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Cardiosphere-Derived Cells and Ischemic Heart Failure.

Wed, 12/06/2017 - 13:45
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Cardiosphere-Derived Cells and Ischemic Heart Failure.

Cardiol Rev. 2018 Jan/Feb;26(1):8-21

Authors: Ashur C, Frishman WH

Abstract
After a myocardial infarction, heart tissue becomes irreversibly damaged, leading to scar formation and inevitably ischemic heart failure. Of the many available interventions after a myocardial infarction, such as percutaneous intervention or pharmacological optimization, none can reverse the ischemic insult on the heart and restore cardiac function. Thus, the only available cure for patients with scarred myocardium is allogeneic heart transplantation, which comes with extensive costs, risks, and complications. However, multiple studies have shown that the heart is, in fact, not an end-stage organ and that there are endogenous mechanisms in place that have the potential to spark regeneration. Stem cell therapy has emerged as a potential tool to tap into and activate this endogenous framework. Particularly promising are stem cells derived from cardiac tissue itself, referred to as cardiosphere-derived cells (CDCs). CDCs can be extracted and isolated from the patient's myocardium and then administered by intramyocardial injection or intracoronary infusion. After early success in the animal model, multiple clinical trials have demonstrated the safety and efficacy of autologous CDC therapy in humans. Clinical trials with allogeneic CDCs showed early promising results and pose a potential "off-the-shelf" therapy for patients in the acute setting after a myocardial infarction. The mechanism responsible for CDC-induced cardiac regeneration seems to be a combination of triggering native cardiomyocyte proliferation and recruitment of endogenous progenitor cells, which most prominently occurs via paracrine effects. A further understanding of the mediators involved in paracrine signaling can help with the development of a stem cell-free therapy, with all the benefits and none of the associated complications.

PMID: 29206745 [PubMed - in process]

The need and opportunity for donation after circulatory death worldwide.

Wed, 12/06/2017 - 13:45
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The need and opportunity for donation after circulatory death worldwide.

Curr Opin Organ Transplant. 2017 Dec 04;:

Authors: Manyalich M, Nelson H, Delmonico FL

Abstract
PURPOSE OF REVIEW: The global shortage of organ donors will not be resolved solely by relying on deceased donation following a brain death determination (DBD). Expansion of deceased donation after circulatory death (DCD) will be needed to address the shortfall of organs for transplantation. Approximately 120 000 organ transplants are performed each year; however, the WHO estimates that this number of transplants only resolves 10% of the annual worldwide transplant need.
RECENT FINDINGS: The report addresses the opportunity of DCD expansion by evaluating the DCD potential that is not being realized, the utility of DCD enabling DBD to emerge in some clinical situations, by the effectiveness of a donor registry in achieving DCD, and by the current clinical research of heart, lung, and liver transplantation from DCD.
SUMMARY: The future of deceased donation must include DCD and ex-vivo organ repair if the organ shortage is to be reconciled even partially to the ongoing demand. Although the religious and legal impediments have been overcome to determine brain death, the possibility of DCD has not been addressed. A program of DCD is feasible in all countries with transplantation services. The excellent results following kidney and lung transplantation suggest opportunities of heart and liver transplantation should be the focus of needed DCD accomplishment in the near future.

PMID: 29206661 [PubMed - as supplied by publisher]

Multi-level factors are associated with immunosuppressant nonadherence in heart transplant recipients: the international bright study.

Wed, 12/06/2017 - 13:45
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Multi-level factors are associated with immunosuppressant nonadherence in heart transplant recipients: the international bright study.

