ABSTRACT

AIMS: Anthracyclines are used in multiple malignancies but are limited by their cardiotoxicity. Statins have been used for primary and secondary prevention of atherosclerotic cardiovascular disease. There exists conflicting and inconclusive evidence on the effect of statins in patients receiving anthracycline chemotherapy therapies. We conducted a meta-analysis to identify summative evidence of the effect of prescribing statins for patients on anthracycline therapy based on prior studies.

METHODS: We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov from inception until April 10, 2023, for randomized controlled trials (RCTs) and comparative observational studies using statins and anthracyclines. Primary endpoints analyzed included the incidence of cardiotoxicity and change in left ventricular ejection fraction (LVEF). Analysis was done using Stata 17.0 with odds ratio (OR) and mean difference (MD) as our effect measures.

RESULTS: We included 3 observational studies and 4 RCTs in our review. The incidence of cardiotoxicity was significantly lower among patients with cancer who were prescribed statins compared to those not prescribed (OR 0.46, 95% CI: 0.33-0.63; I2: 0%). Conversely, prescribing statins was seen to have no significant effect on decline in LVEF from baseline (MD 4.15, 95% CI: -0.69 to 8.99, I2: 97%).

CONCLUSIONS: In this meta-analysis, statins were associated with a reduced incidence of cardiotoxicity among cancer patients treated with anthracyclines, but no significant difference in LVEF change from baseline was found.

PMID:37336312 | DOI:10.1016/j.cpcardiol.2023.101885

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PubMed articles on: Cardio-Oncology

Trastuzumab potentiates doxorubicin-induced cardiotoxicity via activating the NLRP3 inflammasome in vivo and in vitro

Biochem Pharmacol. 2023 Jun 16:115662. doi: 10.1016/j.bcp.2023.115662. Online ahead of print.

ABSTRACT

Trastuzumab (Tra), the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2), is commonly used alongside doxorubicin (Dox) as a combination therapy in HER2-positive breast cancer. Unfortunately, this leads to a more severe cardiotoxicity than Dox alone. NLRP3 inflammasome is known to be involved in Dox-induced cardiotoxicity and multiple cardiovascular diseases. However, whether the NLRP3 inflammasome contributes to the synergistic cardiotoxicity of Tra has not been elucidated. In this study, primary neonatal rat cardiomyocyte (PNRC), H9c2 cells and mice were treated with Dox (15 mg/kg in mice or 1μM in cardiomyocyte) or Tra (15.75 mg/kg in mice or 1μM in cardiomyocyte), or Dox combined Tra as cardiotoxicity models to investigate this question. Our results demonstrated that Tra significantly potentiated Dox-induced cardiomyocyte apoptosis and cardiac dysfunction. These were accompanied by the increased expressions of NLRP3 inflammasome components (NLRP3, ASC and cleaved caspase-1), the secretion of IL-β and the pronounced production of ROS. Inhibiting the activation of NLRP3 inflammasome by NLRP3 silencing significantly reduced cell apoptosis and ROS production in Dox combined Tra-treated PNRC. Compared with the wild type mice, the systolic dysfunction, myocardial hypertrophy, cardiomyocyte apoptosis and oxidative stress induced by Dox combined Tra were alleviated in NLRP3 gene knockout mice. Our data revealed that the co-activation of NLRP3 inflammasome by Tra promoted the inflammation, oxidative stress and cardiomyocytes apoptosis in Dox combined Tra-induced cardiotoxicity model both in vivo and in vitro. Our results suggest that NLRP3 inhibition is a promising cardioprotective strategy in Dox/Tra combination therapy.

PMID:37331637 | DOI:10.1016/j.bcp.2023.115662

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PubMed articles on: Cardio-Oncology

Atrial fibrillation in cancer survivors - a systematic review and meta-analysis

Cardiooncology. 2023 Jun 17;9(1):29. doi: 10.1186/s40959-023-00180-3.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is a common cardiac complication during cancer treatment. It is unclear if cancer survivors have increased AF risk when compared to the population. AF screening is now recommended in patients ≥65 years, however there are no specific recommendations in the oncology population. We sought to compare the AF detection rate of cancer survivors compared to the general population.

METHODS: We searched the Pubmed, Embase and Web of Science databases using search terms related to AF and cancer mapped to subject headings. We included English language studies, limited to adults > 18 years who were > 12 months post completion of cancer treatment. Using a random-effects model we calculated the overall AF detection rate. Meta-regression analysis was performed to assess for potential causes for study heterogeneity.

RESULTS: Sixteen studies were included in the study. The combined AF detection rate amongst all the studies was 4.7% (95% C.I 4.0-5.4%), which equated to a combined annualised AF rate of 0.7% (95% C.I 0.1-0.98%). There was significant heterogeneity between studies (I2 = 99.8%, p < 0.001). In the breast cancer cohort (n = 6 studies), the combined annualised AF rate was 0.9% (95% C.I 0.1-2.3%), with significant heterogeneity (I2 = 99.9%, p < 0.001).

CONCLUSION: Whilst the results should be interpreted with caution due to study heterogeneity, AF rates in patients with cancer survival >12 months were not significantly increased compared to the general population.

STUDY REGISTRATION: Open Science Framework - DOI: https://doi.org/10.17605/OSF.IO/APSYG .

PMID:37330583 | PMC:PMC10276447 | DOI:10.1186/s40959-023-00180-3

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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

2023 National Heart Center/Saudi Heart Association Focused Update of the 2019 Saudi Heart Association Guidelines for the Management of Heart Failure

J Saudi Heart Assoc. 2023 May 25;35(1):71-134. doi: 10.37616/2212-5043.1334. eCollection 2023.

ABSTRACT

BACKGROUND: The burden of cardiovascular diseases is undeniable in local populations, who have high mortality rates and a young age of disease onset. A systematic review of emerging evidence and update of the Saudi Heart Association (SHA) 2019 heart failure (HF) guidelines was therefore undertaken.

METHODOLOGY: A panel of expert cardiologists reviewed recommendations of the 2019 guidelines following the Saudi Heart Association methodology for guideline recommendations. When needed, the panel provided updated and new recommendations endorsed by the national heart council that are appropriate for clinical practice and local resources in Saudi Arabia.

RECOMMENDATIONS AND CONCLUSION: The focused update describes the appropriate use of clinical assessment as well as invasive and non-invasive modalities for the classification and diagnosis of HF. The prevention of HF was emphasized by expanding on both primary and secondary prevention approaches. Pharmacological treatment of HF was supplemented with recommendations on newer therapies, such as SGLT-2 inhibitors. Recommendations were also provided on the management of patients with cardiovascular and non-cardiovascular co-morbidities, with a focus on cardio-oncology and pregnancy. Updated clinical algorithms were included in support of HF management in both the acute and chronic settings. The implementation of this focused update on HF management in clinical practice is expected to lead to improved patient outcomes by providing evidence-based comprehensive guidance for practitioners in Saudi Arabia.

PMID:37323135 | PMC:PMC10263126 | DOI:10.37616/2212-5043.1334

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PubMed articles on: Cardio-Oncology

Burden and prognostic impact of cardiovascular disease in patients with cancer

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PubMed articles on: Cardio-Oncology

Doxorubicin Interaction with Lipid Monolayers Leads to Decreased Membrane Stiffness when Experiencing Compression-Expansion Dynamics

Langmuir. 2023 Jun 15. doi: 10.1021/acs.langmuir.3c00250. Online ahead of print.