bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of visceral adipose tissue with echocardiographic abnormalities in type 2 diabetes patients
Authors: Martinez-Dominguez P , Guerra E C , Gomez-Aviles P , Antonio-Villa N E , Almeda-Valdes P , Espinola-Zavaleta N , Santa Ana-Bayona M J , Martagon Rosado A , Campos-Munoz A
Published: October 2024

Introduction

Ectopic deposition of adipose tissue, particularly visceral adipose tissue (VAT) has been identified as a significant contributor to cardiometabolic complications among individuals with type 2 diabetes (T2D). An increase in VAT has been suggested to cause cardiac dysfunction, which may lead to echocardiographic abnormalities such as alterations in speckle-tracking and left ventricular ejection fraction (LVEF). However, this relationship has not been fully elucidated.

Purpose

This study aims to determine the association between VAT and echocardiographic abnormalities in patients with T2D.

Methods

A cross-sectional study in a tertiary hospital which included 195 individuals with T2D, the diagnosis of autoimmune diabetes was excluded. VAT was measured using electrical bioimpedance (BIA), and cardiac function was determined using echocardiography. A Spearman rank correlation analysis was conducted to evaluate the association between VAT and echocardiographic parameters, with significance set at p < 0.05.

Results

Within our cohort, the median age was 57 years, with 37% men. Based on the third quartile (P75) cutoff (5 liters for men, 3.75 liters for women), the population was categorized into P1-75 and P75-100 (Table). There were significant differences in LVEF (61% in P1-75 vs. 58% in P75-100, p = 0.041), left ventricular global longitudinal strain (LV GLS) (P1-75: -20.3%, P75-100: -19.2%, p = 0.012), and conduit phase of left atrial strain (LAScd) (P1-75: 25%, P75-100: 20%, p = 0.046). Positive correlations (Figure) were observed between VAT and indexed LV mass (r = 0.171, p = 0.020), basal diameter of the right ventricle (r = 0.308, p = 0.001), and LV GLS (r = 0.197, p = 0.006). Additionally, negative correlations were observed between VAT and LVEF (r = -0.342, p = <0.001) and right ventricular fractional area change (r = - 0.227, p= 0.001).

Conclusion

Increased VAT was associated with cardiac dysfunction, as indicated by altered LV GLS and LAScd. This study underscores the relevance of VAT in influencing both functional and structural changes in the left and right ventricles. It also highlights the significance of monitoring VAT for comprehensive cardiovascular risk assessment in T2D patients.Clinical demographics tableScatter plots with correlation graphs
Social differences in subclinical coronary artery atherosclerosis in Sweden
Authors: Rosengren A , Andell P , Djekic D , Nilsson P , Soderberg S , Oldgren J , Ostgren C J
Published: October 2024

Most data indicate an inverse relation between socioeconomic status and clinically manifest coronary heart disease that is only partly explained by modifiable cardiovascular risk factors. Few population-based studies have investigated social factors with respect to differences in subclinical coronary atherosclerosis in a healthy population without prior manifest coronary disease.

Purpose

To examine socioeconomic differences in imaging-detected coronary atherosclerosis, and to which extent potential differences could be explained by modifiable risk factors.

Methods

The Swedish CArdioPulmonary bioImage Study (SCAPIS) randomly invited individuals aged 50 to 64 years from the general population. Out of 30,154 participants, we defined a population of healthy participants without prior myocardial infarction or coronary procedures, with technically satisfactory results from coronary computed tomography angiography (CCTA) and coronary artery calcification scoring (CACs). CCTA outcomes were recorded as 1. any coronary atherosclerosis, 2. coronary stenosis ≥50%, 3. segment involvement score (SIS) ≥4, and 4. coronary artery calcium score (CACs) ≥100.

Results

Among 24,616 participants (49.2% women, mean age 57.4 (SD 4.2) years), those with ≤9 compared to ≥12 years of education were heavier, with mean (SD) BMI 28.0 (4.5) compared to 26.1 (4.0) kg/m2, with more hypertension (23.3% vs 15.0%), and diabetes (9.6% vs 4.6%), and with more active smokers (17.4% vs 3.8%). The prevalence of plaque/significant stenosis is shown in the Figure. Findings with respect to low vs high education and odds ratios (ORs) adjusted for age and sex were: 48.8% vs 35.3% for any coronary atherosclerosis, OR 1.31; 95%CI 1.19-14.4; 6.8% vs 4.4% for coronary stenosis ≥50%, OR 1.21; 95%CI 0.99-1.47; 15.7% vs 9.8% for SIS≥4, OR 1.21; 95% CI 0.99-1.47; and 10.1% vs 7.1% for CACS≥100, 1.29; 95%CI 1.12-1.48 (Table). However, after adjustment for coronary risk factors no significant associations with subclinical coronary atherosclerosis persisted.

