ABSTRACT

Venous thromboembolism (VTE), a condition involving deep vein thrombosis and embolism, can cause death when left untreated. Hospitalized patients and those who have recently undergone surgery or have a cancer diagnosis are at increased risk for VTE development. The updated AORN "Guideline for prevention of venous thromboembolism" provides perioperative nurses with a variety of evidence-based recommendations associated with the topic. This article provides an overview of the guideline and discusses recommendations for a VTE protocol, VTE and bleeding risk assessments, pharmacologic and mechanical VTE prophylaxis, postoperative ambulation, and patient and family education. It also includes a scenario that illustrates the importance of the VTE assessment and the use of mechanical prophylaxis for high-risk patients undergoing operative or other invasive procedures. Perioperative nurses should review the guideline in its entirety and implement recommendations in operative and procedural settings.

PMID:37882602 | DOI:10.1002/aorn.14019

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PubMed articles on: Cancer & VTE/PE

Implementation of routine venous thromboembolism prophylaxis during neoadjuvant chemotherapy for patients with ovarian cancer

Gynecol Oncol. 2023 Oct 11;178:89-95. doi: 10.1016/j.ygyno.2023.10.001. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the venous thromboembolism (VTE) rate in patients with ovarian cancer undergoing neoadjuvant chemotherapy before and after implementing routine thromboprophylaxis.

METHODS: This is a quasi-experimental pre-post study evaluating the VTE rate in patients with ovarian cancer who received neoadjuvant chemotherapy following a quality improvement initiative of routine thromboprophylaxis within a single healthcare system that started in January 2017. Patients were excluded if VTE was diagnosed before initiating chemotherapy. Patient factors and perioperative variables of interest were investigated for their association with VTE through univariate and multivariate models.

RESULTS: Of the 136 patients in the pre-implementation group, 3.7% (n = 5) received thromboprophylaxis. Of the 154 patients in the post-implementation group, 65.6% (n = 101) received thromboprophylaxis. Provider compliance varied from 51% in 2019 to 79.3% in 2021. The overall rate of VTE, from the start of chemotherapy to the end of treatment, was 21.3% (n = 29) pre- and 8.4% (n = 13) in the post-implementation group (p < 0.01). There was no difference in major bleeding events between groups (0% vs. 0.68%, p = 0.63). On univariate analysis, thromboprophylaxis (OR 0.19; 95% CI 0.07-0.52) and post-implementation period (OR 0.34; 95% CI 0.17-0.69) were associated with a decreased risk of any VTE during primary treatment. On multivariate analysis, only thromboprophylaxis remained significantly associated with reduced VTE rates (aOR 0.19; 95% CI 0.07-0.53).

CONCLUSION: Routine thromboprophylaxis during neoadjuvant chemotherapy is associated with reduced risk of VTE throughout primary treatment and is not associated with increased bleeding events.

PMID:37832182 | DOI:10.1016/j.ygyno.2023.10.001

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PubMed articles on: Cancer & VTE/PE

Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis

Medicina (Kaunas). 2023 Oct 20;59(10):1867. doi: 10.3390/medicina59101867.

ABSTRACT

Background and Objectives: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. Materials and Methods: We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). Results: It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I2 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I2 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I2 0%). Conclusions: Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, but without statistical significance. No statistical significance was observed in clinically relevant major or non-major bleeding.

PMID:37893585 | DOI:10.3390/medicina59101867

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PubMed articles on: Cancer & VTE/PE

Intensify Standardized Anticoagulation for Cancer-Associated Pulmonary Embolism: From Single-Center Real-World Data

Clin Ther. 2023 Oct 12:S0149-2918(23)00378-8. doi: 10.1016/j.clinthera.2023.09.014. Online ahead of print.

ABSTRACT

PURPOSE: Pulmonary embolism (PE) is a significant contributor to mortality in patients with cancer. Although anticoagulation serves as the cornerstone of treatment for cancer-associated PE, it has not been emphasized in real-world settings. The aim of this study was to examine the impact of suboptimal anticoagulant treatment on the prognosis of cancer-associated PE.

