ABSTRACT

Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand-foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m2) on day 1 along with ifosfamide (3000 mg/m2 on days 1, 2, and 3 with equidose MESNA) administered every 3 weeks. The overall response rate, yielding 40% (95% CI: 0.29-0.51), resulted in statistical significance; the disease control rate stood at 81% (95% CI: 0.73-0.90), while only 16% (95% CI: 0.08-0.24) of patients experienced a progressive disease. These findings indicate that the combination of NPLD and ifosfamide yields a statistically significant response rate in advanced/metastatic STS with limited toxicity.

PMID:37894403 | PMC:PMC10605752 | DOI:10.3390/cancers15205036

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03:07

PubMed articles on: Cardio-Oncology

The Protective Effect of Citronellol against Doxorubicin-Induced Cardiotoxicity in Rats

Biomedicines. 2023 Oct 18;11(10):2820. doi: 10.3390/biomedicines11102820.

ABSTRACT

Citronellol has been reported to have anti-inflammatory, anti-cancer, and antihypertensive activities, but its effect on myocardial ischemia is still unclear. The aim of this study was to investigate the therapeutic effects and pharmacological mechanisms of citronellol on ischemia. Therefore, a rat model of myocardial ischemia was established using the doxorubicin (DOX) model. To induce cardiotoxicity, the rats were given DOX (2.5 mg/kg) intraperitoneally over a 14-day period. Group I served as the control and received tween 80 (0.2%), group II received the vehicle and DOX, group III received the standard drug dexrazoxane and DOX, whereas groups IV, V, and VI were treated orally with citronellol (25, 50, and 100 mg/kg) and DOX, respectively. After treatment, the rats were euthanized, and blood samples were collected to assess the levels of serum cardiac markers, lipid profiles, and tissue antioxidant enzymes. The gene expressions of eNOS, PPAR-g, IL-10, VEGF, and NFkB-1 were also determined using real-time polymerase chain reactions. Simultaneous treatment with DOX and citronellol reduced cardiac antioxidant enzymes and lipid biomarkers in a dose-dependent manner. Citronellol also increased the expression of anti-inflammatory cytokines while reducing the expression of pro-inflammatory cytokines. Therefore, it can be concluded that citronellol may have potential cardioprotective effects in preventing DOX-induced cardiotoxicity.

PMID:37893193 | PMC:PMC10604204 | DOI:10.3390/biomedicines11102820

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03:07

PubMed articles on: Cardio-Oncology

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF

J Clin Med. 2023 Oct 12;12(20):6486. doi: 10.3390/jcm12206486.

ABSTRACT

The neurohormonal model of heart failure (HF) pathogenesis states that a reduction in cardiac output caused by cardiac injury results in sympathetic nervous system (SNS) activation, that is adaptive in the short-term and maladaptive in the long-term. This model has proved extremely valid and has been applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF), which is due to hypertension (HTN) in the vast majority of the cases. Erroneously, HTN, which is the leading cause of cardiovascular disease and premature death worldwide and is present in more than 90% of HF patients, is tightly linked with SNS overactivity. In this paper we provide a contemporary overview of the contribution of SNS overactivity to the development and progression of hypertensive HF (HHF) as well as the clinical implications resulting from therapeutic interventions modifying SNS activity. Throughout the manuscript the terms HHF with preserved LVEF and HfpEF will be used interchangeably, considering that the findings in most HFpEF studies are driven by HTN.

PMID:37892623 | PMC:PMC10607346 | DOI:10.3390/jcm12206486

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03:07

PubMed articles on: Cardio-Oncology

Exploring the Multifaceted Nexus of Uric Acid and Health: A Review of Recent Studies on Diverse Diseases

Biomolecules. 2023 Oct 13;13(10):1519. doi: 10.3390/biom13101519.

ABSTRACT

The prevalence of patients with hyperuricemia or gout is increasing worldwide. Hyperuricemia and gout are primarily attributed to genetic factors, along with lifestyle factors like consuming a purine-rich diet, alcohol and/or fructose intake, and physical activity. While numerous studies have reported various comorbidities linked to hyperuricemia or gout, the range of these associations is extensive. This review article focuses on the relationship between uric acid and thirteen specific domains: transporters, genetic factors, diet, lifestyle, gout, diabetes mellitus, metabolic syndrome, atherosclerosis, hypertension, kidney diseases, cardiovascular diseases, neurological diseases, and malignancies. The present article provides a comprehensive review of recent developments in these areas, compiled by experts from the Young Committee of the Japanese Society of Gout and Uric and Nucleic Acids. The consolidated summary serves to enhance the global comprehension of uric acid-related matters.

