bluuebunny/crossref_metadata_2025_split huggingface dataset:
VCAM-1 accelerates atrial remodeling in TERT-/- mice
Authors: Wang Z , Zhao R , Zhou Z , Zhang X , Yuan J , Liu D , Wang F , Liu T 
Published: November 2023

Abstract

Background
Aging, an independent risk factor for AF, could significantly increase its morbidity and mortality. The mechanism of AF in the elderly population remains to be further elucidated. Atrial remodeling is considered to be an important mechanism of atrial fibrillation. Telomerase dysfunction and telomere shortening are important signs of aging, and the relationship and mechanism between telomerase dysfunction and atrial remodeling is not very clear.

Purpose
This study aims to explore the mechanism of atrial remodeling caused by telomerase dysfunction.

Methods
The atrial electrophysiology was used to detect refractory period (ERP) and atrial fibrillation inducibility, and the epicardial electrical mapping technique was used to detect the atrial conduction velocity, direction and conduction heterogeneity to evaluate the atrial electrical remodeling. HE and Masson staining were used to evaluate atrial structural remodeling. RNA-seq analysis screened out the differential genes and corresponding pathways in each model.

Results
Compared with wild-type (WT) mice, a third-generation of telomerase reverse-transcriptase knockout mice (F3 TERT-/-, hereafter as TERT-/-) showed a shortened atrial ERP, increased atrial fibrillation inducibility, slowed atrial conduction velocity,change in the direction of propagation, and increased atrial fibrosis, suggesting electrical and structural remodeling in TERT-/- mice. RNA-seq revealed significant changes in cell adhesion molecules (CAMs) of TERT-/- mice compared with the WT, among which vascular adhesion molecule (VCAM-1) changed most significantly. Then, TERT-/- mice were treated with anti-VCAM-1 neutralizing antibodies, atrial electrical and structural remodeling was partially relieved compared to untreated TERT-/- mice. RNA-seq and KEGG enrichment analysis were conducted on differential genes, which were mainly concentrated on extracellular matrix (ECM)-receptor interaction. Furthermore, we found that the extracellular matrix LAMC3, Collgen1 and myofibroblast marker α-SMA were reversed in TERT-/- mice treated with anti-VCAM-1 neutralizing antibodies compared with TERT-/- mice.

Conclusion
VCAM-1 could accelerate the production of extracellular matrix, and ultimately lead to atrial electricity and structural remodeling, and the occurrence of atrial fibrillation in TERT-/- mice.
Age- and sex- specific rate of venous thromboembolism in cancer survivors: a nationwide cohort study
Authors: Sun G L , Fosbol E L , Schou S , Nouravesh N , Lamberts M , Kober L , Butt J H 
Published: November 2023

Abstract

Background
Patients with cancer have an increased risk of venous thromboembolism (VTE) initially, then to decrease over time. VTE might be potentially preventable with pharmacologic prophylaxis, particularly in high-risk patients. The long-term risk of VTE among cancer survivors, however, has not been reported.

Purpose
We investigated the rate of VTE in survivors of various cancers 5 years out from diagnosis, overall and according to age and sex.

Methods
Using Danish nationwide registries, five-year survivors of 20 cancers (diagnosed between 1994 and 2013; &gt;15 years at diagnosis) were matched on age and sex with four non-cancer controls from the general population. Rates of VTE in the cancer and non-cancer groups were compared with Cox regression models, overall and according to age (i.e., 15-39, 40-64, and &gt;65 years) and sex.

