Meta-analysis for the value of colchicine for the therapy of pericarditis and of postpericardiotomy syndrome.

BACKGROUND: Colchicine has been used as anti-inflammatory agent in pericardial effusion (PE). We sought to perform a meta-analysis of randomized trials assessing the efficacy and safety of colchicine in patients with pericarditis or postpericardiotomy syndrome (PPS). METHODS: In the systematic literature search following the PRISMA statement, 10 prospective randomized controlled studies with 1981 patients with an average follow-up duration of 13.6 months were identified. RESULTS: Colchicine reduced the recurrence rate of pericarditis in patients with acute and recurrent pericarditis and reduced the incidence of PPS (RR: 0.57, 95% CI: 0.44-0.74). Additionally, the rate of rehospitalizations as well as the symptom duration after 72 h was significantly decreased in pericarditis (RR 0.33; 95% CI 0.18-0.60; and RR 0.43; 95% CI 0.34-0.54; respectively), but not in PPS. Treatment with colchicine was associated with significantly higher adverse event (AE) rates (RR 1.42; 95% CI 1.05-1.92), with gastrointestinal intolerance being the leading AE. The reported number needed to treat (NNT) for the prevention of recurrent pericarditis ranged between 3 and 5. The reported NNT for PPS prevention was 10, and the number needed to harm (NNH) was 12, respectively. Late colchicine administration > 7 days after heart surgery did not reduce postoperative PE. CONCLUSIONS: Our meta-analysis confirms that colchicine is efficacious and safe for prevention of recurrent pericarditis and PPS, while it reduces rehospitalizations and symptom duration in pericarditis. The clinical use of colchicine for the setting of PPS and postoperative PE after heart surgery should be investigated in further multicenter RCT.

Postpericardial injury syndrome: an autoimmune phenomenon.

Postpericardial injury syndrome (PPIS) is defined as pericarditis or pericardial effusion that results from recent or earlier injury of the pericardium. The clinical features of this syndrome include fever, leukocytosis, and elevated erythrocyte sedimentation rate. Recent studies have established a connection between this clinical presentation and an underlying autoimmune process. The role of the humoral immune response is well established regarding the pathogenesis of PPIS with elevated titers of different antibodies and immune complexes in the circulation correlating with disease activity. Nevertheless, cell-mediated response by different subgroups of T lymphocyte has a significant importance with direct infiltration of pericardial tissue and fluids. The diagnosis of PPIS is still challenging. A strong connection between specific serological immunological markers and the disease would be of great value in diagnosis and treatment.

Anti-heart antibodies in postpericardiotomy syndrome: cause or epiphenomenon? A prospective, longitudinal pilot study.

OBJECTIVES: To assess the role of anti-heart antibodies (AHA) in postpericardiotomy syndrome (PPS) and the timing of their appearance in relation to the initial manifestations of PPS. DESIGN AND SUBJECTS: Twenty patients who were scheduled to undergo elective coronary artery bypass grafting (CABG) were enrolled in a prospective, longitudinal pilot study. METHODS: Serum was sampled for AHA on the day prior to surgery and at regular intervalsfollowing surgery in all patients. In those who developed PPS, the serum AHA was determined on the day that typical clinical manifestations of PPS appeared and at regular intervals following the onset of PPS. RESULTS: All patients were negative for AHA on the day precedingsurgery. Three(15%) patients developed PPS. Their sera were negative for AHA on the day they were diagnosed as sufferingfrom PPS and the sera became positive for AHA within 14 days from the time of diagnosis. The intensity of immunofluorescence decreased markedly 30 days afterwards and AHA had disappeared within 90days after diagnosis of PPS. The other 17 (85%) patients were negative for AHA prior to surgery and remained so during the six-month postoperative follow-up period. CONCLUSION: The findings of this study suggest that serum AHA may not play a causal role inthe pathogenesis of PPS, but may rather be an epiphenomenon, reflecting an immune response to pericardial and/or myocardial injury.

