CIRCULATING BIOMARKERS OF SYSTEMIC INFLAMMATORY RESPONSE IN THE ASSESSMENT OF POSTPERICARDIOTOMY SYNDROME IN PATIENTS AFTER CARDIAC SURGERY

Postpericardiotomy syndrome (PCTS) is one of the most frequent cardiac surgery complications seen in 9-65% of patients. Despite its widespread occurrence, the mechanisms of the development of PCTS are still understudied. drug. The use of colchicine in cardiac surgery patients is of particular interest. Due to the ability of this drug the colchicine mechanisms of action are able to inhibit the mobilization of the NLRP3 inflammasome assembly, to suppress the activation of caspase-1. As a result, it can prevent the release of proinflammatory cytokines, namely IL-1β and IL-18. There are conflicting data on the effect of colchicine on the PCTS progression within the systemic inflammatory response after cardiac surgery. In this regard, it was important to study the dynamics of serum levels of IL-6, IL-10, IL-1β, and TNFα in patients before coronary artery bypass grafting (T1), 6 hours (T2), and 10 days (T3) after surgery, and to evaluate the effect of colchicine on the development of PCTS. The results of our research showed a significant increase of IL-10 in both groups 6 hours after surgery. However, on the 10th day, the increase in the level of IL-10, compared with the initial values, was higher in the 1st group – 2 times, compared with the 2nd group. In both groups, showed significant increase in serum concentration of IL-6 after 6 h surgery, with a subsequent decrease in the expression at the stage of T3, while the IL-6 levels in the 2nd group was statistically notably higher than T1. The incidence of pleurisy was lower in the group of patients taking colchicine. Only in the 1st group IL-6 levels were directly associated with IL-10. In patients with pleurisy, the level of released IL-10 and TNFα was significantly higher in the 2nd group. There were no significant intergroup differences in serum levels of IL-1β and TNFα, as well as significant changes in IL-1β between the stages of observation. Analysis of TNFα expression revealed significant differences in TNFα content in the 1st group between the T1-T3 and T2-T3 stages. In both groups, multiple positive associations were found between the studied indicators. Thus, data were obtained indicating the antiinflammatory effect of colchicine in cardiac surgery patients. This was clinically expressed in a tendency to a lower incidence of pleurisy, and was accompanied by increased expression of IL-10, which has an antiinflammatory and immunomodulatory effect against the background of the drug in the postoperative period.

Peculiarity of clinical course of postpericardiotomy syndrome in different methods of surgery and postoperative antithrombotic therapy

Aim To compare features of the disease course and the effectiveness of nonsteroidal anti-inflammatory drug (NSAID) treatment of postpericardiotomy syndrome (PPS) in patients after coronary bypass (CB) surgery who were treated with antiplatelet drugs and in patients after surgical correction of heart valve disease (CHVD) who received the anticoagulant warfarin for prevention of thrombotic complications. Material and methods This study included 89 patients of whom 53 patients had underwent CB and 36 patients had underwent CHVD. At 15 [13; 15] days after surgery, the severity of inflammatory response, the state of coagulation hemostasis, and hematocrit were studied. At 5 days after the first test, blood count and measurement of C-reactive protein were repeated. Echocardiography was used to determine the presence and volume of pleural effusion. For prevention of thrombotic complications, antiplatelet drugs were administered after CB and warfarin was administered after CHVD. PPS was detected in 35 (66 %) patients after CB and 18 (50 %) patients after CHVD. The ibuprofen treatment (600 mg twice a day) was administered to all patients with PPS. If positive changes in inflammatory markers were absent during the NSAID treatment, ibuprofen was replaced with prednisolone 0.5 mg/kg body weight with subsequent laboratory and instrumental monitoring. Results Patients after CHVD treated with warfarin had higher values of international normalized ratio (INR) and activated partial thromboplastin time (aPPT) and lower values of prothrombin index (PTI), fibrinogen (p<0.001 for all), hemoglobin (p=0.0016), and hematocrit (p=0,0032) than patients after CB treated with antiplatelet drugs. 21 (40 %) patients with PPS required changing the anti-inflammatory therapy from ibuprofen to prednisolone. These patients displayed hypocoagulation, which was evident as reduced PTI (p=0.0023) and fibrinogen (p=0.0209), increased INR (p=0.0291) and aPPT (p=0.0416), and a higher incidence of pericardial effusion (p=0.0080). The insufficient effectivity of NSAIDs that required administration of prednisolone was more frequently observed in patients after CHVD (61 % vs. 29 %, р=0.037).Conclusion Hypocoagulation observed in patients after CHVD due to the anticoagulant treatment with warfarin was associated with more severe course of PPS and lower effectiveness of the NSAID treatment compared to patients after CB. This results in more frequent replacement of NSAIDs with glucocorticoids in the treatment of patients after CHVD.

