bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined mammographic breast density and breast arterial calcification is incrementally predictive of coronary artery disease beyond traditional risk factors
Authors: Aldous E , Goel V , Yeong C , Vasanthakumar S , Tu H , Salib A , Xu E , Nerlekar N 
Published: October 2024

Abstract

Background
Coronary artery disease (CAD) risk is underestimated in women using current risk stratification tools. The mammographic finding of breast arterial calcification (BAC) associates with CAD. Furthermore, breast adipose tissue, measured through breast density (BD) on mammography (low breast density indicates high adiposity) has shown potential to act as a pro-inflammatory, pro-atherogenic fat deposit. Given its uptake in screening programs, mammography may therefore represent a novel risk stratification tool for cardiovascular disease in women.

Purpose
To evaluate the association between the combined mammographic features of BD and BAC, with CAD.

Methods
Single-centre, retrospective, cross-sectional study, including 153 women, mean age 62±10, who had both clinically indicated mammography, and coronary computed tomography angiogram (CCTA) for suspected CAD. CAD risk was identified by the CAD Consortium Score, with a 15% threshold for low and high risk. BD was visually assessed and categorised by 4-level BI-RADS grade with grade A-B representing low density, and C-D representing high density (Figure 1). BAC was visually assessed and categorised as present/absent (Figure 1). CAD was categorised as presence/absence of coronary artery plaque on CCTA. Logistic regression was performed with results presented as Odds Ratio (OR) and [95% Confidence Intervals]. Receiver operator characteristic area under the curve (AUC) was used for model discrimination.

Results
Low BD (n=103 (67%)) was associated with CAD (OR 3.20 [1.58-6.53], p=0.001, as was BAC presence (n=37 (24%), OR 4.36 [1.58-12], p=0.004). There were 51 (33%) with elevated CAD risk. Participants were categorised into 4 subgroups based on low/high BD and presence/absence of BAC: 29 (19%) had low BD and BAC, 74 (48%) had low BD and no BAC, 8 (5%) had high BD and BAC and 42 (27%) had high BD and no BAC. Significantly higher proportions of CAD were noted with low BD and BAC alone, as well as combined low BD and BAC (Figure 2). Compared with high BD/BAC negative, the presence of low BD and BAC independently associated with CAD (OR 5.27 [1.19-23.3], p=0.03). Significant incremental benefit was seen after adding BD/BAC status to CAD Consortium Score (AUC 0.65 vs. 0.72, p=0.004).

Conclusions
Combined, and individual mammographic features of low BD and BAC presence are associated with CAD and improve risk prediction beyond standard coronary risk probabilities. Standardised reporting of these features to inform risk identification may be of further benefit and should be tested in prospective screening studies.
Metformin is associated with lower risks of incident cancers compared to sulphonylurea use: a population-based study with competing risk analyses
Authors: Tse G , Chou O H I , Liu X , Liu T , Wong W T , Zhou J 
Published: October 2024

Abstract

Objective
To investigate the effects of sulphonylurea compared to metformin on the risks new-onset cancers and mortality in patients with type 2 diabetes mellitus.

Methods
This is a retrospective population-based cohort study of patients with type 2 diabetes mellitus between 1st January and 31st December 2009 with follow-up until 31st December 2019. Propensity score matching (1:2 ratio) between metformin and sulphonylurea users was performed. The primary outcome is new diagnosis of any cancer. The secondary outcomes are cancer, cardiovascular, or all-cause mortality. Cox regression was used to identify significant predictors. Competing risks were considered using cause-specific or subdistribution hazard models. Propensity score stratification, inverse probability weighting, and high-dimensional propensity score adjustment were also used.

Results
In the matched cohort, 36487 sulphonylurea and 71306 metformin users were included. Univariable Cox regression showed that compared to metformin users, sulphonylurea users had a higher risks of any new cancer diagnosis (hazard ratio [HR]: 2.26, 95% confidence interval [CI]: 2.18-2.34, P&lt;0.0001), including pancreatic (HR: 4.03 [3.37, 4.82], P&lt;0.0001), colorectal (HR: 2.12 [1.97, 2.27], P &lt;0.0001), genitourinary (HR: 1.73 [1.57, 1.90], P&lt;0.0001), breast (HR: 1.36 [1.22, 1.51], P&lt;0.0001) and lung cancer (HR: 3.37 [3.11, 3.65], P&lt;0.0001) cancers. Sulphonylurea users also had higher risks of cancer-related (HR: 2.38, 95% CI: 1.87-3.03; P&lt;0.0001) and all-cause mortality (HR: 1.92, 95% CI: 1.78 -2.08; P&lt;0.0001).

