The risk profile change in patients with severe chronic thromboembolic pulmonary hypertension treated with subcutaneous treprostinil.

Chronic thromboembolic pulmonary hypertension (CTEPH) is successfully treatable with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty, and medical therapy. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management risk score (RRS) is able to predict long-term outcome in inoperable patients or in patients with residual PH after surgery. We performed a post hoc analysis of RRS in patients who were enrolled in the CTREPH study (NCT01416636), a randomized, double-blind clinical trial comparing high-dose and low-dose subcutaneous (SC) treprostinil in patients with severe CTEPH that was classified by an interdisciplinary CTEPH team as nonoperable, or as persistent or recurrent pulmonary hypertension after PEA. Baseline mean RRS was similar in both treatment groups (8.7 in high-dose arm vs. 8.6 in low-dose arm), but mean RRS change from baseline to Week 24 was greater in the high-dose treprostinil group than in the low-dose treprostinil group (-0.88 vs. -0.17). The difference in RRS change from baseline to Week 24 between high dose versus low dose was statistically significant with mean difference of -0.70 (95% confidence interval: -1.36 to -0.05, p = 0.0352), and was driven mainly by improvement of World Health Organization functional class and N-terminal pro-brain natriuretic peptide concentration. SC treprostinil therapy administered in standard dose had positive effect on the risk profile measured by RRS in patients with inoperable or persistent/recurrent severe CTEPH. Although our study was limited by the small sample size and post hoc nature, assessment of risk profile is of great importance to this particular patient population with very poor prognosis.

Central versus Peripheral CTEPH-Clinical and Hemodynamic Specifications.

Background and Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a chronic progressive disease, resulting from persistent arterial obstruction combined with small-vessel remodeling. Central and peripheral CTEPH are distinguished, according to the dominant lesion's location. This is important for surgical or percutaneous interventional assessment or for medical treatment. Material and Methods: Eighty-one patients (51 male/30 female) with confirmed CTEPH were analyzed, while the CENTRAL type included 51 patients (63%) and the PERIPHERAL type 30 patients (37%). Results: A significant difference in CENTRAL type vs. PERIPHERAL type was determined in gender (male 72.5% vs. 46.7%; p = 0.0198). No difference was found in age, functional status, or echocardiographic parameters. Invasive hemodynamic parameters showed a significant difference in mean pulmonary arterial pressure (46 vs. 58 mmHg; p = 0.0002), transpulmonary gradient (34 vs. 47 mmHg; p = 0.0005), and cardiac index (2.04 vs. 2.5 L.min.m2; p = 0.02) but not in pulmonary vascular resistance. Risk factors showed a significant difference only in acute pulmonary embolism (93.8% vs. 60%; p = 0.0002) and malignancy (2% vs. 13.3%; p = 0.0426). Conclusions: Our study showed hemodynamic differences between CENTRAL type vs. PERIPHERAL type CTEPH with a worse hemodynamic picture in CENTRAL form. This may indicate a different pathophysiological response and/or possible additional influences contributing especially to the peripheral pulmonary bed affection.

Epidemiology of chronic thromboembolic pulmonary hypertension (CTEPH) in the Czech Republic.

This study investigated the epidemiology and survival outcomes of chronic thromboembolic pulmonary hypertension (CTEPH) in the Czech Republic, wherein pulmonary endarterectomy (PEA) surgery was the only targeted treatment option until 2015. This study included all consecutive adults newly diagnosed with CTEPH in the Czech Republic between 2003 and 2016. Incidence/prevalence rates were calculated using general population data extracted from the Institute of Health Information and Statistics of the Czech Republic. Kaplan-Meier estimates of survival from diagnosis until 2018 were calculated. Of a total of 453 patients observed, 236 (52.1%) underwent PEA (median time from diagnosis to PEA: 2.9 months) and 71 (34.1%) had residual pulmonary hypertension (PH) post-PEA. CTEPH incidence rate (95% confidence interval [CI]) between 2006 and 2016 was 4.47 (4.05; 4.91) patients per million (ppm) per year, and the prevalence (95% CI) was 37.43 (33.46; 41.73) ppm in 2016. The rate of CTEPH-related hospitalizations (95% CI) per 100 person-years was 24.4 (22.1; 26.9) for operated patients and 34.2 (30.9; 37.7) for not-operated patients. Median overall survival (95% CI) for all patients from CTEPH diagnosis was 11.2 (9.4; not reached) years. Five-year survival probability (95% CI) was 95.3% (89.9; 97.9) for operated patients without residual PH, 86.3% (75.3; 92.7) for operated patients with residual PH and 61.2% (54.0; 67.6) for not-operated patients. This study reported epidemiological estimates of CTEPH in the Czech Republic consistent with estimates from other national systematic registries; and indicates an unmet medical need in not-operated patients and operated patients with residual PH.