Expanding the potential benefits of colchicine for preventing postpericardiotomy syndrome and atrial fibrillation complications after cardiac surgery: meta-analysis of randomized controlled trials

Funding Acknowledgements Type of funding sources: None. Introduction Postpericardiotomy syndrome (PPS) and atrial fibrillation (AF) are complications occurred in one-third of cardiac surgery patients that increase morbidity and mortality. Colchicine is an anti-inflammatory drug for treating acute pericarditis and pericardial effusion. Previous studies suggested that colchicine also may prevent PPS and AF after cardiac surgery although the results were still inconsistent. Purpose This study intends to determine the efficacy of colchicine for preventing PPS and AF in post-cardiac surgery patients. Methods We conducted comprehensive literature searching in online databases of Pubmed, EMBASE, ScienceDirect, and The Cochrane Library, to include all relevant studies until November 2020. We included all randomized controlled trials (RCTs) that access the incidence of PPS and AF after cardiac surgery in patients who received colchicine before cardiac surgery compared with placebo. We use revised Cochrane risk-of-bias tool (RoB 2) for accessing the bias risk of included studies. We performed analysis to provide pooled risk ratio (RR) with 95% confidence interval (CI) using fixed-effect heterogeneity test. Results We included 9 RCTs with total of 2,372 participants met our inclusion criteria. The administration of colchicine before cardiac surgery decreases the incidence of PPS significantly (pooled RR = 0.55, 95% CI 0.43 – 0.71, p &lt; 0.00001. I² = 0%). Besides, colchicine also significantly lowers the incidence of postoperative AF compared with placebo (pooled RR = 0.79, 95% CI 0.65 – 0.96, p = 0.02. I² = 20%). Conclusions Colchicine showed potential benefits for preventing PPS and AF after cardiac surgery. However, further trials are needed to establish the efficacies.

Steroids for the prevention of postpericardiotomy syndrome: a meta-analysis

Funding Acknowledgements Type of funding sources: None. Background Postpericardiotomy syndrome (PPS) can occur in up to 40% of patients after cardiac surgery. Corticosteroid therapy has long been used for pericarditis and pericardial effusion due to its anti-inflammatory proprieties. The benefit of corticosteroids for the prevention of post pericardiotomy syndrome (PPS) in not consensual. Purpose We performed a systematic review and meta-analysis of trials assessing the efficacy of corticosteroids to prevent PPS in patients submitted to cardiac surgery. Methods We searched MEDLINE, Google Scholar and the Cochrane Library databases using the key terms "corticosteroids" and "post pericardiotomy syndrome" without language or date restriction. Articles were considered for inclusion in the analysis if they comprised a population of patients submitted to cardiac surgery and a comparison between patients treated with corticosteroids for the prevention of PPS and those who were not. Three studies were identified, comprehending a total of 1268 patients. The primary endpoint was the occurrence of PPS. Pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated based on a random effects meta-analysis and were obtained from the pooled adjusted OR of primary studies. Results Studies included in the analysis comprehend a controlled randomized trial in children (1 mg/kg methylprednisolone pre-operative and four additional doses over 24h vs placebo); a controlled randomized trial in adults (1 mg/kg dexamethasone intra-operative vs placebo) and a retrospective study in adults (1 mg/kg intra-operative methylprednisolone vs standard care). Of the total 1268 patients included, 641 received glucocorticoids for the prevention of PPS. Main reason for surgery was correction of a congenital heart defect in 19% of the patients; coronary artery bypass graft in 15% and valvular disease in 66% of the cases. 217 patients had PPS during the follow-up time; 15% in the corticosteroid prophylaxis group and 18% in the placebo/standard care group. Overall, corticosteroid prophylaxis was not useful for the prevention of PPS compared to placebo/standard care (pooled OR: 0.78, 95% CI: 0.51–1.20, I2 = 46%) – Figure 1. Conclusion According to our data, steroid therapy has no role as a preventive therapy of post-pericardiectomy syndrome. Abstract Figure 1 - Pooled analysis

Idiopathic recurrent pericarditis – a new orphan autoinflammatory disease? A retrospective analysis of cases of idiopathic recurrent pericarditis and a design of а double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of RPH-104 treatment in patients with idiopathic recurrent pericarditis

Aim To analyze cases of idiopathic recurrent pericarditis (IRP) in the structure of pericardial diseases of various origins from patient visits to the Multidisciplinary Federal Center.Material and methods A retrospective analysis of case records was performed for patients admitted to the V.A. Almazov National Medical Research Center from January 1, 2015 through January 1, 2020 for pericardial effusion of different etiologies.Results For the study period, 4 981 new cases of pericardial damage of different etiologies were found. Among these cases, postpericardiotomy syndrome accounted for 4 360 cases and pericarditis for 621 cases. IRP was detected in 34 cases, which amounted to 5.4 %. Based on the study data, the estimated IRP prevalence in the Russian Federation can be 1.1 cases per 100 thousand population.Conclusion IRP should be regarded as a new autoinflammatory disease, the prevalence of which borders on that of adult Still disease and should be addressed within the concept of orphan diseases. Current knowledge of the pathogenesis and data from recent studies demonstrated a great importance of interleukin-1 blockade as a leading mechanism for achieving remission. This has justified conduction of a randomized clinical study at the Center.

Colchicine: An ancient drug with multiple benefits

: The history of colchicine dates to ancient Egyptians when it was used for alleviation of swelling and pain. Although its popularity varied throughout the years, colchicine has been a mainstay for the treatment of several diseases, mainly rheumatic and cardiac ones. The mechanism of action of the drug involves several intracellular and extracellular targets, although interaction with tubulin is the most described. Based on several clinical trials and meta-analyses, colchicine is safely recommended as a monotherapy or as an add-on for the treatment and prevention of recurrent pericarditis, postpericardiotomy syndrome, gout, pseudogout, familial Mediterranean fever (FMF), and Behçet’s disease (BD). Notably, a drug safety has been noted during pregnancy and lactation. Besides its major indications, colchicine has shown efficacy and safety in the treatment of various conditions. Because the indications for using colchicine in the prevention of certain conditions such as acute coronary syndrome, stroke, and hepatic cirrhosis and treatment of others such as pneumonia and psoriasis are still debatable, further research works are needed.