PMID:37892201 | PMC:PMC10604821 | DOI:10.3390/biom13101519

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03:07

PubMed articles on: Cardio-Oncology

Simplified rules-based tool to facilitate the application of up-to-date management recommendations in cardio-oncology

Cardiooncology. 2023 Oct 27;9(1):37. doi: 10.1186/s40959-023-00179-w.

ABSTRACT

BACKGROUND: Millions of cancer survivors are at risk of cardiovascular diseases, a leading cause of morbidity and mortality. Tools to potentially facilitate implementation of cardiology guidelines, consensus recommendations, and scientific statements to prevent atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular diseases are limited. Thus, inadequate utilization of cardiovascular medications and imaging is widespread, including significantly lower rates of statin use among cancer survivors for whom statin therapy is indicated.

METHODS: In this methodological study, we leveraged published guidelines documents to create a rules-based tool to include guidelines, expert consensus, and medical society scientific statements relevant to point of care cardiovascular disease prevention in the cardiovascular care of cancer survivors. Any overlap, redundancy, or ambiguous recommendations were identified and eliminated across all converted sources of knowledge. The integrity of the tool was assessed with use case examples and review of subsequent care suggestions.

RESULTS: An initial selection of 10 guidelines, expert consensus, and medical society scientific statements was made for this study. Then 7 were kept owing to overlap and revisions in society recommendations over recent years. Extensive formulae were employed to translate the recommendations of 7 selected guidelines into rules and proposed action measures. Patient suitability and care suggestions were assessed for several use case examples.

CONCLUSION: A simple rules-based application was designed to provide a potential format to deliver critical cardiovascular disease best-practice prevention recommendations at the point of care for cancer survivors. A version of this tool may potentially facilitate implementing these guidelines across clinics, payers, and health systems for preventing cardiovascular diseases in cancer survivors.

TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05377320.

PMID:37891699 | DOI:10.1186/s40959-023-00179-w

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03:07

PubMed articles on: Cardio-Oncology

Methods to assess radiation-induced cardiotoxicity in rodent models

Methods Cell Biol. 2023;180:127-146. doi: 10.1016/bs.mcb.2023.02.014. Epub 2023 Apr 24.

ABSTRACT

Cancer survivors who have received thoracic radiation as part of their primary treatment are at risk for developing radiation-induced cardiotoxicity (RICT) due to incidental radiation delivered to the heart. In recent decades, advancements in radiation delivery have dramatically improved the therapeutic ratio of radiation therapy (RT)-efficiently targeting malignancies while sparing the heart; yet, in many patients, incidental radiation to the heart cannot be fully avoided. Cardiac radiation exposure can cause long-term morbidity and contribute to poorer survival in cancer patients. Severe cardiac effects can occur within 2years of treatment. Currently, there is no way to predict who is at higher or lower risk of developing cardiotoxicity from radiation, and the critical factors that alter RICT have not yet been clearly identified. Thus, pre-clinical investigations are an important step towards better prevention, detection, and management of RICT in cancer survivors. The overarching aim of this chapter is to provide researchers with foundational and technical knowledge in the use of mice and rats for RICT investigations. After a brief overview of RICT pathophysiology and clinical manifestations, we discuss important considerations of RICT study design, including animal selection and radiation planning. We then provide example protocols for murine tissue harvesting and processing that can support use in downstream applications of the reader's choosing.

PMID:37890926 | DOI:10.1016/bs.mcb.2023.02.014

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03:07

PubMed articles on: Cardio-Oncology

Cardiovascular Impact of Near Complete Estrogen Deprivation in Premenopausal Women with Breast Cancer: The CROWN Study

Am Heart J. 2023 Oct 25:S0002-8703(23)00300-9. doi: 10.1016/j.ahj.2023.10.007. Online ahead of print.

ABSTRACT

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and two CCTA scans during the two-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026-2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

PMID:37890547 | DOI:10.1016/j.ahj.2023.10.007

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03:07

PubMed articles on: Cardio-Oncology

Recent advances in pluripotent stem cell-derived cardiac organoids and heart-on-chip applications for studying anti-cancer drug-induced cardiotoxicity

Cell Biol Toxicol. 2023 Oct 27. doi: 10.1007/s10565-023-09835-4. Online ahead of print.

