Clinicopathological features of immunoglobulin G4-related constrictive pericarditis.

AIM: Constrictive pericarditis (CP) is characterised by scarring fibrosis and a loss of pericardial elasticity, which causes heart failure. IgG4 (immunoglobulin G4)-related disease (IgG4-RD) is a systemic fibro-inflammatory disease characterised by the infiltration of IgG4-immunopositive plasmacytes and high serum IgG4 levels that frequently shape tumorous lesions. Although pericardial involvement of IgG4-RD is rare, with indications of CP, pericardial effusion and irregular masses, the clinical and pathological features remain unclear. In this study, we examined the relationship between CP and IgG4-RD. METHODS: Among 35 thick-walled CP cases (histologically pericardial thickening ≥2 mm), eight cases were aetiology identified. Using the diagnostic criteria for IgG4-RD, 11 cases were classified as IgG4-CP, whereas the remainder were considered true idiopathic CP (16 cases) and the clinical pathological features were evaluated. RESULTS: Compared with the other groups, the IgG4-CP group was more common in men and associated with low-grade fever and massive pericardial effusion with frequent recurrence. Deaths resulting from heart failure occurred in a few cases of the IgG4-CP group, but not in other groups. An increase in C-reactive protein and a high positivity rate of anti-nuclear antibodies frequently occurred in the IgG4-CP group. Histologically, the IgG4-CP group included lymphoid follicle, eosinophil infiltration and few calcifications. CONCLUSIONS: Pericardial IgG4-RD occurs not only as nodular lesions, but also as thick-walled CP, and accounts for approximately 40% of thick-walled CP cases of unknown cause. The predominant clinical characteristic was refractory and recurrent pericardial effusion. Recognising IgG4-RD as a cause of CP is important to initiate appropriate therapy.

The Emerging Field of Cardioimmunology: Past, Present and Foreseeable Future.

Over the past 30 years, the field of cardioimmunology has moved from being dismissed as a field that was chasing an epiphenomenon of little biological consequence to a scientific discipline that is providing important new insights into the immunologic basis for hypertension, atherosclerosis, myocarditis, pericarditis, autoimmune heart disease, and heart failure. In this article, we will review the conceptual insights and technical breakthroughs that have allowed the field to move forward, as well as the clinical trials in the cardioimmunology space, to provide a historical context for the articles that will appear in the compendium that is focused on the interface between cardioimmunology, myocardial function, and disease.

Combinational elastography prior to pericardiectomy to assess liver condition in patients with constrictive pericarditis.

A 68-year-old man was diagnosed with pericarditis associated with immunoglobulin G4-related disease and was administered prednisolone 2 years prior to presentation. During the process of tapering off from prednisolone 1 year later, edema of the lower legs and pleural effusion worsened. He gradually developed dyspnea on exertion, and laboratory examinations revealed elevated liver enzyme levels. Diuretics were administered; however, the symptoms did not resolve. Transthoracic echocardiography and cardiac catheterization revealed findings consistent with those of constrictive pericarditis. Pericardiectomy was considered and the perioperative risks due to possible recovery from liver dysfunction were discussed. Combinational elastography was subsequently performed. The results indicated the absence of liver fibrosis, suggesting that liver dysfunction was attributable to liver congestion; thus, the liver dysfunction was considered reversible. Subsequently, pericardiectomy was performed. Given that constrictive pericarditis can lead to liver dysfunction due to congestion, the perioperative risk is often controversial when considering surgical interventions. Learning objective: Combinational elastography may be useful in the preoperative evaluation of patients with cardiac diseases complicated by liver dysfunction to distinguish liver fibrosis, understand the pathogenesis of liver dysfunction, and determine subsequent treatment strategies.

Histoplasmosis Causing Overt Inflammation Presenting as Pericarditis: A Case Report.

