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Xenotransplantation: Where Are We with Potential Kidney Recipients? Recent Progress and Potential Future Clinical Trials.

Wed, 10/11/2017 - 12:45

Xenotransplantation: Where Are We with Potential Kidney Recipients? Recent Progress and Potential Future Clinical Trials.

Curr Transplant Rep. 2017 Jun;4(2):101-109

Authors: Yamada K, Shah JA, Tanabe T, Lanaspa MA, Johnson RJ

Abstract
PURPOSE: Inter-species transplantation, xenotransplantation, is becoming a realistic strategy to solve the organ shortage crisis. Here we focus on seminal publications that have driven research in xenotransplantation, as well as recently published literature and future endeavors.
RECENT FINDINGS: Advances in gene editing technology have allowed for the efficient production of multi-transgenic porcine donors leading improved xenograft survival in baboons, up to 2-years following heterotopic heart xenotransplantation and from weeks to several months following life-supporting kidney xenotransplanation. As technology evolves, additional challenges have arisen, including the development of proteinuria, early graft loss associated with porcine CMV, disparities in organ growth between donors and recipients as well as high-dose continuous immunosuppression requirements. To address these issues, our laboratory developed a tolerance-inducing protocol which has allowed for >6 months survival of a life-supporting kidney with further approaches currently underway to address the challenges mentioned above.
SUMMARY: Our recent findings, reviewed in this article, led us to develop methods to overcome obstacles, which, in conjunction with the work of others, are promising for future clinical applications of xenotransplantation.

PMID: 28989853 [PubMed]

Epigenetics and cardiovascular regenerative medicine in the elderly.

Wed, 10/11/2017 - 12:45

Epigenetics and cardiovascular regenerative medicine in the elderly.

Int J Cardiol. 2017 Sep 27;:

Authors: Costantino S, Camici GG, Mohammed SA, Volpe M, Lüscher TF, Paneni F

Abstract
Cardiovascular disease (CVD) is a recognized age-dependent condition whose incidence is set to increase due to the gradual aging of the population. Moreover, ischemic cardiovascular diseases (i.e. stroke, myocardial infarction, critical limb ischemia) requiring blood vessel growth are associated with a worse outcome in elderly patients. Therefore, understanding the molecular cues regulating the vascular repair process is of paramount importance to prevent undesirable cardiovascular complications in this setting. A growing body of evidence suggests that epigenetic modifications - changes to the genome that do not involve changes in DNA sequence - may significantly derail gene expression trajectories during the life course, thus affecting molecular phenotype and functionality of angiogenic cells, namely mature endothelial cells (ECs), endothelial progenitor cells (EPCs), and bone-marrow (BM)-derived angiogenic cells. In the present review, we discuss the emerging role of epigenetics in age-related impairment of the angiogenic process. Specifically, the following aspects are critically addressed: i) defective angiogenic process in aging; ii) impact of epigenetics (DNA methylation, histone modifications, microRNAs, long noncoding RNAs) on phenotype and function of ECs and BM-derived angiogenic cells; iii) clinical perspectives on epigenetic biomarkers and reprogramming approaches for autologous transplantation. A scrutiny characterization of the "old epigenome" may provide unprecedented insights to develop preventive strategies and regenerative therapeutic interventions in the elderly.

PMID: 28988828 [PubMed - as supplied by publisher]

Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes.

Wed, 10/11/2017 - 12:45

Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes.

J Heart Lung Transplant. 2017 Sep 14;:

Authors: Husain AN, Mirza KM, Fedson SE

Abstract
BACKGROUND: In the past decade, C4d has emerged as a potential marker for antibody-mediated rejection (AMR); however, evidence on its use as a prognostic tool has been controversial. Although the International Society for Heart and Lung Transplantation guideline recommends early routine surveillance of C4d in heart transplantation, there is no consensus on its value in the pathologic assessment of AMR. Herein we present a correlation analysis of C4d immunoreactivity in endomyocardial biopsies with clinical cardiac dysfunction, cellular rejection, human leukocyte antigen (HLA) status, cardiac allograft vasculopathy (CAV) and death.
METHODS: A total of 5,840 endomyocardial biopsies from 296 heart transplant recipients (January 2004 to December 2014) were stained prospectively for C4d. Strong, diffuse endothelial staining was considered positive. All patients had at least 1 year of follow-up. Positive C4d staining was present in 53 biopsies from 28 patients. Sixteen of 28 patients had clinically significant cardiac dysfunction at the time of positive biopsy. In C4d-positive patients, the mean panel-reactive antibody (PRA) level was 33%. Ten patients demonstrated a first C4d positivity within the first year post-transplant, whereas 18 patients had C4d positivity after 1 year post-transplant. At autopsy, all 11 C4d-positive patients examined demonstrated cardiac allograft vasculopathy (CAV) as the underlying cause of death. In contrast, only 2 of 8 (25%) C4d-negative patients had CAV at autopsy. In the surviving cohort, there was an angiographic diagnosis of higher-than-moderate CAV in 10 patients (3.8%).
RESULTS: C4d-positive patients contributed to 67% of the overall institutional mortality in heart transplant recipients. Late C4d positivity (>1 year post-transplant) demonstrated an even higher risk for developing CAV and poor prognosis than early C4d positivity (within 1 year). In the C4d-negative group with postmortem examination, 75% (6 of 8) deaths were due to non-cardiac causes.
CONCLUSIONS: Our findings show a positive association of C4d with CAV and death. We identified a prognostic role for C4d in heart transplantation warranting routine long-term detection of this marker in the pathologic evaluation of cardiac AMR.