Am J Transplant. 2017 Dec 05;:

Authors: Denhaerynck K, Berben L, Dobbels F, Russell CL, Crespo-Leiro MG, Poncelet AJ, Geest S, Behalf of the BRIGHT study team

Abstract
Factors at the level of family/healthcare worker-, organization- and system are neglected in medication nonadherence research in heart transplantation (HTx). The four-continent, eleven-country cross-sectional BRIGHT study used multi-staged sampling to examine 36 HTx centers, including 36 HTx directors, 100 clinicians, and 1397 patients. Nonadherence to immunosuppressants-defined as any deviation in taking or timing adherence and/or dose reduction-was assessed using the BAASIS® interview. Guided by the Integrative Model of Behavioral Prediction and Bronfenbrenner's ecological model, we analyzed factors at these multiple levels using sequential logistic regression analysis (6 blocks). The nonadherence prevalence was 34.1%. Six multi-level factors were associated independently (either positively or negatively) with nonadherence: patient level: barriers to taking immunosuppressants (OR: 11.48); smoking (OR:2.19); family/healthcare provider level: frequency of having someone to help patients read health-related materials (OR:0.85); organization level: clinicians reporting non-adherent patients were targeted with adherence interventions (OR: 0.66); pick-up of medications at physician's office (OR: 2.31); and policy level: monthly out-of-pocket costs for medication (OR: 1.16). Factors associated with nonadherence are evident at multiple levels. Improving medication nonadherence requires addressing not only the patient, but also family/healthcare provider, organization, and policy levels. This article is protected by copyright. All rights reserved.

PMID: 29205855 [PubMed - as supplied by publisher]

Cardiac Transplantation in Dermatomyositis: A case report and literature review.

Wed, 12/06/2017 - 13:45
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Cardiac Transplantation in Dermatomyositis: A case report and literature review.

Hum Pathol (N Y). 2017 Jun;8:55-58

Authors: Bae S, Khanlou N, Charles-Schoeman C

Abstract
Background and objectives: Cardiac involvement has been well recognized in patients with dermatomyositis (DM) and polymyositis (PM) with a variable frequency between 9 and 72%. However, clinically significant heart involvement in DM/PM is relatively infrequent and there have been rare reports of cardiac transplantation in DM. Our aims were to describe a case of severe cardiac involvement in DM requiring heart transplantation and review the literature of cardiac disease in DM and PM.
Methods: A patient with dermatomyositis who was referred to our institution with severe heart failure is described. Pathology of the patient's skeletal and cardiac muscle is reviewed. A MEDLINE database search of reports of cardiac involvement in DM and PM was also conducted.
Results: A 36 year-old man with DM presented with severe heart failure to our institution for evaluation of heart transplantation. After a three month hospitalization he underwent successful cardiac transplantation. Pathological examination of his explant heart revealed a pattern of inflammation and damage similar to DM in skeletal muscle. The patient is currently doing well, 20 months post-transplant, and is maintained on tacrolimus, cellcept, rituximab, and low dose prednisone. To our knowledge, this is the first case report of heart transplantation in dermatomyositis in which the muscle pathology is similar in both heart and skeletal muscle.
Conclusions: Severe cardiac involvement requiring transplantation is rare in dermatomyositis but does occur and appears to be related to a similar inflammatory process as noted in the skeletal muscle.

PMID: 29204355 [PubMed]

Alternative Splicing of NOX4 in the Failing Human Heart.

Wed, 12/06/2017 - 13:45
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Alternative Splicing of NOX4 in the Failing Human Heart.

Front Physiol. 2017;8:935

Authors: Varga ZV, Pipicz M, Baán JA, Baranyai T, Koncsos G, Leszek P, Kuśmierczyk M, Sánchez-Cabo F, García-Pavía P, Brenner GJ, Giricz Z, Csont T, Mendler L, Lara-Pezzi E, Pacher P, Ferdinandy P

Abstract
Increased oxidative stress is a major contributor to the development and progression of heart failure, however, our knowledge on the role of the distinct NADPH oxidase (NOX) isoenzymes, especially on NOX4 is controversial. Therefore, we aimed to characterize NOX4 expression in human samples from healthy and failing hearts. Explanted human heart samples (left and right ventricular, and septal regions) were obtained from patients suffering from heart failure of ischemic or dilated origin. Control samples were obtained from donor hearts that were not used for transplantation. Deep RNA sequencing of the cardiac transcriptome indicated extensive alternative splicing of the NOX4 gene in heart failure as compared to samples from healthy donor hearts. Long distance PCR analysis with a universal 5'-3' end primer pair, allowing amplification of different splice variants, confirmed the presence of the splice variants. To assess translation of the alternatively spliced transcripts we determined protein expression of NOX4 by using a specific antibody recognizing a conserved region in all variants. Western blot analysis showed up-regulation of the full-length NOX4 in ischemic cardiomyopathy samples and confirmed presence of shorter isoforms both in control and failing samples with disease-associated expression pattern. We describe here for the first time that NOX4 undergoes extensive alternative splicing in human hearts which gives rise to the expression of different enzyme isoforms. The full length NOX4 is significantly upregulated in ischemic cardiomyopathy suggesting a role for NOX4 in ROS production during heart failure.

