Efficacy of colchicine in addition to anakinra in patients with recurrent pericarditis.

AIM: Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non-specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL-1, could provide additional benefit to prevent further recurrences. The aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone. METHODS: International, all-comers, multicentre, retrospective observational cohort study analysing all consecutive patients treated with anakinra for corticosteroid-dependent and colchicine-resistant recurrent pericarditis. The efficacy endpoint was recurrence rate and the time to the first recurrence. RESULTS: A total of 256 patients (mean age 45.0±15.4 years, 65.6% females, 80.9% with idiopathic/viral aetiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow-up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively, 18.8% vs 31.3%; p=0.036) and a longer event-free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021). CONCLUSIONS: The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence-free survival.

Purulent pericarditis caused by methicillin-sensitive Staphylococcus aureus bacteriuria.

BACKGROUND: Purulent pericarditis (PP)- a purulent infection involving the pericardial space-requires a high index of suspicion for diagnosis as it often lacks characteristic signs of pericarditis and carries a mortality rate as high as 40% even with treatment. Common risk factors include immunosuppression, diabetes mellitus, thoracic surgery, malignancy, and uremia. Most reported cases of PP occur in individuals with predisposing risk factors, such as immunosuppression, and result from more commonly observed preceding infections, such as pneumonia, osteomyelitis, and meningitis. We report a case of PP due to asymptomatic bacteriuria in a previously immunocompetent individual on a short course of high-dose steroids. CASE PRESENTATION: An 81-year-old male presented for severe epigastric pain that worsened with inspiration. He had been on high-dose prednisone for presumed inflammatory hip pain. History was notable for urinary retention requiring intermittent self-catheterization and asymptomatic bacteriuria and urinary tract infections due to methicillin-sensitive Staphylococcus aureus (MSSA). During the index admission he was found to have a moderate pericardial effusion. Pericardial fluid cultures grew MSSA that had an identical antibiogram to that of the urine cultures. A diagnosis of purulent pericarditis was made. CONCLUSION: PP requires a high index of suspicion, especially in hosts with atypical risk factors. This is the second case of PP occurring as a result of asymptomatic MSSA bacteriuria. Through reporting this case we hope to highlight the importance of early recognition of PP and the clinical implications of asymptomatic MSSA bacteriuria in the setting of urinary instrumentation and steroid use.

Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept.

BACKGROUND: Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment. METHODS AND RESULTS: Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off-treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18-month decision milestone was 0.04 events/patient-year versus 4.4 events/patient-year prestudy while on oral therapies. At the 18-month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18-month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P<0.0001). CONCLUSIONS: In the RHAPSODY long-term extension, continued rilonacept treatment resulted in continued response; treatment suspension at the 18-month decision milestone was associated with pericarditis recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03737110.

Interleukin-1 Blockers in Recurrent and Acute Pericarditis: State of the Art and Future Directions.

Diseases of the pericardium encompass a spectrum of conditions, including acute and recurrent pericarditis, where inflammation plays a pivotal role in the pathogenesis and clinical manifestations. Anti-inflammatory therapy indeed forms the cornerstone of treating these conditions: NSAIDs, colchicine, and corticosteroids (as a second-line treatment) are recommended by current guidelines. However, these medications come with several contraindications and are not devoid of adverse effects. In recent years, there has been an increased focus on the role of the inflammasome and potential therapeutic targets. Recurrent pericarditis also shares numerous characteristics with other autoinflammatory diseases, in which interleukin-1 antagonists have already been employed with good efficacy and safety. The objective of this review is to summarize the available studies on the use of anti-IL-1 drugs both in acute and recurrent pericarditis.

Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin-1.

BACKGROUND: An exuberant and dysregulated inflammatory response contributes to the development and progression of cardiovascular diseases (CVDs). METHODS: This narrative review includes original articles and reviews published over the past 20 years and found through PubMed. The following search terms (or combination of terms) were considered: "acute pericarditis," "recurrent pericarditis," "myocarditis," "cardiac sarcoidosis," "atherosclerosis," "acute myocardial infarction," "inflammation," "NLRP3 inflammasome," "Interleukin-1" and "treatment." RESULTS: Recent evidence supports the role of inflammation across a wide spectrum of CVDs including myocarditis, pericarditis, inflammatory cardiomyopathies (i.e. cardiac sarcoidosis) as well as atherosclerotic CVD and heart failure. Interleukins (ILs) are the signalling mediators of the inflammatory response. The NACHT, leucine-rich repeat and pyrin-domain containing protein 3 (NLRP3) inflammasome play a key role in producing IL-1ß, the prototypical pro-inflammatory cytokine involved in CVDs. Other pro-inflammatory cytokines (e.g. tumour necrosis factor) have been implicated in cardiac sarcoidosis. As a proof of this, IL-1 blockade has been proven efficacious in pericarditis and chronic coronary syndrome. CONCLUSION: Tailored strategies aiming at quenching the inflammatory response have emerged as promising to treat CVDs. In this review article, we summarize recent evidence regarding the role of inflammation across a broad spectrum of CVDs. We also review novel evidence regarding targeted therapeutic strategies.

