age at the time of transplant, with cause-specific mortality profiles suggesting a possible effect of inadequate IS in younger recipients and over-IS in older recipients. Thus, a more personalized approach, possibly including different IS strategies according to recipient age, might result in improved post-transplant survival., (Published by Elsevier Inc.)

Background: Little is known about mixed cellular and antibody-mediated rejection (MR) in heart transplantation. It remains unclear whether cardiac MR has distinctive pathologic and clinical features beyond those of simultaneous cellular rejection (CR) and antibody-mediated rejection (AMR). In this study we systematically explore the pathologic and clinical characteristics of MR in heart transplantation., Methods: The UTAH Cardiac Transplant Program database was queried for transplant recipients who survived long enough to have at least one endomyocardial biopsy (EMB) between 1985 and 2014. Only EMBs with both CR and AMR scores documented were included. In addition to detailed pathologic analyses, we also examined the incidence and prevalence of MR, the likelihood to transition from and to MR, and mortality associated with MR., Results: Patients (n = 1,207) with a total of 28,484 EMBs met the study inclusion criteria. The overall prevalence of MR was 7.8% and it was nearly twice as frequent within the first year post-transplant. Mild MR was by far the most common occurrence and was typically preceded by an immune active state. When CR increased in severity, AMR tended to follow, but the reverse was not true. On pathology, individual features of CR and AMR were more easily separated in cases of mild MR, whereas they substantially overlapped in more severe cases. MR was associated with a significant cardiovascular death risk that was incremental with severity., Conclusions: MR is not common, usually occurs early after transplant, and is associated with worse outcomes. MR reflects a complex interplay between cellular and humoral processes, which varies with rejection severity., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The elevated baseline heart rate (HR) of a heart transplant recipient has previously been considered inconsequential. However, we hypothesized that a resting HR above 100 beats per minute (bpm) may be associated with morbidity and mortality., Methods: The U.T.A.H. Cardiac Transplant Program studied patients who received a heart transplant between 2000 and 2011. Outpatient HR values for each patient were averaged during the first year post-transplant. The study cohort was divided into two groups: the tachycardic (TC) (HR > 100 bpm) and the non-TC group (HR ≤ 100 bpm) in which mortality, incidence of rejection, and cardiac allograft vasculopathy were compared., Results: Three hundred and ten patients were included as follows: 73 in the TC and 237 in the non-TC group. The TC group had a higher risk of a 10-yr all-cause mortality (p = 0.004) and cardiovascular mortality (p = 0.044). After adjustment for donor and recipient characteristics in multivariable logistic regression analysis, the hazard ratio was 3.9, (p = 0.03, CI: 1.2-13.2) and 2.6 (p = 0.02, CI: 1.2-5.5) for cardiovascular mortality and all-cause mortality, respectively., Conclusion: Heart transplant recipients with elevated resting HR appear to have higher mortality than those with lower resting HR. Whether pharmacologically lowering the HR would result in better outcomes warrants further investigation., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although current left ventricular assist device (LVAD) technology has proven more durable than first-generation devices, all mechanical devices are prone to complications that can elevate patient acuity before transplantation. LVAD patients with complications intuitively carry a higher risk profile than other status 1A LVAD patients who are generally stable and use their 30 days of clinically stable status 1A time. We sought to determine if the presence or absence of complications in status 1A LVAD patients at the time of transplant influenced survival after transplant., Methods: The United Network of Organ Sharing database was retrospectively analyzed for 15,253 patients who were listed status 1A from 1998 to 2008. Survival after transplant survival was compared between patients who were and were not listed for LVAD-related complications. Standard statistical analysis was applied., Results: No survival difference was identified at 1 and 10 years after transplant in patients who had device complications compared with those without complications. Of the five complication entries (thromboembolism, infection, malfunction, malignant arrhythmia, and other), only device infection increased mortality risk compared with noncomplicated patients (39% at 1 year, 30% at 10 years, p < 0.01)., Conclusions: Long-term outcomes are generally not affected by the status 1A listing criteria for patients bridged to transplant with LVADs. However, the subset of patients with device infection had worse 1-year and 10-year posttransplant survival. Bridge to transplant patients, despite serious device-related complications, still have excellent transplant outcomes., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Survival of patients on left ventricular assist devices (LVADs) has improved. We examined the differences in risk of adverse outcomes between LVAD-supported and medically managed candidates on the heart transplant waiting list., Methods and Results: We analyzed mortality and morbidity in 33,073 heart transplant candidates registered on the United Network for Organ Sharing (UNOS) waiting list between 1999 and 2011. Five groups were selected: patients without LVADs in urgency status 1A, 1B, and 2; patients with pulsatile-flow LVADs; and patients with continuous-flow LVADs. Outcomes in patients requiring biventricular assist devices, total artificial heart, and temporary VADs were also analyzed. Two eras were defined on the basis of the approval date of the first continuous-flow LVAD for bridge to transplantation in the United States (2008). Mortality was lower in the current compared with the first era (2.1%/mo versus 2.9%/mo; P<0.0001). In the first era, mortality of pulsatile-flow LVAD patients was higher than in status 2 (hazard ratio [HR], 2.15; P<0.0001) and similar to that in status 1B patients (HR, 1.04; P=0.61). In the current era, patients with continuous-flow LVADs had mortality similar to that of status 2 (HR, 0.80; P=0.12) and lower mortality compared with status 1A and 1B patients (HR, 0.24 and 0.47; P<0.0001 for both comparisons). However, status upgrade for LVAD-related complications occurred frequently (28%) and increased the mortality risk (HR, 1.75; P=0.001). Mortality was highest in patients with biventricular assist devices (HR, 5.00; P<0.0001) and temporary VADs (HR, 7.72; P<0.0001)., Conclusions: Mortality and morbidity on the heart transplant waiting list have decreased. Candidates supported with contemporary continuous-flow LVADs have favorable waiting list outcomes; however, they worsen significantly once a serious LVAD-related complication occurs. Transplant candidates requiring temporary and biventricular support have the highest risk of adverse outcomes. These results may help to guide optimal allocation of donor hearts.

