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Alloplastic bypass material below the knee: actual rationale.

Sat, 04/20/2013 - 10:34
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Alloplastic bypass material below the knee: actual rationale.

J Cardiovasc Surg (Torino). 2013 Feb;54(1 Suppl 1):159-66

Authors: Debus ES, Larena-Avellaneda A, Heimlich F, Goertz J, Fein M

Abstract
AIM: The greater saphenous vein is considered as material of first choice for a below-knee bypass. A high number of below knee synthetic, polytetrafluoroethylene or knitted polyester, bypass grafts in the institution of the senior author formed the basis to analyze factors for outcome of below-knee synthetic grafts.
METHODS: A total of 533 patients (327 men, 206 women; age: 71.2 ± 10.3 years), who had their first below knee bypass, were followed-up for up-to 9 (4.1 ± 2.6) years. Survival, primary and secondary patency, and limb salvage were compared between vein bypasses and synthetic grafts by Kaplan Meier analysis. Within the group of 377 patients with synthetic grafts comorbidities, previous interventions, indications, graft diameter, and technical aspects were related to outcome including univariate (log-rank) and multivariate (Cox Proportional Hazard Ratio) statistics.
RESULTS: The greater saphenous vein was superior to synthetic graft in primary and secondary patency as well as limb salvage (5 year limb salvage 73.3% vs. 56.7%, P=0.001). In patients with a synthetic bypass, relevant preoperative factors for higher patency rates were hypertension, coronary heart disease and no previous endovascular intervention. Patency and limb salvage was significantly improved for anastomoses not to a single crural vessel. Adding a St. Mary's Boot as cuff technique did not improve the results. In multivariate analysis, independent factors for higher primary patency were no previous endovascular intervention, low severity of peripheral arterial occlusive disease, coronary heart disease and age above 65. Additionally, femoropopliteal and tibioperoneal anastomoses were related to better limb salvage.
CONCLUSION: The greater saphenous vein reveals the best results for below-knee bypass grafts. However, if a vein is not available, synthetic grafts appear to be an valuable alternative especially in patients with no previous radiologic intervention, coronary heart disease, and age over 65.

PMID: 23443601 [PubMed - indexed for MEDLINE]

Effect of umbilical cord milking in term and near term infants: randomized control trial.

Sat, 04/20/2013 - 10:34
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Effect of umbilical cord milking in term and near term infants: randomized control trial.

Am J Obstet Gynecol. 2013 Feb;208(2):120.e1-6

Authors: Upadhyay A, Gothwal S, Parihar R, Garg A, Gupta A, Chawla D, Gulati IK

Abstract
OBJECTIVE: The objective of the study was to investigate the effect of umbilical cord milking as compared with early cord clamping on hematological parameters at 6 weeks of age among term and near term neonates.
STUDY DESIGN: This was a randomized control trial. Eligible neonates (>35 weeks' gestation) were randomized in intervention and control groups (100 each). Neonates of both groups got early cord clamping (within 30 seconds). The cord of the experimental group was milked after cutting and clamping at 25 cm from the umbilicus, whereas in control group cord was clamped near (2-3 cm) the umbilicus and not milked. Both groups got similar routine care. Unpaired Student t and Fisher exact tests were used for statistical analysis.
RESULTS: Baseline characteristics were comparable in the 2 groups. Mean hemoglobin (Hgb) (11.9 [1.5] g/dL and mean serum ferritin 355.9 [182.6] μg/L) were significantly higher in the intervention group as compared with the control group (10.8 [0.9] g/dL and 177.5 [135.8] μg/L), respectively, at 6 weeks of age. The mean Hgb and hematocrit at 12 hours and 48 hours was significantly higher in intervention group (P = .0001). The mean blood pressure at 30 minutes, 12 hours, and 48 hours after birth was significantly higher but within normal range. No significant difference was observed in the heart rate, respiratory rate, polycythemia, serum bilirubin, and need of phototherapy in the 2 groups.
CONCLUSION: Umbilical cord milking is a safe procedure and it improved Hgb and iron status at 6 weeks of life among term and near term neonates.

PMID: 23123382 [PubMed - indexed for MEDLINE]

Activation of aryl hydrocarbon receptor prolongs survival of fully mismatched cardiac allografts.

Thu, 04/18/2013 - 10:50

Activation of aryl hydrocarbon receptor prolongs survival of fully mismatched cardiac allografts.

