Skip directly to content

PubMed Heart Transplant

Subscribe to PubMed Heart Transplant feed PubMed Heart Transplant
NCBI: db=pubmed; Term=heart transplant
Updated: 2 hours 7 min ago

Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct.

Thu, 08/17/2017 - 15:47
Related Articles

Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct.

Acta Radiol Open. 2017 Aug;6(8):2058460117718407

Authors: Korpi RM, Alestalo K, Ruuska T, Lammentausta E, Borra R, Yannopoulos F, Lehtonen S, Korpi JT, Lappi-Blanco E, Anttila V, Lehenkari P, Juvonen T, Blanco Sequieros R

Abstract
BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation.
PURPOSE: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model.
MATERIAL AND METHODS: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology.
RESULTS: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 89 ± 4% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI.
CONCLUSION: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI.

PMID: 28811932 [PubMed]

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Thu, 08/17/2017 - 15:47
Related Articles

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Transplant Rev (Orlando). 2017 Jul 26;:

Authors: Aguado JM, Silva JT, Fernández-Ruiz M, Cordero E, Fortún J, Gudiol C, Martínez-Martínez L, Vidal E, Almenar L, Almirante B, Cantón R, Carratalá J, Caston JJ, Cercenado E, Cervera C, Cisneros JM, Crespo-Leiro MG, Cuervas-Mons V, Elizalde-Fernández J, Fariñas MC, Gavaldà J, Goyanes MJ, Gutiérrez-Gutiérrez B, Hernández D, Len O, López-Andujar R, López-Medrano F, Martín-Dávila P, Montejo M, Moreno A, Oliver A, Pascual A, Pérez-Nadales E, Román-Broto A, San-Juan R, Serón D, Solé-Jover A, Valerio M, Muñoz P, Torre-Cisneros J, Spanish Society of Transplantation (SET), Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC), Spanish Network for Research in Infectious Diseases (REIPI) (RD16/0016)

Abstract
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

PMID: 28811074 [PubMed - as supplied by publisher]

Receipt of Nephrology Care and Clinical Outcomes Among Veterans With Advanced CKD.

Thu, 08/17/2017 - 15:47
Related Articles

Receipt of Nephrology Care and Clinical Outcomes Among Veterans With Advanced CKD.

Am J Kidney Dis. 2017 Aug 12;:

Authors: Fung E, Chang TI, Chertow GM, Thomas IC, Asch SM, Kurella Tamura M

Abstract
BACKGROUND: Clinical practice guidelines recommend referral to nephrology when estimated glomerular filtration rate (eGFR) decreases to <30mL/min/1.73m(2); however, evidence for benefits of nephrology care are mixed.
STUDY DESIGN: Observational cohort using landmark analysis.
SETTINGS & PARTICIPANTS: A national cohort of veterans with advanced chronic kidney disease, defined as an outpatient eGFR≤30mL/min/1.73m(2) for January 1, 2010, through December 31, 2010, and a prior eGFR<60mL/min/1.73m(2), using administrative and laboratory data from the Department of Veterans Affairs and the US Renal Data System.
PREDICTOR: Receipt and frequency of outpatient nephrology care over 12 months.
OUTCOMES: Survival and progression to end-stage renal disease (ESRD; receipt of dialysis or kidney transplantation) were the primary outcomes. In addition, control of associated clinical parameters over 12 months were intermediate outcomes.
RESULTS: Of 39,669 patients included in the cohort, 14,983 (37.8%) received nephrology care. Older age, heart failure, dementia, depression, and rapidly declining kidney function were independently associated with the absence of nephrology care. During a mean follow-up of 2.9 years, 14,719 (37.1%) patients died and 4,310 (10.9%) progressed to ESRD. In models adjusting for demographics, comorbid conditions, and trajectory of kidney function, nephrology care was associated with lower risk for death (HR, 0.88; 95% CI, 0.85-0.91), but higher risk for ESRD (HR, 1.48; 95% CI, 1.38-1.58). Among patients with clinical parameters outside guideline recommendations at cohort entry, a significantly higher adjusted proportion of patients who received nephrology care had improvement in control of hemoglobin, potassium, albumin, calcium, and phosphorus concentrations compared with those who did not receive nephrology care.
LIMITATIONS: May not be generalizable to nonveterans.
CONCLUSIONS: Among patients with advanced chronic kidney disease, nephrology care was associated with lower mortality, but was not associated with lower risk for progression to ESRD.