ABSTRACT

Cardiovascular disease (CVD) caused by anti-cancer drug-induced cardiotoxicity is now the second leading cause of mortality among cancer survivors. It is necessary to establish efficient in vitro models for early predicting the potential cardiotoxicity of anti-cancer drugs, as well as for screening drugs that would alleviate cardiotoxicity during and post treatment. Human induced pluripotent stem cells (hiPSCs) have opened up new avenues in cardio-oncology. With the breakthrough of tissue engineering technology, a variety of hiPSC-derived cardiac microtissues or organoids have been recently reported, which have shown enormous potential in studying cardiotoxicity. Moreover, using hiPSC-derived heart-on-chip for studying cardiotoxicity has provided novel insights into the underlying mechanisms. Herein, we summarize different types of anti-cancer drug-induced cardiotoxicities and present an extensive overview on the applications of hiPSC-derived cardiac microtissues, cardiac organoids, and heart-on-chips in cardiotoxicity. Finally, we highlight clinical and translational challenges around hiPSC-derived cardiac microtissues/organoids/heart-on chips and their applications in anti-cancer drug-induced cardiotoxicity. • Anti-cancer drug-induced cardiotoxicities represent pressing challenges for cancer treatments, and cardiovascular disease is the second leading cause of mortality among cancer survivors. • Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology. • Emerging evidence supports that hiPSC-derived cardiac organoids and heart-on-chip are promising in vitro platforms for predicting and minimizing anti-cancer drug-induced cardiotoxicity.

PMID:37889357 | DOI:10.1007/s10565-023-09835-4

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03:07

PubMed articles on: Cardio-Oncology

Circulating Cardiovascular Biomarkers in Cancer Therapeutics-Related Cardiotoxicity: Review of Critical Challenges, Solutions, and Future Directions

J Am Heart Assoc. 2023 Oct 27:e029574. doi: 10.1161/JAHA.123.029574. Online ahead of print.

ABSTRACT

Cardiotoxicity is a growing concern in the oncology population. Transthoracic echocardiography and multigated acquisition scans have been used for surveillance but are relatively insensitive and resource intensive. Innovative imaging techniques are constrained by cost and availability. More sensitive, cost-effective cardiotoxicity surveillance strategies are needed. Circulating cardiovascular biomarkers could provide a sensitive, low-cost solution. Biomarkers such as troponins, natriuretic peptides (NPs), novel upstream signals of oxidative stress, inflammation, and fibrosis as well as panomic technologies have shown substantial promise, and guidelines recommend baseline measurement of troponins and NPs in all patients receiving potential cardiotoxins. Nonetheless, supporting evidence has been hampered by several limitations. Previous reviews have provided valuable perspectives on biomarkers in cancer populations, but important analytic aspects remain to be examined in depth. This review provides comprehensive assessment of critical challenges and solutions in this field, with focus on analytical issues relating to biomarker measurement and interpretation. Examination of evidence pertaining to common and serious forms of cardiotoxicity reveals that improved study designs incorporating larger, more diverse populations, registry-based approaches, and refinement of current definitions are key. Further efforts to harmonize biomarker methodologies including centralized biobanking and analyses, novel decision limits, and head-to-head comparisons are needed. Multimarker algorithms incorporating machine learning may allow rapid, personalized risk assessment. These improvements will not only augment the predictive value of circulating biomarkers in cardiotoxicity but may elucidate both direct and indirect relationships between cardiovascular disease and cancer, allowing biomarkers a greater role in the development and success of novel anticancer therapies.

PMID:37889193 | DOI:10.1161/JAHA.123.029574

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03:07

PubMed articles on: Cardio-Oncology

Detection of Early Myocardial Dysfunction by Imaging Biomarkers in Cancer Patients Undergoing Photon Beam vs. Proton Beam Radiotherapy: A Prospective Study

J Cardiovasc Dev Dis. 2023 Oct 4;10(10):418. doi: 10.3390/jcdd10100418.

ABSTRACT

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) were women. The median (interquartile range) of the mean heart dose was lower in the PBT than the PhT group (47 [27-79] vs. 217 [120-596] cGy, respectively; p < 0.001). Ejection fraction did not change in either group. Only the PhT group had reduced systolic tissue Doppler velocities at 3 months. 2D-STE showed changes in endocardial and epicardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing PhT (global longitudinal SRe, pretreatment vs. end of treatment (p = 0.04); global circumferential SRe, pretreatment vs. at 3-month follow-up (p = 0.003); global radial SRe, pretreatment vs. at 3-month follow-up (p = 0.02) for endocardial values). Epicardial strain values decreased significantly only in patients treated with PhT. Patients in the PhT group had a significant decrease in epicardial global longitudinal systolic strain rate (GLSRs) (epicardial GLSRs, at baseline vs. at end of treatment [p = 0.009]) and in GCSRe and GRSRe (epicardial GCSRe, at baseline vs. at 3-month follow-up (p = 0.02); epicardial GRSRe, at baseline vs. at 3-month follow-up (p = 0.03)) during treatment and follow-up. No changes on 2D-STE were detected in the PBT group. 4. Conclusions: Patients who underwent PhT but not PBT had reduced tissue Doppler velocities and SRe values during follow-up, suggesting early myocardial relaxation abnormalities. PBT shows promise as a cardiac-sparing RT technology.

