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Introduction: G-protein coupled receptors (GPCRs) expressed on neutrophils regulate their mobilization from the bone marrow into the blood, their half-live in the circulation, and their pro- and anti-inflammatory activities during inflammation. Chronic kidney disease (CKD) is associated with systemic inflammatory responses, and neutrophilia is a hallmark of CKD onset and progression. Nonetheless, the role of neutrophils in CKD is currently unclear., Methods: Blood and renal tissue were collected from non-dialysis CKD (grade 3 - 5) patients to evaluate GPCR neutrophil expressions and functions in CKD development., Results: CKD patients presented a higher blood neutrophil-to-lymphocyte ratio (NLR), which was inversely correlated with the glomerular filtration rate (eGFR). A higher frequency of neutrophils expressing the senescent GPCR receptor (CXCR4) and activation markers (CD18 + CD11b + CD62L + ) was detected in CKD patients. Moreover, CKD neutrophils expressed higher amounts of GPCR formyl peptide receptors (FPR) 1 and 2, known as neutrophil pro- and anti-inflammatory receptors, respectively. Cytoskeletal organization, migration, and production of reactive oxygen species (ROS) by CKD neutrophils were impaired in response to the FPR1 agonist (fMLP), despite the higher expression of FPR1. In addition, CKD neutrophils presented enhanced intracellular, but reduced membrane expression of the protein Annexin A1 (AnxA1), and an impaired ability to secrete it into the extracellular compartment. Secreted and phosphorylated AnxA1 is a recognized ligand of FPR2, pivotal in anti-inflammatory and efferocytosis effects. CKD renal tissue presented a low number of neutrophils, which were AnxA1 + ., Conclusion: Together, these data highlight that CKD neutrophils overexpress GPCRs, which may contribute to an unbalanced aging process in the circulation, migration into inflamed tissues, and efferocytosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Scharf, Sandri, Rizzetto, Xavier, Grosso, Correia-Silva, Farsky, Gil and Farsky.)

In coronary artery bypass grafting (CABG) the use of the internal thoracic artery (ITA), is a Class I indication for the left anterior descending (LAD) artery. Atherosclerosis is a systemic disease, and peripheral arterial disease (PAD) is an important complicator of CABG, present in about one-third of the patients with coronary disease. In Leriche Syndrome, ITA can be the source of collateral circulation for arteries below the level of occlusion. Its inadvertent use can lead to serious ischemic complications in the dependent territories.

Objectives: Optimal medical therapy in patients with heart failure and coronary artery disease is associated with improved outcomes. However, whether this association is influenced by the performance of coronary artery bypass grafting is less well established. Thus, the aim of this study was to determine the possible relationship between coronary artery bypass grafting and optimal medical therapy and its effect on the outcomes of patients with ischemic cardiomyopathy., Methods: The Surgical Treatment for Ischemic Heart Failure trial randomized 1212 patients with coronary artery disease and left ventricular ejection fraction 35% or less to coronary artery bypass grafting with medical therapy or medical therapy alone with a median follow-up over 9.8 years. For the purpose of this study, optimal medical therapy was collected at baseline and 4 months, and defined as the combination of 4 drugs: angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, statin, and 1 antiplatelet drug., Results: At baseline and 4 months, 58.7% and 73.3% of patients were receiving optimal medical therapy, respectively. These patients had no differences in important parameters such as left ventricular ejection fraction and left ventricular volumes. In a multivariable Cox model, optimal medical therapy at baseline was associated with a lower all-cause mortality (hazard ratio, 0.78; 95% confidence interval, 0.66-0.91; P = .001). When landmarked at 4 months, optimal medical therapy was also associated with a lower all-cause mortality (hazard ratio, 0.82; 95% confidence interval, 0.62-0.99; P = .04). There was no interaction between the benefit of optimal medical therapy and treatment allocation., Conclusions: Optimal medical therapy was associated with improved long-term survival and lower cardiovascular mortality in patients with ischemic cardiomyopathy and should be strongly recommended., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Chronic kidney disease is a known risk factor in cardiovascular disease, but its influence on treatment effect of bypass surgery remains unclear. We assessed the influence of chronic kidney disease on 10-year mortality and cardiovascular outcomes in patients with ischemic heart failure treated with medical therapy (medical treatment) with or without coronary artery bypass grafting., Methods: We calculated the baseline estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula, chronic kidney disease stages 1-5) from 1209 patients randomized to medical treatment or coronary artery bypass grafting in the Surgical Treatment for IsChemic Heart failure trial and assessed its effect on outcome., Results: In the overall Surgical Treatment for IsChemic Heart failure cohort, patients with chronic kidney disease stages 3 to 5 were older than those with stages 1 and 2 (66-71 years vs 54-59 years) and had more comorbidities. Multivariable modeling revealed an inverse association between estimated glomerular filtration rate and risk of death, cardiovascular death, or cardiovascular rehospitalization (all P < .001, but not for stroke, P = .697). Baseline characteristics of the 2 treatment arms were equal for each chronic kidney disease stage. There were significant improvements in death or cardiovascular rehospitalization with coronary artery bypass grafting (stage 1: hazard ratio, 0.71; confidence interval, 0.53-0.96, P = .02; stage 2: hazard ratio, 0.71; confidence interval, 0.59-0.84, P < .0001; stage 3: hazard ratio, 0.76; confidence interval, 0.53-0.96, P = .03). These data were inconclusive in stages 4 and 5 for insufficient patient numbers (N = 28). There was no significant interaction of estimated glomerular filtration rate with the treatment effect of coronary artery bypass grafting (P = .25 for death and P = .54 for death or cardiovascular rehospitalization)., Conclusions: Chronic kidney disease is an independent risk factor for mortality in patients with ischemic heart failure with or without coronary artery bypass grafting. However, mild to moderate chronic kidney disease does not appear to influence long-term treatment effects of coronary artery bypass grafting., (Copyright © 2020 The American Association for Thoracic Surgery. All rights reserved.)

