Application of the International System for Reporting Serous Fluid Cytopathology to pericardial fluid: Root cause analysis of indeterminate diagnoses, cytohistological correlation, and assessment of malignancy risk.

BACKGROUND: This study investigates the utility of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in the categorization of pericardial fluid and assesses the diagnostic performance and risk of malignancy (ROM) for each of the diagnostic categories. METHODS: All pericardial fluid cases at the Yale School of Medicine between January 1, 2017, and December 31, 2020, were reviewed. The diagnoses were reclassified into five categories according to the ISRSFC: nondiagnostic (ND), negative for malignancy (NFM), atypia of uncertain significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). ROM and performance parameters of each category were calculated. RESULTS: After reclassification, the distribution of 465 pericardial fluid cases in each category was as follows: ND, 19 (4.1%); NFM, 332 (71.4%); AUS, 21 (4.5%); SFM, 11 (2.4%); and MAL, 82 (17.6%). Confirmatory follow-ups were available for 16 ND (66.7%), 299 NFM (90%), 15 AUS (71%), 5 SFM (45.5%), and 30 MAL cases (36.6%). The ROM was 0% for ND, 1.3% for NFM (4 of 332), 20% for AUS (3 of 15), and 100% for both SFM (5 of 5) and MAL (27 of 27). The diagnostic performance was as follows: sensitivity, 87% (27 of 31); specificity, 100% (292 of 292); positive predictive value (PPV), 100% (27 of 27); negative predictive value (NPV), 98.6% (292 of 296); and diagnostic accuracy, 98.8% (319 of 323). CONCLUSIONS: The ISRSFC is a highly useful system for the reporting of pericardial fluid and risk assessment, given that it offers high sensitivity, specificity, PPV, NPV, and diagnostic accuracy. The application of this system may help to better categorize pericardial fluid and facilitate the standardization of cytopathology reporting.

Categorisation of serous effusions using the International System for Reporting Serous Fluid Cytopathology and assessment of risk of malignancy with diagnostic accuracy.

CONTEXT: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) standardises the reporting of serous effusion cytology under five categories: Non-Diagnostic (ND), Negative for Malignancy (NFM), Atypia of Undetermined Significance (AUS), Suspicious for Malignancy (SFM), and Malignant (M). Very few studies have been conducted so far to confirm the risk of malignancy of the different categories. AIMS: The main objectives of our study were to classify serous effusions according to the ISRSFC categories and assess their risk of malignancy (ROM) and performance parameters. MATERIALS AND METHODS: All serous effusion samples received from January 2019 to December 2020 were reclassified according to the ISRSFC. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated. RESULTS: A total of 831 pleural effusion samples were reclassified as follows: ND, 3 (0.4%); NFM, 635 (76.4%); AUS, 65 (7.8%); SFM, 60 (7.2%); and M, 68 (8.2%). For 457 peritoneal effusion samples, the reclassifications were ND, 5 (1.1%); NFM, 368 (80.5%); AUS, 19 (4.2%); SFM, 17 (3.7%); and M, 48 (10.5%). All 12 (100%) pericardial effusions belonged to the NFM category. The ROM for the ND, NFM, AUS, SRM, and M categories was 0%, 2.1%, 33.3%, 94.1%, 100%, respectively, in pleural effusions, and 50%, 4.8%, 22.2%, 83.3%, 100%, respectively, in peritoneal effusions. The ROM was 0% for NFM in pericardial effusions. CONCLUSION: The ISRSFC is an excellent system for accurately classifying serous effusions with greater reproducibility of reports and better communication between pathologist and clinician.

Assessment of Pericardial Disease with Cardiovascular MRI.

Disorders of the pericardium are common and can result in significant morbidity and mortality. Advances in multimodality imaging have enhanced our ability to diagnose and stage pericardial disease and improve our understanding of the pathophysiology of the disease. Cardiovascular MRI (CMR) can be used to define pericardial anatomy, identify the presence and extent of active pericardial inflammation, and assess the hemodynamic consequences of pericardial disease. In this way, CMR can guide the judicial use of antiinflammatory and immune modulatory medications and help with timing of pericardiectomy. CMR can also be used to diagnose congenital disorders of the pericardium. Furthermore, CMR can be used to define pericardial masses and understand their malignant potential.

