Pericardial Fluid Accumulates microRNAs That Regulate Heart Fibrosis after Myocardial Infarction.

Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during coronary artery bypass grafting (CABG) from two MI cohorts, patients with non-ST-segment elevation MI (NSTEMI) and patients with ST-segment elevation MI (STEMI), and a control group composed of patients with stable angina and without previous history of MI. The PF miR content was analyzed by small RNA sequencing, and its biological effect was assessed on human cardiac fibroblasts. PF accumulates fibrotic and inflammatory molecules in STEMI patients, namely causing the soluble suppression of tumorigenicity 2 (ST-2), which inversely correlates with the left ventricle ejection fraction. Although the PF of the three patient groups induce similar levels of fibroblast-to-myofibroblast activation in vitro, RNA sequencing revealed that PF from STEMI patients is particularly enriched not only in pro-fibrotic miRs but also anti-fibrotic miRs. Among those, miR-22-3p was herein found to inhibit TGF-ß-induced human cardiac fibroblast activation in vitro. PF constitutes an attractive source for screening diagnostic/prognostic miRs and for unveiling novel therapeutic targets in cardiac fibrosis.

Detection of drug-resistant Mycobacterium tuberculosis in pericardial fluid culture and its correlation with cartridge based nucleic acid amplification test and adenosine deaminase activity.

BACKGROUND: Pericardial effusion is the accumulation of fluid in the pericardial cavity. In nations with high tuberculosis (TB) load, TB is the most common cause of pericardial effusion. 1-2% of patients with pulmonary TB develop Pericardial TB worldwide. Multi-drug-resistant (MDR) TB, including extrapulmonary TB (EPTB) cases, are rising in number. Adenosine Deaminase (ADA) is an enzyme in lymphocytes and myeloid cells, which has certain immune functions in the body. ADA levels are increased in inflammatory conditions, like pleural, pericardial, or joint effusions, of bacterial etiology, granulomatous conditions, neoplasms, and autoimmune pathologies. TB is the only lymphocytosis involving disease with increased ADA levels. MDR EPTB is rare, but cases are on the rise, and tuberculous pericardial effusion is one such example. Hence, it is important to know the percentage of cases detected by a culture that can be identified by cartridge-based nucleic acid amplification test (CBNAAT), their resistance patterns, and to identify potential markers like ADA, which can help in early identification of cases. The objectives of this study were to identify the Mycobacterium tuberculosis (MTB) bacilli in culture, and correlate them with cartridge-based nucleic acid amplification test (CBNAAT) results and their drug-resistance, in the Pericardial tubercular effusion, and to find if Adenosine Deaminase (ADA) levels can be used as a predictor of the presence of MTB in pericardial fluid. METHODOLOGY: We enrolled 52 patients with moderate to large tuberculous pericardial effusion, based on pericardial fluid analysis, CBNAAT, and culture methods, between January 2021 and December 2021. RESULTS: The mean age of the patients was 41.85 + 17.88 years, with a median of 38 years. Males made up 57.7% of the total patients. MTB was detected in 16 (30.8%) patients in the CBNAAT evaluations. 14 (87.5%) of the CBNAAT-positive TB patients were sensitive to Rifampicin, whereas the remaining 2 (12.5%) were resistant to Rifampicin on CBNAAT. MTB was found to be growing in 8 (15.38%) drug sensitivity test cultures. Out of these 8, 6 were sensitive to first-line drugs, whereas 2 were resistant to both Isoniazid and Rifampicin. The presence of cough was found to have a significant difference between CBNAAT-detected MTB positive and negative patients (p = 0.020), whereas an insignificant difference was found for the presence of hypertension, diabetes mellitus, obesity, dyspnea, or fever. There was also an insignificant difference between the number of patients positive for the Tuberculin skin test, between the two groups. ADA was significantly higher in the MTB-detected CBNAAT group (85.91 + 37.60U/L vs 39.78 + 24.31U/L, p = 0.005), whereas the total leukocyte count, lymphocytes, neutrophils, random blood sugar levels, and serum protein levels had no significant difference. The area under the Receiver Operator Curve (CBNAAT positive: dependent variable; ADA: test result variable) was 0.854 (null hypothesis rejected), with a standard error of 0.078. CONCLUSIONS: Culture is the gold standard method to diagnose tuberculosis. Detection of MTB on pericardial fluid culture is very uncommon, though in our study, culture came out positive in 16% of patients, and 4% were resistant to rifampicin and isoniazid. Higher ADA levels in pericardial fluid are an indicator of tuberculous pericardial effusion.