Successful Management of Malignant Pericarditis Using Nivolumab for Metastatic Esophageal Squamous Cell Carcinoma.

Esophageal cancer is a malignant disease with a poor prognosis and is one of the most common causes of cardiac metastasis. Malignant pericarditis may cause the repetitive accumulation of pericardial effusion, which can occasionally pose a clinical challenge. We herein report a case of malignant pericarditis in a patient with metastatic esophageal squamous cell carcinoma with cardiac tamponade, which was successfully managed with single pericardial drainage and systemic nivolumab monotherapy. This is the first case report to suggest that systemic therapy with nivolumab is a promising option for the management of malignant pericarditis.

Relapse of colchicine-intolerant, corticosteroid-dependent recurrent idiopathic pericarditis after perigestational discontinuation of anakinra: uncertain safety of anakinra in pregnancy and the need for shared decision-making.

A nulligravid woman in her mid-20s with colchicine-intolerant, steroid-dependent recurrent idiopathic pericarditis was in remission for 2 years on anakinra monotherapy when she had an unplanned pregnancy. Due to very limited and conflicting data, European Alliance of Associations for Rheumatology and American College of Rheumatology guidelines are equivocal on the use of anakinra in pregnancy, emphasising an individualised approach. Anakinra was discontinued but a month later, in the second month of gestation, the patient had an acute pericarditis flare. A multidisciplinary, patient-centred discussion about the competing risks of infection, obstetric complications and fetal malformations with anakinra versus suboptimally managed recurrent acute pericarditis guided the patient to choosing improved symptom control. Chest pain resolved and CRP normalised after daily anakinra injections were resumed. In the second trimester, the patient had mild COVID-19 infection and streptococcal pharyngitis on anakinra. At 34 weeks gestation, the patient went into preterm labour and had a spontaneous vaginal delivery of a healthy neonate.

Pericarditis Management in Individuals Contemplating Pregnancy, Currently Pregnant, or Breastfeeding.

PURPOSE OF REVIEW: Pericarditis complicates pregnancy planning, pregnancy, or the postpartum period, and the management approach requires special considerations. Here, we aim to summarize the latest research, diagnostic, and treatment strategies. RECENT FINDINGS: Physiologic cardiovascular (CV) adaptations occurring during pregnancy complicate diagnosis, but for most patients, an electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are sufficient to diagnosis pericarditis in the appropriate clinical context. Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) can be used until 20 weeks gestation as needed. The use of colchicine is encouraged at any time point to reduce the risk of recurrence. Glucocorticoids may be used at the lowest possible dose for the least amount of time throughout pregnancy and breastfeeding. For incessant, recurrent, or refractory pericarditis, or when the above therapies are contraindicated, there may be a consideration of the use of IL-1 inhibition during pregnancy, recognizing the limited data in pregnant patients. Finally, we encourage the use of a multidisciplinary team approach including OB-GYN, cardiology, and rheumatology when available. The diagnosis and treatment of pericarditis in female patients of reproductive age require special considerations. Although highly effective treatment options are available, there is a need for greater data and larger international registries to improve treatment recommendations.

Paradigm Shift in Diagnosis and Targeted Therapy in Recurrent Pericarditis.

PURPOSE OF THE REVIEW: We review the pathophysiology, diagnosis, and contemporary treatment for recurrent pericarditis, with focus on interleukin-1 (IL-1) inhibitors. RECENT FINDINGS: Recurrent pericarditis occurs in about 15-30% of patients who have acute pericarditis. With increased understanding of the autoinflammatory pathophysiology of recurrent pericarditis, IL-1 inhibitors including anakinra, canakinumab, and rilonacept have been applied to this condition with great promise. In particular, the RHAPSODY trial found rilonacept significantly improves pain and inflammation, while also reducing recurrence with few adverse events. The next IL-1 inhibitor on the block for pericarditis, goflikicept, is also discussed. Understanding the role of the inflammasome via the autoinflammatory pathway in pericarditis has led to incorporation of IL-1 inhibitors in the treatment of recurrent pericarditis, with proven efficacy and safety and randomized trials. This will lead to increase uptake of this agent which demonstrated lower rates of recurrence and faster time to resolution.

