bluuebunny/crossref_metadata_2025 huggingface dataset:
Sudden cardiac death in women: causes of death at premenopausal and postmenopausal age
Authors: Eskuri M A E , Holmstrom L , Vahatalo J , Kentta T V , Tikkanen J , Pakanen L , Kortelainen M L , Perkiomaki J , Huikuri H V , Junttila M J
Published: November 2023

Background

Among women the incidence of sudden cardiac death (SCD) is lower than in men but still significant. On average menopause occurs at the age of 51.4 years. During the last decades the proportion of nonischemic SCD seems to have increased in both sexes. In postmenopausal women both the incidence and severity of the coronary artery disease (CAD) increase unpredictably 3-fold compared to premenopausal women of similar age.

Purpose

The aim of this study was to determine whether the causes of SCD differ among women at premenopausal and postmenopausal age.

Methods

The Fingesture study has systematically collected clinical and autopsy data from SCD victims in Northern Finland between 1998 and 2017. The cohort consists of 5,869 SCD victims of which 1,238 are women (21.1%). Women aged ≥52 years were considered as postmenopausal and ≤51 years old as premenopausal as the direct information of the menopause lacked due to the retrospective nature of this autopsy-based data.

Results

Approximately one fifth of the SCD victims were women (21.1%; P<0.001). The mean age of female subjects was 70.1±13.1 years (P<0.001). Only 7.9% of the women experienced SCD under the age of 52 years (P<0.001). Causes of death among women at premenopausal and postmenopausal age are represented in Table 1. Amongst all women 71.7% of the SCDs were ischemic (P<0.001). Majority of those women were at postmenopausal age but CAD caused still one third of the SCDs of the women at premenopausal age (33.7%, P<0.001).

Overall nonischemic causes of death were more common at premenopausal age compared to postmenopausal women. Statistically significant nonischemic causes of death were primary myocardial fibrosis (PMF), obesity cardiomyopathy (CM), myocarditis, arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated CM. PMF was considerably more common cause of death among premenopausal women than in postmenopausal women (19.4 % vs. 3.9%, P<0.001), as was also the obesity CM (16.3% vs. 5.3%, P<0.001). Myocarditis caused the death of 5.1% of the premenopausal women but only 1.3% of the postmenopausal women (P=0.004). Both dilated CM (P=0.021) and ARVC (P=0.008) were the cause of death of 2.0% of the premenopausal women and 0.3-0.4% of the postmenopausal women. Subjects with anatomically and histologically normal finding at autopsy were mainly at premenopausal age (2.0% vs. 0.3%, P=0.008) even though the overall amount of cases remained low.

Conclusions

SCD at premenopausal age is rare. One third of the premenopausal SCDs are ischemic even though majority of the SCDs at premenopausal age are nonischemic etiology. Especially the prevalence of PMF and obesity CM were remarkably higher among premenopausal women compared to the postmenopausal age group emphasizing the role of genetics and lifestyle behind the SCD of premenopausal women.Table 1.
Differences in the outcomes of catheter ablation for ventricular tachycardia by sex
Authors: Woelber T , Dhawan R , Desimone C V , Killu A M , Deshmukh A J , Kowlgi G N
Published: November 2023

Background

Catheter ablation of ventricular tachycardia (VT) has emerged as the mainstay of management for these sick patients. There is a lack of long-term data studying the characteristics and outcomes of VT ablation in females and the comparison with males.

Purpose

The purpose of the study was to assess the impact of sex on outcomes of catheter ablation for ventricular tachycardia.

Methods

A single-center retrospective study of 200 procedures in 168 patients undergoing catheter ablation for scar-related VT under GA or MAC sedation was conducted. Data collected included demographics, comorbidities, medications, relevant laboratory abnormalities, electrocardiograms, structural data including echocardiograms and cardiac magnetic resonance imaging, detailed procedural characteristics, and outcomes.

