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. doi: 10.1001/jamacardio.2023.1229. Online ahead of print.

ABSTRACT

IMPORTANCE: 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 | DOI:10.1001/jamacardio.2023.1229

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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: Cardio-Oncology

Quantitative cardiovascular magnetic resonance findings and clinical risk factors predict cardiovascular outcomes in breast cancer patients

PLoS One. 2023 May 30;18(5):e0286364. doi: 10.1371/journal.pone.0286364. eCollection 2023.

ABSTRACT

BACKGROUND: Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes.

OBJECTIVES: To assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy.

METHODS: Breast cancer patients with a CMR from 2013-2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed.

RESULTS: 116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229-0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease.

CONCLUSIONS: In our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity.

PMID:37252927 | PMC:PMC10228774 | DOI:10.1371/journal.pone.0286364

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PubMed articles on: Cardio-Oncology

Cardiotoxicities of Non-Chemotherapeutic Metastatic Breast Cancer Treatments

Curr Oncol Rep. 2023 May 30. doi: 10.1007/s11912-023-01427-z. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Although mortality rates have declined significantly in recent years, breast cancer remains the second most common cause of cancer death in women, with rates significantly higher among women with metastatic disease. New therapeutic agents have improved the prognosis of patients with metastatic breast cancer but raise concerns around the risk of cardiovascular disease. This review aims to discuss the oncologic treatment of the different subtypes of breast cancer along with the cardiac complications associated with each therapy.

RECENT FINDINGS: This article emphasizes human epidermal growth factor receptor targeted therapies with a focus on incidence of cardiotoxicity, reversibility, long-term outcomes, and management in high-risk patients. This review will address the use of cardiac biomarkers to monitor for toxicity, as well as the utility of cardiac imaging, including global longitudinal strain as a prognostic factor. We will also include recent findings on tyrosine kinase inhibitors, cyclin dependent kinase 4/6, and immune checkpoint inhibitors. Cardiotoxicity may lead to premature discontinuation of novel cancer therapies; optimizing cardiovascular risk factors and close monitoring for cardiotoxicity allow patients to maximize their oncologic and cardiovascular outcomes.

PMID:37249834 | DOI:10.1007/s11912-023-01427-z

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PubMed articles on: Cardio-Oncology

Cardio-Oncology for the Primary Care Provider

Rom J Intern Med. 2023 May 30. doi: 10.2478/rjim-2023-0012. Online ahead of print.

ABSTRACT

Cardiovascular disease is a major cause of mortality among oncologic patients. As cancer therapies continue to evolve and advance, cancer survival rates have been increasing and so has the burden of cardiovascular disease within this population. For this reason, cardio-oncology plays an important role in promoting multidisciplinary care with the primary care provider, oncology, and cardiology. In this review, we discuss the roles of different providers, strategies to monitor patients receiving cardiotoxic therapies, and summarize cancer therapy class-specific toxicities. Continued collaboration among providers and ongoing research related to cardiotoxic cancer therapies will enable patients to receive maximal, evidence-based, comprehensive care.

PMID:37249550 | DOI:10.2478/rjim-2023-0012

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PubMed articles on: Cardio-Oncology

The incidence rate of allergic reactions induced by oxaliplatin is higher in patients with rectal cancer compared with colon cancer

Drug Chem Toxicol. 2023 May 29:1-7. doi: 10.1080/01480545.2023.2217700. Online ahead of print.

ABSTRACT

AIM: To explore the diverse profiles of adverse reactions caused by oxaliplatin between colon and rectal cancer, we investigated the toxicity of oxaliplatin in patients with colon and rectal cancer.

METHODS: From January 2017 to December 2021, 200 cases of sporadic CRC patients with adverse reactions after oxaliplatin were collected from Harbin Medical University Cancer Hospital, Harbin, China. All patients received a chemotherapy regimen containing oxaliplatin (100 colon cancer and 100 rectal cancer). We reviewed the adverse reactions induced by oxaliplatin in patients with colon and rectal cancer.

RESULTS: We found there was no significant difference in gastrointestinal toxicity, hematotoxicity, neurotoxicity, hepatotoxicity, respiratory toxicity, and cardiotoxicity caused by oxaliplatin between patients with colon cancer and patients with rectal cancer, but patients with rectal cancer were more prone to allergic reactions than patients with colon cancer after oxaliplatin. In addition, we found neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) were higher in patients with colon cancer than in patients with rectal cancer. This may reflect differences in immune status and inflammatory responses between colon cancer and rectal cancer, which might be the reason for more allergic reactions caused by oxaliplatin in colon cancer patients compared to rectal cancer patients.