Objective: Higher altitudes are associated with chronic hypoxia and elevated pulmonary vascular resistance, both potentially detrimental to patients requiring heart transplantation. The purpose of the present study was to determine whether altitude negatively affects survival among patients undergoing heart transplantation., Methods: The United Network of Organ Sharing database for adult patients undergoing heart transplantation from 1990 to 2008 (n = 36,529) was analyzed, and each patient was assigned an altitude according to their home ZIP code. Survival was compared between patients at less than 2000 ft, 2000 or more to less than 4000 ft, and 4000 ft or more. Adjusted survival was calculated using Cox proportional hazards analysis with propensity-matched stratification., Results: Patients living at above 2000 ft had a 16% reduction in the risk of death at 1 year after transplant (P = .006) compared with those at lower altitudes. At 5 and 10 years, the risk reduction was 6% (P = .21) and 6% (P = .114), respectively. Among patients living above 4000 ft, the 1-, 5-, and 10-year reduction in the risk of death was 20% (P = .022), 12% (P = .057), and 15% (P = .0052) compared with those living below 2000 ft, respectively. Patients at high altitude had a lower incidence of diabetes, used tobacco less often, and accounted for the greatest proportion of status 2 heart transplants. Comparing the factors predicting survival at high and low altitudes, patients with a status 1A listing had improved outcomes at higher altitudes., Conclusions: Patients living above 2000 ft have improved survival after heart transplantation, an advantage even more pronounced at 4000 ft. Although the mechanism of protection remains unclear, the findings might reflect differences in pre-2006 organ allocation., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Growing evidence suggests worse cardiac allograft vasculopathy and mortality in patients with asymptomatic antibody-mediated rejection (AMR). Debate continues about whether therapeutic intervention is warranted to avoid adverse outcomes. In this study we examine the course of individual episodes of untreated asymptomatic AMR on follow-up endomyocardial biopsy (EMB)., Methods: The U.T.A.H. Cardiac Transplant Program database was queried for transplant recipients between 1985 and 2009 who survived beyond 1 year and had at least 1 episode of lone AMR with a follow-up EMB. All EMBs were screened for AMR by immunofluorescence and graded for severity. Data were analyzed based on time from transplant (early, ≤12 months; late, >12 months)., Results: Nine hundred fifty-eight patients with a total of 15,448 biopsies qualified for the study. Average age at transplant was 46.7 years; 13% of the patients were female. Within the first year post-transplant, asymptomatic AMR was diagnosed in 13.6% of biopsies compared with 5.2% beyond 1 year. AMR resolved in 65% (early) vs 75% (late) on follow-up EMB. More severe AMR was less likely to improve regardless of time from transplant. Furthermore, after an episode of AMR had resolved, the recurrence rate at 3, 6 and 12 months was 44%, 50.1% and 56.2%, respectively., Conclusions: The incidence of AMR is higher in the first year post-transplant and the likelihood of resolution is less on follow-up EMB, especially when more severe. A small but significant number of cases became worse or did not change. These new findings may be helpful in planning future studies that test whether therapeutic interventions on asymptomatic AMR favorably impact outcomes., (Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Both pulsatile-flow and continuous-flow left ventricular assist devices (LVADs) successfully provide patients a bridge to transplantation. Some data suggest that continuous-flow pumps increase the risk of allograft rejection, contributing to posttransplantation morbidity and mortality. We sought to analyze the relationship between LVAD flow characteristics and subsequent allograft rejection in bridge to transplant (BTT) patients., Methods: Patients with LVADs from the UTAH Transplant Affiliated Hospitals were retrospectively analyzed. Rejection was determined pathologically according to the International Society for Heart and Lung Transplantation revised cardiac allograft rejection scale. Multimodal statistical analyses were applied., Results: Of 1,076 patients who underwent transplantation over a 26-year period, 151 had LVADs. Of these, 111 (77 pulsatile flow, 34 continuous flow) patients had pathologic data available. There was no difference in overall rejection (grades 1R to 3R) between the pulsatile-flow LVAD and continuous-flow LVAD groups (2.00 ± 1.43 versus 1.50 ± 1.16 episodes/year; p = 0.076.) Patients with pulsatile-flow LVADs had more clinically relevant (grades 2R to 3R) rejection than did patients with continuous-flow LVADs (0.49 ± 0.72 versus 0.12 ± 0.33 episodes/year; p < 0.001). There was no survival difference at 1 year (p = 0.920) or 4 years (p = 0.721) after transplantation., Conclusions: Patients with continuous-flow LVADs have similar overall rejection rates and a reduced rate of clinically relevant rejection compared with patients with pulsatile-flow LVADs during the first year after transplantation. Although there is theoretical concern that nonphysiologic, nonpulsatile flow could alter the neurohormonal profile of patients in heart failure, we are encouraged that the type of LVAD circulation does not influence posttransplantation allograft survival., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients bridged to heart transplantation with left ventricular assist devices (LVADs) have been reported to have higher post-transplant mortality compared with those without LVADs. Our aim was to determine the impact of the type of LVAD and implant era on post-transplant survival., Methods: In this study we included 8,557 patients from the registry of the International Society for Heart and Lung Transplantation. We examined post-transplant outcomes in 1,100 patients bridged to transplant with pulsatile-flow LVADs between January 2000 and June 2004 (first era), 880 patients bridged with pulsatile-flow LVADs between July 2004 and May 2008 (second era), and 417 patients bridged with continuous-flow LVADs in the second era. Patients who required intravenous inotropes but not LVAD support (n = 2,728) and patients who did not require either LVAD or inotropes (n = 3,432) served as controls., Results: Post-transplant survival of patients bridged with pulsatile LVADs improved significantly between the first and the second era (p = 0.03). In the second era, there was no significant difference in post-transplant survival of patients bridged with pulsatile- vs continuous-flow LVADs (p = 0.26), and survival rates in the 2 groups were not statistically different from that of the non-LVAD group. Graft rejection was similar in patients bridged with LVADs compared to those without LVADs., Conclusions: In the most recent era, the use of either pulsatile- or continuous-flow LVADs did not result in increased post-transplant mortality. This finding is important as the proportion of patients with LVADs at the time of transplant has been rising., (Published by Elsevier Inc.)

