bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of liraglutide on cardiotoxicity and gut microbiota changes induced by doxorubicin in rats
Authors: Rodrigues Tonon C , Gaiato Monte M , Fujimori A S S , Ballin P S , Ferreira N F , Vieira N M , Dantas Ribeiro A P , Rufino Garcia L , Okoshi K , Okoshi M P , Zornoff L A M , Paiva S A R , Polegato B F 
Published: October 2024

Abstract

Background
Cancer is one of the main causes of morbidity and mortality worldwide. Despite doxorubicin (DOX) being an effective chemotherapy drug, DOX-induced cardiotoxicity is the most severe side effect, limiting its use. There is no effective treatment for preventing DOX-induced cardiotoxicity. Gut microbiota seems to have a role in cardiovascular disease. Glucagon like peptide-1 (GLP-1) analogs such as liraglutide have shown benefits in cardiovascular diseases and seem to affect gut microbiota.

Purpose
To evaluate the role of liraglutide in modulating acute DOX-induced cardiotoxicity and gut microbiota.

Methods
Sixty male Wistar rats were allocated into four groups: Control (C), DOX (D), Liraglutide (L), and DOX + Liraglutide (DL). Animals in L and DL groups received a subcutaneous injection of 0.6 mg/kg liraglutide daily for 2 weeks. After 12 days, D and DL groups received an intraperitoneal injection of DOX (20 mg/kg). Rats were subjected to echocardiogram and isolated heart functional study 48 hours after DOX injection. At the end of the experiment, feces were collected to evaluate microbiota and short chain fatty acid concentration. Statistical analyses: Generalized linear model (GLM), ANCOVA and PERMANOVA (p&lt;0.05).

Results
DOX-treated rats had worse cardiac function than rats that did not receive DOX in both echocardiography and isolated heart study; liraglutide did not change any functional parameters (Table). In feces, the phylum Bacteroidota was reduced in D and L groups compared to C and the phylum Pseudomonadota was increased in D and DL compared to C and L. Alpha-diversity did not differ between groups. Beta-diversity differed between C, D and L groups, and was similar between D and DL (Figure). Feces short chain fatty acid concentration was reduced in DOX-treated rats, with no effect from liraglutide (Figure).

Conclusion
DOX altered the function and composition of gut microbiota and caused acute cardiotoxicity; liraglutide changed gut microbiota and did not improve cardiac function.Table.Left ventricular functional dataFigure.Microbiota
The prognostic value of advanced lung cancer inflammation index in cancer survivors complicated with cardiovascular disease
Authors: Zhang Y , Shi C , Li Y , Zhang Z , He P , Liu Y 
Published: October 2024

Abstract

Background
The advanced lung cancer inflammation index (ALI) reflects systemic inflammatory and nutritional status, both of which are related to the prognosis of the disease. However, the prognostic value of ALI in cancer survivors with cardiovascular disease (CVD) remains unclear.

Purpose
This study was conducted to investigate the association of ALI with mortality in cancer survivors with CVD.

Methods
This study enrolled 955 cancer survivors with CVD from the National Health and Nutrition Examination Survey (NHANES, 1999-2018), and followed mortality status until December 31, 2019. Cox proportional hazards regression analysis and threshold effect analysis were applied to evaluate the relationship between ALI and all-cause, CVD-specific, and cancer-specific mortality. The prognostic value of ALI was further examined by time-dependent receiver operating characteristic (ROC) curve analysis.

Results
During a median follow-up period of 66.65 months, 490 all-cause deaths were observed, including 181 CVD-specific deaths and 121 cancer-specific deaths. After multivariate adjustment, ALI was inversely associated with all-cause, CVD-specific, and cancer-specific mortality in cancer survivors with CVD. Furthermore, L-shaped associations of ALI with mortality were discovered, with inflection points of 74.18 for all-cause and CVD-specific mortality and 55.50 for cancer-specific mortality. When the ALI was less than the inflection points, a 10-unit increase of ALI was associated with a 16%, 16%, and 25% decreased HR for all-cause, CVD-specific, and cancer-specific mortality, respectively. The time-dependent ROC curve analysis showed that the ALI had moderate predictive value for short- and long-term mortality.