METHODS: A cohort of 356 individuals newly diagnosed with acute PE were enrolled. The primary outcome of the study was recurrent venous thromboembolism (VTE), and the secondary outcomes were all-cause mortality and major bleeding (consisting of a reduction in the hemoglobin level by at least 20 g/L, transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ or fatal bleeding).

FINDINGS: Of the total participants, 156 (43.8%) were diagnosed with cancer. A comparison between the cancer and noncancer groups revealed that patients with cancer were more frequently asymptomatic (41.0% vs 4.5%; P < 0.001), less likely to have right ventricular dysfunction (4.5% vs 14.0%; P = 0.001), received less anticoagulant treatment during hospitalization (85.3% vs 98.5%; P < 0.001), and had a shorter duration of anticoagulation (5.02 [7.40] months vs 14.19 [10.65] months; P < 0.001). In addition, patients with cancer were found to be at a higher risk of recurrent VTE (17.3% vs 4.0%; P < 0.001) and all-cause mortality (23.7% vs 10.5%; P = 0.001). Multiple Cox regression analysis indicated that discontinuation of anticoagulation at 3 months was a significant risk factor for recurrent VTE in the cancer group (HR, 15.815; 95% CI, 3.047-82.079; P = 0.001).

IMPLICATIONS: The brief duration of anticoagulation therapy and elevated likelihood of recurrent VTE serve as cautionary indicators for the need to enhance awareness of standardized anticoagulant treatment for cancer-associated PE. The ultimate goal is to enhance patient prognosis and quality of life.

PMID:37838562 | DOI:10.1016/j.clinthera.2023.09.014

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PubMed articles on: Cancer & VTE/PE

Inhibition of Factor XI: A New Era in the Treatment of Venous Thromboembolism in Cancer Patients?

Int J Mol Sci. 2023 Sep 22;24(19):14433. doi: 10.3390/ijms241914433.

ABSTRACT

Direct oral anticoagulants against activated factor X and thrombin were the last milestone in thrombosis treatment. Step by step, they replaced antivitamin K and heparins in most of their therapeutic indications. As effective as the previous anticoagulant, the decreased but persistent risk of bleeding while using direct oral anticoagulants has created space for new therapeutics aiming to provide the same efficacy with better safety. On this basis, drug targeting factor XI emerged as an option. In particular, cancer patients might be one of the populations that will most benefit from this technical advance. In this review, after a brief presentation of the different factor IX inhibitors, we explore the potential benefit of this new treatment for cancer patients.

PMID:37833881 | PMC:PMC10572808 | DOI:10.3390/ijms241914433

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PubMed articles on: Cancer & VTE/PE

Anti-coagulant Treatment of Cancer-Associated Thrombosis in Frail Patients: Impact of Frailties on the Management of Drug-Drug Interactions

Clin Pharmacokinet. 2023 Nov;62(11):1523-1531. doi: 10.1007/s40262-023-01298-4. Epub 2023 Oct 12.

ABSTRACT

Low molecular weight heparins (LMWH) and anti-Xa direct oral anti-coagulants (DOACs) are recommended for the long-term treatment of cancer-associated thrombosis (CAT) based on well-documented randomised controlled trials. Anti-Xa DOACs are viewed as a first choice for the treatment of patients with CAT. A large number of drug-drug interactions have been reported between DOACs and chemotherapy drugs, modifying circulating levels of DOAC leading to fears of increased bleeding risks or thrombotic recurrence. Progresses in anti-neoplastic therapies have improved the prognosis and the survival, thus increasing the prevalence of frail patients with cancer. However, since frailties tend to be excluded from large trials due to multiple co-morbidities, current guidelines are not fully applicable to this population. The management of these frail patients with CAT is particularly complex and requires a risk assessment on a case-by-case basis with specific focus on cancer, patient-related risk factors and drug-drug interactions. In this brief review we have identified age, co-morbidities and co-medications as key factors of frailty that require careful attention and we have developed a therapeutic decision algorithm to help clinicians optimising the use of anti-coagulants in patients with cancer with CAT, especially in case of anti-Xa DOACs concomitant medications. With the evaluation of the bleeding risk according to the type of cancer, and anticipating drug-drug interactions intensity, taking into account patient frailties allows the optimisation of the anti-coagulant choice. A systematic collaboration between oncologists, vascular pathology specialists and pharmacists is warranted to ensure an optimal patient management. Clinical studies are needed to determine the real impact of these interactions.