Left ventricular assist device (LVAD) implantation before heart transplantation has been associated with formation of antibodies directed against human leukocyte antigens (HLA), often referred to as sensitization. This study investigated whether prior sensitization or LVAD type affected the degree of post-implantation sensitization. The records of consecutive HeartMate (HM) I and HM II LVAD patients were reviewed. Panel reactive antibody (PRA) was assessed before LVAD implantation and biweekly thereafter. Sensitization was defined as PRA > 10%, and high-degree sensitization was defined as PRA > 90%. An HM LVAD was implanted in 64 patients, and 11 received a HM II LVAD as a bridge to transplant. Ten HM I patients (16%) were sensitized before LVAD implantation (HM I-S), and 54 (84%) were not (HM I-Non-S). Nine HM I-S patients (90%) became highly sensitized (PRA > 90%) compared with 9 HM I-Non-S patients (16.7%; p < 0.001). The PRA remained elevated (> 90%) in 8 of the 9 (88.9%) highly sensitized HM I-S patients vs 5 of the 9 (55.6%) HM I-Non-S highly sensitized patients. The PRA levels in the rest of the HM I-S highly sensitized patients declined from 93% +/- 4% to 55% +/- 15% (p = 0.01). Among the 11 HM II patients, 1 (9%) was sensitized before LVAD implantation (PRA, 40%) and the PRA moderately increased to 80%. No other HM II patient became sensitized after implantation. Thus, 1 of 11 (9%) HM II patients became sensitized compared with 29 of 64 (45%) HM I patients (p = 0.04). Pre-sensitized patients are at higher risk for becoming and remaining highly HLA-allosensitized after LVAD implantation. The HeartMate II LVAD appears to cause less sensitization than HeartMate I.

