Disturbances of the transfer of cholesterol to high-density lipoprotein (HDL) in patients with peripheral artery disease with or without type 2 diabetes mellitus.

INTRODUCTION: Low high-density lipoprotein (HDL)-cholesterol is frequent in patients with peripheral artery disease (PAD) and also in type 2 diabetes mellitus (T2DM), the major risk factor for PAD. The transfer of cholesterol from the other lipoproteins to HDL is an important aspect of HDL metabolism and function, and may contribute to atherogenic mechanisms that lead to PAD development. OBJECTIVE: The aim of this study was to investigate the status of cholesterol transfers in patients with PAD without or with T2DM. METHODS: Patients with PAD (n = 19), with PAD and T2DM (PAD + DM, n = 19), and healthy controls (n = 20), all paired for age, sex, and BMI were studied. Transfer of both forms of cholesterol, unesterified (UC) and esterified (EC), was performed by incubating plasma with a donor nanoemulsion containing radioactive UC and EC, followed by chemical precipitation and HDL radioactive counting. RESULTS: Low-density lipoprotein (LDL)-cholesterol and triglycerides were similar in the three groups. Compared to controls, HDL-C was lower in PAD + DM (p < 0.05), but not in PAD. Transfer of UC was lower in PAD + DM than in PAD and controls (4.18 ± 1.17%, 5.13 ± 1.44%, 6.59 ± 1.25%, respectively, p < 0.001). EC transfer tended to be lower in PAD + DM than in controls (2.96 ± 0.60 vs 4.12 ± 0.89%, p = 0.05). Concentrations of cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT), both involved in HDL metabolism, were not different among the three groups. CONCLUSION: Deficient cholesterol transfer to HDL may play a role in PAD pathogenesis. Since UC transfer to HDL was lower in PAD + DM compared to PAD alone, it is possible that defective HDL metabolism may contribute to the higher PAD incidence in patients with T2DM.Keywords.

Influential Factors on the Evaluation of Adamkiewicz Artery Using a 320-Detector Row Computed Tomography Device.

BACKGROUND: Understanding the difference of Adamkiewicz artery (AKA) presentation in healthy and diseased subjects, and the influence of atherosclerotic factors prevalent in aortic disease patients, are important for aortic disease therapeutic planning. This study used a 320-detector row computed tomography (CT) device to examine the impact of clinical aspects of AKA identification in individuals with and without aortic disease. METHODS: Angio-CTs obtained from 115 patients were assessed and the individuals grouped according to the presence or absence of aortic disease. Datasets were analyzed using OsiriX software, and AKA was identified by three-dimensional multiplanar reconstruction. RESULTS: The group without aortic disease (Group A) comprised 32 (52.5%) men and 29 women, with a mean age of 53.7 ± 16.8 years. The group with aortic disease (Group B) comprised 31 (57.4%) men and 23 women, with a mean age of 64.8 ± 11.6 years. AKA was identified in 49 (80.3%) participants of Group A and 23 (42.6%) individuals of Group B (P ≤ 0.0001). In 53 cases (73.6%), AKA originated on the left side. AKA was mainly detected on the left side (73.6%), at the level of T10 to T12 (70%). Tobacco smokers, former smokers, and hypertensive patients had increased odds of having undetected AKA. CONCLUSIONS: Using the method described and a state of the art 320-detector row CT device, AKA was detected more frequently among individuals without aortic disease. Thus, aortic disease and atherosclerotic risk factors hindered AKA detection.

Myocardial gene expression of T-bet, GATA-3, Ror-γt, FoxP3, and hallmark cytokines in chronic Chagas disease cardiomyopathy: an essentially unopposed TH1-type response.

BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg) in CCC, NIC, and heart donor myocardial samples. METHODS AND RESULTS: Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-ß and IL-10) were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. CONCLUSIONS: Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3(+)CTLA4(+) Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation.

Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial.