PMID: 28811048 [PubMed - as supplied by publisher]

Regulatory T-Cell Levels in the Longest Surviving Asian Patient After Heart-Lung Transplant.

Thu, 08/17/2017 - 15:47
Related Articles

Regulatory T-Cell Levels in the Longest Surviving Asian Patient After Heart-Lung Transplant.

Exp Clin Transplant. 2017 Aug 13;:

Authors: Huang L, Ji M, Yi S, Zhou X

Abstract
Heart-lung transplant is the most effective therapy for patients with end-stage cardiopulmonary disease. Here, we report an initial assessment of a 31-year-old man who had survived more than 11 years after heart-lung transplant, which represents the longest survival time in this procedure in Asian studies. At his 11th anniversary after transplant, extensive tests were carried out, especially to detect regulatory T-cell levels for the first time in a surviving heart-lung transplant recipient. Preliminarily data revealed the status of his immunologic function in relation to chronic allograft rejection. All data indicated that the patient was in good condition. This is the first study detecting regulatory T-cell levels in a heart-lung transplant patient.

PMID: 28810825 [PubMed - as supplied by publisher]

Effect of exercise training in heart rate variability, anxiety, depression, and sleep quality in kidney recipients: A preliminary study.

Thu, 08/17/2017 - 15:47
Related Articles

Effect of exercise training in heart rate variability, anxiety, depression, and sleep quality in kidney recipients: A preliminary study.

J Health Psychol. 2016 Nov 01;:1359105316676329

Authors: Barroso R, Silva-Filho AC, Dias CJ, Soares N, Mostarda A, Azoubel LA, Melo L, Garcia AM, Rodrigues B, Mostarda CT

Abstract
The aim of this study was to compare the sleep quality, depression, anxiety, and autonomic function of a group of kidney-transplanted recipients who joined a combined exercise program (KTRt) or remained sedentary (KTRs). A total of 20 kidney-transplanted recipients, split into two groups (10 KTRt and 10 KTRs), joined the study. Heart rate variability, cardiorespiratory capacity, depression, and sleep questionnaires were evaluated. KTRt presented lower Pittsburgh Sleep Quality Index and greater entropy, and increased parasympathetic and decreased sympathetic modulation than KTRs. Anxiety level was minimal and depression was absent in both groups. KTRt group presented better sleep quality and better autonomic modulation than KTRs.

PMID: 28810362 [PubMed - as supplied by publisher]

The Sydney Heart Bank: improving translational research while eliminating or reducing the use of animal models of human heart disease.

Thu, 08/17/2017 - 15:47
Related Articles

The Sydney Heart Bank: improving translational research while eliminating or reducing the use of animal models of human heart disease.

Biophys Rev. 2017 Aug 14;:

Authors: Dos Remedios CG, Lal SP, Li A, McNamara J, Keogh A, Macdonald PS, Cooke R, Ehler E, Knöll R, Marston SB, Stelzer J, Granzier H, Bezzina C, van Dijk S, De Man F, Stienen GJM, Odeberg J, Pontén F, Linke W, van der Velden J

Abstract
The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5-10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent's Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are from donor left ventricles, but right ventricles, atria, interventricular system, and coronary arteries vessels have also been reported. All tissues are stored for long-term use in liquid N or vapor (170-180 °C), and are shipped under nitrogen vapor to avoid degradation of sensitive molecules such as RNAs and giant proteins. We present evidence that the availability of these human heart samples has contributed to a reduction in the use of animal models of human heart failure.

