Hemodynamics of low-pressure cardiac tamponade: An illustrative case report.

A 55-year-old male with acute pericarditis presented with low-pressure cardiac tamponade (LPCT) unresponsive to volume infusion. Subsequent pericardiocentesis resulted in hemodynamic improvement and unmasking of pericardial constriction. This case provides illustrative hemodynamic tracings of LPCT. Additionally, the presence of concurrent pericardial constriction that may indicate a plausible underlying mechanism for the blunted responsiveness to fluid expansion in LPCT. The underlying physiologic processes and the associated hemodynamic tracings are discussed.

Current treatment of recurrent pericarditis: safety considerations and future directions.

INTRODUCTION: Recurrent pericarditis is one of the most troublesome complications of pericarditis affecting a substantial amount of patients and often severely impairing the quality of life. Current medical treatments range from non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids to biological agents (anti IL-1 agents, especially anakinra and rilonacept), intravenous immunoglobulins and immunosuppressive treatments. Safety is a major issue to deal with since the disease often affects relatively young or middle-aged patients. AREAS COVERED: The review is aimed at providing an update on the efficacy and safety of current medical therapies for recurrent pericarditis including most recent advances represented by anti IL-1 agents. EXPERT OPINION: Therapy of recurrent pericarditis has evolved over years leading to a more evidence-based and personalized treatment based on clinical presentation and pathophysiology. The main distinction is between patients with an inflammatory phenotype (e.g. fever, elevation of markers of inflammation, pericardial, and/or pleural effusion) vs. those without an inflammatory phenotype. Colchicine and anti IL-1 agents are especially efficacious and indicated for those with an inflammatory phenotype, while corticosteroids, azathioprine, and immunoglobulins seem more indicated for those without evidence of systemic inflammation.

Post-cardiac injury syndrome triggered by radiofrequency ablation for AVNRT.

BACKGROUND: Post-cardiac injury syndrome (PCIS) is an inflammatory condition following myocardial or pericardial damage. In response to catheter ablation, PCIS most frequently occurs after extensive radiofrequency (RF) ablation of large areas of atrial myocardium. Minor myocardial injury from right septal slow pathway ablation for atrioventricular nodal reentrant tachycardia (AVNRT) is not an established cause of the syndrome. CASE PRESENTATION: A 62-year-old women with a 6-year history of symptomatic narrow-complex tachycardia was referred to perform an electrophysiological study. During the procedure AVNRT was recorded and a total of two RF burns were applied to the region between the coronary sinus and the tricuspid annulus. Pericardial effusion was routinely ruled out by focused cardiac ultrasound. In the following days, the patient developed fever, elevated inflammatory and cardiac markers, new-onset pericardial effusion, characteristic ECG changes, and complained of pleuritic chest pain. An extensive workup for infectious, metabolic, rheumatologic, neoplastic, and toxic causes of pericarditis and myocarditis was unremarkable. Cardiac magnetic resonance imaging showed no signs of ischemia, infiltrative disease or structural abnormalities. The patient was diagnosed with PCIS and initiated on aspirin and low-dose colchicine. At a 1-month follow-up visit the patient was free of symptoms but still had a small pericardial effusion. After three  months of treatment the pericardial effusion had resolved completely. CONCLUSIONS: Inflammatory pericardial reactions can occur after minor myocardial damage from RF ablation without involvement of structures in close proximity to the pericardium.

Pericarditis Recurrence After Initial Uncomplicated Clinical Course.