Results

Females undergoing VT ablation were younger (49.4 ± 15.6 vs. 65.5 ± 12.2 years) [Figure 1]. Females had a lower burden of comorbidities, including congestive heart failure (30.0 % vs. 82.5%), hypertension (27.5% vs. 74.4%), atrial arrhythmias (20.0% vs. 55.6%), chronic kidney disease (25.0% vs. 43.8%), prior myocardial infarction (15.0% & 35.0%), and coronary artery bypass graft surgery (0.0% & 23.8%). Females were on fewer antiarrhythmic drugs at baseline. During the procedure, males had a greater likelihood of undergoing general anesthesia (72.5% vs. 50.0%) and associated hemodynamic instability at baseline (30.0% vs. 12.5%). It was more likely for VT to be induced in males, and females required more induction medications. There was no difference in complication rates between males and females. A greater proportion of males were discharged and maintained on antiarrhythmic drugs after the procedure. There was no significant difference in VT recurrence or long-term mortality. Using Kaplan-Meier analysis, no difference was seen in long-term VT-free survival by sex (p=0.20) [Figure 2]. In a multivariate regression model, female sex had no bearing on the VT-free survival.

Conclusion

Females undergoing catheter ablation for VT are younger and have fewer comorbidities. They tend to be on fewer antiarrhythmic drugs at baseline, and after ablation. Interestingly, despite a healthier baseline profile, females do not experience less VT recurrence or mortality compared to males. Further study would be needed to investigate this association.Figure 1Figure 2
Myosin light chain dephosphorylation by ppp1r12c promotes atrial hypocontractility in atrial fibrillation
Authors: Gonzalez-Gonzalez F J , Perike S , Abu-Taha I , Damen F W , Lizama K , Aboonabi A , Aguilar-Sanchez Y , Ong S G , Darbar D , Goergen C J , Wolska B , Dobrev D , Wehrens X H T , Mccauley M
Published: November 2023

Background

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, increases thromboembolic stroke risk five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C, the PP1 regulatory subunit targeting atrial myosin light chain 2 (MLC2a), causes hypophosphorylation of MLC2a and results in atrial hypocontractility.

Methods

Right atrial appendage tissues were isolated from human AF patients versus sinus rhythm (SR) controls. Western blots, co-immunoprecipitation, and phosphorylation studies were performed to examine how the PP1c-PPP1R12C interaction causes MLC2a de-phosphorylation. In vitro studies of pharmacologic MRCK inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with EP studies.

Results

In human patients with AF, PPP1R12C expression was increased two-fold versus SR controls (P=0.02, n=12,12 in each group) with > 40% reduction in MLC2a phosphorylation (P=0.000001, n=12,12 in each group). PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF (P=0.03 and 0.007 respectively, n=8,8 in each group). In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a, and dephosphorylation of MLC2a. Lenti-12C mice demonstrated a 150% increase in LA size versus controls (P=5.0x10-6, n=12,8,12), with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in Lenti-12C mice was significantly higher than controls (P=0.02 and 0.04 respectively, n= 6,6,5).

Conclusions

AF patients exhibit increased levels of PPP1R12C protein compared to controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key regulator of atrial contractility in AF.
Adverse cardiovascular outcomes and sex-specific differences among older adults with cardiac ageing
Authors: Gao F , Tan R S , Teo L L Y , Ewe S H , Koh W P , Tan K B , Koh A
Published: November 2023

Background

Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit.

Methods

Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included.

Results

956 participants [mean age 63±12.9 years, n=424 males (44%)] were categorized based on mitral peak early to late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI 2.24-3.56), and 0.45 per 100 person-years (95% CI 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes were significantly different among E/A categories (log-rank p=0.0269). E/A<0.8 (HR 1.80, 95%CI 1.031, 3.14, p=0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI 2.62-4.84), and 0.75 per 100 person-years (95% CI 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI 1.56-3.16), and 0.21 per 100 person-years (95% CI 0.067-0.64) for all-cause death. For E/A<0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95%CI 1.18, 5.23, p=0.017).