PMID: 29204124 [PubMed]

Pulmonary Vein Stenosis Following Single-Lung Transplantation Successfully Treated with Intravascular Ultrasound-Guided Angioplasty and Stent Placement.

Wed, 12/06/2017 - 13:45
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Pulmonary Vein Stenosis Following Single-Lung Transplantation Successfully Treated with Intravascular Ultrasound-Guided Angioplasty and Stent Placement.

Am J Case Rep. 2017 Dec 05;18:1289-1295

Authors: Jobanputra YB, Kapadia SR, Johnston DR, Ahmed V, Jones BM, Budev M, Lane CR, Mehta AC

PMID: 29203761 [PubMed - in process]

Examining the role of extracorporeal membrane oxygenation in patients following suspected or confirmed suicide attempts: A case series.

Wed, 12/06/2017 - 13:45
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Examining the role of extracorporeal membrane oxygenation in patients following suspected or confirmed suicide attempts: A case series.

J Crit Care. 2017 Oct 18;:

Authors: Abbasi A, Devers C, Muratore CS, Harrington C, Ventetuolo CE

Abstract
The decision to offer extracorporeal membrane oxygenation (ECMO) is based on a risk/benefit assessment and the likelihood of a treatable underlying condition or the feasibility of destination therapy (durable mechanical support or thoracic organ transplantation) should heart-lung function fail to improve. Patients who present following suspected suicide attempts who fail medical therapy may pose a dilemma for clinicians. An assessment to determine if a patient has a high likelihood of psychiatric recovery such that bridging with ECMO or ultimately destination therapy could or should be offered is not always feasible in the setting of critical illness. This case series reviews our institution's experience with ECMO in the management of five patients who presented following suspected or confirmed suicide attempts. All five patients survived to hospital discharge. Two had subsequent psychiatric admissions, one following a repeat suicide attempt. A discussion of these cases demonstrates the effectiveness of ECMO in supporting this group of patients in the short-term. The self-limited natural history of many psychiatric episodes, poisonings and traumatic injuries makes the use of ECMO a potentially reasonable support strategy. However, careful consideration must be given to psychiatric history and follow-up given the substantial commitment of resources, potential for complications and for stranding patients on extracorporeal therapy without definitive destination therapy.

PMID: 29203213 [PubMed - as supplied by publisher]

Semi-automated QRS score as a predictor of survival in CRT treated patients with strict left bundle branch block.

Wed, 12/06/2017 - 13:45
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Semi-automated QRS score as a predictor of survival in CRT treated patients with strict left bundle branch block.

J Electrocardiol. 2017 Nov 15;:

Authors: Reitan C, Chaudhry U, Atwater B, Jacobsson J, Couderc JP, Xia X, Carlson J, Platonov PG, Borgquist R

Abstract
BACKGROUND: Cardiac Resynchronization Therapy (CRT) is widely used for treating selected heart failure patients, but patients with myocardial scar respond worse to treatment. The Selvester QRS scoring system estimates myocardial scar burden using 12-lead ECG. This study's objective was to investigate the scores correlation to mortality in a CRT population.
METHODS AND RESULTS: Data on consecutive CRT patients was collected. 401 patients with LBBB and available ECG data were included in the study. QuAReSS software was used to perform Selvester scoring. Mean Selvester score was 6.4, corresponding to 19% scar burden. The endpoint was death or heart transplant; outcome was analyzed using Cox proportional hazards models. A Selvester score >8 was significantly associated with higher risk of the combined endpoint (HR 1.59, p=.014, CI 1.09-2.3).
CONCLUSION: Higher Selvester scores correlate to mortality in CRT patients with strict LBBB and might be of value in prognosticating survival.

