ABSTRACT

BACKGROUND: Cardiological complications of oncological treatment, including the most serious one, heart failure, constitute a significant and still unsolved clinical problem. A history of dyslipidemia and complications of atherosclerosis, including coronary artery disease, are established risk factors for cardiotoxicity in cancer patients. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. This protocol describes a study aiming to assess the prognostic value of coronary atherosclerosis burden and the CAC score on the onset of cardiac dysfunction associated with cancer therapy.

METHODS: ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a single-site, prospective, observational study to evaluate the influence of the coronary atherosclerosis and CAC score assessed by computed tomography on the development of left ventricular systolic dysfunction in cancer patients with at least moderate cardiotoxicity risk. A group of 80 patients diagnosed with cancer prior to high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 body weight or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. Patient follow-up is planned for 12 months. In all patients, coronary computed tomographic angiography (CCTA) will be performed once at the beginning of the study. The primary endpoint is the onset of cancer therapy-related cardiovascular toxicity, defined as mild, moderate, severe and very severe according to ESC 2022 Cardio-oncology guidelines. During follow up, echocardiography with GLS assessment will be performed every three months. Additionally, new biomarkers of atherosclerosis (IL-6, MPO, TNF-alpha) will be measured every 6 months. The study registration identifier on clinicaltrials.gov is NCT05118178.

CLINICAL TRIALS REGISTRY: This study is listed on cinicaltrials.gov with identifier NCT05118178.

PMID:37590267 | DOI:10.1371/journal.pone.0288146

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PubMed articles on: Cardio-Oncology

Cardiac Arrhythmias in Oncological Patients-Epidemiology, Risk Factors, and Management within the Context of the New ESC 2022 Guidelines

Curr Oncol Rep. 2023 Aug 17. doi: 10.1007/s11912-023-01445-x. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: To provide an update on epidemiology, risk factors, and management of cardiac arrhythmias in oncological patients within the context of the new European Society of Cardiology 2022 guidelines on cardio-oncology.

RECENT FINDINGS: One of the side effects of different chemotherapeutics is their pro-arrhythmic activity. Both atrial and ventricular arrhythmias may be induced by cancer itself or by anticancer treatment. Recent studies report on the cardiotoxic activity of such promising therapies as BRAF and MEK inhibitors, or CAR-T therapy. Risk factors of arrhythmias in oncological patients overlap with cardiovascular diseases risk factors, but there are some groups of anticancer drugs that increase the risk of cardiotoxicity. It is crucial to be aware of the risks associated with the oncological treatment and know how to act in case of cardiotoxicity.

PMID:37589940 | DOI:10.1007/s11912-023-01445-x

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PubMed articles on: Cardio-Oncology

First-Pass Perfusion Cardiac Magnetic Resonance Imaging for Cancer-Associated Cardiac Masses: First Impressions Count!

JACC Cardiovasc Imaging. 2023 Aug 2:S1936-878X(23)00336-4. doi: 10.1016/j.jcmg.2023.06.020. Online ahead of print.

NO ABSTRACT

PMID:37589606 | DOI:10.1016/j.jcmg.2023.06.020

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PubMed articles on: Cardio-Oncology

Editorial: The influence of lifestyle factors on cancer biology and treatment efficacy

Front Physiol. 2023 Jul 31;14:1254151. doi: 10.3389/fphys.2023.1254151. eCollection 2023.

NO ABSTRACT

PMID:37588853 | PMC:PMC10425544 | DOI:10.3389/fphys.2023.1254151

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PubMed articles on: Cardio-Oncology

Cardioprotection in cardio-oncology: a case for concern?

Cardiovasc Res. 2023 Aug 17:cvad111. doi: 10.1093/cvr/cvad111. Online ahead of print.

NO ABSTRACT

PMID:37587745 | DOI:10.1093/cvr/cvad111

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PubMed articles on: Cardio-Oncology

3D-based strain analysis and cardiotoxicity detection in cancer patients received chemotherapy

BMC Cancer. 2023 Aug 16;23(1):760. doi: 10.1186/s12885-023-11261-y.

