ABSTRACT

BACKGROUND: Mediastinal gray zone lymphoma is a newly recognized rare B cell neoplasm, which is challenging in diagnosis and treatment.

CASE PRESENTATION: In the current study, we aimed to report a 25-year-old pregnant woman at 25 weeks of gestation who presented with chronic cough and progressive shortness of breath, hypotension, tachycardia, and tachypnea. A large circumferential pericardial effusion with compressive effect on the right atrium and right ventricle and a large extracardiac mass with external pressure to mediastinal structures were seen on trans thoracic echocardiography. The emergency pericardiocentesis was performed with the diagnosis of cardiac tamponade. Also, CMR revealed a huge heterogeneous anterior mediastinal mass, and the pathology and the immunohistochemistry of the mass biopsy revealed gray zone lymphoma with positive CD3, CD20, CD30, CD45, PAX5, and negative CD15 expression. Three courses of chemotherapy with the CHOP regimen were performed with an acceptable response every three weeks before delivery. A caesarian section was performed at 37 weeks without any problem for the patient and fetus, and chemotherapy will be started three weeks after delivery.

CONCLUSION: Cardiac tamponade as an emergency condition occurred in this pregnant patient by malignant pericardial effusion and mediastinal mass pressure. Accurate diagnosis and on time interventions caused a significant improvement and a successful delivery.

PMID:37259152 | PMC:PMC10230740 | DOI:10.1186/s40959-023-00173-2

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PubMed articles on: Cardio-Oncology

Morbidity and mortality of patients with diabetic neuropathy treated with pathogenetically oriented alpha-lipoic acid versus symptomatic pharmacotherapies - a nationwide database analysis from Hungary

Diabetes Res Clin Pract. 2023 May 29:110734. doi: 10.1016/j.diabres.2023.110734. Online ahead of print.

ABSTRACT

AIMS: Diabetic neuropathy is associated with increased risk of morbidity and all-cause mortality. It is unclear whether these outcomes differ in patients with diabetic neuropathy treated with pathogenetically oriented vs symptomatic pharmacotherapies.

METHODS: We performed a retrospective (2009-2019) database analysis of patients treated with pathogenetically oriented alpha-lipoic acid (ALA) or symptomatic pharmacotherapies for diabetic neuropathy. We investigated clinical outcomes in propensity score matched patients in Hungary. Changes in hazard ratios and annualized event rates were assessed and sensitivity analyses performed.

RESULTS: Hazard ratios favored treatment with ALA vs symptomatic pharmacotherapies regarding acute myocardial infarction (HR 0.73, 95%CI: 0.60-0.89, p = 0.0016), stroke (HR 0.71, 95%CI: 0.62-0.82, p<0.0001),<0.0001),<0.0001),

CONCLUSIONS: This retrospective database analysis revealed a lower occurrence of cardio- and cerebrovascular morbidity, cancer events and all-cause mortality in patients with diabetic neuropathy treated with pathogenetically oriented ALA vs symptomatic pharmacotherapies. This hypothesis-generating result requires further investigations.

PMID:37257759 | DOI:10.1016/j.diabres.2023.110734

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PubMed articles on: Cardio-Oncology

AKR1B1 inhibition using NARI-29-an Epalrestat analogue-alleviates Doxorubicin-induced cardiotoxicity via modulating Calcium/CaMKII/MuRF-1 axis

Chem Biol Interact. 2023 May 29:110566. doi: 10.1016/j.cbi.2023.110566. Online ahead of print.

