Minoxidil-associated pericardial effusion and impending tamponade.

ABSTRACT: A patient with a large pericardial effusion and impending tamponade exhibited clinical improvement with urgent pericardiocentesis. Further workup ruled minoxidil to be the likely cause of the effusion. After discontinuation of minoxidil, the effusion did not recur.

Pericardial effusion and systemic capillary leak syndrome late post-SARS-CoV-2 vaccination.

We report an interesting case of pericardial effusion associated with idiopathic systemic capillary leak syndrome (ISCLS) following administration of SARS-CoV-2 vaccine. This patient initially presented with dyspnoea and chest pain, with non-pitting oedema and clear lung fields. The diagnosis of ISCLS was made based on the clinical syndrome and laboratory evidence of polycythaemia and hypoalbuminaemia. An enlarging pericardial effusion was diagnosed on transthoracic echocardiogram. Daily point-of-care ultrasound (POCUS)-guided volume management and serial transthoracic echocardiograms contributed to avoidance of refractory shock, cardiac tamponade and critical care admission.

Fluid retention-associated adverse events in patients treated with BCR::ABL1 inhibitors based on FDA Adverse Event Reporting System (FAERS): a retrospective pharmacovigilance study.

OBJECTIVES: This study aimed to conduct a thorough analysis of fluid retention-associated adverse events (AEs) associated with BCR::ABL inhibitors. DESIGN: A retrospective pharmacovigilance study. SETTING: Food and Drug Administration Adverse Event Reporting System (FAERS) database for BCR::ABL inhibitors was searched from 1 January 2004 to 30 September 2021. MAIN OUTCOME MEASURES: Reporting OR (ROR) and 95% CI were used to detect the signals. ROR was calculated by dividing the odds of fluid retention event reporting for the target drug by the odds of fluid retention event reporting for all other drugs. The signal was considered positive if the lower limit of 95% CI of ROR was >1. The analysis was run only considering coupled fluid retention events/BCR::ABL inhibitors with at least three cases. RESULTS: A total of 97 823 reports were identified in FAERS. Imatinib had the most fluid retention signals, followed by dasatinib and nilotinib, while bosutinib and ponatinib had fewer signals. Periorbital oedema (ROR=24.931, 95% CI 22.404 to 27.743), chylothorax (ROR=161.427, 95% CI 125.835 to 207.085), nipple swelling (ROR=48.796, 95% CI 26.270 to 90.636), chylothorax (ROR=35.798, 95% CI 14.791 to 86.642) and gallbladder oedema (ROR=77.996, 95% CI 38.286 to 158.893) were the strongest signals detected for imatinib, dasatinib, nilotinib, bosutinib and ponatinib, respectively. Pleural effusion, pericardial effusion and pulmonary oedema were detected for all BCR::ABL inhibitors, with dasatinib having the highest RORs for pleural effusion (ROR=37.424, 95% CI 35.715 to 39.216), pericardial effusion (ROR=14.146, 95% CI 12.649 to 15.819) and pulmonary oedema (ROR=11.217, 95% CI 10.303 to 12.213). Patients aged ≥65 years using dasatinib, imatinib, nilotinib or bosutinib had higher RORs for pleural effusion, pericardial effusion and pulmonary oedema. Patients aged ≥65 years and females using imatinib had higher RORs for periorbital oedema, generalised oedema and face oedema. CONCLUSIONS: This pharmacovigilance study serves as a clinical reminder to physicians to be more vigilant for fluid retention-associated AEs with BCR::ABL inhibitors.

Peripheral Insulin Edema and Pericardial Effusion in a 12-Year-Old Newly Diagnosed Girl with Type 1 Diabetes.

Introduction: Insulin induced edema (IIE) is a rare condition, usually found in newly diagnosed diabetes patients, either after insulin treatment initiation or after dose increment. It is a self-limited process, rarely associated with serosal effusions. Teenage girls with type 1 diabetes (T1DM) are most commonly affected. Patient and Methods: A 12-year-old girl was diagnosed with ketoacidosis (DKA). Seven days after initiation of the insulin treatment, at a stable total daily dose of insulin (TDDI) of 0.55 IU/kg, she came with two kilograms weight gain in only two days and edema of the feet and calves. Ultrasound of the heart found a 7 mm pericardial effusion. The diagnostic workout included clinical examination, biochemical, hormonal, allergen analyses and imaging which excluded other known causes of swelling. Conclusions: We describe an adolescent girl with newly diagnosed T1DM and a rare association of peripheral insulin-induced edema and pericardial effusion. Short-term diuretic treatment and salt restriction resolved this rare complication of insulin treatment.

