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An Alternative Strategy for Bridge-to-Transplant/Recovery in Small Children with Dilated Cardiomyopathy.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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An Alternative Strategy for Bridge-to-Transplant/Recovery in Small Children with Dilated Cardiomyopathy.

Pediatr Cardiol. 2017 Mar 29;:

Authors: Mets G, Panzer J, De Wolf D, Bové T

Abstract
Dilated cardiomyopathy in children still has a poor prognosis with high rates of mortality and cardiac transplantation (resp. around 20 and 25%). Awaiting transplantation or possible recovery, these pediatric patients are mechanically supported with extracorporeal membrane oxygenation or a paracorporeal ventricular assist device, both resulting in higher survival rates but also entailing considerable risks of infection, thrombosis, or bleeding. A new indication for an old technique, i.e., pulmonary artery banding, presents itself as an interesting alternative to mechanical circulatory support in selected infants and small children with dilated LV cardiomyopathy and preserved RV function. Here we present a brief review of literature and report on two patients in whom PAB has been successfully implemented as either bridge-to-recovery or bridge-to-transplant.

PMID: 28357450 [PubMed - as supplied by publisher]

Categorías: Trasplante cardíaco

Left Ventricular Dysfunction Switches Mesenchymal Stromal Cells Toward an Inflammatory Phenotype and Impairs Their Reparative Properties via Toll-like Receptor-4.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Left Ventricular Dysfunction Switches Mesenchymal Stromal Cells Toward an Inflammatory Phenotype and Impairs Their Reparative Properties via Toll-like Receptor-4.

Circulation. 2017 Mar 29;:

Authors: Naftali-Shani N, Levin-Kotler LP, Palevski D, Amit U, Kain D, Landa N, Hochhauser E, Leor J

Abstract
Background -Little is known about the potentially unfavorable effects of mesenchymal stromal cell (MSC) activation on the heart. MSCs can respond to tissue injury by anti or pro-inflammatory activation. We sought to study the potential negative interaction between left ventricular dysfunction (LVD) and MSC activation. Methods -We isolated MSCs from cardiac (c) and subcutaneous (sc) fat tissues of mice with LVD, 28 days after myocardial infarction (MI), or sham operation. To evaluate the effect of LVD on MSCs, we characterized cMSCs and scMSCs in vitro Subsequently, we injected MSCs or saline into the infarcted myocardium of mice and evaluated left ventricular (LV) remodeling, and function, 28 days after MI. To test the hypothesis that toll-like receptor 4 (TLR4) mediates pro-inflammatory polarization of MSCs, we characterized cMSCs from TLR4(-/-) and wild-type (WT) mice after inflammatory stimulation in vitro Next, we transplanted cMSCs from TLR4(-/-) and WT male mice into the infarcted myocardium of female WT mice and evaluated infarct size, MSC retention, inflammation, remodeling and function, after seven days. Results -LVD switched cMSCs toward an inflammatory phenotype, with increased secretion of inflammatory cytokines, as well as chemokines. The effect of LVD on scMSCs was less remarkable. While transplantation of cMSCs and scMSCs from LVD and sham hearts did not improve LV remodeling and function, cMSCs from LVD exacerbated anterior wall thinning, 28 days after MI. The inflammatory polarization of cMSCs by LVD was mediated by TLR4, as we found less secretion of inflammatory cytokines and higher secretion of anti-inflammatory cytokines from activated cMSCs of TLR4-deficient mice, compared with WT cMSCs. Significantly, TLR4-deficiency preserved the expression of CD47 ("don't eat me" signal) on cMSCs after both TLR4 stimulation in vitro and transplantation into the infarcted heart. Compared with WT cMSCs and saline, TLR4(-/-) cMSCs survived in the cardiac tissue and maintained their reparative properties, reduced infarct size, increased scar thickness and attenuated LV dilatation, seven days after MI. Conclusions -The environment of the failing and infarcted myocardium drives resident and transplanted MSCs toward a pro-inflammatory phenotype, and restricts their survival and reparative effects in a mechanism mediated by TLR4.