J Huazhong Univ Sci Technolog Med Sci. 2013 Apr;33(2):199-204

Authors: Cai LJ, Yu DW, Gao Y, Yang C, Zhou HM, Chen ZH

Abstract
Recent data suggest that activation of aryl hydrocarbon receptor (AhR) by its high-affinity ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in expansion of regulatory T (Treg) cells and suppresses the development of autoimmune and allergic diseases in several models. Treg cells have been increasingly documented to suppress allograft rejection and even to establish stable long-term graft acceptance. However, the involvement of TCDD in the regulation of solid organ transplantation rejection is largely unknown. Here, we examined whether activation of AhR with TCDD altered cardiac allograft rejection in an allogeneic heart transplant model. Recipient C57BL/6 (H-2b) mice were administrated with a single intraperitoneal injection of TCDD, and the murine cardiac transplant models from BALB/c (H-2d) to C57BL/6 (H-2b) were built 24 h later. The complete cessation of cardiac contractility was defined as the observation endpoint. The effect of TCDD on T-cell proliferation was assessed by mixed lymphocyte reaction (MLR). Histological and immunohistochemical analyses were performed to estimate the severity of rejection. The phenotype and cytokine profile of lymphocytes were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Activation of AhR remarkably prolonged the survival of cardiac allografts to more than 20 days. In vitro, TCDD ugregulated the frequency of CD4+CD25+Foxp3+ Treg cells and suppressed the proliferation of T lymphocytes. In vivo, the prolonged survival time was associated with increased number of Treg cells in allografts and spleens. Furthermore, the secretion of interferon-γ (IFN-γ) and interleukin-17 (IL-17) was reduced to less than 50% of that of the PBS treatment control group by TCDD treatment, whereas IL-10 was elevated to 10-fold of that of the PBS treatment control group. Collectively, our data indicate that activation of AhR with a single dose of TCDD significantly prolonged the survival of fully allogeneic cardiac grafts, and the mechanism underlying this effect might be involved in the induction of Treg cells.

PMID: 23592130 [PubMed - as supplied by publisher]

Monocyte Chemotactic Protein-1 Promotes the Myocardial Homing of Mesenchymal Stem Cells in Dilated Cardiomyopathy.

Thu, 04/18/2013 - 10:50

Monocyte Chemotactic Protein-1 Promotes the Myocardial Homing of Mesenchymal Stem Cells in Dilated Cardiomyopathy.

Int J Mol Sci. 2013;14(4):8164-8178

Authors: Guo J, Zhang H, Xiao J, Wu J, Ye Y, Li Z, Zou Y, Li X

Abstract
Dilated cardiomyopathy (DCM) is the most common form of non-ischemic cardiomyopathy that leads to heart failure. Mesenchymal stem cells (MSCs) are under active investigation currently as a potential therapy for DCM. However, little information is available about the therapeutic potential of intravenous administration of MSCs for DCM. Moreover, how MSCs home to the myocardium in DCM is also unclear. DCM was induced by intraperitoneally administering Doxorubicin and MSCs or vehicles were infused through the internal jugular vein. Cardiac functions including the percentage of fractional shortening, left ventricular diastolic dimension, left ventricular end-diastolic pressure, and left ventricular maximum dp/dt were evaluated by echocardiographic and hemodynamic studies. Fibrosis was determined by Masson's trichrome staining. The mRNA expression levels of monocyte chemotactic protein-1 (MCP-1), stromal cell-derived factor-1 (SDF-1), macrophage inflammatory protein-1α (MIP-1α), and monocyte chemotactic protein-3 (MCP-3) were determined using real time polymerase chain reactions and the protein expression level of MCP-1 was detected with Western blot. The MSCs expression of C-C chemokine receptor type 2 (CCR2), a MCP-1 receptor, was confirmed by Western blot and flow cytometry analysis. The chemotactic effects of MCP-1/CCR2 were checked by assessing the migration in vitro and in vivo. MSCs transplantation improved the cardiac function and decreased the myocardial fibrosis of mice with DCM. MCP-1 was up-regulated in dilated myocardial tissue both at the mRNA and protein level while SDF-1, MIP-1α and MCP-3 remain unchanged. CCR2 was present in MSCs. MCP-1 promoted MSCs migration in vitro while CCR2 inhibition decreased the migration of MCP-1 to the dilated heart. This study provides direct evidences that peripheral intravenous infusion of MSCs can support the functional recovery of DCM. In addition, novel insights into the myocardial homing factor of MSCs in DCM are presented. Modulation of MCP-1/CCR2 signaling system might be a novel therapeutic strategy for DCM.

PMID: 23591836 [PubMed - as supplied by publisher]

Impact of Renal Posttransplantation Amputation on Allograft Outcomes: A Study of United States Renal Data System.

Thu, 04/18/2013 - 10:50

Impact of Renal Posttransplantation Amputation on Allograft Outcomes: A Study of United States Renal Data System.

