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1/6/26

ABSTRACT

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is cardiotoxicity. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents that are mainly involved in cardiotoxicity, routine process diagnoses, and methods using omics technology for early and preventive diagnosis. Chemotherapeutic agents and radiation therapies have been implicated as a cause of cardiotoxicity. In response, the area of cardio-oncology has developed into a crucial element of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, routine diagnosis and the monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite the refinements in diagnostics, severe limitations still exist due to the increase in the above-mentioned biomarkers only after significant cardiac damage has occurred. Lately, the research has expanded by introducing new technologies and finding new markers using the omics approach. These new markers could be used not only for early detection but also for the early prevention of cardiotoxicity. Omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide an understanding of the mechanisms of cardiotoxicity beyond traditional technologies.

PMID:37296716 | PMC:PMC10252297 | DOI:10.3390/diagnostics13111864

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PubMed articles on: Cardio-Oncology

Interventional Cardio-Oncology: Unique Challenges and Considerations in a High-Risk Population

Curr Treat Options Oncol. 2023 Jun 10. doi: 10.1007/s11864-023-01110-2. Online ahead of print.

ABSTRACT

Patients with cancer are at risk of developing cardiovascular disease (CVD) including atherosclerotic heart disease (AHD), valvular heart disease (VHD), and atrial fibrillation (AF). Advances in percutaneous catheter-based treatments, including percutaneous coronary intervention (PCI) for AHD, percutaneous valve replacement or repair for VHD, and ablation and left atrial appendage occlusion devices (LAAODs) for AF, have provided patients with CVD significant benefit in the recent decades. However, trials and registries investigating outcomes of these procedures often exclude patients with cancer. As a result, patients with cancer are less likely to undergo these therapies despite their benefits. Despite the inclusion of cancer patients in randomized clinical trial data, studies suggest that cancer patients derive similar benefits of percutaneous therapies for CVD compared with patients without cancer. Therefore, percutaneous interventions for CVD should not be withheld in patients with cancer, as they may still benefit from these procedures.

PMID:37296366 | DOI:10.1007/s11864-023-01110-2

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PubMed articles on: Cardio-Oncology

Cardio-oncology for Pediatric and Adolescent/Young Adult Patients

Curr Treat Options Oncol. 2023 Jun 10. doi: 10.1007/s11864-023-01100-4. Online ahead of print.

ABSTRACT

As chemotherapy continues to improve the lives of patients with cancer, understanding the effects of these drugs on other organ systems, and the cardiovascular system in particular, has become increasingly important. The effects of chemotherapy on the cardiovascular system are a major determinant of morbidity and mortality in these survivors. Although echocardiography continues to be the most widely used modality for assessing cardiotoxicity, newer imaging modalities and biomarker concentrations may detect subclinical cardiotoxicity earlier. Dexrazoxane continues to be the most effective therapy for preventing anthracycline-induced cardiomyopathy. Neurohormonal modulating drugs have not prevented cardiotoxicity, so their widespread, long-term use for all patients is currently not recommended. Advanced cardiac therapies, including heart transplant, have been successful in cancer survivors with end-stage HF and should be considered for these patients. Research on new targets, especially genetic associations, may produce treatments that help reduce cardiovascular morbidity and mortality.

PMID:37296365 | DOI:10.1007/s11864-023-01100-4

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PubMed articles on: Cardio-Oncology

Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue

bioRxiv. 2023 May 25:2023.05.24.542198. doi: 10.1101/2023.05.24.542198. Preprint.

ABSTRACT

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart's energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such as Nmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage.

SIGNIFICANCE STATEMENT: This study uncovers the detrimental impact of chronic oxaliplatin treatment on heart metabolism in mice, linking high accumulative dosages to cardiotoxicity and heart damage. By identifying significant changes in gene expression related to energy metabolic pathways, the findings pave the way for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage. Furthermore, these insights may inform the creation of therapies that compensate for the energy deficit in the heart, ultimately preventing heart damage and improving patient outcomes in cancer treatment.

PMID:37292714 | PMC:PMC10245950 | DOI:10.1101/2023.05.24.542198

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PubMed articles on: Cardio-Oncology

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Lancet Gastroenterol Hepatol. 2023 Jun 5:S2468-1253(23)00141-3. doi: 10.1016/S2468-1253(23)00141-3. Online ahead of print.

ABSTRACT

BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.

METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10<20<1·32·67; NFS: <-1·4550·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.

FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001

INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.

FUNDING: Innovative Medicines Initiative 2.

PMID:37290471 | DOI:10.1016/S2468-1253(23)00141-3

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PubMed articles on: Cancer & VTE/PE

Adult breast, lung, pancreatic, upper and lower gastrointestinal cancer patients with hospitalized venous thromboembolism in the national French hospital discharge database

BMC Cancer. 2023 Jun 10;23(1):531. doi: 10.1186/s12885-023-10877-4.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) and cancer are strongly associated. In France, evidence on patients with pancreatic, upper GI [gastrointestinal], lower GI, lung, or breast cancer-associated VTE and their hospital management is limited. The aims of this study were to provide data on the number of hospitalized VTE events among cancer patients, the patients' characteristics, and their hospital management to estimate the burden of disease and the hospital burden of cancer-related VTE and to provide guidance on research.

METHODS: This longitudinal, observational, and retrospective study was based on the comprehensive hospital discharge database (PMSI). Adult patients (≥ 18 years old) hospitalized with a cancer of interest in 2016 and hospitalized (within 2 years with VTE (captured a as a principal, related, or significant associated diagnosis) were included in the study.

RESULTS: We identified 340,946 cancer patients, of which 7.2% (24,433 patients) were hospitalized with VTE. The proportions of hospitalized VTE were 14.6% (3,237) for patients with pancreatic cancer, 11.2% (8,339) for lung cancer, 9.9% (2,232) for upper GI cancer, 6.7% (7,011) for lower GI cancer, and 3.1% (3,614) for breast cancer. Around two thirds of cancer patients with a hospitalized VTE had active cancer (with metastases and/or receiving chemotherapy during the six months prior to the index date): from 62% of patients with pancreatic cancer to 72% with breast cancer. Around a third of patients were admitted to the hospital through the emergency room, up to 3% of patients stayed in an intensive care unit. The average length of stay ranged from 10 (breast cancer) to 15 days (upper GI cancer). Nine (lower GI cancer) to 18% (pancreatic cancer) of patients died during the VTE hospital stay.

CONCLUSIONS: The burden of cancer-associated VTE is substantial, both in terms of the number of patients affected and in the hospital use. These findings offer guidance on future research on VTE prophylaxis in a very high-risk population, particularly in patients with active cancer.

PMID:37301828 | DOI:10.1186/s12885-023-10877-4

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PubMed articles on: Cancer & VTE/PE

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group

Clin Transl Oncol. 2023 Jun 10. doi: 10.1007/s12094-023-03233-2. Online ahead of print.

ABSTRACT

PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation.

METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification.

RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375).

CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

PMID:37301805 | DOI:10.1007/s12094-023-03233-2