Background: According to the World Health Organization, emerging countries will have an enormous growth in the number of heart attacks and related deaths. The main medical issue in Brazil is mortality caused by acute ST elevation myocardial infarction (STEMI). The Society of Cardiology in the State of São Paulo has never trained non-cardiologists as emergency personnel. Patients usually seek help from emergency departments instead of calling for an ambulance., Objectives: We aimed at reducing in-hospital death rates from acute myocardial infarction by training emergency personnel in the city of Sao Paulo., Methods: We used a training program for the personnel of five hospitals with >100 patients admitted with STEMI per year, and at least 15% in-hospital STEMI-associated mortality rate. We performed internet training, biannual-quarterly symposia for up to 400 participants, informative folders and handouts. Statistical analysis used the two proportion comparison test with p <0.05., Results: Nearly 200 physicians and 350 nurses attended at least one training from May 2010 to December 2013. Initially, many emergency physicians could not recognize an acute myocardial infarction on the electrocardiogram, but tele-electrocardiography is used in some emergency departments to determine the diagnosis. The death rate in the five hospitals decreased from 25.6%, in 2009, to 18.2%, in 2010 (p=0.005). After the entire period of training, the STEMI-associated death rate in all public hospitals of São Paulo decreased from 14.31%, in 2009, to 11.25%, in 2014 (p<0.0001)., Conclusion: Even simple training programs for emergency personnel can greatly reduce acute myocardial infarction death rates in undeveloped countries.

Background: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but <45% is unknown., Methods: Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years., Results: There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, -12.1% [95% CI, -22.6 to -1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, -1.6% [95% CI, -3.8% to 0.7%]; P interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy-associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF., Conclusions: ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Background: Abdominal aortic aneurysm (AAA) is a pathological enlargement of infrarenal aorta close to the aortic bifurcation, and it is an important cause of mortality in the elderly. Therefore, the biomarker identification for early diagnosis is of great interest for clinical benefit. It is known that microRNAs (miRNAs) have important roles via target genes regulation in many diseases. This study aimed to identify miRNAs and their target genes involved in the pathogenesis of AAA., Methods: Tissue samples were obtained from patients who underwent AAA surgery and from organ donors (control group). Quantitative PCR Array was applied to assess 84 genes and 384 miRNAs aiming to identify differentially expressed targets (AAA n = 6, control n = 6), followed by validation in a new cohort (AAA n = 18, control n = 6) by regular qPCR. The functional interaction between validated miRNAs and target genes was performed by the Ingenuity Pathway Analysis (IPA) software., Results: The screening cohort assessed by PCR array identified 10 genes and 59 miRNAs differentially expressed (≥2-fold change, p<0.05). Among these, IPA identified 5 genes and 9 miRNAs with paired interaction. ALOX5, PTGIS, CX3CL1 genes, and miR-193a-3p, 125b-5p, 150-5p maintained a statistical significance in the validation cohort. IPA analysis based on the validated genes and miRNAs revealed that eicosanoid and metalloproteinase/TIMP synthesis are potentially involved in AAA., Conclusion: Paired interactions of differentially expressed ALOX5, PTGIS, CX3CL1 genes, and miR-193b-3p, 125b-5p, 150-5p revealed a potentially significant role of the eicosanoid synthesis and metalloproteinase/TIMP pathways in the AAA pathogenesis., Competing Interests: The authors have declared that no competing interests exist.