Transplantation. 2013 Apr 15;

Authors: Brar A, Jindal RM, Sumrani N, John D, Mondal Z, Tedla F, Salifu MO

Abstract
BACKGROUND: The prevalence of renal posttransplantation amputation and its impact on allograft and patient survival have not been widely reported. METHODS: We used an incident cohort of patients who underwent renal transplantation between June 2004 and September 2009. Amputation data were obtained using Medicare institutional claim forms. Baseline demographics and comorbidities, such as peripheral vascular disease (PVD), diabetes, ischemic heart disease, cerebrovascular disease, hypertension, and smoking, were captured. The chi-square and t tests were used for statistical associations. Kaplan-Meier survival curves were plotted for renal allograft and patient survival. Independent associations between patient factors and amputation were examined using multivariable Cox regression analysis. RESULTS: Of the 85,873 renal transplant recipients, 1062 patients had amputation. The prevalence of amputation was higher in those with PVD versus those without PVD at listing (5.6% vs. 1%; P=0.0001). Mean allograft survival was 55.5±0.55 months in patients with amputation versus 60.6±0.06 months in patients without amputation (P=0.0001). All-cause mortality was higher in patients with amputation versus those without amputation (19.9% vs. 7.3%; P=0.0001). Mean allograft survival was 60.97±0.67 months in non-African Americans without amputation versus 55.7±0.65 months in non-African Americans with amputation. Allograft survival was 59.73±0.13 months in African Americans without amputation versus 54.9±1.06 months in African Americans with amputation. In patients with amputation, race did not have any impact. Infectious complications were noted in 39 patients leading to death. CONCLUSIONS: Amputation is associated with decreased allograft and patient survival. Early detection and preventive strategies for PVD may decrease amputation rate and improve survival.

PMID: 23591760 [PubMed - as supplied by publisher]

Sildenafil and Cardioprotection.

Thu, 04/18/2013 - 10:50

Sildenafil and Cardioprotection.

Curr Pharm Des. 2013 Apr 10;

Authors: Kukreja RC

Abstract
The phosphodiesterese-5 (PDE-5) inhibitors, including sildenafil (Viagra™), vardenafil (Levitra™), tadalafil (Cialis™) and avanafil (Stendra™) have been developed for the treatment of erectile dysfunction. Moreover, sildenafil and tadalafil have also been approved for the management of pulmonary arterial hypertension. A number of preclinical studies have shown that PDE-5 inhibitors have powerful protective effect against several clinical scenarios including myocardial ischemia/reperfusion injury, doxorubicin and post-MI, heart failure, cardiac hypertrophy, heart transplantation, Duchenne muscular dystrophy and preconditioning of stem cells. Based on these studies, it appears that sildenafil and other PDE-5 inhibitors hold promise for further development as novel drug therapies in cardioprotection.

PMID: 23590161 [PubMed - as supplied by publisher]

Dose Distribution in the Heart and Cardiac Chambers Following 4-field Radiation Therapy of Breast Cancer: a Retrospective Study.

Wed, 04/17/2013 - 10:19

Dose Distribution in the Heart and Cardiac Chambers Following 4-field Radiation Therapy of Breast Cancer: a Retrospective Study.

Breast Cancer (Auckl). 2013;7:41-9

Authors: Johansen S, Tjessem KH, Fosså K, Bosse G, Danielsen T, Malinen E, Fosså SD

Abstract
PURPOSE: To evaluate cardiac doses in breast cancer patients with stage II/III treated with 4-field radiotherapy based on computed tomography (CT) dose planning.
METHODS AND MATERIALS: Based on archived CT images, whole heart and cardiac chamber radiation doses were analyzed in 216 (111 left-sided and 105 right-sided) mastectomized or lumpectomized breast cancer patients treated at a single institution, the Norwegian Radium Hospital, between 2000-2002. Individual dose volume histograms for the whole heart and for the four cardiac chambers were obtained, and mean, median and maximum doses to these structures were calculated. The dose (Gy) delivered to the 5% of the volume of each cardiac structure (D5%), and the volume percentage of each structure receiving ≥ 25 Gy (V25Gy) were reported. Normal tissue complication probability (NTCP) calculations were used to estimate the risk for ischemic heart disease (IHD).
RESULTS: Cohort-based medians of the whole heart mean dose (Dmean) for left- and right-sided tumors were 3.2 Gy and 1.3 Gy, respectively, with similar ventricular but lower atrial values. The atrial doses did not differ according to laterality of the breast tumor. In 13 patients with left-sided cancer, 5% of the heart volume was exposed to >25 Gy. The NTCP estimates were generelly low, with a maximum of 2.8%.
CONCLUSIONS: During adjuvant CT-based locoregional radiotherapy of women with breast cancer, the cardiac radiation doses are, at the group level, below recommended threshold values (D5% < 25 Gy), though individual patients with left-sided disease may exceed these limits.

PMID: 23589693 [PubMed - in process]

Allogeneic bone marrow-derived mesenchymal stem cells attenuate hepatic ischemia-reperfusion injury by suppressing oxidative stress and inhibiting apoptosis in rats.

Wed, 04/17/2013 - 10:19

Allogeneic bone marrow-derived mesenchymal stem cells attenuate hepatic ischemia-reperfusion injury by suppressing oxidative stress and inhibiting apoptosis in rats.