Conclusions

After adjustment for conventional modifiable risk factors there was no convincing evidence of any independent association between low education and subclinical coronary atherosclerosis. Further studies are needed to explore which other mechanisms could potentially explain an independent link between low socioeconomic status and clinically manifest coronary heart disease.Figure
Low chronotropic response in post-myocardial infarction exercise test predicts worse prognosis in patients with preserved or mildly reduced left ventricular ejection fraction
Authors: Smarz K , Tysarowski M , Ziolo J , Zaborska B , Jaxa-Chamiec T , Budaj A
Published: October 2024

Background

Chronotropic incompetence is common in post-myocardial infarction (MI) patients and is associated with reduced exercise capacity. However, its prognostic significance and a determination of threshold values for prognosis remain unclear.

Methods & Results

We assessed 96 post-MI patients 4 weeks after their initial event with left ventricular ejection fraction (LVEF) ≥ 40%. All patients underwent combined stress echocardiography and cardiopulmonary exercise tests. The chronotropic response was measured as a percent of the maximal predicted heart rate at peak exercise (%MPHR). Exclusion criteria included patients with exercise limitations for pulmonary or peripheral reasons and those who declined to complete the study. Follow-up was conducted in 86 patients. The primary outcome measured was a composite of all-cause mortality or hospitalization for ischemic heart disease events (acute MI, unstable angina, or revascularization procedures) or heart failure exacerbation. The median follow-up duration was 4.0 (IQR 2, 5.6) years. The median patient age was 60 (IQR 53, 65) years, 64% of patients were males, and 84% were on beta-blockers. Median LVEF was 57 (IQR 51, 62)%, and median peak VO2 was 19 (IQR 15, 22) mL/kg/min. There were 15 composite end-point events, including 3 deaths, during the follow-up period. The %MPHR threshold of 67% had the best predictive value with an area under the curve (AUC) of 77% for predicting the primary outcome (PPV 31%, NPV 97%, sensitivity 93%, specificity 55%). A significant difference (p = 0.0022) in the occurrence of the composite end-point was noted between patients with a %MPHR below versus above this threshold (Figure. Kaplan-Meier curves for survival free of primary outcome). In the multivariate Cox regression analysis adjusting for demographic, clinical variables, and beta-blocker doses, only chronotropic response and current smoking correlated with the primary end-point (Table. The Cox proportional hazards regression model for prediction of the primary outcome).

Conclusions

A low chronotropic response to exercise is a negative prognostic marker in post-myocardial infarction patients with either preserved or mildly reduced left ventricular ejection fraction.Figure.Table.
Development of a systematic referral model to primary care health interventions for patients with atrial fibrillation. a delphi study
Authors: Elnegaard C , Risom S , Borregaard B , Tveskov C , Brandes A , Zwisler A D
Published: October 2024

Background

The European Society of Cardiology (ESC) guidelines for the management of atrial fibrillation (AF) recommend integrated care in AF, combining medical treatment with lifestyle modifications and psychosocial management in a multi-disciplinary set-up. Research show that patients with AF can benefit from lifestyle interventions and psychosocial management, like patient education. According to World Health Organization recommendations, these health interventions are moving from hospitals to primary healthcare settings. Therefore, patients with AF should be systematically referred to these interventions. Yet, an evidence-based referral model that can support this transition is lacking.

Purpose

The purpose is to develop a systematic referral model for primary care health interventions for patients with AF.

Methods

We used the Delphi-technique with three rounds of questionnaires (figure 1). International and national clinical experts in AF across disciplines and health sectors were invited to participate. In the first round, the expert panel evaluated items that could be part of a referral model on relevance, improvability and self-reporting. In the second round, the expert panel evaluated each item as either an inclusion or exclusion criteria, important knowledge to have, or not relevant. In the third round, the expert panel evaluated the items according to data source and outcome status. A final model was drawn based on items reaching consensus. The study was reported according to the guidance on conducting and reporting Delphi studies (CREDES).

