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Myoblast transplantation improves cardiac function after myocardial infarction through attenuating inflammatory responses.

Sat, 06/10/2017 - 12:45
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Myoblast transplantation improves cardiac function after myocardial infarction through attenuating inflammatory responses.

Oncotarget. 2017 May 27;:

Authors: Wang B, Zhang L, Cao H, Yang J, Wu M, Ma Y, Fan H, Zhan Z, Liu Z

Abstract
Myocardial infarction (MI) is a highly prevalent cardiac emergency, which results in adverse cardiac remodeling and then exacerbates progressive heart failure. Inflammatory responses in cardiac tissue after MI is necessary for myocardium repair and wound healing. However, the excessive inflammation is also a key component of subsequent heart failure pathology. Myoblast transplantation after MI have been fulfilled attractive effects on cardiac repair, but the complications of transplantation and the underlying mechanisms have not been fully elucidated. Here, we found that human myoblast transplantation into minipig myocardium decreased the infiltration of inflammatory cells, the expression levels of many pro-inflammatory genes and the activation of inflammation-related signal pathways, while upregulated the expression levels of anti-inflammatory genes such as IL-10 in cardiac tissue of minipig post-MI, which was contributed to the improved cardiac function, the decreased infarct area and the attenuated myocardial fibrosis. Moreover, co-culture of human myoblasts inhibited the production of IL-1β and TNF-α as well as activation of MAPK and NF-κB signaling pathway induced by damage-associated molecular patterns such as HMGB1 and HSP60 in human THP-1 cells, which was partially attributed to the up-regulated production of IL-10. Collectively, these results indicate that myoblast transplantation ameliorates heart injury and improves cardiac function post-MI through inhibiting the inflammatory response, which provides the novel mechanism for myoblast transplantation therapy of MI.

PMID: 28599279 [PubMed - as supplied by publisher]

Long-term diabetes complications after pancreas transplantation.

Sat, 06/10/2017 - 12:45
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Long-term diabetes complications after pancreas transplantation.

Curr Opin Organ Transplant. 2017 Jun 08;:

Authors: Jenssen T, Hartmann A, Birkeland KI

Abstract
PURPOSE OF REVIEW: The intention of this study is to summarize present knowledge about adverse effects of hyperglycemia in diabetes, and in this context review more recent data concerning the effects of pancreas transplantation on a wide range of diabetic complications.
RECENT FINDINGS: Effective blood glucose control by insulin delays progression of microvascular complications and probably improves survival in type 1 diabetes. A successful pancreas transplantation combined with a kidney graft has recently been found to prevent diabetic kidney lesions, and registry data support improved long-term patient survival. Cardiovascular mortality was reduced in one study, even though coronary heart disease was not significantly altered. Advanced coronary lesions may be too advanced in these patients at baseline. However, with a successful single pancreas transplant, which is generally performed in patients with near-normal kidney function, pancreas transplantation may improve left ventricular function. Development of retinopathy and neuropathy is delayed with functioning pancreas grafts, and both quality of life and certain skin lesions may improve after pancreas transplantation.
SUMMARY: In patients with type 1 diabetes, pancreas transplantation may improve cardiac outcomes and ameliorate diabetic lesions in the kidney transplant. Also quality of life, neuropathy, retinopathy, and healing of certain skin lesions may be improved.

PMID: 28598888 [PubMed - as supplied by publisher]

Feasibility and safety of home exercise training in children with sickle cell anemia.

Sat, 06/10/2017 - 12:45
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Feasibility and safety of home exercise training in children with sickle cell anemia.

Pediatr Blood Cancer. 2017 Jun 09;:

Authors: Liem RI, Akinosun M, Muntz DS, Thompson AA

Abstract
Exercise guidelines do not exist for individuals with sickle cell anemia (SCA) despite the impact of disease-related complications on physical functioning. Thirteen subjects (mean 15.1 ± 2.8 years old) with SCA were prescribed three exercise sessions/week for 12 weeks on a stationary bicycle placed at home. In total, 77% of subjects completed 89% of prescribed sessions without exercise-related adverse events, thus meeting feasibility and safety criteria. Adherence to prescribed duration and target heart rate during training decreased during the second half of the study. Future trials are warranted to further evaluate training benefits associated with regular exercise in children with SCA.

PMID: 28598539 [PubMed - as supplied by publisher]

Follow-up tricuspid annular plane systolic excursion predicts survival in pulmonary arterial hypertension.