Conclusion
Metformin use was associated with lower risks of new diagnosis of any cancer, cancer-related and all-cause mortality in patients with type 2 diabetes mellitus.Figure 1.Study flow diagram.FIgure 2.New diagnosis of cancer.
Sex differences in the substrate of atrial fibrillation and the outcome of thoracoscopic ablation
Authors: Keshtkar S , Al-Shama R F , Fabrizi B , Meulendijks E R , Dong Z , Terpstra M M , Zappala P , Driessen H G , De Groot J R 
Published: October 2024

Abstract

Background
Women with atrial fibrillation (AF) suffer more from AF symptoms, a lower quality of life, and have an enhanced risk of stroke. The AF recurrence after ablation is higher in women than in men. We hypothesize that sex specific differences in the atrial fibrotic substrate underlie these differences in clinical outcome. Here, we sought to characterize atrial fibrosis and fibrosis formation in the left atrial appendage (LAA) of women and men undergoing thoracoscopic ablation of AF.

Methods
We used the excised LAA of 30 female and 30 male patients with persistent AF undergoing thoracoscopic AF ablation. Patients were matched for age. In addition propensity score matching was also conducted for adjusting intermediary variables such as AF duration, Age ≥ 75, Body mass index (BMI), and CHA2DS2-VASc score ≥ 4. LAAs were stained with picrosirius red to quantify collagen and with vimentin for fibroblasts. Images were analyzed automatically (Image J version 1.50i) using color deconvolution to identify the area fraction of collagen and fibroblast.

Results
Women had similar age as men (66.4±7.76 vs 66.1 ±7.57, P= 0.85) but had a trend toward more cardiovascular risk factors [CHA2DS2-VASc score ≥ 4, (23.3 vs 6.7)%, P=0.07]. The total percentage of fibroblasts was larger in women 14.98 (9.79-24.95) % than men 13 (5.85-17.46) %, P=.018. In addition, in women fibroblasts were located more in epicardially and endocardially than in the interstitium.[women 8.18 (5.06-13.36) % vs men 6.49 (2.73-9.92) % , P=0.005].There was not a remarkable differences in total amount of collagen between the groups [women 16.03 (9.67-26.98) % vs men 15.50 (9.50-20.90) %, P=0.57 ], but there was a trend towards more epicardial and endocardial collagen in women than men [11.81(5.75-22.11)% vs 10.24 (6.06-15.10) % , P=0.06].

Conclusion
We demonstrate more epicardial and endocardial fibroblasts in the LAA of women compared to men with persistent AF. There was similarly a trend towards more epicardia and endocardial but not interstitial collagen deposition. These findings may –at least in part- underlie sex specific differences in AF pathophysiology and ablation outcome.
Correlative study to assess the predictive power of the ICOS HF calculator in the prediction of development of HER-2 antagonist induced cardiac dysfunction in a single center in Saudi Arabia in 2023
Authors: Al Qaseer M , Alabdullatif M , Alibrahim E , Al-Dobai D , Elfouad Elafly S , Kharasani M , Ismail U , Aljuhaiman A , Elhassan M , Alharbi M 
Published: October 2024

Abstract

Background
Over the past 3 decades, there has been a significant increase in cancer survivors supported by the major advances in cancer therapies. However, most of those therapies are cardio-toxic. In 2022, the European Society of cardiology had published, for the first time, a clinical guideline that describes how to manage this cohort of patients, and endorsed the utilization of a risk calculator to predictor likelihood of development of cancer therapy cardiac dysfunction (CRTCD). We did retrospective review of all consecutive patients that have received Trstuzumab (HER-2 antagonist) in the year 2023 in a single tertiary cardiac center. We assessed their demographics and co-morbidities, incidence of CRTCD, evaluated their ICOS-HF score and looked for any CRTCD in this cohort to assess whether the calculated stratification correlated with development of CRTCD. The objective is to assess the utilization of this tool in our patient population.

Methods
369 unique individuals were identified from the hospital databas that had received HER-2 antagonists. Basic patient demographics were extracted from the information system along with their clinical, laboratory, and echocardiographic data. Their risk profiles were stratified using the ICOS-HF calculator. Follow up echocardiogrphic studies were reviewed to assess the incidence of CRTCD in patients receiving HER-2 antagonists and the correlation between the risk strata using the ICOS-HF and actual development of CRTCD.