Results

In total, 69 of 139 invited experts accepted to participate (50%). These were mostly academics or clinicians (90%), stemming from primary sector (16%), secondary sector (35%) and research (32%). Most were medical doctors (36%) and nurses (35%). However physiotherapist, psychologists, dieticians, and other disciplines along with six patients with AF were also represented. The expert panel (60% females) had a mean age of 50 years, and 65% were from Denmark. For the final referral model (figure 2), AF symptom burden and impaired health-related quality of life, anxiety and poor medicine compliance combined with a risk factor profile were the main inclusion criteria. Furthermore, it was important to know about the patients’ mental well-being, self-management abilities and comorbidities.

Conclusion

Consensus was reached for a generic referral model, which can be further adjusted in the appropriate clinical context. The model includes inclusion criteria which closely correlate with guidelines for AF management focusing on reducing the patients’ symptom and risk factor burden. The referral model is expected to increase the number of patients with AF referred to primary care health interventions, which could lead to better quality of life, fewer hospital admissions and lowered health care costs in AF.
Exploring LGE areas in the atria: Insights from electroanatomical voltage mapping in AF patients
Authors: Ali S Y , Mohsen Y , Mao Y , Sakata K , Prakosa A , Yamamoto C , Kholmovski E , Sinha S , Marine J , Sommer P H , Sohns C H , Stoeckigt F , Spragg D , Trayanova N
Published: October 2024

Introduction

Late gadolinium enhancement MRI (LGE MRI) is a common method for the evaluation of the atrial substrate in atrial fibrillation (AF) patients. The extent of LGE is associated with atrial cardiomyopathy and ablation outcomes. However, previous studies have yielded inconsistent results in detecting low voltage areas (LVA) using bipolar electroanatomical mapping (EAM) in LGE regions.

Objective

Conduct a thorough analysis of the bipolar and unipolar voltage in LGE areas and its relationship with the voltage in non-LGE areas, utilizing high-density (HD) EAM generated by a multipolar HD-mapping catheter.

Methods

In this study, 20 patients undergoing AF ablation were examined using LGE-MRI. A 3D mesh integrating LGE data was generated. HD-EAM (> 4000 points) was performed in sinus rhythm. The EAM map and MRI mesh underwent manual alignment and registration. Using a nearest neighbor algorithm, EAM points nearest to LGE areas were identified, and the corresponding unipolar and bipolar voltage values, along with LGE voxel intensity, were exported for analysis.

Results

LGE areas exhibited a median bipolar voltage amplitude of 0.93 mV, median unipolar voltage of 1.73 mV. In contrast, areas without enhancement displayed median bipolar voltage of 2.33 mV, unipolar voltage of 3.58 mV. We observed a variation in voltage amplitudes across the different LGE areas: bipolar voltage ranged from 0.04 to 2.51 mV and unipolar voltage from 0.22 to 3.75 mV. This variation strongly correlated with voxel intensity in LGE areas (correlation coefficient r = -0.86 [p <0.001]). Irrespective of the voltage amplitude in the examined LGE areas, a significant voltage drop was observed, with an average reduction of 54% in bipolar and 51% in unipolar voltages, compared to the amplitudes in non-LGE areas within the same atria.

Conclusion

Variations in bipolar and unipolar voltage within LGE areas are significantly correlated with local voxel intensity. Despite the inconsistent overlap with the predefined bipolar threshold for LVA, LGE regions exhibit a pronounced and consistent reduction in both bipolar and unipolar voltage compared to non-LGE areas. This pattern suggests notable electrophysiological changes in these areas. These insights underscore the need for further investigation to better understand the implications and mechanisms underlying these alterations in LGE regions.
Patients vaccinated against COVID-19 present better coronary flow, myocardial work and NTproNP levels than non-vaccinated at 4 months post COVID infection
Authors: Ikonomidis I , Kountouri A , Katogiannis K , Pavlidis G , Thymis J , Kostelli G , Katsanaki E , Thomas K , Antoniadou A , Tsiodras S , Frogoudaki A , Vrettou A R , Parissis J , Lambadiari V
Published: October 2024

Introduction

COVID-19 affected patients present impaired subclinical markers of cardiovascular and endothelial function post resolution of infection. Whether vaccination impedes impairment of myocardial and vascular function has not been clarified.

Purpose

We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function in vaccinated and non-vaccinated subjects at four months after the infection.

Methods

We recruited 60 vaccinated and 60 non-vaccinated patients with similar clinical characteristics, who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four months after a confirmed COVID-19 infection. We measured (i) perfused boundary region (PBR) of the sublingual arterial (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) NTproBNP blood levels.