Sat, 06/10/2017 - 12:45
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Follow-up tricuspid annular plane systolic excursion predicts survival in pulmonary arterial hypertension.

Pulm Circ. 2017 Apr-Jun;7(2):361-371

Authors: Mazurek JA, Vaidya A, Mathai SC, Roberts JD, Forfia PR

Abstract
Few studies have examined the utility of serial echocardiography in the evaluation, management, and prognosis of patients with pulmonary arterial hypertension (PAH). Therefore, we sought to evaluate the prognostic significance of follow-up tricuspid annular plane systolic excursion (TAPSE) in PAH. We prospectively studied 70 consecutive patients with PAH who underwent baseline right heart catheterization (RHC) and transthoracic echocardiogram, who survived to follow-up echocardiogram after initiation of PAH therapy. Baseline TAPSE was 1.6 ± 0.5 cm which increased to 2.0 ± 0.4 cm on follow-up ( P < 0.0001). The cohort was dichotomized by TAPSE at one-year follow-up: Group 1 (n = 37): follow-up TAPSE ≥ 2 cm; Group 2 (n = 33): follow-up TAPSE < 2 cm. Group 1 participants were significantly more likely to reach WHO functional class I-II status and achieve a higher six-minute walk distance on follow-up. Of the 68 patients who survived more than one year, 18 died (26.5%) over a median follow-up of 941 days (range, 3-2311 days), with significantly higher mortality in Group 2 versus Group 1 (41.9% vs. 13.5%; P = 0.003). While baseline TAPSE stratified at 2 cm did not predict survival in this cohort, TAPSE ≥ 2 cm at follow-up strongly predicted survival in bivariable models (hazard ratio, 0.21; 95% confidence interval, 0.08-0.60). In conclusion, follow-up TAPSE ≥ 2 cm is a prognostic marker and potential treatment target in a PAH population.

PMID: 28597759 [PubMed - in process]

Longitudinal change in pulmonary arterial capacitance as an indicator of prognosis and response to therapy and in pulmonary arterial hypertension.

Sat, 06/10/2017 - 12:45
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Longitudinal change in pulmonary arterial capacitance as an indicator of prognosis and response to therapy and in pulmonary arterial hypertension.

Pulm Circ. 2017 Apr-Jun;7(2):399-408

Authors: Medrek SK, Kloefkorn C, Nguyen DTM, Graviss EA, Frost AE, Safdar Z

Abstract
Pulmonary arterial hypertension (PAH) is a chronic progressive disease that leads to right heart failure and death. Pulmonary arterial capacitance (PAC), defined as stroke volume divided by the pulmonary pulse pressure, has been identified as a prognostic factor in PAH. The impact of changes in PAC over time, however, is unclear. We evaluated changes in PAC over time to determine if such changes predicted transplant-free survival. A single-center retrospective study of consecutive group 1 PAH patients who had two or more right heart catheterizations (RHC) between January 2007 and June 2016 was undertaken. Hemodynamic data, clinical data, and outcomes were collected. Univariate and multivariate Cox proportional-hazards modelling to identify the contribution of risk factors for a composite outcome of death or lung transplantation was done. Mixed-effects logistic regression was performed to investigate the association between the change in PAC value over time and the composite outcome. A P value < 0.05 was considered significant. In total, 109 consecutive patients with a total of 300 RHC data were identified. PAC correlated inversely with functional status ( P < 0.001) and inversely with pulmonary vascular resistance ( P < 0.001). PAC values increased with the addition of new PAH-specific medications. Mixed effects logistic regression modeling using longitudinal data showed that a decrease in PAC over the study period was associated with increased mortality and transplantation (adjusted P = 0.039) over the study period. Change in PAC was a better predictor of outcome over the study period than baseline PAC or changes in other hemodynamic or clinical parameters. Decreases in PAC were predictive of increased mortality or transplantation in patients with group 1 PAH. There was a trend towards increased PAC in response to the addition of a PAH-specific medication. Our data support the use of PAC as a therapeutic target in PAH.

PMID: 28597758 [PubMed - in process]

Peripartum cardiomyopathy in Denmark: a retrospective, population-based study of incidence, management and outcome.

Sat, 06/10/2017 - 12:45
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Peripartum cardiomyopathy in Denmark: a retrospective, population-based study of incidence, management and outcome.

