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Longitudinal Outcomes of Patients With Single Ventricle After the Fontan Procedure.

Sat, 06/03/2017 - 12:45
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Longitudinal Outcomes of Patients With Single Ventricle After the Fontan Procedure.

J Am Coll Cardiol. 2017 Jun 06;69(22):2735-2744

Authors: Atz AM, Zak V, Mahony L, Uzark K, D'agincourt N, Goldberg DJ, Williams RV, Breitbart RE, Colan SD, Burns KM, Margossian R, Henderson HT, Korsin R, Marino BS, Daniels K, McCrindle BW, Pediatric Heart Network Investigators

Abstract
BACKGROUND: Multicenter longitudinal objective data for survival into adulthood of patients who have undergone Fontan procedures are lacking.
OBJECTIVES: This study sought to describe transplant-free survival and explore relationships between laboratory measures of ventricular performance and functional status over time.
METHODS: Exercise testing, echocardiography, B-type natriuretic peptide, functional health assessment, and medical history abstraction were repeated 9.4 ± 0.4 years after the Fontan Cross-Sectional Study (Fontan 1) and compared with previous values. Cox regression analysis explored risk factors for interim death or cardiac transplantation.
RESULTS: From the original cohort of 546 subjects, 466 were contacted again, and 373 (80%) were enrolled at 21.2 ± 3.5 years of age. Among subjects with paired testing, the percent predicted maximum oxygen uptake decreased (69 ± 14% vs. 61 ± 16%; p < 0.001; n = 95), ejection fraction decreased (58 ± 11% vs. 55 ± 10%; p < 0.001; n = 259), and B-type natriuretic peptide increased (median [interquartile range] 13 [7 to 25] pg/mol vs. 18 [9 to 36] pg/mol; p < 0.001; n = 340). At latest follow-up, a lower Pediatric Quality of Life Inventory physical summary score was associated with poorer exercise performance (R(2) adjusted = 0.20; p < 0.001; n = 274). Cumulative complications since the Fontan procedure included additional cardiac surgery (32%), catheter intervention (62%), arrhythmia treatment (32%), thrombosis (12%), and protein-losing enteropathy (8%). Since Fontan 1, 54 subjects (10%) have received a heart transplant (n = 23) or died without transplantation (n = 31). The interval risk of death or/cardiac transplantation was associated with poorer ventricular performance and functional health status assessed at Fontan 1, but it was not associated with ventricular morphology, the subject's age, or the type of Fontan connection.
CONCLUSIONS: Interim transplant-free survival over 12 years in this Fontan cohort was 90% and was independent of ventricular morphology. Exercise performance decreased and was associated with worse functional health status. Future interventions might focus on preserving exercise capacity. (Relationship Between Functional Health Status and Ventricular Performance After Fontan-Pediatric Heart Network; NCT00132782).

PMID: 28571639 [PubMed - in process]

Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy.

Sat, 06/03/2017 - 12:45
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Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy.

Int J Cardiol. 2017 May 23;:

Authors: Pölzl G, Altenberger J, Baholli L, Beltrán P, Borbély A, Comin-Colet J, Delgado JF, Fedele F, Fontana A, Fruhwald F, Giamouzis G, Giannakoulas G, Garcia-González MJ, Gustafsson F, Kaikkonen K, Kivikko M, Kubica J, von Lewinski D, Löfman I, Malfatto G, Manito N, Martínez-Sellés M, Masip J, Merkely B, Morandi F, Mølgaard H, Oliva F, Pantev E, Papp Z, Perna GP, Pfister R, Piazza V, Bover R, Rangel-Sousa D, Recio-Mayoral A, Reinecke A, Rieth A, Sarapohja T, Schmidt G, Seidel M, Störk S, Vrtovec B, Wikström G, Yerly P, Pollesello P

Abstract
Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.

PMID: 28571618 [PubMed - as supplied by publisher]

Renal association clinical practice guideline in post-operative care in the kidney transplant recipient.

Sat, 06/03/2017 - 12:45
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Renal association clinical practice guideline in post-operative care in the kidney transplant recipient.