Conclusions
The ALI is a significant prognostic indicator of mortality for cancer survivors with CVD. The findings allow for early prevention to improve the overall prognosis in such populations.
Cardiovascular events in CML patients treated with nilotinib: validation of the HFA-ICOS baseline risk score
Authors: Andres M , Fernando F , Claudiani S , Kermani N , Ceccarelli G , Apperley J , Innes A , Khan A , Rosen S D , Lyon A R , Milojkovic D 
Published: October 2024

Abstract

Background
The therapeutic landscape of chronic myeloid leukaemia (CML) has been transformed by tyrosine kinase inhibitors (TKI). Nilotinib, a potent 2nd generation TKI, showed higher rates of major molecular response than imatinib, however was associated with higher rates of cardiovascular (CV) toxicity.

Objectives
To describe the CV events associated with nilotinib in a real-world CML population and assess the predictive value of the HFA-ICOS baseline risk score in clinical practice.

Methods
The HFA-ICOS baseline risk was calculated (low, medium, high /very high) for patients with CML treated with nilotinib between 2006 and 2021. The incidence of all CV events, ischaemic events and Major CV Adverse Events (MACE) were reviewed and compared among the different risk groups.

Results
A total of two hundred and twenty-nine eligible patients were included in the analysis. The incidence of CV events, ischaemic events, and MACE, while on nilotinib, were 20.9% (95% CI: 15.7% to 26.2%), 12.7% (95% CI: 8.4% to 16.9%), and 12.2% (95% CI: 7.9% to 16.5%) respectively, following a median duration of treatment with nilotinib of 34.4 months for the entire cohort. Patients with a higher HFA-ICOS baseline risk score had higher rates of all CV events (low: 11.2%, medium: 28.2% [HR: 2.8, 95% CI: 1.2 to 6.2], high/very high: 32.4% [HR: 3.5, 95% CI: 1.8 to 6.8]), ischaemic events (low: 5.2%, medium: 17.9% [HR: 3.7, 95% CI: 1.2 to 10.9] , high/very high: 21.6% [HR: 3.7, 95% CI: 1.4 to 9.7]) and MACE (low: 7.8% , medium: 10.3% [HR:1.2, 95% CI: 0.38 to 4.1], high/very high: 20.2% [HR: 2.2, 95% CI: 0.9 to 5.3]). The predictive tool presented an 89% NPV, and an area under the ROC curve: 0.65 for all CV events, an NPV of 95% and AUC 0.68 for ischaemic events and NPV 92% and AUC 0.62 for MACE.

Conclusions
The HFA-ICOS risk stratification tool has been shown to be an efficient discriminator at low, medium and high/very high risk of developing cardiovascular events, with an overall positive trend towards increasing cardiotoxicity rates with rising risk categories. This study provides evidence to support the use of this predictive tool in nilotinib treated patients, as it also underscores the potential for further improvement in the overall discriminatory ability of the model.
Real-world analysis of transcatheter aortic valve replacement in patients with prostate cancer and severe aortic stenosis
Authors: Belo Nunes R , Cantarelli M J C , Castello Jr H , Costa L M A , Oliveira R P , Pereira D C , Brito T M , Scudeler T L , Schneidewind R O , Avezum A 
Published: October 2024

Abstract

Background
Patients with prostate cancer have a high prevalence of cardiovascular disease, including degenerative heart valve diseases such as aortic stenosis. It is not uncommon in clinical practice to perform transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis and active prostate cancer. Still, the prognosis after this procedure in this population is not well known.

Purpose
To evaluate 1-year and 3-year survival rates after TAVR in patients with prostate cancer who have undergone TAVR when compared with patients without active cancer.

Methods
Data were extracted from electronic medical records of a large multinational collaborative network (TriNetX) that currently englobes 113 healthcare organizations worldwide with more than 100 million patients. Patients aged 18 years or older with prostate cancer documented up to 12 months before TAVR as well as controls undergoing TAVR without oncologic history before the proceeding were included. The survival analysis for 1 year and 3 years was performed with Kaplan Meier survival plots and log-rank test. Propensity score matching, using clinical and demographic variables, was performed to pair the cohorts.

Results
From a cohort of 26,656 men who had undergone TAVR, we identified 1,040 with prostate cancer diagnosed up to 1 year before TAVR ( prostate cancer group) and 20,231 patients without oncologic history before TAVI (control group). After propensity score matching, analyzing 1,040 patients in each group, the 1-year and 3-year survival probabilities were not different between the prostate cancer group versus the control group ( 89.5% vs 88.9%, log-rank test P=0.70 and 72.6% vs 68.7%, log-rank test P=0.22, respectively). Considering a subgroup of patients with metastatic prostate cancer ( n=229) under androgen deprivation therapy vs the control group ( n =229), we have also not observed a survival difference between the two groups at 1-year and 3-year follow-up ( 88.1 vs 89.1%, log-rank test P=0.69 and 58.7% vs 67.4%, log-rank test P=0.25).