Conclusion

Myocardial ageing was an independent predictor of cardiovascular outcomes. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.Myocardial Ageing in the Community
Risk predicting for acute coronary syndrome with conventional and unstable plaque radiomics features from serial coronary computed tomography angiography
Authors: Sun T I N G , Cao F , Gao S , Wang Y B , Li A N G , Wang X J , Fang Y , Fang Z Y , Li S L
Published: November 2023

Background

Plaques with high-risk features are responsible for most acute cardiac events. However, there are still some lesions with high-risk plaque (HRP) morphology, which will not lead to cardiac events over time. It is crucial to precisely identify features of unstable plaque and to carry out individualized treatment, eventually aiming to reduce the likelihood of plaque rupture and lower the incidence of acute coronary events. Besides, the development of quantitative radiomics in recent years may further help with the diagnostic and predictive performance of coronary CTA.

Purpose

To establish machine learning models by combining traditional coronary CTA features of high-risk plaque and radiomics features of unstable plaque, so as to improve the efficiency of models and to predict acute cardiac events precisely.

Methods

A total of 133 elderly patients (407 lesions) were retrospectively enrolled in this cohort study who underwent serial CCTA with the interval ≥ 2 years between scans. The patients were divided into two groups according to the occurrence of acute coronary events within 1 year after coronary CTA scanning . We recorded anatomical characteristics, high-risk plaque characteristics, and acute coronary events of the elderly patients. Based on the coronary CTA image cohort, we applied 3D Slicer software to segment target lesions, delineate regions of interest, and extract radiomics features. After that, we used LASSO regression to reduce the dimensionality of the radiomics features, and finally screened out unstable radiomics features. Combining the HRP features with the selected radiomics features, we established a prediction model of acute cardiac events with machine learning method. The area under the receiver operating characteristic (ROC) curve (AUC) was analyzed to compare the classification ability of conventional and radiomics models in the validation set.

Results

133 elderly patients were included, with an average age of 65.8 ± 5.3 years. A novel model has been established by combining HRP features and 4 selected unstable radiomics features (2 wavelet features, 1 shape feature and 1 GrayLevel feature) with SVM machine learning method. Compared with conventional HRP model, the novel model displayed a significantly improved predictive performance in the validation set (AUC 0.784 vs. 0.624, P < 0.001).

Conclusions

We have established a novel model by combining the traditional HRP features of coronary CTA and radiomics features of unstable plaque, assisting in better prediction of acute coronary events in elderly . Compared with traditional HRP feature model, the prediction efficiency of novel model was significantly improved.
Frailty prevalence among older decompensated heart failure patients
Authors: Fernandez-Berges D , Vazquez-Jaren E , Mayoral Teston N , Salgado Gil N , Zaro Bastanzuri M J , Fernandez Morillo I , Maese Calvo J , Munoz Salvador L , Arrighi Soria I , Gonzalez Fernandez R
Published: November 2023

Background

Frailty is a clinical syndrome characterized by diminished strenght, endurance and reduced physiologic function that increases an individual’s vulnerability.

This syndrome often coexists in elderly patients with heart failure and can have a negative impact on their health and well-being. In the last few years four domains of frailty had been described: clinical, functional, psyco-cognitive and social.

Purpose

To determine the prevalence of frailty in each domain in patients 65 years of age and older with decompensated heart failure (DHF).

Methods

Prospective and observational study carried out in consecutive patients admitted to hospital due to DHF. Different validated scales were used. Clinical Domain: Charlson Comorbidity Index (CCI), MiniNutritional Assessment (MNA), Clinical Frailty scale CFS), New York Heart Association classification (NYHA); Functional Domain: Timed Up and Go (Up&Go), Short Physical Performance Battery, Fried phenotype (SPPB), Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL); Psyco-cognitive Domain: Minimental State Examination (MMSE), Yesevage Geriatric Depression Scale (YGDS); Social Domain: Old American Resources and Services (OARS).

All patients signed the informed consent and were evaluated when they were clinically stable.

Results

200 consecutive patients were included, aged 81.1 (SD 7.7),108 (54%) were female.