PMID:37887865 | PMC:PMC10607871 | DOI:10.3390/jcdd10100418

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03:07

PubMed articles on: Cardio-Oncology

Correlation of High-Sensitivity Cardiac Troponin I Values and Cardiac Radiation Doses in Patients with Left-Sided Breast Cancer Undergoing Hypofractionated Adjuvant Radiotherapy with Concurrent Anti-HER2 Therapy

Curr Oncol. 2023 Oct 6;30(10):9049-9062. doi: 10.3390/curroncol30100654.

ABSTRACT

Anti HER2 therapy and left breast adjuvant radiation therapy (RT) can both result in cardiotoxicity. The aim of this study was to evaluate the influence of radiation dose on cardiac structures on the values of the early cardiotoxicity marker high-sensitivity cardiac troponin I (hscTnI) in patients with HER2-positive left breast cancer undergoing adjuvant concomitant antiHER2 therapy and radiotherapy, and to establish a correlation between the hscTnI values and cardiac radiation doses. Sixty-one patients underwent left breast hypofractionated radiotherapy in parallel with anti-HER2 therapy: trastuzumab, combined trastuzumab-pertuzumab or trastuzumab emtansine (T-DM1). The hscTnI values were measured prior to and upon completion of radiotherapy. A significant increase in hscTnI was defined as >30% from baseline, with the second value being 4 ng/L or higher. Dose volume histograms (DVH) were generated for the heart, left ventricle (LV) and left anterior descending artery (LAD). The hscTnI levels were corelated with radiation doses on cardiac structures. An increase in hscTnI values was observed in 17 patients (Group 1). These patients had significantly higher mean radiation doses for the heart (p = 0.02), LV (p = 0.03) and LAD (p = 0.04), and AUC for heart and LV (p = 0.01), than patients without hscTnI increase (Group 2). The patients in Group 1 also had larger volumes of heart and LV receiving 2 Gy (p = 0.01 for both) and 4 Gy (p = 0.02 for both). LAD differences were observed in volumes receiving 2 Gy (p = 0.03), 4 Gy (p = 0.02) and 5 Gy (p = 0.02). The increase in hscTnI observed in patients receiving anti-HER2 therapy after adjuvant RT was positively associated with radiation doses on the heart, LV and LAD.

PMID:37887554 | PMC:PMC10605836 | DOI:10.3390/curroncol30100654

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03:07

PubMed articles on: Cardio-Oncology

Cardiac Toxicities in Oncology: Elucidating the Dark Box in the Era of Precision Medicine

Curr Issues Mol Biol. 2023 Oct 15;45(10):8337-8358. doi: 10.3390/cimb45100526.

ABSTRACT

Despite current advancements in chemotherapy, immunotherapy and targeted treatments, the potential for major adverse cardiovascular events, regardless of previous cardiac history, persists. Scoring systems, such as the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) risk assessment tool, can be utilized to evaluate several factors including prior cardiac history, risk factors and cardiac biomarkers to categorize patients into low, moderate, high, and very high-risk groups. Common cardiotoxicity complications include new or worsening left ventricular ejection fraction (LVEF), QT interval prolongation, myocardial ischaemia, hypertension, thromboembolic disease, cardiac device malfunction and valve disease. Baseline electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are routinely performed for all patients commenced on cardiotoxic treatment, while other imaging modalities and biochemical markers have proven useful for monitoring. Management mainly includes early risk stratification and prompt identification of cardiovascular complications, with patient-specific surveillance throughout treatment. A multidisciplinary approach is crucial in determining the relationship between potential treatment benefits and cardiotoxicity, and whether the continuation of treatment is appropriate on a case-by-case basis. Early risk stratification, optimizing the patient's cardiovascular status prior to treatment, and prompt identification of suspected cardiotoxicity are key in significantly reducing risk. This article provides a comprehensive review of the various types of treatment-related cardiotoxicity, offering guidance on identifying high-risk patients, recognizing early signs of cardiotoxicity, and outlining appropriate treatment approaches and follow-up care for such cases.

PMID:37886969 | PMC:PMC10605822 | DOI:10.3390/cimb45100526

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03:07

PubMed articles on: Cardio-Oncology

Retraction: Longitude variation of the microRNA-497/FGF-23 axis during treatment and its linkage with neoadjuvant/adjuvant trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients

Front Surg. 2023 Oct 11;10:1307330. doi: 10.3389/fsurg.2023.1307330. eCollection 2023.

ABSTRACT

[This retracts the article DOI: 10.3389/fsurg.2022.862617.].