Evaluation of Cardiac Adverse Events with Nivolumab Using a Japanese Real-World Database.

BACKGROUND: Nivolumab has been used for the treatment of various types of cancers and has achieved improvements in overall survival. However, nivolumab can cause a variety of adverse events (AEs). Among these, cardiac-specific AEs have received little attention in clinical trials, despite their life-threatening potential. OBJECTIVE: The present study aimed to determine the risk of nivolumab-induced cardiac AEs, time to onset, incidence rates, and post hoc outcomes using the Japanese Adverse Drug Event Report database. METHODS: We analyzed data for the period between April 2004 and March 2021. Data on cardiac AEs were extracted and relative risk of AEs was estimated using the reporting odds ratio (ROR). RESULTS: We analyzed 1,772,494 reports and identified 18,721 reports of AEs caused by nivolumab. Of these, 409 reports involved cardiac AEs. Signals were detected for four cardiac AEs: myocarditis; pericardial effusion; pericarditis; and immune-mediated myocarditis. Among these, myocarditis was the most frequently reported (35.0%) and included fatal cases. A histogram of times to onset showed nivolumab-associated AEs occurring 41-127 days after starting administration, with outlier cases of myocarditis or pericardial effusion occurring after more than one year, both with catastrophic consequences. CONCLUSION: This study focused on cardiac AEs caused by nivolumab as post-marketing AEs. Myocarditis and pericardial effusion have been associated with some fatal cases after administration of nivolumab. Patients should be monitored for signs of onset for these AEs, not only at the start of administration, but also over an extended period after nivolumab administration.

Chylous pericardial effusion with cardiac tamponade in a child treated with imatinib.

Chylous pericardial effusions are extremely rare outside of thoracic and cardiac surgery patients. We report the case of an 8-year-old girl with history of recurrent benign giant cell granulomas who developed a large chylous pericardial effusion with cardiac tamponade soon after beginning therapy with imatinib. In this article, we discuss the presentation, diagnosis, and management and review the published literature of this rarely reported side effect of this medication.

Lenvatinib rechallenge in a patient with advanced thymic carcinoma: A case report.

Advanced thymic carcinomas have limited treatment options. Recently, lenvatinib was approved for advanced thymic carcinoma treatment. However, the clinical benefit of lenvatinib re-administration in patients with advanced thymic carcinoma who developed prior lenvatinib treatment resistance (lenvatinib rechallenge) remains unclear. Here, we present a case treated with lenvatinib rechallenge for advanced thymic carcinoma who was previously treated with lenvatinib as the second-line treatment followed by multiple cytotoxic agents. Disease control rapidly deteriorated after the eighth line of treatment because of uncontrollable right pleural and pericardial effusion, which required repeated thoracic and pericardial drainage. Shortly after lenvatinib re-administration, rapid pleural and pericardial effusion reduction was observed. Thereafter, the patient achieved sustained clinical response with good pleural and pericardial effusion control for approximately 7 months. Our case might suggest lenvatinib rechallenge as a treatment option for patients with advanced thymic carcinoma, especially those with poor pleural and pericardial effusion control.

Pericardial effusion with pembrolizumab.

INTRODUCTION: The treatment of non-small cell lung cancer (NSCLC) has profoundly changed on account of the arrival of new therapies, like immunotherapy. Within this group of drugs, those aimed at the programmed cell death-1 or programmed cell death ligand-1(PD1/PDL-1) are very relevant, for example, Pembrolizumab. Although its adverse reactions are generally mild and well tolerated, it has been associated with certain immune-related adverse events (IrAEs) than can be serious and affect any organ. CASE REPORT: A 62-year-old woman diagnosed with stage IV NSCLC with a single bone metastasis and PD-L1 expression of 60% started treatment with cisplatin-pemetrexed-pembrolizumab, and maintenance with pembrolizumab. MANAGEMENT AND OUTCOME: The patient attended the ER with pericardial effusion that was assumed to be a Pembrolizumab IrAE and was managed with corticosteroids. The patient fully recovered but immunotherapy was not reintroduced due to the severity of the AE. DISCUSSION: The cardiovascular system is among the least affected organs by immunotoxicity, with an incidence between 0.09-0.6%. However, some authors suspect the incidence is underestimated. Median time to onset is highly variable, ranging from 6 weeks since the first dose to 2 years after discontinuation of the treatment. There are not guidelines on the most effective management of the IrAEs, but according to the pharmaceutical reference, corticosteroids should be initiated followed by a progressive reduction. If no response is obtained, another immunosuppressive agent should be added. The determination to restart immunotherapy depends on the severity of the adverse reaction, the availability of other alternative treatments, and the cancer response.