Histoplasma capsulatum is a well-known cause of pulmonary infections, but in the right patient population or host environment, it can cause a vast array of symptoms. The fungus possesses a special set of virulence factors that allows it to evade host immunity and cause infection, particularly in immunosuppressed hosts. Pericarditis is a known presentation of histoplasmosis, but it can be difficult to diagnose and is often treated based on suspicion. We present a case of a healthy young male who mounted a robust inflammatory response to histoplasmosis resulting in pericarditis.

A novel multi-task machine learning classifier for rare disease patterning using cardiac strain imaging data.

To provide accurate predictions, current machine learning-based solutions require large, manually labeled training datasets. We implement persistent homology (PH), a topological tool for studying the pattern of data, to analyze echocardiography-based strain data and differentiate between rare diseases like constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). Patient population (retrospectively registered) included those presenting with heart failure due to CP (n = 51), RCM (n = 47), and patients without heart failure symptoms (n = 53). Longitudinal, radial, and circumferential strains/strain rates for left ventricular segments were processed into topological feature vectors using Machine learning PH workflow. In differentiating CP and RCM, the PH workflow model had a ROC AUC of 0.94 (Sensitivity = 92%, Specificity = 81%), compared with the GLS model AUC of 0.69 (Sensitivity = 65%, Specificity = 66%). In differentiating between all three conditions, the PH workflow model had an AUC of 0.83 (Sensitivity = 68%, Specificity = 84%), compared with the GLS model AUC of 0.68 (Sensitivity = 52% and Specificity = 76%). By employing persistent homology to differentiate the "pattern" of cardiac deformations, our machine-learning approach provides reasonable accuracy when evaluating small datasets and aids in understanding and visualizing patterns of cardiac imaging data in clinically challenging disease states.

Tofacitinib to prevent anti-drug antibody formation against LMB-100 immunotoxin in patients with advanced mesothelin-expressing cancers.

Background: LMB-100 is a mesothelin (MSLN)-targeting recombinant immunotoxin (iTox) carrying a Pseudomonas exotoxin A payload that has shown promise against solid tumors, however, efficacy is limited by the development of neutralizing anti-drug antibodies (ADAs). Tofacitinib is an oral Janus Kinase (JAK) inhibitor that prevented ADA formation against iTox in preclinical studies. Methods: A phase 1 trial testing LMB-100 and tofacitinib in patients with MSLN-expressing cancers (pancreatic adenocarcinoma, n=13; cholangiocarcinoma, n=1; appendiceal carcinoma, n=1; cystadenocarcinoma, n=1) was performed to assess safety and to determine if tofacitinib impacted ADA formation. Participants were treated for up to 3 cycles with LMB-100 as a 30-minute infusion on days 4, 6, and 8 at two dose levels (100 and 140 µg/kg) while oral tofacitinib was administered for the first 10 days of the cycle (10 mg BID). Peripheral blood was collected for analysis of ADA levels, serum cytokines and circulating immune subsets. Results: The study was closed early due to occurrence of drug-induced pericarditis in 2 patients. Pericarditis with the combination was not reproducible in a transgenic murine model containing human MSLN. Two of 4 patients receiving all 3 cycles of treatment maintained effective LMB-100 levels, an unusual occurrence. Sustained increases in systemic IL-10 and TNF-α were seen, a phenomenon not observed in prior LMB-100 studies. A decrease in activated T cell subsets and an increase in circulating immunosuppressive myeloid populations occurred. No radiologic decreases in tumor volume were observed. Discussion: Further testing of tofacitinib to prevent ADA formation is recommended in applicable non-malignant disease settings. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT04034238.

Rituximab and pericardiectomy with waffle procedure in constrictive pericarditis due to IgG4-related disease: A case report.

We should consider IgG4-related disease (IGRD) as one of the potential causes of constrictive pericarditis. In patients with constrictive pericarditis due to IGRD, the combination of surgical treatment and immunosuppressive therapy may be an effective strategy.