A patient with pulmonary hypertension waiting for donor lungs during the pandemic: 194 days on extracorporeal life support including 143 days on pulmonary artery to left atrium shunt.

Patients with pulmonary hypertension and end-stage lung disease are fraught with high mortality while on a waiting list for lung transplant. With sometimes rapid deterioration they may require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as an immediate life-saving technique, which is a time-limited solution. The technique of pulmonary artery to left atrium (PA-LA) shunt fitted with an oxygenator enables bridging the patient to transplant for a longer time period. This low-resistance paracorporeal pumpless lung assist device allows for de-adaptation of the right ventricle back to lower afterload before the lung transplantation is carried out. The PA-LA shunt with an oxygenator also conveys a risk of multiple complications with reported median of 10-26 days until transplant. We report a case of pulmonary capillary hemangiomatosis in a 35-year-old female who had to wait for donor lungs during the pandemic of SARS-CoV-2 for 143 days on PA-LA shunt with oxygenator following 51 days on VA-ECMO. The extremely long course associated with multiple complications including three cerebral embolisms, episodes of sepsis and ingrowth of the return cannula into the left ventricular wall gives insight into the limits of this bridging technique.

The impact of riociguat on clinical parameters and quality of life in patients with chronic thromboembolic pulmonary hypertension - results of a retrospective clinical registry.

AIMS: The primary objective of the registry was to assess the impact of riociguat on clinical parameters and quality of life in patients with chronic thromboembolic pulmonary hypertension (CTEPH) that was inoperable or persistent/recurrent after pulmonary endarterectomy (PEA). In contrast to randomized pivotal trials, this non-interventional registry evaluated the effectiveness and safety of riociguat in a real-world setting. METHODS: Retrospective data were collected from patients' charts as recorded in routine clinical practice from the initiation of riociguat therapy up to approximately 5 months and 1 year after this initiation. RESULTS: In total, 51 patients from a single site were enrolled. After 5 months (mean duration) of riociguat treatment, the following improvements from baseline were observed: change of distance in the 6-minute walking distance (6MWD) (P=0.066); change of score from the quality of life questionnaire (EQ5D-5L) (P=0.020), and overall self-assessment of health status (P=0.001). New York Heart Association (NYHA) class improved in 24.3% of patients. After 11.2 months (mean duration) of riociguat treatment, the following improvements from baseline were observed: change of distance in the 6MWD test (P=0.006), and overall self-assessment of health status (P=0.009). NYHA class improved in 46.4% of patients. Riociguat was well tolerated. In total, 4 patients reported side effects, with hospitalization required in one case and 2 patients who had to discontinue the treatment. Annual survival rate was 89.1%. CONCLUSION: Riociguat improves functional NYHA class, distance in the 6MWD test and quality of life in a real-world patient population.

Lipid Profiling in Epicardial and Subcutaneous Adipose Tissue of Patients with Coronary Artery Disease.