CONCLUSION: Except for a higher incidence of allergic reactions in patients with rectal cancer, no significant difference in the incidence of adverse drug reactions associated with oxaliplatin was noted between patients with colon cancer and rectal cancer. Our results suggested more attention should be paid to the allergic reaction caused by oxaliplatin in patients with colon cancer.

PMID:37246950 | DOI:10.1080/01480545.2023.2217700

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PubMed articles on: Cardio-Oncology

Hyperoside prevents doxorubicin-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway

Phytother Res. 2023 May 28. doi: 10.1002/ptr.7900. Online ahead of print.

ABSTRACT

Clinical application of doxorubicin (Dox) in cancer chemotherapy is limited by its cardiotoxicity. Present study aimed to demonstrate the effect and mechanism of hyperoside in Dox-induced cardiotoxicity. C57BL/6 mice were injected with 12 mg/kg of Dox, and 1 μM Dox was exposed to primary cardiomyocytes. Cardiac function was evaluated by echocardiographic and myocardial enzyme levels. Cardiomyocyts apoptosis was analyzed by TUNEL staining and flow cytometry. Network pharmacology and molecular docking were utilized to explore potential targets of hyperoside. Protein expressions were detected by western blot and enzyme activities were determined by colorimetry. Cardiac dysfunction and cardiomyocyte apoptosis induced by Dox were attenuated by hyperoside. Mechanism of hyperoside was mainly related to "oxidative stress" pathway. Hyperoside exhibited strong binding activities with nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs, the main source of ROS in cardiomyocytes) and cyclooxygenases (COXs). Experiments proved that hyperoside suppressed the ROS generation and the elevated activities of NOXs and COXs induced by Dox. Dox also triggered the activation of NLRP3 inflammasome, which was reversed by hyperoside. Hyperoside bound to NOXs and COXs, which prevents Dox-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway. Hyperoside holds promise as a therapeutic strategy for Dox-induced cardiotoxicity.

PMID:37246409 | DOI:10.1002/ptr.7900

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PubMed articles on: Cardio-Oncology

Alternate-day fasting exacerbates doxorubicin cardiotoxicity in cancer chemotherapy

Trends Endocrinol Metab. 2023 May 26:S1043-2760(23)00093-0. doi: 10.1016/j.tem.2023.05.003. Online ahead of print.

ABSTRACT

Doxorubicin (Dox) is a highly potent chemotherapy drug. Despite its efficacy, Dox's clinical application is limited due to its association with significant complications, namely cardiotoxicity and the risk of heart failure. Recent intriguing findings by Ozcan et al. indicate that alternate-day fasting (ADF) significantly exacerbates the cardiotoxicity of Dox.

PMID:37246117 | DOI:10.1016/j.tem.2023.05.003

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PubMed articles on: Cardio-Oncology

Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice

Nutrients. 2023 May 12;15(10):2287. doi: 10.3390/nu15102287.

ABSTRACT

BACKGROUND: Doxorubicin (Doxo) is a widely prescribed drug against many malignant cancers. Unfortunately, its utility is limited by its toxicity, in particular a progressive induction of congestive heart failure. Doxo acts primarily as a mitochondrial toxin, with consequent increased production of reactive oxygen species (ROS) and attendant oxidative stress, which drives cardiac dysfunction and cell death. A diet containing a special mixture of all essential amino acids (EAAs) has been shown to increase mitochondriogenesis, and reduce oxidative stress both in skeletal muscle and heart. So, we hypothesized that such a diet could play a favorable role in preventing Doxo-induced cardiomyocyte damage.

METHODS: Using transmission electron microscopy, we evaluated cells' morphology and mitochondria parameters in adult mice. In addition, by immunohistochemistry, we evaluated the expression of pro-survival marker Klotho, as well as markers of necroptosis (RIP1/3), inflammation (TNFα, IL1, NFkB), and defense against oxidative stress (SOD1, glutathione peroxidase, citrate synthase).

RESULTS: Diets with excess essential amino acids (EAAs) increased the expression of Klotho and enhanced anti-oxidative and anti-inflammatory responses, thereby promoting cell survival.