Azacitidine-induced massive pericardial effusion in a child with myelodysplastic syndrome.

INTRODUCTION: Pericardial effusions are rare yet potentially fatal conditions in children. Azacitidine is a DNA-hypomethylating agent used in the treatment of myelodysplastic syndrome. Although seldomly described in adults, no cases of azacitidine-induced pericardial effusion have been reported in children. CASE REPORT: A 7-year-old boy with myelodysplastic syndrome presented with a large pericardial effusion with risk for cardiac tamponade after his first azacitidine cycle. MANAGEMENT & OUTCOME: The patient was admitted to a pediatric ICU, antibiotic and steroid therapy were initiated. Pericardiocentesis was done due to hemodynamic instability. Serum and pericardial fluid complementary evaluation excluded infectious and malignant causes. The pericardial effusion did not reappear and additional pleural and ascitic slight effusions responded well to diuretics. Follow-up azacitidine cycles were administered by tapering daily dosages and using adjunctive steroid therapy, with no additional adverse events. DISCUSSION: We report the first pediatric case of large pericardial effusion secondary to azacitidine therapy in a child with MDS. This adverse reaction has not been described in pediatric patients, in which this therapeutic option has been increasingly used. We seek to raise awareness on the potential life-threatening cardiotoxicity of azacitidine in pediatric patients.

Non hemorrhagic pericardial effusion from ibrutinib In a patient without comorbidities.

INTRODUCTION: The most common kind of leukemia in adults is chronic lymphocytic leukemia (CLL). CLL is treated with ibrutinib. During the course of ibrutinib therapy, bleeding and cardiac arrhythmias may occur. Non-hemorrhagic adverse events are extremely infrequent in individuals using ibrutinib. CASE REPORT: A 64 year-old man was diagnosed with CLL in June 2016. He was treated with 6 courses of FCR, he stayed in remission for 3 years and then relapsed. He achieved partial remission after two months of therapy with ibrutinib. The patient was admitted to the hospital with fever and shortness of breath. Pericardial tamponade and effusion was diagnosed during his evaluation. MANAGEMENT & OUTCOME: Non-hemorrhagic exudative effusion was drained by pericardiocentesis and a pericardial catheter was inserted to drain pericardial effusion. In all pleural and pericardial effusion samples, pathological and flow cytometric examination revealed no atypical malignant cells for malignancy, including CLL. Infections, both bacterial and viral, were also undetectable in the samples, as were rheumatological markers of collagen vascular disease. Ibrutinib therapy was discontinued. The pericardial effusion and tamponade were linked to ibrutinib treatment after evaluating the adverse drug reaction probability scale with a total score of 6. Colchicine was administered to reduce the pericardial effusion. The catheter was removed; pericardial effusion did not reoccur during follow up visits. DISCUSSION: Serious adverse events of ibrutinib are seen when treating CLL patients. This group of individuals should be closely monitored for potentially serious complications such as pericardial effusion and cardiac tamponade.

Acute severe pericarditis secondary to rodenticide intoxication in a dog.

Background: Pericardial effusions are well described in dogs; however, their association with rodenticide intoxication in the canine population is not widely described. Case Description: An adult mixed-breed dog was presented for 1-day history of anorexia and cough. Thoracic radiographs revealed moderate generalized cardiomegaly with globoid-shaped cardiac silhouette and mild bilateral pleural effusion. Echocardiography showed mild tamponating pericardial effusion and diffuse severe thickened pericardium. Compete blood count and blood chemistry at presentation were not specific. A coagulation profile was completed and showed severe prolongation of prothrombin time and partial thromboplastin time. Intravenous therapy with vitamin K was started at 5 mg/kg BID and on follow-up echocardiography performed 12 hours later there was evidence of complete regression of the pericardial thickening and pericardial effusion. Conclusion: To the authors' knowledge, this is the first case report describing severe pericardial thickening, constrictive pericarditis, and cardiac tamponade secondary to spontaneous anticoagulant-induced hemopericardium in dogs.