Diabetes was present in 89 (44.7%) patients, arterial hypertension in 182 (91.5%), dyslipidemia in 138 (69.3%), active smoking in 8 (4.1 %), chronic obstructive pulmonary disease in 66 (33.5%), apnea 44 (22.4%), neoplasms in 36 (18.3%), chronic renal failure in 48 (24.4%), previous myocardial infarction in 42 (21.3%), stroke in 245 (12.2%), previous heart failure in 145 (73.6%), atrial fibrillation in 132 (66.7%). 10 (5%) lived in a nursing home. The in-hospital all-cause mortality rate was 7 (3.5%).

Clinical domain: 125 (65.1%) had high comorbidity (CCI). 60 (43.1%) were malnourished (MNA) and 129 (70.9 %) considered as frail (CFS). 151 (77%) were in NYHA Functional Class III-IV.

Functional domain: 165 (99.4 %) (Up&Go) and 170 (97.1 %) (SPPB) were considered at fall risk. 147 (83.5%), frail by the Fried Phenotype. 188 (97.4 %) (ADL) and 173 (89.6 %) (IADL) had some degree of dependence.

Psyco-cognitive: 82 (44.8%) had cognitive impairment (MMSE) and 70 (38%) some depression degree (YGDS).

Social: 28 (15.4%) considered not to have a good social support (OARS).

(See Table for details)

Conclusions

Patients with DHF are a complex and frail population that needs a holistic approach. The prevalence of frailty is high. In order to know how reversible frailty could be in older patients suffering DHF, clinical, functional, psyco-cognitive and social interventional trials are needed.
Outcomes of catheter ablation for ventricular tachycardia in the geriatric population
Authors: Dhawan R , Woelber T , Wight J , Desimone C V , Killu A M , Deshmukh A J , Kowlgi G N
Published: November 2023

Background

Catheter ablation has emerged as the first-line therapy for management of ventricular tachycardia (VT) over the last decade. There is a reluctance for older patients to be referred for catheter ablation with concerns for complications and poor outcomes.

Purpose

The purpose of the study was to assess the safety and outcomes of catheter ablation for VT in patients more than 74 years of age in comparison to younger patients.

Methods

A single-center retrospective study of 200 procedures in 168 patients undergoing catheter ablation for scar-related VT was conducted. Data collected included demographics, comorbidities, medications, relevant laboratory abnormalities, electrocardiograms, Holter, device electrograms, structural data including echocardiograms and cardiac magnetic resonance imaging, detailed procedural characteristics, and outcomes.

Results

The mean age in the older cohort was 77.7 ± 3.7 years compared to 57.6 ± 13.1 years in the younger group (p < 0.01) [Figure 1]. The geriatric patients had more males (93.6% vs. 75.8%) and had greater proportion of comorbidities including congestive heart failure (89.4% vs. 66.7%), hypertension (91.5% & 56.9%), atrial arrhythmias (66.0% vs. 43.1%), chronic kidney disease (68.1% vs. 31.4%), prior myocardial infarction (53.2% vs. 24.2%), and stroke (21.3% vs. 8.5%). The older patients were on more antiarrhythmic drugs at baseline. During the procedure, the number of cases with VT induction and hemodynamic stability was similar in older and younger groups. In cases where VT was induced, the older patients had a greater number of VTs induced (2.7 ± 3.0 vs. 1.9 ± 1.8), with slower cycle lengths (454.9 ± 122.6 vs. 379.3 ± 108.1 milliseconds). There was no difference noted in the procedural complications between the two groups. Older patients were more likely to be discharged on antiarrhythmic medications (87.2% vs. 71.2%) and had higher long-term mortality (29.8% vs. 7.8%). The older group was less likely to have a repeat ablation procedure (8.5% vs 24.2%). There was no difference in long-term VT-free survival rates among the two groups [Figure 2].