Coronary artery disease is one of the most frequent causes of morbidity and mortality worldwide. It is even more prevalent in patients with type 2 diabetes mellitus who suffer from obesity and increased accumulation of epicardial fat with a possible contributing role in the development of coronary artery disease. We performed an MS-based lipidomic analysis of subcutaneous and epicardial adipose tissue in 23 patients with coronary artery disease stratified for the presence/absence of type 2 diabetes mellitus and a control group of 13 subjects aiming at identification of factors from epicardial fat contributing to the development of coronary artery disease. The samples of adipose tissues were obtained during elective cardiac surgery. They were extracted and analyzed with and without previous triacylglycerols separation by high-pressure liquid chromatography-mass spectrometry (HPLC-MS). Multivariate and univariate analyses were performed. Lipidomics data were correlated with biochemical parameters. We identified multiple changes in monoacylglycerols, diacylglycerols, triacylglycerols, glycerophosphatidylserines, glycerophosphatidylethanolamines, glycerophosphatidylcholines, ceramides, sphingomyelins, and derivatives of cholesterol. Observed changes included molecules with fatty acids with odd (15:0, 15:1, 17:0, 17:1) and even (10:0, 12:0, 14:0, 16:0, 16:1, 18:0, 18:1, 18:2, 20:4, 20:1, 22:0) fatty acids in both types of adipose tissue. More pronounced changes were detected in epicardial adipose tissue compared to subcutaneous adipose tissue of patients with coronary artery disease and type 2 diabetes. Lipidomic analysis of subcutaneous and epicardial adipose tissue revealed different profiles for patients with coronary artery disease and type 2 diabetes, which might be related to coronary artery disease and the presence of type 2 diabetes.

Mitral Valve Replacement Using Subvalvular Apparatus: A Systematic Review and Meta-Analysis.

BACKGROUND: To assess clinical outcomes among participants undergoing mitral valve replacement with preservation of subvalvular apparatus. METHODS: Electronic databases, including PubMed, Embase, Science Direct, World of Science, Scopus, Biosis, SciElo and Cochrane library, were probed using an extensive search strategy. Studies that reported at least one clinical outcome, such as morbidity, mortality, early 30-day mortality, myocardial failure, survival, late cerebrovascular events, length of stay, or major operative complications (stroke, prolonged ventilation, and reoperation for bleeding, renal failure, and sternal infection) were considered for inclusion. Data was extracted and pooled into a meta-analysis in RevMan (version 5.3) using a random-effects model. RESULTS: A total of 21 studies with 5,106 participants (age range: 27.3-69.2 years) were included in this meta-analysis. Preservation of the subvalvular apparatus during MVR significantly reduces the risk of long-term mortality (OR: 0.46; 95% CI: 0.33-0.64), but not early mortality (OR: 0.76; 95% CI: 0.12-4.93). No significant difference ejection fraction was observed (SMD: 0.10; 95% CI: -0.44-0.64). Similarly, there was no significant difference in the risk of stroke, renal failure, and pneumonia between C-MVR and in the control group. CONCLUSION: MVR with the preservation of subvalvular apparatus improves clinical outcomes, such as long-term mortality, hospital length of stay, pneumonia, and bleeding. There is no significant difference in the risk of stroke, renal failure, or ICU length of stay. However, there is very limited data available with respect to bleeding, sepsis, and nosocomial infections.

Population pharmacokinetics of riociguat and its metabolite in patients with chronic thromboembolic pulmonary hypertension from routine clinical practice.

Pharmacokinetic data for riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) have previously been reported from randomized clinical trials, which may not fully reflect the population encountered in routine practice. The aim of the current study was to characterize the pharmacokinetic of riociguat and its metabolite M1 in the patients from routine clinical practice. A population pharmacokinetic model was developed in NONMEM 7.3, based on riociguat and its metabolite plasma concentrations from 49 patients with CTEPH. One sample with riociguat and M1 concentrations was available from each patient obtained at different time points after last dose. Age, bodyweight, sex, smoking status, concomitant medications, kidney and liver function markers were tested as potential covariates of pharmacokinetic of riociguat and its metabolite. Riociguat and M1 disposition was best described with one-compartment models. Apparent volume of distribution (Vd/F) for riociguat and M1 were assumed to be the same. Total bilirubin and creatinine clearance were the most predictive covariates for apparent riociguat metabolic clearance to M1 (CLf,M1/F) and for apparent riociguat clearance through remaining pathways (CLe,r/F), respectively. CLf,M1/F, CLe,r/F, Vd/F of riociguat and M1, and clearance of M1 (CLe,M1/F) for a typical individual with 70 mL/min creatinine clearance and 0.69 mg/dL total bilirubin were 0.665 L/h (relative standard error = 17%)), 0.66 (18%) L/h, 3.63 (15%) L and 1.47 (19%) L/h, respectively. Upon visual identification of six outlying individuals, an absorption lag-time of 2.95 (6%) h was estimated for these patients. In conclusion, the only clinical characteristics related to riociguat exposure in patients with CTEPH from routine clinical practice are total bilirubin and creatinine clearance. This confirms the findings of the previous population pharmacokinetic studies based on data from randomized clinical trials.