Results
In total, 197,702 five-year cancer survivors (median age at diagnosis 63 years [IQR: 53 – 71 years]; 38.5% men) were matched with 790,808 non-cancer controls. During a median follow-up of 6.2 years, cancer survivors overall had a higher associated rate of incident VTE than non-cancer controls (incidence rate per 1,000 person-years 5.6 [95% CI, 5.5-5.8] and 3.3 [3.3-3.4] for cancer survivors and non-cancer controls, respectively; adjusted hazard ratio [aHR] 1.77 [1.72-1.83]). The increased rate of VTE in cancer survivors, compared with matched controls, was statistically significant for all 20 cancer subtypes and was more pronounced in multiple myeloma and lung cancer [Figure 1]. The relatively higher rate of VTE in cancer survivors was more pronounced in women, and the younger patients (age group: 15-39 years) (PInteraction&lt;0.01). Though, VTE was more prevalent in men (per 1,000 person-years 6.7 [95% CI, 6.4-6.9]) than in women (5.2 [95% CI, 5.0-5.3]), and in older patients (8.5 [95% CI, 8.2-8.7]) compared with younger patients (2.2 [95% CI, 1.9-2.4]) [Figure 2].

Conclusions
Compared with the general population, five-year cancer survivors had higher associated rates of VTE, irrespective of age and sex. The increased relative rate of VTE was more pronounced in the younger individuals and women.Hazard ratios of venous thromboembolismVenous thromboembolism by age and sex
Current treatment of acute coronary syndromes in cancer patients: the need for improvement
Authors: Carrillo M , Garcia Hernandez N , Hernandez Pineda A H , Leocachin Parra D L , Antezana Castro J F 
Published: November 2023

Abstract

Background
Cancer patients can develop acute coronary syndromes (ACS) due to their oncological therapy exposure or shared risk factors between cancer and cardiovascular disease. Cancer patients have been reported to receive suboptimal treatment in this setting, with lower rates of coronary angiography and or primary percutaneous intervention, despite the clear benefit of these therapies in ACS. This disparity in the care of cancer patients can lead to worse cardiovascular outcomes.

Purpose
To describe the contemporary therapeutic approach in patients with a history of cancer or current cancer presenting with an acute coronary syndrome to a tertiary care cardiology hospital.

Methods
We performed an electronic chart review of patients admitted to the cardiac intensive coronary unit of a tertiary care Cardiology hospital in our city, from May 2021 to February 2023. Patients with a current or historical diagnosis of cancer and acute coronary syndrome (with and without ST segment elevation) were identified. We collected the following information: demographic data, oncological diagnosis, cancer treatment history, ACS type, and ACS management.

Results
Seventy-five patients had diagnosis of current or historical cancer in the selected period. Of them, 40 patients were admitted with diagnosis of acute coronary syndrome. Mean age was 69.8 + 10.0 years. Twenty-one patients (52.5%) had a historical diagnosis of cancer and nineteen patients had diagnosis of current cancer. Of patients with historical cancer the most common type was hematological, followed by prostate and renal cancer. The most common types of active malignancies were prostate, colon, and renal cancer. ST-segment elevation myocardial infarction (STEMI) was the most common type of ACS (27 patients). Notably, only half of the patients presenting with STEMI underwent primary percutaneous coronary intervention, four patients received fibrinolytic treatment, and one third of patients with STEMI did not receive reperfusion therapy. Among patients with STEMI, mean time from symptom onset to reperfusion therapy was 495 minutes. Regarding the 13 patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI), eight underwent an invasive strategy (coronary angiography) in the first 48 hours, of whom six had percutaneous coronary intervention, and one underwent coronary artery bypass graft surgery. Five patients with NSTEMI (38.4%) did not undergo coronary angiography during their hospitalization.

Conclusions
Patients with active or historical cancer presenting with STEMI receive late reperfusion treatment and up to one out of three do not receive reperfusion therapy. An important proportion of cancer patients presenting with NSTEMI do not even undergo invasive strategy. It is imperative to provide optimal care of cancer patients presenting with ACS.
The utility of the HFA-ICOS cardiotoxicity risk assessment tool for HER2-targeted cancer therapies in patients with metastatic breast cancer: from theory to clinical practice
Authors: Leocachin Parra D , Bocardo Galvan J B , Grajales Alvarez R C , Carrillo Estrada M 
Published: November 2023

Abstract

Background
Breast cancer is the most common cancer in women. In developing countries, a considerable proportion of breast cancer diagnoses are made in advanced stages. Nevertheless, the development of targeted therapies, such as trastuzumab and other HER2 targeted agents, has revolutionized the care of these patients, leading to large improvements in disease-free and overall survival. In the other hand, these therapies are associated with cardiac dysfunction. As such, a comprehensive assessment of cardiovascular health before initiation of cancer treatment is fundamental. The HFA-ICOS´s proforma for HER2 targeted therapies is a proposed tool to evaluate the baseline risk of cardiotoxicity in these patients.