ABSTRACT

The clinical use of doxorubicin (Dox) is narrowed due to its carbonyl reduction to doxorubicinol (Doxol) implicating resistance and cardiotoxicity. Hence, in the present study we have evaluated the cardioprotective effect of AKR1B1 (or aldose reductase, AR) inhibitor NARI-29 (epalrestat (EPS) analogue) and its effect in the Dox-modulated calcium/CaMKII/MuRF1 axis. Initially, the breast cancer patient survival associated with AKR1B1 expression was calculated using Kaplan Meier-plotter (KM-plotter). Further, breast cancer, cardiomyoblast (H9c2), and macrophage (RAW 264.7) cell lines were used to establish the in vitro combination effect of NARI-29 and Dox. To develop the cardiotoxicity model, mice were given Dox 2.5 mg/kg (i.p.), biweekly. The effect of AKR1B1 inhibition using NARI-29 on molecular and cardiac functional changes was measured using echocardiography, fluorescence-imaging, ELISA, immunoblotting, flowcytometry, High-Performance Liquid Chromatography with Fluorescence Detection (HPLC-FD) and cytokine-bead array methods. The bioinformatics data suggested that a high expression of AKR1B1 is associated with significantly low survival of breast cancer patients undergoing chemotherapy; hence, it could be a target for chemo-sensitization and chemo-prevention. Further, in vitro studies showed that AKR1B1 inhibition with NARI-29 has increased the accumulation and sensitized Dox to breast cancer cell lines. However, treatment with NARI-29 has alleviated the Dox-induced toxicity to cardiomyocytes and decreased the secretion of inflammatory cytokines from RAW 264.7 cells. In vivo studies revealed that the NARI-29 (25 and 50 mg/kg) has prevented the functional, histological, biochemical, and molecular alterations induced by Dox treatment. Moreover, we have shown that NARI-29 has prevented the carbonyl reduction of Dox to Doxol in the mouse heart, which reduced the calcium overload, prevented phosphorylation of CaMKII, and reduced the expression of MuRF1 to protect from cardiac injury and apoptosis. Hence in conclusion, AKR1B1 inhibitor NARI-29 could be used as an adjuvant therapeutic agent with Dox to prevent cardiotoxicity and synergize anti-breast cancer activity.

PMID:37257577 | DOI:10.1016/j.cbi.2023.110566

13:02

PubMed articles on: Cardio-Oncology

Natriuretic Peptides, Cardio-Oncology

Anatol J Cardiol. 2023 Jun;27(6):298. doi: 10.14744/AnatolJCardiol.2023.6.

NO ABSTRACT

PMID:37257014 | DOI:10.14744/AnatolJCardiol.2023.6

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PubMed articles on: Cardio-Oncology

Cancer Therapy-Related Pulmonary Hypertension: A Review of Mechanisms and Implications for Clinical Practice

Anatol J Cardiol. 2023 Jun;27(6):299-307. doi: 10.14744/AnatolJCardiol.2023.3013.

ABSTRACT

Cancer therapy-related pulmonary hypertension is a rare yet potentially fatal cardiotoxicity. However, it is a reversible cause of pulmonary hypertension if detected in its early stages. Cancer therapy-related pulmonary hypertension has been encountered in patients using tyrosine kinase inhibitors, particularly dasatinib. However, it is also well known that many agents used in cancer treatment such as alkylating agents, proteasome inhibitors, thoracic radiation exposure, and immune checkpoint inhibitors are particularly associated with pulmonary hypertension evolution. In case that history, symptoms, and clinical findings suggest a potential cancer therapy-related pulmonary hypertension, echocardiography is considered as the initial tool to detect pulmonary hypertension. If the possibility of pulmonary hypertension is high based on echocardiographic data, cancer treatment, as the initial step, should be discontinued due to its potential risks and other causes for pulmonary hypertension should be investigated thoroughly. Right heart catheterization should be the next step to establish the final diagnosis, and medical management, where appropriate, should be started without delay in these patients according to their pulmonary hypertension subgroup. There exists limited information regarding the diagnostic and management strategies of cancer therapy-related pulmonary hypertension in the current guidelines. In this review article, we aim to present current literature data on the mechanisms and management of cancer therapy-related pulmonary hypertension along with its follow-up algorithm in the setting of cardio-oncology practice.

PMID:37257013 | DOI:10.14744/AnatolJCardiol.2023.3013

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PubMed articles on: Cardio-Oncology

Dapagliflozin May Protect Against Doxorubicin-Induced Cardiotoxicity

Anatol J Cardiol. 2023 Jun;27(6):339-347. doi: 10.14744/AnatolJCardiol.2023.2825.

ABSTRACT

BACKGROUND: Doxorubicin is a widely used agent in the treatment of cancer, but the cardiotoxicity associated with this drug limits its potential for use. The cardioprotective effects of dapagliflozin, an antidiabetic drug, have the potential to counteract the cardiotoxic effect of doxorubicin therapy. In our study, we aimed to investigate the protective effect of dapagliflozin from possible doxorubicin-induced cardiotoxicity.

METHODS: A total of 40 male Wistar albino rats were divided into 4 groups consisting of 10 each (control = 10, dapagliflozin = 10, doxorubicin = 10, doxorubicin + dapagliflozin = 10). Meanwhile, doxorubicin and doxorubicin + dapagliflozin groups received a total dose of 15 mg/kg doxorubicin intraperitoneally, dapagliflozin and doxorubicin + dapagliflozin groups were gavaged daily with 10 mg/kg dapagliflozin. At the sixth week of the study, rats were examined by echocardiography and electrocardiogram. Furthermore, histopathological method was used to evaluate the level of cardiotoxicity.