PMID: 28356441 [PubMed - as supplied by publisher]

Categorías: Trasplante cardíaco

Engaging with China on organ transplantation.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Engaging with China on organ transplantation.

BMJ. 2017 Feb 07;356:j665

Authors: Rogers WA, Robertson MP, Lavee J

PMID: 28174156 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Calculated panel reactive antibody with decimals: A refined metric of access to transplantation for highly sensitized candidates.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Calculated panel reactive antibody with decimals: A refined metric of access to transplantation for highly sensitized candidates.

Hum Immunol. 2017 Mar;78(3):252-256

Authors: Kransdorf EP, Pando MJ

Abstract
The use of the calculated panel reactive antibody (CPRA) value and the implementation of allocation points for sensitized candidates by the United Network for Organ Sharing (UNOS) have improved access to kidney transplantation for highly sensitized candidates (98% CPRA and above). Despite this, a large population of highly sensitized candidates remain awaiting transplantation. To better define this population, we propose the use of two refinements of the standard UNOS CPRA, the CPRA with decimals or CPRAd, and the likelihood of a compatible donor (LCD). These refined metrics of the standard UNOS CPRA will allow transplant programs to describe their patients' access to transplantation with increased granularity and will help in decisions regarding the use of desensitization.

PMID: 28069404 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Clinical Relevance of Computed Tomography Pulmonary Venography.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Clinical Relevance of Computed Tomography Pulmonary Venography.

Heart Lung Circ. 2016 Dec;25(12):1154-1163

Authors: Braun SD, Platzek I, Danowski D, Zöphel K, Weise M, Kolditz M, Katzke S, Strasser RH, Höffken G, Halank M

Abstract
BACKGROUND: In clinical routine, the pulmonary contrast-enhanced chest computer tomography (CT) is usually focussed on the pulmonary arteries. The purpose of this pictorial essay is to raise the clinicians' awareness for the clinical relevance of CT pulmonary venography.
CASE PRESENTATION: A pictorial case series illustrates the clinical consequences of different pulmonary venous pathologies on systemic, pulmonary and bronchial circulation.
CONCLUSION: Computed tomography pulmonary venography must be considered before atrial septal defect (ASD) closure and pulmonary lobectomy. Computed tomography pulmonary venography should be considered for patients with right ventricular overload and pulmonary hypertension, as well as for patients with unclear recurrent pulmonary infections, progressive dyspnoea, pleural effusions, haemoptysis, and for patients with respiratory distress after lung-transplantation.

PMID: 27451827 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Substernal Colonic Interposition After Previous Coronary Artery Bypass Graft in a Patient With a Patent Left Internal Thoracic Artery Graft: A Surgical Challenge.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Substernal Colonic Interposition After Previous Coronary Artery Bypass Graft in a Patient With a Patent Left Internal Thoracic Artery Graft: A Surgical Challenge.

Ann Thorac Surg. 2016 Nov;102(5):e403-e405

Authors: Hussain ST, Zhen-Yu Tong M, Raja S, Keshavamurthy S, Dietz DW

Abstract
Esophageal reconstruction by a substernal route with a colonic conduit after previous esophagectomy and end-cervical esophagostomy in the presence of a patent left internal thoracic artery graft to the left anterior descending coronary artery is a technically challenging procedure. In this case report, we describe a safe approach to this difficult problem. With proper planning and careful dissection, substernal esophageal reconstruction after previous sternotomy in patients with a patent left internal thoracic artery graft is feasible and can be safely performed.

PMID: 27772592 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Intraoperative Vein Graft Preservation: What Is the Solution?

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Intraoperative Vein Graft Preservation: What Is the Solution?

