Diagnosis, Risk Stratification, and Treatment of Pericarditis: A Review.

Importance: Pericarditis accounts for up to 5% of emergency department visits for nonischemic chest pain in North America and Western Europe. With appropriate treatment, 70% to 85% of these patients have a benign course. In acute pericarditis, the development of constrictive pericarditis (<0.5%) and pericardial tamponade (<3%) can be life-threatening. Observations: Acute pericarditis is diagnosed with presence of 2 or more of the following: sharp, pleuritic chest pain that worsens when supine (≈90%); new widespread electrocardiographic ST-segment elevation and PR depression (≈25%-50%); a new or increased pericardial effusion that is most often small (≈60%); or a pericardial friction rub (<30%). In North America and Western Europe, the most common causes of acute pericarditis are idiopathic or viral, followed by pericarditis after cardiac procedures or operations. Tuberculosis is the most common cause in endemic areas and is treated with antituberculosis therapy, with corticosteroids considered for associated constrictive pericarditis. Treatment of acute idiopathic and pericarditis after cardiac procedures or operations involves use of high-dose nonsteroidal anti-inflammatory drugs (NSAIDs), with doses tapered once chest pain has resolved and C-reactive protein level has normalized, typically over several weeks. These patients should receive a 3-month course of colchicine to relieve symptoms and reduce the risk of recurrence (37.5% vs 16.7%; absolute risk reduction, 20.8%). With a first recurrence of pericarditis, colchicine should be continued for at least 6 months. Corticosteroids are often used if pericarditis does not improve with NSAIDs and colchicine. In certain patients with multiple recurrences, which can occur for several years, interleukin 1 (IL-1) blockers have demonstrated efficacy and may be preferred to corticosteroids. Conclusions: Acute pericarditis is a common cause of nonischemic chest pain. Tuberculosis is the leading cause of pericarditis in endemic areas and is treated with antitubercular therapy. In North America and Western Europe, pericarditis is typically idiopathic, develops after a viral infection, or develops following cardiac procedures or surgery. Treatment with NSAIDs and colchicine leads to a favorable prognosis in most patients, although 15% to 30% of patients develop recurrence. Patients with multiple recurrent pericarditis can have a disease duration of several years or more, are often treated with corticosteroids, and IL-1 blockers may be used for selected patients as steroid-sparing therapy.

Malignant Pericardial Effusion: A Systematic Review.

Background: Malignant pericardial effusion (Eff) is often asymptomatic and has an unknown prevalence, due to its occult presentation. The condition often is identified postmortem on autopsy, and it is associated with a poor prognosis. Given the late presentation of malignant pericardial Effs, a minimal volume of literature has examined the epidemiology, clinical characteristics, and outcomes of these complex patients. We conducted a systematic review to advance present understanding of this condition. Methods: A search of 4 databases resulted in 41 case reports meeting criteria. Inclusion criteria were being a patient aged > 18 years who presented with pericardial Eff in the setting of malignancy. Intervention was medical and/or surgical therapy, and the outcome was mortality. Results: For the 41 patients included, the median age was 54 years, and the majority were male patients (58%). Dyspnea was the leading symptom (90%), and cardiac tamponade was present in 78% of cases. Common cancers included lung, gastrointestinal, and renal neoplasms (59%). Pericardiocentesis occurred in 98% of cases, with a median fluid extraction volume of 1000 mL. Death occurred in 44%, primarily due to disease progression and/or metastasis. Conclusions: This study presents the largest systematic review on malignancy-induced pericardial Effs to date. Notably, solid tumours, and specifically lung adenocarcinomas, are common culprits. Malignant pericardial Effs are often severe, with a majority of patients presenting with cardiac tamponade. Overall, treatment options are limited, and the associated mortality rate is high.