PMID: 28988608 [PubMed - as supplied by publisher]

Abciximab/Heparin Therapy for Left Ventricular Assist Device Implantation in Patients With Heparin-Induced Thrombocytopenia.

Wed, 10/11/2017 - 12:45

Abciximab/Heparin Therapy for Left Ventricular Assist Device Implantation in Patients With Heparin-Induced Thrombocytopenia.

Ann Thorac Surg. 2017 Oct 04;:

Authors: Lee CL, Colombo PC, Eisenberger A, Diuguid D, Jennings DL, Han J, Salna MP, Takeda K, Kurlansky PA, Yuzefpolskaya M, Garan AR, Naka Y, Takayama H

Abstract
BACKGROUND: Optimal anticoagulation strategy remains uncertain in patients with heparin-induced thrombocytopenia (HIT) and undergoing left ventricular assist device (LVAD) implantation. We describe our protocol of abciximab and heparin in these patients.
METHODS: Our protocol is to administer abciximab, 0.25 mg/kg loading dose, followed by continuous infusion of 0.125 μg · kg(-1) · min(-1) throughout cardiopulmonary bypass. Full-dose heparin is then given with subsequent additional doses to maintain an activated clotting time of 400 seconds or longer. The abciximab infusion is stopped 15 minutes after heparin reversal with protamine, and platelets are transfused.
RESULTS: Six patients underwent LVAD implantation with this protocol in our program. HIT was confirmed in 4 patients was suspected in 2, which was negative after the operation. One patient received a HeartMate XVE (Thoratec Corp, Pleasanton, CA) and the others received HeartMate II (Thoratec Corp). There were no thromboembolic complications. One patient required chest reexploration for bleeding and temporary right VAD support. Postoperative anticoagulation with argatroban was restarted on median postoperative day 3 (range, days 1 to 6) and warfarin was started on day 5 (range, days 3 to 12). Median postoperative intensive care unit stay was 9 days (range, 5 to 76 days), and hospital stay was 22 days (range, 18 to 132 days). After the initial LVAD implantation, 1 patient required HeartMate XVE LVAD exchange to HeartMate II and subsequent heart transplant, both of which were performed with the abciximab/heparin protocol. A HeartMate II device was explanted in another patient after myocardial recovery. The remaining 4 patients are alive on device support.
CONCLUSIONS: This is the first report of a novel abciximab/heparin protocol for LVAD implantation in patients with HIT. The preliminary results suggest the feasibility and safety of this protocol.

PMID: 28987395 [PubMed - as supplied by publisher]

Recellularization of a novel off-the-shelf valve following xenogenic implantation into the right ventricular outflow tract.

Wed, 10/11/2017 - 12:45
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Recellularization of a novel off-the-shelf valve following xenogenic implantation into the right ventricular outflow tract.

PLoS One. 2017;12(8):e0181614

Authors: Hennessy RS, Go JL, Hennessy RR, Tefft BJ, Jana S, Stoyles NJ, Al-Hijji MA, Thaden JJ, Pislaru SV, Simari RD, Stulak JM, Young MD, Lerman A

Abstract
Current research on valvular heart repair has focused on tissue-engineered heart valves (TEHV) because of its potential to grow similarly to native heart valves. Decellularized xenografts are a promising solution; however, host recellularization remains challenging. In this study, decellularized porcine aortic valves were implanted into the right ventricular outflow tract (RVOT) of sheep to investigate recellularization potential. Porcine aortic valves, decellularized with sodium dodecyl sulfate (SDS), were sterilized by supercritical carbon dioxide (scCO2) and implanted into the RVOT of five juvenile polypay sheep for 5 months (n = 5). During implantation, functionality of the valves was assessed by serial echocardiography, blood tests, and right heart pulmonary artery catheterization measurements. The explanted valves were characterized through gross examination, mechanical characterization, and immunohistochemical analysis including cell viability, phenotype, proliferation, and extracellular matrix generation. Gross examination of the valve cusps demonstrated the absence of thrombosis. Bacterial and fungal stains were negative for pathogenic microbes. Immunohistochemical analysis showed the presence of myofibroblast-like cell infiltration with formation of new collagen fibrils and the existence of an endothelial layer at the surface of the explant. Analysis of cell phenotype and morphology showed no lymphoplasmacytic infiltration. Tensile mechanical testing of valve cusps revealed an increase in stiffness while strength was maintained during implantation. The increased tensile stiffness confirms the recellularization of the cusps by collagen synthesizing cells. The current study demonstrated the feasibility of the trans-species implantation of a non-fixed decellularized porcine aortic valve into the RVOT of sheep. The implantation resulted in recellularization of the valve with sufficient hemodynamic function for the 5-month study. Thus, the study supports a potential role for use of a TEHV for the treatment of valve disease in humans.

