Isolation of cardiovascular precursor cells from the human fetal heart.

Weakening of cardiac function in patients with heart failure results from a loss of cardiomyocytes in the damaged heart. Cell replacement therapies as a way to induce myocardial regeneration in humans could represent attractive alternatives to classical drug-based approaches. However, a suitable source of precursor cells, which could produce a functional myocardium after transplantation, remains to be identified. In the present study, we isolated cardiovascular precursor cells from ventricles of human fetal hearts at 12 weeks of gestation. These cells expressed Nkx2.5 but not late cardiac markers such as α-actinin and troponin I. In addition, proliferating cells expressed the mesenchymal stem cell markers CD73, CD90, and CD105. Evidence for functional cardiogenic differentiation in vitro was demonstrated by the upregulation of cardiac gene expression as well as the appearance of cells with organized sarcomeric structures. Importantly, differentiated cells presented spontaneous and triggered calcium signals. Differentiation into smooth muscle cells was also detected. In contrast, precursor cells did not produce endothelial cells. The engraftment and differentiation capacity of green fluorescent protein (GFP)-labeled cardiac precursor cells were then tested in vivo after transfer into the heart of immunodeficient severe combined immunodeficient mice. Engrafted human cells were readily detected in the mouse myocardium. These cells retained their cardiac commitment and differentiated into α-actinin-positive cardiomyocytes. Expression of connexin-43 at the interface between GFP-labeled and endogenous cardiomyocytes indicated that precursor-derived cells connected to the mouse myocardium. Together, these results suggest that human ventricular nonmyocyte cells isolated from fetal hearts represent a suitable source of precursors for cell replacement therapies.

Atrial arrhythmias in adult patients with right- versus left-sided congenital heart disease anomalies.

Atrial arrhythmias (AAs) are a common complication in adult patients with congenital heart disease. We sought to compare the lifetime prevalence of AAs in patients with right- versus left-sided congenital cardiac lesions and their effect on the prognosis. A congenital heart disease diagnosis was assigned using the International Disease Classification, Ninth Revision, diagnostic codes in the administrative databases of Quebec, from 1983 to 2005. Patients with AAs were those diagnosed with an International Disease Classification, Ninth Revision, code for atrial fibrillation or intra-atrial reentry tachycardia. To ensure that the diagnosis of AA was new, a washout period of 5 years after entry into the database was used, a period during which the patient could not have received an International Disease Classification, Ninth Revision, code for AA. The cumulative lifetime risk of AA was estimated using the Practical Incidence Estimators method. The hazard ratios (HRs) for mortality, morbidity, and cardiac interventions were compared between those with right- and left-sided lesions after adjustment for age, gender, disease severity, and cardiac risk factors. In a population of 71,467 patients, 7,756 adults developed AAs (isolated right-sided, 2,229; isolated left-sided, 1,725). The lifetime risk of developing AAs was significantly greater in patients with right- sided than in patients with left-sided lesions (61.0% vs 55.4%, p <0.001). The HR for mortality and the development of stroke or heart failure was similar in both groups (HR 0.96, 95% confidence interval [CI] 0.86 to 1.09; HR 0.94, 95% CI 0.80 to 1.09; and HR 1.10, 95% CI 0.98 to 1.23, respectively). However, the rates of cardiac catheterization (HR 0.63, 95% CI 0.55 to 0.72), cardiac surgery (HR 0.40, 95% CI 0.36 to 0.45), and arrhythmia surgery (HR 0.77, 95% CI 0.6 to 0.98) were significantly less for patients with right-sided lesions. In conclusion, patients with right-sided lesions had a greater lifetime burden of AAs. However, their morbidity and mortality were no less than those with left-sided lesions, although the rate of intervention was substantially different.

Enteral nutrition and cardiovascular failure: from myths to clinical practice.