Purpose
To evaluate if the HFA-ICOS´s cardiotoxicity risk assessment tool for HER2-targeted cancer therapies allows to properly identify patients with HER2-positive metastatic breast cancer treated with trastuzumab at high risk for cardiotoxicity.

Methods
We performed an electronic chart review of patients with HER2-positive metastatic breast cancer treated with trastuzumab seen at the outpatient oncology clinic from January 2018 to December 2022. We collected the necessary data to apply the HFA-ICOS´s cardiotoxicity risk assessment tool for HER2-targeted cancer therapies, except for cardiac biomarkers. Cardiotoxicity was defined as 10% drop of left ventricular ejection fraction (LVEF) to a value of less than 50%.

Results
Seventy patients were included in our analysis. Mean age was 54.6+12.5 years. Cardiotoxicity was found in twenty-three patients (32%), of which, nine (39.1%) were classified at high risk for cardiotoxicity, twelve patients (52.1%) at medium risk, and two patients (8.6%) at low risk. Among the group with cardiotoxicity there was a higher proportion of older patients, obesity, borderline LVEF at baseline, prior treatment with anthracyclines, and prior exposure to radiotherapy. A high-risk score was more frequent among patients with cardiotoxicity than in those without cardiotoxicity. Most patients were classified with medium risk in both groups. The proportion of patients with low risk was not different in patients with and without cardiotoxicity. None of the variables evaluated was statistically significant.

Conclusions
There was a higher proportion of patients at high risk according to the HFA-ICO´s proforma for HER2 targeted therapies who developed cardiotoxicity in comparison to patients without cardiotoxicity. However, there were no significant differences in patients classified as medium or low risk. Future studies are needed to precise the most adequate method to stratify cardiotoxicity risk in patients with breast cancer exposed to anti-HER2 therapies, in order to establish effective surveillance and a suitable treatment.Table 1.
Vascular and neurological outcomes in patients with atrial fibrillation treated with edoxaban; effects of cancer
Authors: Cheng K , Tu H P T , Scherrer-Crosbie M S C , Cheng K C C , Hsu T Y H 
Published: November 2023

Abstract

Introduction
Data from novel oral anticoagulants (NOACs) trials has shown superior outcomes of NOACs compared to warfarin in vascular and bleeding events in patients with AF, both with and without cancer, however, little discussion has been provided on their effect in congestive heart failure (CHF). NOACs also may have biological benefits in Alzheimer disease (AD). We investigated the impact of edoxaban on vascular and bleeding events, CHF, and AD, in patients with AF, with and without cancer.

Methods
In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 5683 patients with non-valvular AF (NVAF) treated with edoxaban and matched them for gender and age to 11366 patients treated with warfarin. Subsequently, we similarly matched 703 patients with NVAF and cancer (NVAF-C) treated with edoxaban to 1406 patients treated with warfarin. The crude and adjusted hazard ratios (HRs) were applied for outcome assessments. Outcomes included arterial/venous ischemic events, CHF, Alzheimer disease (AD) , bleeding, acute kidney injury (AKI), and all-cause mortality.Results:Compared to warfarin, edoxaban showed significantly lower adjusted HRs for all-cause mortality (0.37 in NVAF, 0.39 in NVAF with cancer [NVAF-C]), hospitalization for gastrointestinal bleeding (0.74 in NVAF, 0.67 in NVAF-C), and CHF (0.26 in NVAF, 0.31 in NVAF-C) in both NVAF and NVAF-C groups (all p &lt; 0.05). The adjusted HRs of acute myocardial infarction (0.71, p = 0.0051), peripheral artery disease (HR = 0.48, p &lt; 0.001), venous thromboembolism (0.55, p = 0.0003), pulmonary embolism (0.20, p = 0.0002), and AD (0.66, p &lt; 0.001) were also significantly lower for NVAF patients using edoxaban versus warfarin. However, edoxaban was associated with significantly higher adjusted HR of other hospitalized bleeding than warfarin (1.19, p = 0.0016) in NVAF patients but not in NVAF-C patients.