The effect of short-term prophylactic methylprednisolone on the incidence and severity of postpericardiotomy syndrome in children undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: The aim of this study was to determine the effect of prophylactic immune suppression on the incidence and severity ofpostpericardiotomy syndrome (PPS) in children after cardiac surgery with cardiopulmonary bypass (CPB). BACKGROUND: Prophylactic suppression of the inflammatory response has an unknown effect on the incidence and severity of PPS in children undergoing surgery with CPB. METHODS: This randomized double-blind placebo controlled trial included two study groups. Group A received pre-CPB intravenous methylprednisolone (1 mg/kg) plus four additional intravenous doses over 24 h, and Group B received intravenous saline placebo at identical intervals. Data included patient demographics, cardiac diagnosis/operation, CPB time, incidence and severity of PPS. Noncomplicated PPS--temperature >100.5 degrees F, pericardial friction rub, patient irritability, small pericardial +/- pleural effusion. Complicated PPS--noncomplicated PPS plus hospital readmission +/- pericardiocentesis or thoracentesis. RESULTS: We randomized 266 children: 20 exclusions (6 perioperative deaths, 14 reasons unrelated to treatment) leaving Group A (n = 126) and Group B (n = 120). There were no significant group differences in gender, cardiac diagnosis or CPB time. Group mean age differed (p = 0.05) and was treated as a covariate with no substantive outcome effect. In total, 39/246 children (16%) developed PPS (noncomplicated: n = 30, complicated: n = 9). There was no inter-group difference in overall PPS incidence (p = 0.73). However, Group A had a marginally significant increase in complicated PPS (p = 0.05). CONCLUSIONS: Intravenous methylprednisolone at a standard anti-inflammatory dose administered pre-CPB and early post-CPB neither prevents nor attenuates PPS in children. Short-term pre-CPB and post-CPB methylprednisolone treatment may complicate PPS.

An immunological approach to postpericardiotomy syndrome occurrence and its relation with autoimmunity.

OBJECTIVE: An autoimmunological approach to the pathogenesis of post-pericardiotomy syndrome. METHODS: In 100 consecutive patients, after open heart surgery, postpericardiotomy syndrome (PPS) was diagnosed in 15 patients according to clinical and laboratory criteria. These patients were prospectively followed up. Levels of serum autoantibodies against cardiac muscle antigen were studied on the 14th, 21st and 33rd day postoperatively. In order to evaluate the cardiac muscle antibody (CMA), antigenic tissue sections from primate heart tissue in solid phase with intermyofibrillar and sarcolemmal-subsarcolemmal fluorescent staining, were taken as substrate. PPS occurrence was determined according to strongly positive antibody titers on the 14th and 21st day postoperatively. RESULTS: CMA were positive in 18 patients, and 14 of them showed clinical signs of PPS. In one case PPS was apparent clinically although CMA were not detected. There was a significant difference between CMA positive and CMA negative patients on the occurrence of PPS. With the use of monoclonal antihuman IgG in the conjugate of indirect fluorescent antibody test the specificity was enhanced. Also, in our experience, the length of cardiopulmonary bypass (CPB) time was an important factor affecting the development of PPS. CONCLUSION: In this study, we found a positive correlation between the presence of CMA and PPS, which is a practical, secure and cheap criterion for the diagnosis.

Post cardiac injury syndrome--one more cause of false positive IgG, IgM antibodies in pleural fluid against antigen-60 of Mycobacterium tuberculosis.

Post cardiac injury syndrome (PCIS) is known to occur following myocardial infarction, cardiac surgery, blunt chest trauma, percutaneous left ventricular puncture and pace-maker implantation. The diagnosis is one of exclusion. We report a case of PCIS following cardiac surgery who showed false positive IgG, IgM antibodies to antigen A60 of Mycobacterium tuberculosis in pleural fluid.

Postcardiac injury syndrome. An immunologic pleural fluid analysis.

The postcardiac injury syndrome (PCIS) is characterized by inflammation of the pericardium, pleura, and pulmonary parenchyma following a variety of cardiac injuries. Although it has been clinically recognized for decades, confirmation of the syndrome has been problematic owing to lack of a sufficiently diagnostic test. Previously, we have reported pleural fluid characteristics which help to exclude other diagnoses that may mimic the syndrome. We describe the first immunologic assessment, including antimyocardial antibody testing, of pleural fluid from a patient with PCIS which supports a local immunologic mechanism in the pathogenesis of the syndrome. These results support the important role of pleural fluid analysis in the diagnosis of PCIS.

Postpericardiotomy syndrome in pediatric heart transplant recipients. Immunologic characteristics.