Pericardial fluid troponin in cardiac surgery.

BACKGROUND AND OBJECTIVE: Pericardial Fluid (PF) is a rich reservoir of biologically active factors. Due to its proximity to the heart, the biochemical structure of PF may reflect the pathological changes in the cardiac interstitial environment. This manuscript aimed to determine whether the PF level of cardiac troponins changes in patients undergoing cardiac surgery. METHODS: This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, EMBASE, Cochrane, ClinicalTrials.gov, and Google Scholar databases were electronically searched for primary studies using the keywords "pericardial fluid," "troponin," and "cardiac surgery." The primary outcome of interest was changes in troponin levels within the PF preoperatively and postoperatively. Secondary outcomes of interest included comparisons between troponin level changes in the PF compared to plasma. RESULTS: A total of 2901 manuscripts were screened through a title and abstract stage by two independent blinded reviewers. Of those, 2894 studies were excluded, and the remaining seven studies underwent a full-text review. Studies were excluded if they did not provide data or failed to meet inclusion criteria. Ultimately, six articles were included that discussed cardiac troponin levels within the PF in patients who had undergone cardiac surgery. Pericardial troponin concentration increased over time after surgery, and levels were significantly higher in PF compared to serum. All studies found that the type of operation did not affect these overall observations. CONCLUSION: Our review of the literature suggest that the PF level of cardiac troponins increases in patients undergoing cardiac surgery, irrespective of the procedure type. However, these changes' exact pattern and clinical significance remain undefined.

Initial diagnosis of extranodal NK/T-cell lymphoma in pericardial fluid with concomitant hemophagocytic lymphohistiocytosis (HLH).

Extranasal natural killer/T-cell lymphoma arising in the heart is rare and typically presents with non-specific clinical symptoms, necessitating a biopsy for a definitive diagnosis. We report an unusual case of a 48-year-old male who initially presented with chest pain and shortness of breath. Subsequent diagnosis via pericardial fluid analysis, including flow cytometry and immunohistochemical stains, revealed extranasal NK/T-cell lymphoma without sinonasal involvement. The analysis identified neoplastic lymphoid cells expressing CD2, cytoplasmic CD3, Epstein-Barr virus, and CD56 and exhibiting increased Ki-67 staining. Additionally, the patient developed hemophagocytosis lymphocytosis secondary to NK/T cell lymphoma. Treatment included an interleukin-1 receptor antagonist (anakinra), dexamethasone, rituximab, and etoposide. Unfortunately, the patient's condition rapidly deteriorated, leading to multiorgan failure and eventual demise. Given the rarity of this lymphoma, early diagnosis based on a high suspicion level provides the best chance for improved overall survival.

Accumulation of Inflammatory Mediators in the Normal Pericardial Fluid.

There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1ß (IL-1ß); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 ß, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid.

Utilidad de la tomografía computarizada multicorte para la estimación de la composición del derrame pericárdico / Usefulness of computed tomography densities to estimate the composition of pericardial effusion

Resumen El derrame pericárdico (DP) es una entidad frecuente en la práctica diaria, que puede ocurrir por un amplio rango de patologías. Los métodos por imágenes constituyen una herramienta diagnóstica clave en la evaluación del pericardio. El ecocardiograma transtorácico (ETT) se considera de primera línea por su costo-efectividad. La tomografía computarizada multicorte (TCMC), por su parte, representa un valioso complemento ante limitaciones del ETT y en la evaluación de urgencia del paciente con sospecha de DP. El objetivo del trabajo es mostrar la utilidad y rol de la TCMC, mediante la medición de densidades, para estimar la etiología del DP, ilustrado con casos de nuestra institución.

