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BACKGROUND: Interleukin-1 has been implicated as a mediator of recurrent pericarditis. The efficacy and safety of rilonacept, an interleukin-1α and interleukin-1ß cytokine trap, were studied previously in a phase 2 trial involving patients with recurrent pericarditis. METHODS: We conducted a phase 3 multicenter, double-blind, event-driven, randomized-withdrawal trial of rilonacept in patients with acute symptoms of recurrent pericarditis (as assessed on a patient-reported scale) and systemic inflammation (as shown by an elevated C-reactive protein [CRP] level). Patients presenting with pericarditis recurrence while receiving standard therapy were enrolled in a 12-week run-in period, during which rilonacept was initiated and background medications were discontinued. Patients who had a clinical response (i.e., met prespecified response criteria) were randomly assigned in a 1:1 ratio to receive continued rilonacept monotherapy or placebo, administered subcutaneously once weekly. The primary efficacy end point, assessed with a Cox proportional-hazards model, was the time to the first pericarditis recurrence. Safety was also assessed. RESULTS: A total of 86 patients with pericarditis pain and an elevated CRP level were enrolled in the run-in period. During the run-in period, the median time to resolution or near-resolution of pain was 5 days, and the median time to normalization of the CRP level was 7 days. A total of 61 patients underwent randomization. During the randomized-withdrawal period, there were too few recurrence events in the rilonacept group to allow for the median time to the first adjudicated recurrence to be calculated; the median time to the first adjudicated recurrence in the placebo group was 8.6 weeks (95% confidence interval [CI], 4.0 to 11.7; hazard ratio in a Cox proportional-hazards model, 0.04; 95% CI, 0.01 to 0.18; P<0.001 by the log-rank test). During this period, 2 of 30 patients (7%) in the rilonacept group had a pericarditis recurrence, as compared with 23 of 31 patients (74%) in the placebo group. In the run-in period, 4 patients had adverse events leading to the discontinuation of rilonacept therapy. The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections. CONCLUSIONS: Among patients with recurrent pericarditis, rilonacept led to rapid resolution of recurrent pericarditis episodes and to a significantly lower risk of pericarditis recurrence than placebo. (Funded by Kiniksa Pharmaceuticals; RHAPSODY ClinicalTrials.gov number, NCT03737110.).
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Pericardite/tratamento farmacológico , Receptores Tipo I de Interleucina-1/antagonistas & inibidores , Proteínas Recombinantes de Fusão/uso terapêutico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Interleucina-1alfa , Interleucina-1beta , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteínas Recombinantes de Fusão/efeitos adversos , Recidiva , Infecções Respiratórias/etiologia , Adulto JovemRESUMO
BACKGROUND: Numerous studies have reported myocarditis resulting from messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination. However, to date, there have been no reports highlighting the safety of mRNA COVID-19 vaccines in children and adults with a prior history of myocarditis, which was the intent of this study. METHODS AND RESULTS: Children and adults cared for at the Cleveland Clinic were identified through the electronic health records, who had a history of myocarditis before the COVID-19 pandemic and had subsequently received at least 2 doses of the mRNA COVID-19 vaccines (nâ¯=â¯34). Only 1 patient in this series had recurrence of myocarditis confirmed by cardiac magnetic resonance imaging after receiving the second dose. He was a White man who had his first episode of myocarditis at age 20 and was 27 years of age at the time of recurrence. He was hospitalized for 2 days with no need for cardiac support or reported arrhythmias and was stable at outpatient follow-up. CONCLUSIONS: In patients with an old history of non-COVID-19 myocarditis, the risk of recurrent myocarditis after receipt of mRNA COVID-19 vaccination is low, and when it occurs it seems to be self-limiting. Our study will be valuable to clinicians while discussing the risk-benefit ratio of vaccinations in patients with a prior history of myocarditis.
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Vacinas contra COVID-19 , COVID-19 , Miocardite , Adulto , Criança , Humanos , Masculino , Adulto Jovem , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Insuficiência Cardíaca , Miocardite/complicações , Pandemias , RNA MensageiroRESUMO
PURPOSE OF THE REVIEW: Hypertension accounts for the largest proportion of cardiovascular (CV) mortality worldwide and its prevalence continues to rise. While prominent CV societies have offered strong recommendations on the management of hypertension in adults, the role of noninvasive CV imaging in the evaluation of hypertensive patients remains incompletely defined. RECENT FINDINGS: Noninvasive imaging is a rapidly expanding field with a growing number of sophisticated and readily applicable modalities to assess how cardiac structure and function changes after periods of sustained, elevated blood pressure. Echocardiography remains the initial modality to screen these patients while developments in nuclear, computed tomography and cardiac magnetic resonance complement and expand investigations for alternative diagnoses that may complement or conflict with the diagnosis of left ventricular hypertrophy. SUMMARY: In this review article, we summarize the application of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging in the evaluation and management of hypertensive heart disease.