PMID:37824026 | PMC:PMC10582124 | DOI:10.1007/s40262-023-01298-4

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PubMed articles on: Cancer & VTE/PE

Risk of Thrombosis and Bleeding in Gynecologic Cancer Surgery: Systematic Review and Meta-Analysis

Am J Obstet Gynecol. 2023 Oct 10:S0002-9378(23)00735-4. doi: 10.1016/j.ajog.2023.10.006. Online ahead of print.

ABSTRACT

OBJECTIVE: To provide procedure-specific estimates of the risk of symptomatic venous thromboembolism (VTE) and major bleeding, in the absence of thromboprophylaxis, following gynecologic cancer surgery.

DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice.

STUDY ELIGIBILITY CRITERIA: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least one of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic VTE, bleeding requiring reintervention (including re-exploration and angioembolization), bleeding leading to transfusion or post-operative hemoglobin <70

STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks post-surgery stratified by patient VTE risk factors, and used the GRADE approach to rate evidence certainty.

RESULTS: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic VTE risk (in the absence of prophylaxis) was <1%2.0% in 13 of 37 (35%). The risks of VTE varied from 0.1% in low VTE risk patients undergoing cervical conization to 33.5% in high VTE risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1%<1%

CONCLUSIONS: VTE reduction with thromboprophylaxis likely outweighs increase in bleeding requiring reintervention in many gynecologic cancer procedures (e.g., open surgery for ovarian cancer and pelvic exenteration). In some procedures (e.g., laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

PMID:37827272 | DOI:10.1016/j.ajog.2023.10.006

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cancer & VTE/PE

Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cancer & VTE/PE

Thrombin Generation Markers as Predictors of Cancer-Associated Venous Thromboembolism: A Systematic Review

Semin Thromb Hemost. 2023 Oct 9. doi: 10.1055/s-0043-1775856. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good (n = 13), fair (n = 8), to poor (n = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.

PMID:37813372 | DOI:10.1055/s-0043-1775856

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PubMed articles on: Cancer & VTE/PE

Computer image analysis with artificial intelligence: a practical introduction to convolutional neural networks for medical professionals

Postgrad Med J. 2023 Oct 4:qgad095. doi: 10.1093/postmj/qgad095. Online ahead of print.

ABSTRACT

Artificial intelligence tools, particularly convolutional neural networks (CNNs), are transforming healthcare by enhancing predictive, diagnostic, and decision-making capabilities. This review provides an accessible and practical explanation of CNNs for clinicians and highlights their relevance in medical image analysis. CNNs have shown themselves to be exceptionally useful in computer vision, a field that enables machines to 'see' and interpret visual data. Understanding how these models work can help clinicians leverage their full potential, especially as artificial intelligence continues to evolve and integrate into healthcare. CNNs have already demonstrated their efficacy in diverse medical fields, including radiology, histopathology, and medical photography. In radiology, CNNs have been used to automate the assessment of conditions such as pneumonia, pulmonary embolism, and rectal cancer. In histopathology, CNNs have been used to assess and classify colorectal polyps, gastric epithelial tumours, as well as assist in the assessment of multiple malignancies. In medical photography, CNNs have been used to assess retinal diseases and skin conditions, and to detect gastric and colorectal polyps during endoscopic procedures. In surgical laparoscopy, they may provide intraoperative assistance to surgeons, helping interpret surgical anatomy and demonstrate safe dissection zones. The integration of CNNs into medical image analysis promises to enhance diagnostic accuracy, streamline workflow efficiency, and expand access to expert-level image analysis, contributing to the ultimate goal of delivering further improvements in patient and healthcare outcomes.