Acute pericarditis is an inflammatory disease associated with a non-negligible risk of acute complications and future recurrence. However, the exact incidence of pericarditis recurrence in patients with a first uncomplicated clinical course is unknown. We sought to evaluate the incidence and clinical predictors of recurrence after a first episode of acute uncomplicated pericarditis in a large urban hospital in the United States. We conducted a retrospective review, through electronic health records, to complete a database that includes patients admitted with a first episode of acute pericarditis and selected only those with an uncomplicated course (without in-hospital death, large pericardial effusion [>20 mm] or tamponade, constriction, or incessant pericarditis) at the VCU Medical Center (Richmond, Virginia) from 2009 to 2018. A total of 240 patients met acute pericarditis criteria: of the 240 patients, 164 patients (68%) had an uncomplicated course (median age [interquartile range] in years: 50 [32 to 62], 43% females). The median follow-up time was 186 (19 to 467) days. Pericarditis was idiopathic in 84 patients (51%). Fifteen patients (9%) had at least 1 episode of recurrent pericarditis. Compared with those without recurrence, patients with recurrent pericarditis were younger (37 [25 to 59] vs 51 [34 to 62] years, p = 0.034), had a higher prevalence of subacute/delayed presentation (2 [13%] vs 1 [1%], p = 0.023), and less frequently received colchicine (6 [40%] vs 100 [67%], p = 0.036). At multivariate logistic regression analysis, subacute presentation and younger age remained predictors of recurrence at follow-up. In conclusion, 9% of patients with acute pericarditis experienced a recurrence over a 6-month median follow-up despite an initial uncomplicated course. Younger age and subacute presentation were associated with a significantly increased risk of recurrence.

The Torino Pericarditis Score: a new-risk stratification tool to predict complicated pericarditis.

Current guidelines on the management of pericardial diseases suggest to identify high-risk features associated with an increased risk of non-idiopathic aetiology and complications. The aim of this study is to evaluate a "pericarditis score" to assess potential complicated pericarditis in order to facilitate initial clinical triage. Consecutive patients with pericarditis were included in a prospective cohort study from January 2017 to December 2018. Complicated pericarditis was defined as pericarditis with a non-idiopathic aetiology, and/or complications, and/or requiring hospitalization. A clinical and echocardiographic follow-up were performed at 1, 3, 6 months and then every 6 months. The study population was randomized in derivation and validation cohorts. In the derivation cohort, female gender (HR 2.57, p = 0.016), fever > 38 °C (HR 2.86, p = 0.005), previous lack of colchicine use (HR 3.16, p = 0.006), previous use of corticosteroids (HR 3.01, p = 0.009), and echocardiographic signs of constriction (HR 2.26, p = 0.018) were selected by a stepwise procedure in a Cox regression model and constituted the score showing a C-statistics of 0.81. In the validation group, the score was significantly associated with the risk of complicated pericarditis (HR 1.438 per 10-points increase, 95% CI 1.208-1.711, p < 0.001) and showed an increase in event rate with increasing score (low risk ≤ 20 points: complicated pericarditis in 4/19 patients, incidence 21%, p = 0.003, high risk > 40 points: complicated pericarditis in 18/24 patients, incidence 75%, p = 0.006). In this study, we developed and tested a simple score to efficiently identify at presentation patients at high risk of developing complicated pericarditis.

A 70-Year-Old Man With Conspicuous Thigh Pain and ST-Segment Elevations.

CASE PRESENTATION: A 70-year-old man presented to the ED with sudden onset of left thigh pain followed by transient chest discomfort. His history included cerebrovascular disease, hypertension, and cocaine and methamphetamine use. Physical examination revealed an uncomfortable male subject with a temperature of 37 °C, heart rate of 129 beats/min, BP of 130/65 mm Hg, and 98% oxygen saturation on room air. There was point tenderness in the left lateral thigh without erythema, swelling, or overlying skin changes. His cardiac examination revealed an irregular tachycardia at 129 beats/min and normal first and second heart sounds without murmurs, gallops, or rubs. The remainder of the examination was unremarkable.

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.

Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept.