Conclusion
Edoxaban is associated with reduced risks of CHF in both NVAF and NVAF-C patients, and lower incidence of AD in NVAF when comparing to warfarin. These findings further support the use of edoxaban in patients with AF.
Cardiovascular complications of chimeric antigen receptor (CAR)-T cell therapy
Authors: Guerra F , Frangione A , Rrapaj E , Sfredda S , Mancini G , Coretti F , Stronati G , Olivieri A , Dello Russo A 
Published: November 2023

Abstract

Background
Mechanisms of cardiotoxicity during chimeric antigen receptor (CAR)-T cell therapy remain unclear to this day, with the main hypotheses revolving around IL-6 mediated myocardial depression during cytokine release syndrome (CRS), stress-induced or takotsubo cardiomyopathy, and direct toxicity from CAR-T cells. Hereby we present the experience of a regional referral centre for CAR-T therapy and the program developed with a dedicated cardio-oncology centre.

Purpose
To provide preliminary data on cardiovascular-related toxicity of CAR-T therapy in terms of incidence and management.

Methods
All consecutive candidates for CAR-T therapy were prospectively enrolled since the inception of the CAR-T program in our institution (2021). All patients were refractory to at least two lines of immune chemotherapy and had already undergone anthracycline treatment. After conditioning, all patients were treated with autologous CAR-T cells (tisagenlecleucel, Kymriah). Prior to CAR-T cell therapy, all patients underwent baseline cardiac evaluation at our cardio-oncology facility, including a 12-lead ECG, a complete echocardiogram and cardiac biomarkers. The same routine was performed before discharge, after one month. Supplementary evaluations were performed by an on-call cardio-oncology team according to the attending physicians.

Results
Eleven patients (6 males, mean age 60±11 years) underwent CAR-T cell infusion. Over the course of follow-up, six patients (54%) experienced CRS after a median follow-up of 12 days (7-40). Two patients with mild symptoms (Grade I) were managed with non-cardiac-related therapy while three Grade 2 patients had to start cardioprotective drugs (ACE-Is and beta-blockers) for transient left ventricular systolic dysfunction (mean lowest LVEF 44.8±3.7%). One patient experienced a Grade IV CRS due to takotsubo syndrome complicated by cardiogenic shock on day 4 and required high-dose vasopressors and mechanical ventilation. Patients experiencing a CRS had similar demographical characteristics and medical history but standard echocardiogram before CAR-T showed a lower baseline LVEF (54.5±5.6% vs 64.6±6.7%; p=.02) and lower baseline right longitudinal systolic function markers (TAPSE: 19±3 vs. 24±4 mm; p=.02 S': .09±.01 vs .13±.02 m/s; p=.03). Cardiac biomarkers (high-sensitivity Troponin I and NT-proBNP) did not show any significant predictive power at baseline. All CRS patients showed a progressive recovery of ventricular function and survived up to one-year of follow-up.

Conclusions
CAR-T therapy is associated with an increased risk of cardiotoxicity, with up to 36% of all patients requiring unscheduled cardio-oncology evaluation and management both during admission and after discharge. Cardiac adverse events range in degree of severity and should be promptly managed by a dedicated team.
The potentially protective effect of dapagliflozin on the development of cardiotoxicity in cancer patients
Authors: Maragoudakis S , Marketou M , Sideras M , Vittorakis E , Mavroudeas S E , Emiri F , Datseris G , Stratinaki M , Kafkala K 
Published: November 2023

Abstract

Introduction
The clinical trial "DECLARE-TIMI 58" (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), demonstrated that dapagliflozin, a Sodium glucose cotransporter 2 inhibitor, reduces the composite end point of cardiovascular death/hospitalization for heart failure in a broad population of patients with type 2 diabetes mellitus.Chemotherapy is known for its potetial adverse effects on myocardium.We hypothesized that early initiation of treatment with dapagliflozin could prevent cardiotoxicity .