Results
The average age was 53+/- 11 years. 96.8% were females. At baseline, 20% were diabetic, 26.8% were hypertensive, 10.8% were dyslipidemic, 1.9% had prior cardiomyopathy or heart failure, 1.3% had IHD, 1.1% were smoker, 33.3% were obese, and 3.8% had CKD. Overall, in the year 2023, the incidence of HER-2 induced cardiac dysfunction was 10.6%. At baseline, using the ICOS-HF calculator, 57.9% were stratified as low risk, 21% as moderate risk 14.6% as high risk, and 6.5% as very high risk. Approximately 5% of the patients with low to moderate risk developed CRTCD, which rose to 18.5% in the high risk, and significantly rose to 58% in the very high risk population.

Conclusion
The risk stratification using the ICOS-HF calculator in consecutive patients receiving Trastuzumab correlated directly with the likelihood of developing CRTCD. 58% of all of the patients in the very high risk category developed CRTCD. This retrospective analysis validates the use of this tool in our patient population and will aid in the identification of patients that would require to have a more aggressive preemptive management, especially in the high and very high risk population using a multidisciplinary cardio-oncology team to optimize their surveillance and reduce their likelihood of cardiac dysfunction.
Cardiovascular and non-cardiovascular adverse events in patients with hematologic malignacies treated with BTK inhibitors: a real-world analysis
Authors: Belo Nunes R , Baiocchi O C C , Marques M O , Bachour P , Avezum A 
Published: October 2024

Abstract

Background
Bruton tyrosine kinase (BTK) inhibitors play an important role in targeted treatment of B-cell lymphoproliferative disorders. However, adverse events may limit the proper course of treatment in many patients.

Purpose
To compare the risk of cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) treated with first-generation BTK inhibitor ibrutinib versus second-generation acalabrutinib, using real-world data from electronic medical records.

Methods
We used data from a large collaborative multinational network ( TriNetX), that emcompasses more than 100 healthcare organizations worldwide. We queried the databank for patients aged ≥ 18 years with chronic lymphocytic leukemia or small-cell lymphomas treated with ibrutinib or acalabrutinib in the past 10 years before the analysis. We used propensity score matching to balance the cohorts. The 3-year cumulative incidences and hazard ratios for the following outcomes were calculated: atrial flutter or fibrillation, other arrhythmias, heart failure, ischemic stroke or peripheral embolism, acute coronary syndrome, bleeding, and sepsis.

Results
We compared 2,107 patients in each group. The 3-year incidences of atrial fibrillation or flutter in the acalabrutinib and ibrutinib groups were 7.11% and 14.78% respectively, with a lower ratio in patients treated with acalabrutinib than those treated with ibrutinib (hazard ratio, HR 0.68, 95% CI 0.55-0.84). New-onset hypertension occurred during the 3-year follow-up in 16.29% patients in the acalabrutinib group versus 27.8% patients in the ibrutinib group (HR 0,81, 95% CI 0.66-0.98). The incidence of sepsis was 6.49% in patients treated with acalabrutinib versus 11.37% in those treated with ibrutinib group (HR 0.77, 95% CI 0.60-0.98). Concerning the other adverse events, there were no significant differences between the two groups.

Conclusions
In this large real-world analysis, patients with CLL or SLL treated with acalabrutinib had a better cardiovascular and non-cardiovascular safety profile than those treated with ibrutinib, with lower incidence of atrial flutter or fibrillation, new-onset arterial hypertension, and sepsis.Figure 1.Cardiovascular outcomesFigure 2.Non-cardiovascular outcomes
Artificial intelligence applied to electrocardiographic images for the risk stratification of cancer therapeutics-related cardiac dysfunction
Authors: Oikonomou E K , Sangha V , Dhingra L S , Aminorroaya A , Coppi A , Krumholz H M , Baldassarre L A , Khera R 
Published: October 2024

Abstract

Background
Traditional risk stratification strategies for cancer therapeutics-related cardiac dysfunction (CTRCD) rely on serial monitoring by specialized imaging, limiting their scalability and affordability.

Purpose
To examine an artificial intelligence (AI)-enhanced electrocardiographic (AI-ECG) surrogate for imaging-based risk biomarkers, and its association with CTRCD.

