ABSTRACT

Cancer and cardiovascular disease (CVD) commonly coexist, with increasing evidence that long-term cancer survivors are more likely to die from CVD than the general population. Effective management of CVD and its risk factors requires identification of patients at increased risk who may benefit from early intervention and their appropriate monitoring across the disease trajectory. Improving outcomes requires new models of multidisciplinary cancer care supported by care pathways. Such pathways require a clear delineation of the roles and responsibilities of all team members and provision of appropriate enablers for their delivery. These include accessible point-of-care tools/risk calculators, patient resources, and the provision of tailored training opportunities for health care providers.

PMID:37321867 | DOI:10.1016/j.hlc.2023.04.301

02:23

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PubMed articles on: Cardio-Oncology

Burden and prognostic impact of cardiovascular disease in patients with cancer

Heart. 2023 Jun 15:heartjnl-2022-321324. doi: 10.1136/heartjnl-2022-321324. Online ahead of print.

ABSTRACT

The number of patients at the intersection of cancer and cardiovascular disease (CVD) is increasing, reflecting ageing global populations, rising burden of shared cardiometabolic risk factors, and improved cancer survival. Many cancer treatments carry a risk of cardiotoxicity. Baseline cardiovascular risk assessment is recommended in all patients with cancer and requires consideration of individual patient risk and the cardiotoxicity profile of proposed anticancer therapies. Patients with pre-existing CVD are potentially at high or very high risk of cancer-therapy related cardiovascular toxicity. The detection of pre-existing CVD should prompt cardiac optimisation and planning of surveillance during cancer treatment. In patients with severe CVD, the risk of certain cancer therapies may be prohibitively high. Such decisions require multidisciplinary discussion with consideration of alternative anti-cancer therapies, risk-benefit assessment, and patient preference. Current practice is primarily guided by expert opinion and data from select clinical cohorts. There is need for development of a stronger evidence base to guide clinical practice in cardio-oncology. The establishment of multicentre international registries and national-level healthcare data linkage projects are important steps towards facilitating enrichment of cardio-oncology research programmes. In this narrative review, we consider epidemiological trends of cancer and CVD comorbidities and the impact of their co-occurrence on clinical outcomes, current approach to supporting cancer patients with pre-existing CVD and gaps in existing knowledge.

PMID:37321830 | DOI:10.1136/heartjnl-2022-321324

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PubMed articles on: Cardio-Oncology

A comparative review and computational assessment of acetochlor toxicity in fish: A novel endocrine disruptor?

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Jun 14:109685. doi: 10.1016/j.cbpc.2023.109685. Online ahead of print.

ABSTRACT

Acetochlor is a chloroacetamide herbicide applied to various crops worldwide and is one of the top selling herbicides on the global market. Due to rain events and run-off, the potential for acetochlor-induced toxicity is a concern for aquatic species. Here we review the current state of knowledge regarding the concentrations of acetochlor in aquatic ecosystems globally and synthesize the biological impacts of acetochlor exposure to fish. We compile toxicity effects of acetochlor, outlining evidence for morphological defects, developmental toxicity, endocrine and immune system disruption, cardiotoxicity, oxidative stress, and altered behavior. To identify mechanisms of toxicity, we utilized computational toxicology and molecular docking approaches to uncover putative toxicity pathways. Using the comparative toxicogenomics database (CTD), transcripts responsive to acetochlor were captured and graphically depicted using String-DB. Gene-ontology analysis revealed that acetochlor may disrupt protein synthesis, blood coagulation, signaling pathways, and receptor activity in zebrafish. Further pathway analysis revealed potential novel targets for acetochlor disruption at the molecular level (e.g., TNF alpha, heat shock proteins), highlighting cancer, reproduction, and the immune system as biological processes associated with exposure. Highly interacting proteins in these gene networks (e.g., nuclear receptors) were selected to model binding potential of acetochlor using SWISS-MODEL. The models were used in molecular docking to strengthen evidence for the hypothesis that acetochlor acts as an endocrine disruptor, and results suggest estrogen receptor alpha and thyroid hormone receptor beta may be preferential targets for disruption. Lastly, this comprehensive review reveals that, unlike other herbicides, immunotoxicity nor behavioral toxicity have been fully investigated as sub-lethal endpoints for acetochlor, and such mechanisms of toxicity should be emphasized in future research investigating biological responses of fish to the herbicide.

PMID:37328132 | DOI:10.1016/j.cbpc.2023.109685

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PubMed articles on: Cardio-Oncology

Comparing Renin-Angiotensin-Aldosterone Blockade Regimens for Long-Term Chemotherapy-Related Cardiac Dysfunction: A Network Meta-Analysis

Cardiovasc Drugs Ther. 2023 Jun 14. doi: 10.1007/s10557-023-07457-w. Online ahead of print.

ABSTRACT

PURPOSE: Cancer therapies including trastuzumab and anthracyclines are cardiotoxic and cause cardiac dysfunction. To prevent cardiotoxicity, pharmacological agents used in heart failure have been administered concomitantly with cardiotoxic cancer therapy, but few studies to date have performed a head-to-head comparison of these different agents. This systematic review and network meta-analysis of randomized-controlled trials aims to evaluate the efficacy of renin-angiotensin-aldosterone system (RAAS) blockers, namely angiotensin-converting enzyme inhibitors (ACE-Is), aldosterone receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), in primary prevention against chemotherapy-related cardiac dysfunction in patients receiving anthracyclines and/or trastuzumab.

METHODS: A systematic search was performed in major web databases for studies from inception to 15 September 2022. A Bayesian network meta-analysis model was used to assess the relative effects of competing treatments on the primary outcomes of risk of significant decline in left ventricular ejection fraction (LVEF) and mean LVEF decline. Secondary outcomes included left ventricular diastolic function, global longitudinal strain, and cardiac biomarkers. This study is registered with PROSPERO, CRD42022357980.