Echocardiographic assessment of tricuspid regurgitation and pericardial effusion after cardiac device implantation.

BACKGROUND: The frequency of cardiac implantable electronic device (CIED) implantations is constantly increasing. Pericardial effusion (PE) and tricuspid regurgitation (TR) may occur after CIED implantation. The aim of the present study is to evaluate the prevalence and risk factors for new occurrences or progression of TR and PE early after CIED implantation. METHODS: This is an on-going, single-center, observational study of patients after their first CIED implantation, with an echocardiographic evaluation within 60 days before and 7 days after the procedure. Data are presented for first 110 consecutive patients who underwent CIED implantation from August 2015 to July 2016. RESULTS: Median age was 75 years, and 44% were women. In total, 87 (79%) pacemakers, 21 (19%) implantable cardioverter-defibrillators and 2 cardiac resynchronization therapy devices were implanted. After CIED implantation, there was TR progression in 17 (16%) patients: 5 patients developed moderate TR, none developed severe TR. An increase in TR was more often observed after implantations performed by operators in training than by certified operators (35% vs. 12%, p = 0.02). New PE after the procedure was observed in 8 (7%) patients and was trivial ( < 5 mm) in all cases. Patients with new PE after implantation had lower baseline hemoglobin levels and tended to be women. CONCLUSIONS: New PE and an increase in TR severity are rare complications early after CIED implantation. Operator experience might be related to TR progression. Increasing the number of patients in the current on-going study will allow a more reliable assessment of the prevalence and risk factors of these complications.

Pericardial fluid: assessment and examination.

Pericardial fluid is a common finding on echocardiography. Less than 10 mm of fluid on ultrasound scan is not necessarily associated with any significant illness. Clinical examination, blood count, renal and liver enzymes and thyroid function tests as well as inflammatory marker tests are often adequate for a patient who is in good health. A significant amount of fluid requires further investigations, especially in a symptomatic patient. Cancers, infections and various systemic diseases are the most common causes of prominent effusion.

Idiopathic pericarditis and pericardial effusion in children: contemporary epidemiology and management.

BACKGROUND: Multicenter studies on idiopathic or viral pericarditis and pericardial effusion (PPE) have not been reported in children. Colchicine use for PPE in adults is supported. We explored epidemiology and management for inpatient hospitalizations for PPE in US children and risk factors for readmission. METHODS AND RESULTS: We analyzed patients in the Pediatric Health Information System database for (1) a code for PPE; (2) absence of codes for underlying systemic disease (eg, neoplastic, cardiac, rheumatologic, renal); (3) age ≥30 days and <21 years; and (4) discharge between January 1, 2007, and December 31, 2012, from 38 hospitals contributing complete data for each year of the study period. Among 11 364 hospitalizations with PPE codes during the study period, 543 (4.8%) met entry criteria for idiopathic or viral PPE. Significantly more boys were noted, especially among adolescents. No temporal trends were noted. Median age was 14.5 years (interquartile range 7.3 to 16.6 years); 78 patients (14.4%) underwent pericardiocentesis, 13 (2.4%) underwent pericardiotomy, and 11 (2.0%) underwent pericardiectomy; 157 (28.9%) had an intensive care unit stay, including 2.0% with tamponade. Median hospitalization was 3 days (interquartile range 2 to 4 days). Medications used at initial admission were nonsteroidal anti-inflammatory drugs (71.3%), corticosteroids (22.7%), aspirin (7.0%), and colchicine (3.9%). Readmissions within 1 year of initial admission occurred in 46 of 447 patients (10.3%), mostly in the first 3 months. No independent predictors of readmission were noted, but our statistical power was limited. Practice variation was noted in medical management and pericardiocentesis. CONCLUSIONS: Our report provides the first large multicenter description of idiopathic or viral PPE in children. Idiopathic or viral PPE is most common in male adolescents and is treated infrequently with colchicine.

Focused transthoracic echocardiography during critical care medicine training: curriculum implementation and evaluation of proficiency*.