BACKGROUND: Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1ß cytokine trap) to treat RP. METHODS: Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n = 16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n = 9). All participants received rilonacept weekly during a 6-week base treatment period (TP) plus an optional 18-week extension period (EP). Tapering of concomitant medications, including corticosteroids (CS), was permitted during EP. HRQoL was assessed using the PROMIS GH, and patient-reported pain and blood levels of c-reactive protein (CRP) were collected at Baseline and follow-up periods. A secondary, descriptive analysis of the Phase 2 trial efficacy results was completed using HRQoL measures to characterize both the impact of RP and the treatment effect of rilonacept. RESULTS: Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline (mean PROMIS Global Physical Health [GPH] and Global Mental Health [GMH], were lower than population norm average). In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved during EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP). CONCLUSION: This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to CS. TRIAL REGISTRATION: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522 .

Pericarditis in patients with COVID-19: a systematic review.

AIMS: We performed a systematic review to summarize the clinical features, diagnostic methods, treatment, and outcomes of coronavirus disease 2019 (COVID-19) patients with pericarditis. METHODS: We searched electronic databases from inception to 17 December 2020. Studies that reported clinical data on patients with COVID-19 and pericarditis were included. Descriptive statistics were used for categorical and continuous variables [mean ±â€Šstandard deviation or median (interquartile range)]. As an exploratory analysis, differences between patients with acute pericarditis and myopericarditis were compared. RESULTS: A total of 33 studies (32 case reports and 1 case series) involving 34 patients were included. The mean age was 51.6 ±â€Š19.5 years and 62% of patients were men. Sixty-two percentage of patients were diagnosed with myopericarditis. The most frequent electrocardiographic pattern (56%) was diffuse ST-elevation and PR depression. Pericardial effusion and cardiac tamponade were reported in 76 and 35% of cases, respectively. The median values of C-reactive protein [77 mg/dl (12-177)] and white blood cells [12 335 cells/µl (5625-16 500)] were above the normal range. Thirty-eight percent and 53% of patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine, respectively. These drugs were more frequently used in patients with acute pericarditis compared with myopericarditis. The in-hospital mortality was 6% without a significant difference between both groups. CONCLUSION: Our review shows that COVID-19 patients with pericarditis had similar clinical features to other viral cardiotropic infections. However, NSAIDs and colchicine were used in half or less of the cases. Overall, the short-term prognosis was good across groups.

Hemodialysis Emergencies: Core Curriculum 2021.

Since maintenance hemodialysis (HD) first became available in the United States in 1962, there has been tremendous growth in the population of patients with kidney failure. HD has become a routine treatment carried out in outpatient clinics, hospitals, nursing facilities, and in patients' homes. Although it is a complex procedure, HD is quite safe. Serious complications are uncommon due to the use of modern HD machines and water treatment systems as well as the development of strict protocols to monitor various aspects of the HD treatment. The practicing nephrologist must be knowledgeable about life-threatening complications that can occur during HD and be able to recognize, manage, and prevent them. This installment in the AJKD Core Curriculum in Nephrology reviews the pathogenesis, management, and prevention of 9 HD emergencies. The HD emergencies covered include dialyzer reactions, dialysis disequilibrium syndrome, uremic/dialysis-associated pericarditis, air embolism, venous needle dislodgement, vascular access hemorrhage, hemolysis, dialysis water contamination, and arrhythmia episodes.

Pericardial Involvement in Cancer.

Despite the monumental advances in the diagnoses and therapeutics of malignancy, several cancer patients have presented with pericardial involvement, including acute pericarditis, constrictive pericarditis, and pericardial effusion. Multiple factors can contribute to acute pericarditis, including direct metastasis to the heart, pericardial hemorrhage, infections due to immunosuppression, and cancer therapies that include chemotherapy, immunotherapy, and radiation. Pericardial effusion, either due to cancer invasion or cancer treatment, is one of the most common incidental findings in cancer patients, which significantly worsens morbidity and mortality. If left untreated, pericardial effusion is known to cause complications such as pericardial tamponade. Constrictive pericarditis can be due to radiation exposure, chemotherapy, or is a sequela of a previous episode of acute pericarditis. In conclusion, early detection, prompt treatment, and understanding of pericardial diseases are necessary to help improve the quality of life of cancer patients, and we aim to summarize the knowledge of pericardial involvement in patients with cancer.