Clinical features of postpericardiotomy syndrome (PPS) occur in pediatric heart transplant recipients despite immunosuppression, which raises questions about the mechanism of PPS. We studied the clinical and immunologic characteristics of 15 pediatric heart transplant patients, ages 1.1 to 17.8 years (mean, 7.5 years); 7 had clinical evidence of PPS (PPS+), and 8 were without clinical features of PPS (PPS-). Indicators of PPS included fever, irritability, pericardial friction rub, leukocytosis without other cause, and pericardial effusion. The onset of PPS was from 9 to 26 postoperative days (mean, 16 days). Immunosuppressive regimens were comparable up to the day of PPS diagnosis in PPS+ patients, and up to day 16 in PPS- patients (average onset of PPS in PPS+ patients). No differences were found between groups with respect to weight-adjusted dosages of cyclosporin A, azathioprine, or corticosteroids. Mean cyclosporin A levels in PPS+ and PPS- patients were 142 +/- 88 ng/mL (mean +/- standard deviation) and 265 +/- 122 ng/mL (p = 0.045), respectively. Echocardiographic data on 3 PPS+ patients within 1 day of PPS diagnosis revealed pericardial effusions ranging from 5 to 24 mm. No data were available on the remaining 4 PPS+ patients. Minimal pericardial effusions (< 10 mm) were seen in 4 PPS- patients during a comparable time period. One PPS- patient required pericardiocentesis. Endomyocardial biopsy rejection grade did not differ between groups. Means pretransplant soluble interleukin-2 receptor levels did not differ between PPS+ and PPS- patients (758 +/- 410 vs 653 +/- 270 IU/mL); nor did the PPS+ pretransplant levels differ from levels obtained 1 or 2 months postoperatively (700 +/- 437 and 751 +/- 367 IU/mL, respectively). Although pretransplant percentages of the standard T-cell (CD2, CD3, CD4, CD8) and B-cell (DR and CD19) markers differed from post-transplant values, the changes could be explained by the immunosuppressive regimen and did not differ between PPS+ and PPS- patients. In the PPS+ patients, however, there were significant increases in the proportion of activated helper T cells (CD4+/25+) and cytotoxic T cells (Leu-7+/CD8+) following heart transplantation in comparison with pretransplant levels. We speculate that these changes in activation marker in PPS+ patients suggest a possible role for cell-mediated immunity in the pathogenesis of PPS in this group of patients.

The significance of anticardiolipin antibodies and anti-heart muscle antibodies for the diagnosis of postpericardiotomy syndrome.

Postpericardiotomy syndrome (PPS) is a frequent complication after cardiac surgery. In a recent study, elevated anticardiolipin antibody (ACLA) titres were observed in patients with PPS. The value of anti-heart muscle antibodies (AHA) for the diagnosis of PPS remains controversial. Therefore, a prospective double-blind study was performed to test the sensitivity and specificity of ACLA and AHA for the diagnosis of PPS. ACLA titres (ELISA) and AHA, elevated by immunofluorescence, the clinical course and routine laboratory parameters were assessed in 57 patients before and after elective cardiac surgery. ACLA increased and AHA first appeared after surgery in patients both with and without PPS. The sensitivities of a > or = 1.5-fold increase in IgM-ACLA titres, of a > or = 2-fold increase in IgG-ACLA titres and of the occurrence of AHA > or = 2+ for the diagnosis of PPS were 60%, 20% and 20%. The respective specificities were 43%, 79% and 85%. Thus, after cardiac surgery, increased ACLA titres and the occurrence of AHA, as assessed by immunofluorescence, may only contribute to the diagnosis of PPS to a limited extent.

[Preoperative evaluation of the probability of postpericardiotomy syndrome occurrence]. / Przedoperacyjna ocena prawdopodobienstwa wystapienia zespolu po perikardiotomii.

36 women (43%) and 40 men (53%) (total 76) before cardiac surgery underwent the study. The average age was 50 +/- 12,62. The postpericardiotomy syndrome (PPS) was observed in 44 patients (58%). Statistically significant higher mean level CD8 lymphocytes was preoperatively stated in non-PPS patients in comparison with PPS ones (12 PPS pts-38% v.s. 4 non-PPS-9%; p < 0.01). The ratio CD4 to CD8 exceed 1.6 in group of 25 patients (57%) with PPS and only in 9 patients (28%) without PPS (p < 0.05). CD4/CD8 ratio > 1.6 and increased level of lymphocytes with transferrin receptors was more often observed in PPS patients (18 pts; 41%) in comparison with non-PPS ones (3 pts; 9%). The existence of preoperative antimyocardial antibodies did not effect on the higher risk of PPS.