OBJECTIVES: We designed and implemented a focused transthoracic echocardiography curriculum for critical care medicine fellows participating in 1- and 2-year training programs. We quantitatively evaluated their proficiency in focused transthoracic echocardiography. DESIGN: Prospective study evaluating curriculum implementation and objective assessment of focused transthoracic echocardiography proficiency. SETTING: Medical and surgical ICUs at an academic teaching hospital. Simulation laboratory. SUBJECTS: Eighteen critical care medicine fellows. INTERVENTIONS: Training in focused transthoracic echocardiography followed by proficiency testing. MEASUREMENTS AND MAIN RESULTS: We assessed the ability of critical care medicine fellows to obtain and interpret focused transthoracic echocardiography images from critically ill patients and a from transthoracic echocardiography simulator. Using a cognitive examination test, we also evaluated each fellow's knowledge with regard to focused transthoracic echocardiography and each fellow's ability to interpret prerecorded focused transthoracic echocardiography images. After training, critical care medicine fellows were able to rapidly obtain five essential focused transthoracic echocardiography views: parasternal long axis, parasternal short axis, apical four chamber, subcostal four chamber, and subcostal inferior vena cava. Fellows were also able to expeditiously identify four important abnormalities: asystole, left ventricular dysfunction, right ventricular dilation and dysfunction, and a large pericardial effusion. CONCLUSIONS: A focused transthoracic echocardiography curriculum that includes quantitative measures of proficiency can be integrated into critical care medicine fellowship training programs.

Cardiovascular risk assessment of the liver transplant candidate.

Liver transplantation (LT) candidates today are increasingly older, have greater medical acuity, and have more cardiovascular comorbidities than ever before. Steadily rising model for end-stage liver disease (MELD) scores at the time of transplant, resulting from high organ demand, reflect the escalating risk profiles of LT candidates. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output and a compromised ventricular response to stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances are likely mediated by decreased beta-agonist transduction, increased circulating inflammatory mediators with cardiodepressant properties, and repolarization changes. Low systemic vascular resistance and bradycardia are also commonly seen in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes all contribute to the potential for cardiovascular complications, particularly with the altered hemodynamic stresses that LT patients face in the immediate post-operative period. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure, and myocardial infarction. Recognizing the hemodynamic challenges encountered by LT patients in the perioperative period and how these responses can be exacerbated by underlying cardiac pathology is critical in developing recommendations for the pre-operative risk assessment and management of these patients. The following provides a review of the cardiovascular challenges in LT candidates, as well as evidence-based recommendations for their evaluation and management.

[Tumor markers in the assessment of malignant and benign pericardial effusion]. / Tumormarker im Perikarderguss bei malignen und nichtmalignen Perikardergüssen.

BACKGROUND: The differential diagnosis of pericardial effusion is often challenging because different etiologies can be discussed. Of particular therapeutic and prognostic importance is the definitive differentiation of malignant pericardial effusion from benign effusions. The definitive diagnosis of malignant pericardial effusion is established by a positive cytological examination of the pericardial fluid. However, pericardial fluid cytology, although specific has variable sensitivity. Tumor markers are often investigated after pericardiocentesis but their utility as an aid for the diagnosis of malignant pericardial effusion is not well established. The aim of this study was to measure the concentrations of the tumor markers CEA, CA 19-9, CA 72-4, SCC and NSE in malignant and non-malignant pericardial effusions and to assess their diagnostic utility in differentiating malignant from benign pericardial effusion. METHODS: We investigated the pericardial fluid of 29 patients with proven malignant pericardial effusion and 25 patients with non-malignant pericardial effusion. The etiology of the pericardial effusion was defined by pericardial cytology, epicardial histology and PCR for cardiotropic viruses from pericardial and epicardial tissue acquired by pericardioscopy. The group with non-malignant pericardial effusion comprised 15 patients with autoreactive effusion and 10 patients with viral pericardial effusion. We analyzed the following tumor markers in the pericardial fluid: carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, carbohydrate antigen (CA) 72-4, squamous cell carcinoma (SCC) antigen and neuron-specific enolase (NSE). RESULTS: Of the tumor markers tested the mean concentrations of the CEA, CA 72-4 and CA 19-9 were significantly higher in malignant pericardial effusions than in non-malignant effusions (CEA 450.66 ±1620.58 µg/l vs. 0.72 ±1.49 µg/l, p<0.001; CA 19-9 1331.31 ±3420.87 kU/l vs. 58.85 ±17.53 kU/l, p=0.04; CA 72-4 707.90 ±2397.55 kU/l vs. 0.48 ±2.40 kU/l, p<0.001). ROC curve analysis showed that pericardial fluid CA 72-4 yielded an area under the curve (AUC) of 0.85 (95% confidence interval 0.74-0.95), followed by CEA with 0.80 (95% confidence interval 0.68-0.92). Pericardial fluid CA 72-4 levels >1.0 kU/l had 72% sensitivity (95% confidence interval 53%-87%) and 96% specificity (95% confidence interval 80%-99.9%) and CA 72-4 levels >2.5 kU/l had 69% sensitivity (95% confidence interval 49%-85%) and 96% specificity (95% confidence interval 80%-99.9%) in differentiating malignant pericardial effusions from effusions due to benign conditions. CONCLUSION: Malignant pericardial effusions are associated with significantly higher pericardial concentrations of the tumor markers CEA, CA 72-4 and CA 19-9. Of the tested tumor markers, measurement of CA 72-4 levels in pericardial fluid offered the best diagnostic accuracy. Based on our data evaluation of every patient with unexplained pericardial effusion and negative pericardial fluid cytology should include the measurement of pericardial fluid CA 72-4 levels. Under these circumstances the elevation of pericardial fluid CA 72-4 levels should include malignancy as a probable diagnosis.