Cardiovascular toxicity profiles of immune checkpoint inhibitors with or without angiogenesis inhibitors: a real-world pharmacovigilance analysis based on the FAERS database from 2014 to 2022.

Background: Immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) have become increasingly available for multiple types of cancers, although the cardiovascular safety profiles of this combination therapy in real-world settings have not been elucidated to date. Therefore, we aimed to comprehensively investigate the cardiovascular toxicity profiles of ICIs combined with AGIs in comparison with ICIs alone. Methods: The Food and Drug Administration Adverse Event Reporting System (FAERS) database from the 1st quarter of 2014 to the 1st quarter of 2022 was retrospectively queried to extract reports of cardiovascular adverse events (AEs) associated with ICIs alone, AGIs alone and combination therapy. To perform disproportionality analysis, the reporting odds ratios (RORs) and information components (ICs) were calculated with statistical shrinkage transformation formulas and a lower limit of the 95% confidence interval (CI) for ROR (ROR025) > 1 or IC (IC025) > 0 with at least 3 reports was considered statistically significant. Results: A total of 18 854 cardiovascular AE cases/26 059 reports for ICIs alone, 47 168 cases/67 595 reports for AGIs alone, and 3 978 cases/5 263 reports for combination therapy were extracted. Compared to the entire database of patients without AGIs or ICIs, cardiovascular AEs were overreported in patients with combination therapy (IC025/ROR025 = 0.559/1.478), showing stronger signal strength than those taking ICIs alone (IC025/ROR025 = 0.118/1.086) or AGIs alone (IC025/ROR025 = 0.323/1.252). Importantly, compared with ICIs alone, combination therapy showed a decrease in signal strength for noninfectious myocarditis/pericarditis (IC025/ROR025 = 1.142/2.216 vs. IC025/ROR025 = 0.673/1.614), while an increase in signal value for embolic and thrombotic events (IC025/ROR025 = 0.147/1.111 vs. IC025/ROR025 = 0.591/1.519). For outcomes of cardiovascular AEs, the frequency of death and life-threatening AEs was lower for combination therapy than ICIs alone in noninfectious myocarditis/pericarditis (37.7% vs. 49.2%) as well as in embolic and thrombotic events (29.9% vs. 39.6%). Analysis among indications of cancer showed similar findings. Conclusion: Overall, ICIs combined with AGIs showed a greater risk of cardiovascular AEs than ICIs alone, mainly due to an increase in embolic and thrombotic events while a decrease in noninfectious myocarditis/pericarditis. In addition, compared with ICIs alone, combination therapy presented a lower frequency of death and life-threatening in noninfectious myocarditis/pericarditis and embolic and thrombotic events.

Pericarditis related to post-acute COVID infection: A case report and review of the literature.

Cardiovascular involvement has been described in acute and recovered COVID-19 patients. Here, we present a case of symptomatic pericarditis with persistent symptoms for at least six months after the acute infection and report 66 published cases of pericarditis in discharged COVID patients. Patient mean age ± SD was 49.7 ± 13.3 years, ranging from 15 to 75 years and 57.6% were female. A proportion of 89.4% patients reported at least one comorbidity, with autoimmune and allergic disorders, hypertension and dyslipidaemia, as the most frequent. Only 8.3% of patients experienced severe symptoms of acute COVID-19. The time between acute COVID and pericarditis symptoms varied from 14 to 255 days. Chest pain (90.9%), tachycardia (60.0%) and dyspnoea (38.2%) were the most frequent symptoms in post-acute pericarditis. A proportion of 45.5% and 87% of patients had an abnormal electrocardiogram and abnormal transthoracic ultrasound, respectively. Colchicine combined with non-steroidal anti-inflammatory drug (NSAID) or acetylsalicylic acid (aspirin) were prescribed to 39/54 (72%) patients. Of them, 12 were switched to corticosteroid therapy due to non-response to the first-line treatment. Only 6 patients had persisting symptoms and were considered as non-respondent to therapy.Our report highlights that pericarditis should be suspected in COVID-19 patients with persistent chest pain and dyspnoea when pulmonary function is normal. Treatment with non-steroidal anti-inflammatory and colchicine is usually effective but corticosteroids are sometimes required.

Treatment of Idiopathic Recurrent Pericarditis With Goflikicept: Phase II/III Study Results.