CONCLUSION: Our results further extend the current knowledge about the cardioprotective role of EAAs and provide a novel theoretical basis for their preemptive administration to cancer patients undergoing chemotherapy to alleviate the development and severity of Doxo-induced cardiomyopathy.

PMID:37242170 | PMC:PMC10222879 | DOI:10.3390/nu15102287

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PubMed articles on: Cardio-Oncology

p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act

Nutrients. 2023 May 10;15(10):2259. doi: 10.3390/nu15102259.

ABSTRACT

Doxorubicin (DOX) is a highly effective chemotherapeutic drug, but its long-term use can cause cardiotoxicity and drug resistance. Accumulating evidence demonstrates that p53 is directly involved in DOX toxicity and resistance. One of the primary causes for DOX resistance is the mutation or inactivation of p53. Moreover, because the non-specific activation of p53 caused by DOX can kill non-cancerous cells, p53 is a popular target for reducing toxicity. However, the reduction in DOX-induced cardiotoxicity (DIC) via p53 suppression is often at odds with the antitumor advantages of p53 reactivation. Therefore, in order to increase the effectiveness of DOX, there is an urgent need to explore p53-targeted anticancer strategies owing to the complex regulatory network and polymorphisms of the p53 gene. In this review, we summarize the role and potential mechanisms of p53 in DIC and resistance. Furthermore, we focus on the advances and challenges in applying dietary nutrients, natural products, and other pharmacological strategies to overcome DOX-induced chemoresistance and cardiotoxicity. Lastly, we present potential therapeutic strategies to address key issues in order to provide new ideas for increasing the clinical use of DOX and improving its anticancer benefits.

PMID:37242146 | PMC:PMC10222243 | DOI:10.3390/nu15102259

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PubMed articles on: Cardio-Oncology

Prognostic Impact of Global Longitudinal Strain and NT-proBNP on Early Development of Cardiotoxicity in Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy

Medicina (Kaunas). 2023 May 15;59(5):953. doi: 10.3390/medicina59050953.

ABSTRACT

Background. The most important anthracycline side effect is cardiotoxicity, resulting in congestive heart failure (HF). Early detection of cardiac dysfunction and appropriate treatment can improve outcomes and reduce the progression of HF. The aim of our study was to evaluate changes in clinical data, echocardiographic parameters, and NT-proBNP, as well as their associations with early anthracycline-induced cardiotoxicity (AIC) in patients treated with anthracycline-based chemotherapy. Methods and Materials. Patients with breast cancer were prospectively assessed with echocardiography, as well as NT-proBNP testing at baseline, (T0), after two cycles (T1) and four cycles (T2) of chemotherapy. AIC was defined as a new decrease in the LVEF of 10 percentage points, to a value below the lower limit of normal. Results.We evaluated 85 patients aged 54.5 ± 9.3 years. After a cumulative dose of 237.9 mg/m2 of doxorubicin, 22 patients (25.9%) met the criteria of AIC after chemotherapy. Patients who subsequently progressed to cardiotoxicity had demonstrated a significantly larger impairment in LV systolic function compared to those who did not develop cardiotoxicity (LVEF: 54.0 ± 1.6% vs. 57.1 ± 1.4% at T1, p< 0.001, and 49.9 ± 2.1% vs. 55.8 ± 1.6% at T2, p< 0.001; GLS: -17.8 ± 0.4% vs. -19.3 ± 0.9% at T1, p< 0.001, and -16.5 ± 11.1% vs. -18.5 ± 0.9% at T2, p< 0.001, respectively). The levels of NT-proBNP increased significantly from 94.8 ± 43.8 ng/L to 154.1 ± 75.6 ng/L, p< 0.001. A relative decrease in GLS ≤ -18.0% (sensitivity: 72.73%; specificity: 92.06%; AUC, 0.94; p< 0.001) and a relative increase in NT-proBNP > 125 ng/L (sensitivity: 90.0%; specificity: 56.9%; AUC, 0.78; p< 0.001) from baseline to T1 predicted subsequent LV cardiotoxicity at T2. Conclusions. Decrease in GLS and elevation in NT-proBNP were significantly associated with AIC, and these could potentially be used to predict subsequent declines in LVEF with anthracycline-based chemotherapy.

PMID:37241185 | PMC:PMC10224214 | DOI:10.3390/medicina59050953

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PubMed articles on: Cardio-Oncology

Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats

J Pers Med. 2023 Apr 27;13(5):750. doi: 10.3390/jpm13050750.

ABSTRACT

Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone's cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall.

