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.

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.

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.

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.).

Multimodality imaging in pericardial diseases.

With a rapidly growing spectrum, non-specific symptoms and overlapping etiologies, pericardial diseases can represent a real diagnostic challenge. Consequently, multimodality imaging has taken a front seat in the diagnosis and management of these conditions. Cardiac CT offers an excellent anatomical characterization of pericardial thickening, fat stranding and/or presence of calcifications. and is also the preferred modality to assess extra-cardiac structures. Active pericardial inflammation, edema and fibrosis comprise pericardial characterization using CMR and allows for a precise diagnosis, disease staging and patient specific tailoring of therapies. PET scan still occupies a very modest role in the evaluation of pericardial diseases but might help discriminating malignant pericardial effusion and extrapulmonary tuberculous. More than ever, clinicians need to master how these modalities complement each other while avoiding unnecessary cost and to translate this knowledge into a more customized patient's care approach. The aim of this review was to recognize the role of multimodality imaging in the investigation of various pericardial diseases, assess how these modalities can impact the clinical course and treatment of these affections and finally elucidate their role in the patient's prognostication.

Right versus left heart reverse remodelling after treating ischaemic mitral and tricuspid regurgitation.

OBJECTIVES: Repair outcomes of tricuspid regurgitation (TR) associated with ischaemic mitral regurgitation (IMR) are inferior to functional TR in terms of TR recurrence and right ventricular (RV) reverse remodelling. Our objective is to analyse right versus left heart reverse remodelling after surgery for IMR-associated TR. METHODS: From 2001 to 2011, 568 patients with severe IMR underwent mitral valve surgery (repair 87%, replacement 13%), and 131 had concomitant tricuspid valve repair. Median follow-up was 3.0 years; 25% of living patients were followed up for 6.3 years. Longitudinal analysis of 1527 follow-up echocardiograms was performed to assess ventricular reverse remodelling and function. RESULTS: Unlike the left heart, the right heart failed to reverse remodel (failed to recover ventricular function or halt dilatation). During follow-up after surgery, the right ventricle continued to dilate while the left ventricle regressed in size. RV ejection fraction decreased (46% at 1 month and 44% at 5 years), while left ventricular ejection fraction increased (33% and 37%, respectively). RV strain showed early (-11% at 1 month) and late (-12% at 5 years) dysfunction. Patients who underwent tricuspid valve repair had worse RV function. Mitral regurgitation remained stable after surgical intervention, and TR gradually recurred (37% moderate, 20% severe at 7 years). CONCLUSIONS: Surgical treatment of IMR and TR along with revascularization failed to induce reverse remodelling of the right heart. These findings warrant further investigations to identify optimal timing and approach of intervention for IMR-associated TR with respect to RV remodelling.

Erdheim-Chester Disease: a Rare but Important Cause of Recurrent Pericarditis.

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.

Multimodality imaging in patients with post-cardiac injury syndrome.

This review article is focused on the role of echocardiography, cardiac CT and cardiac magnetic resonance (CMR) imaging in diagnosing and managing patients with post-cardiac injury syndrome (PCIS). Clinically, the spectrum of pericardial diseases under PCIS varies not only in form and severity of presentation but also in the timing varying from weeks to months, thus making it difficult to diagnose. Pericarditis developing after recent or remote myocardial infarction, cardiac surgery or ablation if left untreated or under-treated could worsen into complicated pericarditis which can lead to decreased quality of life and increased morbidity. Colchicine in combination with other anti-inflammatory agents (non-steroidal anti-inflammatory drugs) is proven to prevent and treat acute pericarditis as well as its relapses under various scenarios. Imaging modalities such as echocardiography, CT and CMR play a pivotal role in diagnosing PCIS especially in difficult cases or when clinical suspicion is low. Echocardiography is the tool of choice for emergent bedside evaluation for cardiac tamponade and to electively study the haemodynamics impact of constrictive pericarditis. CT can provide information on pericardial thickening, calcification, effusions and lead perforations. CMR can provide pericardial tissue characterisation, haemodynamics changes and guide long-term treatment course with anti-inflammatory agents. It is important to be familiar with the indications as well as findings from these multimodality imaging tools for clinical decision-making.

Myocardial and Pericardial Toxicity Associated With Immune Checkpoint Inhibitors in Cancer Patients.

We recount a single-center experience with cardiac immunity-related adverse effects in patients treated with immune checkpoint inhibitors. Of 2,830 patients, 9 patients (0.3%) developed cardiac immunity-related adverse effects (4 cases of cardiomyopathies, 2 of myocarditis, 2 of acute pericarditis, and 1 of large pericardial effusion). Disease profiles, hospital courses, and outcomes are reported. (Level of Difficulty: Advanced.).