Novel Pathophysiological, Diagnostic and Therapeutic Concepts in Acute and Recurrent Pericarditis.

Acute pericarditis is the most frequent pericardial disease characterized by inflammation of the pericardial layers resulting in pain, dyspnea and fatigue. Often limited to an isolated event, up to 30% of patients experience one or more recurrences. There is limited knowledge about the pathophysiology of this disease, possibly due to the limited availability of animal models. More recently, following seminal clinical trials with colchicine and interleukin-1 (IL-1) blockers and a novel murine model of acute pericarditis using zymosan A, it has become clear that the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome/IL-1 ß axis plays a central role in driving acute pericardial inflammation and in sustaining this process during recurrences. Diagnostic management of pericarditis has been implemented with multimodality imaging including echocardiography, cardiac computed tomography, and cardiac magnetic resonance. These imaging modalities provide essential diagnostic and pathogenetic information, and are able to characterize pericardial inflammation, allowing to refine risk stratification and personalize treatment. Recent acquisitions yield relevant implications with regard to the therapeutic management of acute and recurrent pericarditis. Non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are cornerstone therapies either for acute and recurrent pericarditis. However, the benefits of targeted agents, such as anakinra - a recombinant human IL-1 receptor antagonist - and rilonacept - an IL-1 α /IL-1 ß trap, are being increasingly recognized. To this end, phenotyping patients with pericarditis and addressing such therapies to those presenting with auto-inflammatory features (elevated C-reactive protein, sustained pericardial and systemic inflammation, multiple recurrences) is of utmost importance to identify patients who might be more likely to benefit from NLRP3 inflammasome/IL-1 ß pathway blockade.

Natural Course of Electrocardiogram Changes and the Value of Multimodality Imaging in Acute Pericarditis.

BACKGROUND: ECG is the initial diagnostic tool that in combination with typical symptoms often raises the suspicion of pericarditis. Echocardiography remains the first-line imaging modality for assessment of pericardial diseases, particularly effusion/tamponade, constrictive physiology, and assessment of regional wall motion abnormalities as differential diagnoses. However, cardiac CT and cardiac magnetic resonance may be necessary in complicated cases and to identify pericardial inflammation in specific settings (atypical presentation, new onset constriction), as well as myocardial involvement and monitoring the disease activity. SUMMARY: In acute pericarditis, the most commonly used ECG criteria recommended by international guidelines are the widespread ST-segment elevation or PR depression. However, the classic ECG pattern of widespread ST-segment elevation or PR depression can be seen in less than 60% of patients. In addition, ECG changes are often temporally dynamic, evolve rapidly during the course of disease, and may be influenced by a number of factors such as disease severity, time (stage) of presentation, degree of myocardial involvement, and the treatment initiated. Overall, temporal dynamic changes on ECG during acute pericarditis or myopericarditis have received limited attention. Hence, the aim of this brief clinical review was to increase awareness about the various ECG changes observed during the course of acute pericarditis. KEY MESSAGES: ECG may be normal at presentation or for days after the index episode of chest pain, but serial ECGs can reveal specific patterns of temporally dynamic ST elevation in patients with pericarditis or myopericarditis, particularly during new episodes of chest pain.

Pericardial Manifestations of Thyroid Diseases.

PURPOSE OF REVIEW: Thyroid disorders, especially hypothyroidism, are known to be associated with pericardial diseases. The aim of this paper is to review the current knowledge of the pericardial manifestations of hypothyroidism and hyperthyroidism. RECENT FINDINGS: Many reports have described associations between dysthyroidism, which encompasses hypothyroidism and hyperthyroidism, and several pericardial diseases, including acute pericarditis, constrictive pericarditis, pericardial effusion, and tamponade. The diagnosis of dysthyroidism-induced pericardial diseases consists of a combination of thyroid blood levels that fall outside of the normal range and the exclusion of other causes. Treatment of the thyroid disorder is key, along with treatment of the pericardial disease as recommended by the guidelines. Early recognition of the thyroid disorder is key in patients with pericardial diseases, since treating the underlying cause should assist resolution of the pericardial issues and ideally prevent recurrence and possible future complications of suboptimally treated pericarditis or pericardial effusions.