BMC Nephrol. 2017 Jun 02;18(1):174

Authors: Baker RJ, Mark PB, Patel RK, Stevens KK, Palmer N

Abstract
These guidelines cover the care of patients from the period following kidney transplantation until the transplant is no longer working or the patient dies. During the early phase prevention of acute rejection and infection are the priority. After around 3-6 months, the priorities change to preservation of transplant function and avoiding the long-term complications of immunosuppressive medication (the medication used to suppress the immune system to prevent rejection). The topics discussed include organization of outpatient follow up, immunosuppressive medication, treatment of acute and chronic rejection, and prevention of complications. The potential complications discussed include heart disease, infection, cancer, bone disease and blood disorders. There is also a section on contraception and reproductive issues.Immediately after the introduction there is a statement of all the recommendations. These recommendations are written in a language that we think should be understandable by many patients, relatives, carers and other interested people. Consequently we have not reworded or restated them in this lay summary. They are graded 1 or 2 depending on the strength of the recommendation by the authors, and AD depending on the quality of the evidence that the recommendation is based on.

PMID: 28571571 [PubMed - in process]

IκB Kinase Inhibitor Attenuates Sepsis-Induced Cardiac Dysfunction in CKD.

Sat, 06/03/2017 - 12:45
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IκB Kinase Inhibitor Attenuates Sepsis-Induced Cardiac Dysfunction in CKD.

J Am Soc Nephrol. 2017 Jan;28(1):94-105

Authors: Chen J, Kieswich JE, Chiazza F, Moyes AJ, Gobbetti T, Purvis GS, Salvatori DC, Patel NS, Perretti M, Hobbs AJ, Collino M, Yaqoob MM, Thiemermann C

Abstract
Patients with CKD requiring dialysis have a higher risk of sepsis and a 100-fold higher mortality rate than the general population with sepsis. The severity of cardiac dysfunction predicts mortality in patients with sepsis. Here, we investigated the effect of preexisting CKD on cardiac function in mice with sepsis and whether inhibition of IκB kinase (IKK) reduces the cardiac dysfunction in CKD sepsis. Male C57BL/6 mice underwent 5/6 nephrectomy, and 8 weeks later, they were subjected to LPS (2 mg/kg) or sepsis by cecal ligation and puncture (CLP). Compared with sham operation, nephrectomy resulted in significant increases in urea and creatinine levels, a small (P<0.05) reduction in ejection fraction (echocardiography), and increases in the cardiac levels of phosphorylated IκBα, Akt, and extracellular signal-regulated kinase 1/2; nuclear translocation of the NF-κB subunit p65; and inducible nitric oxide synthase (iNOS) expression. When subjected to LPS or CLP, compared with sham-operated controls, CKD mice exhibited exacerbation of cardiac dysfunction and lung inflammation, greater increases in levels of plasma cytokines (TNF-α, IL-1β, IL-6, and IL-10), and greater increases in the cardiac levels of phosphorylated IKKα/β and IκBα, nuclear translocation of p65, and iNOS expression. Treatment of CKD mice with an IKK inhibitor (IKK 16; 1 mg/kg) 1 hour after CLP or LPS administration attenuated these effects. Thus, preexisting CKD aggravates the cardiac dysfunction caused by sepsis or endotoxemia in mice; this effect may be caused by increased cardiac NF-κB activation and iNOS expression.

PMID: 27153924 [PubMed - indexed for MEDLINE]

Total arterial grafting is associated with improved clinical outcomes compared to conventional myocardial revascularization at 10 years follow-up.

Sat, 06/03/2017 - 12:45
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Total arterial grafting is associated with improved clinical outcomes compared to conventional myocardial revascularization at 10 years follow-up.