Purulent Pericarditis as the First Manifestation of Esophageal Carcinoma.

INTRODUCTION: Purulent pericarditis secondary to esophago-pericardial fistula is a serious complication that has been previously reported in patients with esophageal cancer treated with radio/chemotherapy and esophageal stenting. However, the presence of esophago-pericardial fistula as the first manifestation of advanced carcinoma of the esophagus is exceedingly infrequent. We report the case of a 61-year-old male who presented with sepsis, cardiac tamponade and septic shock who was found to have an esophago-pericardial fistula secondary to squamous carcinoma of the esophagus. Emergency pericardiocentesis was performed with subsequent hemodynamic improvement. The drained pericardial fluid was purulent in nature and cultures were positive for Streptococcus anginosus. A CT scan followed by upper gastrointestinal endoscopy with tissue biopsy confirmed the diagnosis of squamous cell carcinoma of the esophagus. A self-expanding covered stent was endoscopically placed to exclude the fistula and restore the esophageal lumen. In this report, we discuss some aspects related to the diagnosis and management of this serious clinical entity.

COVID-19 mRNA Vaccination-Induced Myopericarditis in an Otherwise Healthy Young Male: An Evidence-Based Approach to Differentiating From Perimyocarditis.

A 29-year-old male, otherwise healthy with no past medical history, presented to the hospital after a two-day history of pleuritic chest pain with a fever. He had received his first dose of the mRNA-1273 coronavirus disease (COVID-19) vaccine (Moderna) two months prior without any adverse reactions. He received his second dose approximately 24 hours before symptom onset and hospital presentation. Work-up was unremarkable for respiratory, autoimmune, and rheumatological etiologies. The patient was found to have electrocardiogram features and symptoms in keeping with pericarditis, C-reactive protein elevation, and a peak high-sensitivity troponin level of 9,992 ng/L suggestive of a component of myocarditis. A dilemma arose regarding whether this patient should be diagnosed with perimyocarditis or myopericarditis, terms often used interchangeably without proper reference to the primary pathology, which can ultimately affect management. A subsequent echocardiogram was unremarkable, with a normal left ventricular systolic function, but cardiac resonance imaging revealed myocardial edema suggestive of myocarditis. Without convincing evidence for an alternative explanation after an extensive work-up of ischemic, autoimmune, rheumatological, and infectious etiologies, this patient was diagnosed with COVID-19 mRNA vaccine-induced myopericarditis. The patient fully recovered after receiving a treatment course of ibuprofen and colchicine. This case explores how the diagnosis of COVID-19 vaccine-induced myopericarditis was made and treated using an evidence-based approach, highlighting its differentiation from perimyocarditis.

Auguste François Chomel (1788-1858) and his Work on Rheumatism: Introducing Rheumatic Heart.

In the early 19th century, Auguste François Chomel gathered the knowledge on rheumatism, systematised it, and published it in his majestic work Pathologie Générale. In his treatise, for the first time, rheumatic heart was discussed. Taking into account the opinions of the ancient Greek physicians, he had described the disease as an acute or chronic manifestation of the inflammation of the heart due to rheumatism. His publication rendered rheumatic heart an issue in vogue for his era, a disease being mentioned in all textbooks of the internal pathology.

The Important Role of Preoperative D-Dimer in Constrictive Pericarditis.