PMID:37794609 | DOI:10.1093/postmj/qgad095

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PubMed articles on: Cancer & VTE/PE

Anticoagulation and venous thromboembolism in patients aged 90 years and older: Data from the RIETE registry

J Am Geriatr Soc. 2023 Oct 10. doi: 10.1111/jgs.18626. Online ahead of print.

ABSTRACT

BACKGROUND: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90

METHODS: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE.

RESULTS: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90

CONCLUSIONS: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.

PMID:37814983 | DOI:10.1111/jgs.18626

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PubMed articles on: Cancer & VTE/PE

A multifaceted quality improvement intervention on venous thromboembolism prophylaxis compliance in hospitalized medical patients at a comprehensive cancer center

J Oncol Pharm Pract. 2023 Oct 6:10781552231205779. doi: 10.1177/10781552231205779. Online ahead of print.

ABSTRACT

INTRODUCTION: Previous studies suggest that quality improvement initiatives focused on hospital-acquired venous thromboembolism have a positive impact on prescribing rates of venous thromboembolism prophylaxis, especially those that incorporate computerized changes.

METHODS: We conducted a quality improvement project to determine whether education and computerized prescriber order entry system changes affect venous thromboembolism prophylaxis compliance rates in hospitalized medical patients at a Comprehensive Cancer Center. Between 1 January 2021 and 31 January 2023, 37,739 non-surgical, adult patient encounters with a length of stay > 48 h were analyzed in our study. From 18 December 2021 to 8 March 2022, provider education was delivered to the three largest admitting services, and computerized prescriber order entry changes were implemented incorporating a mandatory requirement to either order venous thromboembolism prophylaxis or document a contraindication for all patients at moderate venous thromboembolism risk.

RESULTS: Monthly venous thromboembolism prophylaxis compliance rates, as defined by the Centers for Medicare and Medicaid Services VTE-1 metric, increased from a mean of 74% to 93% after the interventions. This change was driven primarily by an increased utilization of mechanical venous thromboembolism prophylaxis from 37% to 53%.

CONCLUSION: Our study demonstrated that a multi-faceted intervention incorporating provider education and computerized prescriber order entry system changes can significantly increase venous thromboembolism prophylaxis compliance rates in cancer patients.

PMID:37801550 | DOI:10.1177/10781552231205779

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PubMed articles on: Cancer & VTE/PE

Tissue factor pathway inhibitor is associated with risk of venous thromboembolism and all-cause mortality in patients with cancer

Haematologica. 2023 Oct 12. doi: 10.3324/haematol.2023.283581. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) is a common complication in patients with cancer. Data on the role of natural inhibitors of coagulation for occurrence of cancerassociated VTE are limited, thus, we investigated the association of tissue factor pathway inhibitor (TFPI) with risk of VTE and all-cause mortality in patients with cancer. Total TFPI antigen levels were measured with a commercially available ELISA in patients included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study with the primary outcome VTE. Competing risk analysis and Cox regression analysis were performed to explore the association of TFPI levels with VTE and all-cause mortality. TFPI was analyzed in 898 patients (median age: 62 years [interquartile range, IQR: 53-68]; 407 [45%] women). Sixtyseven patients developed VTE and 387 died (24-month cumulative risk: 7.5% and 42.1%, respectively). Patients had median TFPI levels at study inclusion of 56.4ng/mL (IQR: 45.7-70.0), with highest levels in tumor types known to have a high risk of VTE (gastroesophageal-, pancreatic and brain-cancer: 62.0ng/mL [IQR: 52.0-75.0]). In multivariable analysis adjusting for age, sex, cancer type and stage, TFPI levels were associated with VTE risk (SHR per doubling: 1.63, 95%CI: 1.03-2.57). When patients with high and intermediate/low VTE risk were analyzed separately, the association remained independently associated in the high risk group only (SHR: 2.63, 95%CI: 1.40-4.94). TFPI levels were independently associated with all-cause mortality (HR: 2.36, 95%CI: 1.85-3.00). In cancer patients increased TFPI levels are associated with VTE risk, specifically in patients with high risk tumor types, and with all-cause mortality.