Eur J Heart Fail. 2017 Jun 08;:

Authors: Ersbøll AS, Johansen M, Damm P, Rasmussen S, Vejlstrup NG, Gustafsson F

Abstract
AIM: Population-based European studies of peripartum cardiomyopathy (PPCM) are few. We aimed to estimate the nationwide incidence and outcome of PPCM in Denmark during 2005-2014.
METHODS AND RESULTS: The Danish National Birth Register and the Danish National Patient Register were linked and searched for cardiomyopathy and heart failure ICD-10 diagnoses in a period of nine months before to 12 months after a delivery from 1 January 2005 through 31 December 2014. Diagnoses were validated and additional data were extracted from patient charts. A total of 61 women met the inclusion criteria equalling 1 in 10 149 deliveries. The majority recovered left ventricular systolic function within one year, but 14.8% suffered a major adverse event with 3.3% mortality, 8.2% mechanical circulatory support requirement and/or heart transplantation and 4.9% persistent severe heart failure. Half of the women had a concomitant hypertensive disorder of pregnancy, and this subgroup had a milder course of the disease. Baseline left ventricular ejection fraction (LVEF) was the only significant predictor of LVEF 10-14 months after diagnosis, and cabergoline therapy to inhibit lactation predicted the dichotomous outcome of complete recovery (LVEF ≥55%).
CONCLUSION: The first validated, population-based European estimate of PPCM incidence is 1 in 10 149 deliveries, which places Denmark between American and Japanese estimates. Clinical outcome in the cohort was similar to those reported in recent cohorts. Women with concomitant hypertensive disorder of pregnancy had a milder course of PPCM. Baseline LVEF predicted LVEF 10-14 months after diagnosis and cabergoline predicted complete recovery.

PMID: 28597481 [PubMed - as supplied by publisher]

[3-D mapping of ventricular tachycardia in patients with dilative cardiomyopathy].

Sat, 06/10/2017 - 12:45
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[3-D mapping of ventricular tachycardia in patients with dilative cardiomyopathy].

Herzschrittmacherther Elektrophysiol. 2017 Jun 08;:

Authors: Steven D, van den Bruck JH, Lüker J, Plenge T, Sultan A

Abstract
Catheter ablation of ventricular tachycardia (VT) is gaining in importance. The current guidelines suggest considering catheter ablation for VT even in patients with a single sustained and documented episode. This is also underlined by recent data indicating that absence of VT predicts lower mortality and longer transplant-free survival. The majority of patients with VTs have a history of prior myocardial infarction; in a smaller proportion, patients present with dilated cardiomyopathy. The latter has a less structured scar pattern which makes it more complicated to apply efficient ablation strategies. Data have shown that the probability of VT recurrence after catheter ablation is higher and an epicardial access more frequently required. Algorithms and strategies to improve catheter ablation results have been developed and evaluated especially on patients with dilated cardiomyopathy (DCM) to further improve outcomes. The present article will strive to acquaint the reader with the current strategies and state of knowledge.

PMID: 28597213 [PubMed - as supplied by publisher]

Cardiovascular assessment in liver transplant for non-alcoholic steatohepatitis patients: What we do, what we should do.

Sat, 06/10/2017 - 12:45
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Cardiovascular assessment in liver transplant for non-alcoholic steatohepatitis patients: What we do, what we should do.

World J Hepatol. 2017 May 28;9(15):697-703

Authors: Sanchez-Torrijos Y, Ampuero J, Romero-Gómez M

Abstract
Non-alcoholic fatty liver disease (NAFLD) is increasing considerably due to the current lifestyle, which means that it is becoming one of the main indications for liver transplantation. On the other hand, there is a strong association between NAFLD and cardiovascular disease. This has been evidenced in many studies revealing a higher presence of carotid plaques or carotid intima-media thickness, leading to cardiovascular events and, ultimately, mortality. According to the liver transplant guidelines, screening for heart disease in transplant candidates should be performed by electrocardiogram and transthoracic echocardiography while a stress echocardiogram should be reserved for those with more than two cardiovascular risk factors or greater than 50 years old. However, there are no specific recommendations in NAFLD patients requiring a liver transplantation, despite its well-known cardiovascular risk association. Many studies have shown that these patients probably require a more exhaustive assessment and a global approach including other specialists such as cardiologists or nutritionists. Also, the incidence of cardiovascular disease is also increased in NAFLD patients in the post-transplantation period in comparison with other etiologies, because of the pre-existent risk factors together with the immunosuppressive therapy. Therefore, an early intervention on the lifestyle and the individualized selection of the immunosuppressive regimen could lead to a modification of the cardiovascular risk factors in NAFLD patients requiring a liver transplantation.