Int J Mol Med. 2013 Apr 9;

Authors: Jin G, Qiu G, Wu D, Hu Y, Qiao P, Fan C, Gao F

Abstract
Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to attenuate ischemia reperfusion (IR) injury in the heart, brain and kidney. However, their exact roles in the liver remain to be defined. Our objective was to investigate the potential effects of BM-MSCs on a hepatic IR rat model during the first 24 h after reperfusion, a crucial period for hepatic IR damage formation. A rat model of normothermic partial hepatic ischemia was obtained by vascular clamping for 60 min. BM-MSCs were transplanted via portal vein injection. Injury severity, oxidative stress response and apoptosis of liver cells were assessed at 2, 6, 12 and 24 h after reperfusion and cell transplantation was evaluated. At 12 and 24 h after reperfusion, rats transplanted with BM-MSCs had significantly lower serum levels of alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST), fewer damaged liver tissues, higher superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and lower malondialdehyde (MDA) levels compared to rats in the sham transplantation group. At 24 h after reperfusion, IR rats transplanted with BM-MSCs had significantly fewer apoptotic hepatocytes, higher levels of B-cell lymphoma 2 (Bcl-2) protein, and lower levels of Bcl-2-associated X (Bax) and caspase-3 (Casp3) proteins compared to sham transplantation rats. In conclusion, BM-MSCs transplanted via the portal vein partially prevent hepatic IR injury by suppressing oxidative stress and inhibiting apoptosis during the first 24 h after reperfusion.

PMID: 23589072 [PubMed - as supplied by publisher]

Minimally invasive aortic valve replacement with orthotopic liver transplantation: report of a case.

Wed, 04/17/2013 - 10:19

Minimally invasive aortic valve replacement with orthotopic liver transplantation: report of a case.

Surg Today. 2013 Apr 16;

Authors: Harrison JD, Selzman CH, Thiesset HF, Box T, Hutson WR, Lu JK, Campsen J, Sorensen JB, Kim RD

Abstract
Cardiac surgery and liver transplantation (LT) are rarely performed at the same time, because of the potential risks of coupling two such complex surgical procedures [1-3]. This combined surgery is typically reserved for patients with structural heart disease, including multivessel obstructive coronary artery disease and severe valvular disease with heart failure and end-stage liver disease, in whom the untreated organ may decompensate if only one organ is addressed [4]. Combined aortic valve replacement (AVR) and LT is the rarest of such combined surgery, with only ten cases published previously. We present the first reported case of combined minimally invasive AVR and LT and review the literature on similar combined surgery.

PMID: 23589056 [PubMed - as supplied by publisher]

Frequency of Superior Vena Cava Obstruction in Pediatric Heart Transplant Recipients and Its Relation to Previous Superior Cavopulmonary Anastomosis.

Wed, 04/17/2013 - 10:19

Frequency of Superior Vena Cava Obstruction in Pediatric Heart Transplant Recipients and Its Relation to Previous Superior Cavopulmonary Anastomosis.

Am J Cardiol. 2013 Apr 12;

Authors: Aldoss O, Arain NI, Vinocur JM, Menk J, Ameduri RK, Bryant R, Kochilas LK, Gruenstein DH

Abstract
The risk factors for superior vena cava (SVC) obstruction after pediatric orthotopic heart transplantation (OHT) have not been identified. This study tested the hypothesis that pretransplant superior cavopulmonary anastomosis (CPA) predisposes patients to SVC obstruction. A retrospective review of the Pediatric Cardiac Care Consortium registry from 1982 through 2007 was performed. Previous CPA, other cardiac surgeries, gender, age at transplantation, and weight at transplantation were assessed for the risk of developing SVC obstruction. Death, subsequent OHT, or reoperation involving the SVC were treated as competing risks. Of the 894 pediatric OHT patients identified, 3.1% (n = 28) developed SVC obstruction during median follow-up of 1.0 year (range: 0 to 19.5 years). Among patients who developed SVC obstruction, 32% (n = 9) had pretransplant CPA. SVC surgery before OHT was associated with posttransplant development of SVC obstruction (p <0.001) after adjustment for gender, age, and weight at OHT and year of OHT. Patients with previous CPA had increased risk for SVC obstruction compared with patients with no history of previous cardiac surgery (hazard ratio 10.6, 95% confidence interval: 3.5 to 31.7) and to patients with history of non-CPA cardiac surgery (hazard ratio 4.7, 95% confidence interval: 1.8 to 12.5). In conclusion, previous CPA is a significant risk factor for the development of post-heart transplant SVC obstruction.

PMID: 23587279 [PubMed - as supplied by publisher]

Role of baseline echocardiography in the preoperative management of liver transplant candidates.

Wed, 04/17/2013 - 10:19
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Role of baseline echocardiography in the preoperative management of liver transplant candidates.