Comparison of Different Thawing Protocols in Human Cryopreserved Venous Grafts.

BACKGROUND: The aim of our study was to assess the impact of different thawing protocols on morphological changes arising in cryopreserved human saphenous vein grafts. METHODS: The study was performed in 12 saphenous vein grafts harvested in brain death donors. Storage in the vapor phase of liquid nitrogen for 3 or 5 years followed. Two thawing protocols were tested: slow thawing in a refrigerator at temperature +4°C for 2 hr and rapid thawing-in a water bath at +37°C. Grafts were processed for scanning electron microscopy. Comparisons of continuous parameters under study between experimental groups were performed using the t-test (age, cold ischemia time, exposure to cryoprotectant, time of storage, total thawing time, mean thawing rate, morphology scoring of thawed HSVG) and the median test (HSVG length). Categorical parameters (sex and blood group) were formally tested using the chi-square test. RESULTS: All samples were evaluated according to morphological changes and scored in terms of morphologically intact endothelium, confluent endothelium with structural inhomogeneity, disruption of the intercellular contacts, separation of the endothelial cells, complete loss of the endothelium, and damage of the subendothelial layers. There is no statistically significant difference between the sample sets at the significance level of 0.05. There was no association with donors' age, sex, and time of storage. CONCLUSIONS: Human cryopreserved saphenous vein grafts in our experimental work showed no difference in terms of structural deterioration of the endothelial surface and basal membrane depending on different thawing protocols used.

Serum albumin in patients undergoing transcatheter aortic valve replacement: A meta-analysis.

Transcatheter aortic valve replacement is becoming a more common therapeutic option for the treatment of aortic stenosis in patients at high risk for invasive surgery, but detecting which patients will benefit clinically can be challenging. Hypoalbuminemia is a useful prognostic marker for chronic inflammation in this population. We carried out a systematic review and meta-analysis of studies evaluating the prognostic value of serum albumin level in patients undergoing transcatheter aortic valve replacement. A literature search of PubMed, Embase, ScienceDirect, Web of Science, SciELO, BIOSIS, Wanfang, and CNKI databases was conducted. Articles published between January 2000 and December 2017 reporting on the prognostic value of low levels of serum albumin in patients undergoing transcatheter aortic valve replacement were analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. 11 studies including 6456 patients met inclusion criteria for meta-analysis. A lower serum albumin level was associated with a lower survival rate at follow-up in patients who underwent transcatheter aortic valve replacement. A sub-group analysis of eight studies reporting adjusted hazard ratios indicated that low serum albumin was independently correlated with increased post-operative mortality. The hazard ratio of mortality risk associated with each 1 g/dL increment in serum albumin level was 0.46, suggesting a potential dose-response relationship between increased serum albumin level and increased survival rate in patients undergoing transcatheter aortic valve replacement. This meta-analysis provides strong evidence for the utility of serum albumin as a prognostic marker in aortic stenosis patients undergoing transcatheter aortic valve replacement, with low serum albumin levels (2.5-3.5 g/dL) suggesting poor prognosis.

The number and phenotype of myocardial and adipose tissue CD68+ cells is associated with cardiovascular and metabolic disease in heart surgery patients.