RESULTS: Ejection fraction decreased by 15% in the doxorubicin group, and this reduction in ejection fraction was alleviated in the doxorubicin + dapagliflozin group. In addition, a 65% increase in QRS duration was observed in the group given doxorubicin, while an increase of 7% was observed in doxorubicin + dapagliflozin group. Corrected QT duration increased by 12% in the doxorubicin group, compared to 2% in doxorubicin + dapagliflozin group. Meanwhile, sarco-myolysis, inflammatory cell infiltration, and necrotic changes were examined heavily in doxorubicin group, they were minimal in doxorubicin + dapagliflozin group.

CONCLUSION: Our study showed that dapagliflozin has the potential to reduce the effects of doxorubicin-induced cardiotoxicity.

PMID:37257007 | DOI:10.14744/AnatolJCardiol.2023.2825

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PubMed articles on: Cardio-Oncology

Association of Circulating Cardiomyocyte Cell-Free DNA With Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Treatment for ERBB2-Positive Breast Cancer

JAMA Cardiol. 2023 May 31:e231229. doi: 10.1001/jamacardio.2023.1229. Online ahead of print. ABSTRACTIMPORTANCE: Cancer therapy-related cardiac dysfunction (CTRCD) is a potentially serious cardiotoxicity of treatments for ERBB2-positive breast cancer (formerly HER2). Identifying early biomarkers of cardiotoxicity could facilitate an individualized approach to cardiac surveillance and early pharmacologic intervention. Circulating cell-free DNA (cfDNA) of cardiomyocyte origin is present during acute cardiac injury but has not been established as a biomarker of CTRCD.

OBJECTIVE: To determine whether circulating cardiomyocyte cfDNA is associated with CTRCD in patients with ERBB2-positive breast cancer treated with anthracyclines and ERBB2-targeted therapy.

DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort of 80 patients with ERBB2-positive breast cancer enrolled at an academic cancer center between July 2014 and April 2016 underwent echocardiography and blood collection at baseline, after receiving anthracyclines, and at 3 months and 6 months of ERBB2-targeted therapy. Participants were treated with doxorubicin-based chemotherapy followed by trastuzumab (+/- pertuzumab). The current biomarker study includes participants with sufficient biospecimen available for analysis after anthracycline therapy. Circulating cardiomyocyte-specific cfDNA was quantified by a methylation-specific droplet digital polymerase chain reaction assay. Data for this biomarker study were collected and analyzed from June 2021 through April 2022.

MAIN OUTCOMES AND MEASURES: The outcome of interest was 1-year CTRCD, defined by symptomatic heart failure or an asymptomatic decline in left ventricular ejection fraction (≥10% from baseline to less than lower limit of normal or ≥16%). Values for cardiomyocyte cfDNA and high-sensitivity cardiac troponin I (hs-cTnI) measured after patients completed treatment with anthracyclines were compared between patients who later developed CTRCD vs patients who did not using the Wilcoxon rank sum test, and the association of post-anthracycline cardiomyocyte cfDNA level with CTRCD was estimated using logistic regression.

RESULTS: Of 71 patients included in this study, median (IQR) age was 50 (44-58) years, all were treated with dose-dense doxorubicin, and 48 patients underwent breast radiotherapy. Ten of 71 patients (14%) in this analysis developed CTRCD. The level of cardiomyocyte cfDNA at the post-anthracycline time point was higher in patients who subsequently developed CTRCD (median, 30.5 copies/mL; IQR, 24-46) than those who did not (median, 7 copies/mL; IQR, 2-22; P = .004). Higher cardiomyocyte cfDNA level after completion of anthracycline chemotherapy was associated with risk of CTRCD (hazard ratio, 1.02 per 1-copy/mL increase; 95% CI, 1.00-1.03; P = .046).

CONCLUSIONS AND RELEVANCE: This study found that higher cardiomyocyte cfDNA level after completion of anthracycline chemotherapy was associated with risk of CTRCD. Cardiomyocyte cfDNA quantification shows promise as a predictive biomarker to refine risk stratification for CTRCD among patients with breast cancer receiving cardiotoxic cancer therapy, and its use warrants further validation.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02177175.

PMID:37256614 | PMC:PMC10233452 | DOI:10.1001/jamacardio.2023.1229

13:02

PubMed articles on: Cardio-Oncology

Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors

J Interv Card Electrophysiol. 2023 May 31. doi: 10.1007/s10840-023-01575-z. Online ahead of print.

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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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.