Early introduction of anakinra improves acute pericarditis and prevents tamponade in Staphylococcal sepsis.

The clinical response to anakinra observed by this patient concurrently treated with antibiotics indirectly confirms the potentially pathogenic role of IL-1 in maintaining the pericardial disease and shows how IL-1 blockade might allow avoiding the pericardiocentesis procedure. The report supports the hypothesis that anakinra is an effective and safe tool in the early treatment of acute pericarditis of presumed bacterial origin nonresponding to targeted antibiotic therapy.

Update οn the diagnosis and management of systemic lupus erythematosus.

Clinical heterogeneity, unpredictable course and flares are characteristics of systemic lupus erythematosus (SLE). Although SLE is-by and large-a systemic disease, occasionally it can be organ-dominant, posing diagnostic challenges. To date, diagnosis of SLE remains clinical with a few cases being negative for serologic tests. Diagnostic criteria are not available and classification criteria are often used for diagnosis, yet with significant caveats. Newer sets of criteria (European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019) enable earlier and more accurate classification of SLE. Several disease endotypes have been recognised over the years. There is increased recognition of milder cases at presentation, but almost half of them progress overtime to more severe disease. Approximately 70% of patients follow a relapsing-remitting course, the remaining divided equally between a prolonged remission and a persistently active disease. Treatment goals include long-term patient survival, prevention of flares and organ damage, and optimisation of health-related quality of life. For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses. Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance. New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use.

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.

Burden of Recurrent Pericarditis on Health-Related Quality of Life.

The extent to which recurrences of pericarditis episodes impact patients' health-related quality of life (HRQOL) remains poorly understood. This study aimed to evaluate HRQOL and work productivity in patients with recurrent pericarditis (RP). Adult patients from a centralized recruitment database for the rilonacept Phase 2/3 clinical trials were invited to participate in a survey. Inclusion criteria were confirmed RP diagnosis and ≥1 recurrence within the previous 12 months. The 11-Point Pain Numeric Rating Scale, Patient Global Impression of Pericarditis Severity, Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health v1.2, PROMIS Short Form Sleep Disturbance 8b, Work Productivity and Activity Impairment v2.0, and customized questions about fear and economic impact were used. In total, 83 patients (55% female, average age = 49.3 years) completed the survey. The median time since pericarditis diagnosis was 3.0 years at the time of survey completion; 49% experienced ≥3 recurrences in the previous 12 months. Forty percent had an emergency room visit, and 25% were hospitalized for their most recent recurrence. Sixty-six percent of participants rated the symptoms of their last recurrence as severe. The mean value for worst pericarditis pain (0 to 10 scale) during the most recent recurrence was 6.1. The average T-scores for PROMIS physical and mental health were 37.6 and 42.8, respectively, compared with 50 in the general population. Participants reported 50% of overall work impairment and 62% of activity impairment due to RP. In conclusion, patients with RP experienced a high number of recurrences with severe symptoms that substantially reduced their HRQOL and work productivity.

TRPV4 blockade suppresses atrial fibrillation in sterile pericarditis rats.

Atrial fibrillation (AF) commonly occurs after surgery and is associated with atrial remodeling. TRPV4 is functionally expressed in the heart, and its activation affects cardiac structure and functions. We hypothesized that TRPV4 blockade alleviates atrial remodeling and reduces AF induction in sterile pericarditis (SP) rats. TRPV4 antagonist GSK2193874 or vehicle was orally administered 1 day before pericardiotomy. AF susceptibility and atrial function were assessed using in vivo electrophysiology, ex vivo optical mapping, patch clamp, and molecular biology on day 3 after surgery. TRPV4 expression increased in the atria of SP rats and patients with AF. GSK2193874 significantly reduced AF vulnerability in vivo and the frequency of atrial ectopy and AF with a reentrant pattern ex vivo. Mechanistically, GSK2193874 reversed the abnormal action potential duration (APD) prolongation in atrial myocytes through the regulation of voltage-gated K+ currents (IK); reduced the activation of atrial fibroblasts by inhibiting P38, AKT, and STAT3 pathways; and alleviated the infiltration of immune cells. Our results reveal that TRPV4 blockade prevented abnormal changes in atrial myocyte electrophysiology and ameliorated atrial fibrosis and inflammation in SP rats; therefore, it might be a promising strategy to treat AF, particularly postoperative AF.