BACKGROUND AND AIMS: CD68+ cells are a potent source of inflammatory cytokines in adipose tissue and myocardium. The development of low-grade inflammation in adipose tissue is implicated in the pathogenesis of obesity-associated disorders including type 2 diabetes mellitus (T2DM) and cardiovascular disease. The main aim of the study was to characterize and quantify myocardial and adipose tissue CD68+ cells and adipose tissue crown-like structures (CLS) in patients with obesity, coronary artery disease (CAD) and T2DM. METHODS AND RESULTS: Samples were obtained from the right atrium, epicardial (EAT) and subcutaneous adipose tissue (SAT) during elective heart surgery (non-obese, n = 34 patients; obese, n = 24 patients). Immunohistochemistry was used to visualize CD68+ cells. M1-polarized macrophages were visualized by immunohistochemical detection of CD11c. The proportion of CD68+ cells was higher in EAT than in SAT (43.4 ± 25.0 versus 32.5 ± 23.1 cells per 1 mm2; p = 0.015). Myocardial CD68+ cells were more abundant in obese patients (45.6 ± 24.5 versus 27.7 ± 14.8 cells per 1 mm2; p = 0.045). In SAT, CD68+ cells were more frequent in CAD patients (37.3 ± 23.0 versus 23.1 ± 20.9 cells per 1 mm2; p = 0.012). Patients having CLS in their SAT had higher average BMI (34.1 ± 6.4 versus 29.0 ± 4.5; p = 0.024). CONCLUSIONS: Regional-based increases in the frequency of CD68+ cells and changes of their phenotype in CLS were detected in obese patients and CAD patients. Therapeutic modulation of adipose tissue inflammation may represent a target for treatment of obesity.

Dendritic Cells in Subcutaneous and Epicardial Adipose Tissue of Subjects with Type 2 Diabetes, Obesity, and Coronary Artery Disease.

Dendritic cells (DCs) are professional antigen-presenting cells contributing to regulation of lymphocyte immune response. DCs are divided into two subtypes: CD11c-positive conventional or myeloid (cDCs) and CD123-positive plasmacytoid (pDCs) DCs. The aim of the study was to assess DCs (HLA-DR+ lineage-) and their subtypes by flow cytometry in peripheral blood and subcutaneous (SAT) and epicardial (EAT) adipose tissue in subjects with (T2DM, n = 12) and without (non-T2DM, n = 17) type 2 diabetes mellitus undergoing elective cardiac surgery. Subjects with T2DM had higher fasting glycemia (8.6 ± 0.7 vs. 5.8 ± 0.2 mmol/l, p < 0.001) and glycated hemoglobin (52.0 ± 3.4 vs. 36.9 ± 1.0 mmol/mol, p < 0.001) and tended to have more pronounced inflammation (hsCRP: 9.8 ± 3.1 vs. 5.1 ± 1.9 mg/ml, p = 0.177) compared with subjects without T2DM. T2DM was associated with reduced total DCs in SAT (1.57 ± 0.65 vs. 4.45 ± 1.56% for T2DM vs. non-T2DM, p = 0.041) with a similar, albeit insignificant, trend in EAT (0.996 ± 0.33 vs. 2.46 ± 0.78% for T2DM vs. non-T2DM, p = 0.171). When analyzing DC subsets, no difference in cDCs was seen between any of the studied groups or adipose tissue pools. In contrast, pDCs were increased in both SAT (13.5 ± 2.0 vs. 4.6 ± 1.9% of DC cells, p = 0.005) and EAT (29.1 ± 8.7 vs. 8.4 ± 2.4% of DC, p = 0.045) of T2DM relative to non-T2DM subjects as well as in EAT of the T2DM group compared with corresponding SAT (29.1 ± 8.7 vs. 13.5 ± 2.0% of DC, p = 0.020). Neither obesity nor coronary artery disease (CAD) significantly influenced the number of total, cDC, or pDC in SAT or EAT according to multiple regression analysis. In summary, T2DM decreased the amount of total dendritic cells in subcutaneous adipose tissue and increased plasmacytoid dendritic cells in subcutaneous and even more in epicardial adipose tissue. These findings suggest a potential role of pDCs in the development of T2DM-associated adipose tissue low-grade inflammation.

Prognostic Role of Admission C-Reactive Protein Level as a Predictor of In-Hospital Mortality in Type-A Acute Aortic Dissection: A Meta-Analysis.