PMID: 28763463 [PubMed - indexed for MEDLINE]

Glutaraldehyde Treatment of Allografts and Aortic Outcomes Post-Norwood: Challenging Surgical Decision.

Wed, 10/11/2017 - 12:45
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Glutaraldehyde Treatment of Allografts and Aortic Outcomes Post-Norwood: Challenging Surgical Decision.

Ann Thorac Surg. 2017 Oct;104(4):1395-1401

Authors: Martin BJ, Kaestner M, Peng M, Ross DB, Urschel S, West LJ, Rebeyka IM

Abstract
BACKGROUND: Glutaraldehyde (GA) treatment of allografts used for arch reconstruction prevents the immunologic sensitization that occurs with untreated allografts, but its use may cause tissue changes that predispose to recurrent obstruction. The objective was to determine whether GA treatment of allografts used in Norwood procedures increases the risk of recurrent aortic obstruction.
METHODS: All infants who underwent a Norwood procedure between 2000 and 2015 were included. Cryopreserved pulmonary allografts were used for all arch reconstructions; starting in 2005 all were treated with GA before use. Complete follow-up was obtained, including survival, transplantation, and all repeat procedures. Competing risks analyses were used to assess for differences in aortic reintervention over time.
RESULTS: Two hundred six infants (132 male) were included. There were 60 deaths and 14 transplantations; 5-year transplantation-free survival was 71.9%. GA treatment of patches (n = 142, 68.9%) was not predictive of death (hazard ratio [HR] 1.38, 95% confidence interval [CI]: 0.61 to 3.08). Fifty-five patients had at least one aortic reintervention and 31 patients (15.0%) required surgical aortic reintervention. At 1-year, freedom from all aortic reintervention was similar between patients with and without treated patches, but freedom from surgical aortic reintervention was lower in the treated group (87.6% versus 95.3%, p = 0.0256). GA treatment was not associated with the combined end point of catheter-based or surgical reintervention but was associated with specific need for surgical reintervention (HR 4.05, 95% CI: 1.19 to 13.77).
CONCLUSIONS: GA treatment is associated with increased late surgical aortic reintervention. The advantages of decreased sensitization with GA treatment need to be balanced against the risk of aortic reobstruction.

PMID: 28577843 [PubMed - indexed for MEDLINE]

Comparative Evaluation of αCD40 (2C10R4) and αCD154 (5C8H1 and IDEC-131) in a Nonhuman Primate Cardiac Allotransplant Model.

Wed, 10/11/2017 - 12:45
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Comparative Evaluation of αCD40 (2C10R4) and αCD154 (5C8H1 and IDEC-131) in a Nonhuman Primate Cardiac Allotransplant Model.

Transplantation. 2017 Sep;101(9):2038-2047

Authors: OʼNeill NA, Zhang T, Braileanu G, Sun W, Cheng X, Hershfeld A, Laird CT, Kronfli A, Hock LA, Dahi S, Kubicki N, Sievert E, Hassanein W, Cimeno A, Pierson RN, Azimzadeh AM

Abstract
BACKGROUND: Specific blockade of T cell costimulation pathway is a promising immunomodulatory approach being developed to replace our current clinical immunosuppression therapies. The goal of this study is to compare results associated with 3 monoclonal antibodies directed against the CD40/CD154 T cell costimulation pathway.
METHODS: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with either IDEC-131 (humanized αCD154, n = 9), 5C8H1 (mouse-human chimeric αCD154, n = 5), or 2C10R4 (mouse-rhesus chimeric αCD40, n = 6) monotherapy using a consistent, comparable dosing regimen for 3 months after transplant.
RESULTS: Relative to the previously reported IDEC-131-treated allografts, median survival time (35 ± 31 days) was significantly prolonged in both 5C8H1-treated (142 ± 26, P < 0.002) and 2C10R4-treated (124 ± 37, P < 0.020) allografts. IDEC-131-treated grafts had higher cardiac allograft vasculopathy severity scores during treatment relative to either 5C8H1 (P = 0.008) or 2C10R4 (P = 0.0002). Both 5C8H1 (5 of 5 animals, P = 0.02) and 2C10R4 (6/6, P = 0.007), but not IDEC-131 (2/9), completely attenuated IgM antidonor alloantibody (alloAb) production during treatment; 5C8H1 (5/5) more consistently attenuated IgG alloAb production compared to 2C10R4 (4/6) and IDEC-131 (0/9). All evaluable explanted grafts experienced antibody-mediated rejection. Only 2C10R4-treated animals exhibited a modest, transient drop in CD20 lymphocytes from baseline at day 14 after transplant (-457 ± 152 cells/μL) compared with 5C8H1-treated animals (16 ± 25, P = 0.037), and the resurgent B cells were primarily of a naive phenotype.
CONCLUSIONS: In this model, CD154/CD40 axis blockade using IDEC-131 is an inferior immunomodulatory treatment than 5C8H1 or 2C10R4, which have similar efficacy to prolong graft survival and to delay cardiac allograft vasculopathy development and antidonor alloAb production during treatment.