Conclusion

Patients more than 74 years of age undergoing catheter ablation for structural VT have a greater comorbidity burden but demonstrate similar procedural complications and VT-free survival rates, when compared to the younger cohort.Figure 1Figure 2
Cardiovascular risk in elderly persons without established atherosclerotic cardiovascular disease
Authors: Hudzik B , Zuranski W , Nowak J , Danikiewicz A , Zubelewicz-Szkodzinska B
Published: November 2023

Introduction

Age is the dominant driver of atherosclerotic cardiovascular disease (ASCVD) risk, and the estimated 10-year ASCVD risk of almost all individuals ≥70 years exceeds conventional risk thresholds. Treatment of risk factors should be considered taking ASCVD risk modifiers, including frailty, lifetime treatment benefit, comorbidities, polypharmacy, socio-economic status, and patient preferences into account.

Aim

Because of problems with risk prediction in the elderly most ASCVD risk scores do not function well, so there is limited ability to quantify ASCVD risk in persons 70 years of age or older. Therefore, we sought out to estimate ASCVD risk in apparently healthy elderly persons.

Methods

We enrolled 253 apparently healthy elderly persons ≥70 years without established ASCVD. The Systemic Coronary Risk Estimation 2 - Older Persons (SCORE2-OP) score was used to estimate the 10-year risk of ASCVD. A 10-year risk ≥15% was generally considered ‘very high risk’, and 7.5% to <15% was considered ‘high risk’. Based on age study population was divided into four groups: (1) 70–74 years (N=61), (2) 75–79 years (N=73), 80–84 (N=76), and (4) 85-89 years (N=43).

Results

The median 10-year ASCVD risk in the entire cohort was 23% (17%–32%). There was no person with low ASCVD risk (<7.5%). 41 out of 253 persons (16.2%) were high-risk and 212 (83.8%) were very high-risk. The number of persons at very high risk of ASCVD increased dramatically with age. Roughly, almost all persons aged ≥75 years were deemed very high risk (Table 1). Multimorbidity defined as the presence of two or more chronic conditions and polypharmacy defined as the use of at least 5 medications were highly prevalent in all four study groups. Hypertension was the most prevalent condition – roughly eight in 10 persons had hypertension. The rate of overweight/obese patients was higher in younger persons. This fact was further reflected by the body composition of study participants and the rate of malnutrition (Table 1). Age ≥75 years was highly predictive for identifying persons at very high risk for ASCVD with a C-statistics of 0.92 (positive predictive value 99%, negative predictive value 53%; P<0.001) (Figure 1).

Conclusions

Older people without established ASCVD are a heterogeneous group. Most of them were found to be at very high risk of ASCVD. Age and high blood pressure were the dominant drivers of that risk. In addition, ASCVD risk modifiers such as multimorbidity, polypharmacy, and malnutrition were highly prevalent. These findings have important clinical and public health and individualized decisions regarding preventative and therapeutic strategies for elderly persons are needed.Table 1Baseline characteristicsFigure 1.ROC analysis
Age disparity among severe aortic stenosis patients: AVR treatment rates and clinical outcomes among octogenarians
Authors: Shimoni O , Rapp O , Klempner R , Segev A , Pounds C , Massalha E
Published: November 2023

Introduction

Aortic valve replacement (AVR) is considered one of the most effective disease-modifying procedures among patients with severe Aortic Stenosis (sAS). Accordingly, we can witness a consistent increase in procedure rates in recent years. Nevertheless, the elderly population, particularly octogenarians, remains relatively undertreated.

Purpose

The current study aims to document the baseline characteristics, disparities in AVR rates, and prognostic significance of AVR among octogenarian vs. non-octogenarian patients with sAS.

Methods

A vast database of Maccabi health services, the second largest health maintenance organization (HMO) in Israel, counting nearly 2.8 million members, was retrospectively analyzed from 2005 to 2021 for all patients over 60 years, with a detailed echocardiography report compatible with a diagnosis of sAS. Patients who underwent AVR previously or on the same day of their diagnostic echocardiography were excluded. The database was extracted using the MDClone ADAMS healthcare data platform, generating synthetic data reliably representing the original population. All-cause mortality was set to be the primary outcome, and survival models utilizing adjusted multivariable analyses for several clinical and echocardiographic parameters were applied.