ABSTRACT

BACKGROUND: Chemotherapy-induced cardiotoxicity has become a prevalent complication. Regular monitoring of patients who received chemotherapy using 3D strain parameters may aid in early detection of myocardial damage and its prevention. The purpose of this study was to evaluate the effectiveness of three-dimensional speckle tracking imaging (3D-STI) in diagnosing and predicting the likelihood of cardiotoxicity. This was achieved by conducting a systematic review of original research articles.

OBJECTIVES: To evaluate the role of 3D speckle tracking echocardiography in early detection of cardiotoxicity.

METHODS: Relevant case control studies published prior to December 2022 were extracted to assess cardiotoxicity by 3D STE in patients after chemotherapy.

RESULTS: A total of 1991 chemotherapy treated patients and control patients were included in the present review via pooling 22 studies.

CONCLUSIONS: 3D speckle tracking echocardiography has the utility of non-invasive and objective evaluation of changes in left ventricular function in cancer patients undergoing chemotherapy.

ROSPERO REGISTRATION NO: Study ID, CRD42023383790 on PROSPERO: International prospective register of systematic reviews.

PMID:37587421 | DOI:10.1186/s12885-023-11261-y

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PubMed articles on: Cardio-Oncology

Association of radiation dose to cardiac substructures with major ischaemic events following breast cancer radiotherapy

Eur Heart J. 2023 Aug 16:ehad462. doi: 10.1093/eurheartj/ehad462. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Patients with left-sided breast cancer receive a higher mean heart dose (MHD) after radiotherapy, with subsequent risk of ischaemic heart disease. However, the optimum dosimetric predictor among cardiac substructures has not yet been determined.

METHODS AND RESULTS: This study retrospectively reviewed 2158 women with breast cancer receiving adjuvant radiotherapy. The primary endpoint was a major ischaemic event. The dose-volume parameters of each delineated cardiac substructure were calculated. The risk factors for major ischaemic events and the association between MHD and major ischaemic events were analysed by Cox regression. The optimum dose-volume predictors among cardiac substructures were explored in multivariable models by comparing performance metrics of each model. At a median follow-up of 7.9 years (interquartile range 5.6-10.8 years), 89 patients developed major ischaemic events. The cumulative incidence rate of major ischaemic events was significantly higher in left-sided disease (P = 0.044). Overall, MHD increased the risk of major ischaemic events by 6.2% per Gy (hazard ratio 1.062, 95% confidence interval 1.01-1.12; P = 0.012). The model containing the volume of the left ventricle receiving 25 Gy (LV V25) with the cut-point of 4% presented with the best goodness of fit and discrimination performance in left-sided breast cancer. Age, chronic kidney disease, and hyperlipidaemia were also significant risk factors.

CONCLUSION: Risk of major ischaemic events exist in the era of modern radiotherapy. LV V25 ≥ 4% appeared to be the optimum parameter and was superior to MHD in predicting major ischaemic events. This dose constraint could aid in achieving better heart protection in breast cancer radiotherapy, though a further validation study is warranted.

PMID:37585426 | DOI:10.1093/eurheartj/ehad462

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PubMed articles on: Cardio-Oncology

Radiation-Induced Pericardial Disease: Mechanisms, Diagnosis, and Treatment

Curr Cardiol Rep. 2023 Aug 16. doi: 10.1007/s11886-023-01933-3. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: We aim to give a concise overview of the different clinical manifestations of both acute and long-term radiotherapy-related pericardial diseases, the underlying pathophysiology as well as the diagnosis and treatment options.