IMPORTANCE: Most acute kidney injury observed in the hospital is defined by sudden mild or moderate increases in the serum creatinine concentration, which may persist for several days. Such acute kidney injury is associated with lower long-term kidney function. However, it has not been demonstrated that an intervention that reduces the risk of such acute kidney injury better preserves long-term kidney function. OBJECTIVES: To characterize the risk of acute kidney injury with an intervention in a randomized clinical trial and to determine if there is a difference between the 2 treatment groups in kidney function 1 year later. DESIGN, SETTING, AND PARTICIPANTS: The Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY) enrolled 4752 patients undergoing first isolated coronary artery bypass graft (CABG) surgery at 79 sites in 19 countries. Patients were randomized to receive CABG surgery either with a beating-heart technique (off-pump) or with cardiopulmonary bypass (on-pump). From January 2010 to November 2011, 2932 patients (from 63 sites in 16 countries) from CORONARY were enrolled into a kidney function substudy to record serum creatinine concentrations during the postoperative period and at 1 year. The last 1-year serum creatinine concentration was recorded on January 18, 2013. MAIN OUTCOMES AND MEASURES: Acute kidney injury within 30 days of surgery (≥50% increase in serum creatinine concentration from prerandomization concentration) and loss of kidney function at 1 year (≥20% loss in estimated glomerular filtration rate from prerandomization level). RESULTS: Off-pump (n = 1472) vs on-pump (n = 1460) CABG surgery reduced the risk of acute kidney injury (17.5% vs 20.8%, respectively; relative risk, 0.83 [95% CI, 0.72-0.97], P = .01); however, there was no significant difference between the 2 groups in the loss of kidney function at 1 year (17.1% vs 15.3%, respectively; relative risk, 1.10 [95% CI, 0.95-1.29], P = .23). Results were consistent with multiple alternate continuous and categorical definitions of acute kidney injury or kidney function loss, and in the subgroup with baseline chronic kidney disease. CONCLUSIONS AND RELEVANCE: Use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury, without evidence of better preserved kidney function with off-pump CABG surgery at 1 year. In this setting, an intervention that reduced the risk of mild to moderate acute kidney injury did not alter longer-term kidney function. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00463294.

Behavior of lyophilized biological valves in a chronic animal model.

Glutaraldehyde is used in order to improve the mechanical and immunogenic properties of biological tissues, such as bovine pericardium membranes, used to manufacture heart valve bioprostheses. Lyophilization, also known as freeze-drying, preserves biological material without damage by freezing the water content and removing ice by sublimation. Through this process, dehydrated products of high quality may be obtained; also, the material may be easily handled. The lyophilization process reduces aldehyde residues in biological tissue previously treated with glutaraldehyde, thus promoting reduction of cytotoxicity, increasing resistance to inflammation, and possibly decreasing the potential for tissue calcification. The objective of this study was to chronically evaluate the calcification of bovine pericardium heart valve prostheses, previously lyophilized or not, in an animal model. Six-month-old sheep received implants of lyophilized and unlyophilized heart valve prostheses in the pulmonary position with right bypass. The study followed 16 animals for a period of 90 days. Right ventricle-pulmonary artery (RV/PA) transvalvular pressure gradient was evaluated before and immediately after implantation and before explantation, as were tissue calcium, inflammation intensity, and thrombosis and pannus formation. The t-test was used for statistical analysis. Twelve animals survived to the end of the experiment, but one of the animals in the control group had endocarditis and was excluded from the data. Four animals died early. The mean RV/PA gradient on implantation was 2.0 ± 1.6 mm Hg in the control group and 6.2 ± 4.1 mm Hg in the lyophilized group (P = 0.064). This mean gradient increased at explantation to 7.7 ± 3.9 mm Hg and 8.6 ± 5.8 mm Hg, respectively (P = 0.777). The average calcium content in the tissue leaflets after 3 months was 21.6 ± 39.1 mg Ca(2+)/g dry weight in the control group, compared with an average content of 41.2 ± 46.9 mg Ca(2+)/g dry weight in the lyophilized group (P = 0.478). In this experimental study there was no reduction of calcification after lyophilization. However, histological analysis showed less inflammation over the lyophilized tissue when compared with the control.

Correlation of bacterial coinfection versus matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 expression in aortic aneurysm and atherosclerosis.