BACKGROUND: Acute aortic dissection (AD) is a lethal vascular disease, accounting for over 90% cases of acute aortic syndrome. Despite advances in understanding associated risk factors, the long-term prognosis for AD patients is still poor. Several prognostic biomarkers have been used for AD as per the IRAD, such as older age (>70 years), onset of chest pain and hypotension, but they are not effective in all patients. Instead, C-reactive protein (CRP) is a consistent inflammatory marker. CRP levels are abnormally increased in AD. However, the prognostic value of serum CRP level in AD remains unclear. OBJECTIVE: To perform a systematic review and meta-analysis (registration no CRD42017056205) to evaluate whether CRP is a biomarker associated with in-hospital mortality in type-A AD. METHODS: PubMed, Web of Science, CNKI, SciELO, and EMBASE were searched for papers published from January 2000 to October 2017 for studies on the prognostic role of CRP at admission in type-A AD patients. Outcome data were extracted and pooled hazard ratios (HRs) were calculated. RESULTS: 18 (N = 2875 patients) studies met the inclusion criteria. Elevated CRP level was associated with a significantly increased risk of in-hospital mortality in patients with type-A AD (HR = 1.15, 95% CI: 1.06-1.25, p = 0.001). The pooled sensitivity of CRP in type-A AD patients was 77% (95% CI 69%-84%, p < 0.001), and the specificity was 72% (95% CI 66%-78%, p < 0.001). CONCLUSION: Elevated CRP level is significantly associated with increased risks of in-hospital mortality in patients with type-A AD. CRP is a convenient prognostic factor in type-A AD patients.

Aortic root surgery with the CARDIOROOT vascular graft: results of a prospective multicenter post-market surveillance study.

BACKGROUND: Sparing Aortic Valve procedure requires to reproduction of the geometry of the physiologic anatomy of the aortic root. Thus, the materials adopted may make a difference. CARDIOROOT is a one-piece collagen-coated woven vascular graft with pseudo-sinuses, which was designed for use in the treatment of aortic root disease. We report the results of a prospective, multicenter, observational post-market surveillance study evaluating the safety and performance of the CARDIOROOT in patients requiring aortic root surgery. METHODS: Patients with aortic root disease suitable for treatment with a vascular graft with pseudo-sinuses CARDIOROOT graft were eligible for participation. The enrolled patients were assessed intraoperatively, post-operatively, at discharge and at 1-year. Sites assessed complications at each visit, and recorded any reported adverse events. The study endpoint was mortality and complications through 1-year post-procedure. RESULTS: Fifty-two patients were enrolled from 6 European centers. All procedures were technically successful. Operative mortality was 1.9%: one patient suffered hemorrhagic shock unrelated to the graft 1 day following surgery. At 1-year follow-up the survival rate was 96.2%, with a late death due to pneumonia 5 months post-procedure. Eleven serious adverse events occurred in 7 patients, which included cardiac complications (pericardial effusion, myocardial infarction and ventricular arrhythmia), infection (pericardial infection, deep sternal infection and superficial sternal infection), vascular disorders, including hemorrhagic shock and pleural effusion requiring drainage. Nine of the 11 events were deemed procedure-related by the local investigator, and all were deemed unrelated to the device. There were no reports of graft-related adverse events, infection, occlusion or graft failure. CONCLUSIONS: The results of this 1-year follow-up study showed that the CARDIOROOT vascular graft is safe and effective for the treatment of aneurysmal aortic root in immediate and mid-term follow-up. However, longer term follow-up is needed before conclusions can be made on the long-term safety and effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01609270. Registered 31 May 2012.

Coronary Artery Disease Is Associated with an Increased Amount of T Lymphocytes in Human Epicardial Adipose Tissue.