RECENT FINDINGS: Radiotherapy-related pericardial disease is common, but despite radiotherapy being a cornerstone of many cancer treatments, this disease entity is relatively underrepresented in clinical trials, resulting in a paucity of research data on pathophysiology and management. Since the development of innovative cancer treatments, survival has significantly improved. Therefore, the importance of long-term treatment-related side effects increases, most notably cancer treatment-related cardiovascular toxicity. In patients undergoing radiotherapy as a part of their cancer treatment, radiotherapy-related pericardial disease can manifest early (during or shortly after radiotherapy administration) or very late (several years to decades after treatment). This exceptionally long latency period confronts physicians with treatment-related side effects of radiotherapy regimens that may have been abandoned already.

PMID:37584875 | DOI:10.1007/s11886-023-01933-3

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PubMed articles on: Cardio-Oncology

Discovery of 2-Aminopyrimidine Derivatives as Potent Dual FLT3/CHK1 Inhibitors with Significantly Reduced hERG Inhibitory Activities

J Med Chem. 2023 Aug 16. doi: 10.1021/acs.jmedchem.3c00245. Online ahead of print.

ABSTRACT

FLT3 inhibitors as single agents have limited effects because of acquired and adaptive resistance and the cardiotoxicity related to human ether-a-go-go-related gene (hERG) channel blockade further impedes safe drugs to the market. Inhibitors having potential to overcome resistance and reduce hERG affinity are highly demanded. Here, we reported a dual FLT3/CHK1 inhibitor 18, which displayed potencies to overcome varying acquired resistance in BaF3 cells with FLT3-TKD and FLT3-ITD-TKD mutations. Moreover, 18displayed high selectivity over c-KIT more than 1700-fold and greatly reduced hERG affinity, with an IC50 value of 58.4 μM. Further mechanistic studies demonstrated 18can upregulate p53 and abolish the outgrowth of adaptive resistant cells. In the in vivo studies, 18demonstrated favorable PK profiles and good safety, suppressed the tumor growth in the MV-4-11 cell inoculated mouse xenograft model, and prolonged the survival in the Molm-13 transplantation model, supporting its further development.

PMID:37584545 | DOI:10.1021/acs.jmedchem.3c00245

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PubMed articles on: Cardio-Oncology

Association of immune checkpoint inhibitors therapy with arterial thromboembolic events in cancer patients: A retrospective cohort study

Cancer Med. 2023 Aug 16. doi: 10.1002/cam4.6455. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for various malignancies. However, research indicates blocking the immune checkpoint pathway may exacerbate atherosclerotic lesions.

OBJECTIVES: We aimed to investigate whether ICI therapy increases the risk of arterial thromboembolic events (ATEs).

METHODS: A retrospective cohort study was conducted on patients with histologically confirmed cancer at our institution between 2018 and 2021, using the propensity score matching method. The primary endpoint was ATEs occurrence, comprising acute coronary syndrome, stroke/transient ischemic attack, and peripheral arterial thromboembolism. Subgroup analyses assessed whether the ICI treatment effect on ATEs varied over time by limiting the maximum follow-up duration. Logistic regression analysis identified ATE risk factors in ICI-treated patients.

RESULTS: Overall, the ICI group (n = 2877) demonstrated an ATEs risk 2.01 times higher than the non-ICI group (RR, 2.01 [95% CI (1.61-2.51)]; p < 0.001). Subgroup analysis revealed no significant increase in ATEs risk for ICI-treated patients within 1 year (Limited to a max 9-month follow-up, p = 0.075). However, ATEs risk in the ICI group rose by 41% at 1 year (p = 0.010) and 97% at 4 years (p ≤ 0.001). Age, diabetes, hypertension, peripheral atherosclerosis, atrial fibrillation, chronic ischemic heart disease, distant cancer metastasis, and ICI treatment cycles contributed to ATEs risk elevation in ICI-treated patients.

CONCLUSION: ICI-treated patients may exhibit a higher risk of ATEs, especially after 1 year of treatment.

PMID:37584246 | DOI:10.1002/cam4.6455

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PubMed articles on: Cancer & VTE/PE

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19

JAMA Oncol. 2023 Aug 17. doi: 10.1001/jamaoncol.2023.2934. Online ahead of print.