BACKGROUND: We searched for any relationship between Chlamydophila pneumoniae, Mycoplasma pneumoniae, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in aneurysmatic atherosclerotic lesions, and whether this relationship differed from that in atherosclerotic nonaneurysmatic lesions. METHODS: Twenty-eight tissue samples paired by age and sex were grouped as follows: group 1 included 14 nonaneurysmal atherosclerotic fragments obtained from abdominal aortas collected from necropsies; group 2 included 14 aneurysmatic atherosclerotic aortic fragments obtained from patients during corrective surgery. Immunohistochemistry reactions were evaluated for C pneumoniae, M pneumoniae, MMP-9, and TIMP-1 antigens. Both groups were compared using the Mann-Whitney test, and the correlations among variables were obtained using the Spearman correlation test. P ≤ 0.05 was considered statistically significant. RESULTS: C pneumoniae and M pneumoniae antigens were detected in 100% of cases. A higher amount of C pneumoniae (P = 0.005), M pneumoniae (P = 0.002), and MMP-9 (P = 0.021) was found in adventitia of group 2 with aneurysm. A positive correlation was found in the aneurysm group, as follows: intima C pneumoniae versus adventitia thickness (r = 0.70; P = 0.01), media C pneumoniae versus adventitia C pneumoniae (r = 0.75; P = 0.002), intima C pneumoniae versus media C pneumoniae (r = 0.8; P = 0.00), and adventitia C pneumoniae versus intima M pneumoniae (r = 0.54; P = 0.05); negative correlations were as follows: adventitia thickness and adventitia M pneumoniae (r = -0.65; P = 0.01), media MMP-9 and media thickness (r = -0.55; P = 0.04), TIMP-1 media versus adventitia C pneumoniae (r = -0.86; P = 0.00), and TIMP-1 media versus M pneumoniae intima (r = -0.67; P = 0.03). Nonaneurysmal atherosclerotic group 1 results are as follows: adventitia C pneumoniae versus TIMP-1 media (r = 0.75; P = 0.01) and media C pneumoniae and adventitia C pneumoniae (r = 0.59; P = 0.03). CONCLUSIONS: The present work favors a role for coinfection of both M pneumoniae and C pneumoniae in the development of aortic atherosclerotic aneurysm, with increased adventitial inflammation, inhibition of TIMP-1 activity, and increased collagen degradation.

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial.

BACKGROUND: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. METHODS/DESIGN: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. DISCUSSION: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.

In vitro and in vivo evaluation of lyophilized bioprosthetic valve.

Freeze-drying of biological tissues allows for dry storage and gamma ray sterilization, which may improve their use as a medical prosthesis. The objective of this study was to evaluate the rehydration characteristics and hydrodynamic performance of prosthetic valves before and after lyophilization. Two size 23 bovine pericardium aortic valve prostheses from different manufacturers were evaluated in a Shelhigh (Union, NJ, USA) pulse duplicator (80 ppm, 5 L/min) before and after lyophilization. Flow and transvalvular pressure gradient were registered in vitro and in vivo, and images of opening and closing of the prosthesis were obtained in the pulse duplicator in a digital camera. Rehydration was evaluated by comparison of dry valve weight with valve weight after 15 min, and 1, 24, 48, and 72 h in saline solution, inside the pulse duplicator. In vivo performance was assessed by surgical implantation in Santa Inês young male sheep in the pulmonary position after 30 min rehydration with 0.9% saline. Transvalvular pressure gradient and flow measurements were obtained immediately after implantation and 3 months after surgery when valves were explanted. Captured images showed a change in the profile opening and closing of valve prosthesis after lyophilization. The gradient measured (in vitro) in two valves was 17.08 ± 0.57 and 18.76 ± 0.70 mm Hg before lyophilization, and 34.24 ± 0.59 and 30.40 ± 0.97 mm Hg after lyophilization. Rehydration of both lyophilized valves was approximately 82%. Drying changed the profile of the opening and closing of valve prostheses, and increased on average by 83% the gradient in vitro tests. The result of the in vivo tests suggests maintaining pressure levels of the animal with the lyophilized prostheses within acceptable levels.

Use of paclitaxel carried in lipid nanoparticles to treat aortic allograft transplantation in rats.

OBJECTIVES: The aim of this study was to test whether lipid core nanoparticles loaded with paclitaxel (LDE-PTX) protect rat aortic allograft from immunological damage. METHODS: Fisher and Lewis rats were used differing in minor histocompatibility loci. Sixteen Lewis rats were allocated to four-animal groups: SYNG (syngeneic), Lewis rats receiving aorta grafts from Lewis rats; ALLO (allogeneic), Lewis rats receiving aortas from Fisher rats; ALLO+LDE (allogeneic transplant treated with LDE), Lewis rats receiving aortas from Fisher rats, treated with LDE (weekly injection for 3 weeks); ALLO+LDE-PTX (allogeneic transplant treated with LDE-PTX), Lewis rats receiving aortas from Fisher rats treated with LDE-PTX (4 mg/kg weekly for 3 weeks). Treatments began on transplantation day. RESULTS: Thirty days post-transplantation, SYNG showed intact aortas. ALLO and ALLO+LDE presented intense neointimal formation. In ALLO+LDE-PTX, treatment inhibited neointimal formation; narrowing of aortic lumen was prevented in ALLO and ALLO+LDE. LDE-PTX strongly inhibited proliferation and intimal invasion by smooth muscle cells, diminished 4-fold presence of apoptotic/dead cells in the intima, reduced the invasion of aorta by macrophages and T-cells and gene expression of pro-inflammatory tumour necrosis factor-alpha (TNFα), interferon gamma (IFNγ) and interleukin-1 beta (IL-1ß). CONCLUSIONS: LDE-PTX was effective in preventing the vasculopathy associated with rejection and may offer a potent therapeutic tool for post-transplantation.