Contexte: L'épanchement péricardique malin (EPM) est un état généralement asymptomatique, de prévalence inconnue en raison de son tableau clinique occulte. Il est souvent reconnu post-mortem, à l'autopsie, et est associé à un pronostic médiocre. En raison de la consultation tardive pour un EPM, les données publiées relatives à l'épidémiologie, aux caractéristiques cliniques et à l'issue de ces cas complexes sont limitées. Nous avons réalisé une analyse systématique dans le but d'élargir les connaissances sur cette affection. Méthodologie: Une recherche réalisée dans quatre bases de données a permis de repérer 41 rapports de cas qui répondaient aux critères de recherche. Les critères d'inclusion étaient les suivants : être âgé de plus de 18 ans; présenter un épanchement péricardique en présence d'un cancer; intervention pharmacologique et/ou chirurgicale; issue mortelle. Résultats: L'âge médian des 41 patients inclus était de 54 ans; la majorité d'entre eux étaient des hommes (58 %). Le symptôme principal était la dyspnée (90 %), et une tamponnade cardiaque était présente dans 78 % des cas. Les cancers les plus fréquents étaient le cancer du poumon, le cancer gastro-intestinal et les néoplasmes rénaux (59 %). Une péricardiocentèse a été réalisée dans 98 % des cas. Le volume de drainage médian était de 1 000 mL. Quarante-quatre pour cent des sujets sont décédés, principalement en raison de la progression de la maladie et/ou de métastases. Conclusions: Cette étude est la plus vaste analyse systématique réalisée à ce jour sur l'EPM. Les tumeurs solides, et plus particulièrement les adénocarcinomes pulmonaires, sont des causes fréquentes. L'EPM est souvent grave, la majorité des patients présentant une tamponnade cardiaque. Les traitements disponibles sont généralement limités, et le taux de mortalité associé est élevé.

Pericardial Diseases and Best Practices for Pericardiectomy: JACC State-of-the-Art Review.

Remarkable advances have occurred in the understanding of the pathophysiology of pericardial diseases and the role of multimodality imaging in this field. Medical therapy and surgical options for pericardial diseases have also evolved substantially. Pericardiectomy is indicated for chronic or irreversible constrictive pericarditis, refractory recurrent pericarditis despite optimal medical therapy, or partial agenesis of the pericardium with a complication (eg, herniation). A multidisciplinary evaluation before pericardiectomy is essential for optimal patient outcomes. Overall, given the good outcomes reported, radical pericardiectomy on cardiopulmonary bypass, if feasible, is the preferred approach. Due to patient complexity, as well as the technical aspects of the surgery, pericardiectomy should be performed at high-volume centers that have the required expertise. The current review highlights the essential features of this multidisciplinary approach from diagnosis to recovery in patients undergoing pericardiectomy.

Immune checkpoint inhibitors and pericardial disease: a systematic review.

INTRODUCTION: Despite the growing use of immune checkpoint inhibitors (ICI) in cancer treatment, data regarding ICI-associated pericardial disease are primarily derived from case reports and case series. ICI related pericardial disease can be difficult to diagnose and is associated with significant morbidity. We conducted a systematic review to further characterize the epidemiology, clinical presentation, and outcomes of this patient population. METHODS: A search of four databases resulted in 31 studies meeting inclusion criteria. Patients > 18 years old who presented with ICI mediated pericardial disease were included. Intervention was medical + surgical therapy and outcomes were development of cardiac tamponade, morbidity, and mortality. RESULTS: Thirty- eight patients across 31 cases were included. Patients were majority male (72%) with a median age of 63. Common symptoms included dyspnea (59%) and chest pain (32%), with 41% presenting with cardiac tamponade. Lung cancer (81%) was the most prevalent, and nivolumab (61%) and pembrolizumab (34%) were the most used ICIs. Pericardiocentesis was performed in 68% of patients, and 92% experienced symptom improvement upon ICI cessation. Overall mortality was 16%. DISCUSSION: This study provides the most comprehensive analysis of ICI-mediated pericardial disease to date. Patients affected were most commonly male with lung cancer treated with either Nivolumab or Pembrolizumab. Diagnosis may be challenging in the setting of occult presentation with normal EKG and physical exam as well as delayed onset from therapy initiation. ICI-associated pericardial disease demonstrates high morbidity and mortality, as evidenced by a majority of patients requiring pericardiocentesis.

