Oral geranylgeranylacetone treatment increases heat shock protein expression in human atrial tissue

BACKGROUND Heat shock proteins (HSPs) are important chaperones that regulate the maintenance of healthy protein quality control in the cell. Impairment of HSPs is associated with aging-related neurodegenerative and cardiac diseases. Geranylgeranylacetone (GGA) is a compound well known to increase HSPs through activation of heat shock factor-1 (HSF1). GGA increases HSPs in various tissues, but whether GGA can increase HSP expression in human heart tissue is unknown. OBJECTIVE The purpose of this study was to test whether oral GGA treatment increases HSP expression in the atrial appendages of patients undergoing cardiac surgery. METHODS HSPB1, HSPA1, HSPD1, HSPA5, HSF1, and phosphorylated HSF1 levels were measured by western blot analysis in right and left atrial appendages (RAAs and LAAs, respectively) collected from patients undergoing coronary artery bypass grafting (CABG) who were treated with placebo (n = 13) or GGA 400 mg/da(n = 13) 3 days before surgery. Myofilament fractions were isolated from LAAs to determine the levels of HSPB1 and HSPA1 present in these fractions. RESULTS GGA treatment significantly increased HSPB1 and HSPA1 expression levels in RAA and LAA compared to the placebo group, whereas HSF1, phosphorylated HSF1, HSPD1, and HSPA5 were unchanged. In addition, GGA treatment significantly enhanced HSPB1 levels at the myofilaments compared to placebo. CONCLUSION Three days of GGA treatment is associated with higher HSPB1 and HSPA1 expression levels in RAA and LAA of patients undergoing CABG surgery and higher HSPB1 levels at the myofilaments. These findings pave the way to study the role of GGA as a protective compound against other cardiac diseases, including postoperative atrial fibrillation

Local Use of Hydrogel with Amiodarone in Cardiac Surgery: Experiment and Translation to the Clinic

The objective of this study was to study the use of the hydrogel biopolymer based on sodium alginate (“Colegel”) with a drug substance—amiodarone—for the prevention of postoperative atrial fibrillation (POAF) in cardiac surgery. The experimental part of the study was performed on 46 rabbits. Five groups were formed: in the first group, the dose of amiodarone in hydrogel was 1 mg; in the second group—3 mg; in the third group—6 mg; in the fourth group, hydrogel was used without amiodarone; in the fifth group, 60 mg amiodarone was administered intravenously. The animals from each group were removed from the experiment for the pathomorphological study of the heart after 3, 7 and 14 days. The studied endpoints were: the heart rate control; the development of the blockades of the conduction system of the heart; and the development of inflammation according to laboratory pathomorphological studies. The translational clinical part involved a randomized clinical trial which included 60 patients, with an average age of 62 ± 8.5 years. All patients were randomized into two groups: the study group (n = 30, with the application of amiodarone hydrogel) and the control group (n = 30, without the application of amiodarone hydrogel). The dose of amiodarone in the hydrogel material was 60 mg for all patients. The heart rhythm was monitored during 5 days. The primary endpoint was the development of POAF. Secondary endpoints were: the dynamics of heart rate; the duration of the QT and PQ intervals; the development of blockades of the cardiac conduction system; as well as the dynamics of AST and ALT. According to the results of the experimental part, it was found that the method of the local epicardial delivery of amiodarone by the hydrogel material was safe. Hydrogel with amiodarone is effective for reducing the heart rate in the animal experiment in comparison to the control group and the group with the intravenous administration of the drug. The optimal dose of amiodarone in hydrogel was 1 mg per 1 kg. According to the results of the clinical part, it was found that the method of the local epicardial delivery of amiodarone as a hydrogel material proved its safety. Hydrogel with amiodarone at a dose of 60 mg was effective in preventing POAF in patients after coronary artery bypass grafting (CABG) operations in comparison to the control group (p < 0.001). The age and procedure of application of the amiodarone gel were significantly associated with POAF (p = 0.009 and p = 0.011, respectively). The use of hydrogel with amiodarone reduced the probability of developing POAF 18.9-fold. The method of the local epicardial delivery of amiodarone in the form of a hydrogel material is safe. The use of hydrogel with amiodarone after CABG reduced the probability of developing POAF