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Cardiopatias , Hipertensão , Humanos , Coração , Ecocardiografia , Hipertensão/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Imageamento por Ressonância MagnéticaRESUMO
ABSTRACT: Recurrent pericarditis (RP) is the most troublesome complication of acute pericarditis reflecting an unresolving inflammation of the pericardial sac around the heart and associated with significant morbidity. Recent studies have shown interleukin-1 (IL-1) signaling to be central to the pathophysiology of cases of RP with evidence of activation of systemic inflammation. We herein review the literature and clinical trials discussing the utility of IL-1 blockade for RP. The early experience of IL-1 blockade with anakinra (Kineret) and its favorable safety profile paved the way for the clinical development of rilonacept (Arcalyst) and subsequent approval by the US FDA for RP. In patients with RP who have become colchicine-resistant and glucocorticoid-dependent, IL-1 blockade with rilonacept or anakinra effectively treats recurrences and prevents future flares, and significantly improves quality of life.
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A 16-year-old male with past medical history of congenital atrial septal defect surgical repair, presented with recurrent pericarditis secondary to post-cardiotomy injury syndrome (PCIS), After failing medical therapy, he ultimately underwent pericardiectomy for symptom resolution, PCIS is underdiagnosed in children and should be considered in patients with recurrent chest, pain.
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Traumatismos Cardíacos , Comunicação Interatrial , Pericardite Constritiva , Pericardite , Masculino , Criança , Humanos , Adolescente , Pericardite Constritiva/diagnóstico , Pericardite/complicações , Pericardiectomia , Síndrome , Comunicação Interatrial/complicações , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/cirurgia , Traumatismos Cardíacos/diagnóstico por imagem , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/cirurgiaRESUMO
A 46-year-old woman underwent pericardiocentesis and pericardial window for recurrent pericardial effusion. She presented 17 months later with signs and symptoms consistent with constrictive pericarditis. Cardiac magnetic resonance imaging revealed an infiltrative mass surrounding the pericardium. A transcutaneous core needle biopsy of the pericardium confirmed the diagnosis of pericardial mesothelioma.
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PURPOSE OF REVIEW: The purpose of this review is to highlight the echo Doppler parameters that form the cornerstone for the evaluation of diastolic function as per the guideline documents of the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI). In addition, the individual Doppler-based parameters will be explored, with commentary on the rationale behind their use and the multi-parametric approach to the assessment of diastolic dysfunction (DD) using echocardiography. RECENT FINDINGS: Previous guidelines for assessment of diastolic function are complex with modest diagnostic performance and significant inter-observer variability. The most recent guidelines have made the evaluation of DD more streamlined with excellent correlation with invasive measures of LV filling pressures. This is a review of the echo-derived Doppler parameters that are integral in the diagnosis and gradation of DD. A brief description of the physiological principles that govern changes in echocardiographic parameters during normal and abnormal diastolic function is also discussed for the appropriate diagnosis of DD using non-invasive Doppler echocardiography techniques.
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Ecocardiografia , Disfunção Ventricular Esquerda , Humanos , Diástole/fisiologia , Ecocardiografia Doppler/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda/fisiologiaRESUMO
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.
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Pericardite , Humanos , Pericardite/tratamento farmacológico , Pericardite/induzido quimicamente , Inflamação , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Recidiva , Interleucina-1RESUMO
Anti-interleukin (IL)-1 agents have been developed for the treatment of autoinflammatory and rheumatic conditions, where overproduction of IL-1 is an important pathophysiologic process. IL-1α and IL-1ß are the most studied members of the IL-1 family of cytokines and have the strongest proinflammatory effects. A naturally occurring antagonist (IL-1Ra) mitigates their proinflammatory effects. Overproduction of both IL-1α (released by inflamed/damaged pericardial cells) and IL-1ß (released by inflammatory cells) is now a well-recognized therapeutic target in patients with recurrent idiopathic pericarditis. Currently, there are three available anti-IL-1 agents: anakinra (recombinant human IL-1Ra), rilonacept (a soluble decoy receptor 'trap', binding both IL-1α and IL-1ß), and canakinumab (human monoclonal anti-IL-1ß antibody). For patients with corticosteroid-dependent and colchicine-resistant recurrent pericarditis with evidence of systemic inflammation, as evidenced by elevated C-reactive protein, the efficacy and safety of anakinra (2 mg/kg/day up to 100 mg/day subcutaneously usually for at least 6 months, then tapered) and rilonacept (320 mg subcutaneously for the first day followed by 160 mg subcutaneously weekly) have been clearly demonstrated in observational studies and randomized controlled clinical trials. Severe side effects are rare and discontinuation rates are very low (<4%). The most common reported side effect is injection site reactions (>50% of patients). In this article, we describe the historical and pathophysiological background and provide a comprehensive review of these agents, which appear to be the most significant advance in medical therapy of recurrent pericarditis in the last 5 years.