PMID: 28596817 [PubMed - in process]

Hematopoietic Id Deletion Triggers Endomyocardial Fibrotic and Vascular Defects in the Adult Heart.

Sat, 06/10/2017 - 12:45
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Hematopoietic Id Deletion Triggers Endomyocardial Fibrotic and Vascular Defects in the Adult Heart.

Sci Rep. 2017 Jun 08;7(1):3079

Authors: Chang C, Zhao Q, Gonzalez JP, Kim JH, Alzahrani K, Del Re D, Fraidenraich D

Abstract
Inhibitor of DNA binding (Id) proteins play important roles in regulating cardiac development via paracrine signaling. Id1/Id3 knockout mice die at mid-gestation with multiple cardiac defects. Single Id knockout studies have not reported cardiomyopathies. To bypass embryonic lethality we used Tie2CRE-mediated recombination to conditionally delete Id1 against global Id3 ablation (Id cDKOs), which develops adult-onset dilated cardiomyopathy. We confirm upregulation of thrombospondin-1 (TSP1) in Id cDKO hearts. Colocalization studies reveal increased TSP1 expression in the vicinity of endothelial cells and near regions of endocardial fibrosis/disruption. Downstream fibrotic molecules were upregulated. Endocardial capillary density was reduced with evidence of vascular distention. Treatment of Id cDKO cardiac explants with LSKL, a peptide antagonist of TSP1 activation of TGFβ, reversed the increased expression of fibrotic molecules. We conducted bone marrow transplant experiments in which we transferred bone marrow cells from Id cDKO mice into lethally irradiated WT mice. The majority of WT recipients of Id cDKO bone marrow cells phenocopied Id cDKO cardiac fibrosis 4 months post-transplantation. Injection of LSKL into adult Id cDKO mice led to downregulation of fibrotic molecules. The results prompt caution when bone marrow transfers from individuals potentially carrying mutations in the Id axis are applied in clinical settings.

PMID: 28596553 [PubMed - in process]

Cre/lox Studies Identify Resident Macrophages as the Major Source of Circulating Coagulation Factor XIII-A.

Sat, 06/10/2017 - 12:45
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Cre/lox Studies Identify Resident Macrophages as the Major Source of Circulating Coagulation Factor XIII-A.

Arterioscler Thromb Vasc Biol. 2017 Jun 08;:

Authors: Beckers CML, Simpson KR, Griffin KJ, Brown JM, Cheah LT, Smith KA, Vacher J, Cordell PA, Kearney MT, Grant PJ, Pease RJ

Abstract
OBJECTIVE: To establish the cellular source of plasma factor (F)XIII-A.
APPROACH AND RESULTS: A novel mouse floxed for the F13a1 gene, FXIII-A(flox/flox) (Flox), was crossed with myeloid- and platelet-cre-expressing mice, and cellular FXIII-A mRNA expression and plasma and platelet FXIII-A levels were measured. The platelet factor 4-cre.Flox cross abolished platelet FXIII-A and reduced plasma FXIII-A to 23±3% (P<0.001). However, the effect of platelet factor 4-cre on plasma FXIII-A was exerted outside of the megakaryocyte lineage because plasma FXIII-A was not reduced in the Mpl(-/-) mouse, despite marked thrombocytopenia. In support of this, platelet factor 4-cre depleted FXIII-A mRNA in brain, aorta, and heart of floxed mice, where FXIII-A(pos) cells were identified as macrophages as they costained with CD163. In the integrin αM-cre.Flox and the double copy lysozyme 2-cre.cre.Flox crosses, plasma FXIII-A was reduced to, respectively, 75±5% (P=0.003) and 30±7% (P<0.001), with no change in FXIII-A content per platelet, further consistent with a macrophage origin of plasma FXIII-A. The change in plasma FXIII-A levels across the various mouse genotypes mirrored the change in FXIII-A mRNA expression in aorta. Bone marrow transplantation of FXIII-A(+/+) bone marrow into FXIII-A(-/-) mice both restored plasma FXIII-A to normal levels and replaced aortic and cardiac FXIII-A mRNA, while its transplantation into FXIII-A(+/+) mice did not increase plasma FXIII-A levels, suggesting that a limited population of niches exists that support FXIII-A-releasing cells.
CONCLUSIONS: This work suggests that resident macrophages maintain plasma FXIII-A and exclude the platelet lineage as a major contributor.