Hemopericardium in the Setting of Direct Oral Anticoagulant Use: An Updated Systematic Review.

BACKGROUND: Spontaneous hemopericardium, associated with direct oral anticoagulant (DOAC) use, is one of the uncommon complications with high morbidity that has not been extensively studied We aimed to determine demographic characteristics, clinical features, lab evaluation, management, and outcomes of the studies focusing on hemopericardium as a DOAC use. METHODS: PubMed, Web of Science, Google Scholar, and CINAHL databases were searched for relevant articles using MeSH key-words and imported into referencing/review software. The data regarding demographics, clinical characteristics, cardiac investigations, and management were analyzed in IBM Statistics SPSS 21. t-Test and Chi-square test were used. A P score of <0.05 was considered statistically significant. RESULTS: After literature search, a total of 41 articles were selected for analysis. The mean age of the patients was 70.09 ± 11.06 years (p < 0.05); the majority of them were males (58.5%). Most of the patients presented with shortness of breath (75.2%) and had more than 3 co-morbid conditions (43.9%). The most frequently used anticoagulant was rivaroxaban (15/41; 36.6%); the common indication being arrhythmia (78.0%). CYP4503A4/P-Gp inhibitors (22.2%) were commonly used by the patients. Majority of the cases had a favorable outcome (95.1%). Pericardial tamponade was noted in 31/41 cases. Pericardiocentesis was performed in 37/41 cases. CONCLUSIONS: Hemopericardium from DOAC use has a favorable outcome but requires urgent pericardiocentesis. However, long term mortality, monitoring of DOAC activity, and drug-drug interactions have not been widely studied.

The Efficacy, Safety, and Side Effects of Intrapericardial Triamcinolone Treatment in Children with Post-surgical Pericardial Effusion: A Case Series.

Intrapericardial triamcinolone can be used to treat chronic pericardial effusion (PE) in adults; however, pediatric data are lacking. In this case series we aim to evaluate the efficacy, safety, and side effects of intrapericardial triamcinolone in children with PE. The incidence and treatment of post-surgical PE from 2009 to 2019 were determined using the institutional surgical database and electronic patient records. Furthermore, a retrospective analysis of efficacy, safety, and side effects of intrapericardial triamcinolone treatment for chronic post-surgical PE was performed. The incidence of postoperative PE requiring treatment was highest after atrial septal defect (ASD) closure when compared to other types of cardiac surgery (9.7% vs 4.3%). Intrapericardial treatment with triamcinolone resolved pericardial effusion in 3 out of 4 patients. All patients developed significant systemic side effects. Surgical ASD closure is associated with an increased risk of development of PE requiring treatment. Intrapericardial triamcinolone is an effective treatment for chronic postoperative PE in children, but is always associated with significant systemic side effects. Close monitoring and treatment of adrenal insufficiency are mandatory in these cases.

Immunotherapy related pericardial effusion on chest CT.

BACKGROUND: Immunotherapy has become a critical class of anticancer therapy in recent years, functioning by releasing brakes on the immune system that ultimately results in immune cell activation which eliminates cancer cells. Immune related adverse events (IRAEs) are a specific type of adverse event described in patients taking checkpoint inhibitor immunotherapy which results from unrestrained immune activation. Immune related pericardial effusion has been described however has not been comprehensively characterized. Here, we present the most extensive report to date detailing this adverse event. METHODS: We queried our medical record system to retrospectively identify patients on checkpoint inhibitor therapy for lung cancer who subsequently developed pericardial effusion. We analyzed the clinical and radiographic characteristics, prior therapies, treatment for the effusion, and outcomes in patients with immune related pericardial effusion and compared them to similar patients with pericardial effusion not attributable to checkpoint inhibitor therapy. RESULTS: Our data demonstrate that most of these pericardial effusions were small and not clinically significant. The majority were successfully treated with steroids or resolved spontaneously. Anti-PD-1 inhibitors were the most common checkpoint inhibitor preceding pericardial effusion, and a significant number of patients who went on to develop IRAE pericardial effusion previously had treatment with carboplatin for their cancer. CONCLUSIONS: These data suggest that IRAE pericardial effusion is not a clinically significant adverse event however it sometimes leads to permanent discontinuation of checkpoint inhibitor therapy which is not necessary.