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Cardiologistas , Pericardite , Colchicina/uso terapêutico , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Pericardite/tratamento farmacológicoRESUMO
Advances in multi-modality cardiac imaging have aided the evaluation, surveillance and treatment guidance of pericardial diseases, which have traditionally been a challenging group of conditions to manage. Although echocardiography remains the first-line imaging modality to assess the pericardium, both computed tomography (CT) and magnetic resonance imaging (MRI) have valuable complimentary roles. It is critical for clinicians to have a clear understanding of the utilities, advantages and disadvantages of these cardiac imaging modalities in pericardial pathologies. This contemporary review provides an update regarding the applications of multi-modality cardiac imaging in the evaluation of pericardial syndromes including acute/recurrent pericarditis, effusion/tamponade, constriction, masses and congenital anomalies.
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BACKGROUND: Coronary vasomotion abnormalities have been described in small studies but not studied systematically. We aimed to review the present literature and analyze it to improve our understanding of chronic kidney disease (CKD) related-coronary microvascular dysfunction. OBJECTIVE: Coronary flow reserve (CFR) is a well-known measure of coronary vasomotion. We aimed to assess the difference in CFR among participants with and without CKD. METHODS: PubMed, Embase, and Cochrane CENTRAL were systematically reviewed to identify studies that compared CFR in participants with and without CKD. We estimated standardized mean differences in mean CFR reported in these studies. We performed subgroup analyses according to imaging modality, and the presence of significant epicardial coronary artery disease. RESULTS: In 14 observational studies with 5966 and 1410 patients with and without CKD, the mean estimated glomerular filtration rate (eGFR) was 29 ± 04 and 87 ± 25 ml/min/1.73 m2 , respectively. Mean CFR was consistently lower in patients with CKD in all studies and the cumulative mean difference was statistically significant (2.1 ± .3 vs. 2.7 ± .5, standardized mean difference -.8, 95% CI -1.1, -.6, p < .05). The lower mean CFR was driven by both significantly higher mean resting flow velocity (.58 cm/s, 95% CI .17, .98) and lower mean stress flow velocity (-.94 cm/s, 95% CI -1.75, -.13) in studies with CKD. This difference remained significant across diagnostic modalities and even in absence of epicardial coronary artery disease. In meta-regression, there was a significant positive relationship between mean eGFR and mean CFR (p < .05). CONCLUSION: Patients with CKD have a significantly lower CFR versus those without CKD, even in absence of epicardial coronary artery disease. There is a linear association between eGFR and CFR. Future studies are required to understand the mechanisms and therapeutic implications of these findings. KEY POINTS: In this meta-analysis of observational studies, there was a significant reduction in coronary flow reserve in studies with chronic kidney disease versus those without. This difference was seen even in absence of epicardial coronary artery disease. In meta-regression, a lower estimate glomerular filtration rate was a significant predictor of lower coronary flow reserve. Coronary microvascular dysfunction, rather than atherosclerosis-related epicardial disease may underly increase cardiovascular risk in a patient with chronic kidney disease.
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Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Isquemia Miocárdica , Insuficiência Renal Crônica , Humanos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico por imagem , Taxa de Filtração Glomerular , Coração , Circulação Coronária , Vasos Coronários/diagnóstico por imagem , Estudos Observacionais como AssuntoRESUMO
PURPOSE OF REVIEW: We reviewed the contemporary literature and clinical trials to discuss the applications of the interleukin-1 (IL-1) inhibitor rilonacept to treat pericarditis, with regards to pathophysiology, pharmacology, efficacy, and safety. RECENT FINDINGS: Rilonacept is an emerging novel agent for treating recurrent pericarditis, with phase II and III clinical trials recently published. Rilonacept rapidly resolved pericarditis pain and inflammation, markedly reduced recurrent pericarditis episodes, and had few adverse events indicating a high safety profile. Recurrent pericarditis is associated with significant morbidity and unmet need for novel therapies. Inflammasomes and the IL-1 pathways were found to be critical in its pathophysiology, leading to IL-1 inhibitors being developed. The high efficacy and safety of rilonacept for recurrent pericarditis means it could potentially be considered as a second-line therapy ahead of or as an alternative to corticosteroids, and highlight the great promise of targeted immunomodulatory therapy in this field.