PMID: 28557955 [PubMed - indexed for MEDLINE]

Bilateral internal mammary artery Y construct with multiple sequential grafting improves survival compared to bilateral internal mammary artery with additional vein grafts: 10-year experience at 2 different institutions†.

Wed, 10/11/2017 - 12:45
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Bilateral internal mammary artery Y construct with multiple sequential grafting improves survival compared to bilateral internal mammary artery with additional vein grafts: 10-year experience at 2 different institutions†.

Eur J Cardiothorac Surg. 2017 02 01;51(2):368-375

Authors: Glineur D, Etienne PY, Kuschner CE, Shaw RE, Ferrari G, Rioux N, Papadatos S, Brizzio M, Mindich B, Zapolanski A, Grau JB

Abstract
OBJECTIVES: Utilization of bilateral internal mammary arteries (BIMAs) has been shown to improve long-term outcomes in patients undergoing coronary artery bypass grafting. To achieve complete revascularization, BIMAs may be used as either sole conduits for revascularization through a Y-graft configuration (BIMA-Y) or deployed with additional grafts used in conjunction with BIMAs. The purpose of this study was to compare the long-term outcomes of two institutions that predominantly used either the BIMA-Y configuration or BIMA plus additional grafts to achieve optimal revascularization.
METHODS: From 1 January 2000 to 31 December 2010, 436 patients were revascularized using a non-sequential BIMA grafting at one institution (Group A), with veins being used for additional targets. At the second institution (Group B), 771 patients were revascularized using a BIMA-Y graft for all distal targets. Kaplan–Meier analysis was used to compare unadjusted survival between the groups. Cox proportional hazards regression modelling was used to provide an adjusted comparison of survival between the groups.
RESULTS: There was no statistically significant difference between the average number of anastomotic sites used in Group A and Group B (A = 4.0 ± 0.7 vs B = 4.0 ± 0.7; P = 0.24). Group A did not have a significantly greater in-hospital mortality (0.7% vs 1.0% P = 0.39), stroke (0.5% vs 0.8% P = 0.40), deep sternal wound infection (0.0% vs 0.6% P = 0.11) or reoperation for bleeding (1.6% vs 0.6% P = 0.10) than Group B. Cox proportional hazards analyses demonstrated that at 14 years, Group B had a significantly improved survival compared to Group A (Group B = 88% vs Group A = 81%) with an overall reduction in mortality (adjusted hazard ratio 0.780, 95% confidence interval 0.448–0.849; P = 0.043).
CONCLUSION: Utilization of the BIMA-Y configuration was associated with improved survival when compared to BIMA grafting with additional vein grafts. Further studies are necessary to evaluate the efficacy of BIMA-Y grafting against other means of providing complete arterial revascularization.

PMID: 28186272 [PubMed - indexed for MEDLINE]

Association Between Hematologic and Inflammatory Markers and 31 Thrombotic and Hemorrhagic Events in Berlin Heart Excor Patients.

Wed, 10/11/2017 - 12:45
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Association Between Hematologic and Inflammatory Markers and 31 Thrombotic and Hemorrhagic Events in Berlin Heart Excor Patients.