PMID: 28596376 [PubMed - as supplied by publisher]

Angiotensin-Converting Enzyme Inhibitors for Cardiac Allograft Vasculopathy After Heart Transplantation.

Sat, 06/10/2017 - 12:45
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Angiotensin-Converting Enzyme Inhibitors for Cardiac Allograft Vasculopathy After Heart Transplantation.

J Am Coll Cardiol. 2017 Jun 13;69(23):2842-2844

Authors: Eisen HJ, Hankins S, Wang D

PMID: 28595701 [PubMed - in process]

Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation.

Sat, 06/10/2017 - 12:45
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Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation.

J Am Coll Cardiol. 2017 Jun 13;69(23):2832-2841

Authors: Fearon WF, Okada K, Kobashigawa JA, Kobayashi Y, Luikart H, Sana S, Daun T, Chmura SA, Sinha S, Cohen G, Honda Y, Pham M, Lewis DB, Bernstein D, Yeung AC, Valantine HA, Khush K

Abstract
BACKGROUND: Cardiac allograft vasculopathy (CAV) remains a leading cause of mortality after heart transplantation (HT). Angiotensin-converting enzyme inhibitors (ACEIs) may retard the development of CAV but have not been well studied after HT.
OBJECTIVES: This study tested the safety and efficacy of the ACEI ramipril on the development of CAV early after HT.
METHODS: In this prospective, multicenter, randomized, double-blind, placebo-controlled trial, 96 HT recipients were randomized to undergo ramipril or placebo therapy. They underwent coronary angiography, endothelial function testing; measurements of fractional flow reserve (FFR) and coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR); and intravascular ultrasonography (IVUS) of the left anterior descending coronary artery, within 8 weeks of HT. At 1 year, the invasive assessment was repeated. Circulating endothelial progenitor cells (EPCs) were quantified at baseline and 1 year.
RESULTS: Plaque volumes at 1 year were similar between the ramipril and placebo groups (162.1 ± 70.5 mm(3) vs. 177.3 ± 94.3 mm(3), respectively; p = 0.73). Patients receiving ramipril had improvement in microvascular function as shown by a significant decrease in IMR (21.4 ± 14.7 to 14.4 ± 6.3; p = 0.001) and increase in CFR (3.8 ± 1.7 to 4.8 ± 1.5; p = 0.017), from baseline to 1 year. This did not occur with IMR (17.4 ± 8.4 to 21.5 ± 20.0; p = 0.72) or CFR (4.1 ± 1.8 to 4.1 ± 2.2; p = 0.60) in the placebo-treated patients. EPCs decreased significantly at 1 year in the placebo group but not in the ramipril group.
CONCLUSIONS: Ramipril does not slow development of epicardial plaque volume but does stabilize levels of endothelial progenitor cells and improve microvascular function, which have been associated with improved long-term survival after HT. (Angiotensin Converting Enzyme [ACE] Inhibition and Cardiac Allograft Vasculopathy; NCT01078363).

PMID: 28595700 [PubMed - in process]

Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension: Comparison With Validated Models.

Fri, 06/09/2017 - 15:46
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Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension: Comparison With Validated Models.

Circ Cardiovasc Imaging. 2017 Jun;10(6):

Authors: Amsallem M, Sweatt AJ, Aymami MC, Kuznetsova T, Selej M, Lu H, Mercier O, Fadel E, Schnittger I, McConnell MV, Rabinovitch M, Zamanian RT, Haddad F