PMID:37822244 | DOI:10.3324/haematol.2023.283581

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PubMed articles on: Cancer & VTE/PE

Arterial and Venous Thromboembolic Complications in 832 Patients with BCR-ABL-Negative Myeloproliferative Neoplasms

Hamostaseologie. 2023 Oct 9. doi: 10.1055/a-2159-8767. Online ahead of print.

ABSTRACT

Arterial (ATE) and venous (VTE) thromboembolic complications are common causes of morbidity and mortality in BCR-ABL-negative myeloproliferative neoplasms (MPNs). However, there are few studies that include all MPN subtypes and focus on both MPN-associated ATE and VTE. In our single-center retrospective study of 832 MPN patients, a total of 180 first thromboembolic events occurred during a median follow-up of 6.6 years (range: 0-37.6 years), of which 105 were VTE and 75 were ATE. The probability of a vascular event at the end of the follow-up period was 36.2%, and the incidence rate for all first ATE/VTE was 2.43% patient/year. The most frequent VTE localizations were deep vein thrombosis with or without pulmonary embolism (incidence rate: 0.59% patient/year), while strokes were the most frequent ATE with an incidence rate of 0.32% patient/year. When comparing the group of patients with ATE/VTE (n = 180) and the group without such an event (n = 652) using multivariate Cox regression analyses, patients with polycythemia vera (hazard ratio [HR]: 1.660; [95% confidence interval [CI] 1.206, 2.286]) had a significantly higher risk of a thromboembolic event than the other MPN subtypes. In contrast, patients with a CALR mutation had a significantly lower risk of thromboembolism compared with JAK2-mutated MPN patients (HR: 0.346; [95% CI: 0.172, 0.699]). In summary, a high incidence of MPN-associated VTE and ATE was observed in our retrospective study. While PV patients or generally JAK2-mutated MPN patients had a significantly increased risk of such vascular events, this risk was reduced in CALR-mutated MPN patients.

PMID:37813367 | DOI:10.1055/a-2159-8767

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PubMed articles on: Cancer & VTE/PE

A - 119 A Case Study: the Cognitive Functioning of an Adult Patient with Recurrent Craniopharyngiomas

Arch Clin Neuropsychol. 2023 Oct 20;38(7):1291. doi: 10.1093/arclin/acad067.136.

ABSTRACT

OBJECTIVE: Craniopharyngiomas are extremely rare (incidence rate of 1.34 per million). Due to its proximity to the sellar/suprasellar prefrontal regions region, cognitive impairment, behavioral changes, and adverse endocrinological outcomes are common. Further, surgery and radiotherapy can further impact functioning. Currently, there is no parsimonious cognitive profile of adult patients following interventions. This case highlights the role of neuropsychological evaluations in monitoring global psychological functioning and frontal behavioral syndrome in an adult with recurrent craniopharyngioma.

METHOD: The patient is a 39-year-old Black female first evaluated as an inpatient prior to resection surgery. She was evaluated on four additional times post-surgically. At the most recent evaluation, she and her family reported memory problems, apathy, and gait instability. Complicating factors included hypothyroidism, chronic kidney disease, diabetes, obstructive sleep apnea, pulmonary embolism, hypotension, COVID-19, and recurrent tachycardia, with inconsistent adherence to treatment recommendations.

RESULTS: She displayed global cognitive deficits two years post-surgery, particularly in language and memory. Neurobehaviorally, she exhibited pervasive signs of severe frontal lobe syndrome, including, abulia, hypophonic and dysarthric speech, psychomotor retardation, bradyphrenia, and anosognosia.