Impairment of Multiple Mitochondrial Energy Metabolism Pathways in the Heart of Chagas Disease Cardiomyopathy Patients.

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC.

Transplantation for Chagas' disease: an overview of immunosuppression and reactivation in the last two decades.

Over the last 20 yr, the immunosuppression protocols in chagasic heart-transplanted patients have gone through three phases, and we have identified several changes and discoveries about Chagas' disease reactivation, mortality, and neoplasia development. The first phase was especially important because until that time, Chagas' disease was an absolute contraindication for transplantation. The second phase started when an adjustment was made to the immunosuppression protocol, a lower dosage being adopted to avoid adverse effects, especially neoplasias and reactivation episodes. Currently, strategies to change the immunosuppression, especially replacement of mycophenolate mofetil by azathioprine or low doses of mycophenolate in this special situation, have been shown to be effective in reducing Chagas' disease reactivation. Cardiac transplantation for Chagas' disease is a reality. Although patients with Chagas' disease may experience particular complications when undergoing transplantation compared with transplantation for other etiologies, these difficulties are well known, and treatment and preventive strategies are also better established. In other organs and tissues, transplantation in patients with Chagas' disease also has good outcomes. Blood monitoring for parasitemias is mandatory as is the institution of therapy in the case of a reactivation diagnosis. Acute Chagas' disease may occur in patients who received organs from donors with Chagas' disease.

Can tricuspid annuloplasty of the donor heart reduce valve insufficiency following cardiac transplantation with bicaval anastomosis?

BACKGROUND: The aim of this study was to evaluate the degree of tricuspid valve insufficiency after orthotopic cardiac transplantation with bicaval anastomosis and prophylactic donor heart annuloplasty. METHODS: At present, our cardiac transplantation experience includes 478 cases. After January 2002, we included 30 consecutive patients in this study who had undergone orthotopic cardiac transplantation and survived >6 months. The patients were divided into 2 groups: group I, 15 patients who underwent transplantation with prophylactic tricuspid annuloplasty on the donor heart with the De Vega technique; and group II, 15 patients who underwent transplantation without this procedure. Their preoperative clinical characteristics were the same. During the late postoperative follow-up, the degree of tricuspid insufficiency was evaluated by transthoracic Doppler echocardiography and assessed according to the Simpson scale: 0, absent; 1, mild; 2, moderate; and 3, severe. Hemodynamic parameters were evaluated invasively by means of a Swan-Ganz catheter during routine endomyocardial biopsies. RESULTS: The mean follow-up time was 26.9 +/- 5.4 months (range, 12-36 months). In group I, 1 patient (6.6%) died from infection in the 18th month after the operation; the death was not related to the annuloplasty. In group II, 1 death (6.6%) occurred after 10 months because of rejection (P > .05). After the 24-month follow-up, the mean degree of tricuspid insufficiency was 0.4 +/- 0.5 in group I and 1.7 +/- 0.9 in group II (P < .05). Similarly, the 2 groups were significantly different with respect to the right atrium pressure, which was higher in group II. CONCLUSIONS: Prophylactic tricuspid annuloplasty on the donor heart was able to reduce significantly the degree of valvular insufficiency, even in cardiac transplantation with bicaval anastomosis; however, it did not modify significantly the hemodynamic performance of the allograft during the investigation period. It is very important to extend the observation period and casuistics to verify other benefits that this technique may offer.

Clinical profile of patients enroled in a cell therapy trial for severe coronary artery disease.