PMID: 28808947 [PubMed - as supplied by publisher]

Prognostic significance of myocardial energy expenditure and myocardial efficiency in patients with heart failure with reduced ejection fraction.

Thu, 08/17/2017 - 15:47
Related Articles

Prognostic significance of myocardial energy expenditure and myocardial efficiency in patients with heart failure with reduced ejection fraction.

Int J Cardiovasc Imaging. 2017 Aug 14;:

Authors: Cetin MS, Ozcan Cetin EH, Canpolat U, Sasmaz H, Temizhan A, Aydogdu S

Abstract
In heart failure with reduced ejection fraction (HFrEF) patients, myocardial blood flow (MBF), myocardial energy expenditure (MEE), myocardial efficiency has been poorly evaluated because of the necessity of invasive procedures in the determination of these parameters. Transthoracic echocardiography (TTE) can provide reliable data for MEE, MBF (via coronary sinus (CS) flows). Also, myocardial efficiency can be evaluated by the MEE to MBF ratio. We aim to assess MBF, MEE and energy efficiency and the prognostic value of these parameters in HFrEF. In this prospective study, a total of 80 patients with HFrEF due to either ischemic or non-ischemic etiology and 20 healthy control subjects were included. Median follow-up duration was 901 (27-1004) days. MBF was calculated via coronary sinus blood flow. MEE was measured from circumferential end-systolic stress, stroke volume and left ventricular ejection time. MEE to MBF ratio was determined as MEf. Primary composite end-point (CEP) was cardiovascular mortality, heart transplantation or mechanical circulatory support. MEE and MEf were lower and MBF per minute was higher in HF group compared to control subjects whereas MBF per 100 g left ventricular mass was not different. MEE and MEf have significantly negative correlation with troponin I, BNP, uric acid and positive correlation with epicardial fat thickness. In Cox regression analysis, per one calorie decrease of MEE was associated 4.3 times increased risk [HR 4.396 (95% CI 1.230-15.716)] and per one percent decrease of MEf was associated 3.3 times increased risk of CEP [HR 3.343 (95% CI 1.025-10.905)]. Our study demonstrated that while MEE and MEf diminished in HFrEF, MBF preserved with the symptomatic progression of HF. MEE and MEf were found to be associated with important prognostic markers and independent predictors of CEP in HFrEF. Evaluation of MEE, MBF and MEf with echocardiography may provide an additional data regarding prognostic assessment of HFrEF population.

PMID: 28808841 [PubMed - as supplied by publisher]

Response by Loupy et al to Letters Regarding Article, "Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection".

Thu, 08/17/2017 - 15:47
Related Articles

Response by Loupy et al to Letters Regarding Article, "Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection".

Circulation. 2017 Aug 15;136(7):698-699

Authors: Loupy A, Hidalgo L, Duong JP, Bruneval P, Jouven X, Halloran PF

PMID: 28808152 [PubMed - in process]

Letter by Rowshani et al Regarding Article, "Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection".

Thu, 08/17/2017 - 15:47
Related Articles

Letter by Rowshani et al Regarding Article, "Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection".

Circulation. 2017 Aug 15;136(7):694-695

Authors: Rowshani AT, Caliskan K, von der Thüsen JH

PMID: 28808150 [PubMed - in process]

Health characteristics of heart transplant recipients surviving into their 80s.

Thu, 08/17/2017 - 15:47
Related Articles

Health characteristics of heart transplant recipients surviving into their 80s.

J Surg Res. 2017 Aug;216:99-102

Authors: Tabachnick DR, Bowen ME, Stehlik J, Kfoury AG, Caine WT, Selzman CH, McKellar SH, Utah Cardiac Transplant Program (UCTP)