CONCLUSION: Neuropsychological evaluations remain critical in monitoring the patient's neurocognitive status and provide valuable insights into treatment planning and need for additional support and care to optimize patients' quality of life in the context of significant cognitive disability.

PMID:37807245 | DOI:10.1093/arclin/acad067.136

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PubMed articles on: Cancer & VTE/PE

Risk factors for bleeding in cancer patients treated with conventional dose followed by low dose apixaban for venous thromboembolism

Thromb Haemost. 2023 Oct 10. doi: 10.1055/a-2188-8773. Online ahead of print.

ABSTRACT

BACKGROUND: Incidence of and risk factors for bleeding in cancer patients with venous thromboembolism (VTE) treated with apixaban are poorly described.

METHODS: We analyzed data from the prospective CAP study where 298 cancer patients with any type of VTE received 5 mg apixaban twice daily for 6 months, and then 2.5 mg apixaban twice daily for 30 months. For most analyses major bleedings and clinically relevant non-major bleedings were merged to "clinically relevant bleedings". Risk factors were estimated by odds ratios (OR) and 95% confidence intervals (CI).

RESULTS: The incidence of clinically relevant bleedings was 38% per person year during the first 6 months of treatment, 21% per person year from 7 to 12 months, and between 4% and 8% per person year from 13 to 36 months. Clinically relevant bleedings were associated with age above 74 years (OR 2.0, 95% CI 1.0-4.1), BMI below 21.7 (OR 2.3, 95% CI 1.1-4.8), and hemoglobin at baseline below 10.5 for females (OR 2.8, 95% CI 1.1-7.3) and 11.1 for males (OR 3.3, 95% CI 1.3-8.4) during the first 6 months. Gastrointestinal (GI) or urogenital cancer were not associated with clinically relevant bleedings compared with other cancers. Among patients with luminal GI-cancer, non-resected cancer had increased risk of bleeding (OR 3.4, 95% CI 1.0-11.6) compared with resected GI-cancer.

CONCLUSION: It was very few bleedings while patients were on low-dose apixaban. Factors associated with bleeding in patients treated with full-dose apixaban were high age, low BMI, and low hemoglobin, and probably non-resected luminal GI-cancer.

PMID:37816388 | DOI:10.1055/a-2188-8773

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PubMed articles on: Cancer & VTE/PE

Impact of mild thrombocytopenia on bleeding and recurrent thrombosis in cancer

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PubMed articles on: Cancer & VTE/PE

Chronic inflammatory diseases increase the risk of post-thrombotic syndrome: A prospective cohort study

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PubMed articles on: Cancer & VTE/PE

Persistent underuse of extended venous thromboembolism prophylaxis in patients undergoing major abdominal cancer operations

J Surg Oncol. 2023 Oct 6. doi: 10.1002/jso.27473. Online ahead of print.

ABSTRACT

BACKGROUND: Guidelines recommend extended venous thromboembolism (VTE) prophylaxis for high-risk populations undergoing major abdominal cancer operations. Few studies have evaluated extended VTE prophylaxis in the Medicare population who are at higher risk due to age.

METHODS: We performed a retrospective study using a 20% random sample of Medicare claims, 2012-2017. Patients ≥65 years with an abdominal cancer undergoing resection were included. Primary outcome was the proportion of patients receiving new extended VTE prophylaxis prescriptions at discharge. Secondary outcomes included postdischarge VTE and hemorrhagic events.

RESULTS: The study included 72 983 patients with a mean age of 75. Overall, 8.9% of patients received extended VTE prophylaxis. This proportion increased (7.2% in 2012, 10.6% in 2017; p < 0.001). Incidence of postdischarge hemorrhagic events was 1.0% in patients receiving extended VTE prophylaxis and 0.8% in those who did not. The incidence of postdischarge VTE events was 5.2% in patients receiving extended VTE prophylaxis and 2.4% in those who did not.

CONCLUSION: Adherence to guideline-recommended extended VTE prophylaxis in high-risk patients undergoing major abdominal cancer operations is low. The higher rate of VTE in the prophylaxis group may suggest we captured some therapeutic anticoagulation, which would mean the actual rate of thromboprophylaxis is lower than reported herein.