RHAPSODY: Rationale for and design of a pivotal Phase 3 trial to assess efficacy and safety of rilonacept, an interleukin-1α and interleukin-1ß trap, in patients with recurrent pericarditis.

Recurrent pericarditis (RP) occurs in 15% to 30% of patients following a first episode, despite standard treatment with nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids; many patients become dependent on corticosteroids. Rilonacept (KPL-914), an interleukin-1α and ß inhibitor, is in development for the treatment of RP. RHAPSODY, a double-blind, placebo-controlled, randomized-withdrawal (RW) pivotal Phase 3 trial (NCT03737110), enrolls patients 12 years or older presenting with at least a third pericarditis episode, pericarditis pain score ≥4 (11-point numeric rating scale [NRS]), and C-reactive protein ≥1 mg/dL at screening. After a subcutaneous loading dose (adults, 320 mg; children, 4.4 mg/kg), all patients receive blinded weekly subcutaneous rilonacept (adults, 160 mg; children, 2.2 mg/kg) during the run-in period. Patients must taper and discontinue concomitant pericarditis medications during the blinded run-in period and achieve clinical response (C-reactive protein ≤0.5 mg/dL and weekly average NRS ≤2.0 during the 7 days prior to and including the day of randomization) by end of the run-in (while on rilonacept monotherapy) to be randomized to either continued rilonacept or placebo in the RW period. Primary efficacy end point was time to adjudicated pericarditis recurrence during the RW period; secondary efficacy end points were proportion of patients maintaining clinical response, percentage of days with NRS ≤2, and percentage of patients with no-to-minimal pericarditis symptoms at week 16 of the RW period. Safety evaluations include adverse event monitoring, physical examinations, and laboratory tests. The RHAPSODY trial will evaluate the efficacy and safety of rilonacept in the treatment of RP to improve outcomes and patient health-related quality of life.

Anakinra for constrictive pericarditis associated with incessant or recurrent pericarditis.

OBJECTIVE: Frequent flares of pericardial inflammation in recurrent or incessant pericarditis with corticosteroid dependence and colchicine resistance may represent a risk factor for constrictive pericarditis (CP). This study was aimed at the identification of CP in these patients, evaluating the efficacy and safety of anakinra, a third-line treatment based on interleukin-1 inhibition, to treat CP and prevent the need for pericardiectomy. METHODS: Consecutive patients with recurrent or incessant pericarditis with corticosteroid dependence and colchicine resistance were included in a prospective cohort study from 2015 to 2018. Enrolled patients received anakinra 100 mg once daily subcutaneously. The primary end point was the occurrence of CP. A clinical and echocardiographic follow-up was performed at 1, 3, 6 months and then every 6 months. RESULTS: Thirty-nine patients (mean age 42 years, 67% females) were assessed, with a baseline recurrence rate of 2.76 flares/patient-year and a median disease duration of 12 months (IQR 9-20). During follow-up, CP was diagnosed in 8/39 (20%) patients. After anakinra dose of 100 mg/day, 5 patients (63%) had a complete resolution of pericardial constriction within a median of 1.2 months (IQR 1-4). In other three patients (37%), CP became chronic, requiring pericardiectomy within a median of 2.8 months (IQR 2-5). CP occurred in 11 patients (28%) with incessant course, which was associated with an increased risk of CP over time (HR for CP 30.6, 95% CI 3.69 to 253.09). CONCLUSIONS: In patients with recurrent or incessant pericarditis, anakinra may have a role in CP reversal. The risk of CP is associated with incessant rather than recurrent course.