Pericardial Disease in Cardiac Amyloidosis: A Comprehensive Review.

In patients with cardiac amyloidosis, pericardial involvement is common, with up to half of patients presenting with pericardial effusions. The pathophysiological mechanisms of pericardial pathology in cardiac amyloidosis include chronic elevations in right-sided filling pressures, myocardial and pericardial inflammation due to cytotoxic effects of amyloid deposits, and renal involvement with subsequent uremia and hypoalbuminemia. The pericardial effusions are typically small; however, several cases of life-threatening cardiac tamponade with hemorrhagic effusions have been described as a presenting clinical scenario. Constrictive pericarditis can also occur due to amyloidosis and its identification presents a clinical challenge in patients with cardiac amyloidosis who concurrently manifest signs of restrictive cardiomyopathy. Multimodality imaging, including echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, is useful in the evaluation and management of this patient population. The recognition of pericardial effusion is important in the risk stratification of patients with cardiac amyloidosis as its presence confers a poor prognosis. However, specific treatment aimed at the effusions themselves is seldom indicated. Cardiac tamponade and constrictive pericarditis may necessitate pericardiocentesis and pericardiectomy, respectively.

Effect of Tafamidis on Cardiac Function in Patients With Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial.

Importance: Tafamidis has been shown to improve survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with placebo. However, its effect on cardiac function has not been fully characterized. Objective: To examine the effect of tafamidis on cardiac function in patients with ATTR-CM. Design, Setting, and Participants: This was an exploratory, post hoc analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), a multicenter, international, double-blind, placebo-controlled phase 3 randomized clinical trial conducted from December 2013 to February 2018. The ATTR-ACT included 48 sites in 13 counties and enrolled patients aged 18 to 90 years with ATTR-CM. Data were analyzed from July 2018 to September 2023. Intervention: Patients were randomized to tafamidis meglumine, 80 mg or 20 mg, or placebo for 30 months. Main Outcomes and Measures: Patients were categorized based on left ventricular (LV) ejection fraction at enrollment as having heart failure with preserved ejection fraction (≥50%), mildly reduced ejection fraction (41% to 49%), or reduced ejection fraction (≤40%). Changes from baseline to month 30 in LV ejection fraction, LV stroke volume, LV global longitudinal strain, and the ratio of early mitral inflow velocity to septal and lateral early diastolic mitral annular velocity (E/e') were compared in patients receiving tafamidis, 80 mg, vs placebo. Results: A total of 441 patients were randomized in ATTR-ACT, and 436 patients had available echocardiographic data. Of 436 included patients, 393 (90.1%) were male, and the mean (SD) age was 74 (7) years. A total of 220 (50.5%), 119 (27.3%), and 97 (22.2%) had heart failure with preserved, mildly reduced, and reduced LV ejection fraction, respectively. Over 30 months, there was less pronounced worsening in 4 of the echocardiographic measures in patients receiving tafamidis, 80 mg (n = 176), vs placebo (n = 177) (least squares mean difference: LV stroke volume, 7.02 mL; 95% CI, 2.55-11.49; P = .002; LV global longitudinal strain, -1.02%; 95% CI, -1.73 to -0.31; P = .005; septal E/e', -3.11; 95% CI, -5.50 to -0.72; P = .01; lateral E/e', -2.35; 95% CI, -4.01 to -0.69; P = .006). Conclusions and Relevance: Compared with placebo, tafamidis, 80 mg, attenuated the decline of LV systolic and diastolic function over 30 months in patients with ATTR-CM. Approximately half of patients had mildly reduced or reduced LV ejection fraction at enrollment, suggesting that ATTR-CM should be considered as a possible diagnosis in patients with heart failure regardless of underlying LV ejection fraction. Trial Registration: ClinicalTrials.gov Identifier: NCT01994889.

Successful Treatment of Recurrent Pericarditis With Rilonacept in Acute Promyelocytic Leukemia.