Cardiovascular failure and low flow states may arise in very different conditions from both cardiac and noncardiac causes. Systemic hemodynamic failure inevitably alters splanchnic blood flow but in an unpredictable way. Prolonged low splanchnic blood flow causes intestinal ischemia, increased mucosal permeability, endotoxemia, and distant organ failure. Mortality associated with intestinal ischemia is high. Why would enteral nutrition (EN) be desirable in these complex patients when parenteral nutrition could easily cover energy and substrate requirements? Metabolic, immune, and practical reasons justify the use of EN. In addition, continuous enteral feeding minimizes systemic and myocardial oxygen consumption in patients with congestive heart failure. Further, early feeding in critically ill mechanically ventilated patients has been shown to reduce mortality, particularly in the sickest patients. In a series of cardiac surgery patients with compromised hemodynamics, absorption has been maintained, and 1000-1200 kcal/d could be delivered by enteral feeding. Therefore, early EN in stabilized patients should be attempted, and can be carried out safely under close clinical monitoring, looking for signs of incipient intestinal ischemia. Energy delivery and balance should be monitored, and combined feeding considered when enteral feeds cannot be advanced to target within 4-6 days.

Le nébivolol: un bêta-bloquant pourvu de propriétés vasodilatatrices [Nebivolol: a beta blocker with vasodilator properties]

Nebivolol is a new cardioselective beta-blocking agent possessing vasodilatory properties involving the endothelium. This compound is a dl-racemic mixture. The d-enantiomer is responsible for the beta-blocking properties whereas the l-enantiomer induces a vasodilation via a nitric oxide (NO) mechanism. Nebivolol is an unique agent that appears promising for the management of patients with hypertension, coronary heart disease or congestive heart failure.

Heart transplantation: current practice and outlook to the future.

QUESTIONS UNDER STUDY: The field of heart transplantation has seen substantial progress in the last 40 years. The breakthroughs in long-term survival were followed by a period of stagnation in the last decade. This review summarises current recommendations for the identification of candidates for heart transplantation and their immunological and non-immunological postoperative follow-up. RESULTS: The progress made in the treatment of patients with advanced heart failure has considerably changed the profile of candidates for heart transplantation. Patients are older, and the load of co-morbidities is more important requiring careful evaluation for candidacy. Long-standing research in the field of immunosuppression made available various drugs, which decrease the risk of acute allograft rejection and prolong survival after heart transplantation. Powerful new molecules are entering early phase clinical studies, suggesting further improvement in the near future. As a consequence, treatment of non-immunological co-morbidity after heart transplantation will gain in importance, however, the base of evidence guiding current recommendations is poor. CONCLUSIONS: The substantial progress in heart failure treatment and immunosuppression after heart transplantation has changed the profile of heart transplant recipients. The arrival of new molecules will provide additional alternatives for immunosuppressive treatment while studies have to address non-immunological treatment in order to improve long-term survival after heart transplantation.

Long-term continuous-flow left ventricular assist devices (LVAD) as bridge to heart transplantation.

Heart transplantation (HTx) is the treatment of choice for end-stage heart failure but the limited availability of heart's donors still represents a major issue. So long-term mechanical circulatory support (MCS) has been proposed as an alternative treatment option to assist patients scheduled on HTx waiting list bridging them for a variable time period to cardiac transplantation-the so-called bridge-to-transplantation (BTT) strategy. Nowadays approximately 90% of patients being considered for MCS receive a left ventricular assist device (LVAD). In fact, LVAD experienced several improvements in the last decade and the predominance of continuous-flow over pulsatile-flow technology has been evident since 2008. The aim of the present report is to give an overview of continuous-flow LVAD utilization in the specific setting of the BTT strategy taking into consideration the most representative articles of the scientific literature and focusing the attention on the evolution, clinical outcomes, relevant implications on the HTx strategy and future perspectives of the continuous-flow LVAD technology.