Conclusions
In this real-world analysis, patients with prostate cancer and severe aortic stenosis who underwent TAVR, including patients with metastatic disease, the 1-year and 3-year survival rates were not significantly different when compared to patients without oncologic hystory who underwent TAVR.
Unveiling the heartbeat of hope: exploring cardiovascular morbidity, mortality, and socioeconomic threads in 65,173 Child, Adolescent, and Young Adult (caya) cancer patients
Authors: Sodling J , Panagiotis M , Hytting J , Hedayati E , Keskisarkka R , Singull M , Hubbert L 
Published: October 2024

Abstract

Background
Despite significant progress in managing cancer in children, adolescents, and young adults (CAYAs), persistent complications impact their quality of life with some being severe or life-threatening.(1,2) Long-term outcomes depend on common risk factors for malignancy and cardiovascular diseases (CVD) that overlap, and treatments are known to increase the risk for CVD. (3,4) Healthcare inequality due to socioeconomic status is omnipresent and may significantly impact outcomes.

Purpose
This study aims to comprehensively cover morbidity, mortality, demographic, and socioeconomic factors among CAYAs and investigate their impact on cardiovascular outcomes.

Methods
This retrospective matched cohort study included the entire Swedish population under 25 with cancer from 1958 to 2021. The study population was identified from the National Board of Health and Welfare's Cancer Register, with controls paired 1:5 based on age, sex, and residence. Multiple registers provided data on morbidity, mortality, and demographics.

Results
Covering 63 years, identified 65,173 CAYAs (1.24 million patient-years) and matched with 312,935 controls (7.45 million person-years), a total of 378,108 individuals (74% females). The mean follow-up was 19.5 (SD16.9) years for CAYAs, and 23.8 (16.8) for controls, (p&lt;0.001). At the end of the study, the median age of CAYAs was 33.4 (IQR 27.9) years and controls 39.2 (28.3) (p&lt;0.0001), with an age span of &lt;1-88 years in both groups. CVD was detected in 16.9 % of the CAYAs, representing a 1.21-time elevated risk (95% CI 1.18-1.23, p&lt;0.0001) compared to controls. CAYAs had a higher mortality rate, and 5-years survivors lived a mean of 26.9 years shorter than controls. CV mortality was also increased in CAYAs, (1.9% compared to 0.7% in controls) but at a higher age, although at a mean of 22.8 years younger than their controls. The 5-year survivors were older at CV mortality and lived in mean 6.5 years shorter than controls (p&lt;0.0001). After adjusting for socioeconomic factors, individuals born outside Europe and those with greater sick leave had a higher mortality risk, while education and marriage showed a beneficial association with mortality. (p&lt;0.0001).

Interpretation
The Rebuc study, spanning six decades, revealed a significantly increased risk of serious complications among young cancer patients in Sweden. Not only do young cancer patient survivors face a significantly higher risk for cardiovascular disease, but the higher mortality risk before middle age also underscores the severity of the health challenges they confront. Furthermore, these young individuals are more susceptible to socioeconomic factors that may adversely affect their survival.
Validation of the HFA-ICOS risk assessment tool with real-world data from a prospective cohort of breast cancer patients in treatment with anthracyclines and trastuzumab
Authors: Guerra E C , Espinola-Zavaleta N , Barac A , Asch F , Antonio-Villa N E , Espinosa-Fernandez J R , Luna-Alcala S , Martinez-Dominguez P , Proano-Bernal L , Aparicio-Ortiz A D , Alexanderson-Rosas E , Williams H , Santa Ana-Bayona M J 
Published: October 2024

Abstract

Background
The increasing prevalence of cancer therapy-related cardiovascular toxicity (CTRCD) poses a significant challenge to patient management, necessitating accurate risk assessments. Previous methodologies have struggled with precise risk stratification, partly due to varying definitions of CTRCD and the specificity of cancer treatments.

Purpose
This study aimed to evaluate the assessment tool proposed by the Heart Failure Association and the International Cardio-Oncology Society (HFA-ICOS) in predicting the risk of CTRCD in patients undergoing anthracycline and trastuzumab treatment for breast cancer at a national reference center.