Abstract
BACKGROUND: Right ventricular (RV) end-systolic dimensions provide information on both size and function. We investigated whether an internally scaled index of end-systolic dimension is incremental to well-validated prognostic scores in pulmonary arterial hypertension.
METHODS AND RESULTS: From 2005 to 2014, 228 patients with pulmonary arterial hypertension were prospectively enrolled. RV end-systolic remodeling index (RVESRI) was defined by lateral length divided by septal height. The incremental values of RV free wall longitudinal strain and RVESRI to risk scores were determined. Mean age was 49±14 years, 78% were female, 33% had connective tissue disease, 52% were in New York Heart Association class ≥III, and mean pulmonary vascular resistance was 11.2±6.4 WU. RVESRI and right atrial area were strongly connected to the other right heart metrics. Three zones of adaptation (adapted, maladapted, and severely maladapted) were identified based on the RVESRI to RV systolic pressure relationship. During a mean follow-up of 3.9±2.4 years, the primary end point of death, transplant, or admission for heart failure was reached in 88 patients. RVESRI was incremental to risk prediction scores in pulmonary arterial hypertension, including the Registry to Evaluate Early and Long-Term PAH Disease Management score, the Pulmonary Hypertension Connection equation, and the Mayo Clinic model. Using multivariable analysis, New York Heart Association class III/IV, RVESRI, and log NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) were retained (χ(2), 62.2; P<0.0001). Changes in RVESRI at 1 year (n=203) were predictive of outcome; patients initiated on prostanoid therapy showed the greatest improvement in RVESRI. Among right heart metrics, RVESRI demonstrated the best test-retest characteristics.
CONCLUSIONS: RVESRI is a simple reproducible prognostic marker in patients with pulmonary arterial hypertension.

PMID: 28592589 [PubMed - in process]

Validation of a new proposal to avoid donor resuscitation in controlled donation after circulatory death with normothermic regional perfusion.

Thu, 06/08/2017 - 12:45
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Validation of a new proposal to avoid donor resuscitation in controlled donation after circulatory death with normothermic regional perfusion.

Resuscitation. 2017 Jun 04;:

Authors: Villares JMP, Rubio JJ, Río FD, Miñambres E

Abstract
AIM: The use of abdominal normothermic regional perfusion (nRP) and premortem interventions in controlled donation after circulatory death (cDCD) may represent a significant advance to increase the number and quality of grafts recovered in cDCD. The main limitation for the widespread acceptance of nRP in cDCD is the concerns of restoring circulation to the brain once death has been declared should the thoracic aorta not be adequately blocked.
METHODS: We describe and validate a specific methodology to ensure an appropriate blocking of the thoracic aorta in a multicenter study using this technique.
RESULTS: A total of 78 procedures with premortem cannulation and abdominal nRP were performed in four different hospitals. No case of heart or brain resuscitation was observed after nRP CONCLUSION: The use of premortem interventions before nRP and the aortic occlusion balloon may increase the number of grafts recovered in cDCD. Our proposed methodology avoids the ethical problem of resuscitation by guaranteeing that circulation to the heart and brain is not restored after nRP.

PMID: 28591558 [PubMed - as supplied by publisher]

Case 2/2017 - 56-Year-Old Male with Refractory Heart Failure, Systemic Arterial Hypertension and Aortic Valve Stenosis That Led to Heart Transplantation.

Thu, 06/08/2017 - 12:45
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Case 2/2017 - 56-Year-Old Male with Refractory Heart Failure, Systemic Arterial Hypertension and Aortic Valve Stenosis That Led to Heart Transplantation.

Arq Bras Cardiol. 2017 May;108(5):473-479

Authors: Favarato D, Gutierrez PS

PMID: 28591324 [PubMed - in process]

The Conundrum of Equitable Organ Allocation in Heart Transplantation: The Moving Target of Candidate Risk Score.

Thu, 06/08/2017 - 12:45
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The Conundrum of Equitable Organ Allocation in Heart Transplantation: The Moving Target of Candidate Risk Score.

Transplantation. 2017 Jun 06;:

Authors: Potena L, Khush KK

PMID: 28590947 [PubMed - as supplied by publisher]

Metoprolol-induced Severe Liver Injury and Successful Management with Therapeutic Plasma Exchange.

Thu, 06/08/2017 - 12:45
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Metoprolol-induced Severe Liver Injury and Successful Management with Therapeutic Plasma Exchange.

Cureus. 2017 May 02;9(5):e1209

Authors: Philips C, Paramaguru R, Mahadevan P, Ravindranath J, Augustine P

Abstract
Liver injury caused by metoprolol is very rare with current reports limited to an isolated elevation in transaminases. We report the first case of severe icteric liver injury leading to hepatic encephalopathy secondary to metoprolol use in a patient diagnosed with coronary heart disease. We also describe the histopathology of metoprolol-related liver injury, discuss mechanisms of injury with new insights on the immunological phenomenon, and shed light on the successful utility of early plasmapheresis as a salvage therapy in metoprolol-induced severe liver damage.

