Activated clotting time value as an independent predictor of postoperative bleeding and transfusion.

OBJECTIVES: Activated clotting time (ACT) is commonly used to monitor anticoagulation during cardiac surgeries. Final ACT values may be essential to predict postoperative bleeding and transfusions, although ideal values remain unknown. Our aim was to evaluate the utility of ACT as a predictor of postoperative bleeding and transfusion use. METHODS: Retrospective study (722 patients) submitted to surgery between July 2018-October 2021. We compared patients with final ACT < basal ACT and final ACT ≥ basal ACT and final ACT < 140 s with ≥140 s. Continuous variables were analysed with the Wilcoxon rank-sum test; categorical variables using Chi-square or Fisher's exact test. A linear mixed regression model was used to analyse bleeding in patients with final ACT < 140 and ≥140. Independent variables were analysed with binary logistic regression models to investigate their association with bleeding and transfusion. RESULTS: Patients with final ACT ≥ 140 s presented higher postoperative bleeding than final ACT < 140 s at 12 h (P = 0.006) and 24 h (**P = 0.004). Cardiopulmonary bypass (CPB) time [odds ratio (OR) 1.009, 1.002-1.015, 95% confidence interval (CI)] and masculine sex (OR 2.842,1.721-4.821, 95% CI) were significant predictors of bleeding. Patients with final ACT ≥ 140 s had higher risk of UT (OR 1.81, 1.13-2.89, 95% CI; P = 0.0104), compared to final ACT < 140 s. CPB time (OR 1.019,1.012-1.026, 95% CI) and final ACT (OR 1.021,1.010-1.032, 95% CI) were significant predictors of transfusion. Female sex was a predictor of use of transfusion, with a probability for use of 27.23% (21.84-33.39%, 95% CI) in elective surgeries, and 60.38% (37.65-79.36%, 95% CI) in urgent surgeries, higher than in males. CONCLUSIONS: Final ACT has a good predictive value for the use of transfusion. Final ACT ≥ 140 s correlates with higher risk of transfusion and increased bleeding. The risk of bleeding and transfusion is higher with longer periods of CPB. Males have a higher risk of bleeding, but females have a higher risk of transfusion.

The impact of cardiopulmonary bypass time on the Sequential Organ Failure Assessment score after cardiac surgery.

OBJECTIVES: Postoperative organ dysfunction is common after cardiac surgery, particularly when cardiopulmonary bypass (CPB) is used. The Sequential Organ Failure Assessment (SOFA) score is validated to predict morbidity and mortality in cardiac surgery. However, the impact of CPB duration on postoperative SOFA remains unclear. METHODS: This is a retrospective study. Categorical values are presented as percentages. The comparison of SOFA groups utilized the Kruskal-Wallis chi-squared test, complemented by ad hoc Dunn's test with Bonferroni correction. Multinomial logistics regressions were employed to evaluate the relationship between CPB time and SOFA. RESULTS: A total of 1032 patients were included. CPB time was independently associated with higher postoperative SOFA scores at 24 h. CPB time was significantly higher in patients with SOFA 4-5 (**P = 0.0022) or higher (***P < 0.001) when compared to SOFA 0-1. The percentage of patients with no/mild dysfunction decreased with longer periods of CPB, down to 0% for CPB time >180min (50% of the patients with >180m in of CPB presented SOFA ≥ 10). The same trend is observed for each of the SOFA variables, with higher impact in the cardiovascular and renal systems. Severe dysfunction occurs especially >200 min of CPB (cardiovascular system >100 min; other systems mainly >200 min). CONCLUSIONS: CPB time may predict the probability of postoperative SOFA categories. Patients with extended CPB durations exhibited higher SOFA scores (overall and for each variable) at 24 h, with higher proportion of moderate and severe dysfunction with increasing times of CPB.

Surgical aortic valve replacement in octogenarians: Single-center perioperative outcomes and five-year survival.

