ABSTRACT


BACKGROUND: More than half of patients with embolic stroke of undetermined source (ESUS) suffer from recurrent ischaemic stroke, despite the absence of atrial fibrillation (AF) on invasive cardiac monitoring (ICM). This study investigated the predictors and prognosis of recurrent stroke in ESUS without AF on ICM.


METHOD: This prospective study included patients with ESUS at two tertiary hospitals from 2015 to 2021 who underwent comprehensive neurological imaging, transthoracic echocardiography, and inpatient continuous electrographic monitoring for ≥48 hours prior to ICM for definitive exclusion of AF. Recurrent ischaemic stroke, all-cause mortality, and functional outcome by the modified Rankin scale (mRS) at 3 months were evaluated in patients without AF.


RESULTS: Of 185 consecutive patients with ESUS, AF was not detected in 163 (88%) patients (age 62±12 years, 76% men, 25% prior stroke, median time to ICM insertion 26 [7, 123] days), and stroke recurred in 24 (15%) patients. Stroke recurrences were predominantly ESUS (88%), within the first 2 years (75%), and involved a different vascular territory from qualifying ESUS (58%). Pre-existing cancer was the only independent predictor of recurrent stroke (adjusted hazard ratio [AHR] 5.43, 95% CI 1.43-20.64), recurrent ESUS (AHR 5.67, 95% CI 1.15-21.21), and higher mRS score at 3 months (ß 1.27, 95% CI 0.23-2.42). All-cause mortality occurred in 17 (10%) patients. Adjusting for age, cancer, and mRS category (≥3 vs <3),


CONCLUSIONS: Patients with recurrent ESUS are a high-risk subgroup. Studies elucidating optimal diagnostic and treatment strategies in non-AF-related ESUS are urgently required.


PMID:37291002 | DOI:10.1016/j.hlc.2023.05.010

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PubMed articles on: Cancer & VTE/PE

Congenital hepatic hemangioma: an unusual case report of pulmonary hypertension


BMC Pediatr. 2023 Jun 7;23(1):284. doi: 10.1186/s12887-023-04096-w.


ABSTRACT


BACKGROUND: Pulmonary hypertension (PH) in newborns is a rare but serious condition that often requires immediate intervention and quick diagnosis of the correct etiology to prevent mortality. Congenital hepatic hemangioma (CHH) is an example of an extrathoracic etiology of PH.


CASE PRESENTATION: Herein, we report the case of a newborn with a giant liver hemangioma, who presented with an early onset of PH and was successfully treated with intra-arterial embolization.


CONCLUSIONS: This case illustrates the importance of suspicion and prompt evaluation of CHH and related systemic arteriovenous shunts among infants with unexplained PH.


PMID:37286954 | PMC:PMC10245545 | DOI:10.1186/s12887-023-04096-w

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PubMed articles on: Cancer & VTE/PE

Covariate-specific ROC curve analysis can accommodate differences between covariate subgroups in the evaluation of diagnostic accuracy


J Clin Epidemiol. 2023 Jun 7:S0895-4356(23)00142-7. doi: 10.1016/j.jclinepi.2023.06.001. Online ahead of print.


ABSTRACT


OBJECTIVE: We present an illustrative application of methods that account for covariates in receiver operating characteristic (ROC) curve analysis, using individual patient data on D-dimer testing for excluding pulmonary embolism.


STUDY DESIGN AND SETTING: Bayesian nonparametric covariate-specific ROC curves were constructed to examine the performance/positivity thresholds in covariate subgroups. Standard ROC curves were constructed. Three scenarios were outlined based on comparison between subgroups and standard ROC curve conclusion: (1) identical distribution/identical performance, (2) different distribution/identical performance, and (3) different distribution/different performance. Scenarios were illustrated using clinical covariates. Covariate-adjusted ROC curves were also constructed.


RESULTS: Age groups had prominent differences in D-dimer concentration, paired with differences in performance (Scenario 3). Different positivity thresholds were required to achieve the same level of sensitivity. D-dimer had identical performance, but different distributions for YEARS algorithm items (Scenario 2), and similar distributions for sex (Scenario 1). For the later covariates, comparable positivity thresholds achieved the same sensitivity. All covariate-adjusted models had AUCs comparable to the standard approach.


CONCLUSION: Subgroup differences in performance and distribution of results can indicate that the conventional ROC curve is not a fair representation of test performance. Estimating conditional ROC curves can improve the ability to select thresholds with greater applicability.


PMID:37295733 | DOI:10.1016/j.jclinepi.2023.06.001

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PubMed articles on: Cancer & VTE/PE

Dynamic Patterns and Persistence of Anticoagulation Therapy in Patients with Venous Thromboembolism in South Korea: A Nationwide Cohort Study


Thromb Haemost. 2023 Jun 7. doi: 10.1055/a-2107-0815. Online ahead of print.