PMID:37800390 | DOI:10.1002/jso.27473

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PubMed articles on: Cancer & VTE/PE

Risk and timing of venous thromboembolism after surgery for lung cancer: a nationwide cohort study

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cancer & VTE/PE

Pulmonary Embolism Unplugged: Catheter-Directed Therapies for Intermediate-Risk Pulmonary Embolism

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PubMed articles on: Cancer & VTE/PE

Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients

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PubMed articles on: Cancer & VTE/PE

Unveiling Lung Adenocarcinoma: Non-bacterial Thrombotic Endocarditis as the Debut Sign

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PubMed articles on: Cancer & VTE/PE

A Novel Model to Prevent Venous Thromboembolism in Patients with Lung Cancer

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PubMed articles on: Cancer & VTE/PE

Crucial safety issues on Janus kinase inhibitors in rheumatoid arthritis might be associated with the lack of LDL-cholesterol management: a reasoned literature analysis

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PubMed articles on: Cardio-Oncology

C

07:08

Cardiotoxicity News

PubMed articles on: Cardio-Oncology

SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy-Related Cardiac Dysfunction

JACC Heart Fail. 2023 Oct 12:S2213-1779(23)00596-6. doi: 10.1016/j.jchf.2023.08.026. Online ahead of print.

ABSTRACT

BACKGROUND: Certain antineoplastic therapies are associated with an increased risk of cardiomyopathy and heart failure (HF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in patients with HF.

OBJECTIVES: This study aims to examine the efficacy of SGLT2 inhibitors in patients with cancer therapy-related cardiac dysfunction (CTRCD) or HF.

METHODS: The authors conducted a retrospective cohort analysis of deidentified, aggregate patient data from the TriNetX research network. Patients aged ≥18 years with a history of type 2 diabetes mellitus, cancer, and exposure to potentially cardiotoxic antineoplastic therapies, with a subsequent diagnosis of cardiomyopathy or HF between January 1, 2013, and April 30, 2020, were identified. Patients with ischemic heart disease were excluded. Patients receiving guideline-directed medical therapy were divided into 2 groups based on SGLT2 inhibitor use. After propensity score matching, odds ratios (ORs) and Cox proportional HRs were used to compare outcomes over a 2-year follow-up period.

RESULTS: The study cohort included 1,280 patients with CTRCD/HF (n = 640 per group; mean age: 67.6 years; 41.6% female; 68% White). Patients on SGLT2 inhibitors in addition to conventional guideline-directed medical therapy had a lower risk of acute HF exacerbation (OR: 0.483 [95% CI: 0.36-0.65]; P < 0.001) and all-cause mortality (OR: 0.296 [95% CI: 0.22-0.40]; P = 0.001). All-cause hospitalizations or emergency department visits (OR: 0.479; 95% CI: 0.383-0.599; P < 0.001), atrial fibrillation/flutter (OR: 0.397 [95% CI: 0.213-0.737]; P = 0.003), acute kidney injury (OR: 0.486 [95% CI: 0.382-0.619]; P < 0.001), and need for renal replacement therapy (OR: 0.398 [95% CI: 0.189-0.839]; P = 0.012) were also less frequent in patients on SGLT2 inhibitors.

CONCLUSIONS: SGLT2 inhibitor use is associated with improved outcomes in patients with CTRCD/HF.

PMID:37897456 | DOI:10.1016/j.jchf.2023.08.026

07:08

PubMed articles on: Cardio-Oncology

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy

Pharmaceuticals (Basel). 2023 Oct 11;16(10):1441. doi: 10.3390/ph16101441.