PMID:37886634 | PMC:PMC10599136 | DOI:10.3389/fsurg.2023.1307330

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03:07

PubMed articles on: Cardio-Oncology

Irbesartan ameliorates inflammation via transendothelial leukocyte migration due to VCAM-1/NOX-1 signaling in cisplatin-induced cardiotoxicity

Iran J Basic Med Sci. 2023;26(11):1298-1304. doi: 10.22038/IJBMS.2023.70997.15422.

ABSTRACT

OBJECTIVES: Cisplatin (CP) is frequently used in various types of cancers. The cardiotoxic effects of this agent limit its usage. Our study seeks to investigate the protective effects of Irbesartan (IRB) on CP-induced cardiotoxicity.

MATERIALS AND METHODS: The following four groups comprised thirty-two rats: control, CP, CP+IRB, and IRB. On the fourth day of the experiment, 5 mg/kg of CP was given to CP and CP+IRB groups intraperitoneally, and for seven days, water or IRB 50 mg/kg (orally) was administered. Vascular endothelial growth factor (VEGF), caspase-3 (Cas-3), vascular cell adhesion molecule-1 (VCAM-1), NADPH oxidase-1 (NOX-1), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were measured.

RESULTS: The levels of VCAM-1, NOX-1, VEGF, Cas-3, and LDH were increased in the CP group. The treatment with IRB decreased VCAM-1, NOX-1, VEGF, Cas-3, and LDH levels significantly (P0.05). Histopathological examination revealed normal heart architecture in Control and IRB groups. While marked hyperemia and myocardial cell degeneration were noticed in the CP group, significant amelioration was observed in the CP+IRB group. Aortas in the CP group showed endothelial damage and desquamation. IRB treatment markedly ameliorated histopathological findings in the CP+IRB group. Cardiac and aortic damage caused by CP was attenuated by IRB treatment owing to the anti-inflammatory and antiapoptotic effects of IRB.

CONCLUSION: IRB may help reduce the severity of CP-induced cardiac injury by limiting leukocyte migration and reducing inflammation and apoptosis.

PMID:37885998 | PMC:PMC10598814 | DOI:10.22038/IJBMS.2023.70997.15422

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03:07

PubMed articles on: Cardio-Oncology

The (pro)renin Receptor - A Regulatory Nodal Point in Disease Networks

Curr Drug Targets. 2023 Oct 25. doi: 10.2174/0113894501250617231016052930. Online ahead of print.

ABSTRACT

Experimental inhibition of the (pro)renin receptor [(P)RR] is a promising therapeutic strategy in different disease models ranging from cardiorenal to oncological entities. Here, we briefly review the direct protein-protein interaction partners of the (P)RR and the plethora of distinct diseases in which the (P)RR is involved. The first structural work on the (P)RR using AlphaFold, which was recently published by Ebihara et al., is the center of this mini-review since it can mechanistically link the protein-protein interaction level with the pathophysiological level. More detailed insights into the 3D structure of the (P)RR and its interaction domains might guide drug discovery on this novel target. Finally, antibody- and small molecule-based approaches to inhibit the (P)RR are shortly discussed.

PMID:37885110 | DOI:10.2174/0113894501250617231016052930

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03:07

PubMed articles on: Cardio-Oncology

Thymus alterations and susceptibility to immune checkpoint inhibitor myocarditis

Nat Med. 2023 Oct 26. doi: 10.1038/s41591-023-02591-2. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors (ICI) have transformed the therapeutic landscape in oncology. However, ICI can induce uncommon life-threatening autoimmune T-cell-mediated myotoxicities, including myocarditis and myositis. The thymus plays a critical role in T cell maturation. Here we demonstrate that thymic alterations are associated with increased incidence and severity of ICI myotoxicities. First, using the international pharmacovigilance database VigiBase, the Assistance Publique Hôpitaux de Paris-Sorbonne University data warehouse (Paris, France) and a meta-analysis of clinical trials, we show that ICI treatment of thymic epithelial tumors (TET, and particularly thymoma) was more frequently associated with ICI myotoxicities than other ICI-treated cancers. Second, in an international ICI myocarditis registry, we established that myocarditis occurred earlier after ICI initiation in patients with TET (including active or prior history of TET) compared to other cancers and was more severe in terms of life-threatening arrythmias and concurrent myositis, leading to respiratory muscle failure and death. Lastly, we show that presence of anti-acetylcholine-receptor antibodies (a biological proxy of thymic-associated autoimmunity) was more prevalent in patients with ICI myocarditis than in ICI-treated control patients. Altogether, our results highlight that thymic alterations are associated with incidence and seriousness of ICI myotoxicities. Clinico-radio-biological workup evaluating the thymus may help in predicting ICI myotoxicities.