Acute Pericarditis: Update.

PURPOSE OF REVIEW: Since 2015, when ESC guidelines for the diagnosis and management of pericardial diseases were published, ongoing research has enhanced the current state of knowledge on acute pericarditis. This review is an update on the latest developments in this field. RECENT FINDINGS: In recurrent acute pericarditis, autoinflammation has been included among causative mechanisms restricting the vague diagnoses of "idiopathic" pericarditis. Cardiac magnetic resonance that detects ongoing pericardial inflammation may guide treatment in difficult-to-treat patients. Development of risk scores may assist identification of patients at high risk for complicated pericarditis, who should be closely monitored and aggressively treated. Treatment with IL-1 inhibitors has been proven efficacious in recurrent forms with a good safety profile. Finally, acute pericarditis has recently attracted great interest as it has been reported among side effects post COVID-19 vaccination and may also complicate SARS-CoV-2 infection. Recent advancements in acute pericarditis have contributed to a better understanding of the disease allowing a tailored to the individual patient approach. However, there are still unsolved questions that require further research.

[Red man syndrome as a complication of vancomycin therapy]. / Zespól czerwonego czlowieka jako powiklanie leczenia wankomycyna.

Red man syndrome (RMS) is a side effect of vancomycin therapy and manifests itself mainly by a red blotchy rash with itching and sometimes muscle pain and a decrease of arterial blood pressure. A CASE REPORT: 24-year-old patient admitted to hospital with a history of chest pain radiating to the back. EKG has shown the depression of PQ, in the ECHO mark of liquid in the pericardial cavity and the increase of CRP and troponin concentrations. The patient was diagnosed with acute pericarditis and treated with ibuprofen and colchicine. Due to the increasing parameters of inflammation, a bacterial etiology was suspected and vancomycin was administered. During antibiotic therapy, there were symptoms of a mild adverse reaction in the form of a maculopapular rash and periodic decreases in blood pressure. RMS was diagnosed and symptoms resolved after treatment with cetirizine. CONCLUSIONS: RMS should be distinguished from anaphylaxis and treated according to the diagnosis.

A risk score for pericarditis recurrence.

BACKGROUND: Currently, we remain uncertain about which patients are at increased risk for recurrent pericarditis. We developed a risk score for pericarditis recurrence in patients with acute pericarditis. MATERIALS AND METHODS: We prospectively recruited 262 patients with a first episode of acute pericarditis. Baseline patients' demographics, clinical, imaging and laboratory data were collected. Patients were followed up for a median of 51 months (interquartile range 21-71) for recurrence. Variables with <10% missingness were entered into multivariable logistic regression models with stepwise elimination to explore independent predictors of recurrence. The final model performance was assessed by the c-index whereas model's calibration and optimism-corrected c-index were evaluated after 10-fold cross-validation. RESULTS: We identified six independent predictors for pericarditis recurrence, that is age, effusion size, platelet count (negative predictors) and reduced inferior vena cava collapse, in-hospital use of corticosteroids and heart rate (positive predictors). The final model had good performance for recurrence, c-index 0.783 (95% CI 0.725-0.842), while the optimism-corrected c-index after cross-validation was 0.752. Based on these variables, we developed a risk score point system for recurrence (0-22 points) with equally good performance (c-index 0.740, 95% CI 0.677-0.803). Patients with a low score (0-7 points) had 21.3% risk for recurrence, while those with high score (≥12 points) had a 69.8% risk for recurrence. The score was predictive of recurrence among most patient subgroups. CONCLUSIONS: A simple risk score point system based on 6 variables can be used to predict the individualized risk for pericarditis recurrence among patients with a first episode of acute pericarditis.

Age- and sex-based differences in patients with acute pericarditis.