Heart Vessels. 2017 Feb;32(2):109-116

Authors: Bisleri G, Di Bacco L, Giroletti L, Muneretto C

Abstract
The use of arterial conduits is associated with incremental benefits when compared to conventional CABG surgery, albeit there is a paucity of data regarding the long-term outcomes of either techniques. Among 973 consecutive patients undergoing CABG, a propensity-match study was performed to compare total arterial revascularization technique (G1) with a conventional approach (LITA on LAD plus additional SVGs, G2). The study population was propensity-matched based on preoperative characteristics (age, sex, risk factors). Mean number of grafted vessels (G1 = 2.39 ± 0.55 vs G2 = 2.37 ± 0.7; p = 0.79) and aortic cross-clamp time (G1 = 36 ± 6 vs G2 = 35 ± 6 min; p = 0.31) were similar while CPB time was significantly longer in Group 2 (G1 = 50 ± 7 vs G2 = 70 ± 8 min; p = 0.03). Hospital mortality (G1 = 0.6 % vs G2 = 1.3 %; p = 0.41) and overall incidence of postoperative complications were also comparable. Cox regression analysis depicted conventional CABG as an independent predictor for MACCEs (HR = 4.53, CI 95 % = 2-10.28; p < 0.001). Median follow-up time was 112 months: actuarial survival free from cardiac death (G1 = 100 % vs G2 = 95 ± 2.1 %; p = 0.046) and MACCEs (G1 = 97.3 ± 1.5 % vs G2 = 79.4 ± 3.8 %; p < 0.001) was significantly improved in patients undergoing total arterial grafting. Total arterial myocardial revascularization is associated with significantly improved outcomes at 10 years follow-up in terms of cardiac-related mortality and overall event-free survival.

PMID: 27142066 [PubMed - indexed for MEDLINE]

Transcatheter Tricuspid Valve Replacement in Orthotopic Heart Transplant.

Fri, 06/02/2017 - 12:45
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Transcatheter Tricuspid Valve Replacement in Orthotopic Heart Transplant.

J Invasive Cardiol. 2017 Jun;29(6):E75-E76

Authors: Hafiz AM, Shih J, Kakouros N

Abstract
A patient with history of orthotopic heart transplant (OHT) followed by tricuspid valve replacement and two subsequent balloon valvuloplasties was offered transcatheter tricuspid valve replacement (TTVR) to avoid what would have been his fourth sternotomy. TTVR in patients with OHT can be a valuable approach to prevent further open-heart surgeries, which carry added morbidity and mortality.

PMID: 28570244 [PubMed - in process]

Clinical significance of anti-HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis.

Fri, 06/02/2017 - 12:45
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Clinical significance of anti-HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis.

Pediatr Transplant. 2017 Jun 01;:

Authors: Magdo HS, Schumacher KR, Yu S, Gajarski RJ, Friedland-Little JM

Abstract
While VAD use in pediatric patients has previously been associated with anti-HLA antibody production, the clinical significance of these antibodies is unclear. We investigated the clinical impact of anti-HLA antibodies associated with VAD use in a large cohort of pediatric HTx recipients. From 2004 to 2011, pediatric cardiomyopathy patients post-HTx (N=1288) with pre-HTx PRA levels were identified from the United Network for Organ Sharing database. PRA levels were compared between VAD patients and those with no history of MCS. Incidence of rejection and overall survival were compared between VAD and non-MCS groups after stratification by PRA and age. VAD recipients were more likely to produce anti-HLA antibodies than non-MCS patients (25.5% vs 10.5% had PRA>10%, P<.0001). Sensitized VAD patients (PRA>10%) had a higher incidence of rejection within 15 months of HTx compared to sensitized non-MCS patients (57.1% vs 35.9%, P=.02). There was no intergroup difference in 15-month mortality. Among pediatric cardiomyopathy patients supported with a VAD, the presence of anti-HLA antibodies prior to HTx is associated with an increased risk of rejection. The mechanism of the association between VAD-associated antibodies and early rejection is unclear and warrants further investigation.

PMID: 28568969 [PubMed - as supplied by publisher]

Investigation and treatment for iron deficiency in heart failure: the unmet need in Lower and Middle Income Countries.

Fri, 06/02/2017 - 12:45
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Investigation and treatment for iron deficiency in heart failure: the unmet need in Lower and Middle Income Countries.

Br J Haematol. 2017 May 31;:

Authors: Makubi A, Roberts DJ

Abstract
Frank iron deficiency has been associated with a wide range of cardiac and pulmonary abnormalities including non-ischaemic cardiomyopathy. Iron deficiency anaemia and isolated iron deficiency are well-defined adverse prognostic factors in non-ischaemic cardiac failure. Furthermore, iron-deficient patients in chronic heart failure with a serum ferritin of <100 μg/l or <300 μg/l with reduced transferrin saturation of <20%, who were given intravenous iron showed improved clinical outcomes. Iron deficiency with or without anaemia affects over a quarter of the world's population, but the impact of iron deficiency in heart failure and the effective management of iron deficiency in heart failure in Lower and Middle Income Countries (LMICs) is not well described. Heart failure in African cohorts occurs at a younger age than in North America and Europe and is more likely to be due to hypertension. Recent studies suggest that iron deficiency anaemia, which is very common in heart failure patients in Africa, and iron deficiency are independently associated with a poor prognosis in heart failure. Preliminary data suggest that iron deficiency in patients with heart failure can be treated with oral iron, with significant beneficial effects on haematological and physiological variables. Cost may prohibit the use of intravenous iron on a large scale in LMICs and optimal regimes to treat iron deficiency in heart failure patients with oral iron therapy remain to be defined.