Vancomycin-associated nephrotoxicity, a case control study

Background: Vancomycin is a cornerstone antibiotic for the management of severe Gram positive infections. However, high doses of vancomycin are associated with a risk of nephrotoxicity. This study aimed to evaluate the relationship between the evolution of vancomycin trough concentration and the occurrence of nephrotoxicity, and to identify risk factors for both vancomycin-associated nephrotoxicity and vancomycin overexposure. Methods: A total of 1240 patients records from our hospital therapeutic drug monitoring database between 2007 and 2011 were screened and grouped according to predefined criteria defining vancomycin overexposure (one or more occurrence of a trough level ≥ 20 mg/L) and treatment-related nephrotoxicity (rise of serum creatinine by ≥ 50% over baseline). A representative sample of 150 cases was selected for in depth analysis. Weighted logistic regression analyses were used to test associations between vancomycin overexposure, nephrotoxicity and other predictors of interest. Results: Patients with high trough concentrations were found to be more likely to develop nephrotoxicity (odds ratio: 4.12; p <0.001). Specific risk factors, notably concomitant nephrotoxic treatments and comorbid conditions (heart failure), were found to independently increase the risk of either nephrotoxicity or vancomycin exposure. Finally, the exploration of temporal relationships between variations of vancomycin trough concentrations and creatinine levels were in line with circular causality with some antecedence of vancomycin on creatinine changes. Conclusion: Our results confirm the important nephrotoxic potential of vancomycin and indicate that the utilisation of this drug deserves thorough individualization for conditions susceptible to increase its concentration exposure and reactive adjustment based on therapeutic drug monitoring.

Outcome of patients admitted with acute coronary syndrome on palliative treatment: insights from the nationwide AMIS Plus Registry 1997-2014.

OBJECTIVE: Compliance with guidelines is increasingly used to benchmark the quality of hospital care, however, very little is known on patients admitted with acute coronary syndromes (ACS) and treated palliatively. This study aimed to evaluate the baseline characteristics and outcomes of these patients. DESIGN: Prospective cohort study. SETTING: Eighty-two Swiss hospitals enrolled patients from 1997 to 2014. PARTICIPANTS: All patients with ACS enrolled in the AMIS Plus registry (n=45,091) were analysed according to three treatment groups: palliative treatment, defined as use of aspirin and analgesics only and no reperfusion; conservative treatment, defined as any treatment including antithrombotics or anticoagulants, heparins, P2Y12 inhibitors, GPIIb/IIIa but no pharmacological or mechanical reperfusion; and reperfusion treatment (thrombolysis and/or percutaneous coronary intervention during initial hospitalisation). The primary outcome measure was in-hospital mortality and the secondary measure was 1-year mortality. RESULTS: Of the patients, 1485 (3.3%) were palliatively treated, 11,119 (24.7%) were conservatively treated and 32,487 (72.0%) underwent reperfusion therapy. In 1997, 6% of all patients were treated palliatively and this continuously decreased to 2% in 2013. Baseline characteristics of palliative patients differed in comparison with conservatively treated and reperfusion patients in age, gender and comorbidities (all p<0.001). These patients had more in-hospital complications such as postadmission onset of cardiogenic shock (15.6% vs 5.2%; p<0.001), stroke (1.8% vs 0.8%; p=0.001) and a higher in-hospital mortality (25.8% vs 5.6%; p<0.001).The subgroup of patients followed 1 year after discharge (n=8316) had a higher rate of reinfarction (9.2% vs 3.4%; p=0.003) and mortality (14.0% vs 3.5%; p<0.001). CONCLUSIONS: Patients with ACS treated palliatively were older, sicker, with more heart failure at admission and very high in-hospital mortality. While refraining from more active therapy may often constitute the most humane and appropriate approach, we think it is important to also evaluate these patients and include them in registries and outcome evaluations. CLINICAL TRIAL NUMBER: ClinicalTrials.gov Identifier: NCT01 305 785.

Cardiologie [Cardiology update in 2014].

Important clinical trials and therapeutic advances in the field of cardiology have been presented in 2014. New evidences on the management of acute myocardial infarction and the duration of dual antiplatelet therapy after coronary stent implantation have been published. A new class of therapeutic agents seems to offer promising perspectives for patients with heart failure and reduced ejection fraction. The new generation of subcutaneous or MRI-compatible implantable defibrillators is a major technological breakthrough. Finally, the European Society of Cardiology published new recommendations for the management of patients with cardiovascular diseases. This selective review of the literature summarizes the most important studies in the field of interventional cardiology, rhythmology, heart failure and cardiac imaging.