INTRODUCTION AND OBJECTIVES: Aortic stenosis is the most common valvular heart disease. The number of octogenarians proposed for intervention is growing due to increased lifespan. In this manuscript we aim to evaluate perioperative outcome and long-term survival after surgical aortic valve replacement (SAVR) in octogenarians, comparing patients with low surgical risk (EuroscoreII <4%) with intermediate-high risk (EuroscoreII ≥4%). METHODS: A retrospective observational single-center cohort study with 195 patients aged ≥80 years old, who underwent SAVR between 2017 and 2021, was conducted. Patients were divided into two groups according to EuroscoreII: (1) Low risk (EuroscoreII <4%) with intermediate-high risk (EuroscoreII ≥4%). Continuous variables are presented in median (IQR), analyzed using Wilcoxon rank sum test; categorical variables in percentages, analyzed using chi-squared test; and survival was analyzed by Kaplan-Meier, open cohort, and the log-rank test was performed. RESULTS: The overall median age was 82 (IQR 81-83), with 4.6% of the patients ≥85 years old. 23.6% of the patients presented EuroscoreII ≥4%. No complications were observed in 26.2%, with a significantly higher rate in intermediate-high risk patients. Postoperative need for hemodynamic support was the most frequent complication, followed by postoperative acute kidney injury and the use of blood products. Overall median ICU stay was three days (2-4) and hospital length of stay (LOS) six days (5-8). Patients with intermediate-high risk and those with complications had longer ICU LOS. At 12 months, overall survival was 96.4%, at three years 94.1% and 5 years 75.4%. Patients with low surgical risk had higher survival proportions up to 5 years. CONCLUSION: SAVR in patients ≥80 years is associated with low in-hospital mortality, although a significant proportion of patients develop complications. Long-term follow-up up to five years after surgery is acceptable in octogenarians with low surgical risk.

Sutureless bioprosthesis for aortic valve replacement: Surgical and clinical outcomes.

BACKGROUND: Aortic valve stenosis is the most common adult valve disease in industrialized countries. The aging population and the increase in comorbidities urge the development of safer alternatives to the current surgical treatment. Sutureless bioprosthesis has shown promising results, especially in complex procedures and in patients requiring concomitant surgeries. OBJECTIVES: Assess the clinical and hemodynamic performance, safety, and durability of the Perceval® prosthetic valve. METHODS: This single-center retrospective longitudinal cohort study collected data from all adult patients with aortic valve disease who underwent aortic valve replacement with a Perceval® prosthetic valve between February 2015 and October 2020. Of the 196 patients included (mean age 77.20 ± 5.08 years; 45.4% female; mean EuroSCORE II 2.91 ± 2.20%), the majority had aortic stenosis. RESULTS: Overall mean cross-clamp and cardiopulmonary bypass times were 33.31 ± 14.09 min and 45.55 ± 19.04 min, respectively. Mean intensive care unit and hospital stay were 3.32 ± 3.24 days and 7.70 ± 5.82 days, respectively. Procedural success was 98.99%, as two explants occurred. Four valves were reimplanted due to intraoperative misplacement. Mean transvalvular gradients were 7.82 ± 3.62 mmHg. Pacemaker implantation occurred in 12.8% of patients, new-onset atrial fibrillation in 21.9% and renal replacement support was necessary for 3.1%. Early mortality was 2.0%. We report no structural valve deterioration, strokes, or endocarditis, and one successfully treated valve thrombosis. CONCLUSIONS: Our study confirms the excellent clinical and hemodynamic performance and safety of a truly sutureless aortic valve, up to a 5-year follow-up. These results were consistent in isolated and concomitant interventions, solidifying this device as a viable option for the treatment of isolated aortic valve disease.

Role of Omega-6 Fatty Acid Metabolism in Cardiac Surgery Postoperative Bleeding Risk.