Abstract
BACKGROUND: Heart transplantation (HTx) is the preferred treatment for patients with end-stage heart failure and has been successful for >30 y. The clinical course of recipients at the extreme of age is unknown. We reviewed our experience to determine the overall health and prevalence of Tx-related medical problems for recipients in their ninth decade.
METHODS: We reviewed the UCTP experience from 1985 to present to identify patients who survived into their 80s and matched (1:1) with other recipients for gender and age at HTx, but did not survive to ≥80 y. The end point was the prevalence of medical problems.
RESULTS: Since 1985, 1129 adult HTx have been performed and 14 patients (1.2%) survived to ≥80 y old. The mean age at HTx was 63 ± 4 y. Of octogenarians, the majority were males with ischemic cardiomyopathy. The average survival after transplant was 19 ± 5 y in the octogenarians and 5 ± 5 y in the controls (P < 0.01). Over time, the prevalence of comorbidities increased. Compared with nonoctogenarians, we observed higher prevalence of dyslipidemia (P = 0.02), and chronic renal insufficiency (P = 0.02) during follow-up. Cardiac function was normal (ejection fraction > 55%) for all octogenarians at age 80 y.
CONCLUSIONS: Despite improvements in posttransplant care, survival of HTx patients into the ninth decade is rare (1%). For those surviving into their 80s, cardiac function is preserved but dyslipidemia, renal insufficiency, and skin cancers are common. As the age of Htx patients continues to increase, posttransplant care should be tailored to minimize post-HTx complications and further extend survival.

PMID: 28807220 [PubMed - in process]

First report of Sneathia sanguinegens together with Mycoplasma hominis in postpartum prosthetic valve infective endocarditis: a case report.

Thu, 08/17/2017 - 15:47
Related Articles

First report of Sneathia sanguinegens together with Mycoplasma hominis in postpartum prosthetic valve infective endocarditis: a case report.

BMC Infect Dis. 2017 Aug 14;17(1):563

Authors: Kotaskova I, Nemec P, Vanerkova M, Malisova B, Tejkalova R, Orban M, Zampachova V, Freiberger T

Abstract
BACKGROUND: The presence of more than one bacterial agent is relatively rare in infective endocarditis, although more common in prosthetic cases. Molecular diagnosis from a removed heart tissue is considered a quick and effective way to diagnose fastidious or intracellular agents.
CASE PRESENTATION: Here we describe the case of postpartum polymicrobial prosthetic valve endocarditis in a young woman. Sneathia sanguinegens and Mycoplasma hominis were simultaneously detected from the heart valve sample using broad range 16S rRNA polymerase chain reaction (PCR) followed by sequencing while culture remained negative. Results were confirmed by independent PCR combined with denaturing gradient gel electrophoresis. Before the final agent identification, the highly non-compliant patient left from the hospital against medical advice on empirical intravenous treatment with aminopenicillins, clavulanate and gentamicin switched to oral amoxycillin and clavulanate. Four months after surgery, no signs of inflammation were present despite new regurgitation and valve leaflet flail was detected. However, after another 5 months the patient died from sepsis and recurrent infective endocarditis of unclarified etiology.
CONCLUSIONS: Mycoplasma hominis is a rare causative agent of infective endocarditis. To the best of our knowledge, presented case is the first report of Sneathia sanguinegens detected in this condition. Molecular techniques were shown to be useful even in polymicrobial infective endocarditis samples.

PMID: 28806998 [PubMed - in process]

Chronic kidney disease in hypertensive subjects ≥60 years treated in Primary Care.

Thu, 08/17/2017 - 15:47
Related Articles

Chronic kidney disease in hypertensive subjects ≥60 years treated in Primary Care.

Nefrologia. 2017 Jul - Aug;37(4):406-414

Authors: Salvador-González B, Mestre-Ferrer J, Soler-Vila M, Pascual-Benito L, Alonso-Bes E, Cunillera-Puértolas O, en representación del grupo de investigación del proyecto MARREC-HTA