Am J Cardiol. 2012 Dec 15;110(12):1852-5

Authors: Harinstein ME, Iyer S, Mathier MA, Flaherty JD, Fontes P, Planinsic RM, Edelman K, Katz WE, Lopez-Candales A

Abstract
Liver transplantation (LT) has not traditionally been offered to patients with intracardiac shunts (ICSs) or pulmonary hypertension (PH). There is a paucity of data regarding cardiac structural characteristics in LT candidates. We examined echocardiographic characteristics and their role in managing LT candidates diagnosed with ICS and PH. We identified 502 consecutive patients (318 men, mean age 55 ± 11 years) who underwent LT and had preoperative echocardiogram. Demographics, cardiovascular risk factors, and echocardiographic variables were recorded and data were analyzed for end-stage liver disease diagnosis. ICSs were diagnosed with contrast echocardiography and PH was defined as estimated pulmonary artery systolic pressure >40 mm Hg. Primary end points included short-term (30-day) and long-term (mean 41-month) mortalities and the correlation between pre- and perioperative stroke. In our studied population >50% had >2 cardiovascular risk factors and with increasing frequency ICSs were diagnosed in 16%, PH in 25%, and intrapulmonary shunts in 41% of LT candidates. There was no correlation between short- and long-term mortality and ICS (p = 0.71 and 0.76, respectively) or PH (p = 0.79 and 0.71). Importantly, in those with ICS, no strokes occurred. In conclusion, structural differences exist between various end-stage liver disease diagnoses. ICSs diagnosed by echocardiography are not associated with an increased risk of perioperative stroke or increased mortality. A diagnosis of mild or moderate PH on baseline echocardiogram is not associated with worse outcomes and requires further assessment. Based on these findings, patients should not be excluded from consideration for LT based solely on the presence of an ICS or PH.

PMID: 23021513 [PubMed - indexed for MEDLINE]

A luminance-based heart chip assay for assessing the efficacy of graft preservation solutions in heart transplantation in rats.

Tue, 04/16/2013 - 11:45
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A luminance-based heart chip assay for assessing the efficacy of graft preservation solutions in heart transplantation in rats.

Heart Asia. 2013;5(1):7-14

Authors: Maeda M, Kasahara N, Doi J, Iijima Y, Kikuchi T, Teratani T, Kobayashi E

Abstract
OBJECTIVE: We developed a novel luciferase-based viability assay for assessing the viability of hearts preserved in different solutions. We examined whether this in vitro system could predict heart damage and survival after transplantation in rats.
DESIGN: By our novel system, preserved heart viability evaluation and transplanted heart-graft functional research study.
SETTING: University basic science laboratory.
INTERVENTIONS: Isolated Luciferase-transgenic Lewis (LEW) rat cardiac-tissue-chips were plated on 96-well tissue-culture plates and incubated in preservation solutions at 4°C. Viability was measured as photon intensity by using a bio-imaging system. Heart-grafts preserved in University of Wisconsin (UW), extracellular-trehalose-Kyoto (ETK), Euro-Collins (EC), histidin-tryptophan-ketoglutarat solution (HTK), lactated Ringer's (LR) or normal saline solution were transplanted cervically by using a cuff-technique or into the abdomens of syngeneic wild-type LEW rats by using conventional microsurgical suture techniques.
MAIN OUTCOME MEASURES: Imaging an evaluation of preservation heart-graft and functional analysis.
RESULTS: Cardiac-tissue-chips preserved with UW, HTK or ETK solution gave higher luminance than those preserved with EC, LR or normal saline (p<0.03). After 24 h of preservation of hearts in each solution at 4°C, the beating of the isolated hearts was evaluated. The success rate, evaluation of beating, of cervical heart transplants using UW and ETK solution exceeded 70%, but those using other preservation solutions were lower (UW: 100%, ETK: 75%, EC: 42.86%, HTK: 14.29%, normal saline: 0%). Histological analysis of cervical heart-grafts after 3 h preservation by myeloperoxidase (MPO), zona occludens-1(ZO-1), and caspase-3 immunostaining revealed different degrees of preservation damage in all grafts.
CONCLUSIONS: Our novel assay system is simple and can test multiple solutions. It should therefore be a powerful tool for developing and improving new heart-graft preservation solutions.

PMID: 23585802 [PubMed - as supplied by publisher]

Echocardiography for detection of portopulmonary hypertension in liver transplantation candidates: Analysis of cutoff values.

Tue, 04/16/2013 - 11:45
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Echocardiography for detection of portopulmonary hypertension in liver transplantation candidates: Analysis of cutoff values.

