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10/30/25

ABSTRACT

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of hematologic malignancies. Limited studies have shown an association between treatment-limiting arrhythmias and TKI, particularly ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. We sought to comprehensively assess the arrhythmia burden in patients receiving ibrutinib vs non-BTK TKI vs non-TKI therapies.

METHODS: We performed a retrospective analysis of consecutive patients who received long-term cardiac event monitors while on ibrutinib, non-BTK TKIs, or non-TKI therapy for a hematologic malignancy between 2014 and 2022.

RESULTS: One hundred ninety-three patients with hematologic malignancies were included (ibrutinib = 72, non-BTK TKI = 46, non-TKI therapy = 75). The average duration of TKI therapy was 32 months in the ibrutinib group vs 64 months in the non-BTK TKI group (p = 0.003). The ibrutinib group had a higher prevalence of atrial fibrillation (n = 32 [44%]) compared to the non-BTK TKI (n = 7 [15%], p = 0.001) and non-TKI (n = 15 [20%], p = 0.002) groups. Similarly, the prevalence of non-sustained ventricular tachycardia was higher in the ibrutinib group (n = 31, 43%) than the non-BTK TKI (n = 8 [17%], p = 0.004) and non-TKI groups (n = 20 [27%], p = 0.04). TKI therapy was held in 25% (n = 18) of patients on ibrutinib vs 4% (n = 2) on non-BTK TKIs (p = 0.005) secondary to arrhythmias.

CONCLUSIONS: In this large retrospective analysis of patients with hematologic malignancies, patients receiving ibrutinib had a higher prevalence of atrial and ventricular arrhythmias compared to those receiving other TKI, with a higher rate of treatment interruption due to arrhythmias.

PMID:37256462 | DOI:10.1007/s10840-023-01575-z

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PubMed articles on: Cardio-Oncology

An unusual case of checkpoint-inhibitor-induced pleuropericarditis

J Oncol Pharm Pract. 2023 May 30:10781552231179369. doi: 10.1177/10781552231179369. Online ahead of print.

ABSTRACT

INTRODUCTION: Pembrolizumab is an immune checkpoint inhibitor that promotes effector T-cell functions on malignant cells by binding to programmed cell death protein 1 (PD-1). Pembrolizumab is well tolerated in most cases with an adverse event profile consisting mainly of pruritus, fatigue, and anorexia. Cardiotoxicity comprises 1% of the total adverse events.

CASE REPORT: We present a case of a 64-year-old female with non-small cell lung cancer (NSCLC) who developed pleuropericarditis following pembrolizumab therapy.

MANAGEMENT & OUTCOME: The patient was successfully managed with colchicine, furosemide, and timely initiation of methylprednisolone with the improvement of her symptoms. The decision to discontinue pembrolizumab was made, and six months after this intervention, the patient has remained asymptomatic.

DISCUSSION: Clinicians should recognize these potential immune-mediated adverse effects to provide effective and timely management and optimize patient care.

PMID:37254508 | DOI:10.1177/10781552231179369

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Cardiotoxicity News

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PubMed articles on: Cancer & VTE/PE

Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer: A Randomized Clinical Trial

JAMA. 2023 Jun 2. doi: 10.1001/jama.2023.7843. Online ahead of print.

ABSTRACT

IMPORTANCE: In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain.

OBJECTIVE: To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event.

DESIGN, SETTING, AND PARTICIPANTS: Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020.

INTERVENTION: Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses.

MAIN OUTCOMES AND MEASURES: The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin.

RESULTS: Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death.

CONCLUSIONS AND RELEVANCE: Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02744092.

PMID:37266947 | DOI:10.1001/jama.2023.7843

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PubMed articles on: Cancer & VTE/PE

Cerebral infarction related to nonbacterial thrombotic endocarditis in a middle-aged woman with uterine adenomyosis: A case report

Medicine (Baltimore). 2023 Jun 2;102(22):e33871. doi: 10.1097/MD.0000000000033871.