A 40-year-old woman presented with recurrent pericarditis and pericardial effusion while receiving treatment with all-trans retinoic acid and arsenic trioxide for recently diagnosed acute promyelocytic leukemia. She was successfully treated with the interleukin-1 inhibitor rilonacept after experiencing multiple recurrences with triple therapy with aspirin, colchicine, and steroids. (Level of Difficulty: Advanced.).

Pericardial mesothelioma presenting as constrictive pericarditis.

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.

Lymphocytic Perimyocarditis Masquerading as Steroid-Dependent Recurrent Pericarditis.

Lymphocytic myocarditis is a pattern of myocardial inflammation typically associated with viral, autoimmune, or idiopathic causes. We present a case of lymphocytic perimyocarditis masquerading as steroid-dependent recurrent pericarditis. This case shows the advantages of using multimodal cardiac imaging and endomyocardial biopsy in clarifying diagnosis in treatment-resistant cases. (Level of Difficulty: Advanced.).

A Rare Case of Constrictive Pericarditis: Inflammatory Myofibroblastic Tumor.

A previously healthy 15-year-old adolescent female presented with dependent edema, ascites, and dyspnea on exertion. The result of her initial evaluation was consistent with constrictive pericarditis in the setting of local low-grade spindle cell sarcoma. She was unresponsive to traditional medical management and required concurrent mass resection and radical pericardiectomy for definitive treatment. (Level of Difficulty: Intermediate.).

Transition to rilonacept monotherapy from oral therapies in patients with recurrent pericarditis.

OBJECTIVE: Polypharmacy management of recurrent pericarditis (RP) often involves long-term therapies, often with negative effects. Slow tapering of oral therapies is often required to avoid recurrence. A post hoc analysis of the phase III trial Rilonacept inHibition of interleukin-1 Alpha and beta for recurrent Pericarditis: a pivotal Symptomatology and Outcomes Study (RHAPSODY) evaluated investigator approaches to transitioning to IL-1 blockade monotherapy with rilonacept, which was hypothesised to allow accelerated withdrawal of common multidrug pericarditis regimens. METHODS: RHAPSODY was a multicentre (Australia, Israel, Italy, USA), double-blind, placebo-controlled, randomised-withdrawal trial in adults and adolescents with RP. Investigators initiated rilonacept at the labelled dose level and discontinued oral pericarditis therapies during the 12-week run-in; randomised patients received study drug as monotherapy. Time to rilonacept monotherapy was quantified in patients receiving multidrug regimens at baseline who achieved rilonacept monotherapy during run-in. RESULTS: In 86 enrolled patients, mean time to rilonacept monotherapy was 7.9 weeks, with no recurrences. Of these, 64% (n=55) entered on multidrug regimens: non-steroidal anti-inflammatory drugs (NSAIDs) plus colchicine (44% (24/55)), colchicine plus glucocorticoids (24% (13/55)), or NSAIDs, colchicine, plus glucocorticoids (33% (18/55)). Investigators transitioned patients receiving colchicine and glucocorticoids at baseline to rilonacept monotherapy without recurrence regardless of taper approach: sequential (n=14; median, 7.7 weeks) or concurrent (n=17; median, 8.0 weeks). Median time to rilonacept monotherapy was similar regardless of glucocorticoid dose and duration: ≤15 mg/day (n=21): 7.3 weeks; >15 mg/day (n=18): 8.0 weeks; long-term (≥28 days): 7.6 weeks. CONCLUSIONS: Rapid discontinuation of oral RP therapies while transitioning to rilonacept monotherapy was feasible without triggering pericarditis recurrence. TRIAL REGISTRATION NUMBER: NCT03737110.

Coronary flow abnormalities in chronic kidney disease: A systematic review and meta-analysis.

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.

Complex Management Decisions in a Professional Athlete With Recurrent Pericarditis.

A 32-year-old professional athlete developed chronic recurrent pericarditis despite standard medical therapy. Etiology included postpericardiotomy syndrome, viral, or COVID-19 vaccine related, all potentially exacerbated by intense exercise. Treatment and return-to-play decisions were complicated by potential side-effect profile of therapies and ability to limit exercise as a professional athlete. (Level of Difficulty: Intermediate.).