Abstract Pericardial effusion (PE) is a common entity in daily practice, which can occur due to a wide range of conditions. Imaging methods are a key diagnostic tool in the evaluation of the pericardium. Transthoracic echocardiogram (TTE) is the first line imaging method because of its cost-effectiveness. Multi-slice Computed Tomography (MSCT), on the other hand, represents a valuable complement to the limitations of TTE and in emergency evaluation of the patient with suspected PE. The objective of this review is to show the usefulness and role of the MSCT —through the measurement of densities— to estimate the etiology of PE, illustrated with cases of our Institution.

Soluble ST2 as a Potential Biomarker in Pericardial Fluid of Coronary Artery Patients

Abstract Introduction: The growth Stimulation expressed gene 2 (ST2) (or interleukin 1 receptor-like 1, also known as IL1RL1) is considered a biomarker of poor prognosis in cardiovascular diseases. The aims of this study are to investigate ST2 in the pericardial fluid (PF) of coronary artery disease patients and to contribute to the understanding of the pathophysiology of coronary artery disease. Methods: 40 patients (blood plasma and PF) who underwent coronary artery bypass surgery and 40 controls (blood plasma only) were included in this study. Soluble ST2 (sST2) level was determined by enzyme-linked ımmunosorbent assay method in plasma and PF, and sST2 gene expression was determined by quantitative real-time polymerase chain reaction (QRT-PCR) method. Results: The sST2 level was found to be 44.89 ng/ml and 390.357 ng/ml in the control and patient groups' plasma, and 223.992 ng/ml in the PF of the patient group. An increase in sST2 level was detected in the patient group compared to the control group (P<0.001). The sST2 expression in plasma was higher in the patient group than in the control group. Additionally, sST2 was more expressed in the plasma of the patient group than PF (P<0.001). Conclusion: The fact that sST2 was detected for the first time in a high level in PF showed that this biomarker was closely related with the heart and strengthened its potential to be used as a biomarker. Therefore, sST2 can contribute to the understanding of the pathophysiology of coronary artery disease.

Caso Clínico: Mesotelioma primario de pericardio / Case Report: Primary Pericardial Mesothelioma / Case Report: Primary Pericardial Mesothelioma

INTRODUCCIÓN: El mesotelioma primario de pericardio (MPP) es un tumor de origen mesodérmico muy raro dentro de las patologías oncológicas; con una incidencia muy baja. Se han descrito aproximadamente 350 casos alrededor del mundo, siendo la mayoría diagnósticos post mortem. El pronóstico es malo a corto plazo, independientemente del tratamiento a instaurarse, siendo este por lo general únicamente paliativo. A continuación presentamos un caso clínico a propósito de esta patología. CASO CLÍNICO: Paciente de 69 años hospitalizado con cuadro de disnea progresiva y anemia severa. En exámenes complementarios de imagen se evidenció derrame pleural y derrame pericárdico. El reporte histopatológico del líquido pericárdico fue positivo para mesotelioma pericárdico. EVOLUCIÓN: Debido a derrame pericárdico recurrente se decidió realizar pericardiectomía más pleurectomía izquierda como tratamiento paliativo, para aliviar la sintomatología del paciente. Se propuso continuar con quimioterapia, sin embargo, el estado general del paciente se deterioró llevando al fallecimiento. CONCLUSIÓN: El mesotelioma primario de pericárdico es un tumor extremadamente raro, cuya clínica se caracteriza por sintomatología asociada al derrame pericárdico, siendo debido a su baja incidencia un diagnóstico difícil. El pronóstico es malo a corto plazo y no se encuentra un protocolo establecido con resultados que mejoren la mortalidad.

BACKGROUND: Primary pericardial mesothelioma is an extremely rare mesodermal tumor, among oncological diseases, with a very low incidence. About 350 cases have been described around the world, most of them diagnosed post-mortem. The short term prognosis is poor, regardless of the treatment, which is mostly palliative. We present a case report regarding this pathology. CASE REPORT: 69 year old patient hospitalized with dyspnea and severe anemia. Complementary workup showed pleural effusion and pericardial effusion. Histopathology report of the pericardial fluid revealed pericardial mesothelioma. EVOLUTION: Due to recurrence of pericardial effusion, it was decided to perform pericardiectomy and left pleurectomy as palliative treatment, to alleviate the patient's symptoms. Chemotherapy was planned after the procedure, but the patient's general condition deteriorated severely leading to his death. CONCLUSION: Primary pericardial mesothelioma is a rare tumor, whose symptoms are characterized by the associated pericardial effusion, making the diagnosis difficult due to it low incidence. The prognosis is poor in short- term, and there isn't an established protocol for the treatment with results that showed improve in mortality.