Results

Among vaccinated patients 54,2% had mild disease, 33,3% had moderate disease and 12,5% had severe disease, while among non-vaccinated 29,1% had mild disease, 32,9% had moderate disease and 38% had severe disease(p<0.05).

At four months, vaccinated patients presented with higher LVGLS, GCW values and CFR compared to non-vaccinated (p>0.05 table), while GWI, GWW and GWE were similar between the two groups(p>0.5). Moreover, in vaccinated patients RVGLS and RV FWLS were significantly higher than in non-vaccinated patients (p>0.05). Also, NTproBNP leves were significantly lower in vaccinated than in non-vaccinated patients (p<0.05).

At four months, in vaccinated patients , we observed a marginally lower brachial and central systolic blood pressure compared with non-vaccinated (p=0.045, p=0.048 respectively.) Vaccinated patients displayed similar FMD and PWV values compared to non-vaccinated (p>0.05 for all the comparisons).

Conclusion

Patients vaccinated against COVID-19 suffered from milder disease resulting to better cardiac function and lower NTproNP levels than non-vaccinated 4 months post COVID infection.
Serum proteomic profiling reveals potential inflammatory biomarkers in long-COVID patients: a comparative analysis with healthy controls
Authors: De Angelis M , Togni G , Praderio A , Fioretti F , Sammartino A , Rizziello A , Calzoni A , Nodari S
Published: October 2024

Background

Long-COVID (also known as post-acute sequelae of SARS-CoV-2 infection, PASC), is defined as the persistence, or the new onset, of symptoms after recovery from the acute phase of COVID-19.

It consists of a multiorgan syndrome expressing itself with a wide variety of cardiovascular and non-cardiovascular symptoms such us chest pain, fatigue, shortness of breath, autonomic dysfunction, cognitive impairment and sleep disorders even in the absence of a clear evidence of organ dysfunction.

Some previous studies have suggested the potential role of an abnormal inflammatory response after SARS-CoV-2 infection, however the specific underlying mechanisms remain unclear.

In this study we performed a proteomic analysis of the serum of 80 long-COVID patients to identify potential biomarkers that may act as indicators or therapeutic targets for long COVID.

Methods and results

We compared the levels of the proteins in both long-COVID group and a control group using multivariate and univariate analysis. Both PLS-DA and PCA analysis showed a clear distinction between the two groups; clustering analysis also clearly separated control from long-COVID patients. Proteins were then filtered based on (a) statistical analysis, considering proteins with a VIP>1 (PLSDA) and p<0.05 (t-test); (b) coefficient of variation (CV), where only proteins with CV<10 were considered; (c) and fold change (FC), for which proteins with FC<0.67 or FC>1.5 were selected for further analysis.

The selected proteins were then subjected to a ROC curve analysis to identify antithrombin as a potential biomarker with an area under the curve (AUC) near 1. Other proteins, displaying an AUC > 0.98, were also identified as potential biomarkers (Sirtuin 1, NatriureticPeptide B, Hemopexin Arachidonate 5-Lipoxygenase). In addition, a multivariate ROC method, using linear SVM as classification method, identified that a combination of ten proteins would also result in an AUC near 1.

Finally, a correlation analysis between the proteins of interest and the clinical manifestations was performed. A positive correlation (above 0.5) was found between dyspnea and Glucocorticoid Receptor and between memory deficit and Antithrombin. Arachidonate 5-Lipoxygenase was negatively correlated (below -0.5) with tremors and hair loss, MannoseBinding Lectin 2 was found to be positively linked to asthenia, Antithrombin with concentration deficit and Endothelin-2 with muscles aches.

Conclusions

The identified biomarkers are associated with inflammatory processes, corroborating literature evidence that long-COVID patients develop an inflammatory state that damages many tissues. Further studies are needed to validate this data in larger cohorts to identify specific biomarkers, and guide future preventive strategies or treatments to address long COVID and its cardiovascular and non-cardiovascular sequelae.
Prognostic evaluation with cardiac magnetic resonance in patients with systemic sclerosis
Authors: Fernandez J R , Guillen Del Castillo A , Airale L , Giustiniani A , Valente F V , Illuminato F , Simeon C P , Rodriguez Palomares J F
Published: October 2024

Systemic sclerosis (SSc) is an autoimmune disease with multiorgan involvement. Cardiac involvement is common and impact in prognosis. Cardiac magnetic resonance (CMR) allows an evaluation in ventricular and atrial function and hemodynamics forces.

Our study aimed to assess RVD prevalence in SSc patients and analyze its impact on cardiovascular events.