ABSTRACT


Background Venous thromboembolism (VTE) is associated with increased morbidity, mortality, and healthcare expenditure. However, the comprehensive utilization of anticoagulation therapy in patients with VTE, especially regarding active cancer, in real-world practice remains unclear. Objective To describe the prescription, persistence, and patterns of anticoagulation therapy among patients with VTE stratified according to active cancer. Methods Using Korean nationwide claims data, we identified an incident, treatment-naïve cohort of patients with VTE from 2013 to 2019 and classified them according to the presence/absence of active cancer. We explored the secular trends, treatment patterns (e.g., discontinuation, interruption, and switch), and persistence of anticoagulation therapy. Results There were 48,504 and 7,255 patients without and with active cancer, respectively. NOACs were the most common anticoagulant in both groups (65.1% and 57.9%, respectively). The prescription of non-vitamin K antagonist oral anticoagulants (NOACs) increased steeply over time, regardless of active cancer, whereas parenteral anticoagulants (PACs) plateaued and warfarin decreased sharply. A heterogeneous pattern was observed between the groups without and with active cancer (3-month persistence was 60.8%, 62.9%, 57.2%, and 3.4%, respectively; 6-month persistence was 42.3%, 33.5%, 25.9%, and 1.2% vs. 9.9%). Median duration of continuous anticoagulant therapy for warfarin, NOAC, and PAC were 183, 147, and 3 days in non-active cancer patients, and 121, 117, and 44 days in active cancer patients. Conclusion Our findings suggest that there were substantial differences in persistence, patterns, and patient characteristics of anticoagulant therapy based on index anticoagulant and active cancer.


PMID:37285903 | DOI:10.1055/a-2107-0815

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PubMed articles on: Cardio-Oncology

Vernonia amygdalina Ethanol Extract Protects against Doxorubicin-Induced Cardiotoxicity via TGFβ, Cytochrome c, and Apoptosis


Molecules. 2023 May 24;28(11):4305. doi: 10.3390/molecules28114305.


ABSTRACT


Doxorubicin (DOX) has been extensively utilized in cancer treatment. However, DOX administration has adverse effects, such as cardiac injury. This study intends to analyze the expression of TGF, cytochrome c, and apoptosis on the cardiac histology of rats induced with doxorubicin, since the prevalence of cardiotoxicity remains an unpreventable problem due to a lack of understanding of the mechanism underlying the cardiotoxicity result. Vernonia amygdalinaethanol extract (VAEE) was produced by soaking dried Vernonia amygdalinaleaves in ethanol. Rats were randomly divided into seven groups: K- (only given doxorubicin 15 mg/kgbw), KN (water saline), P100, P200, P400, P4600, and P800 (DOX 15 mg/kgbw + 100, 200, 400, 600, and 800 mg/kgbw extract); at the end of the study, rats were scarified, and blood was taken directly from the heart; the heart was then removed. TGF, cytochrome c, and apoptosis were stained using immunohistochemistry, whereas SOD, MDA, and GR concentration were evaluated using an ELISA kit. In conclusion, ethanol extract might protect the cardiotoxicity produced by doxorubicin by significantly reducing the expression of TGF, cytochrome c, and apoptosis in P600 and P800 compared to untreated control K- (p < 0.001). These findings suggest that Vernonia amygdalinamay protect cardiac rats by reducing the apoptosis, TGF, and cytochrome c expression while not producing the doxorubicinol as doxorubicin metabolite. In the future, Vernonia amygdalinacould be used as herbal preventive therapy for patient administered doxorubicin to reduce the incidence of cardiotoxicity.


PMID:37298779 | DOI:10.3390/molecules28114305

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PubMed articles on: Cardio-Oncology

Toll-like Receptor 4 Inflammatory Perspective on Doxorubicin-Induced Cardiotoxicity


Molecules. 2023 May 24;28(11):4294. doi: 10.3390/molecules28114294.


ABSTRACT


Doxorubicin (Dox) is one of the most frequently used chemotherapeutic drugs in a variety of cancers, but Dox-induced cardiotoxicity diminishes its therapeutic efficacy. The underlying mechanisms of Dox-induced cardiotoxicity are still not fully understood. More significantly, there are no established therapeutic guidelines for Dox-induced cardiotoxicity. To date, Dox-induced cardiac inflammation is widely considered as one of the underlying mechanisms involved in Dox-induced cardiotoxicity. The Toll-like receptor 4 (TLR4) signaling pathway plays a key role in Dox-induced cardiac inflammation, and growing evidence reports that TLR4-induced cardiac inflammation is strongly linked to Dox-induced cardiotoxicity. In this review, we outline and address all the available evidence demonstrating the involvement of the TLR4 signaling pathway in different models of Dox-induced cardiotoxicity. This review also discusses the effect of the TLR4 signaling pathway on Dox-induced cardiotoxicity. Understanding the role of the TLR4 signaling pathway in Dox-induced cardiac inflammation might be beneficial for developing a potential therapeutic strategy for Dox-induced cardiotoxicity.