ABSTRACT

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy regimen for colorectal, gastric, and breast cancers, cardiotoxicity caused by 5-fluorouracil might affect anywhere from 1.5% to 18% of patients. The precise mechanisms underlying cardiotoxicity associated with CRC treatment are complex and may involve the modulation of various signaling pathways crucial for maintaining cardiac health including TKI ErbB2 or NRG-1, VEGF, PDGF, BRAF/Ras/Raf/MEK/ERK, and the PI3/ERK/AMPK/mTOR pathway, resulting in oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, ultimately damaging cardiac tissue. Thus, the identification and management of cardiotoxicity associated with CRC drug therapy while minimizing the negative impact have become increasingly important. The purpose of this review is to catalog the potential cardiotoxicities caused by anticancer drugs and targeted therapy used to treat colorectal cancer as well as strategies focused on early diagnosing, prevention, and treatment of cardiotoxicity associated with anticancer drugs used in CRC therapy.

PMID:37895912 | PMC:PMC10610064 | DOI:10.3390/ph16101441

07:08

PubMed articles on: Cardio-Oncology

Multimodality Cardiovascular Imaging of Cardiotoxicity Due to Cancer Therapy

Life (Basel). 2023 Oct 23;13(10):2103. doi: 10.3390/life13102103.

ABSTRACT

Cancer therapies have revolutionized patient survival rates, yet they come with the risk of cardiotoxicity, necessitating effective monitoring and management. The existing guidelines offer a limited empirical basis for practical approaches in various clinical scenarios. This article explores the intricate relationship between cancer therapy and the cardiovascular system, highlighting the role of advanced multimodality imaging in monitoring patients before, during, and after cancer treatment. This review outlines the cardiovascular effects of different cancer therapy classes, offering a comprehensive understanding of their dose- and time-dependent impacts. This paper delves into diverse imaging modalities such as echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, and nuclear imaging, detailing their strengths and limitations in various conditions due to cancer treatment, such as cardiac dysfunction, myocarditis, coronary artery disease, Takotsubo cardiomyopathy, pulmonary hypertension, arterial hypertension, valvular heart diseases, and heart failure with preserved ejection fraction. Moreover, it underscores the significance of long-term follow-up for cancer survivors and discusses future directions.

PMID:37895484 | PMC:PMC10608651 | DOI:10.3390/life13102103

07:08

PubMed articles on: Cardio-Oncology

H-Dot Mediated Nanotherapeutics Mitigate Systemic Toxicity of Platinum-Based Anticancer Drugs

Int J Mol Sci. 2023 Oct 23;24(20):15466. doi: 10.3390/ijms242015466.

ABSTRACT

Platinum-based anticancer agents have revolutionized oncological treatments globally. However, their therapeutic efficacy is often accompanied by systemic toxicity. Carboplatin, recognized for its relatively lower toxicity profile than cisplatin, still presents off-target toxicities, including dose-dependent cardiotoxicity, neurotoxicity, and myelosuppression. In this study, we demonstrate a delivery strategy of carboplatin to mitigate its off-target toxicity by leveraging the potential of zwitterionic nanocarrier, H-dot. The designed carboplatin/H-dot complex (Car/H-dot) exhibits rapid drug release kinetics and notable accumulation in proximity to tumor sites, indicative of amplified tumor targeting precision. Intriguingly, the Car/H-dot shows remarkable efficacy in eliminating tumors across insulinoma animal models. Encouragingly, concerns linked to carboplatin-induced cardiotoxicity are effectively alleviated by adopting the Car/H-dot nanotherapeutic approach. This pioneering investigation not only underscores the viability of H-dot as an organic nanocarrier for platinum drugs but also emphasizes its pivotal role in ameliorating associated toxicities. Thus, this study heralds a promising advancement in refining the therapeutic landscape of platinum-based chemotherapy.

PMID:37895146 | PMC:PMC10607179 | DOI:10.3390/ijms242015466

07:08

PubMed articles on: Cardio-Oncology

Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas

Cancers (Basel). 2023 Oct 18;15(20):5036. doi: 10.3390/cancers15205036.

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

07:08

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

07:08

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

07:08

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

07:08

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

07:08

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

07:08

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

07:08

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

07:08

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

07:08

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

07:08

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

07:08

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

07:08

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.