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Interleucina-1 , Pericardite , Humanos , Inflamassomos , Pericardite/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , RecidivaRESUMO
PURPOSE OF THE REVIEW: The purpose of this review is to understand the underlying mechanism that leads to pericarditis in systemic autoimmune and autoinflammatory diseases. The underlying mechanism plays a vital role in the appropriate management of patients. In addition, we will review the current landscape of available cardiac imaging modalities with emphasis on pericardial conditions as well as proposed treatment and management tailored toward pericardial autoimmune and autoinflammatory processes. RECENT FINDINGS: Approximately 22% of all cases of pericarditis with a known etiology are caused by systemic autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and vasculitis. In recent years, there have been advancements of imaging modalities including cardiac MRI, cardiac CT scan, and PET scan and their respective nuances in regard to contrast use, technique, and views which clinicians may utilize to better understand the extent of a patient's pericardial pathology and the trajectory of his or her disease process. In this review, we will discuss systemic autoimmune and autoinflammatory diseases that involve the pericardium. We will also review different imaging modalities that are currently used to further characterize such conditions. Having a deeper understanding of such techniques will improve patient outcomes by helping clinicians tailor treatment plans according to the unique underlying condition.
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Doenças Hereditárias Autoinflamatórias , HumanosRESUMO
PURPOSE OF REVIEW: To review myocarditis and pericarditis developing after COVID-19 vaccinations and identify the management strategies. RECENT FINDINGS: COVID-19 mRNA vaccines are safe and effective. Systemic side effects of the vaccines are usually mild and transient. The incidence of acute myocarditis/pericarditis following COVID-19 vaccination is extremely low and ranges 2-20 per 100,000. The absolute number of myocarditis events is 1-10 per million after COVID-19 vaccination as compared to 40 per million after a COVID-19 infection. Higher rates are reported for pericarditis and myocarditis in COVID-19 infection as compared to COVID-19 vaccines. COVID-19 vaccine-related inflammatory heart conditions are transient and self-limiting in most cases. Patients present with chest pain, shortness of breath, and fever. Most patients have elevated cardiac enzymes and diffuse ST-segment elevation on electrocardiogram. Presence of myocardial edema on T2 mapping and evidence of late gadolinium enhancement on cardiac magnetic resonance imaging are also helpful additional findings. Patients were treated with non-steroidal anti-inflammatory drugs and colchicine with corticosteroids reserved for refractory cases. At least 3-6 months of exercise abstinence is recommended in athletes diagnosed with vaccine-related myocarditis. COVID-19 vaccination is recommended in all age groups for the overall benefits of preventing hospitalizations and severe COVID-19 infection sequela.
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Vacinas contra COVID-19 , COVID-19 , Miocardite , Pericardite , Humanos , Meios de Contraste , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Gadolínio , Inflamação , Miocardite/induzido quimicamente , Pericardite/induzido quimicamente , Pericárdio/fisiopatologiaRESUMO
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 .
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Anti-Inflamatórios/uso terapêutico , Pericardite/tratamento farmacológico , Qualidade de Vida , Proteínas Recombinantes de Fusão/uso terapêutico , Adolescente , Corticosteroides/administração & dosagem , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Redução da Medicação , Feminino , Estado Funcional , Humanos , Entrevistas como Assunto , Masculino , Saúde Mental , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Pericardite/diagnóstico , Pericardite/fisiopatologia , Pericardite/psicologia , Projetos Piloto , Pesquisa Qualitativa , Proteínas Recombinantes de Fusão/efeitos adversos , Recidiva , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The presence of human coronavirus HKU1 infection associated with pericardial inflammation is not reported. We are reporting a young woman with systemic lupus erythematosus, who was positive for HKU1 during her pericarditis flare. Diagnostic imaging demonstrated pericardial effusion, edema, and late gadolinium enhancement on cardiac magnetic resonance imaging and echocardiography. She was on multiple anti-inflammatory medications and achieved remission with anakinra. Her management and a brief literature review is also presented.