PMID:37884625 | DOI:10.1038/s41591-023-02591-2

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03:07

PubMed articles on: Cardio-Oncology

Clinical outcomes of takotsubo syndrome in patients with cancer: a systematic review and meta-analysis

Front Cardiovasc Med. 2023 Sep 29;10:1244808. doi: 10.3389/fcvm.2023.1244808. eCollection 2023.

ABSTRACT

BACKGROUND: Recent studies suggested a relationship between Takotsubo syndrome (TTS) and malignancy. However, clinical outcomes of TTS associated with cancer have not been assessed completely. This study was aimed to investigate the outcomes of patients with TTS and cancer.

METHODS: We performed a systematic review and meta-analysis to evaluate the clinical outcomes of TTS in patients with and without malignancy. We systematically reviewed and analyzed 14 studies (189,210 patients) published in PubMed and Cochrane Library databases until December 2022. The primary outcome was all-cause mortality at the longest follow-up.

RESULTS: The prevalence of current or previous malignancy in patients with TTS was 8.7% (16,461 patients). Patients with TTS and malignancy demonstrated a higher risk of mortality at the longest follow-up than those with TTS alone (odds ratio [OR], 2.41; 95% confidence interval [CI]; 1.95-2.98; P < 0.001). Moreover, cancer was significantly associated with an increased risk of in-hospital or 30-day mortality (OR 2.36; 95% CI, 1.67-3.33; P < 0.001), shock (OR 1.42; 95% CI, 1.30-1.55; P < 0.001), mechanical respiratory support (OR 1.68; 95% CI, 1.59-1.77; P < 0.001), arrhythmia (OR 1.27; 95% CI, 1.21-1.34; P < 0.001), and major adverse cardiac events (OR 1.69; 95% CI, 1.18-2.442; P < 0.001).

CONCLUSIONS: This study revealed significant associations between previous or active cancer and an increased risk of all-cause mortality and in-hospital adverse events in patients with TTS.

PMID:37840966 | PMC:PMC10570743 | DOI:10.3389/fcvm.2023.1244808

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03:07

PubMed articles on: Cardio-Oncology

Pyothorax and Constrictive Pericarditis after Chemoradiotherapy for Esophageal Cancer: A Case Report

Intern Med. 2023 Oct 13. doi: 10.2169/internalmedicine.2502-23. Online ahead of print.

ABSTRACT

A 75-year-old man underwent chemoradiotherapy for advanced esophageal cancer. After nine years, he was hospitalized for left pyothorax. Consequently, the patient underwent drainage and window opening surgery. He experienced cardiopulmonary arrest but was resuscitated. Based on cardiac catheterization data, the patient was diagnosed with constrictive pericarditis. Unfortunately, extracorporeal circulation did not improve his condition, and he ultimately died. An autopsy revealed adhesion between the pericardium and pleura, especially the pericardium in contact with the left thoracic cavity, which was markedly thickened. This suggests that constrictive pericarditis, a latent complication of chemoradiotherapy, is aggravated by pyothorax.

PMID:37839880 | DOI:10.2169/internalmedicine.2502-23

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03:07

PubMed articles on: Cardio-Oncology

Association of chronic kidney disease with cardiovascular disease in cancer patients: a cross-sectional study

Cardiorenal Med. 2023 Oct 14. doi: 10.1159/000534182. Online ahead of print.

ABSTRACT

INTRODUCTION: Due to the cardiotoxicity of cancer treatment and traditional risk factors for cardiovascular disease (CVD) such as obesity, diabetes, dyslipidemia, and hypertension, cancer patients are at higher risk of developing CVD. However, limited research exists on the correlation between chronic kidney disease (CKD) and CVD risk in cancer patients.

METHODS: This cross-sectional study selected cancer patients aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) conducted from 2015 to 2020. Multivariable logistic regression was used to assess the association between CKD and CVD in cancer patients. Additionally, subgroup analyses were conducted to investigate the association among different groups of cancer patients.

RESULTS: We included 1700 adult cancer patients (52.53% were female). After multivariable adjustment for covariates including traditional CVD factors, CKD was significantly associated with CVD, with an odds ratio (95% confidence interval) and P-value of 1.61(1.18,2.19) and 0.004. Subgroup analyses after multivariable adjustment showed a significant correlation between CKD and increased CVD risk in the following populations: age ≥60 years, males, White ethnicity, and individuals with or without traditional CVD factors (obesity, diabetes, dyslipidemia, and hypertension).