Predictors of Mortality Following Aortic Valve Replacement in Aortic Stenosis Patients

Background: Understanding of the risk factors for the development of adverse outcomes after aortic valve replacement is necessary to develop timely preventive measures and to improve the results of surgical treatment. Methods: We analyzed patients with aortic stenosis (n = 742) who underwent surgical treatment in the period 2014–2020. The average age was 63 (57;69) years—men 58%, women 42%. Results: The hospital mortality rate was 3% (22 patients). The following statistically significant threshold values (cut-off points) were obtained in the ROC analysis: aortic cross-clamp time > 93 min AUC (CI) 0.676 (0.640–0.710), p = 0.010; cardiopulmonary bypass time > 144 min AUC (CI) 0.809 (0.778–0.837), p < 0.0001, hemoglobin before op <120 g/L. AUC (CI) 0.762 (0.728–0.793), p < 0.0001, hematocrit before op <39% AUC (CI) 0.755 (0.721–0.786), p < 0.001, end-diastolic dimension index >2.39 AUC (CI) 0.647 (0.607–0.686), p = 0.014, end-systolic dimension index > 1.68 AUC (CI) 0.657 (0.617–0.695), p = 0.009. Statistically significant independent predictors of hospital mortality were identified: BMI > 30 kg/m2 (OR 2.84; CI 1.15–7.01), ischemic heart disease (OR 3.65; CI 1.01–13.2), diabetes (OR 3.88; CI 1.38–10.9), frequent ventricular ectopy before operation (OR 9.78; CI 1.91–50.2), mitral valve repair (OR 4.47; CI 1.76–11.3), tricuspid valve repair (OR 3.06; CI 1.09–8.58), 3 and more procedures (OR 4.44; CI 1.67–11.8). Conclusions: The hospital mortality rate was 3%. The main indicators associated with the risk of death were: diabetes, overweight (body mass index more than 30 kg/m2), frequent ventricular ectopy before surgery, hemoglobin level below 120 g/L, hematocrit level below 39%, longer cardiopulmonary bypass time and aortic cross-clamp time, additional mitral and tricuspid valve interventions

Quantitative Criteria for the Degree of Pathological Remodeling of the Aortic Duct

Analysis of the properties of the aorta was carried out by numerous researchers using several parameters. However, the general laws of change in the dynamic geometry of the aortic flow channel in connection with the hydrodynamics of the swirling blood flow have not been studied properly. Therefore, at present, attempts to correct various diseases are carried out based on the location of the aneurysm, and not in accordance with the general patterns of changes in the dynamic geometry of the entire aortic channel. For a proper understanding of the aortic flow channel remodeling mechanisms, it is necessary to determine the quantitative parameters that formalize the geometry of this channel. The geometric shape of the aorta primarily depends on the hydrodynamics of the flow inside the aortic flow channel, which is the only source of force impact on its walls. The main result of the present study was that we obtained the new quantitative parameters that characterize the normal aorta and the degree of its shape deviations caused by pathological changes of the aortic duct. These parameters were calculated based on the software processing of the three-dimensional aortic reconstruction in normal conditions and in the case of differently localized aortic aneurysm

Total cavopulmonary connection with a new restorative vascular graft: results at 2 years.

Background To present a 2-year follow-up regarding safety and hemodynamic performance of a new restorative vascular graft used as extracardiac cavo-pulmonary connection in patients with univentricular congenital heart malformations. Methods The graft was implanted in five patients (aged 4-12 years) as extracardiac connection between the inferior vena cava and the pulmonary artery. The conduit consists of a bioabsorbable polymer-based implant able to generate endogenous tissue restoration leading to a fully functional neo-vessel while the polymer progressively absorbs. All patients have reached more than 24 months following surgery and underwent echocardiography and magnetic resonance imaging. Results All patients are doing well at 24 months follow-up, with no graft-related serious adverse events. Transthoracic echocardiography demonstrated adequate function of the conduit in all patients while magnetic resonance imaging showed anatomical and functional stability of the restorative grafts. Conclusions The new restorative conduit has been successfully used for the second step of the Fontan procedure as extracardiac total cavopulmonary connection. The results are promising because they suggest that complete transformation of a bioabsorbable polymer and replacement through endogenous tissue may represent a major advantage in the treatment of congenital heart disease patients. Further monitoring will allow to evaluate the long-term behavior of this new graft, in terms of clinical and hemodynamic performance, thrombogenicity and ability to grow