Pediatr Cardiol. 2017 Apr;38(4):770-777

Authors: Iyengar A, Hung ML, Asanad K, Kwon OJ, Jackson NJ, Reemtsen BL, Federman MD, Biniwale RM

Abstract
Bleeding and thrombotic events remain a significant cause of morbidity in pediatric patients supported with ventricular assist devices (VADs). The objective of this study is to identify the association between markers of anticoagulation and bleeding and thrombosis events during Berlin Heart ExCor support. A retrospective, single-center analysis of 9 patients supported with the Berlin Heart ExCor was performed. Inflammatory and anticoagulation parameters including C-reactive protein, fibrinogen, partial thromboplastin time (PTT), and platelet count were measured at 48 and 24 h before and after bleeding or thrombosis events. Patients served as their own controls, and the same parameters were measured during a control period where subjects did not experience either event. All patients received the anticoagulation regimen proposed by Berlin Heart. A total of 31 bleeding or thrombotic events were identified and matched to 18 control events. Patient with predominantly thrombotic events tended to weigh less than those with bleeding events (Δ7.7 kg, p < 0.001). PTT levels were higher before and after bleeding (Δ17.36, p = 0.002) and thrombosis (Δ8.75, p < 0.001) events relative to control. Heparin dose decreased after a thrombosis event (Δ-5.67, p = 0.097), and this decrease was significantly different from control (p = 0.032). Non-collinearity between heparin dose and PTT should prompt further inflammatory and hematological investigation. In addition, heavier patients were more prone to bleeding complications. The role of inflammation in the development of thrombus or hemorrhages in the pediatric VAD population needs to be studied further.

PMID: 28184979 [PubMed - indexed for MEDLINE]

Expanded criteria donor and donation after circulatory death renal allografts in the West of Scotland: Their place in the kidney allocation process.

Wed, 10/11/2017 - 12:45
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Expanded criteria donor and donation after circulatory death renal allografts in the West of Scotland: Their place in the kidney allocation process.

Surgeon. 2016 Jun;14(3):136-41

Authors: Hesse K, Aitken E, Clancy M, Vesey A

Abstract
INTRODUCTION: Due to the rising disparity between demand and availability, organs from expanded criteria donors (ECD) and donors after determination of circulatory death (DCD) are increasingly used. The purpose of this study was to report outcomes in recipients of ECD and DCD renal allografts from a single centre.
METHODS: A retrospective analysis from a single centre for all renal transplants performed between 2001 and 2010 inclusive was undertaken. SCD (standard criteria donor) and ECD organs were compared, as were DCD and DBD (donation after determination of brain stem death) organs. Baseline data and predefined standard transplant outcomes were collected and compared using appropriate statistical tests. P < 0.05 was defined as significant.
RESULTS: 729 renal transplants were performed. Comparing ECD to SCD organs, there was a significant difference in graft survival between groups (logrank for trend, p = 0.032) with ECD organs doing worse than SCD organs. Short-term outcomes showed a similar disparity with a higher 1-year post-transplant creatinine and delayed graft function (DGF) rate in ECD grafts. Nevertheless, outcomes were still clinically acceptable. When comparing DCD to DBD organs, no such differences were apparent, with DCD organs appearing to perform at least as well as DBD organs. In our cohort, unlike some previous studies, DGF rates were similar in both DCD and DBD groups.
CONCLUSIONS: Although ECD organs perform less well than SCD organs, outcomes are still acceptable and our results support their continuing use. When considering DCD organs, our data support the view that they should no longer be necessarily regarded as marginal grafts. Our low DGF rates are perhaps explained by local factors contributing to a short CIT.

PMID: 25214206 [PubMed - indexed for MEDLINE]

Chronic Obstructive Pulmonary Disease as a Risk Factor for Ventricular Arrhythmias Independent of Left Ventricular Function.

Sun, 10/08/2017 - 12:45

Chronic Obstructive Pulmonary Disease as a Risk Factor for Ventricular Arrhythmias Independent of Left Ventricular Function.

Heart Rhythm. 2017 Oct 03;:

Authors: Konecny T, Somers KR, Park JY, John A, Orban M, Doshi R, Scanlon PD, Asirvatham SJ, Rihal CS, Brady PA

Abstract
BACKGROUND: The association between chronic obstructive pulmonary disease (COPD) and sudden cardiac death has not been fully elucidated.
OBJECTIVE: Investigate if decreased left ventricular ejection fraction (LVEF) can explain the increased rate of ventricular tachycardias (VT) in COPD.
METHODS: In this retrospective study, we included consecutive adult patients who underwent pulmonary function testing (PFT), Holter monitoring, and trans-thoracic echocardiography. COPD was correlated with the frequency of VT in a multivariate analysis which adjusted for known confounders including LVEF. Long term all-cause mortality of patients with COPD and VT was examined.
RESULTS: From 6351 patients who were included in this study (age 66±15 years, 48% woman, 92% Caucasian, LVEF 59±12%), 2800 (44%) had PFT indicative of COPD. VT was nearly twice as likely to occur during the Holter monitoring in COPD patients (13%vs.23%;p<0.001), and the severity of COPD correlated with the risk of VT (21%vs.28%vs.37% for mild-moderate, severe, and very severe COPD;p<0.001). COPD and VT remained independently associated (p<0.001) even after adjusting for LVEF, demographics, and co-morbidities (age, sex, body mass index, hypertension, chronic kidney disease, coronary artery disease, cancer history, diabetes mellitus). COPD was associated with all-cause mortality independently of LVEF (p<0.001).
CONCLUSIONS: COPD patients are at a higher risk of VT and mortality. This may not be fully attributed to the confounding effect of systolic heart failure measured by LVEF. Further studies are needed to explore the mechanistic interactions between VT and COPD in order to identify if anti-arrhythmic strategies would apply especially to the severe COPD patients.