Abstract
BACKGROUND: Hypertension (HT) is the second leading cause of kidney failure. In hypertensive patients with chronic kidney disease (CKD), blood pressure (BP) control is the most important intervention to minimise progression. For CKD diagnosis, standardised creatinine and estimated glomerular filtration rate (eGFR) testing by CKD-EPI is recommended.
OBJECTIVES: To describe the prevalence and factors associated with a moderate decrease in eGFR (by CKD-EPI) and BP control in subjects with HT.
METHODS: Cross-sectional descriptive study in subjects ≥ 60 years included in the SIDIAP plus database with hypertension and standardised serum creatinine and BP tests in the last 2years.
EXCLUSION CRITERIA: eGFR<30, dialysis or kidney transplantation, prior cardiovascular disease, home care. Primary endpoint: eGFR by CKD-EPI formula. Covariates: demographic data, examination, cardiovascular risk factors, heart failure and auricular fibrillation diagnosis, and drugs (antihypertensive agents acting on renal function, antiplatelet and lipid lowering agents). BP control criteria: ≤130/80mmHg in individuals with albuminuria, ≤140/90 in all other subjects.
RESULTS: Prevalence of eGFR <60=18.8%. Associated factors: age, gender, heart failure, albumin/creatinine ratio, auricular fibrillation, smoking, dyslipidaemia, diabetes and obesity. BP control: 66.14 and 63.24% in eGFR≥60 and eGFR <60, respectively (P<.05). Exposure to drugs was higher in eGFR<60.
CONCLUSION: One in 5hypertensive patients without cardiovascular disease ≥60 years in primary care presented with a moderate decrease in eGFR. In addition to age and sex, albuminuria and heart failure were the main associated factors. Despite the increased exposure to drugs, BP control was lower in CKD.

PMID: 28750875 [PubMed]

Corrigendum to "Calculated panel reactive antibody with decimals: A refined metric of access to transplantation for highly sensitized candidates" [Hum. Immunol. 78(3) (2017) 252-256].

Thu, 08/17/2017 - 15:47
Related Articles

Corrigendum to "Calculated panel reactive antibody with decimals: A refined metric of access to transplantation for highly sensitized candidates" [Hum. Immunol. 78(3) (2017) 252-256].

Hum Immunol. 2017 Jul - Aug;78(7-8):522

Authors: Kransdorf EP, Pando MJ

PMID: 28743386 [PubMed - in process]

Prognostic Implications of Left Ventricular Global Longitudinal Strain in Predialysis and Dialysis Patients.

Thu, 08/17/2017 - 15:47
Related Articles

Prognostic Implications of Left Ventricular Global Longitudinal Strain in Predialysis and Dialysis Patients.

Am J Cardiol. 2017 Aug 01;120(3):500-504

Authors: Hensen LCR, Goossens K, Delgado V, Rotmans JI, Jukema JW, Bax JJ

Abstract
Chronic kidney disease (CKD) is a worldwide growing epidemic associated with an increased risk of cardiovascular morbidity and mortality. Left ventricular (LV) global longitudinal strain (GLS) is a measure of LV systolic function associated with prognosis in the general population. However, little is known about the association between LV GLS and survival in patients with CKD. The aim of the present study was to investigate the prognostic implications of LV GLS in predialysis and dialysis patients specifically. LV GLS was measured in a retrospective cohort of predialysis and dialysis patients (CKD stage 3b to 5) who underwent clinically indicated echocardiography between 2004 and 2015. Patients were divided into 4 groups according to quartiles of LV GLS: first quartile (LV GLS ≤10.6%, worst function), second quartile (LV GLS 10.7% to 15.1%), third quartile (LV GLS 15.2% to 17.8%), and fourth quartile (LV GLS ≥17.9%, best function). The primary end point was all-cause mortality. Of 304 patients (62 ± 14 years, 66% male), 65% were in predialysis and 35% in dialysis. During a median follow-up of 29 months (interquartile range 16 to 58 months), 34% of patients underwent renal transplantation and 36% died. Patients with LV GLS ≤10.6% showed significantly worse prognosis compared with the other groups (log-rank test, p <0.001). LV GLS ≤10.6% was significantly associated with increased risk of all-cause mortality (hazard ratio 2.18, 95% CI 1.17 to 4.06, p = 0.014) after correcting for age, gender, albumin levels, atrial fibrillation, and renal transplantation. In conclusion, in predialysis and dialysis patients, severely impaired LV GLS is independently associated with an increased risk of mortality.