BACKGROUND: Acute pericarditis has a wide spectrum of clinical presentations largely depending on underlying aetiologies. We assessed the role of age and sex in the clinical features and outcome of acute pericarditis. MATERIALS AND METHODS: A total of 240 consecutive patients hospitalized with a first episode of acute pericarditis were included. At baseline demographics, clinical features, laboratory and imaging findings and medical therapy were recorded. Patients were followed up for at least 18 months for complications. Data comparisons were performed according to sex and age (≤60 or >60 years). RESULTS: The male/female ratio was 1.42, and 56% of patients were >60 years. Younger patients depicted more often chest pain (P = .001), fever and rubs (P < .001 for both), ST elevation and PR depression (P = .032 and .009, respectively), higher CRP values (P = .009) and less often dyspnoea (P = .046) and pericardial effusion (P = .036). Moreover, they received less often glucocorticoids (P < .001) and depicted less atrial fibrillation (P = .003) and a higher rate of recurrent pericarditis (P = .013). After multivariate adjustment for confounders, age >60 years remained an independent predictor for a lower risk of recurrent pericarditis (hazard ratio 0.60, 95% CI: 0.39-0.96, P = .033). Regarding sex, females were older (P = .007), showed less often ST elevation and PR depression (P < .001 and .002, respectively) and had a higher baseline heart rate (P = .02). Sex was not associated with recurrent pericarditis risk. CONCLUSIONS: Patients with acute pericarditis have distinct presenting clinical, biochemical and prognostic features according to age and sex. Awareness of such differences is important for clinical decision-making.

Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease.

PURPOSE OF REVIEW: Pericarditis is a generally benign disease, although complications and/or recurrences may occur in up to 30% of cases. New evidence on the pathophysiology of the disease has accumulated in recent years. RECENT FINDINGS: Recently, it has been shown that the activation of the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome is central in the pathophysiology of pericarditis. These findings derive from clinical data, an experimental animal model of acute pericarditis supporting a role for the NLRP3 inflammasome in pericarditis, and from indirect evidence of inhibitors of NLRP3 inflammasome in clinical trials. Pericarditis is regarded as a stereotypical response to an acute damage of the mesothelial cells of the pericardial layers. NLRP3 inflammasome, a macromolecular structure sensing damage and releasing pro-inflammatory cytokines, is centrally involved as it releases interleukin (IL)-1ß, whose auto-induction feeds an autoinflammatory disease, mostly responsible for recurrences. Colchicine, an inhibitor of NLRP3 inflammasome formation, and IL-1-targeted therapies, such as anakinra and rilonacept, were found to effectively blunt the acute inflammation and reduce the risk for recurrences.

Established and Emerging Techniques for Pericardial Imaging with Cardiac Magnetic Resonance.

PURPOSE OF REVIEW: Pericardial diseases include a wide range of pathologies and their diagnosis can often be challenging. The goal of this review is to describe the established and emerging CMR imaging techniques used in the assessment of common pericardial diseases and explain the role of pericardial characterization in their diagnosis and management. RECENT FINDINGS: CMR is indicated in cases of diagnostic uncertainty and for a comprehensive evaluation of the pericardium and its impact on the heart. This includes assessment of pericardial anatomy and associated cardiac hemodynamics, quantification and characterization of an effusion, disease staging, tissue characterization, guiding management, and even prognostication in some diseases of the pericardium. An emerging technique, pericardial characterization, utilizes various sequences to diagnose and stage pericardial inflammation, act as a biomarker in recurrent pericarditis, and guide management in inflammatory pericardial conditions. Beyond imaging, it has ushered in an era of tailored therapy for patients with pericardial diseases. Future directions should aim at exploring the role of tissue characterization in various pericardial diseases.

Acute pericarditis: A peculiar manifestation of common variable immune deficiency.

Common variable immune deficiency (CVID) is known as the most prevalent symptomatic inborn error of immunity associated with autoimmune and inflammatory complications in addition to recurrent infections. In this study, we investigated the prevalence of acute pericarditis as a complication in the past medical history of 337 CVID patients. We found five patients (1.5%) that had experienced acute pericarditis, and described the medical history of three patients.

Responses to Treatment According to the Cytokine Profiles of Pericardial Effusion in Two Children with Idiopathic Pericarditis.