Background: The impact of coagulation indicators on postoperative outcomes of patients with constrictive pericarditis undergoing pericardiectomy has been poorly investigated. This study aimed to assess the prognostic role of preoperative coagulation indicators in these patients. Methods: We retrospectively included 158 patients with constrictive pericarditis undergoing pericardiectomy. The diagnostic values of coagulation indicators for postoperative complications were evaluated by ROC curves. Patients were divided into two groups according to the cutoff value calculated by ROC curve. Postoperative outcomes were compared between the two groups. Logistic regression analysis was performed to identify risk factors of postoperative complications. Results: ROC curve showed that among different coagulation indicators, preoperative D-dimer (DD) level could effectively identify patients with postoperative complications (AUC 0.771, 95% CI 0.696-0.847, P < 0.001). Patients were divided into the low DD group and the high DD group. The comparison of postoperative outcomes suggested that high preoperative DD level was significantly associated with longer durations of vasoactive agents using (P = 0.018), intubation (P = 0.020), ICU stay (P = 0.008), chest drainage (P=0.004) and hospital stay (P = 0.002). Multivariable analysis showed that high preoperative DD level was the independent risk factor of postoperative complications (OR 6.892, 95% CI 2.604-18.235, P < 0.001). Conclusion: High preoperative DD level was significantly linked to poor postoperative outcomes and could provide an effective prediction ability for postoperative complications in patients with constrictive pericarditis.

Pericardial Diseases Mortality Trends in Brazil From 2000 to 2022.

Background Pericardial diseases manifest in various clinical forms, including acute pericarditis, constrictive pericarditis, pericardial effusion, and cardiac tamponade, with acute pericarditis being the most prevalent. These conditions significantly contribute to mortality rates. Therefore, this article aimed to analyze mortality trends in the Brazilian population based on age and sex, shedding light on the impact of pericardial diseases on public health outcomes. Methods  This is a retrospective time-series analysis of pericardial disease mortality rates in Brazil (2000-2022). Data was obtained from the Department of Informatics of the Unified Health System (DATASUS), and the 10th edition of the International Classification of Diseases (ICD-10) codes: I30, I31, and I32 were included for analysis. We gathered population and demographic data categorized by age range and sex from the Brazilian Institute of Geography and Statistics (IBGE). Subsequently, we computed the age-standardized mortality rate per 100,000 individuals and assessed the annual percentage changes (APCs) and average annual percentage changes (AAPCs) using joinpoint regression, along with their corresponding 95% confidence intervals (CIs). Results  In terms of mortality trends based on sex, overall mortality rates remained stable for males and combined sexes over the study period. However, there was a notable increase in mortality rates among females (AAPC=1.18), particularly between 2020 and 2022, with a significant APC of 27.55. Analyzing pericardial diseases across different age groups (20 to 80 years and above), it wasobserved that mortality rates significantly increased in the 70-79 and 80 years and above age groups throughout the study period (AAPC=1.0339 and AAPC=3.4587, respectively). These two age groups experienced the highest significant rise in mortality between 2020 and 2022. Other age groups did not exhibit a significant change in AAPC. Conclusions  This comprehensive analysis spanning two decades (2000-2022), examined the mortality trends of pericardial diseases in Brazil and revealed relative stability overall. Males exhibited an overall higher mortality number due to pericardial diseases; however, females showed the most significant increase in mortality trend throughout the whole period. In the first segment (2000-2015), mortality rose across all cohorts, which was attributed to substandard healthcare facilities and infectious diseases like tuberculosis. The second segment (2016-2020) saw a decline in mortality, likely due to improved healthcare, particularly the increased availability of echocardiograms. However, the third segment (2020-2022) witnessed a sharp rise in mortality, coinciding with the COVID-19 pandemic, with post-COVID-19 symptoms, particularly pericarditis. Pericarditis-related death rates declined compared to pericardial effusion, and mortality rates correlated directly with age, with older cohorts experiencing higher mortality due to increased comorbidities, and decline in health and immunocompetency.

Bacterial Pericarditis With Underlying Severe Aortic Stenosis and Myelodysplastic Syndrome.

We herein describe a case of a 79-year-old male who presented with severe aortic stenosis with myelodysplastic syndrome. He was hospitalized to undergo presurgical evaluation and puncture of pericardiocentesis. After the placement of pericardial drainage, he developed bacterial pericarditis. His heart failure had worsened due to new onset of atrial fibrillation and pericardial constriction. Methicillin-sensitive Staphylococcus aureus was identified as the pathogen from the puncture. A pericardial windowing was performed so that his circulatory status was stabilized. An aortic valve replacement as well as resection of pericardial fibrosis was finally performed, and he was discharged without any sequela.