Disease association and clinical assessment of feline pericardial effusion.

Records were reviewed from 83 cases to determine the main causes and clinical significance of feline pericardial effusion. The most common causes included hypertrophic cardiomyopathy with congestive heart failure, neoplasia, and systemic infection. Most cases had concurrent or secondary pleural effusion or pulmonary edema, with clinical signs of respiratory disease. However, several cases appeared to be affected solely by pericardial effusion rather than pulmonary pathology. Feline pericardial effusion remains an infrequent diagnosis, but its clinical relevance and association with severe cardiac and extracardiac disease warrant diagnostic evaluation.

The diagnosis of pericardial effusion and cardiac tamponade by 12-lead ECG. A technology assessment.

OBJECTIVE: This study was designed to determine the diagnostic value of 12-lead ECG for pericardial effusion and cardiac tamponade. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENTS: Hospitalized patients with and without pericardial effusion and cardiac tamponade. MEASUREMENTS AND RESULTS: In a blinded manner, we reviewed 12-lead ECGs from 136 patients with echocardiographically diagnosed pericardial effusions (12 of whom had cardiac tamponade) and from 19 control subjects without effusions. We examined the diagnostic value of three ECG signs: low voltage, PR segment depression, and electrical alternans. We found that all three ECG signs were specific but not sensitive for pericardial effusion (specificity, 89 to 100%; sensitivity, 1 to 17%) and cardiac tamponade (specificity, 86 to 99%; sensitivity, 0 to 42%). None of the ECG signs were associated with pericardial effusions of all sizes, but low voltage was associated with large and moderate pericardial effusions (odds ratio = 2.5; 95% confidence interval [CI] = 0.9 to 6.5; p = 0.06) and with cardiac tamponade (odds ratio = 4.7; 95% CI = 1.1 to 21.0; p = 0.004). In contrast, PR segment depression was associated only with cardiac tamponade (odds ratio = 2.0; 95% CI = 1.0 to 4.0; p = 0.05), while electrical alternans was not associated with either pericardial effusion or cardiac tamponade. CONCLUSIONS: Low voltage and PR segment depression are ECG signs that are suggestive, but not diagnostic, of pericardial effusion and cardiac tamponade. Because these ECG findings cannot reliably identify these conditions, we conclude that 12-lead ECG is poorly diagnostic of pericardial effusion and cardiac tamponade.

M mode and Doppler echocardiographic assessment of left ventricular diastolic function in primary antiphospholipid syndrome.