Autoantibody production after cardiopulmonary bypass with special reference to postpericardiotomy syndrome.

A prospective study of children undergoing open heart surgery with cardiopulmonary bypass showed that many of them produced autoantibodies. No association was found between these antibodies, including anticardiolipin antibodies, and the occurrence of postpericardiotomy syndrome.

Antiheart antibodies following open heart surgery: incidence and correlation with postpericardiotomy syndrome.

One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis of myocardial proteins followed by Western blotting is a sensitive method for the detection of antiheart antibodies after cardiac transplantation. In a previous study we found that the majority of patients made antiheart antibodies after cardiac transplantation. It is possible that these antibodies were formed in response to cardiac damage caused during the surgical procedure rather than being specific to the transplantation situation. In this study we have evaluated the role of open cardiac surgery in the formation of antiheart antibodies for the first 9 months of the postoperative period using the Western blotting technique and correlated that with the development of post-pericardiotomy syndrome. Only 25% (9/36) of patients showed any increase in the pre-existing level of antiheart antibodies or developed antiheart antibodies with new reactivities. None of the patients in the study developed manifestations specific for post-pericardiotomy syndrome during the period of follow-up. The results support the contention that the high incidence of antiheart antibodies formed after cardiac transplantation is due to a humoral immune response to the presence of alloantigens on the grafted heart rather than as a result of the surgical procedure itself.

Postoperative immunological response against contractile proteins after coronary bypass surgery.

The pathogenesis of post-cardiac injury syndrome was studied prospectively in 62 patients who underwent coronary bypass grafting. Preoperative and serial postoperative titres of actin and myosin antibodies were measured by an enzyme linked immunosorbent assay. Perioperative cumulative release of serum aspartate and alanine aminotransferases, lactate dehydrogenase, and creatine kinase was calculated by approximation formulas that are used to estimate infarct size. Complete post-cardiac injury syndrome developed in eight (13%) patients and an incomplete syndrome developed in 16 (26%). There was a significant correlation between frequency and intensity of the syndrome and the ratio of postoperative to preoperative titres of actin and myosin antibodies. Furthermore, there was a significant correlation between the cumulative release of lactate dehydrogenase, serum aspartate aminotransferase, and creatine kinase and the number of coronary vessels that were grafted, but no correlation was found between the incidence of post-cardiac injury syndrome and the number of coronary bypasses grafted or between the cumulative enzyme release and the postoperative immunological response against the major contractile proteins, actin and myosin. The amount of enzymes released during coronary bypass surgery seems to be a good indicator of the extent of myocardial damage during operation but it does not determine either the incidence of post-cardiac injury syndrome or the postoperative immunological response against the main contractile proteins actin and myosin.

Complement levels and C3 breakdown products in open-heart surgery: association of C3 conversion with the postpericardiotomy syndrome.

The role of the complement system in the pathogenesis of the post-pericardiotomy syndrome (PPS) was evaluated in a prospective study by measuring the levels of complement (C) components, total haemolytic complement activity and circulating C3 breakdown products in serial plasma and serum samples of 45 patients undergoing open-heart surgery. A consistent reduction in the levels of C3 and C4 but not of factor B was seen on the second post-operative day. During the second post-operative week the antigenic levels of each C component increased significantly. At this time six patients developed the post-pericardiotomy syndrome. Circulating C3 conversion products (C3bi and C3c) were demonstrated in the plasma samples from five of these patients by the immunofixation technique, the mean conversion percentage being 14.3 +/- 10.6. The samples from 15 of the 39 other patients also showed C3 conversion, but the mean percentage was significantly lower (4.5 +/- 6.1%, P less than 0.05). Before the second post-operative week C3 conversion was rare in both groups. The C3d levels of plasma samples, as detected by rocket immunoelectrophoresis, followed a similar pattern. Reduced total haemolytic complement activity was found in three patients suffering from the PPS. These results suggest a role for complement in the non-infectious, inflammatory response during the late post-operative period after open heart surgery, and especially in the post-pericardiotomy syndrome.