Assessment of Radiation Induced Pneumonitis and Pericarditis in Patients Undergoing Breast Conservative Treatment Using Hypofractionated Simultaneous Integrated Boost Technique.

INTRODUCTION: To determine the proportion of radiationinduced pneumonitis and pericarditis in patients who have received Hypo-fractionated Radiation along with simultaneous integrated boost technique after breast conservative surgery using a prospective observational study from a tertiary hospital. MATERIALS & METHODS: The incidence of radiationinduced pneumonitis and pericarditis was evaluated in all adult patients with biopsy-proven early-stage unilateral breast cancer who underwent breast-conserving surgery followed by hypo-fractionated radiation with a simultaneous integrated boost technique. Baseline assessments including a six-minute walk test, highresolution computed tomography (HRCT), pulmonary function tests (PFTs), electrocardiography (ECG) and echocardiography (ECHO) were performed. At three months post-radiation treatment, patients underwent follow-up assessments with a six-minute walk test, ECG and ECHO. At six months post-radiation treatment, patients underwent further assessments with a six-minute walk test, ECG, ECHO, PFTs, and HRCT of the thorax. Data analysis was performed using SPSS version 19. RESULTS: Our study investigated the incidence of acute radiation-induced pneumonitis and pericarditis in patients treated with hypofractionated VMAT-SIB technique in 20 eligible early breast cancer patients. The study found that the technique is feasible and achieves encouraging dosimetric parameters, including well achieved ipsilateral lung and heart doses. The reduced treatment time of 3-4 weeks compared to the previous 6-7 weeks with sequential boost was also found to be desirable in resource-constrained settings. The incidence of acute radiation pneumonitis and pericarditis was acceptable and comparable to existing data, with 90% of patients experiencing grade 1 radiation pneumonitis according to CTCAE v5.0. Post-treatment pulmonary function tests showed significant changes, particularly in patients who had received neoadjuvant chemotherapy and nodal irradiation. The six-minute walk test and Borg scale also showed a significant positive correlation with pulmonary function tests. There was no significant pericarditis during the follow-up. The study proposes that the hypofractionated radiotherapy using VMAT-SIB is a suitable alternative to conventional fractionation, with acceptable acute toxicities, but longer follow-up is required to assess the impact on late toxicities. CONCLUSION: Our research has shown that hypofractionated adjuvant radiotherapy with SIB is a safe and feasible treatment for patients with early breast cancer. This treatment method doesn't pose any significant short-term risks to the lungs or heart, and the SIB technique provides better coverage, conformity and sparing of organs at risk. Additionally, patients have reported positive cosmetic outcomes with this treatment. However, to make more accurate conclusions, we need to conduct further studies with larger sample sizes and longer follow-up periods to evaluate the potential longterm side effects of this treatment using VMAT in whole breast radiation.

Outcomes and Risk Factors Associated with Pericardiectomy in Patients with Constrictive Pericarditis: A Retrospective Study from China.

PURPOSE: Pericardiectomy is the definitive treatment option for constrictive pericarditis and is associated with a high prevalence of morbidity and mortality. However, information on the associated outcomes and risk factors is limited. We aimed to report the mid-term outcomes of pericardiectomy from a single center in China. METHODS: We retrospectively reviewed data collected from patients who underwent pericardiectomy at our institute from April 2018 to January 2023. RESULTS: Eighty-six consecutive patients (average age, 46.1 ± 14.7 years; 68.6 men) underwent pericardiectomy through midline sternotomy. The most common etiology was idiopathic (n = 60, 69.8%), and 82 patients (95.3%) were in the New York Heart Association function class III/IV. In all, 32 (37.2%) patients underwent redo sternotomies, 36 (41.9%) underwent a concomitant procedure, and 39 (45.3%) required cardiopulmonary bypass. The 30-day mortality rate was 5.8%, and the 1-year and 5-year survival rates were 88.3% and 83.5%, respectively. Multivariable analysis revealed that preoperative mitral insufficiency (MI) ≥moderate (hazard ratio [HR], 6.435; 95% confidence interval [CI] [1.655-25.009]; p = 0.007) and partial pericardiectomy (HR, 11.410; 95% CI [3.052-42.663]; p = 0.000) were associated with increased 5-year mortality. CONCLUSION: Pericardiectomy remains a safe operation for constrictive pericarditis with optimal mid-term outcomes.