Long-Term Preoperative Atorvastatin or Rosuvastatin Use in Adult Patients before CABG Does Not Increase Incidence of Postoperative Acute Kidney Injury: A Propensity Score-Matched Analysis

Background: Acute kidney injury (AKI) is among the expected complications of cardiac surgery. Statins with pleiotropic anti-inflammatory and antioxidant effects may be effective in the prevention of AKI. However, the results of studies on the efficacy and safety of statins are varied and require further study. Methods: We conducted a retrospective cohort study to evaluate long-term preoperative intake of atorvastatin and rosuvastatin on the incidence of AKI, based on the “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria in the early postoperative period after coronary artery bypass graft surgery (CABG). We performed propensity score matching to compare the findings in our study groups. The incidence of AKI was assessed on day 2 and day 4 after the surgery. Results: The analysis included 958 patients after CABG. After 1:1 individual matching, based on propensity score, the incidence of AKI was comparable both on day 2 after the surgery (7.4%) between the atorvastatin group and rosuvastatin group (6.5%) (OR: 1.182; 95%Cl 0.411–3.397; p = 0.794), and on postoperative day 4 between the atorvastatin group (3.7%) and the rosuvastatin group (4.6%) (OR: 0.723, 95%Cl 0.187–2.792; p = 0.739). Additionally, there were no statistically significant differences in terms of incidence of AKI after 1:1 individual matching, based on propensity score, between the rosuvastatin group and the control group both on postoperative day 2 (OR: 0.692; 95%Cl 0.252–1.899; p = 0.611) and day 4 (OR: 1.245; 95%Cl 0.525–2.953; p = 0.619); as well as between the atorvastatin group and the control group both on postoperative day 2 (OR: 0.549; 95%Cl 0.208–1.453; p = 0.240) and day 4 (OR: 0.580; 95%Cl 0.135–2.501; p = 0.497). Conclusion: Long-term statin use before CABG did not increase the incidence of postoperative AKI. Further, we revealed no difference in the incidence of post-CABG AKI between the atorvastatin and rosuvastatin groups

Colchicine for Prevention of Atrial Fibrillation after Cardiac Surgery in the Early Postoperative Period

Background. Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. It has been proven to be associated with an increase in the incidence of early complications and mortality, an increase in the rate of hospital stay duration, and economic costs of their treatment. One of the pharmaceutical drugs recommended by the American College of Cardiology (ACC)/American Heart Association (AHA) for preventing POAF is colchicine (class IIB). However, the results of research on the efficacy and safety of colchicine are ambiguous and, consequently, require further study. Objective. Evaluating the efficacy of short-term colchicine administration in the prevention of POAF in patients after open-heart surgery. Materials and methods. Double-blind, randomized, placebo-controlled clinical trial. The subjects were randomly assigned to two groups: treatment group (n = 50) with subjects receiving 1 mg of colchicine 24 h before the surgery, as well as on days 2, 3, 4, and 5 in the postoperative period; and the control group (n = 51), receiving placebo on the same schedule. The primary endpoint was the frequency of POAF in both groups within 7 days after surgery. Results. The study included 101 patients (82 men, 19 women). Baseline clinical, laboratory, instrumental, and intraoperative data did not differ statistically significantly between the groups. POAF was detected in 9 patients (18%) of the treatment group and 15 subjects (29.4%) of the control group, which had no statistical significance (odds ratio, OR 0.527; 95% Cl 0.206–1.349; p = 0.178). No statistically significant differences were revealed for most secondary endpoints, as well as between the groups for all laboratory parameters. There were statistically significant differences between the groups solely in the frequency of diarrhea: 16 (32%) patients in the treatment group and 6 (11.8%) subjects in the control group (OR 3.529; 95% Cl 1.249–9.972; p = 0.010). Conclusions. We did not detect any statistical differences between the groups in terms of primary endpoints, which could be due to the insufficient volume of the sample of the study. However, we detected some trends of statistical differences among the groups in terms of some parameters. Clinical Trials Registration. ClinicalTrials. Unique identifier: NCT04224545