PMID: 28568509 [PubMed - as supplied by publisher]

Clinical Characteristics and Outcome of Acute Heart Failure in Korea: Results from the Korean Acute Heart Failure Registry (KorAHF).

Fri, 06/02/2017 - 12:45
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Clinical Characteristics and Outcome of Acute Heart Failure in Korea: Results from the Korean Acute Heart Failure Registry (KorAHF).

Korean Circ J. 2017 May;47(3):341-353

Authors: Lee SE, Lee HY, Cho HJ, Choe WS, Kim H, Choi JO, Jeon ES, Kim MS, Kim JJ, Hwang KK, Chae SC, Baek SH, Kang SM, Choi DJ, Yoo BS, Kim KH, Park HY, Cho MC, Oh BH

Abstract
BACKGROUND AND OBJECTIVES: The burden of heart failure has increased in Korea. This registry aims to evaluate demographics, clinical characteristics, management, and long-term outcomes in patients hospitalized for acute heart failure (AHF).
SUBJECTS AND METHODS: We prospectively enrolled a total of 5625 consecutive subjects hospitalized for AHF in one of 10 tertiary university hospitals from March 2011 to February 2014. Descriptive statistics were used to determine the baseline characteristics of the study population and to compare them with those from other registries.
RESULTS: The mean age was 68.5±14.5 years, 53.2% were male, and 52.2% had de novo heart failure. The mean systolic and diastolic blood pressures were 131.2±30.3 mmHg and 78.6±18.8 mmHg at admission, respectively. The left ventricular ejection fraction was ≤40% in 60.5% of patients. Ischemia was the most frequent etiology (37.6%) and aggravating factor (26.3%). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and aldosterone antagonists were prescribed in 68.8%, 52.2%, and 46.6% of the patients at discharge, respectively. Compared with the previous registry performed in Korea a decade ago, extracorporeal membrane oxygenation (ECMO) and heart transplantation have been performed more frequently (ECMO 0.8% vs. 2.8%, heart transplantation 0.3% vs. 1.2%), and in-hospital mortality decreased from 7.6% to 4.8%. However, the total cost of hospital care increased by 40%, and one-year follow-up mortality remained high.
CONCLUSION: While the quality of acute clinical care and AHF-related outcomes have improved over the last decade, the long-term prognosis of heart failure is still poor in Korea. Therefore, additional research is needed to improve long-term outcomes and implement cost-effective care.

PMID: 28567084 [PubMed - in process]

Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis.

Fri, 06/02/2017 - 12:45
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Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis.

J Immunol. 2017 May 31;:

Authors: Amarsaikhan N, Sands EM, Shah A, Abdolrasouli A, Reed A, Slaven JE, Armstrong-James D, Templeton SP

Abstract
The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall β-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A. fumigatus induced by caspofungin that was associated with airway eosinophil recruitment in neutropenic mice with invasive pulmonary aspergillosis (IA). More importantly, caspofungin treatment of mice with IA resulted in a pattern of increased fungal burden and severity of disease that was reversed in eosinophil-deficient mice. Additionally, the eosinophil granule proteins major basic protein and eosinophil peroxidase were more frequently detected in the bronchoalveolar lavage fluid of lung transplant patients diagnosed with IA that received caspofungin therapy when compared with azole-treated patients. Eosinophil recruitment and inhibition of fungal clearance in caspofungin-treated mice with IA required RAG1 expression and γδ T cells. These results identify an eosinophil-mediated mechanism for paradoxical caspofungin activity and support the future investigation of the potential of eosinophil or fungal chitin-targeted inhibition in the treatment of IA.

PMID: 28566368 [PubMed - as supplied by publisher]

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study.

Fri, 06/02/2017 - 12:45
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Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study.