PMID: 28589058 [PubMed - in process]

Elevated trimethylamine-N-oxide (TMAO) is associated with poor prognosis in primary sclerosing cholangitis patients with normal liver function.

Thu, 06/08/2017 - 12:45
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Elevated trimethylamine-N-oxide (TMAO) is associated with poor prognosis in primary sclerosing cholangitis patients with normal liver function.

United European Gastroenterol J. 2017 Jun;5(4):532-541

Authors: Kummen M, Vesterhus M, Trøseid M, Moum B, Svardal A, Boberg KM, Aukrust P, Karlsen TH, Berge RK, Hov JR

Abstract
BACKGROUND: Trimethylamine-N-oxide (TMAO) is produced in the liver from trimethylamine, which is exclusively generated by gut bacteria.
OBJECTIVE: The objective of this article is to investigate the relationship between TMAO and primary sclerosing cholangitis (PSC) and its clinical characteristics.
METHODS: Serum TMAO was measured in 305 PSC patients, 90 ulcerative colitis patients and 99 healthy controls.
RESULTS: In PSC patients with normal liver function (n = 197), TMAO was higher in patients reaching liver transplantation or death during follow-up than those who did not, with an optimal TMAO cut-off of 4.1 µM (AUC = 0.64, p < 0.001). PSC patients with high TMAO (>4.1 µM, n = 77) exhibited shorter transplantation-free survival than patients with low TMAO (n = 120, log-rank test: p < 0.0001). High TMAO (>4.1 µM) was associated with reduced transplantation-free survival (HR 1.87, p = 0.011), independently of the Mayo risk score (HR 1.74, p < 0.001). Overall, PSC patients demonstrated reduced TMAO values compared with ulcerative colitis and healthy controls, mainly caused by PSC patients with reduced liver function (INR > 1.2), suggesting impaired oxidation of trimethylamine to TMAO. PSC patients with and without inflammatory bowel disease had similar TMAO levels.
CONCLUSION: In PSC patients with normal liver function, elevated TMAO was associated with shorter transplantation-free survival, potentially reflecting clinically relevant metabolic changes resulting from dietary interactions with the gut microbiota.

PMID: 28588885 [PubMed - in process]

Additional coronary sinus shocking lead as rescue therapy after multiple internal and external defibrillation failures.

Thu, 06/08/2017 - 12:45
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Additional coronary sinus shocking lead as rescue therapy after multiple internal and external defibrillation failures.

Clin Case Rep. 2017 Jun;5(6):923-926

Authors: Chauveau S, Dulac A, Sebbag L, Morel E, Chevalier P

Abstract
High defibrillation threshold (DFT) and defibrillation failure can lead to intractable ventricular arrhythmias. Additional coronary sinus coil is an effective strategy to achieve marked reduction in DFT. However, physicians should retain this might prevent future coronary sinus lead placement in case the patient would develop complete left bundle branch block.

PMID: 28588840 [PubMed - in process]

Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers.

Thu, 06/08/2017 - 12:45
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Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers.

Sci Rep. 2017 Jun 06;7(1):2840

Authors: Lemieux H, Blier PU, Gnaiger E

Abstract
Fuel substrate supply and oxidative phosphorylation are key determinants of muscle performance. Numerous studies of mammalian mitochondria are carried out (i) with substrate supply that limits electron flow, and (ii) far below physiological temperature. To analyze potentially implicated biases, we studied mitochondrial respiratory control in permeabilized mouse myocardial fibers using high-resolution respirometry. The capacity of oxidative phosphorylation at 37 °C was nearly two-fold higher when fueled by physiological substrate combinations reconstituting tricarboxylic acid cycle function, compared with electron flow measured separately through NADH to Complex I or succinate to Complex II. The relative contribution of the NADH pathway to physiological respiratory capacity increased with a decrease in temperature from 37 to 25 °C. The apparent excess capacity of cytochrome c oxidase above physiological pathway capacity increased sharply under hypothermia due to limitation by NADH-linked dehydrogenases. This mechanism of mitochondrial respiratory control in the hypothermic mammalian heart is comparable to the pattern in ectotherm species, pointing towards NADH-linked mt-matrix dehydrogenases and the phosphorylation system rather than electron transfer complexes as the primary drivers of thermal sensitivity at low temperature. Delineating the link between stress and remodeling of oxidative phosphorylation is important for understanding metabolic perturbations in disease evolution and cardiac protection.

PMID: 28588260 [PubMed - in process]

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