PMID: 28986334 [PubMed - as supplied by publisher]

A bioprosthetic total artificial heart for end-stage heart failure: Results from a pilot study.

Sun, 10/08/2017 - 12:45

A bioprosthetic total artificial heart for end-stage heart failure: Results from a pilot study.

J Heart Lung Transplant. 2017 Sep 14;:

Authors: Latrémouille C, Carpentier A, Leprince P, Roussel JC, Cholley B, Boissier E, Epailly E, Capel A, Jansen P, Smadja DM

Abstract
BACKGROUND: The electro-hydraulically actuated Carmat total artificial heart (C-TAH) is designed to replace the heart in patients with end-stage heart failure, either as bridge to transplant or destination therapy. It provides pulsatile flow and contains bio-prosthetic blood contacting materials. A clinical feasibility study was conducted to evaluate the C-TAH safety and performance.
METHODS: Hospitalized patients, at imminent risk of death from irreversible biventricular failure despite optimal medical management, and not eligible for transplant or eligible but on extracorporeal life support, were enrolled. The primary endpoint was 30-days survival.
RESULTS: Four patients were implanted with the C-TAH, three as destination therapy (ages 76, 68, 74) and one as bridge to transplant (age 58). They had implant times of 74, 270, 254 and 20 days respectively. All patients were free from hemolysis, clinical neurologic events, clinical evidence of thrombus and device-related infections. Hemodynamic and physical recovery allowed two patients to be discharged home for a cumulative duration of 7 months. The anticoagulation management strategy comprised initial unfractionated heparin, from postoperative day 2, followed by low molecular weight heparin and aspirin. An increased D-dimer level was observed in all patients during months 1 to 4. Temporary suspension of heparin anticoagulation resulted in thrombocytopenia and increased fibrin monomer, reversed by resuming anticoagulation with heparin. Causes of death were device-related (2 cases), respiratory failure and multi-organ failure.
CONCLUSIONS: Preliminary clinical results with the C-TAH demonstrated good safety and performance profiles in patients suffering from biventricular failure, which need to be confirmed in a pivotal study.

PMID: 28986001 [PubMed - as supplied by publisher]

Early declaration of death by neurologic criteria results in greater organ donor potential.

Sun, 10/08/2017 - 12:45

Early declaration of death by neurologic criteria results in greater organ donor potential.

J Surg Res. 2017 Oct;218:29-34

Authors: Resnick S, Seamon MJ, Holena D, Pascual J, Reilly PM, Martin ND

Abstract
BACKGROUND: Aggressive management of patients prior to and after determination of death by neurologic criteria (DNC) is necessary to optimize organ recovery, transplantation, and increase the number of organs transplanted per donor (OTPD). The effects of time management are understudied but potentially pivotal component. The objective of this study was to analyze specific time points (time to DNC, time to procurement) and the time intervals between them to better characterize the optimal timeline of organ donation.
METHODS: Using data over a 5-year time period (2011-2015) from the largest US OPO, all patients with catastrophic brain injury and donated transplantable organs were retrospectively reviewed. Active smokers were excluded. Maximum donor potential was seven organs (heart, lungs [2], kidneys [2], liver, and pancreas). Time from admission to declaration of DNC and donation was calculated. Mean time points stratified by specific organ procurement rates and overall OTPD were compared using unpaired t-test.
RESULTS: Of 1719 Declaration of Death by Neurologic Criteria organ donors, 381 were secondary to head trauma. Smokers and organs recovered but not transplanted were excluded leaving 297 patients. Males comprised 78.8%, the mean age was 36.0 (±16.8) years, and 87.6% were treated at a trauma center. Higher donor potential (>4 OTPD) was associated with shorter average times from admission to brain death; 66.6 versus 82.2 hours, P = 0.04. Lung donors were also associated with shorter average times from admission to brain death; 61.6 versus 83.6 hours, P = 0.004. The time interval from DNC to donation varied minimally among groups and did not affect donation rates.
CONCLUSIONS: A shorter time interval between admission and declaration of DNC was associated with increased OTPD, especially lungs. Further research to identify what role timing plays in the management of the potential organ donor and how that relates to donor management goals is needed.

PMID: 28985863 [PubMed - in process]

Renin-angiotensin-aldosterone system parameters as biomarker in heart failure patients with preserved ejection fraction: focus on angiotensinogen.

Sat, 10/07/2017 - 12:45

Renin-angiotensin-aldosterone system parameters as biomarker in heart failure patients with preserved ejection fraction: focus on angiotensinogen.