PMID: 29203081 [PubMed - as supplied by publisher]

The viability of transplanting organs from donors who underwent cardiopulmonary resuscitation: A systematic review.

Wed, 12/06/2017 - 13:45
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The viability of transplanting organs from donors who underwent cardiopulmonary resuscitation: A systematic review.

Resuscitation. 2016 Nov;108:27-33

Authors: West S, Soar J, Callaway CW

Abstract
AIMS: To identify reports of patients who underwent cardiopulmonary resuscitation (CPR) prior to solid organ donation and compare recipient and organ function outcomes to those that did not undergo CPR. Donation after restoration of circulation then progressing to death and those donating with on-going CPR who would have otherwise have termination of efforts were both included.
METHODS: Systematic review. Clinical studies comparing the outcome of patients and organs retrieved from donors who underwent CPR with those that did not require CPR. Full-text articles were searched on EmBASE, MEDLINE, Cochrane Database of Systematic Reviews and the Cochrane Register of Controlled Trials.
RESULTS: Twenty-two observational studies were included. There were 12,206 adult and 2552 paediatric organ transplantation identified. Comparing donation after restoration of circulation there was no difference in immediate, one year, and five-year graft function. Donation with on-going CPR was associated with reduced immediate graft function for both renal and hepatic transplantation, however long term function was not different.
CONCLUSIONS: CPR does not appear to adversely affect graft function. Patients who have restored circulation after resuscitation and subsequently progress to death should be evaluated for organ donation. Those with on-going CPR should be considered for hepatic and renal transplantation but there may be worse initial graft function.

PMID: 27568108 [PubMed - indexed for MEDLINE]

Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection.

Tue, 12/05/2017 - 13:45

Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection.

J Clin Invest. 2017 Nov 20;:

Authors: Chen CC, Pouliquen E, Broisat A, Andreata F, Racapé M, Bruneval P, Kessler L, Ahmadi M, Bacot S, Saison-Delaplace C, Marcaud M, Van Huyen JD, Loupy A, Villard J, Demuylder-Mischler S, Berney T, Morelon E, Tsai MK, Kolopp-Sarda MN, Koenig A, Mathias V, Ducreux S, Ghezzi C, Dubois V, Nicoletti A, Defrance T, Thaunat O

Abstract
Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models. Live imaging revealed that DSAs were sequestrated in the circulation of the recipients and failed to reach the endocrine cells of grafted islets. We used murine heart transplantation models to confirm that endothelial cells were the only accessible targets for DSAs, which induced the development of typical microvascular lesions in allogeneic transplants. In contrast, the vasculature of DSA-exposed allogeneic islet grafts was devoid of lesions because sprouting of recipient capillaries reestablished blood flow in grafted islets. Thus, we conclude that endothelial chimerism combined with vascular sequestration of DSAs protects islet grafts from humoral rejection. The reduced immunoglobulin concentrations in the interstitial tissue, confirmed in patients, may have important implications for biotherapies such as vaccines and monoclonal antibodies.

PMID: 29202467 [PubMed - as supplied by publisher]

Combining Adoptive Treg Transfer with Bone Marrow Transplantation for Transplantation Tolerance.

Tue, 12/05/2017 - 13:45

Combining Adoptive Treg Transfer with Bone Marrow Transplantation for Transplantation Tolerance.