Background: Little has been reported on the clinical significance of asymptomatic antibody-mediated rejection (AMR) alone or mixed rejection (MR), defined as concurrent cellular rejection (CR) and AMR in heart transplantation. In this study, we examined whether a differential impact on cardiovascular mortality (CVM) existed when comparing asymptomatic AMR, to stable MR or CR., Methods: The Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program pathology database of all heart transplant recipients between 1985 and 2004 was queried. Patients were classified as cellular, antibody-mediated, or mixed rejectors based on their predominant pattern of rejection type in the first three months post-transplant. Kaplan-Meier survival curves were fit to each of the three groups and analyses were adjusted for age at the time of transplant, gender, and underlying primary cardiac disease., Results: Eight hundred and sixty nine heart transplant recipients qualified for analysis. Over the study period, patients with asymptomatic AMR or stable MR patterns had significantly worse CVM when compared to patients with stable CR pattern (AMR, 21.2%; MR, 18.0%; CR, 12.6%; AMR vs. CR, p = 0.009; MR vs. CR, p = 0.001). In contrast, CVM was comparable in patients with asymptomatic AMR or stable MR patterns (p = 0.9)., Conclusions: Asymptomatic or subclinical AMR and MR are clinically relevant, should be recognized, and deserve consideration for therapeutic intervention in hopes of avoiding adverse outcomes.

Background: Heart failure (HF) patients may require cardiac assist device implantation prior to transplantation (Tx) because of either acute cardiogenic shock (ACS), with no prior history of HF, or for progression of pump failure in the setting of chronic HF., Aims: To investigate whether patients implanted with a cardiac assist device for ACS, have similar post-Tx outcomes as those who underwent cardiac assist device implantation because of progressive chronic HF., Methods and Results: We compared post-Tx outcomes of consecutive patients bridged due to ACS (Acute Group) with the outcomes of patients bridged due to deterioration of chronic HF (Chronic Group). Seventy-three patients had a cardiac assist device implanted and underwent subsequent cardiac Tx. Thirty-five patients (48%) had a cardiac assist device implanted due to ACS, most often caused by massive acute myocardial infarction, and 38 patients (52%) because of progressive chronic HF. Despite greater compromise at the time of implantation, the Acute Group recovered satisfactorily and underwent Tx with similar post-Tx survival rates as the Chronic Group patients [1-year survival: 88.6% vs 86.8%, p=0.80, actuarial survival (mean follow-up 4.2 years): 80.0% vs 81.6%, p=0.86)]. Furthermore, no significant differences were observed between the 2 groups in various post-Tx events., Conclusion: Patients with ACS who underwent emergency cardiac assist device implantation as bridge to Tx had similar post-Tx outcomes as their more chronically ill counterparts who underwent device implantation on a non-urgent basis.