Purpose
We aimed to study if dapagliflozin could exert cardioprotective effects in anthracycline,carfilzomib and trastuzumab-induced cardiotoxicity through the analysis of ejection fraction, global longitudinal strain (GLS) of both left and right ventricle.

Methods
32 diabetic patients who were diagnosed with cancer at our medical center were randomized (16 dapagliflozin;16 placebo). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). Our patients, receiving potentially cardiotoxic treatment: 52% were treated with only trastuzumab, 34% were treated with only anthracycline and 14% with carfilzomib. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%.

Results
In the first trimester of observation compared to baseline, patients treated with dapagliflozin did not show a deterioration of LV GLS [(GLS = −20,2±3,1% vs −19,8±3,1%, p=0,551] .Similarly in the placebo group [(GLS= −23,02±3,6% vs −22,6±3,5%, p=0,572). No significant changes were found in LVEF after treatment with dapagliflozin (57,9±5,6% vs 57,6±6,1%, p=0,733) or the placebo (60,1±5,6% vs 57,8±6,6%, p=0,166).There was a trend in GLS reduction of left ventricle in 2 patients receiving carfilzomib treatment in the placebo group (p=0.058)

Conclusions
At the best of our knowledge, our study is the first to investigate the early prophylactic use of dapagiflozin in the development of non-ischemic cardiomyopathy in patients receiving anthracycline or trastuzumab,carflilzomib therapies. During the first trimester of observation there was no benefit by dapagliflozin administration but 2 of our patients in the placebo group demonstrated reduction in GLS of left ventricle.
Differences in the prevalence of cardiovascular toxicity in a cohort of female breast cancer patients according to the different cardiotoxicity definitions
Authors: Herrera J , Esteban F , Delgado M , Rodriguez A , Ruiz M , Maestre L C , Torres A , Diaz M A , Romo E , Fernandez-Aviles C , Heredia G M , Resua A , Perea J , Mesa D , Pan M 
Published: November 2023

Abstract

Background
The definition of cancer therapy-related cardiac dysfunction (CTRCD) has evolved in the past ten years, as Cardio Oncology has consolidated as a new medical discipline. However, great heterogeneity is noted among the published criteria of the different types of cardiotoxicities by the different scientific societies.
In order to mitigate this variability, a new definition of CTRCD has been recently proposed by the International Cardio-Oncology Society (IC-OS) and endorsed by the latest 2022 ESC Guidelines on cardio-oncology. CTRCD is now classified into different degrees of severity according to symptoms, left ventricular ejection fraction (LVEF) reduction guided by echocardiography and elevation of cardiac biomarkers.

Purpose
we aimed to assess the impact of the new consensus definition of CTRCD in the reclassification of cardiotoxicity in a breast cancer cohort of female patients receiving potentially cardiotoxic therapies (CT) attended in our third-level hospital.

Methods
we retrospectively analyzed and compared the incidence of the different subtypes of CTRCD in a cohort of female breast cancer patients evaluated in our hospital from 2018 to 2021 according to both the previous 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity and the latest 2021 ICOS definition.

Results
a cohort of 193 women with a breast cancer diagnosis and receiving CT was analyzed. Mean age was 58 ± 11 years and 57 % of the patients (110) had a least one cardiovascular risk factor, with no past history of cardiac disease. According to the previous ESC 2016 criteria, 16 patients (8.3%) had cardiac dysfunction associated with cancer treatment whereas with the 2021 IC-OS new definition, a total of 23 women (12%) would have been satisfied the CTRCD criteria. Of Those, 11 were asymptomatic and 7 had severe CTRCD. Overall, this would have translated into a 30% rise in the incidence of patients experiencing any type of cardiotoxicty (p &lt; 0.0001).

Conclusion(s)
by using the new IC-OS criteria for CTRCD, a significant increase in the prevalence of cardiotoxicity was noted in our population, which may translate the higher sensitivity of the proposed criteria to detect clinical or subclinical cardiovascular damage derived from cancer treatment.