Curr Transplant Rep. 2017;4(4):253-261

Authors: Pilat N, Granofszky N, Wekerle T

Abstract
Purpose of Review: The mixed chimerism approach is an exceptionally potent strategy for the induction of donor-specific tolerance in organ transplantation and so far the only one that was demonstrated to work in the clinical setting. Regulatory T cells (Tregs) have been shown to improve chimerism induction in experimental animal models. This review summarizes the development of innovative BMT protocols using therapeutic Treg transfer for tolerance induction.
Recent Findings: Treg cell therapy promotes BM engraftment in reduced conditioning protocols in both, mice and non-human primates. In mice, transfer of polyclonal recipient Tregs was sufficient to substitute cytotoxic recipient conditioning. Treg therapy prevented chronic rejection of skin and heart allografts related to tissue-specific antigen disparities, in part by promoting intragraft Treg accumulation.
Summary: Adoptive Treg transfer is remarkably effective in facilitating BM engraftment in reduced-intensity protocols in mice and non-human primates. Furthermore, it promotes regulatory mechanisms that prevent chronic rejection.

PMID: 29201599 [PubMed]

Early intervention in the management of pulmonary arterial hypertension: clinical and economic outcomes.

Tue, 12/05/2017 - 13:45

Early intervention in the management of pulmonary arterial hypertension: clinical and economic outcomes.

Clinicoecon Outcomes Res. 2017;9:731-739

Authors: Burger CD, Ghandour M, Padmanabhan Menon D, Helmi H, Benza RL

Abstract
Pulmonary arterial hypertension (PAH) has a high morbidity rate and is fatal if left untreated. Increasing evidence supports early intervention, possibly with initial combination therapy. PAH-specific pharmaceuticals, however, are expensive and may have serious adverse effects, particularly when used in combination. The currently dynamic health care economy reinforces the need for a review of early intervention from both outcomes and economic perspectives. We aimed to review the clinical and economic impact of PAH therapy, particularly examining drug cost, hospitalization burden, and health care economics impact, and the effect of early intervention on clinical outcomes. We searched PubMed, Scopus, Ovid, and MEDLINE databases from 2005 to 2017 for studies comparing drug cost, clinical outcomes, and hospitalization burden associated with therapy for PAH. Emerging data indicate that early therapy is effective, but drug therapy is expensive, particularly with combination therapy. Efficacy studies also generally show benefit of combination therapy for patients in World Health Organization functional class II, with a consistent decrease in hospitalization. Pharmacoeconomic studies are limited but indicate that increased pharmacy costs are at least partially offset by decreased health care utilization, particularly inpatient care. Modeling also shows a cost benefit with combination therapy at 2 years. Nonetheless, more rigorously collected health care economic data should be incorporated into future drug efficacy trials to provide a clearer understanding of the impact and the associated cost benefit of early PAH therapy. Increasing evidence in support of early intervention and combination therapy for PAH is associated with rising medication costs that are largely offset by reduced hospitalization, on the basis of the currently available literature. Nonetheless, the studies performed to date have methodologic limitations that highlight the need for prospective studies using more robust economic modeling.

PMID: 29200882 [PubMed]

Impact of temperature on the Narcotrend Index during hypothermic cardiopulmonary bypass in children with sevoflurane anesthesia.

Tue, 12/05/2017 - 13:45

Impact of temperature on the Narcotrend Index during hypothermic cardiopulmonary bypass in children with sevoflurane anesthesia.

Perfusion. 2017 Dec 01;:267659117746234

Authors: Dennhardt N, Beck C, Boethig D, Heiderich S, Horke A, Tiedge S, Boehne M, Sümpelmann R