Cardiac surgery is frequently associated with significant postoperative bleeding. Platelet-dysfunction is the main cardiopulmonary bypass (CPB)-induced hemostatic defect. Not only the number of platelets decreases, but also the remaining are functionally impaired. Although lipid metabolism is crucial for platelet function, little is known regarding platelet metabolic changes associated with CPB-dysfunction. Our aim is to explore possible contribution of metabolic perturbations for platelet dysfunction after cardiac surgery. DESIGN: Prospective cohort study. SETTING: Tertiary academic cardiothoracic-surgery ICU. PATIENTS: Thirty-three patients submitted to elective surgical aortic valve replacement. INTERVENTIONS: Samples from patients were collected at three time points (preoperative, 6- and 24-hr postoperative). Untargeted metabolic analysis using high-performance liquid chromatography-tandem mass spectrometry was performed to compare patients with significant postoperative bleeding with patients without hemorrhage. Principal component analyses, Wilcoxon matched-pairs signed-rank tests, adjusted to FDR, and pairwise comparison were used to identify pathways of interest. Enrichment and pathway metabolomic complemented the analyses. MEASUREMENTS AND MAIN RESULTS: We identified a platelet-related signature based on an overrepresentation of changes in known fatty acid metabolism pathways involved in platelet function. We observed that arachidonic acid (AA) levels and other metabolites from the pathway were reduced at 6 and 24 hours, independently from antiagreggation therapy and platelet count. Concentrations of preoperative AA were inversely correlated with postoperative chest tube blood loss but were not correlated with platelet count in the preoperative, at 6 or at 24 hours. Patients with significant postoperative blood-loss had considerably lower values of AA and higher transfusion rates. Values of postoperative interleukin-6 were strongly correlated with AA variability. CONCLUSIONS AND RELEVANCE: Our observations suggest that an inflammatory-related perturbation of AA metabolism is a signature of cardiac surgery with CPB and that preoperative levels of AA may be more relevant than platelet count to anticipate and prevent postoperative blood loss in patients submitted to cardiac surgery with CPB.

Sequential Organ Failure Assessment Score in the ICU As a Predictor of Long-Term Survival After Cardiac Surgery.

OBJECTIVES: The Sequential Organ Failure Assessment (SOFA) score is a predictor of mortality in ICU patients. Although it is widely used and has been validated as a reliable and independent predictor of mortality and morbidity in cardiac ICU, few studies correlate early postoperative SOFA with long-term survival. DESIGN: Retrospective observational cohort study. SETTING: Tertiary academic cardiac surgery ICU. PATIENTS: One-thousand three-hundred seventy-nine patients submitted to cardiac surgery. INTERVENTIONS: SOFA 24 hours, SOFA 48 hours, mean, and highest SOFA scores were correlated with survival at 12 and 24 months. Wilcoxon tests were used to analyze differences in variables. Multivariate logistic regressions and likelihood ratio test were used to access the predictive modeling. Receiver operating characteristic curves were used to assess accuracy of the variables in separating survivor from nonsurvivors. MEASUREMENTS AND MAIN RESULTS: Lower SOFA scores have better survival rates at 12 and 24 months. Highest SOFA and SOFA at 48 hours showed to be better predictors of outcome and to have higher accuracy in distinguishing survivors from nonsurvivors than initial SOFA and mean SOFA. A decreasing score during the first 48 hours had mortality rates of 4.9%, while an unchanged or increased score was associated with a mortality rate of 5.7%. CONCLUSIONS: SOFA score in the ICU after cardiac surgery correlated with survival at 12 and 24 months. Patients with lower SOFA scores had higher survival rates. Differences in survival at 12 months were better correlated with the absolute value at 48 hours than with its variation. SOFA score may be useful to predict long-term outcomes and to stratify patients with higher probability of mortality.