CONCLUSIONS: CKD remains a significant factor in the higher risk of CVD among adult cancer patients in the United States, even after adjustment for traditional CVD risk factors. Therefore, to reduce the risk of CVD in cancer patients, it is important to treat CKD as a non-traditional risk factor for CVD and actively manage it.

PMID:37839394 | DOI:10.1159/000534182

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03:07

PubMed articles on: Cardio-Oncology

Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection

Redox Biol. 2023 Nov;67:102894. doi: 10.1016/j.redox.2023.102894. Epub 2023 Oct 6.

ABSTRACT

The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury and cardioprotection. In the first part, the continued need for cardioprotection beyond that by rapid reperfusion of acute myocardial infarction is emphasized. Then, pathomechanisms of myocardial ischemia/reperfusion to the myocardium and the coronary circulation and the different modes of cell death in myocardial infarction are characterized. Different mechanical and pharmacological interventions to protect the ischemic/reperfused myocardium in elective percutaneous coronary interventions and coronary artery bypass grafting, in acute myocardial infarction and in cardiotoxicity from cancer therapy are detailed. The second part keeps the focus on ROS providing a comprehensive overview of molecular and cellular mechanisms involved in ischemia/reperfusion injury. Starting from mitochondria as the main sources and targets of ROS in ischemic/reperfused myocardium, a complex network of cellular and extracellular processes is discussed, including relationships with Ca2+ homeostasis, thiol group redox balance, hydrogen sulfide modulation, cross-talk with NAPDH oxidases, exosomes, cytokines and growth factors. While mechanistic insights are needed to improve our current therapeutic approaches, advancements in knowledge of ROS-mediated processes indicate that detrimental facets of oxidative stress are opposed by ROS requirement for physiological and protective reactions. This inevitable contrast is likely to underlie unsuccessful clinical trials and limits the development of novel cardioprotective interventions simply based upon ROS removal.

PMID:37839355 | PMC:PMC10590874 | DOI:10.1016/j.redox.2023.102894

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03:07

PubMed articles on: Cardio-Oncology

Empagliflozin treatment of cardiotoxicity: A comprehensive review of clinical, immunobiological, neuroimmune, and therapeutic implications

Biomed Pharmacother. 2023 Oct 13;168:115686. doi: 10.1016/j.biopha.2023.115686. Online ahead of print.

ABSTRACT

Cancer and cardiovascular disorders are known as the two main leading causes of mortality worldwide. Cardiotoxicity is a critical and common adverse effect of cancer-related chemotherapy. Chemotherapy-induced cardiotoxicity has been associated with various cancer treatments, such as anthracyclines, immune checkpoint inhibitors, and kinase inhibitors. Different methods have been reported for the management of chemotherapy-induced cardiotoxicity. In this regard, sodium-glucose cotransporter-2 inhibitors (SGLT2i), a class of antidiabetic agents, have recently been applied to manage heart failure patients. Further, SGLT2i drugs such as EMPA exert protective cardiac and systemic effects. Moreover, it can reduce inflammation through the mediation of major inflammatory components, such as Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes, Adenosine 5'-monophosphate-activated protein kinase (AMPK), and c-Jun N-terminal kinase (JNK) pathways, Signal transducer and activator of transcription (STAT), and overall decreasing transcription of proinflammatory cytokines. The clinical outcome of EMPA administration is related to improving cardiovascular risk factors, including body weight, lipid profile, blood pressure, and arterial stiffness. Intriguingly, SGLT2 suppressors can regulate microglia-driven hyperinflammation affecting neurological and cardiovascular disorders. In this review, we discuss the protective effects of EMPA in chemotherapy-induced cardiotoxicity from molecular, immunological, and neuroimmunological aspects to preclinical and clinical outcomes.

PMID:37839109 | DOI:10.1016/j.biopha.2023.115686

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03:08

PubMed articles on: Cardio-Oncology

CDK4/6 inhibitors: basics, pros, and major cons in breast cancer treatment with specific regard to cardiotoxicity - a narrative review

Ther Adv Med Oncol. 2023 Oct 11;15:17588359231205848. doi: 10.1177/17588359231205848. eCollection 2023.