BACKGROUND: Idiopathic recurrent pericarditis (IRP) is a rare autoinflammatory disease. Interleukin (IL)-1α and IL-1ß are the pivotal cytokines in the pathophysiology of acute pericarditis and its recurrence. We created a phase II/III study with a new IL-1 inhibitor-goflikicept in IRP. OBJECTIVES: This study sought to evaluate the efficacy and safety of goflikicept treatment in patients with IRP. METHODS: We conducted a 2-center open-label study of goflikicept in patients with IRP with and without recurrence at time of enrollment. The study consisted of 4 periods: screening, run-in (open-label treatment period), randomized withdrawal, and follow-up. Patients with clinical response to goflikicept in the run-in period were randomized (1:1) to a placebo-controlled withdrawal period, where the time to first pericarditis recurrence (primary endpoint) was evaluated. RESULTS: We enrolled 22 patients, and 20 of these patients were randomized. Reduction of C-reactive protein level accompanied by reduction of chest pain and pericardial effusion compared to baseline was demonstrated during the run-in period. Recurrence of pericarditis occurred in 9 of 10 patients in the placebo group, and there were no recurrence events in goflikicept group within 24 weeks after randomization (P < 0.001). A total of 122 adverse events were reported in 21 patients (95.5%), with no deaths and no new safety signals identified for goflikicept. CONCLUSIONS: Treatment with goflikicept prevented recurrences and maintained IRP remission with a favorable risk-benefit ratio. Goflikicept reduced the risk of recurrence compared with placebo. (Study to Evaluate the Efficacy and Safety of RPH-104 Treatment in Patients With Idiopathic Recurrent Pericarditis; NCT04692766).

Can the current monkeypox affect the heart? A systematic review of case series and case report.

BACKGROUND: Monkeypox is a zoonotic viral infection first reported in May 2022. Monkeypox cases present with prodromal symptoms, rash, and/or systemic complications. This study systematically reviews the monkeypox cases presented with any cardiac complications. METHODS: A systematic literature search was done to locate papers that discuss any cardiac complications associated with monkeypox; then, data were analyzed qualitatively. RESULTS: Nine articles, including the 13 cases that reported cardiac complications of the disease, were included in the review. Five cases previously had sex with men, and two cases had unprotected intercourse, which reveals the importance of the sexual route in disease transmission. All cases have a wide spectrum of cardiac complications, such as acute myocarditis, pericarditis, pericardial effusion, and myopericarditis. CONCLUSION: This study clarifies the potential for cardiac complications in monkeypox cases and provides avenues for future research to determine the underlying mechanism. Also, we found that the cases with pericarditis were treated with colchicine, and those with myocarditis were treated with supportive care or cardioprotective treatment (Bisoprolol and Ramipril). Furthermore, Tecovirimat is used as an antiviral drug for 14 days.

Gonococcal pericarditis with tamponade - use of molecular technology to improve diagnosis and management.

We report a case of gonococcal pericarditis, which was unexpected due to its extremely unusual occurrence. A 42-year-old man presented with fever, chest pain, dyspnea, and tachycardia. He was initially stable but rapidly deteriorated, developing pericardial effusion with tamponade requiring a pericardial window. Incompletely decolorized gram stain of the pericardial fluid initially suggested the presence of gram-positive diplococci, which wrongly directed treatment toward possible pneumococcal infection. Because cultures were negative, identification of the causative organism was attempted by molecular and genotyping analysis. These techniques identified Neisseria gonorrhoeae-multi-antigen sequence type 14994 (por 5136/tbpB 33) as the etiology, which has been associated with disseminated gonococcal disease. Real-time polymerase chain reaction showed no evidence of mutations within the N. gonorrhoeae penA gene responsible for causing ceftriaxone resistance. This was crucial in guiding antibiotic treatment, in light of the high prevalence of multi-drug-resistant N. gonorrhoeae. This case highlights the utility of diagnostic molecular techniques in identifying N. gonorrhoeae as the etiology of an exceedingly rare case of pericarditis.

From the Gut to the Heart: A Rare Case of Salmonella dublin Pericarditis.