PMID: 28579125 [PubMed - indexed for MEDLINE]

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

Thu, 08/17/2017 - 15:47
Related Articles

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

J Cardiovasc Med (Hagerstown). 2017 Apr;18(4):283-290

Authors: Greene SJ, Epstein SE, Kim RJ, Quyyumi AA, Cole RT, Anderson AS, Wilcox JE, Skopicki HA, Sikora S, Verkh L, Tankovich NI, Gheorghiade M, Butler J

Abstract
AIMS: This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance.
STUDY DESIGN: This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion.
CONCLUSION: This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

PMID: 26479144 [PubMed - indexed for MEDLINE]

Olaparib, a clinically used poly(ADP-ribose) polymerase inhibitor protects against oxidant-induced cardiac myocyte death in vitro and improves cardiac contractility during early phase after heart transplantation in a rat model in vivo.

Tue, 08/15/2017 - 12:45

Olaparib, a clinically used poly(ADP-ribose) polymerase inhibitor protects against oxidant-induced cardiac myocyte death in vitro and improves cardiac contractility during early phase after heart transplantation in a rat model in vivo.

Br J Pharmacol. 2017 Aug 14;:

Authors: Korkmaz-Icöz S, Szczesny B, Marcatti M, Li S, Ruppert M, Lasitschka F, Loganathan S, Szabo C, Szabó G

Abstract
BACKGROUND AND PURPOSE: Olaparib, rucaparib and niraparib, potent inhibitors of poly(ADP-ribose) polymerase (PARP) have recently been approved for human use for oncological indications. Considering the previously demonstrated role of PARP in various forms of acute and chronic myocardial injury, we tested the effect of olaparib in in-vitro models of oxidative stress in cardiomyocytes, and in an in-vivo model of cardiac transplantation.
EXPERIMENTAL APPROACH: H9c2-embryonic rat heart-derived myoblasts pretreated with vehicle or olaparib (10μM) were challenged with either hydrogen-peroxide (H2 O2 ) or with glucose-oxidase (GOx, which generates H2 O2 in the tissue culture medium). Cell viability assays (MTT, lactate dehydrogenase) and Western blotting for PARP and its product, PAR was conducted. In-vivo studies of heterotopic heart transplantation were performed in an isogenic Lewis to Lewis rat strain; recipients were treated either with vehicle or olaparib (10mg/kg). Left-ventricular function of the transplanted heart was monitored via a Millar-catheter-system. Multiple gene expression in the transplanted hearts was measured by qPCR.
KEY RESULTS: Olaparib blocked autoPARylation of PARP1 and attenuated the H2 O2 -induced rapid-onset H9c2 cell-death, but did not affect cell-death in response to chronic, prolonged oxidative stress induced by GOx. In rats, after transplantation, left-ventricular systolic and diastolic function were significantly improved by olaparib. Olaparib was also associated with reduced gene expression in the transplanted hearts for c-jun, caspase-12, catalase, and NADPH-oxidase-2.
CONCLUSIONS AND IMPLICATIONS: Olaparib reduces oxidative stress-induced myocyte injury in-vitro and improves cardiac function in a transplantation model in-vivo. These findings raise the possibility of repurposing of this clinically approved oncology drug to be used in heart transplantation.

PMID: 28806493 [PubMed - as supplied by publisher]

Serotonergic 5-HT2B receptors in mitral valvulopathy: bone marrow mobilization of endothelial progenitors.

Tue, 08/15/2017 - 12:45

Serotonergic 5-HT2B receptors in mitral valvulopathy: bone marrow mobilization of endothelial progenitors.