Bioprosthetic Aortic Valve Degeneration: a Review from a Basic Science Perspective

Abstract Introduction: The increase in the prevalence of aortic stenosis due to an aging population has led to an increasing number of surgical aortic valve replacements. Over the past 20 years, there has been a major shift in preference from mechanical to bioprosthetic valves. However, despite efforts, there is still no "ideal" bioprosthesis. It is crucial to understand the structure, biology, and function of native heart valves to design more intelligent, strong, durable, and physiological heart valve tissues. Methods: A comprehensive review of the literature was performed to identify articles reporting the basic mechanisms of bioprosthetic valve dysfunction and the biology of native valve cells. Searches were run in PubMed, MEDLINE® (the Medical Literature Analysis and Retrieval System Online), and Google Scholar. Terms for subject heading and keywords search included "biological heart valve dysfunction", "bioprosthesis dysfunction", "bioprosthesis degeneration", and "tissue heart valves". Results: All the relevant findings are summarized in the appropriate subsections. Structural dysfunction is a logical and expected consequence of the chemical, mechanical, and immunological processes that occur during fixation, manufacture, and implantation. Conclusion: Biological prosthesis valve dysfunction is a clinically significant process. It has become a major issue considering the growing rate of bioprosthesis implantation and improved long-term patient survival. Understanding bioprosthetic aortic valve degeneration from a basic science perspective is a key point to improve technologic advances and specifications that lead to a new generation of bioprostheses.

Low Mean Arterial Pressure During Cardiopulmonary Bypass and the Risk of Acute Kidney Injury: A Propensity Score Matched Observational Study.

INTRODUCTION: Low mean arterial pressure (MAP) periods occur frequently during cardiopulmonary bypass (CPB), and their management remains controversial. Our aim was to correlate MAP during CPB with the occurrence of post-operative acute kidney injury (AKI), considering two different parameters: consecutive and cumulative low MAP periods. METHODS: Single-centre observational retrospective study including 250 patients submitted to non-emergent aortic valve replacement, with tepid to mild hypothermia (not below 32°C). The primary outcome was the occurrence of AKI. A propensity scored matching of 43 patients was used to adjust both populations (AKI and No AKI). MAP measures were automatically and continuously recorded during CPB. Low MAP periods were analysed employing two parameters: consecutive and the cumulative sum of time. RESULTS: Patients who experienced at least 5 min with MAP <50 mmHg had an increased risk of post-operative AKI (OR infinity; 95% CI, 1.47 to infinity; P = .026). The risk is also significant with MAP <40 mmHg (OR 2.78; 95% CI 1.1-6.9; = .044) and <30 mmHg (OR 3.36; 95% CI 1.2-9.2; P = .029). Post-operative AKI was associated with cumulative and consecutive periods of low MAP. Patients with periods of low MAP had higher levels of post-operative creatinine and reduced glomerular filtration rate (GFR). Patients with AKI had prolonged endotracheal ventilation time, and ICU and ward lengths of stay. CONCLUSION: Low MAP periods during CPB are associated with an increased occurrence of post-operative AKI, leading to 1) higher creatinine levels; 2) decreased GFR and 3) longer ICU and ward lengths of stay. Both consecutive and cumulative periods of low MAP are associated with an increased risk of AKI. MAP appears to be an important contributor to post-operative AKI and should be carefully managed during CPB. Further studies must address if MAP variations lead to definitive and long-term consequences.

Bioprosthetic Aortic Valve Degeneration: a Review from a Basic Science Perspective.

INTRODUCTION: The increase in the prevalence of aortic stenosis due to an aging population has led to an increasing number of surgical aortic valve replacements. Over the past 20 years, there has been a major shift in preference from mechanical to bioprosthetic valves. However, despite efforts, there is still no "ideal" bioprosthesis. It is crucial to understand the structure, biology, and function of native heart valves to design more intelligent, strong, durable, and physiological heart valve tissues. METHODS: A comprehensive review of the literature was performed to identify articles reporting the basic mechanisms of bioprosthetic valve dysfunction and the biology of native valve cells. Searches were run in PubMed, MEDLINE® (the Medical Literature Analysis and Retrieval System Online), and Google Scholar. Terms for subject heading and keywords search included "biological heart valve dysfunction", "bioprosthesis dysfunction", "bioprosthesis degeneration", and "tissue heart valves". RESULTS: All the relevant findings are summarized in the appropriate subsections. Structural dysfunction is a logical and expected consequence of the chemical, mechanical, and immunological processes that occur during fixation, manufacture, and implantation. CONCLUSION: Biological prosthesis valve dysfunction is a clinically significant process. It has become a major issue considering the growing rate of bioprosthesis implantation and improved long-term patient survival. Understanding bioprosthetic aortic valve degeneration from a basic science perspective is a key point to improve technologic advances and specifications that lead to a new generation of bioprostheses.