RESULTS AND CONCLUSION: Nineteen studies reported the effects of 13 interventions (N = 1905 patients). Only enalapril (RR 0.05, 95% CI 0.00-0.20) was associated with reduced risk of patients developing significant decline in LVEF relative to placebo. Subgroup analysis showed that the beneficial effect of enalapril was driven by protection against anthracycline-associated toxicity. In addition, no RAAS-inhibiting agents showed efficacy in protection against treatment with both anthracycline and trastuzumab. The use of RAAS inhibition therapy did not conclusively impact on other markers of cardiac function, including left ventricular diastolic function and cardiac biomarkers.

PMID:37314568 | DOI:10.1007/s10557-023-07457-w

02:23

PubMed articles on: Cardio-Oncology

Cardioprotective Effects of Octreotide against Sepsis-Induced Cardiotoxicity in Mice

Arch Razi Inst. 2023 Feb 28;78(1):53-61. doi: 10.22092/ARI.2022.358339.2201. eCollection 2023 Feb.

ABSTRACT

Sepsis is a systemic inflammatory consequence resulting from microbial infection, assessed as a worldwide healthcare issue. Sepsis can result in multiorgan dysfunction, including cardiac, renal, hepatic, and cerebral dysfunction. Cardiotoxicity can occur in humans and rodents during sepsis, leading to increased mortality. The current study aims to explore the possible cardioprotective effects of octreotide during sepsis-induced cardiotoxicity. This study was done with a total of forty male albino Swiss mice, aged 8-12 weeks and weighing 25-30 gm. These animals had free access to food and water. After two weeks of adaptation, mice were divided into four groups (n=10): 1) Normal group: healthy mice; 2) CLP group: mice underwent CLP operation; 3) Vehicle group: mice received DMSO. 4) Octreotide group: mice received octreotide (10 mg/kg) subcutaneously in 2 divided doses for 5 consecutive days. All groups underwent CLP operation on the 4th day, then sacrificed on the 5th day then blood, and tissue sampling was done. The Octreotide group demonstrated a significant (P<0.05)P<0.05)P<0.05)P<0.05)P<0.05)

PMID:37312717 | PMC:PMC10258294 | DOI:10.22092/ARI.2022.358339.2201

02:23

PubMed articles on: Cardio-Oncology

Amentoflavone mitigates doxorubicin-induced cardiotoxicity by suppressing cardiomyocyte pyroptosis and inflammation through inhibition of the STING/NLRP3 signalling pathway

Phytomedicine. 2023 Aug;117:154922. doi: 10.1016/j.phymed.2023.154922. Epub 2023 Jun 10.

ABSTRACT

BACKGROUND: Doxorubicin (DOX) is a potent anticancer chemotherapeutic agent whose clinical application is substantially constrained by its cardiotoxicity. The pathophysiology of DOX-induced cardiotoxicity manifests as cardiomyocyte pyroptosis and inflammation. Amentoflavone (AMF) is a naturally occurring biflavone possessing anti-pyroptotic and anti-inflammatory properties. However, the mechanism through which AMF alleviates DOX-induced cardiotoxicity remains undetermined.

PURPOSE: This study aimed at investigating the role of AMF in alleviating DOX-induced cardiotoxicity.

STUDY DESIGN AND METHODS: To assess the in vivo effect of AMF, DOX was intraperitoneally administered into a mouse model to induce cardiotoxicity. To elucidate the underlying mechanisms, the activities of STING/NLRP3 were quantified using the NLRP3 agonist nigericin and the STING agonist amidobenzimidazole (ABZI). Primary cardiomyocytes isolated from neonatal Sprague-Dawley rats were treated with saline (vehicle) or DOX with or without AMF and/or ABZI. The echocardiogram, haemodynamics, cardiac injury markers, heart/body weight ratio, and pathological alterations were monitored; the STING/NLRP3 pathway-associated proteins were detected by western blot and cardiomyocyte pyroptosis was analysed by immunofluorescence staining of cleaved N-terminal GSDMD and scanning electron microscopy. Furthermore, we evaluated the potential of AMF in compromising the anticancer effects of DOX in human breast cancer cell lines.

RESULTS: AMF substantially alleviated cardiac dysfunction and reduced heart/body weight ratio and myocardial damage in mice models of DOX-induced cardiotoxicity. AMF effectively suppressed DOX-mediated upregulation of IL-1β, IL-18, TNF-α, and pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and cleaved N-terminal GSDMD. The levels of apoptosis-related proteins, namely Bax, cleaved caspase-3, and BCL-2 were not affected. In addition, AMF inhibited STING phosphorylation in DOX-affected hearts. Intriguingly, the administration of nigericin or ABZI dampened the cardioprotective effects of AMF. The in vitro anti-pyroptotic effect of AMF was demonstrated in attenuating the DOX-induced reduction in cardiomyocyte cell viability, upregulation of cleaved N-terminal GSDMD, and pyroptotic morphology alteration at the microstructural level. AMF exhibited a synergistic effect with DOX to reduce the viability of human breast cancer cells.

CONCLUSION: AMF alleviates DOX-induced cardiotoxicity by suppressing cardiomyocyte pyroptosis and inflammation via inhibition of the STING/NLRP3 signalling pathway, thereby validating its efficacy as a cardioprotective agent.

PMID:37321078 | DOI:10.1016/j.phymed.2023.154922

02:23

PubMed articles on: Cardio-Oncology

Novel molecular mechanisms of doxorubicin cardiotoxicity: latest leading-edge advances and clinical implications

Mol Cell Biochem. 2023 Jun 13. doi: 10.1007/s11010-023-04783-3. Online ahead of print.