Br J Pharmacol. 2017 Aug 14;:

Authors: Ayme-Dietrich E, Lawson R, Côté F, de Tapia C, Da Silva S, Ebel C, Hechler B, Gachet C, Guyonnet J, Rouillard H, Stoltz J, Quentin E, Banas S, Daubeuf F, Frossard N, Gasser B, Mazzucotelli JP, Hermine O, Maroteaux L, Monassier L

Abstract
BACKGROUND: Valvular heart disease is highly prevalent in industrialized countries. Chronic use of anorexigens, amphetamine or ergot derivatives targeting the serotonin system has been associated with valvular heart disease.
PURPOSE AND EXPERIMENTAL APPROACH: Here, we investigated the contribution of serotonin receptors in a mouse model of valve degeneration induced by nordexfenfluramine, the main metabolite of the anorexigens dexfenfluramine and benfluorex.
KEY RESULTS: Chronically activated 5-HT2B receptors by nordexfenfluramine in mice mimicked early steps of mitral valve remodelling attested by increased valve thickness, and cell density in a thick extracellular matrix. Lesions were totally prevented by inhibition of both 5-HT2A and 5-HT2B receptors by antagonists and in transgenic Htr2B(-/-) , or Htr2A/2B(-/-) mice. Surprisingly, we found that valve lesions are mainly formed by numerous non-proliferative CD34(+) endothelial progenitors. We show that these progenitors originate from bone marrow as revealed by bone marrow transplantation. Initial steps of mitral valve remodelling involve bone-marrow derived CD34(+) CD31(+) cells mobilization by 5-HT2B receptor stimulation. Moreover, the analysis of human mitral valve prolapse, showing spontaneous degenerative lesions highlights the presence of non-proliferating CD34(+) /CD309(+) /NOS3(+) endothelial progenitors expressing 5-HT2B receptors.
CONCLUSIONS AND IMPLICATIONS: This work reveals a crucial contribution of bone-marrow derived endothelial progenitor cells in valve tissue remodelling and highlights the contribution of this new mechanism involved in human valvular heart disease.

PMID: 28806488 [PubMed - as supplied by publisher]

Incidence and outcomes of primary central nervous system lymphoma in solid organ transplant recipients.

Tue, 08/15/2017 - 12:45

Incidence and outcomes of primary central nervous system lymphoma in solid organ transplant recipients.

Am J Transplant. 2017 Aug 14;:

Authors: Mahale P, Shiels MS, Lynch CF, Engels EA

Abstract
Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed HIV-infected people. Using data from the United States transplant registry linked with 17 cancer registries (1987-2014), we studied PCNSL and systemic non-Hodgkin lymphoma (NHL) in 288,029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio=65.1; N=168), and this elevation was stronger than for systemic NHL (standardized incidence ratio=11.5; N=2,043). Compared to kidney recipients, PCNSL incidence was lower in liver recipients (adjusted incidence rate ratio [aIRR]=0.52), similar in heart and/or lung recipients, and higher in other/multiple organ recipients (aIRR=2.45). PCNSL incidence was higher in Asians/Pacific Islanders than non-Hispanic whites (aIRR=2.09); after induction immunosuppression with alemtuzumab (aIRR=3.12), monoclonal antibodies (aIRR=1.83), or polyclonal antibodies (aIRR=2.03); in recipients who were Epstein-Barr virus-seronegative at the time of transplant and at risk of primary infection (aIRR=1.95); and within the first 1.5 years after transplant (aIRR>2.00). Compared to other recipients, those with PCNSL had increased risk of death (adjusted hazard ratio [aHR]=11.79) or graft failure/retransplantation (aHR=3.24). Recipients with PCNSL also had higher mortality than those with systemic NHL (aHR=1.48). In conclusion, PCNSL risk is highly elevated among transplant recipients, and it carries a poor prognosis. This article is protected by copyright. All rights reserved.

PMID: 28805292 [PubMed - as supplied by publisher]

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

Tue, 08/15/2017 - 12:45

Impact of beta-blockers on cardiopulmonary exercise testing in patients with advanced liver disease.