Ann Thorac Surg. 2016 Nov;102(5):1736-1746

Authors: Woodward LC, Antoniades C, Taggart DP

Abstract
Saphenous vein graft (SVG) disease and subsequent vein graft failure remain a major problem after coronary artery bypass graft operations. In an effort to mitigate loss of endothelial viability, the vein is stored, intraoperatively, in a preservation solution. However, human SVG samples demonstrate endothelial denudation and dysfunction after such storage, the severity of which varies, depending on the medium. The paucity of clinical data evaluating preservation solutions is illustrated by the absence of optimal procedural protocol. This review evaluates the potential efficacy of different storage solutions in preserving vein grafts, in relation to a mechanistic understanding of SVG pathophysiology.

PMID: 27624295 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury.

Int J Mol Sci. 2016 Sep 14;17(9):

Authors: Cho SR, Suh H, Yu JH, Kim HH, Seo JH, Seo CH

Abstract
Transplantation of mesenchymal stem cells (MSCs) has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE) in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O₂ for 90 min). At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS)-control (CON), PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.

PMID: 27649153 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

First Successful Clinical Application of the In Vivo Tissue-Engineered Autologous Vascular Graft.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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First Successful Clinical Application of the In Vivo Tissue-Engineered Autologous Vascular Graft.

Ann Thorac Surg. 2016 Oct;102(4):1387-90

Authors: Kato N, Yamagishi M, Kanda K, Miyazaki T, Maeda Y, Yamanami M, Watanabe T, Yaku H

Abstract
PURPOSE: The ideal material for pediatric pulmonary artery (PA) augmentation is autologous pericardium. However, its utility for multistaged operations is limited. In this study, we applied an in vivo tissue-engineered autologous Biotube graft to a patient with congenital heart disease for the first time.
DESCRIPTION: For molds of the Biotubes, two silicone 19F drain tubes were embedded in the subcutaneous spaces of a 2-year-old girl with a diagnosis of pulmonary atresia and ventricular septal defect with major aortopulmonary collateral arteries during palliative surgical procedures. When definitive repair was performed after 8 months, the implants were removed to prepare Biotubes, one of which was cut open and autologously implanted into the PA for patch augmentation.
EVALUATION: Seven months after implantation, the Biotube patch-augmented PA tolerated balloon angioplasty (BAP) for residual stenosis of the peripheral PA. Computed tomography images after BAP showed the well-preserved shape of the Biotube patch-augmented PA. Neither aneurysm formation nor stenosis was observed.
CONCLUSIONS: The safety and feasibility of Biotubes for pediatric PA patch augmentation are described. Because Biotubes are completely autologous, they may be ideal material for pediatric PA augmentation.

PMID: 27645948 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Radiofrequency ablation of ventricular fibrillation: correlation between electroanatomical mapping and gross pathology.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Radiofrequency ablation of ventricular fibrillation: correlation between electroanatomical mapping and gross pathology.

QJM. 2016 Dec;109(12):821

Authors: McKeag N

PMID: 27634972 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

[Programmed necrosis: a new target for
ischemia reperfusion injury].

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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[Programmed necrosis: a new target for
ischemia reperfusion injury].

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016 Jul;41(7):765-70

Authors: Li X, Ming Y, Niu Y, Liu Q, Ye Q

Abstract
Recent years, the researchers have found a new type of cell death, referred to programmed necrosis or necroptosis, which involves the death receptor and the ligand binds and is initiated under the inhibition of apoptosis pathway. Programmed necrosis possesses the morphological features of typical necrosis accompanied by inflammation. The receptor interacting protein kinase 1/3(RIPK1/3) can be inhibited by the specific inhibitors, such as necrostatin-1. RIPK1/3 could regulate programmed necrosis and play a key role in the process. The significance of programmed necrosis in ischemia-reperfusion injury (IRI) has been attracted great attention at present. Simultaneously, a series of studies have found it also involves in the IRI of heart, kidney, brain and retina.