Lancet Diabetes Endocrinol. 2017 May 26;:

Authors: Zewinger S, Kleber ME, Tragante V, McCubrey RO, Schmidt AF, Direk K, Laufs U, Werner C, Koenig W, Rothenbacher D, Mons U, Breitling LP, Brenner H, Jennings RT, Petrakis I, Triem S, Klug M, Filips A, Blankenberg S, Waldeyer C, Sinning C, Schnabel RB, Lackner KJ, Vlachopoulou E, Nygård O, Svingen GFT, Pedersen ER, Tell GS, Sinisalo J, Nieminen MS, Laaksonen R, Trompet S, Smit RAJ, Sattar N, Jukema JW, Groesdonk HV, Delgado G, Stojakovic T, Pilbrow AP, Cameron VA, Richards AM, Doughty RN, Gong Y, Cooper-DeHoff R, Johnson J, Scholz M, Beutner F, Thiery J, Smith JG, Vilmundarson RO, McPherson R, Stewart AFR, Cresci S, Lenzini PA, Spertus JA, Olivieri O, Girelli D, Martinelli NI, Leiherer A, Saely CH, Drexel H, Mündlein A, Braund PS, Nelson CP, Samani NJ, Kofink D, Hoefer IE, Pasterkamp G, Quyyumi AA, Ko YA, Hartiala JA, Allayee H, Tang WHW, Hazen SL, Eriksson N, Held C, Hagström E, Wallentin L, Åkerblom A, Siegbahn A, Karp I, Labos C, Pilote L, Engert JC, Brophy JM, Thanassoulis G, Bogaty P, Szczeklik W, Kaczor M, Sanak M, Virani SS, Ballantyne CM, Lee VV, Boerwinkle E, Holmes MV, Horne BD, Hingorani A, Asselbergs FW, Patel RS, GENIUS-CHD consortium, Krämer BK, Scharnagl H, Fliser D, März W, Speer T

Abstract
BACKGROUND: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.
METHODS: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.
FINDINGS: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies.
INTERPRETATION: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.
FUNDING: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.

PMID: 28566218 [PubMed - as supplied by publisher]

[Deceased donation in renal transplantation].

Fri, 06/02/2017 - 12:45
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[Deceased donation in renal transplantation].

Prog Urol. 2016 Nov;26(15):909-939

Authors: Thuret R, Kleinclauss F, Terrier N, Timsit MO

Abstract
OBJECTIVES: To review epidemiologic data's and medical results of deceased donation in renal transplantation.
MATERIAL AND METHODS: Relevant publications were identified through Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) database using the following keywords, alone or in association, "brain death; cardiac arrest; deceased donation; organ procurement; transplantation". Articles were selected according to methods, language of publication and relevance. The reference lists were used to identify additional historical studies of interest. Both prospective and retrospective series, in French and English, as well as review articles and recommendations were selected. In addition, French national transplant and health agencies (http://www.agence-biomedecine.fr and http://www.has-sante.fr) databases were screened using identical keywords. A total of 2498 articles, 8 official reports and 17 newspaper articles were identified; after careful selection 157 publications were eligible for our review.
RESULTS: Deceased donation may involve either brain death or non-heartbeating donors (NHBD). Organ shortage led to the procurement of organs from expanded-criteria donors, with an increased age at donation and extended vascular disease, leading to inferior results after transplantation and underlining the need for careful donor management during brain death or cardiac arrest. Evolution of French legislation covering bioethics allowed procurement from Maastricht categories II and recently III non-heartbeating donors.
CONCLUSION: The increase of organ shortage emphasizes the need for a rigorous surgical technique during procurement to avoid loss of transplants. A history or current neoplasm in deceased-donors, requires attention to increase the pool of organs without putting the recipients at risk for cancer transmission. French NHBD program, especially from Maastricht category III, may stand for a potential source of valuable organs.

PMID: 27727092 [PubMed - indexed for MEDLINE]

Biodistribution and Clearance of Human Mesenchymal Stem Cells by Quantitative Three-Dimensional Cryo-Imaging After Intravenous Infusion in a Rat Lung Injury Model.

Fri, 06/02/2017 - 12:45
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Biodistribution and Clearance of Human Mesenchymal Stem Cells by Quantitative Three-Dimensional Cryo-Imaging After Intravenous Infusion in a Rat Lung Injury Model.