Methods

In this retrospective study, we included patients diagnosed with SSc and followed-up in a specialized unit. We collected clinical, hemodynamic, and imaging data, including baseline CMR studies. Pulmonary function tests were also performed.

RVD was defined as a right ventricular ejection fraction ≤52% in men and ≤51% in women.

Patients were monitored for a composite endpoint consisting of cardiovascular death and/or admissions due to heart failure (HF). We assessed the predictors of this endpoint using Cox regression analysis.

Results

The study included 74 patients with SSc, most were female (81 %) with a mean age of 60±12 years. RVD prevalence was 32 %. Patients with RVD had greater ventricular volumes (160±44.9 vs 130±36.2; p=0.003), lower right ventricular global strain (-18 % vs. -26 %; p <0.001) and lower right atria strain (19% vs 29%; p=<0.001). We don’t found differences in presence of LGE of both ventricles.

In the multivariate analysis RVEF (HR 2.9.; p = 0.022), pulmonary trunk dilatation (HR 1.15; p= 0.004, pulmonary hypertension at baseline (HR 2.98; 0.09); RV GLS (HR 1.08; p = 0.03) and RA GLS (HR 0.96; p = 0.024) were predictors of composite outcome of cardiovascular death and/or heart failure hospitalization. During a mean follow-up of 46 months, patients with RVD had higher rates of heart failure admissions (38% vs. 12%; p = 0.01) and cardiovascular mortality (29% vs. 6%; p 0.01). No ventricular arrhythmias occurred.

Conclusion

RVD is common among SSc patients. RVEF and pulmonary hypertension are the strongest variables linked to increased adverse cardiovascular clinical events and decreased survival in these patients.
Are novel ASCVD risk factors more prevalent in young middle eastern women who have classical risk factors
Authors: Alkhawaldeh M , Al-Akhras A , Abedal- Kareem K , Baker M , Abu Dayah S , Alsahan M , Almansi J , Eid S , Hammoudeh A , Ibdah R , Shehadeh J , Mahmoud S , Asfour H , Ababneh A
Published: October 2024

Introduction

Urbanization is an important contributor to atherosclerotic cardiovascular disease (ASCVD) in the Middle East, especially in the younger age groups. There is a scarcity of data on clinical profiles and cardiovascular risk factors (RFs) in urban young women compared with those who reside in rural areas in this region.

Purpose

To study the demographic and clinical profiles and prevalence of traditional and novel CV RFs in a cohort study of young urban Middle Eastern women compared with those in rural areas.

Methods

The prevalence of 19 traditional and novel cardiovascular RFs were compared in urban vs. rural young women residents (18-50 years of age), who were enrolled in 12 centers (August 2020 to October 2023).

Results

Of 627 young women enrolled (mean age 44.2 ± 5.1 years old), 463 (74%) were urban residents and 164 (26%) were rural residents. ASCVD was diagnosed in 32% of urban and 37.3% of rural young women. Table shows the prevalence of traditional and novel, sex-specific RFs with significant differences in the 2 groups. Other RFs with no significant differences included hypertension, diabetes and gestational diabetes, preterm delivery, persistent weight gain after delivery, radiation for breast cancer, and polycystic ovary syndrome.

Conclusion

In this cohort of Middle Eastern young women, despite heterogeneity, those who were urban residents had worse clinical profiles with higher prevalence of certain classical and sex-specific risk factors.
Sex sifferences in lifes essential eight and its association with mortality among adults without known CVD
Authors: Kobo O , Kaur G , Gulati M , Mamas M
Published: October 2024

Background

The American Heart Association’s Life’s Essential 8 (LE8) score is a helpful tool to quantify cardiovascular health (CVH) metrics. Sex differences in relation to LE8 and its association with mortality are not known.

Methods

The National Health and Nutrition Examination Survey (NHANES) between 2009 and 2018 was utilized to evaluate the prevalence of health metrics included in LE8 among adult patients, stratified by sex. Health metrics were further subdivided into health behaviors (diet, physical activity, nicotine exposure, and sleep) and health factors (body mass index, non–high density lipoprotein cholesterol, blood glucose, and blood pressure). LE8 scores were also evaluated based on age, race/ethnicity, and socioeconomic status. Cox proportional hazard models were used to evaluate the association between the levels of CVH and risk of all-cause and cardiovascular mortality.