Methods
A prospective cohort study was conducted, encompassing 172 patients treated from January 2022 to July 2023. Patients were assessed at baseline, three months, and six months post-treatment initiation, with exclusion criteria including baseline left ventricular ejection fraction (LVEF) &lt;50%, history of heart failure, and stage IV breast cancer. The study utilized the HFA-ICOS tool for risk stratification and CTRCD was defined with the current criteria of the European Society of Cardiology guideline. Descriptive statistics were calculated, and incidence rates and Cox proportional-hazards models were developed according to the risk category.

Results
In our study, 138 (80.2%) patients were classified as low risk, 23 (13.4%) as moderate risk and 11 (6.4%) as high risk. We identified 81 (47.1%) patients that developed CTRCD in follow-up. Descriptive characteristics can be found in Table 1. The global incidence rate for CTRCD in our cohort was of 2.4 new cases per 1000 person-days, however no differences in incidence rates were found when stratifying by risk category (Figure 1A). Moreover, patients with moderate to high risk according to the HFA-ICOS tool did not show a significantly increased hazard ratio for cardiotoxicity (HR 0.41, 95%CI 0.15-1.12, p=0.082 and HR 1.39, 95%CI 0.50-3.86, p=0.5, respectively) as shown in Figure 1B.

Conclusion
While the HFA-ICOS tool provides a structured framework for assessing cardiotoxicity risk, its predictive value in this cohort was limited. The findings underscore the complexity of cancer therapy-related cardiotoxicity and the need for enhanced, individualized risk assessment tools. Future research should focus on refining risk prediction models, incorporating broader clinical and genetic factors to improve patient outcomes in cardio-oncology.Table 1.Clinical CharacteristicsFigure 1.Incidence rates and Cox models
Heart rate variability-based prediction of early cardiotoxicity in breast-cancer patients treated with anthracyclines and trastuzumab
Authors: Espinola-Zavaleta N , Luna-Alcala S , Espejel-Guzman A , Lerma C , Leon P , Guerra E C , Espinoza Fernandez J R , Martinez-Dominguez P , Serrano-Roman J , Cabello-Ganem A , Aparicio-Ortiz A D , Keirns C , Lerma A , Santa Ana-Bayona M J 
Published: October 2024

Abstract

Background
Cardiotoxicity is a recognized complication in breast cancer (BC) patients undergoing chemotherapy with anthracyclines with or without trastuzumab. However, the prognostic value of heart rate variability (HRV) indexes for early cardiotoxicity development remains unknown.

Purpose
This study aimed to investigate cardiac autonomic responses to physiological stimuli in BC patients treated with anthracyclines with or without trastuzumab, and to evaluate the predictive value of transthoracic echocardiography (TTE) findings and HRV indexes for early cardiotoxicity.

Methods
A prospective cohort study involving 50 BC patients was conducted at a tertiary hospital with TTE assessments performed before and three months after chemotherapy. HRV indexes were obtained from continuous electrocardiograms in supine position with spontaneous breathing, active standing, and supine position with controlled breathing. The magnitude of change (Δ) between supine-standing and supine-controlled breathing was calculated. Variables were compared using t-test or ANOVA. Cardiotoxicity predictive value was assessed by ROC curve analysis. A p value of &lt; 0.05 was considered significant.

Results
In our cohort, the mean age was 50 ± 8 years, and reported comorbidities included diabetes (n= 9), hypertension (n= 17), and dyslipidemia (n= 11). Twenty-three patients fulfilled echocardiographic and troponin cardiotoxicity criteria or both. TTE revealed reduced left atrial conduit strain in the cardiotoxicity group. Mean heart rate increased during all maneuvers at follow-up, with no differences in HRV indexes between patients with or without cardiotoxicity. However, a lower Δ in supine-controlled breathing of several HRV indexes predicted early cardiotoxicity identified by echocardiography (e.g. SDNN ≤ -8.44 ms: Sensitivity = 75%, Specificity = 69%).

Conclusion
BC patients treated with chemotherapy maintain cardiac autonomic responses to physiological stimuli after 3 months of chemotherapy. However, a lower Δ during active standing and controlled breathing before chemotherapy may predict early cardiotoxicity.Table 1.ROC curve analysisFigure 1.HRV-indexes
Transcatheter mitral edge-to-edge repair in patients with prior cancer diagnosis
Authors: Gonzalez-Manzanares R , Ojeda S , Carrasco F , Benito T , Pascual I , Nombela L , Serrador A , Estevez R , Del Trigo M , Andraka L , Cepas P , Diez J L , Cruz I , Pan M , Mesa D 
Published: October 2024

Abstract

Background
Transcatheter edge-to-edge repair (TEER) is a safe and effective therapy for mitral regurgitation (MR). Despite oncological patients have an increased risk of functional and organic MR due to cardiotoxic treatment exposure, the use of TEER in this setting remains underexplored.