PMID:37240920 | PMC:PMC10221553 | DOI:10.3390/jpm13050750

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PubMed articles on: Cardio-Oncology

Echocardiographic Findings in Asymptomatic Mediastinal Lymphoma Survivors Years after Treatment Termination

J Clin Med. 2023 May 12;12(10):3427. doi: 10.3390/jcm12103427.

ABSTRACT

Patients treated due to mediastinal lymphomas are at risk of cardiovascular complications, as they receive chemotherapy, usually containing anthracyclines, often combined with thoracic radiotherapy. The aim of this prospective study was to assess early asymptomatic cardiac dysfunction using resting and dobutamine stress echocardiography (DSE) at least 3 years after the end of mediastinal lymphoma treatment. Two groups of patients were compared: those treated with chemoradiotherapy and those exclusively treated with chemotherapy. Left ventricular contractile reserve (LVCR) during DSE was assessed using changes in LV ejection fraction (LVEF), LV global longitudinal strain (LV GLS), and a novel parameter-Force, which is the ratio of the systolic blood pressure to the LV end-systolic volume. The study included 60 patients examined at a median of 89 months after the end of treatment. Resting echocardiography showed normal LVEF of 58.9 ± 9.6%, borderline LV GLS of -17.7 ± 3%, decreased mean stroke volume (SV) of 51.4 ± 17 mL, and indexed SV of 27.3 ± 8 mL/m2, and the right ventricular free wall longitudinal strain (LS) was impaired in some patients but not in all. There were no significant differences between the groups, with the exception of arterial hypertension, which was more common in the chemotherapy group (32% vs. 62.5%, p= 0.04). In resting echocardiography, only LV posterior wall LS differed significantly and was impaired in patients treated with chemotherapy (-19.1 ± 3.1% vs. -16.5 ± 5.1%, p= 0.04). DSE, performed in 21 patients after a median of 166 months from the end of cancer treatment, detected new contractility disorders in 1 patient (4.8%) and decreased LVCR in the majority of patients when determined using changes in LVEF or LV GLS, and in all patients when assessed with changes in Force. Conclusions: Most asymptomatic mediastinal lymphoma survivors showed preserved ventricular function on resting echocardiography. However, all of them showed impaired LV contractile reserve on DSE, as assessed with a simple parameter-Force. This may indicate subtle LV dysfunction and confirms the need for long-term monitoring of patients with potentially cardiotoxic cancer treatment.

PMID:37240533 | PMC:PMC10219019 | DOI:10.3390/jcm12103427

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PubMed articles on: Cardio-Oncology

Primary Cardiac Schwannoma: A Meta-Analysis of Individual Case Reports

J Clin Med. 2023 May 9;12(10):3356. doi: 10.3390/jcm12103356.

ABSTRACT

Primary cardiac schwannoma (PCS) is a neurogenic tumor that arises from Schwann cells. Malignant schwannoma (MSh) is an aggressive cancer comprising 2% of all sarcomas. Information on the proper management of these tumors is limited. Four databases were searched for case reports/series of PCS. The primary outcome was overall survival (OS). Secondary outcomes included therapeutic strategies and the corresponding outcomes. Among 439 potentially eligible studies, 53 met the inclusion criteria. The patients included had 43.72 ± 17.76 years and 28.3% were males. Over 50% of patients had MSh, with 9.4% also demonstrating metastases. Schwannoma commonly occurs in the atria (66.0%). Left-sided PCS were more common than right-sided ones. Surgery was performed in almost 90% of the cases; chemotherapy and radiotherapy were used in 16.9% and 15.1% of cases, respectively. Compared to benign cases, MSh occurs at a younger age and is commonly located on the left side. OS of the entire cohort at 1 and 3 years were 60.7%, and 54.0%, respectively. Females and males OS were similar up to 2 years follow-up. Surgery was associated with higher OS (p < 0.01). Surgery is the primary treatment option for both benign and malignant cases and was the only factor associated with a relative improvement in survival.

PMID:37240461 | PMC:PMC10219427 | DOI:10.3390/jcm12103356

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PubMed articles on: Cardio-Oncology

Recurrent cardiotoxicity in a fluoropyrimidine treated cancer patient - case report and practical recommendations

Arch Clin Cases. 2023 May 18;10(2):55-60. doi: 10.22551/2023.39.1002.10241. eCollection 2023.