Am J Hypertens. 2017 Sep 08;:

Authors: Uijl E, Danser AHJ

PMID: 28985283 [PubMed - as supplied by publisher]

Pregnancy and the kidney transplant recipient.

Sat, 10/07/2017 - 12:45

Pregnancy and the kidney transplant recipient.

Curr Opin Nephrol Hypertens. 2017 Nov;26(6):494-500

Authors: Vijayan M, Pavlakis M

Abstract
PURPOSE OF REVIEW: The current article reviews the available literature on the incidence, complications, outcomes, and management of pregnancies in kidney transplant recipients.
RECENT FINDINGS: Pregnancy can be a reasonable option for women with a kidney transplant. More than 4700 successful pregnancies have been reported after kidney transplantation. New data have emerged regarding the risk of allograft dysfunction following pregnancy. There is a lack of consensus on the optimal time for conception, immunosuppressive targets, the safety of allograft biopsy, and infection surveillance. Successful pregnancies have recently been reported in ABO-incompatible transplant recipients and recipients of combined heart-kidney transplants.
SUMMARY: The ideal contraceptive method, timing of conception, immunosuppressant protocol, infection surveillance, and the method of delivery should be individualized depending on the patient's age and medical conditions.

PMID: 28985190 [PubMed - in process]

Multidisciplinary Approach to Cardiac and Pulmonary Vascular Disease Risk Assessment in Liver Transplantation: An Evaluation of the Evidence and Consensus Recommendations.

Sat, 10/07/2017 - 12:45

Multidisciplinary Approach to Cardiac and Pulmonary Vascular Disease Risk Assessment in Liver Transplantation: An Evaluation of the Evidence and Consensus Recommendations.

Am J Transplant. 2017 Oct 06;:

Authors: VanWagner LB, Harinstein ME, Runo JR, Darling C, Serper M, Hall S, Kobashigawa JA, Hammel LL

Abstract
Liver transplant (LT) candidates today are older, have greater medical severity of illness, and have more cardiovascular comorbidities than ever before. In addition, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Cirrhotic cardiomyopathy, a condition characterized by increased cardiac output and a reduced ventricular response to stress, is present in up to 30% of patients with cirrhosis thus challenging perioperative management. Current noninvasive tests that assess for subclinical coronary and myocardial disease have low sensitivity, and altered hemodynamics during the LT surgery can unmask latent cardiovascular disease either intraoperatively or in the immediate postoperative period. Therefore, this review, assembled by a group of multidisciplinary experts in the field and endorsed by the American Society of Transplantation Liver and Intestine and Thoracic and Critical Care Communities of Practice, provides a critical assessment of the diagnosis of cardiac and pulmonary vascular disease and interventions aimed at managing these conditions in LT candidates. Key points and practice-based recommendations for the diagnosis and management of cardiac and pulmonary vascular disease in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations. This article is protected by copyright. All rights reserved.

PMID: 28985025 [PubMed - as supplied by publisher]

Postoperative changes of liver enzymes can distinguish between biliary stricture and graft rejection after living donor liver transplantation: A longitudinal study.

Sat, 10/07/2017 - 12:45

Postoperative changes of liver enzymes can distinguish between biliary stricture and graft rejection after living donor liver transplantation: A longitudinal study.

Medicine (Baltimore). 2017 Oct;96(40):e6892

Authors: Woo YS, Lee KH, Lee KT, Lee JK, Kim JM, Kwon CHD, Joh JW, Kang D, Cho J

Abstract
There is no known useful clinical parameter that can specifically predict a biliary stricture and differentiate it from other related complications after living donor liver transplantations (LDLT). The aims of this study were to determine whether the changes of liver enzymes can predict postoperative biliary stricture apart from other complications. We reviewed the medical records of 203 patients who underwent LDLT with duct to duct anastomosis from 2008 to 2010. The longitudinal changes of liver enzyme over time and the occurrence of complication were evaluated. A total of 124 patients had no complication up to 2 years after LDLT, and 74 patients had complications including biliary stricture and graft rejection. Complications developed more frequently in patients who's alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) did not return to the baseline plateau at 30 days after LDLT (ALP; P = .045, GGT; P = .047). Aspartate transaminase (AST) and alanine transaminase (ALT) increased continuously until the diagnosis of complication in both stricture and rejection groups with more rapid increase in enzymes in the rejection versus stricture group (P < .05). In addition, AST and ALT were 2-fold higher in the rejection than the stricture group at the diagnosis of each complication (AST; P < .05, ALT; P < .05). The increasing slope and final levels of AST and ALT are potentially helpful parameters to differentiate rejection and stricture, the 2 most common posttransplantation complications.

PMID: 28984750 [PubMed - in process]

Effects of donor age on human adipose-derived adherent stromal cells under oxidative stress conditions.