BACKGROUND Salmonella infections manifest typically as self-limiting gastroenteritis after the consumption of contaminated food. Extra-intestinal manifestations of Salmonella infections such as pericarditis are rare and are usually seen in severely immunocompromised individuals. Prior case reports suggest high rates of morbidity and mortality associated with Salmonella pericarditis. Here, we present a rare case of Salmonella dublin pericarditis. CASE REPORT A 45-year-old man presented to the Emergency Department reporting chest pressure and shortness of breath. An echocardiogram showed a large pericardial effusion without tamponade physiology. Pericardial window was performed, with removal of 700 cubic centimeters of bloody fluid, with presence of fibrinous debris in the pericardial cavity. A pericardial biopsy showed chronic pericarditis, and a lymph node biopsy was negative for malignancy. Antinuclear antibody (ANA), Lyme antibodies, and human immunodeficiency virus (HIV) testing were negative. Tissue culture revealed Salmonella species. Subsequent blood cultures grew Salmonella spp. Further history-taking revealed frequent travel and recent treatment with steroids for suspected Bell's palsy. Initially, the patient was treated with ceftriaxone, which was switched to ciprofloxacin after susceptibility testing revealed ceftriaxone resistance. Final identification of the organism revealed Salmonella dublin. The patient was discharged on colchicine, ibuprofen, and a 4-week course of ciprofloxacin. Outpatient follow-up showed improvement in inflammatory markers and symptoms. CONCLUSIONS This case illustrates the rarity of Salmonella-associated pericarditis, the importance of assessing a patient's risk factors, and obtaining an extensive history when searching for an etiology of pericarditis. Investigation into why a patient was susceptible to an infection with this organism should include medication assessment and age-appropriate cancer screening. Prompt identification and treatment of the offending organism can help prevent mortality.

Recurrent pericarditis. / Residiverende perikarditt.

Pericarditis is an important differential diagnosis in patients with chest pain. The two most common causes in the developed world are idiopathic pericarditis and inflammation following cardiac surgery or myocardial infarction. Recurrence of pericarditis affects up to 30 % of patients, half of whom experience multiple episodes, and approximately 10 % develop steroid-dependent and colchicine-refractory pericarditis. Recurrence is due to autoinflammatory processes in the pericardium. Advanced diagnostic imaging and treatment with colchicine and interleukin-1 inhibitors has helped reduce morbidity considerably in recent years. In this clinical review, we summarise up-to-date knowledge about the diagnostic evaluation and treatment of patients with recurrent primary pericarditis.

Cardiovascular Toxicities Associated with Anaplastic Lymphoma Kinase Inhibitors: A Disproportionality Analysis of the WHO Pharmacovigilance Database (VigiBase).

INTRODUCTION: Recently, cases of cardiovascular toxicities, such as pericarditis, caused by anaplastic lymphoma kinase (ALK) inhibitors have been reported; however, whether these adverse events are common among all ALK inhibitors remains unclear. AIMS: This study aimed to clarify the cardiovascular toxicity profile of ALK inhibitors using an adverse event spontaneous report database. METHODS: We analyzed data from VigiBase, the WHO global database of individual safety reports, from its inception in 1968 to December 2021. We calculated the reporting odds ratio to evaluate the association between ALK inhibitors (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib) and 21 cardiovascular adverse events. Time to onset of pericarditis from ALK inhibitor administration was analyzed. RESULTS: Of the 27,994,584 reports, 19,911 involved treatment with ALK inhibitors. Among the 21 cardiovascular toxicities, only pericarditis signals were detected with all five ALK inhibitors (crizotinib [reporting odds ratios (ROR), 4.7; 95% CI 3.63-6.15], ceritinib [ROR, 12.9; 95% CI 9.37-17.79], alectinib [ROR, 4.8; 95% CI 3.15-7.42], brigatinib [ROR, 3.5; 95% CI 1.33-9.46], and lorlatinib [ROR, 6.4; 95% CI 3.60-11.22]). For torsade de pointes/QT prolongation, signals were detected with crizotinib (ROR, 5.0; 95% CI 3.72-6.77) and ceritinib (ROR, 4.2; 95% CI 2.17-8.05), whereas for hypertension, they were identified only with brigatinib (ROR, 3.9; 95% CI 2.88-5.20), and for heart failure, they were detected with alectinib (ROR, 2.2; 95% CI 1.60-2.90), crizotinib (ROR, 2.1; 95% CI 1.72-2.48), and lorlatinib (ROR, 2.0; 95% CI 1.27-3.23). Regarding time-to-onset analysis from drug administration to adverse event reporting, for pericarditis, it ranged from 52.5 days for alectinib to 166.5 days for crizotinib. CONCLUSIONS: Systematic evaluation of ALK inhibitor-associated adverse events revealed differences in the cardiotoxicity profiles among ALK inhibitors. Understanding the differences in the cardiovascular toxicity profile of each ALK inhibitor will contribute to safe drug therapy when switching between ALK inhibitors.