ABSTRACT

RATIONALE: Few isolated case reports and case series have reported arterial and venous thromboembolism related to adenomyosis; however, the underlying mechanism remains unclear.

PATIENT CONCERNS: A 47-year-old woman presented with dizziness, nausea, vomiting, and loss of consciousness after red blood cell transfusion. She was being treated for menorrhagia and severe anemia.

DIAGNOSES: Magnetic resonance imaging showed multiple infarctions in right cerebellum and bilateral frontal, parietal, and occipital lobes. Echocardiography performed during the evaluation for the source of emboli revealed multiple echogenic masses on the tricuspid aortic valve. There was no evidence of infection, and the masses on the aortic valve were diagnosed as nonbacterial thrombotic endocarditis. The levels of autoimmune antibodies and tumor markers except for carbohydrate antigen 19-9 and cancer antigen 125 were within the normal range. Uterine ultrasound showed a large adenomyosis. The patient was diagnosed with multiple cerebral and cerebellar infarctions due to nonbacterial thrombotic endocarditis, and hormone therapy and anticoagulation with warfarin were initiated.

INTERVENTIONS: The patient did not develop recurrent infarction during anticoagulant therapy; however, menorrhagia worsened requiring total hysterectomy.

OUTCOMES: The patient did not experience recurrent infarction despite the absence of anticoagulant therapy during the 3-year follow-up period.

LESSONS: The present case adds to the limited number of previously reported cases and supports that, albeit rare, adenomyosis can be associated with embolic infarction and suggests that nonbacterial thrombotic endocarditis might be the link between adenomyosis and embolic infarction.

PMID:37266639 | DOI:10.1097/MD.0000000000033871

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PubMed articles on: Cancer & VTE/PE

Body Mass Index (BMI) Related Morbidity with Thyroid Surgery

Laryngoscope. 2023 Jun 2. doi: 10.1002/lary.30789. Online ahead of print.

ABSTRACT

OBJECTIVES: The increase in incidence of thyroid cancer correlates with strict increases in body mass index (BMI) and obesity in the United States. Thyroid hormone dysregulation has been shown to precipitate circulatory volume, peripheral resistance, cardiac rhythm, and even cardiac muscle health. Theoretically, thyroid surgery could precipitate injury to the cardiopulmonary system.

METHODS: The American College of Surgery National Quality Improvement Program database was queried for thyroidectomy cases in the 2007-2020 Participant User files. Continuous and categorical associations between BMI and cardiopulmonary complications were investigated as reported in the database.

RESULTS: The query resulted 186,095 cases of thyroidectomy procedures in which the mean age was 51.3 years and sample was 79.3% female. No correlation was evident in univariate and multivariate analyses between BMI and the incidence of postoperative stroke or myocardial infarction. The incidence of complications was extremely low. However, risk of deep venous thrombosis correlated with BMI in the categorical, univariate, and multivariate (OR 1.036, CI 1.014-1.057, p < 0.01) regression analysis. Additionally, increased BMI was associated with increased risk of pulmonary embolism (PE) (OR 1.050 (1.030, 1.069), p < 0.01), re-intubation (OR 1.012 (1.002, 1.023), p = 0.02), and prolonged intubation (OR 1.031 (1.017, 1.045), p < 0.01).

CONCLUSION: Despite the rarity of cardiopulmonary complications during thyroid surgery, patients with very high BMI carry a significant risk of deep venous thrombosis, PE, and prolonged intubation.

LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2023.

PMID:37265205 | DOI:10.1002/lary.30789

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PubMed articles on: Cancer & VTE/PE

Prevention of venous thromboembolism in patients with cancer

BMJ. 2023 Jun 1;381:e072715. doi: 10.1136/bmj-2022-072715.