Liver Transpl. 2013 Apr 13;

Authors: Raevens S, Colle I, Reyntjens K, Geerts A, Berrevoet F, Rogiers X, Troisi RI, Van Vlierberghe H, De Pauw M

Abstract
Background Portopulmonary hypertension (POPH), a complication of chronic liver disease, may be a contraindication to liver transplantation because of the elevated risk of peri- and post-transplantation morbidity and mortality. Because POPH is frequently asymptomatic, screening with echocardiography is recommended. The only reliable technique, however, to diagnose POPH is right heart catheterization. The aims of this study were to evaluate the current cutoff value of 30 mmHg estimated systolic pulmonary artery pressure (sPAP) and to determine a better cutoff value. Methods One hundred fifty-two patients had a pre-transplantation echocardiography between January 2005 and December 2010. These echocardiographic results were compared with pulmonary artery pressures measured during pre-transplantation work-up or at the beginning of the transplantation procedure, both by catheterization. Results Using a cutoff value of 30 mmHg, 74 of 152 patients met the criteria for POPH on echocardiography, although the diagnosis was confirmed in only 7 patients during catheterization, which results in a specificity of 54%. More accurate would be using a cutoff value of 38 mmHg, which carries a maximal specificity of 82%, at the same time guaranteeing a sensitivity and negative predictive value of 100%. By incorporating the presence or absence of right ventricular dilatation, the specificity even increases to 93% for this new cutoff value. Conclusions In this study, the prevalence of POPH among liver transplantation candidates was 4,6%. We can advise that liver transplantation candidates with a sPAP more than 38 mmHg should be referred for right heart catheterization. By increasing the cutoff value from 30 mmHg to 38 mmHg, the amount of patients who should undergo an invasive right heart catheterization at evaluation could be safely reduced. Liver Transpl , 2013. © 2013 AASLD.

PMID: 23584902 [PubMed - as supplied by publisher]

Enalapril And Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction in Patients with Malignant Hemopathies. The OVERCOME Trial.

Tue, 04/16/2013 - 11:45
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Enalapril And Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction in Patients with Malignant Hemopathies. The OVERCOME Trial.

J Am Coll Cardiol. 2013 Apr 9;

Authors: Bosch X, Rovira M, Sitges M, Domènech A, Ortiz-Pérez JT, de Caralt TM, Morales-Ruiz M, Perea RJ, Monzó M, Esteve J

Abstract
OBJECTIVES: To evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction (LVSD) in patients with hematological malignancies. BACKGROUND: Current chemotherapy may induce LVSD. Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy. METHODS: In this randomized, controlled study, 90 patients recently diagnosed of acute leukemia (n=36) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation (HSCT; n=54) and without LVSD were randomly assigned to receive enalapril and carvedilol (n=45) or to a control group (n=45). Echocardiographic and cardiac magnetic resonance (CMR) imaging studies were performed before and 6 months after randomization. The primary efficacy endpoint was the absolute change from baseline in LVEF. RESULTS: The mean age of patients was 50±13 yr and 43% were woman. At 6 months, LVEF did not change in the intervention group but significantly decreased in controls, resulting in a -3.1% absolute difference by echocardiography (p=0.035), and -3.4% (p=0.09) in the 59 patients that underwent CMR. The corresponding absolute difference (95% CI) in LVEF was -6.38% (-11.9 to -0.9) in patients with acute leukemia and -1.0% (-4.5 to 2.5) in patients undergoing autologous HSCT (p=0.08 for interaction between treatment effect and disease category). Compared to controls, patients in the intervention group had a lower incidence of the combined event of death or heart failure (6.7% vs. 22%, p=0.036), and of death, heart failure or a final LVEF<45% (6.7% vs. 24.4%, p=0.02). CONCLUSIONS: The combined treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with intensive chemotherapy. The clinical relevance of this strategy should be confirmed in larger future studies.

PMID: 23583763 [PubMed - as supplied by publisher]

Patent Ductus Arteriosus with Eisenmenger Syndrome.

Tue, 04/16/2013 - 11:45
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Patent Ductus Arteriosus with Eisenmenger Syndrome.

Heart Lung Circ. 2013 Apr 11;

Authors: Moustafa S, Patton DJ, Balon Y, Connelly MS, Alvarez N

Abstract
Herein we report a 21 year-old woman with a previously documented patent ductus arteriosus and Eisenmenger physiology. She presented with increasing cyanosis and exercise intolerance which could be explained by a new finding of right to left shunting through an interatrial communication. She was started on Bosentan therapy aiming to reduce the pulmonary pressure with consideration for heart-lung transplantation should any further deterioration occur.

PMID: 23583537 [PubMed - as supplied by publisher]

Pulmonary hypertension is a mild comorbidity in end-stage cystic fibrosis patients.

Tue, 04/16/2013 - 11:45
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Pulmonary hypertension is a mild comorbidity in end-stage cystic fibrosis patients.