Background: Conflicting data exist regarding the impact of reversible pulmonary hypertension (PHTN) on post-transplant (Tx) outcomes. In this study we sought to determine the influence of reversible PHTN on outcomes after Tx., Methods: We retrospectively reviewed the records of adult patients who underwent heart Tx from 1993 to 2002. Patients were grouped depending on their measured pulmonary vascular resistance (PVR). Group 1 patients had a pre-Tx pulmonary vascular resistance (PVR) of < 3 Wood units (WU). Patients with reversible PHTN, defined as pre-Tx PVR > or = 3 WU and reversing to < 3 WU either with sub-lingual or intravenous vasodilatory agents, were divided into two groups based on their PVR before the reversibility test (PVR: Group 2, 3 to 4.5 WU; Group 3, > 4.5 WU)., Results: Records for 222 adult heart recipients were reviewed (Group 1, n = 171; Group 2, n = 35; Group 3, n = 16). Baseline clinical characteristics (age, gender, heart failure etiology, history of diabetes, ischemic time, donor age and gender) were similar in the three groups and the average follow-up was 58 months. One-month and 1-year mortality (Groups 1, 2 and 3: 2%, 0% and 13%; and 8%, 0% and 13%, respectively) did not differ significantly between groups. Actuarial mortality was assessed using Cox regression analysis, adjusted for age and gender, and no increased risk of death was demonstrated for patients with reversible PHTN (for Group 2: multivariate hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.17 to 1.32, p = 0.15; for Group 3: HR 0.98, CI 0.34 to 2.84, p = 0.97). No differences were observed between the three groups for various post-Tx events, such as hospital stay, ICU stay, extubation time, transfusions, acute allograft dysfunction, acute hepatic dysfunction, acute and chronic renal dysfunction, infections, neurologic complications, gastrointestinal complications and coronary allograft vasculopathy., Conclusions: Reversible pulmonary hypertension is associated with similarly good post-transplant survival outcomes and morbidity, regardless of severity.

Background: Determining which pretransplantation (TX) characteristics predict the development of chronic renal dysfunction (CRD) or death after heart TX would enable more accurate risk assessment at the time of candidate evaluation., Methods: A cohort of 278 patients underwent TX in three hospitals between 1993 and 2002. Predictive models for CRD (serum creatinine consistently above 2 mg/dL) and allograft loss (death or re-TX) were constructed using logistic and Cox regression, respectively., Results: Using logistic regression, CRD was more likely to develop in TX patients if they had a larger body surface area (odds ratio [OR] = 5.8 per m2, 95% confidence interval [CI] = 1.04 to 31.9, p = 0.04) or were inotrope dependent (OR = 1.8, 95% CI = 0.90 to 3.7, p = 0.09). Notably, the implementation of mechanical circulatory support as bridge to transplantation decreased the risk of CRD (OR = 0.30, 95% CI = 0.12 to 0.72, p = 0.007). Cox analysis demonstrated independent predictive ability of improved survival for males (hazard ratio [HR] = 0.42, 95% CI = 0.21 to 0.83, p = 0.01). Worse survival was observed with prior sternotomy (HR = 3.5, 95% CI = 2.0 to 6.0, p < 0.001), diabetes mellitus (HR = 1.9, 95% CI = 0.98 to 3.9, p = 0.06), and elevated serum creatinine (HR = 2.8 per mg/dL, 95% CI = 1.3 to 5.8, p = 0.007)., Conclusions: Certain pretransplant characteristics clearly predispose a patient to the development of CRD or increased mortality after heart transplantation. Interestingly, the risk of CRD after heart transplantation is greater for patients bridged to transplant with inotropes than with mechanical circulatory support. When hemodynamically indicated, timely implementation of pretransplant mechanical circulatory support should be considered.