Sat, 10/07/2017 - 12:45

Effects of donor age on human adipose-derived adherent stromal cells under oxidative stress conditions.

J Int Med Res. 2017 Jan 01;:300060517731684

Authors: Kim SW, Choi JW, Lee CY, Lee J, Shin S, Lim S, Lee S, Kim IK, Lee HB, Hwang KC

Abstract
Objective Adipose-derived stromal vascular fractions (SVFs) are heterogeneous complex populations of cells with therapeutic efficacy for tissue generation and vascular stabilization. SVFs have cardiomyogenic potential, and many researchers have examined the possibility of SVF transplantation for heart disease. In cell-based therapies, donor age affects the regenerative capability, cell yield, and differentiation potential of adult tissues; however, opposing or controversial results have been found in humans. We examined whether SVF transplantation into impaired heart tissue shows differential effects according to donor age. Methods We investigated differences in protein expression in human umbilical vein endothelial cells (HUVECs) co-cultured with adipose-derived adherent stromal cells (ADASs) from donors of different ages [>40-year-olds (40s group) and >60-year-olds (60s group)] under oxidative stress conditions. Results Although co-culturing HUVECs with ADASs ameliorated inflammation due to increased oxidative stress conditions, few differences were observed between the ADASs from the 40s and 60s groups. Moreover, the Database for Annotation, Visualization, and Integrated Discovery classification tool revealed differentially expressed genes in the Kyoto Encyclopedia of Genes and Genomes pathway associated with cytokine-cytokine receptor interaction in response to ADASs. Conclusion Protein expression profiles were unchanged in HUVECs induced by isolated ADASs from donors of different ages under oxidative stress conditions.

PMID: 28984178 [PubMed - as supplied by publisher]

Management of patients with cardiogenic shock on temporary mechanical circulatory support: urgent transplantation or on to the next pump?

Sat, 10/07/2017 - 12:45

Management of patients with cardiogenic shock on temporary mechanical circulatory support: urgent transplantation or on to the next pump?

Eur J Heart Fail. 2017 Oct 06;:

Authors: Gustafsson F

PMID: 28984061 [PubMed - as supplied by publisher]

In search of an efficient strategy to monitor disease status of chronic heart failure outpatients: added value of blood biomarkers to clinical assessment.

Sat, 10/07/2017 - 12:45

In search of an efficient strategy to monitor disease status of chronic heart failure outpatients: added value of blood biomarkers to clinical assessment.

Neth Heart J. 2017 Oct 05;:

Authors: van Boven N, Akkerhuis KM, Anroedh SS, Battes LC, Caliskan K, Yassi W, Manintveld OC, Cornel JH, Constantinescu AA, Boersma H, Umans VA, Kardys I

Abstract
INTRODUCTION: Blood biomarkers have the potential to monitor the severity of chronic heart failure (CHF). Studies correlating repeated measurements of blood biomarkers with repeatedly assessed New York Heart Association (NYHA) class over a prolonged follow-up period, and concomitantly investigating their associations with clinical endpoints, have not yet been performed.
METHODS: Between 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3 months, we measured N‑terminal pro-B-type natriuretic (NT-proBNP), high-sensitivity troponin T (Hs-TnT) and C‑reactive protein (CRP), and assessed NYHA class. The primary endpoint comprised heart failure hospitalisation, cardiovascular mortality, cardiac transplantation or left ventricular assist device implantation. Time-dependent Cox models were used.
RESULTS: Mean age was 67 ± 13 years, 72% were men and 27% were in NYHA class III-IV. We obtained 886 repeated measures (median 3 [IQR 2-5] per patient). The primary endpoint was reached in 41 patients during a median follow-up of 1.0 [0.6-1.4] year. Repeatedly measured NT-proBNP and Hs-TnT were significantly associated with repeatedly assessed NYHA class, whereas CRP was not (NT-proBNP: β [95% CI]: 1.56 [1.17-2.06]ln(ng/l) increase per point increase in NYHA class, p = 0.002; HsTNT: β [95% CI]: 1.58 [1.21-2.07]). Serially measured NT-proBNP (HR [95% CI]:2.86 [1.73-4.73]), CRP (1.69 [1.21-2.34]) and NYHA class (2.33 [1.51-3.62]) were positively and independently associated with the primary endpoint, whereas Hs-TnT lost statistical significance after multivariable adjustment. A model containing serially measured NYHA class and NT-proBNP displayed a C-index of 0.84, while serially measured NYHA class and CRP showed a C-index of 0.82.
CONCLUSION: Temporal NT-proBNP, CRP and NYHA class patterns are independently associated with adverse clinical outcome. Serially measured NT-proBNP and NYHA class are best suited for monitoring CHF outpatients.

PMID: 28983818 [PubMed - as supplied by publisher]

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