ABSTRACT

Breast cancer is characterized by the uncontrolled proliferation of breast cells, with a high incidence reported in 2020 to have affected over 2 million women. In recent years, the conventional methods of treating breast cancer have involved radiotherapy and chemotherapy. However, the emergence of CDK4/6 inhibitors has shown potential as a promising cancer therapy. Cyclin-dependent kinases (CDK) inhibitors are a class of molecules that impede the formation of an active kinase complex, thereby hindering its activity and consequently halting the progression of the cell cycle. It was discovered that they have a significant impact on impeding the progression of the cancer. This is evident with the Food and Drug Administration's approval of drugs such as palbociclib, ribociclib, and abemaciclib for hormone receptor-positive metastatic breast cancer in combination with specific endocrine therapies. In spite of enormous success in breast cancer treatment, certain obstacles have emerged, such as therapy resistance, side effects, and most of all, cardiotoxicity. Some of these drawbacks have been successfully overcome by dosage reduction, different combinations of the drugs, and the assessment of each patient's condition and suitability prior to treatment. Yet other drawbacks still require tenacious research, especially certain cases of cardiotoxicities. This article delves into the biological mechanisms of CDK4/6 in the cell cycle and cancer, as well as the clinical advantages and most common adverse events (AEs) associated with CDK4/6 inhibitors. The primary objective of this review is to provide a comprehensive analysis of cardiotoxic AEs and elucidate the underlying pathophysiological mechanisms responsible for the cardiotoxicity of CDK4/6 inhibitors.

PMID:37841752 | PMC:PMC10571689 | DOI:10.1177/17588359231205848

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03:08

PubMed articles on: Cardio-Oncology

Brugada phenocopy with altered ST-segment elevation in pericardial diffuse large B-cell lymphoma and effusive-constrictive pericarditis: a case report

Eur Heart J Case Rep. 2023 Oct 17;7(10):ytad463. doi: 10.1093/ehjcr/ytad463. eCollection 2023 Oct.

ABSTRACT

BACKGROUND: Cardiac lymphoma is a rare disease. Effusive-constrictive pericarditis can be a characteristic of pericardial involvement in patients with this disease. Conversely, a phenotype with electrocardiogram changes similar to those of Brugada syndrome is called Brugada phenocopy, and these changes improve after treatment.

CASE SUMMARY: A 71-year-old man was transported to our hospital with chest pain, hypotension, and ST-segment elevation in V1 and V2 leads during maintenance dialysis for renal failure. After arrival at the hospital, his ST-segment elevation disappeared, and emergency coronary angiography scan revealed no significant coronary artery stenoses or obstructions. His computed tomography and echocardiography scans revealed pericardial effusion and an intrapericardial mass. Further, his blood pressure dropped and ST-segment elevation recurred during dialysis after 7 days. Thus, pericardiocentesis was performed, but haemodynamic improvement was insufficient, and right catheterization findings suggested effusive-constrictive pericarditis. Meanwhile, flow cytometry of the pericardial fluid suggested the diagnosis of B-cell lymphoma; however, radical chemoradiotherapy was impossible because of cardiogenic shock. The patient died on Day 17. Further, autopsy revealed diffuse large B-cell lymphoma with pericardial and myocardial infiltration.

DISCUSSION: Cardiac lymphoma is rare but can be associated with effusive-constrictive pericarditis, which may be difficult to manage even with pericardial drainage. In such cases, radical treatment, including chemotherapy, should be promptly considered, if possible. Our patient presented with Brugada-type electrocardiogram but no syncope or family history, suggesting Brugada phenocopy and not true Brugada syndrome due to cardiac lymphoma. Notably, temporary improvement in ST-segment elevation was observed despite the absence of treatment.

PMID:37854103 | PMC:PMC10580269 | DOI:10.1093/ehjcr/ytad463

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03:08

PubMed articles on: Cardio-Oncology

Microparticles and cardiotoxicity secondary to doxorubicin-based chemotherapy in breast cancer patients

Int J Cardiol. 2023 Oct 16:131435. doi: 10.1016/j.ijcard.2023.131435. Online ahead of print.

ABSTRACT

Doxorubicin (DOXO)-cardiotoxicity is a limiting factor for breast cancer chemotherapy. The relationship between microparticles (MPs) and cardiotoxicity remains unclear. MPs can be released under varying pathophysiological conditions. Thereby, this study aimed to assess MPs derived from cardiomyocytes (CardioMPs), platelets (PMPs) and those that expresses tissue factor (TFMPs) in 80 women with breast cancer undergoing DOXO-based chemotherapy, with or without cardiotoxicity in a one-year follow-up. We observed in the cardiotoxicity group higher count of total-MPs at T0 (prior chemotherapy) (p = 0.034), CardioMPs at T0 and T1 (just after chemotherapy) (p = 0.009 and p = 0.0034) and TFMPs at T0 (p = 0.011) compared to non-cardiotoxicity group. The results suggest that MPs could be associated to cardiotoxicity due to DOXO treatment in breast cancer patients.

PMID:37852542 | DOI:10.1016/j.ijcard.2023.131435

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03:08

PubMed articles on: Cardio-Oncology

Multimodal Imaging of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer-A State-of-the-Art Review

J Clin Med. 2023 Sep 29;12(19):6295. doi: 10.3390/jcm12196295.