Stem Cells Transl Med. 2016 12;5(12):1668-1675

Authors: Schmuck EG, Koch JM, Centanni JM, Hacker TA, Braun RK, Eldridge M, Hei DJ, Hematti P, Raval AN

Abstract
: Cell tracking is a critical component of the safety and efficacy evaluation of therapeutic cell products. To date, cell-tracking modalities have been hampered by poor resolution, low sensitivity, and inability to track cells beyond the shortterm. Three-dimensional (3D) cryo-imaging coregisters fluorescent and bright-field microcopy images and allows for single-cell quantification within a 3D organ volume. We hypothesized that 3D cryo-imaging could be used to measure cell biodistribution and clearance after intravenous infusion in a rat lung injury model compared with normal rats. A bleomycin lung injury model was established in Sprague-Dawley rats (n = 12). Human mesenchymal stem cells (hMSCs) labeled with QTracker655 were infused via jugular vein. After 2, 4, or 8 days, a second dose of hMSCs labeled with QTracker605 was infused, and animals were euthanized after 60, 120, or 240 minutes. Lungs, liver, spleen, heart, kidney, testis, and intestine were cryopreserved, followed by 3D cryo-imaging of each organ. At 60 minutes, 82% ± 9.7% of cells were detected; detection decreased to 60% ± 17% and 66% ± 22% at 120 and 240 minutes, respectively. At day 2, 0.06% of cells were detected, and this level remained constant at days 4 and 8 postinfusion. At 60, 120, and 240 minutes, 99.7% of detected cells were found in the liver, lungs, and spleen, with cells primarily retained in the liver. This is the first study using 3D cryo-imaging to track hMSCs in a rat lung injury model. hMSCs were retained primarily in the liver, with fewer detected in lungs and spleen.
SIGNIFICANCE: Effective bench-to-bedside clinical translation of cellular therapies requires careful understanding of cell fate through tracking. Tracking cells is important to measure cell retention so that delivery methods and cell dose can be optimized and so that biodistribution and clearance can be defined to better understand potential off-target toxicity and redosing strategies. This article demonstrates, for the first time, the use of three-dimensional cryo-imaging for single-cell quantitative tracking of intravenous infused clinical-grade mesenchymal stem cells in a clinically relevant model of lung injury. The important information learned in this study will help guide future clinical and translational stem cell therapies for lung injuries.

PMID: 27460855 [PubMed - indexed for MEDLINE]

Left ventricular assist device exchange: the Toronto General Hospital experience.

Thu, 06/01/2017 - 12:45

Left ventricular assist device exchange: the Toronto General Hospital experience.

Can J Surg. 2017 Jun 01;60(4):11316

Authors: Tsubota H, Ribeiro RVP, Billia F, Cusimano RJ, Yau TM, Badiwala MV, Stansfield WE, Rao V

Abstract
BACKGROUND: As support times for left ventricular assist devices (LVADs) become longer, several complications requiring device exchange may occur. To our knowledge, this is the first Canadian report regarding implantable LVAD exchange.
METHODS: We retrospectively reviewed the cases of consecutive, unique patients implanted with an LVAD between June 2006 and October 2015 at Toronto General Hospital.
RESULTS: In total, 122 patients were impanted with an LVAD during the study period. Eight patients required LVAD exchange, and 1 patient had 2 replacements (9 of 122, 7.3%). There were 7 HeartMate II (HMII), 1 HVAD and 1 DuraHeart pumps exchanged. Two of these exchanges occurred early at the time of initial implant, whereas 7 occurred late (range 8-623 days). Six exchanges were made owing to pump thrombosis. Of the 3 exchanges made for other causes, 1 HMII exchange was owing to a driveline fracture, 1 DuraHeart patient had early inflow obstruction requiring exchange to HMII at the initial implant, and the third had a suspected inflow obstruction with no evidence of thrombosis at the time of the procedure. The mean support time before exchange was 225 days, and time from exchange to transplant, death or ongoing support was 245 days. Three patients were successfully bridged to transplant, and at the time of data collection 2 were supported awaiting transplant. Three patients died after a mean duration of 394.3 days (range 78-673 days) of support postreplacement. Four cases were successfully performed using a subcostal approach.
CONCLUSION: Pump thrombosis is the most common cause for LVAD exchange, which can be performed with acceptable morbidity and mortality. The subcostal approach may be the preferred procedure for an HMII exchange when indicated.