PMID: 27592584 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Veno-Arterial ECMO in the Setting of Post-Infarct Ventricular Septal Defect: A Bridge to Surgical Repair.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Veno-Arterial ECMO in the Setting of Post-Infarct Ventricular Septal Defect: A Bridge to Surgical Repair.

Heart Lung Circ. 2016 Nov;25(11):1063-1066

Authors: McLaughlin A, McGiffin D, Winearls J, Tesar P, Cole C, Vallely M, Clarke A, Fraser J

Abstract
Extracorporeal membrane oxygenation (ECMO) is a complex rescue therapy utilised to provide circulatory and/or respiratory support to critically ill patients who have failed maximal conventional therapy. The use of ECMO in adult cardiac surgery is not routine, occurring in a minority of critically ill patients, typically postoperatively. Presented here are three cases of post-infarct ventricular septal defect with cardiogenic shock managed preoperatively with ECMO support as a bridge to definitive surgical closure. We present a review of ECMO in the adult cardiac surgical population and highlight the potential role of preoperative ECMO for cardiogenic shock in the setting of post-infarct ventricular septal defect (PI VSD) as a bridge to definitive closure.

PMID: 27374861 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

A Systematic Review of Mitral Valve Repair With Autologous Pericardial Leaflet Augmentation for Rheumatic Mitral Regurgitation.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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A Systematic Review of Mitral Valve Repair With Autologous Pericardial Leaflet Augmentation for Rheumatic Mitral Regurgitation.

Ann Thorac Surg. 2016 Oct;102(4):1400-5

Authors: Mihos CG, Pineda AM, Capoulade R, Santana O

Abstract
A systematic review was conducted to assess the efficacy of mitral valve repair using glutaraldehyde-treated autologous pericardial leaflet augmentation for rheumatic mitral regurgitation (MR). Five retrospective studies were identified, which included 196 patients with moderate or greater MR. There was 1 operative death (0.5%). At a mean follow-up of 3.2 ± 2.2 years, moderate or greater MR reoccurred in 22 patients (11.2%), reoperation was required in 9 (4.6%), and the cumulative survival was 98.9%. Finally, outcomes were similar between the patients who underwent augmentation of the anterior vs the posterior mitral leaflet. Pericardial leaflet augmentation is a viable technique for the treatment of rheumatic MR.

PMID: 27319989 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Worsening Hypoxia Post Lung Transplant: What has Changed?

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Worsening Hypoxia Post Lung Transplant: What has Changed?

Heart Lung Circ. 2016 Nov;25(11):e155-e157

Authors: Shah AH, Leventhal A, Horlick E, Oechslin E, Osten M

Abstract
Platypnoea-orthodeoxia is a rare, but under-diagnosed clinical entity, characterised by postural hypoxia and breathlessness. Underlying pathology is inter-atrial shunt or pulmonary vascular malformation, but what anatomical distortion / physiological alterations initiates right to left shunt, usually against the pressure gradient remains unknown.

PMID: 27283447 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Outcomes After Resection of T4 Non-Small Cell Lung Cancer Using Cardiopulmonary Bypass.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Outcomes After Resection of T4 Non-Small Cell Lung Cancer Using Cardiopulmonary Bypass.

Ann Thorac Surg. 2016 Sep;102(3):902-10

Authors: Langer NB, Mercier O, Fabre D, Lawton J, Mussot S, Dartevelle P, Fadel E