Background: Mechanical circulatory support (MCS) before heart transplantation was previously associated with worse post-transplant outcomes than when MCS was not required. Given the changes in technology, expertise, patient selection, and timing of subsequent transplantation, we hypothesized that patients who require MCS before heart transplantation have similar outcomes after transplantation as those not requiring pre-transplant MCS., Methods: We retrospectively reviewed 278 patients who underwent cardiac transplantation from 1993 to 2002. MCS was required in 72 patients (HeartMate LVAS in 66, CardioWest Total Artificial Heart in 6) and was not required in 206 patients. The influence of pre-transplant MCS on post-transplant outcomes was assessed in the 2 groups., Results: Baseline clinical characteristics (age, gender, etiology of heart failure, history of diabetes mellitus, and donor age and gender) were similar in the 2 groups. One-month and 1-year survival after transplantation did not differ between the groups (MCS, 92% and 85%, respectively vs no MCS, 97% and 92%, respectively). Similar proportions of patients were free from rejection (International Society for Heart and Lung Transplantation score >or=3A) at 1 year of follow-up (MCS, 56% vs no MCS, 52%, p = 0.60). No difference was observed between MCS and no MCS patients in other post-transplant events such as hospital stay, intensive care unit stay, extubation time, acute allograft dysfunction, reoperation rates, acute renal dysfunction, acute hepatic dysfunction, infections, arrhythmias, thromboembolic complications, neurologic complications, gastrointestinal complications and the development of cardiac allograft vasculopathy. The incidence of chronic renal insufficiency was actually lower in the MCS Group (15.3% vs 37.9%, p = .001)., Conclusion: Post-transplant outcomes after pre-transplant use of MCS are similar to those when MCS is not required.

BACKGROUND: Current organ allocation policy and the rapid growth of mechanical support favor heart transplant (HT) candidates on left ventricular assist devices. HT candidates with hypertrophic cardiomyopathy (HCM) are usually not left ventricular assist device candidates and may have a disadvantage compared with dilated forms of cardiomyopathy. METHODS AND RESULTS: Adult HT candidates registered in the Scientific Registry of Transplant Recipients database between 1999 and 2016 were included. HCM candidates were compared with ischemic cardiomyopathy (ICM) and non-ICM patients. Two eras were defined on the basis of the approval date of the first continuous-flow left ventricular assist device for bridge-to-transplant in the United States (2008). Patients outcomes were evaluated while on the waitlist and after HT. The proportion of patients with HCM listed for HT increased by 44% in era 2 compared with era 1. Waitlist mortality in patients with ICM (15.5%-8.7%) and non-ICM (14.2%-8.2%) declined across eras, but minimal decline was observed in HCM patients (11.7%-9.6%; P=0.06). In era 2, the 12-month rate of HT in HCM (64.8%) was comparable to that of ICM (60.9%) and non-ICM (62.7%) patients (P=0.06). Post-transplant survival in HCM patients was the most favorable in the most recent era (1 year: 91.6% and 5 years: 82.5%; P<0.05 for all comparisons). CONCLUSIONS: The number of patients with HCM in need of HT is increasing. Although post-transplant survival in HCM is excellent, waitlist mortality is substantial and with minimal decline in the most recent era, despite the frequent use of listing status upgrade by exception in this patient cohort. Different strategies to improve the performance of the organ allocation system in patients with HCM are needed. [ABSTRACT FROM AUTHOR]

The article offers information on the role of the lymphatic system in the modulation of cardiac disease, leading to an enhanced interest in the potential therapeutic manipulation of cardiac lymphangiogenesis. Information on chronic rejection and cardiac allograft vasculopathy as well as the modulation of the cardiac lymphatic response to injury to attenuate disease is presented.