Immunocompetent cells including lymphocytes play a key role in the development of adipose tissue inflammation and obesity-related cardiovascular complications. The aim of the study was to explore the relationship between epicardial adipose tissue lymphocytes and coronary artery disease (CAD). To this end, we studied the content and phenotype of lymphocytes in peripheral blood, subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT) in subjects with and without CAD undergoing elective cardiac surgery. Eleven subjects without CAD (non-CAD group) and 22 age-, BMI-, and HbA1C-matched individuals with CAD were included into the study. Blood, SAT, and EAT samples were obtained at the beginning of surgery. Lymphocyte populations were quantified as % of CD45+ cells using flow cytometry. Subjects with CAD had a higher total lymphocyte amount in EAT compared with SAT (32.24 ± 7.45 vs. 11.22 ± 1.34%, p = 0.025) with a similar trend observed in non-CAD subjects (29.68 ± 7.61 vs. 10.13 ± 2.01%, p = 0.067). T (CD3+) cells were increased (75.33 ± 2.18 vs. 65.24 ± 4.49%, p = 0.032) and CD3- cells decreased (21.17 ± 2.26 vs. 31.64 ± 4.40%, p = 0.028) in EAT of CAD relative to the non-CAD group. In both groups, EAT showed an elevated percentage of B cells (5.22 ± 2.43 vs. 0.96 ± 0.21%, p = 0.039 for CAD and 12.49 ± 5.83 vs. 1.16 ± 0.19%, p = 0.016 for non-CAD) and reduced natural killer (NK) cells (5.96 ± 1.32 vs. 13.22 ± 2.10%, p = 0.012 for CAD and 5.32 ± 1.97 vs. 13.81 ± 2.72%, p = 0.022 for non-CAD) relative to SAT. In conclusion, epicardial adipose tissue in subjects with CAD shows an increased amount of T lymphocytes relative to non-CAD individuals as well as a higher number of total and B lymphocytes and reduced NK cells as compared with corresponding SAT. These changes could contribute to the development of local inflammation and coronary atherosclerosis.

Minor lipids profiling in subcutaneous and epicardial fat tissue using LC/MS with an optimized preanalytical phase.

Analysis of bioactive lipids in adipose tissue could lead to better understanding of the pathogenesis of obesity and its complications. However, current MS methods are limited by a high content of triacylglycerols (TAGs), which markedly surpasses the amount of other lipids and suppresses their ionization. The aim of our study was thus to optimize the preanalytical phase of lipid analysis in adipose tissue, focusing in particular on less-abundant lipids. Next, the optimized method was used to describe the differences between epicardial and subcutaneous adipose tissues obtained from patients undergoing cardiac surgery. Lipids were extracted using a modified Folch method with subsequent detachment of TAGs by thin layer chromatography (TLC). The extracts with/without TAGs were analyzed by tandem LC/MS. The repeatability of the presented method expressed by the median of the coefficients of variation was 12/5% for analysis with/without TAGs separation, respectively. The difference in the relative abundance of TAGs gained with/without TLC was, on average, 19% and did not reach significance (p value > 0.05) for any identified TAG. The novel preanalytical step allowed us to detect 37 lipids, which could not have been detected without TAG separation, because their signal to noise ratio is <5 in current methods of untargeted lipidomics. These lipids belong predominately to ceramides, glycerophosphatidylserines, glycerophosphatidylinsitols, sphingomyelins, glycerophosphatidylcholines, glycerophosphatidylethanolamines, diacylglycerols. The two adipose tissue depots differed mainly in the following lipid classes: glycerophosphatidylcholines, glycerophosphatidylinositols, glycerophosphatidylethanolamine, and sphingomyelins. Moreover, other major lipids showed distinctly different distributions between the two adipose tissues. Among these, the changes in TAGs were the most striking, which correspond to previously published data describing the differences between omental and subcutaneous adipose tissue. Implementation of the TLC step for the elimination of TAGs was crucial for enhancing the MS detection limit of minor lipids in adipose tissue. The differences between the overall lipid profiles of subcutaneous and epicardial tissue reflect their different functions arising from their location.

Fibrin sealants in cardiac surgery: The last five years of their development and application.