PMID:37298770 | DOI:10.3390/molecules28114294

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PubMed articles on: Cardio-Oncology

Feasibility of a Virtual Educational Programme for Behaviour Change in Cardiac Patients from a Low-Resource Setting


Int J Environ Res Public Health. 2023 May 24;20(11):5934. doi: 10.3390/ijerph20115934.


ABSTRACT


Patient education is an integral part of recovery from a critical cardiac life event and a core component of cardiac rehabilitation (CR) programmes. This study addressed the feasibility of a virtual educational programme for behaviour change in CR patients from a low-resource setting in Brazil. Cardiac patients from a CR programme closed due to the pandemic received a 12-week virtual educational intervention (WhatsApp messages and bi-weekly calls from healthcare providers). Acceptability, demand, implementation, practicality, and limited efficacy were tested. Overall, 34 patients and 8 healthcare providers agreed to participate. The intervention was considered practical and acceptable by the participants, who reported a satisfaction median of 9.0 (7.4-10.0)/10 (patients) and 9.8 (9.6-10.0)/10 (providers). The main difficulties in carrying out the intervention activities were related to technology, motivation to self-learning, and a lack of in-person orientation. All the patients reported that the information included in the intervention was aligned with their information needs. The intervention was associated with changes in exercise self-efficacy, sleep quality, depressive symptoms, and performance of high-intensity physical activity. In conclusion, the intervention was considered feasible to educate cardiac patients from a low-resource setting. It should be replicated and expanded to support patients that face barriers to onsite CR participation. Challenges related to technology and self-learning should be addressed.


PMID:37297538 | DOI:10.3390/ijerph20115934

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PubMed articles on: Cardio-Oncology

Cardiovascular Complications of Pan-Cancer Therapies: The Need for Cardio-Oncology


Cancers (Basel). 2023 Jun 5;15(11):3055. doi: 10.3390/cancers15113055.


ABSTRACT


It is more likely that a long-term survivor will have both cardiovascular disease and cancer on account of the progress in cancer therapy. Cardiotoxicity is a well-recognized and highly concerning adverse effect of cancer therapies. This side effect can manifest in a proportion of cancer patients and may lead to the discontinuation of potentially life-saving anticancer treatment regimens. Consequently, this discontinuation may adversely affect the patient's survival prognosis. There are various underlying mechanisms by which each anticancer treatment affects the cardiovascular system. Similarly, the incidence of cardiovascular events varies with different protocols for malignant tumors. In the future, comprehensive cardiovascular risk assessment and clinical monitoring should be considered for cancer treatments. Baseline cardiovascular evaluation risk should be emphasized prior to initiating clinical therapy in patients. Additionally, we highlight that there is a need for cardio-oncology to avoid or prevent cardiovascular side effects. Cardio-oncology service is based on identifying cardiotoxicity, developing strategies to reduce these toxicities, and minimizing long-term cardiotoxic effects.


PMID:37297017 | DOI:10.3390/cancers15113055

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PubMed articles on: Cardio-Oncology

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


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


ABSTRACT


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


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


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

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PubMed articles on: Cardio-Oncology

The Role of the Cardiac Biomarkers in the Renal Cell Carcinoma Multidisciplinary Management


Diagnostics (Basel). 2023 May 30;13(11):1912. doi: 10.3390/diagnostics13111912.


ABSTRACT


Renal cell carcinoma, an aggressive malignancy, is often incidentally diagnosed. The patient remains asymptomatic to the late stage of the disease, when the local or distant metastases are already present. Surgical treatment remains the choice for these patients, although the plan must adapt to the characteristics of the patients and the extension of the neoplasm. Systemic therapy is sometimes needed. It includes immunotherapy, target therapy, or both, with a high level of toxicity. Cardiac biomarkers have prognosis and monitoring values in this setting. Their role in postoperative identification of myocardial injury and heart failure already have been demonstrated, as well as their importance in preoperative evaluation from the cardiac point of view and the progression of renal cancer. The cardiac biomarkers are also part of the new cardio-oncologic approach to establishing and monitoring systemic therapy. They are complementary tests for assessment of the baseline toxicity risk and tools to guide therapy. The goal must be to continue the treatment as long as possible with the initiation and optimisation of the cardiological treatment. Cardiac atrial biomarkers are reported to have also antitumoral and anti-inflammatory properties. This review aims to present the role of cardiac biomarkers in the multidisciplinary management of renal cell carcinoma patients.


PMID:37296764 | DOI:10.3390/diagnostics13111912

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PubMed articles on: Cardio-Oncology

Prognostic Factors for Cardiotoxicity among Children with Cancer: Definition, Causes, and Diagnosis with Omics Technologies


Diagnostics (Basel). 2023 May 26;13(11):1864. doi: 10.3390/diagnostics13111864.


ABSTRACT


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


PMID:37296716 | DOI:10.3390/diagnostics13111864

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PubMed articles on: Cardio-Oncology

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


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


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