Purpose: Cardiac allograft vasculopathy (CAV) continues to hinder the long-term success of heart transplant recipients. Redo-transplantation is currently the only definitive treatment for advanced CAV. We examined whether these patients are at similar CAV-risk with the second transplant. Methods: Heart recipients from 1985 to 2011 at the UTAH program were included in the study and those with CAV as an indication for redo-transplantation were identified. CAV diagnosis was made by coronary angiography and based on the 2010 ISHLT standardized nomenclature for CAV. Patient demographics, rejection history, and CAV incidence were analyzed. Results: Of the 1,169 eligible patients, 135 (11.5%) developed CAV post their first transplant; 78 cases within 10 years and 54 beyond 10 years. The mean time to CAV was 6.58 years. Of the 135 patients who developed CAV, only 21 (15.5%) ended up requiring a redo-transplant. Of the 21 retransplanted patients, 4 (19.0%) developed CAV again; 2 patients within 10 years and 2 patients beyond 10 years indicating a similar risk for CAV occurrence for first and redo-transplant. Conclusions: Our results indicate that CAV is as likely to develop in redo-transplants despite recent advances in immunosuppression and the standardized use of lipid-lowering agents. Although outcomes in redo-transplantation for the indication of CAV are favorable, efforts to better understand and minimize CAV are needed, especially in the face of scarce donor organs. [ABSTRACT FROM AUTHOR]

The article discusses a study on the use of Left ventricular (LV) assist devices (LVADs) as a tool for end-stage heart failure (HF) patients to heart transplantation or as a permanent therapy. It mentions that increase in clinical use of LVADs presents a key opportunity for in-depth investigations of the biology of the failing human heart. It also informs that trough biological and clinical outcomes it is possible to identify new therapeutic strategies of myocardial recovery and regeneration.

The role of ventricular-assist devices in the management of end-stage heart failure is growing. Initially developed as a ‘bridge to transplantation’, they are now implanted permanently in patients who need cardiac replacement but are not candidates for cardiac transplantation (‘destination therapy’). Furthermore, observations from expert centers indicate that a significant proportion of patients under long-term mechanical assistance can be weaned from mechanical circulatory support after significant functional recovery of their native heart (‘bridge to recovery’). This review discusses the emerging roles of mechanical circulatory support and their direct implications in clinical practice. Evolution of devices, important aspects of candidate selection, challenging issues in the management of ventricular-assist device patients (infection, device malfunction, anticoagulation-thromboembolic complications, psychosocial issues and cost) and ongoing research targeting sustained myocardial recovery are discussed. [ABSTRACT FROM AUTHOR]

Background Within the past 10 years, continuous-flow left ventricular assist devices (LVADs) have replaced pulsatile-flow LVADs as the standard of care for both destination therapy and bridging patients to heart transplantation. Despite the rapid clinical adoption of continuous-flow LVADs, an understanding of the effects of continuous-flow physiology, as opposed to more natural pulsatile-flow physiology, is still evolving. Materials and methods A thorough review of the relevant scientific literature regarding the physiological and clinical effects of continuous-flow physiology was performed. These effects were analyzed on an organ system basis and include an evaluation of the cardiovascular, respiratory, hematologic, gastrointestinal, renal, hepatic, neurologic, immunologic, and endocrine systems. Results Continuous-flow physiology is, generally speaking, well tolerated over the long term. However, several changes are manifest at the organ system level. Although many of these changes are without appreciable clinical significance, other changes, such as an increased rate of gastrointestinal bleeding, appear to be associated with continuous-flow physiology. Conclusions Continuous-flow LVADs confer a significant advantage over their pulsatile-flow counterparts with regard to size and durability. From a physiological standpoint, continuous-flow physiology has limited clinical effects at the organ system level. Although improved over previous generations, challenges with this technology remain. Approaching these problems with a combination of clinical and engineering solutions may be needed to achieve continued progression in the field of durable mechanical circulatory support. [ABSTRACT FROM AUTHOR]