Pericardial Parietal Mesothelial Cells: Source of the Angiotensin-Converting-Enzyme of the Bovine Pericardial Fluid / Células Mesoteliais Pericárdicas Parietais: Fonte da Enzima Conversora de Angiotensina Existente no Líquido Pericárdico Bovino

Abstract Background: Angiotensin II (Ang II), the primary effector hormone of the renin-angiotensin system (RAS), acts systemically or locally, being produced by the action of angiotensin-converting-enzyme (ACE) on angiotensin I. Although several tissue RASs, such as cardiac RAS, have been described, little is known about the presence of an RAS in the pericardial fluid and its possible sources. Locally produced Ang II has paracrine and autocrine effects, inducing left ventricular hypertrophy, fibrosis, heart failure and cardiac dysfunction. Because of the difficulties inherent in human pericardial fluid collection, appropriate experimental models are useful to obtain data regarding the characteristics of the pericardial fluid and surrounding tissues. Objectives: To evidence the presence of constituents of the Ang II production paths in bovine pericardial fluid and parietal pericardium. Methods: Albumin-free crude extracts of bovine pericardial fluid, immunoprecipitated with anti-ACE antibody, were submitted to electrophoresis (SDS-PAGE) and gels stained with coomassie blue. Duplicates of gels were probed with anti-ACE antibody. In the pericardial membranes, ACE was detected by use of immunofluorescence. Results: Immunodetection on nitrocellulose membranes showed a 146-KDa ACE isoform in the bovine pericardial fluid. On the pericardial membrane sections, ACE was immunolocalized in the mesothelial layer. Conclusions: The ACE isoform in the bovine pericardial fluid and parietal pericardium should account at least partially for the production of Ang II in the pericardial space, and should be considered when assessing the cardiac RAS.

Resumo Fundamentos: Angiotensina II (Ang II), o hormônio efetor primário do sistema renina-angiotensina (SRA), atuando em níveis sistêmicos ou locais, é produzida pela ação da enzima conversora de angiotensina (ECA) sobre a angiotensina I. Embora diversos SRAs teciduais, como o SRA cardíaco, tenham sido descritos em muitos estudos, dados de um SRA no líquido pericárdico e sua origem não são ainda disponíveis. A Ang II localmente produzida tem efeitos parácrinos e autócrinos, induzindo a hipertrofia ventricular esquerda, fibrose, insuficiência e disfunção cardíacas. Devido às dificuldades inerentes à obtenção de líquido pericárdico humano, modelos experimentais apropriados são muito úteis para obter dados relativos às suas características bem como dos tecidos contíguos. Objetivos: Obter evidências da presença de constituintes das vias de produção de Ang II no líquido pericárdico e no pericárdio parietal bovinos. Métodos: Extratos brutos de líquido pericárdico bovino sem albumina (sobrenadantes), imunoprecipitados com anticorpo anti-ECA, foram submetidos a eletroforese (SDS-PAGE) e os géis corados com Coomassie Blue. Duplicatas dos géis foram sondadas com anticorpo anti-ECA. A detecção de ECA nas membranas pericárdicas foi realizada por imunofluorescência. Resultados: A imunodetecção sobre as membranas de nitrocelulose mostrou uma isoforma de ECA com 146 KDa no líquido pericárdico bovino. Nas secções de membrana pericárdica, a ECA foi imunolocalizada na camada mesotelial. Conclusões: A isoforma de ECA do líquido pericárdico bovino e do pericárdio parietal deve ser, pelo menos em parte, responsável pela produção de Ang II no espaço pericárdico, devendo ser considerada quando o SRA cardíaco for avaliado.