Clinical Presentation and Outcomes of Acute Pericarditis in a Large Urban Hospital in the United States of America.

BACKGROUND: Acute pericarditis is the most common presentation of pericardial diseases. Although generally benign, complications such as constrictive pericarditis, cardiac tamponade, and recurrence can occur. RESEARCH QUESTION: What are the clinical factors associated with adverse outcomes in acute pericarditis? STUDY DESIGN AND METHODS: We used an informatics-based search engine to search for International Classification of Diseases codes related to pericardial disease between January 1, 2009 and November 14, 2018 and then extracted clinical information, including only patients meeting the European Society of Cardiology criteria for acute pericarditis. We then evaluated the predictive value of clinical characteristics for adverse outcomes (cardiac tamponade, constrictive pericarditis, failure of therapy, recurrences, or death). RESULTS: We identified 240 patients with a first episode of pericarditis (51 [34-62] years, 56% males and 50% white). Pericarditis was determined to be idiopathic in 126 (53%) cases and related to cardiac injury in 79 (33%). During a median follow-up time of 179 (20-450) days, 82 (34%) patients experienced at least one adverse outcome. Subacute presentation was an independent predictor of adverse outcomes. Patients with postcardiac injury pericarditis had a lower incidence in the composite of failure of treatment and recurrence (13% vs 26%; P = .022) compared with patients with idiopathic pericarditis. Troponin I measurements were obtained in 167 patients (70%). Elevated troponin I levels were associated with lower incidence of recurrences (4% vs 17%; P = .024) and of the composite outcome (13% vs 36%; P = .004). INTERPRETATION: Acute pericarditis is associated with at least one adverse outcome in 34% of patients. Subacute presentation and idiopathic etiology are associated with higher incidence of adverse outcomes, whereas elevated troponin I levels identify a group with reduced risk of recurrences.

Failure of anti Interleukin-1 ß monoclonal antibody in the treatment of recurrent pericarditis in two children.

BACKGROUND: Recurrent pericarditis (RP) is a complication (15-30%) of acute pericarditis with an unknown etiology. Treatment regimen consists of a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, with the addition of corticosteroids in resistant or intolerant cases. In the last decade anakinra was shown as an effective treatment in patients with colchicine resistant and steroid-dependent RP, initially in anecdotal reports in children and more recently in a randomized trial. Canakinumab is a monoclonal antibody selectively blocking IL-1ß and its use is only anecdotally reported to treat pericarditis. We report two pediatric patients with refractory recurrent pericarditis, who presented an optimal response to anakinra treatment but prompt relapse after switch to canakinumab. CASE PRESENTATION: The first patient is a girl with Recurrent Pericarditis started in April 2015, after heart surgery. NSAIDs and oral steroids were started, with prompt relapse after steroid suspension. The child showed a steroid-dependent RP; anakinra was therefore started with excellent response, but discontinued after 2 weeks for local reactions. In July 2016 therapy with canakinumab was started. She experienced four relapses during canakinumab therapy despite dosage increase and steroid treatment. In January 2018 a procedure of desensitization from anakinra was performed, successfully. Anakinra as monotherapy is currently ongoing, without any sign of flare. The second patient is a girl with an idiopathic RP, who showed an initial benefit from NSAIDs and colchicine. However, 10 days after the first episode a relapse occurred and therapy with anakinra was established. Two months later, while being in complete remission, anakinra was replaced with canakinumab due to patient's poor compliance to daily injections. She experienced a relapse requiring steroids 10 days after the first canakinumab injection. Anakinra was subsequently re-started with complete remission, persisting after 24 months follow-up. CONCLUSIONS: We describe two cases of failure of the treatment with anti-IL-1ß monoclonal antibodies in steroid- dependent idiopathic RP. This anecdotal and preliminary observation suggests a different efficacy of the two IL-1 blockers in the management of RP and support a possible pivotal role of IL-1α in the pathogenesis of this condition.