ABSTRACT

Fluoropyrimidines remain some of the most used chemotherapeutics, despite the appearance in the therapeutic arsenal of targeted therapy and immunotherapy. Fluropyrimidines related cardiotoxicity is an undesirable adverse event and affects almost 20% of patients. The mechanisms of fluoropyrimidine toxicity are closely related to deficient allelic variants of DPYD, but considering the low penetrance and interindividual variability, not all adverse reactions are explained by their presence. In this case, we report a patient with recurrent fluoropyrimidine toxicity without a deficient allelic variant and how this case was managed by the oncologist and cardiologist, considering the need to use fluoropyrimidine in the treatment.

PMID:37215066 | PMC:PMC10194170 | DOI:10.22551/2023.39.1002.10241

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PubMed articles on: Cardio-Oncology

Will nanomedicine become a good solution for the cardiotoxicity of chemotherapy drugs?

Front Pharmacol. 2023 May 4;14:1143361. doi: 10.3389/fphar.2023.1143361. eCollection 2023.

ABSTRACT

Cancer is one of the leading causes of death worldwide, and with the continuous development of life sciences and pharmaceutical technology, more and more antitumor drugs are being used in clinics to benefit cancer patients. However, the incidence of chemotherapy-induced cardiotoxicity has been continuously increasing, threatening patients' long-term survival. Cardio-oncology has become a research hot spot, and the combination of nanotechnology and biomedicine has brought about an unprecedented technological revolution. Nanomaterials have the potential to maximize the efficacy and reduce the side effects of chemotherapeutic drugs when used as their carriers, and several nano-formulations of frequently used chemotherapeutic drugs have already been approved for marketing. In this review, we summarize chemotherapeutic drugs that are highly associated with cardiotoxicity and evaluate the role of nano-delivery systems in reducing cardiotoxicity based on studies of their marketed or R&D nano-formulations. Some of the marketed chemotherapy drugs are combined with nano-delivery systems that can effectively deliver chemotherapy drugs to tumors and cannot easily penetrate the endothelial barrier of the heart, thus decreasing their distribution in the heart and reducing the cardiotoxicity to some extent. However, many chemotherapy nanomedicines that are marketed or in R&D have not received enough attention in determining their cardiotoxicity. In general, nanomedicine is an effective method to reduce the cardiotoxicity of traditional chemotherapy drugs. However, cardiovascular complications in cancer treatment are very complex diseases, requiring the application of multiple measures to achieve effective management and prevention.

PMID:37214453 | PMC:PMC10194942 | DOI:10.3389/fphar.2023.1143361

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PubMed articles on: Cardio-Oncology

Poorer Survival after Out-of-Hospital Cardiac Arrest among Cancer Patients - A Population-Based Register Study

Eur Heart J Acute Cardiovasc Care. 2023 May 20:zuad053. doi: 10.1093/ehjacc/zuad053. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The association between cancer and survival after out-of-hospital cardiac arrest (OHCA) has not been thoroughly investigated. We aimed to address this knowledge gap using national, population-based registries.

METHODS: For this study, 30,163 OHCA patients (≥18 years) were included from the Swedish Register of Cardiopulmonary Resuscitation. Via linkage to the National Patient Registry, 2,894 patients (10%) with cancer diagnosed within 5 years prior to OHCA were identified. Differences in 30-day survival between cancer patients and controls (defined as OHCA patients without previous cancer diagnosis) were assessed related to cancer stage (locoregional vs metastasized cancer) and cancer site (i.e. lung cancer, breast cancer etc.) using logistic regression adjusted for prognostic factors. Long-term survival is presented as a Kaplan-Meier curve.

RESULTS: For locoregional cancer no statistically significant difference in return of spontaneous circulation (ROSC) was seen compared to controls, metastasized disease was associated with poorer chance of ROSC. Cancer was associated with lower 30-day survival for all cancers (Adjusted odds ratio, OR, 0.57, CI 0.49-0.66), locoregional cancer (Adjusted OR 0.68, CI 0.57-0.82) and metastasized cancer (Adjusted OR 0.24, CI 0.14-0.40) compared to controls. Lower 30-day survival compared to controls was seen for lung cancer, gynaecological and haematological cancers.

CONCLUSION: Cancer is associated with poorer 30-day survival after OHCA. This study suggests that cancer site and disease stage are more relevant factors than cancer in general with regard to its effect on survival after OHCA.

PMID:37210580 | DOI:10.1093/ehjacc/zuad053

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PubMed articles on: Cardio-Oncology

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