ABSTRACT

Venous thromboembolism (VTE) is a major cause of both morbidity and mortality in patients with cancer. Venous thromboembolism, which includes both deep vein thrombosis and pulmonary embolism, affects a sizable portion of patients with malignancy and can have potentially life threatening complications. Accurate assessment of risk as well as diagnosis and treatment of this process is paramount to preventing death in this high risk population. Various risk models predictive of venous thromboembolism in patients with cancer have been developed, and knowledge of these rubrics is essential for the treating oncologist. Subgroups of particular interest are inpatients receiving chemotherapy, postoperative patients after surgical debulking, and patients undergoing radiotherapy. Numerous newer drugs have become available for the prevention of venous thromboembolism in patients with cancer who are at high risk of developing the disease. These include the class of drugs called direct oral anticoagulants, (DOACs) which do not require the same monitoring that other modalities have previously required and are taken by mouth, preventing the discomfort associated with subcutaneous strategies. The appropriate risk stratification and intervention to prevent venous thromboembolism are vital to the treatment of patients with cancer.

PMID:37263632 | DOI:10.1136/bmj-2022-072715

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PubMed articles on: Cancer & VTE/PE

Accuracy of the Physicians' Intuitive Risk Estimation in the Diagnostic Management of Pulmonary Embolism: An Individual Patient Data Meta-Analysis

J Thromb Haemost. 2023 May 30:S1538-7836(23)00438-5. doi: 10.1016/j.jtha.2023.05.023. Online ahead of print.

ABSTRACT

BACKGROUND: In patients clinically suspected of pulmonary embolism (PE), physicians often rely on an intuitive estimation ('gestalt') of PE presence. Although shown to be predictive, gestalt is criticized for its assumed variation across physicians and lack of standardization.

OBJECTIVES: To assess the diagnostic accuracy of gestalt in diagnosing PE and gain insight into its possible variation.

METHODS: We performed an individual patient data meta-analysis including patients suspected of PE. The primary outcome was the diagnostic accuracy of gestalt for diagnosing PE, quantified as a risk ratio (RR) between gestalt and PE from a two-stage random-effect log-binomial meta-analysis regression as well as gestalts' sensitivity and specificity. Variability of these measures was explored across different healthcare settings, publication period, PE prevalence, patient subgroups (sex, heart failure, chronic lung disease, and items of the Wells score other than gestalt), and age.

RESULTS: We analysed 20,770 patients suspected of PE from 16 original studies. The prevalence of PE in patients with and without a positive gestalt was 28.8% versus 9.1%, respectively. The overall RR was 3.02 (95%CI 2.35, 3.87) and overall sensitivity and specificity were 74% (95%CI 68-79%) and 61% (95%CI 53-68%). Although variation was observed across individual studies (I2-90.63%), diagnostic accuracy was consistent across all subgroups and healthcare settings.

CONCLUSIONS: A positive gestalt was associated with a threefold increased risk of PE in suspected patients. Although variation was observed across studies, the RR of gestalt was similar across prespecified subgroups and healthcare settings, exemplifying its diagnostic value for all patients suspected of PE.

PMID:37263381 | DOI:10.1016/j.jtha.2023.05.023

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PubMed articles on: Cancer & VTE/PE

Thrombosis in the Neonatal Intensive Care Unit

Neoreviews. 2023 Jun 1;24(6):e356-e369. doi: 10.1542/neo.24-6-e356.

ABSTRACT

Neonates, particularly critically ill and premature infants, have one of the highest risks of thromboembolic complications, particularly venous thromboembolism (VTE), in the pediatric population. Recent data suggest that the incidence of VTE has significantly increased in neonates over the last few decades. Critically ill and premature infants exhibit multiple risk factors that place them at a high risk for thromboembolic events including developmental hemostasis, propensity to infections, and frequent need for central venous access. The clinical presentation, diagnostic modalities, and treatment strategies for thromboembolic complications in neonates vary based on several factors, including the etiology of the thromboembolic event, the anatomic site affected, and the patient's underlying comorbidities. Although guidelines for management are available, they are mostly based on consensus recommendations and on extrapolation from adult data due to a lack of high-quality data in the neonatal population. Current guidelines recommend anticoagulation for specific scenarios. More studies are necessary to elucidate optimal management strategies for newborns with thromboembolic complications.

PMID:37258498 | DOI:10.1542/neo.24-6-e356