Abstract
BACKGROUND: During cardiopulmonary bypass (CPB) in children, anesthesia maintained by sevoflurane administered via the oxygenator is increasingly common. Anesthetic uptake and requirement may be influenced by the non-physiological conditions during hypothermic CPB. Narcotrend-processed EEG monitoring may, therefore, be useful to guide the administration of sevoflurane during this phase.
OBJECTIVE: The objective of this prospective, clinical, observational study was to assess the correlation between body temperature, Narcotrend Index (NI) and administered sevoflurane in children during CPB.
METHODS: Forty-four children aged 0 to 10 years undergoing hypothermic cardiac surgery were studied. On bypass, anesthesia was maintained with sevoflurane administered via the oxygenator of the heart-lung machine. Nasopharyngeal temperature, NI and minimum alveolar concentration (MAC) of sevoflurane were recorded in intervals of 10 minutes. Expiratory gas was sampled from the oxygenator's sole expiratory port via a separate connecting line and the MAC was measured by the agent analyzer of the anesthesia machine.
RESULTS: Raw (r = 0.74) and corrected (r = 0.73) r-values show that narcosis depth (as indicated by NI) can primarily be explained by the interaction of MAC and temperature. The analysis of variance (without the interaction term) confirms the significant and independent association of both factors, MAC (p<0.004, 95%CI: 0.19 to 0.46) and temperature (p<0.0001, 95%CI: 0.68 to 0.78), with the NI. During hypothermia, sevoflurane had been reduced significantly (r = 0.41, p<0.0001, 95%CI: 0.33 to 0.48).
CONCLUSION: Perfusionists and anesthetists should be aware of the results of processed electroencephalograph (EEG) monitoring during CPB. Sevoflurane requirements differ inter-individually; they may decrease during cooling and increase during rewarming. Therefore, it seems reasonable to include the results of processed EEG monitoring when administering sevoflurane during CPB in children, but further studies are necessary to confirm this thesis.

PMID: 29199541 [PubMed - as supplied by publisher]

Induction regimen and survival in simultaneous heart-kidney transplant recipients.

Tue, 12/05/2017 - 13:45

Induction regimen and survival in simultaneous heart-kidney transplant recipients.

J Heart Lung Transplant. 2017 Nov 15;:

Authors: Ariyamuthu VK, Amin AA, Drazner MH, Araj F, Mammen PPA, Ayvaci M, Mete M, Ozay F, Ghanta M, Mohan S, Mohan P, Tanriover B

Abstract
BACKGROUND: Induction therapy in simultaneous heart-kidney transplantation (SHKT) is not well studied in the setting of contemporary maintenance immunosuppression consisting of tacrolimus (TAC), mycophenolic acid (MPA), and prednisone (PRED).
METHODS: We analyzed the Organ Procurement and Transplant Network registry from January 1, 2000, to March 3, 2015, for recipients of SHKT (N = 623) maintained on TAC/MPA/PRED at hospital discharge. The study cohort was further stratified into 3 groups by induction choice: induction (n = 232), rabbit anti-thymoglobulin (r-ATG; n = 204), and interleukin-2 receptor-α (n = 187) antagonists. Survival rates were estimated using the Kaplan-Meier estimator. Multivariable inverse probability weighted Cox proportional hazard regression models were used to assess hazard ratios associated with post-transplant mortality as the primary outcome. The study cohort was censored on March 4, 2016, to allow at least 1-year of follow-up.
RESULTS: During the study period, the number of SHKTs increased nearly 5-fold. The Kaplan-Meier survival curve showed superior outcomes with r-ATG compared with no induction or interleukin-2 receptor-α induction. Compared with the no-induction group, an inverse probability weighted Cox proportional hazard model showed no independent association of induction therapy with the primary outcome. In sub-group analysis, r-ATG appeared to lower mortality in sensitized patients with panel reactive antibody of 10% or higher (hazard ratio, 0.19; 95% confidence interval, 0.05-0.71).
CONCLUSION: r-ATG may provide a survival benefit in SHKT, especially in sensitized patients maintained on TAC/MPA/PRED at hospital discharge.

PMID: 29198930 [PubMed - as supplied by publisher]

Racial differences in the development of de-novo donor-specific antibodies and treated antibody-mediated rejection after heart transplantation.

Tue, 12/05/2017 - 13:45

Racial differences in the development of de-novo donor-specific antibodies and treated antibody-mediated rejection after heart transplantation.