J Heart Lung Transplant. 2013 Apr 9;

Authors: Belle-van Meerkerk G, Cramer MJ, Kwakkel-van Erp JM, Nugroho MA, Tahri S, de Valk HW, van de Graaf EA

Abstract
BACKGROUND: This study investigated the prevalence of pulmonary hypertension (PH) in cystic fibrosis (CF) patients awaiting lung transplantation (LTx) and its influence on survival. We also explored the feasibility of using echocardiography as a first assessment for diagnosing PH. METHODS: The study included 93 CF patients (46 women [50%]) evaluated for LTx between 2001 and 2010. Median age was 29 years. PH was defined as a mean pulmonary artery pressure (mPAP) measured by right heart catheterization (mPAPcath) of ≥ 25mm Hg with a wedge pressure of ≤ 15mm Hg. Echocardiographic results were divided into 3 categories based on current guidelines as "unlikely," "possible," or "likely" to have PH. RESULTS: In 23 patients (25%) the mPAPcath was between 25 and 35mm Hg, and 1 (1%) had severe PH (mPAPcath of ≥ 35mm Hg). PH did not influence survival after enlistment (p = 0.7) and after LTx (p = 0.8). For 62 patients (67%), the sPAPecho could be measured, and PH was unlikely in 24 (39%). In another 19 patients (20%), PH was unlikely based on the absence of tricuspid regurgitation. The negative-predictive value (NPV) of measuring PH by echocardiography was 88% in whom PH was estimated to be unlikely (n = 43); whereas in 24 patients with a measurable low sPAPecho, the NPV was 96%. CONCLUSIONS: PH exists in 26% of end-stage CF patients and has no effect on survival on the waiting list for LTx or after LTx. Echocardiography might be used as the first tool to rule out PH, showing a NPV of 88%.

PMID: 23582476 [PubMed - as supplied by publisher]

Regulation of connective tissue growth factor gene expression and fibrosis in human heart failure.

Tue, 04/16/2013 - 11:45
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Regulation of connective tissue growth factor gene expression and fibrosis in human heart failure.

J Card Fail. 2013 Apr;19(4):283-94

Authors: Koshman YE, Patel N, Chu M, Iyengar R, Kim T, Ersahin C, Lewis W, Heroux A, Samarel AM

Abstract
BACKGROUND: Heart failure (HF) is associated with excessive extracellular matrix (ECM) deposition and abnormal ECM degradation leading to cardiac fibrosis. Connective tissue growth factor (CTGF) modulates ECM production during inflammatory tissue injury, but available data on CTGF gene expression in failing human heart and its response to mechanical unloading are limited.
METHODS AND RESULTS: Left ventricle (LV) tissue from patients undergoing cardiac transplantation for ischemic (ICM; n = 20) and dilated (DCM; n = 20) cardiomyopathies and from nonfailing (NF; n = 20) donor hearts were examined. Paired samples (n = 15) from patients undergoing LV assist device (LVAD) implantation as "bridge to transplant" (34-1,145 days) also were analyzed. There was more interstitial fibrosis in both ICM and DCM compared with NF hearts. Hydroxyproline concentration was also significantly increased in DCM compared with NF samples. The expression of CTGF, transforming growth factor (TGF) β1, collagen (COL) 1-α1, COL3-α1, matrix metalloproteinase (MMP) 2, and MMP9 mRNA in ICM and DCM were also significantly elevated compared with NF samples. Although TGF-β1, CTGF, COL1-α1, and COL3-α1 mRNA levels were reduced by unloading, there was only a modest reduction in tissue fibrosis and no difference in protein-bound hydroxyproline concentration between pre- and post-LVAD tissue samples. The persistent fibrosis may be related to a concomitant reduction in MMP9 mRNA and protein levels following unloading.
CONCLUSIONS: CTGF may be a key regulator of fibrosis during maladaptive remodeling and progression to HF. Although mechanical unloading normalizes most genotypic and functional abnormalities, its effect on ECM remodeling during HF is incomplete.

PMID: 23582094 [PubMed - in process]

Dietary Habits are Related to Outcomes in Patients With Advanced Heart Failure Awaiting Heart Transplantation.

Tue, 04/16/2013 - 11:45
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Dietary Habits are Related to Outcomes in Patients With Advanced Heart Failure Awaiting Heart Transplantation.

J Card Fail. 2013 Apr;19(4):240-50

Authors: Spaderna H, Zahn D, Pretsch J, Connor SL, Zittermann A, Schulze Schleithoff S, Bramstedt KA, Smits JM, Weidner G

Abstract
BACKGROUND: Empirical evidence supporting the benefits of dietary recommendations for patients with advanced heart failure is scarce. We prospectively evaluated the relation of dietary habits to pre-transplant clinical outcomes in the multisite observational Waiting for a New Heart Study.
METHODS AND RESULTS: A total of 318 heart transplant candidates (82% male, age 53 ± 11 years) completed a Food Frequency Questionnaire (foods high in salt, saturated fats, poly-/monounsaturated fats [PUFA+MUFA], fruit/vegetables/legumes, and fluid intake) at time of waitlisting. Cox proportional hazard models controlling for heart failure severity (eg, Heart Failure Survival Score, creatinine) estimated cause-specific hazard ratios (HRs) associated with each dietary habit individually, and with all dietary habits entered simultaneously. During follow-up (median 338 days, range 13-1,394), 54 patients died, 151 received transplants (110 in high-urgency status, 41 electively), and 45 became delisted (15 deteriorated, 30 improved). Two robust findings emerged: Frequent intake of salty foods, which correlated positively with saturated fat and fluid intake, was associated with transplantation in high-urgency status (HR 2.90, 95% confidence interval [CI] 1.55-5.42); and frequent intake of foods rich in PUFA+MUFA reduced the risk for death/deterioration (HR 0.49, 95% CI 0.26-0.92).
CONCLUSIONS: These results support the importance of dietary habits for the prognosis of patients listed for heart transplantation, independently from heart failure severity.