Late-onset Pleural and Pericardial Effusion as Immune-related Adverse Events after 94 Cycles of Nivolumab.

A 67-year-old man with primary lung adenocarcinoma was hospitalized due to massive bilateral pleural effusion and pericardial effusion after 94 cycles of nivolumab therapy. We were unable to identify the cause of these effusions using blood tests, cytology tests, or bacterial culture of pleural effusion and thoracoscopy. Finally, we administrated corticosteroids, which immediately improved the fluid accumulation. This case may support the introduction of corticosteroids for late-onset pleural and pericardial effusion during immune checkpoint inhibitor (ICI) treatment. However, the safety of rechallenge of ICIs after the improvement of fluid accumulation is controversial.

Trastuzumab-emtansine induced pleural and pericardial effusions.

INTRODUCTION: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate which combine trastuzumab (T), a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), and a cytotoxic molecule derived from maytansine (DM1). CASE REPORT: We report the first case of T-DM1-associated pleural and pericardial effusions three weeks after the second course of T-DM1 in a patient with breast cancer. Drug-induced pleural and pericardial effusions was implicated in the absence of other etiologies. The Naranjo Scale indicated a probable drug-induced adverse reaction.Management & outcome: The patient fully recovered after thoracentesis and discontinuation of T-DM1. The patient has reported no side effect after the sixth course of trastuzumab. DISCUSSION: To our knowledge, this is the first case in the literature of bilateral pleural and pericardial effusions in a patient treated with T-DM1. The successful initiation of treatment with trastuzumab following withdrawal of T-DM1 suggests that emtansine played a role in the development of bilateral pleural and pericardial effusions. We hypothesize that the patient's condition was a result of a local inflammatory reaction to emtansine by direct toxicity.

Pericardial Effusion After Renal Transplantation: Timing and Clinical Characteristics.

BACKGROUND: Pericardial effusion and tamponade have been recognized as potentially serious complications in patients who have undergone renal transplantation. Our study aims to analyze the association between sirolimus and the development of pericardial effusion in renal transplant recipients. METHODS: This is a single-center retrospective study of 585 consecutive patients who underwent renal transplantation between 2005 and 2016. The study included 82 patients (14%) who developed new pericardial effusion after transplantation. Baseline demographics, medical comorbidities, medication use, echocardiographic parameters, and time to occurrence of effusion were assessed. Patients were divided into 2 groups based on timing of effusion development: early onset, ≤4 years after transplantation (51%); and late onset, >4 years after transplantation (49%). We examined the likelihood of immunosuppressant use and timing of effusion development using univariate and multivariate logistic regression analysis. RESULTS: The mean age of the cohort was 55.1 ± 11.5 years, 58.5% were men, 81.7% were white, and mean time from transplantation to the development of effusion was 4 ± 3.1 years. There were no significant differences between the early and late effusion groups in the demographic characteristics and medical comorbidities. However, sirolimus therapy was more common in the late effusion group. Furthermore, after adjusting for comorbidities, sirolimus use was associated with greater risk for developing late-onset effusion, adjusted odds ratio of 3.58 (95% confidence interval 1.25-10.20, P = .017). CONCLUSION: Pericardial effusion is prevalent in renal transplant recipients. In our cohort, treatment with sirolimus was associated with late-onset pericardial effusion. Awareness of pericardial disease in this population is important, and further studies are needed to identify predisposing factors.

Signs of early cardiac tamponade induced by Minoxidil.

Minoxidil is an antihypertensive that works by directly dilating peripheral vessels. This medication is typically reserved for patients with resistant hypertension, whose blood pressure remains above goal despite being on multiple agents. A rare but potentially dangerous side effect of Minoxidil is drug-induced pericardial effusion. Here we report a case of a patient who was taking Minoxidil and subsequently developed a large pericardial effusion, with concerns for impending cardiac tamponade.