Abstract
BACKGROUND: Complete, en bloc resection offers the greatest chance of long-term survival in T4 non-small cell lung cancer (NSCLC). The use of cardiopulmonary bypass (CPB) to achieve an en bloc resection is controversial because of potentially increased bleeding, lung dysfunction, and tumor dissemination. We reviewed our institutional experience to assess CPB's effect on survival.
METHODS: All patients who underwent resection for T4 NSCLC at our institution between 1980 and 2013 were retrospectively reviewed and stratified according to whether they did (CPB group, n = 20) or did not (No CPB group, n = 355) undergo CPB. Primary outcomes of interest were overall and disease-free survival and perioperative complications.
RESULTS: Baseline characteristics and medical therapy were similar between the groups. Median overall survival for all patients was 31 months, with 1-, 3-, 5-, and 10-year survival of 73%, 47%, 40%, and 26%, respectively. Median disease-free survival for all patients was 19 months, with 1-, 3-, 5-, and 10-year disease-free survival of 61%, 40%, 33%, and 21%, respectively. No difference was found in overall or disease-free survival at 1, 3, 5, and 10 years between the No CPB and CPB groups (p = 0.89 and p = 0.88). In addition, no differences were found in the rates of major perioperative complications.
CONCLUSIONS: The use of CPB allows for complete, en bloc resection in otherwise inoperable patients with T4 NSCLC and offers similar overall and disease-free survival to patients resected without CPB. All thoracic surgeons who manage T4 NSCLC should consider the use of CPB if it is necessary to achieve a complete, en bloc resection.

PMID: 27209605 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Role of the mTOR Signalling Pathway in Experimental Rabbit Vein Grafts.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Role of the mTOR Signalling Pathway in Experimental Rabbit Vein Grafts.

Heart Lung Circ. 2016 Nov;25(11):1124-1132

Authors: Wang Q, Wan L, Liu L, Liu J

Abstract
BACKGROUND: Coronary artery bypass grafting is employed for the treatment of multiple-vessel lesions. Studies have shown that continued maladaptive remodelling expedites atherosclerosis and that excessive remodelling leads to graft restenosis. However, few studies have focussed on mechanistic target of rapamycin (mTOR) signalling involved during remodelling of transplanted veins.
METHODS: Rabbits were randomly allocated to groups undergoing vein-graft restenosis or sham surgery. At 1, 3, 7, 14, 28 and 90 days after surgery, we removed bypassed grafts and placed them in groups named T1, T2, T3, T4, T5 and T6, respectively. Group T0 denoted the control group. Analysis included vessel thickness, electron microscope data, TUNEL staining, and expression of the proliferation-associated gene proliferating cell nuclear antigen (PCNA). We chose specific time-points of gene expression, and then observed changes in the mTOR signalling.
RESULTS: The early stage of vein grafting (one to three days after surgery) led to apoptosis and degradation of the extracellular matrix. Seven days after surgery, cells began to proliferate. RICTOR expression in mTOR complex 2 (mTORC2) and that of its downstream substrate protein kinase C was enhanced in the early stage (T1 and T3), and was higher in T1. mTORC1's upstream gene regulation decreased in T1 and increased in T3. Its downstream genes eIF4b and 4E-BP showed similar changes. Expression of eIF4e and eIF4b increased, and led to an increase in protein composition.
CONCLUSIONS: After transplantation, mTORC1 function and its upstream and downstream genes were inhibited on the first day after grafting, but mTORC2 function was enhanced. One week after surgery, mTORC2 was still overexpressed when mTORC1 function had recovered and became enhanced. Hence, mTORC2 plays a major role in arterialisation of veins.

PMID: 27185657 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Comparison of Radial Artery and Saphenous Vein Graft Stenosis More Than 5 Years After Coronary Artery Bypass Grafting.

Trasplante cardíaco - Vie, 03/31/2017 - 15:17
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Comparison of Radial Artery and Saphenous Vein Graft Stenosis More Than 5 Years After Coronary Artery Bypass Grafting.