Results

Among 22,761 participants, 52% were female. Overall CVH score was similar in both females and males (65.8 vs. 65.9). Females had higher health factors score (64.3 vs. 63.1, p <0.001) and lower health behaviors score (67.2 vs 68.6, p <0.001). Amongst individual metrics, blood pressure score was higher in females (73.2 vs. 67.7, p <0.001) while males had higher physical activity score (70.6 vs. 54.9, p <0.001). For individuals under 65 years of age, overall CVH and health factors scores were higher in females while in those age 65 or older, males had higher scores. The most prominent sex differences were noted in non-Hispanic Black females who had significantly lower CVH scores than Black males. High or moderate LE8 scores vs. low LE8 scores demonstrated lower all-cause and CV mortality in both sexes (p-interaction 0.98 and 0.9). High or moderate health behaviors scores also demonstrated a significant association with lower all-cause and CV mortality, with the reduction in mortality being more prominent in females (p-interaction 0.01 and 0.03).

Conclusions

We demonstrate important sex differences in CVH metrics along with notable variations based on age and race/ethnicity. Furthermore, we highlight sex differences in the association of CVH metrics with mortality. These findings underscore the importance of designing and implementing effective strategies for both sexes, aimed at targeting these specific factors.
Sex-differences in the clinical features, managements and outcomes of early-onset atherosclerotic coronary artery disease in China
Authors: Shali S , Yao K , Luo L F , Xu L L , Huang M G , Shi F , Li J X , Qian J Y , Zheng Y , Dai Y X , Ge J B
Published: October 2024

Background/Introduction

There is an alarming rise in the incidence of atherosclerotic coronary artery disease (CAD) among young adults, particularly in young women. Sex disparities of early-onset CAD in the context of contemporary cardiovascular practice are not well understood.

Purpose

We aimed to delineate the differences in clinical profiles and prognosis between young men and women with established early-onset CAD.

Methods

This is a nationwide, hospital-based, longitudinal prospective cohort study. Young patients (aged ≥18 years and ≤ 45 years) with angiographically confirmed severe atherosclerotic obstructive coronary arteries (luminal narrowing ≥ 70%) were included from 38 hospitals across China between May 2017 and May 2020. Coronary risk factors, clinical features and treatments were compared between men and women at baseline. Participants were followed for 3 years. The outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), unplanned revascularization, and ischemic stroke. The Cox regression analyses were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for outcome.

Results

There were 1524 patients (female: 4.4%) included in this study. The female patients were older than the male patients (41.1±4.0 years for females vs. 39.6±4.4 years for males, p=0.006). They showed a lower prevalence of hypertension, lipid disorders, and smoking or drinking (all p<0.01). The female patients were less likely to have at least 1 modifiable risk factors (female: n=45 (67.2%) vs. male: n=1382 [94.6 %], p<0.001); they showed more favorable laboratory results at baseline, including lipids, serum creatinine and uric acid (all p<0.05) as compared to male patients. Besides, young females presented more often with stable angina on admission, whereas young males tended to present with acute MI (p<0.001). There was no significant sex difference in Gensini Score (p=0.15). Female patients were less likely to undergo revascularization procedures than male patients (73.1% vs. 85.3%, p=0.01). During the 3 years of follow-up, female patients were at a significantly higher risk of MACE compared to their male counterparts (13.4% vs. 5.8%, adjusted HR: 3.07, 95% CI:1.36–6.94, p=0.007) after adjusting for age, smoking, drinking, body mass index, hypertension, diabetes, dyslipidemia, diagnosis and revascularization.

Conclusions

Distinct sex disparities, unfavorable to young females, were documented among patients with early-onset CAD, with the largest gaps noted in the treatment and prognosis. Despite more favorable baseline profiles, young female patients had insufficient care and 3-fold greater risk for MACE compared to young males. These results highlight the need for strengthening the treatment strategies for this vulnerable disease entity.Figure 1
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

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

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<0.0001), including pancreatic (HR: 4.03 [3.37, 4.82], P<0.0001), colorectal (HR: 2.12 [1.97, 2.27], P <0.0001), genitourinary (HR: 1.73 [1.57, 1.90], P<0.0001), breast (HR: 1.36 [1.22, 1.51], P<0.0001) and lung cancer (HR: 3.37 [3.11, 3.65], P<0.0001) cancers. Sulphonylurea users also had higher risks of cancer-related (HR: 2.38, 95% CI: 1.87-3.03; P<0.0001) and all-cause mortality (HR: 1.92, 95% CI: 1.78 -2.08; P<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

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

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

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

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 <50%), as well as a more specific secondary outcome of LVEF decrease <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 <0.1, to -12% [-15 to -9%] for ≥0.5, p<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 <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

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 >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