Combined glucocorticoid resistance and hyperlactatemia contributes to lethal shock in sepsis.

Sepsis is a potentially lethal syndrome resulting from a maladaptive response to infection. Upon infection, glucocorticoids are produced as a part of the compensatory response to tolerate sepsis. This tolerance is, however, mitigated in sepsis due to a quickly induced glucocorticoid resistance at the level of the glucocorticoid receptor. Here, we show that defects in the glucocorticoid receptor signaling pathway aggravate sepsis pathophysiology by lowering lactate clearance and sensitizing mice to lactate-induced toxicity. The latter is exerted via an uncontrolled production of vascular endothelial growth factor, resulting in vascular leakage and collapse with severe hypotension, organ damage, and death, all being typical features of a lethal form of sepsis. In conclusion, sepsis leads to glucocorticoid receptor failure and hyperlactatemia, which collectively leads to a lethal vascular collapse.

Primary cardiac hydatic cyst with multiple locations: an unusual case of chest pain.

Cardiac echinococcosis is a rare manifestation of Echinococcus infection, affecting 0.5-2% of the patients. Since it may be a life-threatening condition, surgical treatment should be always considered. Herein, here we present a case of a 66-year-old male with chest pain. Subsequent exams confirmed the diagnosis of multiple cardiac hydatic cysts. The patient initiated treatment with albendazole and was submitted to a surgical resection with cardiopulmonary bypass. A complete surgical resection was achieved, and patient remains asymptomatic without disease signs of recurrence on imaging exams. We highlight the necessity of cardiac screening in echinococcosis cases and the surgical management in this case.

Age Is Not Just A Number For A Rapid Deployment Valve In Octogenarians.

INTRODUCTION: Aortic valve stenosis (AS) is the most common valvular pathology in the elderly and surgery (AVR) remains the gold-standard. However, transcatheter aortic valve replacement (TAVI) has become an emerging alternative to surgery. In a recent survey from the European Society of Cardiology, 9,4% stated that age was the main reason to propose for TAVI. METHODS: Single-center retrospective study including 353 patients (149 ≥80 years-old;204 with 60-69 years-old) submitted to AVR between 2013-2016. Primary endpoint was survival. Secondary outcomes included the rate of post- -operative complications. Long-term survival was determined by Kaplan-Meier survival analysis. Continuous variables were analyzed with t-test and linear regression and categorical variables with chi-square or Fisher. RESULTS: clinical characteristics were similar between the two groups. Both had similar survival at 30 days, 12 (93,29% 60-69yo vs 91,47% ≥80yo) and 24 months (88,34% 60-69yo vs 86,11% ≥80yo). However, rapid deployment valves (RD) had better survival rates in elderly patients. Cross-clamp time was lower in ≥80yo group, with higher percentage of RD valves (20,1% vs 4.9% in 60-69yo). The rate of post-operative atrial fibrillation was higher in >80yo group (29,06% vs. 17,28%,p=0,0147). In all patients, cross-clamp time was directly related to ventilation time(p=0,025) and chest drainage(p=0,0015). CONCLUSION: AVR after 80yo is safe. Cross-clamp time is directly correlated with ventilation time and bleeding, with a stronger correlation in patients over 80yo. RD valves reduce cross-clamp times, so their use in elderly may improve surgery outcome. Prospective studies are needed to evaluate if age may be clinical criteria for a RD.

CXCL5-mediated recruitment of neutrophils into the peritoneal cavity of Gdf15-deficient mice protects against abdominal sepsis.

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to an infection. Here we report that the circulating levels of growth and differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, we find that peptidoglycan is a potent ligand that signals through the TLR2-Myd88 axis for the secretion of GDF15, and that Gdf15-deficient mice are protected against abdominal sepsis due to increased chemokine CXC ligand 5 (CXCL5)-mediated recruitment of neutrophils into the peritoneum, leading to better local bacterial control. Our results identify GDF15 as a potential target to improve sepsis treatment. Its inhibition should increase neutrophil recruitment to the site of infection and consequently lead to better pathogen control and clearance.