Background: The objectives of this study are to validate the Quality of Life in Cardiovascular Surgery (QLCS) questionnaire and to observe the evolution of quality of life in the first year of postoperative follow-up of patients who underwent coronary artery bypass grafting (CABG)., Methods: This was a prospective observational study of patients undergoing CABG from July 2016 to June 2017 who survived and answered the QLCS with 1, 6, and 12 months of follow-up. Validation was evaluated for internal consistency by Cronbach's alpha, test-retest reproducibility by correlation coefficient of concordance, and accuracy for interrater reliability by the kappa statistic. The nonparametric analysis of variance test was used for analysis of repeated measures, during follow-up, of the QLCS was considered significant at p < 0.05., Results: Included were 360 patients, with a mean age of 63 years; 72% were men. Cronbach's alpha was 0.82, demonstrating adequate internal consistency. The correlation coefficient of concordance was 0.93 and accuracy 0.99, showing good precision and accuracy. The kappa statistic for questions ranged from 0.58 to 0.78, which ensures a moderate reproducibility. Scores of the QLCS in patients undergoing CABG of 17.69, 18.82, and 19.52 were found at 1, 6, and 12 months, respectively. Thus there was a progressive improvement in quality of life over the first year of follow-up (p < 0.0001)., Conclusions: The QLCS proved to be a good questionnaire in this population, with adequate internal consistency and moderate reproducibility. Its use revealed a progressive and significant improvement in the quality of life of patients undergoing CABG., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The role of assessment of myocardial viability in identifying patients with ischemic cardiomyopathy who might benefit from surgical revascularization remains controversial. Furthermore, although improvement in left ventricular function is one of the goals of revascularization, its relationship to subsequent outcomes is unclear., Methods: Among 601 patients who had coronary artery disease that was amenable to coronary-artery bypass grafting (CABG) and who had a left ventricular ejection fraction of 35% or lower, we prospectively assessed myocardial viability using single-photon-emission computed tomography, dobutamine echocardiography, or both. Patients were randomly assigned to undergo CABG and receive medical therapy or to receive medical therapy alone. Left ventricular ejection fraction was measured at baseline and after 4 months of follow-up in 318 patients. The primary end point was death from any cause. The median duration of follow-up was 10.4 years., Results: CABG plus medical therapy was associated with a lower incidence of death from any cause than medical therapy alone (182 deaths among 298 patients in the CABG group vs. 209 deaths among 303 patients in the medical-therapy group; adjusted hazard ratio, 0.73; 95% confidence interval, 0.60 to 0.90). However, no significant interaction was observed between the presence or absence of myocardial viability and the beneficial effect of CABG plus medical therapy over medical therapy alone (P = 0.34 for interaction). An increase in left ventricular ejection fraction was observed only among patients with myocardial viability, irrespective of treatment assignment. There was no association between changes in left ventricular ejection fraction and subsequent death., Conclusions: The findings of this study do not support the concept that myocardial viability is associated with a long-term benefit of CABG in patients with ischemic cardiomyopathy. The presence of viable myocardium was associated with improvement in left ventricular systolic function, irrespective of treatment, but such improvement was not related to long-term survival. (Funded by the National Institutes of Health; STICH ClinicalTrials.gov number, NCT00023595.)., (Copyright © 2019 Massachusetts Medical Society.)

Objective: Elaboration and internal validation of the Quality of Life in Cardiovascular Surgery (QLCS) questionnaire adapted to the reality of Brazilian cardiovascular surgery., Methods: Cross-sectional pilot study of a prospective cohort included in the Documentation and Surgical Registry Center (CEDREC) for internal validation of the QLCS questionnaire. Four hundred forty-five patients submitted to cardiovascular surgery and who answered a QLCS questionnaire 30 days after hospital discharge were included. It was applied via telephone. To verify the questions' internal consistency, Cronbach's alpha was used. The total QLCS score was calculated as the sum of 5 questions, ranging from 5 to 25 points. Mann-U-Whitney test was used to relate the symptoms with the quality of life (QoL). Level of significance was 5%., Results: After 30 days of surgery, about 95% of the patients had already returned to normal routine and 19% of them were already performing physical activity. In the evaluation of the QLCS's internal consistency, a Cronbach's alpha of 0.74 was found, suggesting that this was probably an adequate questionnaire to evaluate QoL in this population. In the comparison between the presence and absence of symptoms and the median of QoL, the presence of pain at the incision (P=0.002), chest pain (P<0.001), shortness of breath (P<0.001), and return to physical activity (P<0.001) were statistically significant., Conclusion: The process of elaboration and validation of questionnaires includes a series of steps. The QLCS questionnaire is probably an adequate tool for the evaluation of QoL in the postoperative patient of cardiovascular surgery, in this first stage of internal validation.