Acute pericarditis is inflammation of the pericardium with or without pericardial effusion. In the pediatric population, most patients with acute pericarditis are diagnosed with idiopathic pericarditis. Herein, we present two children with idiopathic pericarditis who underwent immunological assessment of pericardial effusion for the first time. Both patients showed equally high levels of interleukin-6 in the pericardial effusion. However, they had different treatment responses, in accordance with the pericardial effusion and serum interleukin-10 concentrations. Our present cases suggest that interleukin-10 may be associated with the response to anti-inflammatory therapy in idiopathic acute pericarditis.

Idiopathic Pericarditis-an Autoinflammatory Disease?

PURPOSE OF THE REVIEW: Idiopathic acute and recurrent pericarditis are rare diseases of unknown origin. Here, we review trigger factors, pathomechanism, and treatment options for acute and recurrent pericarditis. RECENT FINDINGS: Acute pericarditis can be triggered by viral infections, myocardial ischemia, heart catheter interventions, cardiac surgery or seem to occur without any trigger. Earlier reports about viral nucleic acids in the effusion or myocardial autoantibodies in serum were detected only in a minority of patients. The current pathomechanistic concept focuses on the innate immune system. Clinical trials revealed that colchicine and anti-IL1ß-targeted medication were effective to control acute and recurrent attacks. Activation of the innate immune system in pericarditis suggests that autoinflammation contributes to acute and recurrent pericarditis. The efficacy of colchicine and anti-IL1ß-targeted medication in clinical trials indicates that acute and recurrent pericarditis should be regarded as an autoinflammatory disease. Therefore, idiopathic pericarditis should be considered as an autoinflammatory disease.

Multimodality Imaging for the Assessment of Pericardial Diseases.

PURPOSE OF REVIEW: The diagnosis of pericardial syndromes, while occasionally straightforward, includes a wide range of pathologies and is often a well-recognized clinical challenge. The aim of this review is to highlight the key role of the various imaging modalities for the diagnosis and management of the spectrum of pericardial diseases. RECENT FINDINGS: Cardiac imaging has become an integral part of the diagnostic process often beginning with echocardiography and supported by advanced imaging modalities including computed tomography, magnetic resonance imaging, and positive emission tomography. These modalities go beyond the simple identification of the pericardium, to identifying increased pericardial thickness, active pericardial edema and inflammation, and its effect on cardiac hemodynamics. Multimodality imaging has significantly facilitated the diagnosis and long-term management of patients with pericardial diseases. The role of these imaging modalities in overall prognosis and prevention remains to be investigated.

Acute and recurrent pericarditis.

Pericardial diseases have been until recently relatively neglected entity; however, there has been a markedly increased interest in these disorders in the last decade due to new diagnostic as well as therapeutic options. Various clinical manifestations of pericardial diseases may be generally grouped into pericardial syndromes including pericarditis, pericardial effusion, cardiac tamponade and constrictive pericarditis. In this review, the comprehensive analysis of acute and recurrent pericarditis is presented. Acute and recurrent pericarditis represent the most common pericardial disorders in clinical practice, in which major changes in therapeutic procedures occurred based on recently published trials, particularly the introduction of colchicine therapy.

The Role of Epicardial Fat in Pericardial Diseases.

PURPOSE OF REVIEW: Despite the recent advancements in diagnostic modalities and therapeutic options available, the pathophysiology of pericardial syndromes remains poorly understood. In this review article, we explore the possible links between cardiac adiposity and pericardial syndromes. RECENT FINDINGS: Over the last years, the notion of cardiac adipose tissue has radically changed, and its pivotal role in myocardial diseases has been acknowledged. Recent evidence suggests a cross-talk between epicardial fat and the heart. Imaging of epicardial and pericardial adipose tissue has an independent predictive/prognostic value in cardiovascular disease. Recent data suggests that imaging of epicardial adipose tissue may also provide prognostic information on the clinical course of patients with acute pericarditis. Evidence from clinical and translational studies suggests possible links between epicardial fat and pericardial diseases, which need to be further explored. Epicardial adipose tissue could have a role both as a prognostic biomarker in pericardial syndromes and as potential therapeutic target for pericardial diseases. The findings of future research in the field are eagerly anticipated.

Prognostic implications of epicardial fat volume quantification in acute pericarditis.