Aliment Pharmacol Ther. 2017 Aug 14;:

Authors: Wallen MP, Hall A, Dias KA, Ramos JS, Keating SE, Woodward AJ, Skinner TL, Macdonald GA, Arena R, Coombes JS

Abstract
BACKGROUND: Patients with advanced liver disease may develop portal hypertension that can result in variceal haemorrhage. Beta-blockers reduce portal pressure and minimise haemorrhage risk. These medications may attenuate measures of cardiopulmonary performance, such as the ventilatory threshold and peak oxygen uptake measured via cardiopulmonary exercise testing.
AIM: To determine the effect of beta-blockers on cardiopulmonary exercise testing variables in patients with advanced liver disease.
METHODS: This was a cross-sectional analysis of 72 participants who completed a cardiopulmonary exercise test before liver transplantation. All participants remained on their usual beta-blocker dose and timing prior to the test. Variables measured during cardiopulmonary exercise testing included the ventilatory threshold, peak oxygen uptake, heart rate, oxygen pulse, the oxygen uptake efficiency slope and the ventilatory equivalents for carbon dioxide slope.
RESULTS: Participants taking beta-blockers (n = 28) had a lower ventilatory threshold (P <.01) and peak oxygen uptake (P = .02), compared to participants not taking beta-blockers. After adjusting for age, the model of end-stage liver-disease score, liver-disease aetiology, presence of refractory ascites and ventilatory threshold remained significantly lower in the beta-blocker group (P = .04). The oxygen uptake efficiency slope was not impacted by beta-blocker use.
CONCLUSIONS: Ventilatory threshold is reduced in patients with advanced liver disease taking beta-blockers compared to those not taking the medication. This may incorrectly risk stratify patients on beta-blockers and has implications for patient management before and after liver transplantation. The oxygen uptake efficiency slope was not influenced by beta-blockers and may therefore be a better measure of cardiopulmonary performance in this patient population.

PMID: 28805258 [PubMed - as supplied by publisher]

Comparison of intrathecal morphine and surgical-site infusion of ropivacaine as adjuncts to intravenous patient-controlled analgesia in living-donor kidney transplant recipients.

Tue, 08/15/2017 - 12:45

Comparison of intrathecal morphine and surgical-site infusion of ropivacaine as adjuncts to intravenous patient-controlled analgesia in living-donor kidney transplant recipients.

Singapore Med J. 2017 Aug 14;:

Authors: Jun JH, Kim GS, Lee JJ, Ko JS, Kim SJ, Jeon PH

Abstract
INTRODUCTION: This prospective observational study compared the postoperative analgesic effectiveness of intrathecal morphine (ITM) and surgical-site infusion (SSI) of ropivacaine as adjuncts to intravenous (IV) patient-controlled analgesia (PCA) (fentanyl) in living-donor kidney transplant recipients.
METHODS: Patients undergoing living-donor kidney transplantation receiving ITM or SSI in addition to IV PCA were included. Rescue analgesia was achieved with IV meperidine, as required. Primary outcome was pain at rest and when coughing using Numeric Pain Rating Scale (NRS). Patients were assessed for 48 hours after surgery.
RESULTS: 53 patients (ITM, n = 32; SSI, n = 21) were included in the study. The ITM group showed significantly lower NRS at rest, and when coughing for up to 12 hours and 8 hours. NRS scores were comparable between the groups at other times. Postoperative systemic opioid requirements in the first 24 hours were significantly fewer in the ITM group, but there was no significant difference in systemic opioid consumption between the groups on postoperative day (POD) 2. 3 (9.4%) patients in the ITM group presented with bradypnoea and 1 (3.1%) presented with excessive sedation in the first 12 postoperative hours. More patients in the ITM group developed pruritus requiring treatment during the first 24 hours. There were no differences between the groups in terms of other outcomes (e.g. nausea/vomiting, change in pulmonary and kidney functions).
CONCLUSION: ITM, compared with SSI, reduced immediate postoperative pain and IV opioid consumption during POD 1 after living-donor kidney transplantation, but at the cost of increased pruritus and respiratory depression.

PMID: 28805236 [PubMed - as supplied by publisher]

Pages