A Case of Tubercular Pericardial Tamponade With Anti-tuberculosis Treatment-Induced Hepatitis.

Pericarditis can be a common complication of tuberculosis (TB) in developing countries like India. It is associated with fever, fatigue, and weight loss and can often be accompanied by shortness of breath and chest pain. Other common causes of pericardial effusion include malignancy, renal failure, autoimmune disease, and viral and bacterial infections. When the pericardial fluid is bloody, TB is likely to be present in developing countries. It can often get complicated with cardiac tamponade, which has a high mortality rate. We present a case of a 55-year-old female with no co-morbidities who presented with shortness of breath, fatigue for two weeks, and chest pain for one week. She had no history of fever, chills, or rigour, and no history of TB contact. Clinical examination revealed low blood pressure with raised jugular venous pressure (JVP). Her electrocardiography (ECG) showed sinus tachycardia with a low-voltage complex. Echocardiography (ECHO) showed a large pericardial effusion, compromising ventricular function. We performed pericardiocentesis, drained 1.4 L of bloody fluid, and sent the pericardial fluid for analysis. Pericardial fluid adenosine deaminase (ADA) and cartridge-based nucleic acid amplification testing (CBNAAT) came positive for Mycobacterium TB. The patient was started on anti-tubercular treatment (ATT) and broad-spectrum antibiotics with drainage. Other routine investigations and autoimmune immune workups were normal. The patient also developed ATT-induced hepatitis, for which modified ATT was initiated. The patient improved clinically and symptomatically, was discharged, and was advised to follow up in the outpatient department (OPD).

Constrictive physiology is not present in all dogs with idiopathic chylothorax.

OBJECTIVE: To determine whether subtotal pericardectomy affects recurrence and long-term outcomes in dogs with idiopathic chylothorax (IC). ANIMALS: 12 client-owned dogs diagnosed with IC between July 26, 2016, and March 23, 2023. METHODS: The diagnosis of constrictive physiology (CP) was established with cardiac catheterization and defined as elevated and equal diastolic pressures in all 4 cardiac chambers. Dogs were then entered into the constrictive physiology (CP) group or non-CP (NCP) group. All dogs received at least a thoracic duct ligation (TDL). The dogs in the CP group had a subtotal pericardectomy performed in addition to TDL. Repeated surgical interventions, recurrence, long-term outcomes, and survival times were recorded. RESULTS: 8 dogs were entered into the CP group and underwent TDL and subtotal pericardectomy. Four dogs were entered in the NCP group and underwent only a TDL. Four dogs in the CP group and 1 in the NCP group required multiple surgeries for recurrent chylothorax. The 1-, 2-, and 3-year disease-free rates were, respectively, 100%, 100%, and 50% for the NCP group and 87.5%, 72.9%, and 72.9% for the CP group (P = .935). The 1-, 2-, and 3-year survival rates were, respectively, 100%, 100%, and 100% for the NCP group and 87.5%, 72.9%, and 72.9% for the CP group (P = .317). CLINICAL RELEVANCE: Constrictive physiology should be evaluated by cardiac catheterization before surgical treatment of IC in dogs. If CP is not diagnosed, subtotal pericardectomy may not be required.

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.