AIMS AND OBJECTIVES: To compare the clinical profile of patients included in a clinical trial of autologous bone marrow cells as an adjunctive therapy to coronary artery bypass grafting with that of patients undergoing routine coronary artery bypass grafting. BACKGROUND: The therapeutic potential of autologous bone marrow cells has been explored in the treatment of severe coronary artery disease. There are few data regarding the clinical and socio-economic profile of patients included in clinical trials using bone marrow cell. DESIGN: Case-control study. METHOD: Sixty-seven patients (61 SD 9) years, 82% men) with multivessel coronary artery disease were divided into two groups: patients in the bone marrow cell group (n = 34) underwent incomplete coronary artery bypass grafting + intramyocardial injection of autologous bone marrow cells (lymphomonocytic fraction -2.0 (SD 0.2 x 10(8)) cells/patient) in the ischaemic, non-revascularised myocardium, whereas patients in the coronary artery bypass grafting group (n = 33) underwent routine bypass surgery. Demographics, socio-economic status, clinical and echocardiographic data were collected. Statistical analysis included the Fisher's exact test (categorical variables) and the Student's t-test (continuous variables). RESULTS: There were no significant differences between groups regarding age, gender, BMI, heart rate, blood pressure and echo data. There was a greater prevalence of obesity (65 vs. 33%; OR = 3.7 [1.3-10.1]), of previous myocardial infarction (68 vs. 39%; OR = 3.2 [1.2-8.8]) and prior revascularisation procedures (59 vs. 24%; OR = 4.5 [1.6-12.7]) in the autologous bone marrow cells group and of smokers in the coronary artery bypass grafting group (51 vs. 23%; OR = 3.5 [1.2-10.4]). CONCLUSIONS: Patients included in this clinical trial of autologous bone marrow cells for severe coronary artery disease presented a greater prevalence of myocardial revascularisation procedures, indicating a more severe clinical presentation of the disease. Fewer smokers in this group could be attributable to life style changes after previous cardiovascular events and/or interventions. RELEVANCE TO CLINICAL PRACTICE: The knowledge of the clinical profile of patients included in cell therapy trials may help researchers in the identification of patients that may be enroled in future clinical trials of this new therapeutic strategy.

Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial.

CONTEXT: Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. OBJECTIVE: To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. DESIGN, SETTING, AND PATIENTS: The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. INTERVENTION: Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). MAIN OUTCOME MEASURE: Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). RESULTS: Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P = .002). CONCLUSION: Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01021631.

Does Prior Percutaneous Coronary Intervention Influence the Outcomes of Coronary Artery Bypass Surgery?

INTRODUCTION: Percutaneous coronary intervention (PCI) has been increasingly performed to treat coronary artery disease. The performance of multiple PCI has also been increasing. Consequently, the percentage of patients presenting for coronary artery bypass graft (CABG) surgery is reported to vary from 13 to 40%. The influence of previous PCI on CABG outcomes has been studied in single center, regional studies, registries and meta-analyses. Some reports showed a negative effect on mortality and morbidity in early or long-term follow-up, but others did not find this influence. METHODS AND RESULTS: A cohort of 3007 patients consecutively operated for CABG, 261 of them with previous PCI, were included in this analysis. Comparison of the groups "previous PCI" and "primary CABG" was made in the original cohort and in a propensity score matched cohort of 261 patients. There were some differences in preoperative clinical characteristics in both types of cohort, even in the matched one. Outcomes were compared at 30 days, 1 year and 5 years of follow-up. There were no statistically significant differences in mortality in any period or cohort. There were some differences in other outcomes as readmission and composite events, including cardiovascular death at 1 and 5 years of follow-up. These differences, neverthless, were not confirmed in comparison with the matched cohort. CONCLUSION: Although there are some limitations in this study, it was not found consistent negative influence of previous PCI on CABG.

Prevention of venous thrombosis by warfarin after permanent transvenous leads implantation in high-risk patients.

BACKGROUND: The incidence of venous lesions following transvenous cardiac device implantation is high. Previous implantation of temporary leads ipsilateral to the permanent devices, and a depressed left ventricular ejection fraction have been associated with an increased risk of venous lesions, though the effects of preventive strategies remain controversial. This randomized trial examined the effects of warfarin in the prevention of these complications in high-risk patients. METHOD: Between February 2004 and September 2007, we studied 101 adults who underwent a first cardiac device implantation, and who had a left ventricular ejection fraction < or =0.40, or a temporary pacing system ipsilateral to the permanent implant, or both. After device implantation, the patients were randomly assigned to warfarin to a target international normalized ratio of 2.0-3.5, or to placebo. Clinical and laboratory evaluations were performed regularly up to 6 months postimplant. Venous lesions were detected at 6 months by digital subtraction venography. RESULTS: Venous obstructions of various degrees were observed in 46 of the 92 patients (50.0%) who underwent venography. The frequency of venous obstructions was 60.4% in the placebo, versus 38.6% in the warfarin group (P = 0.018), corresponding to an absolute risk reduction of 22% (relative risk = 0.63; 95% confidence interval = 0.013-0.42). CONCLUSIONS: Warfarin prophylaxis lowered the frequency of venous lesions after transvenous devices implantation in high-risk patients.