Background: Studies have pointed out a higher mortality after coronary artery bypass surgery (CABG) in patients with stent., Objective: To evaluate inflammatory markers in peripheral blood cells and in coronary artery tissue samples obtained during CABG in patients with stent compared to controls., Methods: The case series consisted of two groups, one with previous stent implantation (n = 41) and one control (n = 26). The expression of the LIGHT, IL-6, ICAM, VCAM, CD40, NFKB, TNF, IFNG genes was analyzed in peripheral blood cells collected preoperatively. The coronary artery was evaluated for: interleukin-6, ICAM, VCAM, CD40, NFKB, TNF-alpha and IFN-gamma by immunohistochemistry. A total of 176 tissue samples were grouped for analysis in: A1- arteries with stent (n = 38); A2- native arteries from patients with stent in another artery (n = 68); and A3- arteries without stent from controls undergoing routinely CABG surgery (n = 70). A significance level of 0.05 was adopted., Results: Patients with stent showed higher TNF (p = 0.03) and lower CD40 gene expression (p = 0.01) in peripheral blood cells than controls without stent. In coronary artery samples, the TNF-alpha protein staining was higher in the group A1, not only in the intima-media layer (5.16 ± 5.05 vs 1.90 ± 2.27; p = 0.02), but also in the adipose tissue (6.69 ± 3.87 vs 2.27 ± 4.00; p < 0.001). Furthermore, group A1 had a higher interleukin-6 protein staining in adipose tissue than group A3 (p = 0.04)., Conclusion: We observed a persistently higher systemic TNF expression associated with exacerbated TNF-alpha and interleukin-6 local production in patients with stents. This finding may contribute to a worse clinical outcome.

Background: Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study)., Methods: The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex., Results: At baseline, women were older (63.4 versus 59.3 years; P =0.016) with higher body mass index (27.9 versus 26.7 kg/m 2 ; P =0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all P <0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all P <0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52-0.86; P =0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48-0.89; P =0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all P >0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%; P =0.187) between sexes among patients randomized to CABG per protocol as initial treatment., Conclusions: Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595., (© 2018 American Heart Association, Inc.)

Objective: To correlate blood transfusions and clinical outcomes during hospitalization in coronary artery bypass grafting surgery (CABG)., Methods: Transfusion, clinical and hematological data were collected for 1,378 patients undergoing isolated or combined CABG between January 2011 and December 2012. The effect of blood transfusions was evaluated through multivariate analysis to predict three co-primary outcomes: composite ischemic events, composite infectious complications and hospital mortality. Because higher risk patients receive more transfusions, the hospital mortality outcome was also tested on a stratum of low-risk patients to isolate the effect of preoperative risk on the results., Results: The transfusion rate was 63.9%. The use of blood products was associated with a higher incidence of the three coprimary outcomes: composite infectious complications (OR 2.67, 95% CI 1.70 to 4.19; P<0.001), composite ischemic events (OR 2.42, 95% CI 1.70 to 3.46; P<0.001) and hospital mortality (OR 3.07, 95% CI 1.53 to 6.13; P<0.001). When only patients with logistic EuroSCORE ≤ 2% were evaluated, i.e., low-risk individuals, the mortality rate and the incidence of ischemic events and infectious complications composites remained higher among the transfused patients [6% vs. 0.4% (P<0.001), 11.7% vs. 24,3% (P<0.001) and 6.5% vs. 12.7% (P=0.002), respectively]., Conclusion: The use of blood components in patients undergoing CABG was associated with ischemic events, infectious complications and hospital mortality, even in low-risk patients.

The dehiscence after median transesternal sternotomy used as surgical access for cardiac surgery is one of its complications and it increases the patient's morbidity and mortality. A variety of surgical techniques were recently described resulting to the need of a classification bringing a measure of objectivity to the management of these complex and dangerous wounds. The different related classifications are based in the primary causal infection, but recently the anatomical description of the wound including the deepness and the vertical extension showed to be more useful. We propose a new classification based only on the anatomical changes following sternotomy dehiscence and chronic wound formation separating it in four types according to the deepness and in two sub-groups according to the vertical extension based on the inferior insertion of the pectoralis major muscle.