BACKGROUND: High titres of serum antiphospholipid antibodies are a possible pathogenic factor for cardiac lesions in patients with systemic lupus erythematosus. OBJECTIVE: To test the hypothesis of a causal link between high titres of antiphospholipid antibodies in the serum and myocardial involvement in patients without systemic lupus erythematosus. PATIENTS AND DESIGN: 18 patients with primary antiphospholipid syndrome (recurrent fetal loss, arterial and/or venous thrombosis, high titres of antiphospholipid antibodies, and no criteria for systemic lupus erythematosus) were prospectively studied by cross sectional, M mode, and pulsed Doppler echocardiography, and compared with 18 healthy controls. The pulsed Doppler indices of left ventricular diastolic function included isovolumic relaxation time and four mitral outflow indices: peak velocity of early flow, peak velocity of late flow, early to late peak flow velocity ratio, and rate of deceleration of early flow. Four computerised M mode indices were also measured: peak rate of left ventricular enlargement in diastole, peak rate of posterior wall thinning, peak velocity of lengthening of the posterior wall, and velocity of circumferential chamber lengthening. RESULTS: Compared with controls, patients with primary antiphospholipid syndrome had higher values for isovolumic relaxation time and peak velocity of late mitral outflow and lower values for early to late mitral peak outflow velocity ratio, rate of deceleration of early mitral outflow, peak rate of left ventricular enlargement in diastole, peak rate of posterior wall thinning, peak velocity of lengthening of the posterior wall and velocity of circumferential chamber lengthening. CONCLUSION: This abnormal pattern reflects an impairment of myocardial relaxation and filling dynamics of the left ventricle in patients with primary antiphospholipid syndrome who were free of any clinically detectable heart disease. These data suggest that high serum titres of antiphospholipid antibodies may be associated with subclinical myocardial damage.

Assessment of experimental pericardial effusion using nuclear magnetic resonance imaging techniques.

An experimental canine model of pericardial effusion was designed to validate previous clinical nuclear magnetic resonance imaging (NMR) studies. Saline (n = 7), serum (n = 4), blood (10% hematocrit [n = 5]; 20% hematocrit [n = 5]), and lipid (n = 4) effusions were chosen to resemble: (1) transudative/exudative, (2) nonhemorrhagic/hemorrhagic, and (3) chylous effusions, respectively. There was a linear correlation between the infused volume and the pericardial/epicardial distance measurements on the nuclear magnetic resonance images. Hemorrhagic and nonhemorrhagic exudative effusions were distinguished from transudative effusions by the low signal intensity of transudative effusions images obtained at a TR (repetition time) of 400 and 800 msec. Nonhemorrhagic effusions had significantly lower effusion-to-myocardial signal intensity ratio at TR of 400 msec than did hemorrhagic effusions. Differences in hematocrit were not appreciated qualitatively or quantitatively. Compared with other effusion types, only chylous effusions were hyperintense to myocardium at a TR of 400 msec. Chylous effusions were further uniquely characterized by a decreasing effusion-to-myocardial signal intensity ratio with increasing TR. These experimental findings corroborate the findings of earlier clinical reports and suggest that NMR can provide important assistance in the evaluation of pericardial effusions.

Contribuiton of M-mode echocardiography to cardiac diagnosis. An assessment in 1,000 successive patients.

The contribution of M-mode echocardiography to cardiac diagnosis was evaluated in a series of 1,000 successive patients. Among subjects in whom a presumptive clinical diagnosis had been made, echocardiography demonstrated totally unexpected findings in 10 per cent, supported the clinical diagnosis in 50 per cent and was entirely within normal limits in 19 per cent. Among patients with evidence of heart disease but no firm clinical diagnosis, echocardiography established the diagnosis in 23 per cent, including 20 per cent of all patients referred for evaluation of chest pain or arrhythmia of unclear etiology. "Missed" clinical diagnosis frequently involved patients with mitral valve prolapse, congestive cardiomyopathy, pericardial disease or asymmetrical septal hypertrophy of the heart. This study quantifies the amount of independent information contributed by echocardiography to cardiac diagnosis and demonstrates that this technic provides data of important clinical relevance in a surprisingly large number of cardiac patients.

Pericardial effusion and electrical alternans: echocardiographic assessment.

Clinical diagnosis of pericardial effusion is often difficult, and assessment of the effects of effusion on cardiac hemodynamics is often imprecise. Electrical alternans is a reasonably specific ECG indicator of the presence of a large effusion and imminent or actual cardiac tamponade. If echocardiography verifies the presennce of pericardial fluid and shows abnormal cardiac motion, a diagnosis of cardiac tamponade can be made without further, more invasive, studies.