Worsened Tricuspid Regurgitation Following Pericardiectomy for Constrictive Pericarditis.

BACKGROUND: Worsening tricuspid regurgitation (TR) severity may occur after pericardiectomy surgery for constrictive pericarditis patients; however, its mechanisms and predictors are not well established. We evaluated the clinical characteristics, associated factors, and outcomes of worsening TR after pericardiectomy. METHODS: Consecutive patients undergoing pericardiectomy for constrictive pericarditis without tricuspid valve surgery and with pre- and postoperative echocardiography available during 2000 to 2017 were retrospectively studied. Clinical, imaging, hemodynamic, and mortality characteristics were analyzed by those with and without worsening TR by at least one grade. RESULTS: Among 381 patients (age 61 [17] years, 318 [83.5%] male), 193 (50.7%) had worsening TR post-operatively, and 75 died during the 2.5 (5.4) years follow-up. In univariable analysis, worsening TR was associated with a history of congestive heart failure (47.2% versus 31.9%, P=0.003), increased left atrial volume indexed (23 versus 20 mL/m2, P=0.020), reduced right ventricular fractional area change (47% versus 54%, P<0.001), and worsening mitral regurgitation (39.7% versus 16.6%, P<0.001). Worsened TR had a trend toward reduced survival during follow-up (log-rank P=0.080), especially those with worsened TR but no recovery of TR grade on subsequent echocardiography within the first year compared with those without worsened TR (log-rank P=0.02). In multivariable analysis, right ventricular fractional area change, left atrial volume indexed, left ventricular mass indexed, pulmonary artery systolic pressure, and right atrial pressure/pulmonary capillary wedge pressure ratio were most associated with worsened TR, while blood urea nitrogen, hematocrit, lateral and medial e' tissue Doppler and heart rate were most associated with mortality during follow-up. CONCLUSIONS: Worsening TR severity was prevalent after pericardiectomy and had a trend toward reduced survival, especially if TR severity did not recover on subsequent echocardiography. Presence of parameters associated with worsened TR and reduced survival should alert clinicians to carefully manage these patients during follow-up.

Emerging Therapies for Recurrent Pericarditis: Interleukin-1 inhibitors.

Recurrent pericarditis (RP) is a complex inflammatory disorder associated with adverse outcomes and poor quality of life. After the first episode of acute pericarditis, a non-negligible group of patients will fail to achieve complete remission despite treatment and will be challenged by side effects from the chronic use of medications like corticosteroids. The cause of RP remains unknown in the majority of cases, mainly due to a gap in knowledge of its complex pathophysiology. Over the past 2 decades, the interleukin-1 (IL-1) pathway has been uncovered as a key element in the inflammatory cascade, allowing the development of pharmacological targets known as IL-1 inhibitors. This group of medications has emerged as a treatment option for patients with RP colchicine-resistance and steroid dependents. Currently, anakinra and rilonacept, have demonstrated beneficial impact in clinical outcomes with a reasonable safety profile in randomized clinical trials. There is still paucity of data regarding the use of canakinumab in the treatment of patients with RP. Although further studies are needed to refine therapeutic protocols and taper of concomitant therapies, IL-1 inhibitors, continue to consolidate as part of the pharmacological armamentarium to manage this complex condition with potential use as monotherapy. The aim of this review is to highlight the role of IL-1 pathway in RP and discuss the efficacy, safety, and clinical applicability of IL-1 inhibitors in the treatment of RP based on current evidence.

Symptomatic Recurrent Chylopericardium: How to Manage This Rare Entity?

Recurrent chylopericardium after cardiac surgery is a rare entity. This paper presents the case of a 69-year-old female who developed a large recurrent chylopericardium related to surgical myectomy and resection of sub-aortic membrane for hypertrophic sub-valvular aortic stenosis. Treatment required pericardiocentesis followed by lymphangiogram with glue embolization of the lymphatic leak. (Level of Difficulty: Intermediate.).