[The post-pericardiotomy syndrome. Incidence of clinical and immunological changes]. / El síndrome post-pericardiotomía. Incidencia de alteraciones inmunológicas y clínicas.

We report the clinical and serological studies in patients who underwent pericardiotomy. Seventy three per cent of them developed antisarcolemma antibodies 4 weeks after surgery, and a third of them also had antimitochondrial antibodies. However, clinical post-pericardiotomy syndrome was rare; only 7% of the patients fulfilled the criteria for this diagnosis. Although immune responses against tissue antigens are frequent as a consequence of surgical trauma, the clinical manifestations are rare.

Association of anti-heart antibodies and circulating immune complexes in the post-pericardiotomy syndrome.

The post-pericardiotomy syndrome (PPS) is a common complication of cardiac surgery. In order to better understand the pathogenesis of this complication we undertook a prospective, triple blind study of consecutive long term survivors of cardiac surgery. We followed 82 patients and determined anti-heart antibodies (AHA), circulating immune complexes (CIC) and anti-viral antibodies (AVA) on sera pre-operatively and serially post-operatively. According to the clinical features of pericarditis, fever and leucocytosis, patients were divided into three groups: (1) complete PPS with all three symptoms, (2) incomplete PPS with two symptoms and (3) no PPS with one or no symptoms. Clinical PPS was found in 16 patients (19.6%). All of these patients had positive AHA, 12 patients (75%) had increased CIC and five patients (31%) had a four-fold or greater rise in titre to viruses studied. Twenty-four patients (29.2%) had an incomplete PPS. It was accompanied by positive AHA in 17 patients (70.8%), increased CIC in 14 patients (58.3%) and a four-fold rise or greater in virus titre in seven patients (29.2%). No PPS was found in forty-two patients (51.2%). It was accompanied by positive AHA in eight patients (19%), increased CIC in 10 patients (24%) and a four-fold or greater rise in virus titre in 12 patients (28.6%). There was a good correlation between the presence of PPS, AHA, CIC and the type of operation. Heart valve replacement surgery was more frequently complicated by PPS. Development of post-operative AHA and increased CIC were also more frequently found. We found a good correlation between PPS, positive AHA and increased CIC. No correlation was found between PPS and virus serology.

[Secondary immunopathogenesis of cardiac diseases]. / Zur sekundären Immunopathogenese kardialer Erkrankungen.

Antimyolemmal antibodies can be demonstrated in sera of patients with coxsackie B, influenza, mumps and Q-fever perimyocarditis, in sera of patients with postpericardiotomy and postinfarction syndromes, in part of the sera of patients with endocarditis and in some patients with dilated heart disease most likely due to secondary immunopathogenesis after perimyocarditis. Antimyolemmal antibodies in titres greater than 1: 40 are complement fixing and cytolytic when added to cultures of vital myocytes. In vitro cardiocytolysis indicates that humoral effector mechanisms could also play a pathogenetic role in vivo. In vitro antibody dependent and independent cellular cytotoxicity of patients lymphocytes against isolated cardiocytes could not be observed in perimyocarditis and postmyocarditic cardiomyopathy. It could be demonstrated, however, in patients with postpericardiotomy syndrome and in some patients with dilated cardiomyopathies. Immunological investigations are therefore not only of diagnostic significance but have widened our knowledge of the etiology and pathogenesis of perimyocardial diseases. Furthermore they are helpful in the follow-up and prognosis of patients with protracted perimyocardial affections.

Cell-mediated immune responsiveness to cardiac extracts by peripheral blood leukocytes from patients after myocardial infarction or open-heart surgery.

A microdroplet in vitro procedure measuring migration inhibition was utilized to assess cell-mediated immune reactions by peripheral blood leukocytes from patients after myocardial infarction or cardiac surgery. The antigen preparations were derived from human cardiac tissue. Whereas whole-cell extracts and human myoglobin preparations had little effect on migration, mitochondrial preparations markedly inhibited the migration of blood leukocytes from a majority of the patients. Inhibition of migration appeared to reflect development of cell-mediated immunity to heart antigens after myocardial infarction or surgery. These results extend observations of anticardiac immune development in patients following cardiac injury. Two patients demonstrated a direct relationship between enhanced migration inhibition and clinical disease. It is likely that autoreactive responses to cardiac tissue may be involved and influence subsequent physiological events following initial cardiac infarction or surgery.