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Coronavirus , Lúpus Eritematoso Sistêmico , Pericardite , Meios de Contraste , Feminino , Gadolínio , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pericardite/complicações , Pericardite/diagnósticoRESUMO
PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID19) involves the heart, including pericardium. This article reviews the possible pathophysiological mechanisms in pericardial involvement in COVID19 and pericardial manifestations of COVID19. It also summarizes the patients with pericarditis secondary to COVID19 and outlines the contemporary treatment strategies in this patient population. RECENT FINDINGS: A high degree of suspicion is required to identify the pericardial involvement in COVID19 patients. It is proposed that an underlying hyperinflammatory reaction in COVID19 leads to pericardial inflammation. Acute pericarditis with or without myocardial involvement is diagnosed on clinical presentation, serum inflammatory markers, electrocardiogram, and echocardiogram. Multimodality imaging may also have an additional diagnostic value. Patients are usually managed medically, but some patients develop a life-threatening pericardial tamponade necessitating pericardial drainage. Pericardial involvement is an important clinical manifestation of COVID19 requiring a proper workup. Timely diagnosis and a specific management plan based on the presentation and concomitant organ involvement usually lead to a complete recovery.
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COVID-19 , Tamponamento Cardíaco , Derrame Pericárdico , Pericardite , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/etiologia , Humanos , Pericardite/diagnóstico por imagem , Pericardite/terapia , Pericárdio/diagnóstico por imagem , SARS-CoV-2RESUMO
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.
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Monitoramento de Medicamentos/métodos , Pericardite , Qualidade de Vida , Proteínas Recombinantes de Fusão , Prevenção Secundária/métodos , Adolescente , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Interleucina-1alfa/antagonistas & inibidores , Interleucina-1beta/antagonistas & inibidores , Masculino , Pericardite/diagnóstico , Pericardite/tratamento farmacológico , Pericardite/fisiopatologia , Pericardite/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversosRESUMO
BACKGROUND: Atrial fibrillation ablation increased over the last two decades by its high success rate. However, the trend of inpatient adverse outcomes is limited. The aim of this study to examine the frequency and predictors of acute pericarditis resulting from catheter ablation. METHODS: Using the National Inpatient Sample, we identified all patients who underwent AF ablation. Univariate and multivariate logistic regressions were performed for the primary outcome of in-hospital acute pericarditis post-AF ablation. Variance-weighted regression has been used to test for linear and curvilinear trends in disease characteristics and outcomes over time. RESULTS: From 2002 to 2014, our study included 122,993 patients, acute pericarditis was found in 984 (0.8%) patients who underwent AF ablation. The trend of acute pericarditis showed inconsistent fluctuation leaning towards reduction over the years. Multivariate analysis showed that patients of female gender are at a 40% higher risk of acute pericarditis post-ablation compared with males. Additionally, obese patients have a 40% higher risk of developing acute pericarditis compared with patients who have BMI < 30. Furthermore, anaemia and rheumatoid arthritis have the odds ratio (OR: 2.63; 95% [CI] 2.04-3.39) and (OR: 1.64; 95% [CI] 1.08-2.48). CONCLUSION: Post-AF ablation, in-hospital acute pericarditis showed inconsistent fluctuation leaning towards reduction. Female gender and obesity are at higher risk for developing acute pericarditis post-AF ablations. Proper evaluation might alter those complications.
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Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Pericardite/epidemiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Anemia/epidemiologia , Artrite Reumatoide/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Pericardite/etiologia , Fatores de Risco , Fatores Sexuais , Estados Unidos/epidemiologiaRESUMO
PURPOSE OF REVIEW: Erdheim-Chester disease (ECD) is a very rare neoplasm of the non-Langerhans cell histiocytes. Pericardial involvement is uncommon, and we aim to review the current knowledge on the epidemiology, clinical manifestations, and management of recurrent pericarditis due to ECD. We also aim to raise awareness of the importance of considering ECD as a differential diagnosis for recurrent pericarditis in the appropriate clinical settings. RECENT FINDINGS: The prevalence of pericardial involvement in ECD is estimated to be 40% and is getting more recognized recently. Up to 68% of patients carry the BRAFV600E mutation, and targeted treatment with vemurafenib, an inhibitor of BRAF kinase, showed an excellent response in those who carry this mutation. Pericardial disease appears to be the most common cardiac presentation (in 80% of cases). Although pericardial involvement is frequently asymptomatic, patients with ECD can present with typical pericarditis chest pain and signs of right heart failure if constriction is present. The diagnosis of ECD requires a biopsy of the pericardium or another affected organ. If BRAFV600E mutation is absent, limited data exist, and many medications have been tried, like interferon alfa, anakinra, and infliximab.