J Heart Lung Transplant. 2017 Nov 04;:

Authors: Cole RT, Gandhi J, Bray RA, Gebel HM, Yin M, Shekiladze N, Young A, Grant A, Mahoney I, Laskar SR, Gupta D, Bhatt K, Book W, Smith A, Nguyen D, Vega JD, Morris AA

Abstract
BACKGROUND: Despite improvements in outcomes after heart transplantation, black recipients have worse survival compared with non-black recipients. The source of such disparate outcomes remains largely unknown. We hypothesize that a propensity to generate de-novo donor-specific antibodies (dnDSA) and subsequent antibody-mediated rejection (AMR) may account for racial differences in sub-optimal outcomes after heart transplant. In this study we aimed to determine the role of dnDSA and AMR in racial disparities in post-transplant outcomes.
METHODS: This study was a single-center, retrospective analysis of 137 heart transplant recipients (81% male, 48% black) discharged from Emory University Hospital. Patients were classified as black vs non-black for the purpose of our analysis. Kaplan-Meier and Cox regression analyses were used to evaluate the association between race and selected outcomes. The primary outcome was the development of dnDSA. Secondary outcomes included treated AMR and a composite of all-cause graft dysfunction or death.
RESULTS: After 3.7 years of follow-up, 39 (28.5%) patients developed dnDSA and 19 (13.8%) were treated for AMR. In multivariable models, black race was associated with a higher risk of developing dnDSA (hazard ratio [HR] 3.65, 95% confidence interval [CI] 1.54 to 8.65, p = 0.003) and a higher risk of treated AMR (HR 4.86, 95% CI 1.26 to 18.72, p = 0.021) compared with non-black race. Black race was also associated with a higher risk of all-cause graft dysfunction or death in univariate analyses (HR 2.10, 95% CI 1.02 to 4.30, p = 0.044). However, in a multivariable model incorporating dnDSA, black race was no longer a significant risk factor. Only dnDSA development was significantly associated with all-cause graft dysfunction or death (HR 4.85, 95% CI 1.89 to 12.44, p = 0.001).
CONCLUSION: Black transplant recipients are at higher risk for the development of dnDSA and treated AMR, which may account for racial disparities in outcomes after heart transplantation.

PMID: 29198929 [PubMed - as supplied by publisher]

Lung autoantibodies: Ready for prime time?

Tue, 12/05/2017 - 13:45

Lung autoantibodies: Ready for prime time?

J Heart Lung Transplant. 2017 Nov 08;:

Authors: Milross L, Hachem R, Levine D, Glanville AR

Abstract
Despite advances in our understanding of the immunology of lung allograft tolerance and a reduction in the rate of acute allograft rejection using contemporary immunosuppressive protocols, the rate of chronic lung allograft dysfunction (CLAD), both obstructive and restrictive, remains unacceptably high. CLAD, particularly the restrictive phenotype, is a harbinger of a foreshortened survival. The development of a consensus approach to the diagnosis of antibody-mediated rejection by the International Society for Heart and Lung Transplantation has highlighted the need for a uniform approach toward the investigation, diagnosis, implications and management of both human leukocyte antigen (HLA) and non-HLA-related antibody formation. This Perspective summarizes the current information that underpins the way forward in recognizing the potential importance of non-HLA-related antibody formation with respect to allograft injury and outcomes.

PMID: 29198928 [PubMed - as supplied by publisher]

Morphologic and immunohistochemical features of pulmonary vasculopathy in end-stage left ventricular systolic failure.

Tue, 12/05/2017 - 13:45

Morphologic and immunohistochemical features of pulmonary vasculopathy in end-stage left ventricular systolic failure.

J Heart Lung Transplant. 2017 Nov 15;:

Authors: Ribeiro de Campos PT, Lopes AA, Issa VS, Aiello VD

PMID: 29198927 [PubMed - as supplied by publisher]

Targeting resolution of pulmonary edema in primary graft dysfunction after lung transplantation: Is inhaled AP301 the answer?

Tue, 12/05/2017 - 13:45

Targeting resolution of pulmonary edema in primary graft dysfunction after lung transplantation: Is inhaled AP301 the answer?

J Heart Lung Transplant. 2017 Nov 16;:

Authors: Ware LB

PMID: 29198870 [PubMed - as supplied by publisher]

The ratio of circulating regulatory cluster of differentiation 4 T cells to endothelial progenitor cells predicts clinically significant acute rejection after heart transplantation.

Tue, 12/05/2017 - 13:45

The ratio of circulating regulatory cluster of differentiation 4 T cells to endothelial progenitor cells predicts clinically significant acute rejection after heart transplantation.