Methods
Between 2013-2023, across 5 hospitals of a large U.S.-based health system, we identified patients with breast cancer or non-Hodgkin lymphoma (NHL) who received anthracyclines (AC) and/or trastuzumab (TZM), as well as a (negative) control cohort of patients receiving immune checkpoint inhibitors (ICI). We deployed a validated AI model of left ventricular systolic dysfunction (LVSD) to ECG images (≥0.1=positive screen) (ref 1) and explored the association between the model’s predictions and: i) global longitudinal strain (GLS) measurements within 15 days; ii) future CTRCD (defined as a new cardiomyopathy, heart failure, or left ventricular ejection fraction (LVEF) decrease to &lt;50%), as well as a more specific secondary outcome of LVEF decrease &lt;40%. In a negative control analysis of patients receiving ICI, we correlated baseline AI-ECG LVSD predictions with downstream myocarditis.

Results
Higher AI-ECG LVSD predictions were associated with progressively worse GLS (-18% [IQR: -20 to -17%] for AI-ECG predictions &lt;0.1, to -12% [-15 to -9%] for ≥0.5, p&lt;0.001, n=7,271) (A). In 1,308 patients receiving AC/TZM (age 59 [IQR 49-67] years, 999 [76.4%] women, 80 [IQR 42-115] follow-up months) a positive baseline AI-ECG LVSD screen was associated with higher incidence of CTRCD (n=404 events, adjusted HR 2.22 [95%CI: 1.63-3.02]) and/or LVEF &lt;40% (n=72 events, adjusted HR 4.76 [95%CI: 2.62-8.66]) (B). In a negative control analysis of 2,056 patients receiving ICI (age 65 [IQR 57-73] years, 913 (44.4%) women, follow-up 63 [IQR 28-99] months) AI-ECG predictions were not associated with downstream myocarditis (adjusted HR 1.36 [0.47-3.93]).

Conclusions
AI applied directly to baseline ECG images may stratify the risk of CTRCD associated with anthracycline or trastuzumab exposure.
Cardiovascular events and consequent risk of death in hematopoietic stem cell transplant recipients
Authors: Guerra F , Rrapaj E , Frangione A , Alfieri M , Mancini G , Saraceni F , Scortechini I , Fazeli A , Gulli F , Stronati G , Olivieri A , Dello Russo A 
Published: October 2024

Abstract

Background
Hematopoietic stem cell transplant (HSCT) represents a potentially curative approach for various hematologic cancers and bone marrow disorders. Advancements in safety and efficacy have broadened the application of HSCT to older individuals and those with concurrent medical conditions predisposing them to cardiovascular (CV) issues.
Despite the significant survival benefits offered by HSCT, it is accompanied by both short- and long-term complications, leading to considerable morbidity and mortality. CV complications, including heart failure, arrhythmias, acute thrombosis, pulmonary hypertension, and pericardial effusions, are among the potential adverse events following HSCT. Aim for the present registry is to determine how much CV complications are related to short-term survival in patients after HSCT.

Methods
Observational, monocentric cohort study consecutively enrolling all patients undergoing HSCT from 2019 to 2023. Inclusion criteria was &gt;18 years, autologous or allogeneic HSCT, and written informed consent for the participation in the study. All patients underwent a complete cardiological examination, including 12-lead ECG, echocardiography, and cardiac biomarkers, before HSCT, and after 2,6 and 12-months. CV-related adverse events were defined as systolic dysfunction (even asymptomatic), thromboembolism (both VTE and PE), stroke, arrhythmias, pericarditis and hypertensive crises.

Results
91 patients (34% female; mean age 54 +/- 12 years) were followed-up for a median of 2 years after HSCT. Major risk factors' prevalence was overall low (hypertension 28%, dyslipidaemia 33%, diabetes 9%, and only 11 patients (12%) had a positive history for CV events (6 atrial fibrillation, 4 coronary heart disease, 1 stroke) before HSCT. During follow-up, 26 patients (29%) experienced at least one CV-related adverse event, of which 7 (8%) were serious enough to require an hospital admission. CV adverse events included 5 new heart failure diagnosis, 5 new atrial fibrillation diagnosis, 10 episodes of VTE/PE, 4 pericarditis, one stroke and one hypertensive crisis. Twenty of all CV-related adverse events were reported within the first six months after HSCT (77%). Having a CV-related AE within the first six months after HSCT is associated with an increased risk of all-cause death (39% vs. 17%; log-rank p=.01; Figure 1).