Sanitary quality of edible bivalve mollusks in Southeastern Brazil using an UV based depuration system

The increase in seafood production, especially in mariculture worldwide, has brought out the need of continued monitoring of shellfish production areas in order to ensure safety to human consumption. The purpose of this research was to evaluate pathogenic protozoa, viruses and bacteria contamination in oysters before and after UV depuration procedure, in brackish waters at all stages of cultivation and treatment steps and to enumerate microbiological indicators of fecal contamination from production site up to depuration site in an oyster cooperative located at the Southeastern estuarine area of Brazil. Oysters and brackish water were collected monthly from September 2009 to November 2010. Four sampling sites were selected for enteropathogens analysis: site 1- oyster growth, site 2- catchment water (before UV depuration procedure), site 3 - filtration stage of water treatment (only for protozoa analysis) and site 4- oyster's depuration tank. Three microbiological indicators ! were examined at sites 1, 2 and 4. The following pathogenic microorganisms were searched: Giardia cysts, Cryptosporidium oocysts, Human Adenovirus (HAdV), Hepatitis A virus (HAV), Human Norovirus (HnoV) (genogroups I and II), JC strain Polyomavirus (JCPyV) and Salmonella sp. Analysis consisted of molecular detection (qPCR) for viruses (oysters and water samples); immunomagnetic separation followed by direct immunofluorescence assay for Cryptosporidium oocysts and Giardia cysts and also molecular detection (PCR) for the latter (oysters and water samples); commercial kit (Reveal-Neogee (R)) for Salmonella analysis (oysters). Giardia was the most prevalent pathogen in all sites where it was detected: 36.3%, 18.1%, 36.3% and 27.2% of water from sites 1, 2, 3 and 4 respectively; 36.3% of oysters from site 1 and 54.5% of depurated oysters were harboring Giardia cysts. The huge majority of contaminated samples were classified as Giardia duodenalis. HAdv was detected in water and o! ysters from growth site and HnoV GI in two batches of oysters ! (site 1) in huge concentrations (2.11 x 10(13), 3.10 x 10(12) gc/g). In depuration tank site, Salmonella sp., HAV (4.84 x 10(3)) and HnoV GII (7.97 x 10(14)) were detected once in different batches of oysters. Cryptosporidium spp. oocysts were present in 9.0% of water samples from site four. These results reflect the contamination of oysters even when UV depuration procedures are employed in this shellfish treatment plant. Moreover, the molecular comprehension of the sources of contamination is necessary to develop an efficient management strategy allied to shellfish treatment improvement to prevent foodborne illnesses. (C) 2011 Elsevier Ltd. All rights reserved.

Duration of anticoagulation after venous thromboembolism in real world clinical practice.

INTRODUCTION: Venous thromboembolism (VTE) carries a considerable risk of recurrence and anticoagulants should be administered for a minimum of three months. Since little is known about real life management of VTE, we aimed to describe current practice in the secondary prevention of VTE. MATERIALS AND METHODS: Using the database of an international, prospective registry on patients treated for VTE, RIETE, information was collected on risk factors for VTE and bleeding, anticoagulant treatment, and clinical outcomes during follow up. Multivariate analysis using logistic regression was performed to identify predictors of treatment duration. RESULTS: Of 6944 patients with a first episode of VTE 41.1% had unprovoked VTE, 31.8% had transient risk factors, 27.1% had cancer. After the exclusion of patients who died during the first year of observation, the rate of patients treated for >12 months was 55.1%, 41.9%, and 43.2%, respectively (p<0.001). Pulmonary embolism at presentation, recurrence while on treatment, chronic heart failure and age >65 years were independently associated with treatment for >12 months. Body weight <75 kg, anemia, cancer, and the presence of transient risk factors were associated with treatment for 12 months or less. Major bleeding occurred more frequently than recurrent VTE in patients with VTE secondary to transient risk factors and cancer; fatal bleeding was more frequent than fatal recurrent PE in all subgroups. CONCLUSIONS: We observed heterogeneous duration of anticoagulant treatment for the secondary prevention of VTE. A substantial proportion of patients, in particular those with VTE secondary to transient risk factors, may be exposed to a possibly unnecessary risk of bleeding.