PMID: 23582090 [PubMed - in process]

Protein carbamylation in chronic systolic heart failure: relationship with renal impairment and adverse long-term outcomes.

Tue, 04/16/2013 - 11:45
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Protein carbamylation in chronic systolic heart failure: relationship with renal impairment and adverse long-term outcomes.

J Card Fail. 2013 Apr;19(4):219-24

Authors: Tang WH, Shrestha K, Wang Z, Borowski AG, Troughton RW, Klein AL, Hazen SL

Abstract
BACKGROUND: Protein carbamylation, a posttranslational modification promoted during uremia and catalyzed by myeloperoxidase (MPO) at sites of inflammation, is linked to altered protein structure, vascular dysfunction, and poor prognosis. We examine the relationship between plasma protein-bound homocitrulline (PBHCit) levels, a marker of protein lysine residue carbamylation, with cardiorenal function and long-term outcomes in chronic systolic heart failure (HF).
METHODS AND RESULTS: In 115 patients with chronic systolic HF (left ventricular ejection fraction ≤35%), we measured plasma PBHCit by quantitative mass spectrometry and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse long-term events (death, cardiac transplantation) were tracked for 5 years. In our study cohort, the median PBHCit level was 87 (interquartile range 59-128) μmol/mol lysine. Higher plasma PBHcit levels were associated with poorer renal function (estimated glomerular filtration rate [eGFR]: Spearman r = -0.37; P < .001), cystatin C (r = 0.31; P = .001), and elevated plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (r = 0.26; P = .006), but not with markers of systemic inflammation or oxidant stress (high-sensitivity C-reactive protein and myeloperoxidase [MPO]: P > .10 for each). Furthermore, elevated plasma PBHCit levels were not related to indices of cardiac structure or function (P > .10 for all examined) except modestly with increased right atrial volume index (r = 0.31; P = .002). PBHCit levels predicted adverse long-term events (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.3-2.6; P < .001), including after adjustment for age, eGFR, MPO, and NT-proBNP (HR 1.9, 95% CI 1.2-3.1; P = .006).
CONCLUSIONS: In chronic systolic HF, protein carbamylation is associated with poorer renal but not cardiac function, and portends poorer long-term adverse clinical outcomes even when adjusted for cardiorenal indices of adverse prognosis.

PMID: 23582087 [PubMed - in process]

ECLS for children with late (post-discharge) rejection after heart transplantation.

Tue, 04/16/2013 - 11:45
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ECLS for children with late (post-discharge) rejection after heart transplantation.

Pediatr Transplant. 2013 Apr 14;

Authors: Lammers AE, Burch M, Brown KL, Hoschtitzky JA, Lunnon-Wood T, Wray J, van Doorn C, Goldman AP, Hoskote A

Abstract
Rejection with acute hemodynamic compromise after OHT is rare in children, and is associated with poor survival. We retrospectively reviewed the management, course and outcome of recipients with late (following initial hospital discharge) rejection with acute hemodynamic compromise who were supported on ECLS. Of 197 consecutive children undergoing OHT (84 male; mean [SD] age 8.3 [5.7] [range 0.1-18.8 yr]) between 2/2002 and 10/2012, 187 children survived and were discharged from hospital. Mean (SD) follow-up was 5.0 (3.1) (range 0.1-10.6) yr. During follow-up, seven presented with severe hemodynamic compromise after transplantation (of whom one patient had been transplanted elsewhere). All seven children, who presented in hemodynamic collapse with poor cardiac function refractory to inotropic support, were placed on ECLS-two following in-hospital cardiac arrest. The median duration of ECLS was 6 (range 5-15) days. All survived to decannulation, with one death from overwhelming sepsis 20 days after presentation. The median (range) duration (in days) of inotropic requirement post ECLS was 11 (5-27), the median ventilation time was 8 (7-30), median ICU length of stay was 14 (10-54), and median hospitalization was 24 (19-118). In all, ventricular function normalized (FS >28%) within 10 (7-22) days. There was significant short-term morbidity; however, over a median follow-up of 5.9 (range 0.7-9.2) yr, all survivors have good functional status with no significant apparent neurological sequelae. ECLS thus appears to be a good rescue therapy for children with severe acute rejection post OHT, refractory to conventional treatment, leading to good medium-term outcome.

PMID: 23581792 [PubMed - as supplied by publisher]

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