This review article describes the use of fibrin glue or fibrin sealants and their development over the past 5 years, with a focus on cardiac surgery. The roles of various types of sealants that are available in hemostasis control are reviewed briefly, together with the various potential risks and side effects of their use. The results of experimental work reported during the last 5 years, clinical data from the same period and the safety aspects of fibrin-based glues and sealants are summarized, showing many advantages of their clinical application over the use of synthetic glues or sealants that may be stronger in some cases, but less safe. It can be concluded that the widespread use of fibrin sealants is fully justified, as it benefits the patient as well as the surgeon through the improved control of hemostasis without increasing any adverse effects or complications during surgical procedures.

Residual pulmonary hypertension after pulmonary endarterectomy: A meta-analysis.

OBJECTIVE: Chronic thromboembolic pulmonary hypertension is surgically treated through pulmonary endarterectomy. Although pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension in terms of both functional outcomes and survival, many patients experience persistent pulmonary hypertension after pulmonary endarterectomy. The study objective was to calculate the pooled estimates of outcomes after pulmonary endarterectomy, including persistent pulmonary hypertension. METHODS: Meta-analyses were conducted on published studies reporting residual/persistent/recurrent pulmonary hypertension in 4868 patients with chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy. The rate of persistent pulmonary hypertension and change in mean pulmonary artery pressure, pulmonary vascular resistance, and 6-minute walk distance after pulmonary endarterectomy were outcomes of interest. RESULTS: Twenty-five percent of patients with chronic thromboembolic pulmonary hypertension were diagnosed with persistent pulmonary hypertension after pulmonary endarterectomy. Pulmonary endarterectomy reduced mean pulmonary artery pressure and pulmonary vascular resistance by approximately 21 mm Hg (standardized mean difference, 1.75; 95% confidence interval, -1.62 to 1.88; P < .00001) and 561 dyn.s/cm5 (standardized mean difference, 1.64; 95% confidence interval, -1.58 to 1.70; P < .00001), respectively. Conversely, 6-minute walk distance increased by 96 m (standardized mean difference, -0.83; 95% confidence interval, -0.91 to -0.76; P < .00001) after pulmonary endarterectomy. CONCLUSIONS: Pulmonary endarterectomy is the gold standard treatment for chronic thromboembolic pulmonary hypertension and provides immediate correction of hemodynamic parameters in most patients. However, in up to one quarter of operable cases, pulmonary hypertension persists after surgery. In those patients with persistent pulmonary hypertension, continued medical management with newer agents may be required to improve pulmonary hemodynamics and, therefore, patient outcomes.

Role of Dipyrone in the High On-Treatment Platelet Reactivity amongst Acetylsalicylic Acid-Treated Patients Undergoing Peripheral Artery Revascularisation.

OBJECTIVE: To evaluate the effects of dipyrone on sensitivity to aspirin (acetylsalicylic acid [ASA]) in patients who underwent peripheral artery vascular reconstruction. SUBJECTS AND METHODS: Impedance aggregometry and light transmission aggregometry were used to determine the effects of dipyrone on ASA treatment in 21 patients. Blood samples were drawn in a 7-day period after the surgery. The cut-off value for high on-treatment platelet reactivity (HTPR) was set at < 65% of aggregation inhibition for impedance aggregometry. For light transmission aggregometry the cut-off value for arachidonic acid-induced aggregation was set at > 20% of aggregating platelets, and the cut-off value for epinephrine-induced aggregation was > 44% of aggregating platelets. The cut-off value for each method was derived from a large number of patients treated with a daily dose of 100 mg of ASA. RESULTS: We found HTPR in 14 (67%) of the 21 patients. None had primary resistance to ASA, i.e., after the addition of ASA in vitro all samples showed antiplatelet efficacy. Regression analysis showed a possible correlation between lower efficacy of ASA treatment and higher daily doses of dipyrone (p = 0.005 for impedance aggregometry, p = 0.04 for light transmission aggregometry), higher platelet count (p = 0.005 for impedance aggregometry), and shorter time from surgery (p = 0.03 for impedance aggregometry). CONCLUSION: HTPR occurs in 67% of ASA-treated patients after lower limb vascular surgery. The occurrence of HTPR correlates with the daily dose of dipyrone. Therefore, dipyrone should not be used as a postoperative analgesic in ASA-treated patients after peripheral artery revascularisation due to its influence on the effectiveness of ASA.