Ann Thorac Surg. 2016 Sep;102(3):712-9

Authors: Yamasaki M, Deb S, Tsubota H, Moussa F, Kiss A, Cohen EA, Radhakrishnan S, Dubbin J, Ko D, Schwartz L, Fremes SE, Radial Artery Patency Study Investigators

Abstract
BACKGROUND: Graft stenosis may be associated with future graft failure. The purpose of this investigation was to compare graft stenosis between radial artery (RA) grafts and saphenous vein grafts (SVGs) at least 5 years postoperatively using the multicenter Radial Artery Patency Study (RAPS) data.
METHODS: Two hundred thirty-four patients underwent late invasive angiography after coronary artery bypass operations. The study population consists of 163 patients with thrombolysis in myocardial infarction (TIMI) 3 flow of both the RA graft and study SVGs. Angiograms were reviewed centrally and in a blinded fashion. Graft stenosis was recorded for the proximal anastomosis, graft body, and distal anastomosis; significant stenosis was defined as greater than or equal to 50%. Major adverse cardiac events (MACE) were reported in patients with and those without significant graft stenosis.
RESULTS: There was no difference in significant graft stenosis of the patent RA grafts and SVGs (14 of 163 [8.6%] versus 19 of 163 [11.7%]) or in the proximal anastomosis (5 of 163 [3.1%] versus 5 of 163 [3.1%]), graft body (6 of 163 [3.7%] versus 13 of 163 [8.0%]), or distal anastomosis (4 of 163 [2.5%] versus 5 of 163 [3.1%]) considered separately. However, the overall burden of graft body disease was higher in SVGs (p = 0.03). MACE was higher in patients with significant graft stenosis than in patients without stenosis (10 of 28 [35.7%] versus 7 of 135 [5.2%]; p < 0.0001).
CONCLUSIONS: There was no significant difference in the rates of significant stenosis of patent RA grafts and SVGs more than 5 years postoperatively. However, the burden of graft body stenosis was less in RA grafts compared with SVGs, suggesting that the RA grafts will continue to outperform the SVGs late after operation.

PMID: 27154160 [PubMed - indexed for MEDLINE]

Categorías: Trasplante cardíaco

Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells.

Trasplante cardíaco - Jue, 03/30/2017 - 14:47
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Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells.

PLoS One. 2017;12(3):e0174242

Authors: Al-Maqtari T, Hong KU, Vajravelu BN, Moktar A, Cao P, Moore JB, Bolli R

Abstract
Although transplantation of c-kit+ cardiac progenitor cells (CPCs) significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for improving the efficacy of the regenerative cardiac cell therapy. We assessed the hypothesis that differentiation of human c-kit+ CPCs can be enhanced by priming them with cardiac transcription factors (TFs). We introduced five different TFs (Gata4, MEF2C, NKX2.5, TBX5, and BAF60C) into CPCs, either alone or in combination, and then examined the expression of marker genes associated with the major cardiac cell types using quantitative RT-PCR. When introduced individually, Gata4 and TBX5 induced a subset of myocyte markers. Moreover, Gata4 alone significantly induced smooth muscle cell and fibroblast markers. Interestingly, these gene expression changes brought by Gata4 were also accompanied by morphological changes. In contrast, MEF2C and NKX2.5 were largely ineffective in initiating cardiac gene expression in CPCs. Surprisingly, introduction of multiple TFs in different combinations mostly failed to act synergistically. Likewise, addition of BAF60C to Gata4 and/or TBX5 did not further potentiate their effects on cardiac gene expression. Based on our results, it appears that GATA4 is able to potentiate gene expression programs associated with multiple cardiovascular lineages in CPCs, suggesting that GATA4 may be effective in priming CPCs for enhanced differentiation in the setting of stem cell therapy.

PMID: 28355297 [PubMed - in process]

Categorías: Trasplante cardíaco

A case report of PVOD patient combined with pulmonary embolism: Anticoagulation or not?

Trasplante cardíaco - Jue, 03/30/2017 - 14:47
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A case report of PVOD patient combined with pulmonary embolism: Anticoagulation or not?