PMID: 28562236 [PubMed - as supplied by publisher]

The promising therapeutic agents for heart diseases: Histone Methyltransferase inhibitors.

Thu, 06/01/2017 - 12:45

The promising therapeutic agents for heart diseases: Histone Methyltransferase inhibitors.

Int J Cardiol. 2017 Jul 15;239:6

Authors: Jiang DS, Fang Z, Zhu XH, Wei X

PMID: 28560987 [PubMed - in process]

Outcomes of pulmonary arterial hypertension therapy in Australia: is monotherapy adequate?

Thu, 06/01/2017 - 12:45
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Outcomes of pulmonary arterial hypertension therapy in Australia: is monotherapy adequate?

Intern Med J. 2017 May 31;:

Authors: Moonen A, Garsia R, Youssef P, Torzillo P, Corte T, Boehm C, Cordina R, Celermajer D, Lau E

Abstract
BACKGROUND: In Australia, government-subsidised treatment of pulmonary arterial hypertension (PAH) is limited to monotherapy. Recent international guidelines advocate that initial combination therapy be considered for all symptomatic PAH patients. We sought to characterise "real-life" outcomes in PAH patients initiated on monotherapy.
METHODS: We performed a retrospective analysis of 100 consecutive PAH patients at a single centre, who were commenced on monotherapy for PAH between 2004 and 2015. The composite clinical endpoint of 'treatment failure' was prospectively defined as (1) >15% fall in 6-minute walk distance on follow-up, (2) physician judgement of inadequate treatment response, (3) adverse drug effect requiring cessation, (4) death or transplantation.
RESULTS: At initiation of therapy, mean age was 54 ± 18 years and underlying diagnoses included idiopathic (36%), connective tissue disease associated (37%), and congenital heart disease associated-PAH (25%). Baseline 6MWD was 360 ± 140 m and 75% were in either New York Heart Association functional class III or IV. Over median follow-up of 38 months (IQR 20-67), 62% of subjects met criteria for a clinical failure event. Median time to monotherapy failure was 24 months (95% CI 14-34) with death or transplantation being the most common clinical failure event. Estimated 1-, 3- and 5-yr survivals from time of treatment initiation were 92%, 75% and 66%.
CONCLUSION: The majority of patients failed initial monotherapy therapy within two years of treatment initiation. Broader access to approved PAH agents is needed to enable combination therapy in line with evidence based international guidelines.

PMID: 28560817 [PubMed - as supplied by publisher]

Consecutive Sessions of Rescue Balloon Atrial Septostomy for an Idiopathic Pulmonary Arterial Hypertension Patient with Refractory Right Heart Failure - Usefulness of Intracardiac Echocardiography Guidance.

Thu, 06/01/2017 - 12:45
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Consecutive Sessions of Rescue Balloon Atrial Septostomy for an Idiopathic Pulmonary Arterial Hypertension Patient with Refractory Right Heart Failure - Usefulness of Intracardiac Echocardiography Guidance.

Acta Cardiol Sin. 2017 May;33(3):310-314

Authors: Chen YW, Pan HC, Wang KY, Liang KW

Abstract
For idiopathic pulmonary artery hypertension (PAH) patients with end-stage right heart failure who received maximal medical therapy, balloon atrial septostomy (BAS) is recommended by most guidelines as a palliative therapy or a bridging treatment before lung transplantation. In this report, we described a 32-year-old woman with idiopathic PAH, who received maximal PAH-specific medical treatment, including intravenous prostacyclin, but still suffered from refractory right heart failure. The markedly enlarged right atrium (RA), high mean RA pressure of 23 mmHg, low systemic arterial oxygen saturation of 86% and concomitant pancytopenia all increased the patient's risk for BAS. We used intracardiac echocardiography (ICE) guidance to facilitate trans-septal puncture, and performed graded BAS four times within 7 months to stabilize the patient. Our case showed that with dedicated PAH treatment, an experienced structural heart interventionist and ICE guidance, BAS could be done safely even in a patient in unfavorable clinical and hemodynamic condition.

PMID: 28559663 [PubMed - in process]

Recommendations for the Use of Mechanical Circulatory Support: Ambulatory and Community Patient Care: A Scientific Statement From the American Heart Association.