J Heart Lung Transplant. 2017 Oct 22;:

Authors: Choi DH, Chmura SA, Ramachandran V, Dionis-Petersen KY, Kobayashi Y, Nishi T, Luikart H, Dimbil S, Kobashigawa J, Khush K, Lewis DB, Fearon WF

Abstract
BACKGROUND: The aim of this study was to determine the value of the ratio of the percentage of circulating regulatory cluster of differentiation 4 T cells (%Tregs) to the percentage of endothelial progenitor cells (%EPCs; Treg/EPC ratio) for predicting clinically significant acute rejection.
METHODS: Peripheral blood %Tregs and %EPCs were quantified in 91 cardiac transplant recipients using flow cytometry at a mean of 42 ± 13 days after transplant. The primary end point was clinically significant acute rejection, defined as an event that led to an acute augmentation of immunosuppression in conjunction with an International Society for Heart and Lung Transplantation grade ≥ 2R in a right ventricular endomyocardial biopsy specimen or non-cellular rejection (specimen-negative rejection) with hemodynamic compromise (decrease in left ventricular ejection fraction by > 25%).
RESULTS: Significant rejection occurred in 27 recipients (29.7%) during a median of 49.4 months (interquartile range, 37.0-62.0 months). The mean %Tregs and %EPCs were not significantly different between those with and without an episode of significant rejection, but the mean Treg/EPC ratio was significantly lower in recipients with significant rejection (44.9 vs 106.7, p = 0.001). Receiver operating characteristic curve analysis showed an area under the curve value for significant rejection for a Treg/EPC ratio of 0.712. The best cutoff value of the Treg/EPC ratio that distinguished between those with or without significant rejection was ≤ 18 by receiver operating characteristic curve analysis. Kaplan-Meier analysis revealed that patients with a Treg/EPC ratio of ≤ 18 had a significantly higher rate of rejection than those with a Treg/EPC ratio > 18 (61.5% vs 16.9%, log-rank p < 0.0001). A low Treg/EPC ratio was an independent predictor of significant rejection.
CONCLUSIONS: A low Treg/EPC ratio measured soon after heart transplantation is an independent predictor of acute rejection. The Treg/EPC ratio has potential as an early biomarker after heart transplantation for predicting acute rejection.

PMID: 29198869 [PubMed - as supplied by publisher]

An Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of hospitalization, functional status, and mortality after mechanical circulatory support in adults with congenital heart disease.

Tue, 12/05/2017 - 13:45

An Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of hospitalization, functional status, and mortality after mechanical circulatory support in adults with congenital heart disease.

J Heart Lung Transplant. 2017 Nov 17;:

Authors: Cedars A, Vanderpluym C, Koehl D, Cantor R, Kutty S, Kirklin JK

Abstract
BACKGROUND: Adult congenital heart disease (ACHD) prevalence is increasing worldwide, with advanced heart failure (HF) as a leading cause of death. Limited data are available on durable mechanical circulatory support (MCS) in ACHD patients.
METHODS: ACHD patients from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database were identified and propensity matched with non-ACHD patients using risk factors from the INTERMACS Seventh Annual Report. We compared these groups for the primary outcome of post-MCS mortality. We also investigated adverse event rates, functional status, and health-related quality of life.
RESULTS: ACHD (n = 128) and non-ACHD (n = 512) patients were appropriately matched by baseline characteristics. ACHD patients had a longer length of stay at MCS implant (24 vs 19 days, p = 0.006) but similar rates of post-MCS adverse events and hospitalization. There were similar improvements in functional status and health related quality of life post-MCS in both groups. ACHD patients had significantly higher mortality post-MCS exclusively during the first 5 months after implant (p = 0.003) and a lower probability of receiving a transplant (p = 0.003). Risk factors for early mortality were biventricular or total artificial heart device implant and age > 50 years.
CONCLUSIONS: ACHD patients experience a higher early mortality after MCS but have similar adverse event rates and similar improvements in functional capacity and quality of life compared with non-ACHD patients. These data support expansion of MCS use in selected ACHD patients.

PMID: 29198868 [PubMed - as supplied by publisher]

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