Conclusions
CV-related adverse events are common in patients undergoing HSCT and strikes an overall young and healthy population. Having a CV-related adverse event in the six months following HSCT is a heavy prognostic factor for all-cause mortality. Therefore, an optimal prevention strategy including arrhythmia monitoring, echocardiographic follow-up and guideline-driven thromboembolic prophilaxis could improve patients' survival after HSCT.Figure 1
Incidence of cardiovascular diseases among breast cancer patients: a nationwide registry study 2013-2020
Authors: Engebretsen I , Oteiza F , Birkelund E F , Brandal S M , Bugge C , Halvorsen S 
Published: October 2024

Abstract

Background and aims
There is evidence to suggest that breast cancer (BC) treatment is associated with an increased risk of developing cardiovascular disease (CVD). Several countries have introduced clinical measures to reduce the impact of breast cancer treatment on cardiovascular function including activated breathing control during radiotherapy, lower radiation doses, and maximum anthracycline doses. The overall aim of this study was therefore to investigate whether breast cancer patients still exhibit higher rates of cardiovascular disease than the general population.

Methods
We conducted a registry-based cohort study using linked data from four nationwide health registries. Out study population included all Norwegian patients diagnosed with BC between 2013-2020 and matched them by age to 10 controls without BC. Health outcomes were measured from 2008 to 2021. We estimated the cumulative incidence from index date, for ten selected CVDs. For BC patients, the index date was defined as date of BC diagnosis. For controls, the index date was defined as the date of BC diagnosis for the matched BC patient. A wash-out period of 5 years was applied to identify incident cases of CVD.

Results
The study population included 27,535 patients with BC and 269,9994 matched controls. Median age in both groups was 62 years (IQR: 20). Prior to index date, there were no significant differences in the prevalence of heart valve disease, chronic ischemic heart disease heart failure and peripheral vascular disease in BC patients compared to controls (p&gt;0.05) (Table 1). Hypertensive heart disease, pulmonary embolism, atrial fibrillation, and other cardiac arrythmias were more prevalent in BC patients, while angina pectoris and acute myocardial infarction were more prevalent among controls. After the index date, the incidence proportion for heart valve disease, hypertensive heart disease, pulmonary embolism, atrial fibrillation, other cardiac arrythmias, and heart failure were higher in BC patients compared to controls (p&lt;0.001) (Table 2). No significant differences were found for angina pectoris, acute myocardial infarction, chronic ischemic heart disease, and peripheral vascular disease.

Conclusion
Breast cancer is still associated with an increased risk of developing several CVDs in current clinical practice, compared to matched controls without breast cancer.Baseline characteristicsIncidence of CVD
Influence of disturbed blood flow on endothelial function in people living with HIV
Authors: Preveden A , Maric D , Stojsic Milosavljevic A , Preveden M , Bjelobrk M , Velicki L , Barak O , Brkic S , Garipi E 
Published: October 2024

Abstract

Introduction
People infected with human immunodeficiency virus (HIV) are more susceptible to endothelial dysfunction due to the virus itself, side effects of the antiretroviral therapy and classical risk factors. Endothelial damage is most prominent at the locations where laminar blood flow is disturbed and oscillatory shear stress with retrograde blood flow is dominating.

Purpose
The goal of this study was to assess the endothelial function in people with HIV, and to determine whether their endothelium is more susceptible to a short-term increase in retrograde blood flow in comparison to healthy individuals.

Methods
The study included 62 people with HIV infection and 38 people without HIV infection, in whom endothelial function was assessed using flow-mediated dilatation, which was presented in absolute (FMD) and relative (FMD%) values. The intervention produced oscillatory shear stress and retrograde blood flow during 20 minutes, after which the endothelial function assessment was repeated.

Results
Baseline FMD (0.30±0.07 vs. 0.36±0.07 mm; p&lt;0.05) and FMD% (6.84±1.57 vs. 7.89±1.19 %, p&lt;0.05) were lower in the HIV group in compare to controls. FMD and FMD% decreased in the HIV group by 0.03 mm and 0.7% (p&lt;0.05), while in the control group they decreased by 0.09 mm and 2.0% (p&lt;0.05). The post-intervention FMD and FMD% were not different between the groups (p&gt;0.05).

Conclusion
People with HIV infection express worse endothelial function in compare to healthy individuals. Retrograde blood flow and oscillatory shear stress deteriorate endothelial function in both HIV patients and healthy controls, although this decline is more pronounced in healthy individuals.