Thu, 06/01/2017 - 12:45
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Recommendations for the Use of Mechanical Circulatory Support: Ambulatory and Community Patient Care: A Scientific Statement From the American Heart Association.

Circulation. 2017 May 30;:

Authors: Cook JL, Colvin M, Francis GS, Grady KL, Hoffman TM, Jessup M, John R, Kiernan MS, Mitchell JE, Pagani FD, Petty M, Ravichandran P, Rogers JG, Semigran MJ, Toole JM, American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; and Council on Cardiovascular Surgery and Anesthesia

PMID: 28559233 [PubMed - as supplied by publisher]

Targeting the pathway of GSK-3β/nerve growth factor to attenuate post-infarction arrhythmias by preconditioned adipose-derived stem cells.

Thu, 06/01/2017 - 12:45
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Targeting the pathway of GSK-3β/nerve growth factor to attenuate post-infarction arrhythmias by preconditioned adipose-derived stem cells.

J Mol Cell Cardiol. 2017 Mar;104:17-30

Authors: Lee TM, Harn HJ, Chiou TW, Chuang MH, Chen CH, Lin PC, Lin SZ

Abstract
Adipose-derived stem cell (ADSC) transplantation is a promising new therapy to improve cardiac function after myocardial infarction. However, its low efficacy of transdifferentiation hampers its usefulness. Glycogen synthase kinase-3β (GSK-3β) signal has been shown to play a role in preconditioning-induced cardioprotection. We assessed whether n-butylidenephthalide (BP) primed ADSCs can attenuate arrhythmias by a GSK-3β-dependent pathway after myocardial infarction. Male Wistar rats after coronary ligation was randomly allocated to receive intramyocardial injection of vehicle, ADSCs, BP-preconditioned ADSCs, (BP+lithium)-preconditioned ADSCs, (BP+SB216763)-preconditioned ADSCs, and (BP+LY294002)-preconditioned ADSCs. ADSCs were primed for 16h before implantation. After 4weeks of implantation, ADSCs were retained in myocardium, reduced fibrosis and improved cardiac function. Sympathetic hyperinnervation was blunted after administering ADSCs, assessed by immunofluorescent analysis, and Western blotting and real-time quantitative RT-PCR of nerve growth factor. Arrhythmic scores during programmed stimulation in the ADSC-treated infarcted rats were significantly lower than vehicle. BP-preconditioned ADSCs had superior cardioprotection, greater ADSC engraftment and transdifferentiation, and antiarrhythmic effects compared with ADSCs alone. Simultaneously, BP increased the levels of phospho-Akt and down-regulated GSK-3β activity. The effects of BP against sympathetic hyperinnervation were blocked by LY294002, a PI3K inhibitor. Addition of either lithium or SB216763 did not have additional effects compared with BP alone. Compared with ADSC alone, BP-primed ADSC implantation improved stem cell engraftment and attenuated sympathetic hyperinnervation and arrhythmias through a PI3K/Akt/GSK-3β-dependent pathway, suggesting that a synergic action was achieved between BP pretreatment and ADSCs.

PMID: 28130118 [PubMed - indexed for MEDLINE]

Anaortic off-pump bilateral internal mammary grafting in severe left ventricular dysfunction - Case report.

Thu, 06/01/2017 - 12:45
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Anaortic off-pump bilateral internal mammary grafting in severe left ventricular dysfunction - Case report.

Indian Heart J. 2016 Sep;68 Suppl 2:S54-S56

Authors: Saha KK, Goel S, Kumar A, Saha KK

Abstract
A 64 years old male diabetic patient with ejection fraction of 16% and renal dysfunction underwent off-pump CABG using both in situ internal mammary artery grafts. Left internal mammary artery was used to bypass left anterior descending artery and right internal mammary artery was used as composite graft. Patient had uneventful recovery and left ventricular ejection fraction improved to 34% within 8 months after surgery. In presence of left ventricular dysfunction, both internal thoracic artery grafting should be preferred for better patency rate and flow reserve. This is the first ever case report of anaortic off-pump bilateral internal thoracic artery grafting in a patient with left ventricular ejection fraction less than 20%.

PMID: 27751328 [PubMed - indexed for MEDLINE]

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