Background Antibody-mediated rejection (AMR) in cardiac transplant recipients is a serious form of rejection with adverse patient outcomes. The International Society of Heart and Lung Transplantation (ISHLT) has published a consensus schema for the pathologic diagnosis of various grades of antibody-mediated rejection (pathology antibody-mediated rejection [pAMR]). We sought to determine whether the ISHLT pAMR grading schema correlates with patient outcomes. Methods Using our database, which contains a semi-quantitative scoring of all pathologic descriptors of pAMR, we retrospectively used these descriptors to convert the previous AMR categories to the current ISHLT pAMR categories. Cox proportional hazard models were fit with cardiovascular (CV) death or retransplant as the outcome. The pAMR value was included as a categorical variable, and cellular rejection (CR) values were included in a separate model. Results There were 13,812 biopsies from 1,014 patients analyzed. The pAMR grades of pAMR1h, pAMR1i, and pAMR2 conferred comparable increased risk for CV mortality. Significantly increased risk of CV mortality was conferred by biopsies graded as severe AMR (pAMR3). Conclusions The new ISHLT pAMR grading schema identifies patients at increased risk of CV mortality, consistent with risks published from several programs before 2011. The current schema is validated by this analysis in a large biopsy database. Because pAMR1h, pAMR1i, and pAMR2 have similar CV risks associated with them, the threshold for a positive diagnosis of pAMR should be re-evaluated in future iterations of the ISHLT schema. [ABSTRACT FROM AUTHOR]

Background Continuous-flow (CF) left ventricular assist devices (LVADs) are standard of care for bridging patients to cardiac transplantation. However, existing data about preoperative factors influencing early post-transplant survival in these patients are limited. We sought to determine risk factors for mortality using a large international database. Methods All patients in the International Society for Heart and Lung Transplantation Transplant Registry who were bridged to transplantation with CF LVADs between June 2008 and June 2012 were included. Risk factors for mortality within 30 days of transplant were identified. Statistical analysis included multivariable analysis and Kaplan-Meier survival analysis. Results During the study period, 2,152 patients with CF LVADs underwent heart transplantation. Post-transplant survival was 95.5% at 30 days. Risk factors for mortality during this window included ventilator support at transplant (hazard ratio [HR] = 5.00, 95% confidence interval [CI] = 1.51–16.58), female recipient/male donor (compared with all other combinations, HR = 3.29, 95% CI = 1.90–5.72), history of hemodialysis (HR = 2.51, 95% CI = 1.14–5.51), and history of coronary bypass grafting (HR = 1.89, 95% CI = 1.19–3.00). Increasing recipient age ( p = 0.002), body mass index ( p = 0.002), creatinine ( p = 0.004), and total bilirubin ( p < 0.001) also were associated with an increase in mortality. Conclusions In patients supported with CF LVADs, risk factors for early mortality can be identified before transplant, including ventilator support, female recipient/male donor, increasing recipient age, and body mass index. Despite the inherent complexities of a reoperative surgery, patients bridged to transplant with CF LVADs have excellent peri-operative survival. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the diagnostic accuracy of coronary computed tomography angiography (CCTA) for detecting cardiac allograft vasculopathy (CAV) in comparison with conventional coronary angiography (CCAG) alone or with intravascular ultrasound (IVUS). Background: CAV limits long-term survival after heart transplantation, and screening for CAV is performed on annual basis. CCTA is currently not recommended for CAV screening due to the limited accuracy reported by early studies. Technological advances, however, might have resulted in improved test performance and might justify re-evaluation of this recommendation. Methods: A systematic review of Medline, Cochrane, and Embase for all prospective trials assessing CAV using CCTA was performed using a standard approach for meta-analysis for diagnostic test and a bivariate analysis. Results: Thirteen studies evaluating 615 patients (mean age 52 years, 83% male) and 9,481 segments fulfilled inclusion criteria. Patient-based analyses comparing CCTA versus CCAG for the detection of any CAV (> luminal irregularities) and significant CAV (stenosis ≥50%), showed mean weighted sensitivities of 97% and 94%, specificities of 81% and 92%, a negative predictive value (NPV) of 97% and 99%, a positive predictive value (PPV) of 78% and 67%, and diagnostic accuracies of 88% and 94%, respectively. There was a strong trend toward improved sensitivity (97% vs. 91%, p = 0.06) and NPV (99% vs. 97%, p = 0.06) to detect significant CAV with 64-slice compared with 16-slice CCTA. A patient-based analysis of 64-slice CCTA versus IVUS showed a mean weighted sensitivity and specificity of 81% and 75% to detect CAV (intimal thickening >0.5 mm), whereas the PPV and NPV were 93% and 50%, respectively. Conclusions: CCTA using currently available technology is a reliable noninvasive imaging alternative to coronary angiography with an excellent sensitivity, specificity, and NPV for the detection of CAV. [Copyright &y& Elsevier]