Purpose
To evaluate the safety and efficacy of TEER in patients with MR and prior cancer diagnosis.

Methods
Observational, retrospective, multicenter study based on the Spanish national TEER registry. Patients from those centers providing oncological specific data were included in this analysis. Patients with and without history of cancer were propensity score matched (PSM) in a 1:1 ratio. The primary efficacy outcome was a composite of death from any cause or unplanned hospitalization for heart failure at 1 year.

Results
A total of 1237 patients with MR who underwent TEER between 2010 and 2022 across 14 centers in Spain were included. The mean age was 73 ± 11 years and 34% were female. MR etiology was functional in 58%, organic in 27% and mixed in 15%. Of them, 164 had a history of cancer. Baseline characteristics of the unmatched cohort are shown in Figure 1. Median time from cancer diagnosis to TEER was 7 (3-17) years and the most common cancer types were breast (20%), leukemia/lymphoma (19%) and colorectal (11%). PSM resulted in 163 pairs with a good balance of baseline characteristics (Figure 1). Procedural success rate was high and similar between the groups (93% vs 96%, p=0.217), as were periprocedural complication rates (Figure 2A). The primary efficacy endpoint occurred in 38 (23%) patients in the cancer group and 29 (18%) patients in the control group (Hazard ratio 1.36, CI 95% 0.84 to 2.20, p= 0.214) (Figure 2B).

Conclusion
In routine practice, a notable proportion of patients undergoing mitral TEER have a prior cancer diagnosis. Immediate and 1-year clinical outcomes appear comparable to those observed in non-cancer patients. These findings suggest that mitral TEER should not be withheld from this growing population.
miRNAs profile as a signature for cardiovascular disease in long-term breast cancer female survivors: a pilot study
Authors: Greatti A , Sicurella M , Ghirardini C , Finello V , Mindicini N , Samiolo M , Sanz J M , Schirone A , Frassoldati A , Calabro' L , Passaro A , Neri L M , Raparelli V 
Published: October 2024

Abstract

Background/Introduction
Cardiovascular diseases (CVD) is a matter of immediate concern among long term breast cancer (BC) survivors. An early identification of those patients who are at higher risk of developing CVD is warranted to tailor prevention strategies and improve their quality of life.

Purpose
To identify whether a specific miRNA signature exists in breast cancer female survivors who develop CVD in a long term follow up.

Methods
We performed cross-sectional comparison of miRNA expression between female BC survivors (i.e. individual with a diagnosis of invasive ductal carcinoma who were free from cancer at 10-year follow up and without known CVD before BC diagnosis) with CVD (n=11) and without CVD (n=11) matched for age, BC grade, treatment received and traditional cardiovascular risk factors. CVD was defined as the incidence of established atherosclerotic cardio- or cerebro-vascular diseases (i.e., ischemic heart disease, carotid endarterectomy, stroke, heart failure), atrial fibrillation or venous thromboembolism. Thirteen miRNAs were selected since they were involved in either BC and CVD. On plasma derived samples, miRNAs expression profile analysis was performed by retro-transcription and real-time PCR assays, using miRNA-specific probes.

Results
The BC female survivors (mean age 73 years, 70% hypertension, 60% histological grade 2 and 3) were treated with surgery. The majority (76%) received hormone therapy after surgery according to the BC receptor expression. In half of the cohort, radiotherapy was performed. Those female BC survivors developing CVD experienced more commonly cerebral or cardiovascular atherosclerotic events (70%). As reported in Figure 1, some miRNAs analyzed (miR-19a; miR-21; miR-24; miR-125b; miR-195) are upregulated in BC survivors who developed CVD. Of note miR-19a, miR-21 (and miR-195) increase is so significantly relevant to consider these miRNAs as candidate biomarkers.

Conclusion(s)
In this discovery cohort, a specific miRNA profile signature identified female BC survivors experiencing CVD. Validation of such signatures is needed in a larger cohort as well as mechanistic studies to understand what is the pathophysiological link between the miRNAs identified and vascular health. Nevertheless these miRNAs in both cancer and cardiac diseases are mainly associated with promotion of cell proliferation and inhibition of apoptotic processes. The clinical implications of using a specific miRNA profile as a likely early biomarker of adverse cardiovascular events are indeed of great interest to better preserve BC survivors' health.Figure 1