Medicine (Baltimore). 2017 Mar;96(13):e6507

Authors: Yuan X, Hou X, Guo W, Jiang H, Zheng J, Paudyal S, Lyu Y

Abstract
RATIONALE: Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary arterial hypertension (PAH). Oral anticoagulation is confined to patients with idiopathic PAH (IPAH), but no oral anticoagulation has been recommended for PVOD, because occult pulmonary hemorrhage was a common finding in PVOD.
PATIENT CONCERNS: We report a case of PVOD, who was misdiagnosed as IPAH for 5 years with worsening dyspnea and two episodes of pulmonary embolism (PE).
DIAGNOSES: He was confirmed as PVOD combined with PE by biopsy of the explanted lung specimen.
INTERVENTIONS: He took oral anticoagulation, warfarin, to treat his first-time PE in July 2010, and his disease was kept stable for about 4 years, until he discontinued the anticoagulation therapy by himself sometime in 2014. Later on, a life-threatening PE recurred in January 2015, so he resumed the anticoagulation therapy.
OUTCOMES: Fortunately, the bilateral sequential lung transplantation that was performed in July 2015 in time saved his life. He has been living well without dyspnea and the echocardiography showed the normalizations of the once increased pulmonary arterial pressure and the once enlarged right ventricle of his heart. In addition, to the best of my knowledge, he was the first PVOD patient receiving lung transplantation in China.
LESSONS: We recommend that PVOD patients combined with PE should be treated with anticoagulation therapy indefinitely to prevent the recurrence of life-threatening PE until they get a chance for lung transplantation.

PMID: 28353604 [PubMed - in process]

Categorías: Trasplante cardíaco

Effect of Milrinone Infusion on Pulmonary Vasculature and Stroke Work Indices: A Single-Center Retrospective Analysis in 69 Patients Awaiting Cardiac Transplantation.

Trasplante cardíaco - Jue, 03/30/2017 - 14:47
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Effect of Milrinone Infusion on Pulmonary Vasculature and Stroke Work Indices: A Single-Center Retrospective Analysis in 69 Patients Awaiting Cardiac Transplantation.

Am J Cardiovasc Drugs. 2017 Mar 28;:

Authors: Abramov D, Haglund NA, Di Salvo TG

Abstract
BACKGROUND: Although milrinone infusion is reported to benefit left ventricular function in chronic left heart failure, few insights exist regarding its effects on pulmonary circulation and right ventricular function.
METHODS: We retrospectively reviewed right heart catheterization data at baseline and during continuous infusion of milrinone in 69 patients with advanced heart failure and analyzed the effects on ventricular stroke work indices, pulmonary vascular resistance and pulmonary arterial compliance.
RESULTS: Compared to baseline, milrinone infusion after a mean 58 ± 61 days improved mean left ventricular stroke work index (1540 ± 656 vs. 2079 ± 919 mmHg·mL/m(2), p = 0.0007) to a much greater extent than right ventricular stroke work index (616 ± 346 vs. 654 ± 332, p = 0.053); however, patients with below median stroke work indices experienced a significant improvement in both left and right ventricular stroke work performance. Overall, milrinone reduced left and right ventricular filling pressures and pulmonary and systemic vascular resistance by approximately 20%. Despite an increase in pulmonary artery capacitance (2.3 ± 1.6 to 3.0 ± 2.0, p = 0.013) and a reduction in pulmonary vascular resistance (3.8 ± 2.3 to 3.0 ± 1.7 Wood units), milrinone did not reduce the transpulmonary gradient (13 ± 7 vs. 12 ± 6 mmHg, p = 0.252), the pulmonary artery pulse pressure (25 ± 10 vs. 24 ± 10, p = 0.64) or the pulmonary artery diastolic to pulmonary capillary wedge gradient (2.0 ± 6.5 vs. 2.4 ± 6.0, p = 0.353).
CONCLUSION: Milrinone improved left ventricular stroke work indices to a greater extent than right ventricular stroke work indices and had beneficial effects on right ventricular net input impedance, predominantly via augmentation of left ventricular stroke volume and passive unloading of the pulmonary circuit. Patients who had the worst biventricular performance benefited the most from chronic milrinone infusion.

PMID: 28353026 [PubMed - as supplied by publisher]

Categorías: Trasplante cardíaco
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