Occult Metastatic Melanoma Presenting as an Acute Coronary Syndrome.

Melanoma is a tumor that virtually involves any tissue and commonly metastasizes to the heart. It is usually not diagnosed because of the absent/nonspecific cardiac signs and symptoms. Herein, we present a case of a 41-year-old man without any cardiovascular risk factor, admitted to the emergency room with chest pain, diagnosed with a myocardial infarction. Due to the presence of a mass adjacent to the mitral valve on the cardiac ultrasound examination, causing mitral regurgitation, the patient was referred to surgery. Pathological analysis of the excised specimens diagnosed the melanoma. The chemotherapy was started and achieved a partial response. Cardiac metastases usually affect the myocardium, leaving the valves unaffected. In this case, the acute coronary syndrome was the first manifestation of the malignant melanoma. We highlight the high level of suspicion needed in these cases.

Occult metastatic melanoma presenting as an acute coronary syndrome

Abstract Melanoma is a tumor that virtually involves any tissue and commonly metastasizes to the heart. It is usually not diagnosed because of the absent/nonspecific cardiac signs and symptoms. Herein, we present a case of a 41-year-old man without any cardiovascular risk factor, admitted to the emergency room with chest pain, diagnosed with a myocardial infarction. Due to the presence of a mass adjacent to the mitral valve on the cardiac ultrasound examination, causing mitral regurgitation, the patient was referred to surgery. Pathological analysis of the excised specimens diagnosed the melanoma. The chemotherapy was started and achieved a partial response. Cardiac metastases usually affect the myocardium, leaving the valves unaffected. In this case, the acute coronary syndrome was the first manifestation of the malignant melanoma. We highlight the high level of suspicion needed in these cases.

One-step synthesis of high-density peptide-conjugated gold nanoparticles with antimicrobial efficacy in a systemic infection model.

The increase in antibiotic drug resistance and the low number of new antibacterial drugs approved in the last few decades requires the development of new antimicrobial strategies. Antimicrobial peptides (AMPs) are very promising molecules to fight microbial infection since they kill quickly bacteria and, in some cases, target bacterial membrane. Although some AMPs may be stable against proteolytic degradation by chemical modification, in general, low AMP activity and stability in the presence of serum and proteolytic enzymes as well as their cytotoxicity have impaired their clinical translation. Here, we describe a one-step methodology to generate AMP-conjugated gold nanoparticles (Au NPs), with a high concentration of AMPs (CM-SH) (≈240 AMPs per NP), controlled size (14 nm) and low polydispersity. AMP-conjugated Au NPs demonstrated higher antimicrobial activity and stability in serum and in the presence of non-physiological concentrations of proteolytic enzymes than soluble AMP, as well as low cytotoxicity against human cells. Moreover, the NPs demonstrated high antimicrobial activity after in vivo administration in a chronic wound and in an animal model of systemic infection.

Sepsis: the need for tolerance not complacency.

Sepsis is a life-threatening condition that arises as a systemic inflammatory response syndrome to an infection. Its uncontrolled progression can in frequent cases lead to multiple organ failure, which is still associated with high mortality rates. Modern antibiotics made clear that the infection is only an initiating, and not always necessary, event of this syndrome as many patients with sepsis die despite effective eradication of the inciting pathogen. This observation critically contributed to a paradigm shift that focused the pathogenesis of sepsis on the host and not on the pathogen. However, therapeutic strategies based on the inhibition of proinflammatory critical mediators of sepsis or immunostimulation have so far failed to improve sepsis outcome and, therefore, this condition urgently needs transformative therapeutic ideas and strategies. Here we argue that the induction of tolerance, a defence strategy that minimises the impact of an infection on organ function without directly affecting the pathogen burden, is perhaps the missing but essential element to add to the current components of sepsis care and treatment.