BACKGROUND: The pathophysiology of acute pericarditis remains largely unknown, and biomarkers are needed to identify patients susceptible to complications. As adipose tissue has a pivotal role in cardiovascular disease pathogenesis, we hypothesized that quantification of epicardial fat volume (EFV) provides prognostic information in patients with acute pericarditis. MATERIALS AND METHODS: Fifty (n = 50) patients with first diagnosis of acute pericarditis were enrolled in this study. Patients underwent a cardiac computerized tomography (CT) scan to quantify EFV on a dedicated workstation. Patients were followed up in hospital for atrial fibrillation (AF) development and up to 18 months for the composite clinical endpoint of development of constrictive, recurrent or incessant pericarditis or poor response to nonsteroidal anti-inflammatory drugs. RESULTS: Patients presenting with chest pain had lower EFV vs. patients without chest pain (167·2 ± 21·7 vs. 105·1 ± 11·1 cm3 , respectively, P < 0·01); EFV (but not body mass index) was strongly positively correlated with pericardial effusion size (r = 0·395, P = 0·007) and associated with in-hospital AF. At follow-up, patients that reached the composite clinical endpoint had lower EFV (P < 0·05). After adjustment for age, EFV was associated with lower odds ratio for the composite clinical endpoint point of poor response to NSAIDs or the development of constrictive, recurrent or incessant pericarditis during follow-up (per 20 cm3 increase in EFV: OR = 0·802 [0·656-0·981], P < 0·05). CONCLUSIONS: We report for the first time a significant association of EFV with the clinical features and the outcome of patients with acute pericarditis. Measurement of EFV by CT may have important prognostic implications in these patients.

Accuracy of computed tomography findings in acute pericarditis.

BACKGROUND: Acute pericarditis is a close clinical mimic of pulmonary embolism (PE) in the emergency department, and thus many of these patients are evaluated with chest computed tomography (CT). PURPOSE: To study whether CT findings can be diagnostic of acute pericarditis. MATERIAL AND METHODS: Using the electronic medical record, we retrospectively identified 46 cases of acute pericarditis and 46 control patients with pericardial effusions due to volume overload, all of whom underwent CT examination. Cases were reviewed by two blinded academic thoracic radiologists. RESULTS: The majority, 67%, of the pericarditis cases were evaluated with PE-protocol CTs. Pericardial thickening/enhancement was the most accurate single parameter for pericarditis, with sensitivity of 54-59% and specificity of 91-96%. CONCLUSION: CT findings, while not sensitive for pericarditis, are diagnostic, with few false-positives. Radiologists should be attentive to pericardial thickening or enhancement on CT studies done for chest pain, as they may be able to suggest pericarditis as an alternative diagnosis for the chest pain.

Pericarditis recurrence is associated with milder electrocardiographic, echocardiographic, and laboratory findings.

Recurrent pericarditis (RP) complicates approximately 30% of acute pericarditis (AP) cases. We sought to compare the prevalence and severity of objective findings seen in patients with RP. A retrospective single-center study during 2010-2019, including 765 patients diagnosed with AP. Clinical, electrocardiographic, echocardiographic, and laboratory findings were extracted from the local electronic health records. Recurrence during follow-up was documented in 134 patients (17.5%), with a median time to recurrence of 101 (± 59-251) days. The median age was 60 years (IQR 45-72), 68% were male. Most patients were defined as having idiopathic\viral pericarditis (64%). The clinical manifestation during the recurrent event of pericarditis was less prominent or attenuated when compared to the initial event-ECG signs (ST elevation 12% vs. 26%; p = 0.006, Knuckle sign 13% vs. 33%; p < 0.001, ST larger in lead L2 than L3 4% vs. 19%; p < 0.001), pericardial effusion moderate and above (11% vs. 30%; p = 0.02), and inflammatory markers (mean peak CRP levels 66 mg/l vs. 97 mg/l; p < 0.001). Similar results were seen in the subgroup of patients defined as having idiopathic\viral pericarditis. Up to 20% of patients who did not have ECG signs or a significant pericardial effusion in their 1st event demonstrated these findings during the recurrence, though still to a lesser extent compared with those who had these signs in their 1st event. The objective findings of AP are less pronounced during recurrent events. Future studies should focus on the role of advanced biomarkers and imaging in defining true RP events.