Assessment of a new experimental model of isolated right ventricular failure.

We assessed a new experimental model of isolated right ventricular (RV) failure, achieved by means of intramyocardial injection of ethanol. RV dysfunction was induced in 13 mongrel dogs via multiple injections of 96% ethanol (total dose 1 mL/kg), all over the inlet and trabecular RV free walls. Hemodynamic and metabolic parameters were evaluated at baseline, after ethanol injection, and on the 14th postoperative day (POD). Echocardiographic parameters were evaluated at baseline, on the sixth POD, and on the 13th POD. The animals were then euthanized for histopathological analysis of the hearts. There was a 15.4% mortality rate. We noticed a decrease in pulmonary blood flow right after RV failure (P = 0.0018), as well as during reoperation on the 14th POD (P = 0.002). The induced RV dysfunction caused an increase in venous lactate levels immediately after ethanol injection and on the 14th POD (P < 0.0003). The echocardiogram revealed a decrease in the RV ejection fraction on the sixth and 13th PODs (P = 0.0001). There was an increased RV end-diastolic volume on the sixth (P = 0.0001) and 13th PODs (P = 0.0084). The right ventricle showed a 74% +/- 0.06% transmural infarction area, with necrotic lesions aged 14 days. Intramyocardial ethanol injection has allowed the creation of a reproducible and inexpensive model of RV failure. The hemodynamic, metabolic, and echocardiographic parameters assessed at different protocol times are compatible with severe RV failure. This model may be useful in understanding the pathophysiology of isolated right-sided heart failure, as well as in the assessment of ventricular assist devices.

[Heart transplantation: the experience of patients with Chagas disease]. / Transplante cardíaco (TC): a experiência do portador da Doença de Chagas.

Successful heart transplantation in patients with Chagas disease depends on special care to be provided during all phases of the transplantation process, and requires specific and rigorous follow-up by the health care team. Recipients must be aware of the permanence of the trypanosome in their organisms as well as of the possibility of infection reactivation after transplantation. Therefore, the patient's knowledge regarding this condition and his active participation in his own treatment are of utmost importance. This study aimed at investigating heart transplantation as experienced by patients with Chagas disease, seeking to understand the meanings that they attribute to such an experience. The methodological procedures included: patient selection; interviews; data analysis, indication of the meaning units and individual analysis; search for discourse convergence; and hermeneutic analysis of convergences. From the data analysis, the following themes emerged: the time lived by recipients with Chagas Disease; the conception of heart transplantation presented by patients with Chagas Disease; and care in the course of heart transplantation.

Collagen is reduced and disrupted in human aneurysms and dissections of ascending aorta.

In ascending aorta aneurysms, there is an enlargement of the whole vessel, whereas aortic dissections (ADs) are characterized by the cleavage of the wall into 2 sheets at the external half. We searched if alterations in collagen could be related to these diseases. Sections of aortas from 14 case patients with acute dissections, 10 case patients with aneurysms, and 9 control subjects were stained with picrosirius. Slides were analyzed under polarized microscopy to evaluate the structure of collagen fibers. The proportion of collagen was calculated in each half of the medial layer by color detection in a computerized image analysis system. Collagen appearance under polarized light was consistent with collagenolysis. The mean collagen proportions at the inner and outer halves, respectively, were 0.50 +/- 0.13 and 0.40 +/- 0.08 in the control group, 0.20 +/- 0.10 and 0.18 +/- 0.12 in the AD group, and 0.33 +/- 0.12 and 0.19 +/- 0.12 in the aneurysm group. The AD (P < .01) and control (P = .04) groups had less collagen at the external half; no difference was found in the aneurysm group (P = .71). In both halves, there was less collagen in the case patients than in the control subjects (all P < .01), but at the internal half, the decrease was significantly greater in the case patients with aneurysms than in those with dissections (P = .03; at the external half, P = .99). Aortic dissections and aneurysms show a decrease in collagen content that could be related to a weakness of the wall underlying the diseases, but the locations of the decrease differ: in dissections, it is situated mostly at the external portion of the media (site of cleavage), whereas in aneurysms, it is more diffuse, consistent with the global enlargement.