Results

A total of 1359 patients with high-gradient sAS were included in the final analysis, of which 574 (42%) are octogenarians. The octogenarian group included more females (56% vs. 48%), and they had a significantly higher prevalence of hypertension (83% vs. 78%), atrial fibrillation (22% vs. 14%), previous myocardial infarction (12% vs. 8%) and heart failure (20% vs. 10%).

Substantial differences were documented regarding AVR-treatment rates between the two groups, with the undertreatment of the octogenarian group (39% vs. 60% of AVR within 18 months from diagnosis of sAS, p<0.001). Differences remained significant in a fully adjusted time-to-event model (HR 0.54, 95% CI 0.46-0.64, p<0.001 for octogenarians)

A time-dependent analysis showed that AVR was associated with reduced all-cause mortality (HR 0.30, 95% CI 0.23-0.41, p<0.001) within the octogenarian group in 5 years. A similar protective effect was shown in the non-octogenarian group (HR 0.32, 95% CI 0.22-0.46, p<0.001).

Conclusions

Despite having comparable survival benefits, octogenarian patients with sAS still receive lower AVR treatment rates than non-octogenarians
Gene expression underscores the impact of impaired mobility on peri-operative/interventional complications in older cardiac patients
Authors: Baritello O , Vogel H , Suendermann S , Voeller H , Espinosa-Garnica K , Salzwedel A
Published: November 2023

Background/Introduction

The frailty syndrome is highly prevalent in elderly patients with heart disease. Phenotypes of physical frailty such as deterioration of mobility, strength or gait speed are relevant in clinical practice. These phenotypes are associated with a worse prognosis. The specific physiological pathways are not yet clearly understood. Transcriptomic analysis in skeletal muscle can provide information about these processes, and finally can be used to develop novel treatment options.

Purpose

Determination of gene expression levels in physical frailty phenotypes predictive for perioperative/interventional complications in older patients undergoing cardiac surgery (e.g. coronary artery bypass graft) or transcatheter aortic valve implantation (TAVI).

Methods

From 06/2021 to 07/2022, patients ≥ 70 year of age referred for elective cardiac surgery or TAVI were included in the study. At hospital admission, physical frailty was assessed in terms of low gait speed (5-meter Walk Test; ≥ 6 sec), moderately/severe impaired mobility (Timed Up-and-Go (TUG); ≥ 10 sec), and reduced handgrip strength (dynamometer; ≤ 27 kg ♂; ≤ 16 kg ♀). Total RNA was isolated and sequenced from muscle specimens (M. quadriceps femoris) collected during surgery/intervention. Perioperative complications (mortality and major morbidity) were primary endpoints. Differential gene expression analysis was performed using DESeq2, adjusted for age, sex, estimated glomerular filtration rate (eGFR) and number of comorbidities.

Results

63 patients (77.6 ± 4.3 years) referred to cardiac surgery (n= 34, 54%) or TAVI (n= 29, 46%) were enrolled (Table 1). Overall, 19 patients (30.6%) were characterized as frail by low gait speed, 43 (68.3%) by moderately/severe impaired mobility, and 19 (30.2%) by low handgrip strength. In total, 37 patients (59%) experienced ≥ 1 complication (e.g. need of transfusion, atrial fibrillation, delirium); one patient died. Frail patients showed altered gene expression levels (e.g. TAVI: 89 down- and 78 up-regulated genes). Interestingly, the expression of the genes MYLK4 (Fold Change - 1.8), KANSL1-AS1 (FC 2.0) and JMJD4 (FC 1.4) were significantly altered (Figure 1) in all three phenotypes of physical frailty, but only in TAVI patients.

Conclusion

Dysregulation of genetic determinants in the muscle was associated with reduced mobility. The detection of corresponding biomarkers (e.g. in plasma) could improve the accuracy of detection of physical frailty phenotypes predictive for post-intervention complications in elderly patients in clinical practice.Table 1.Patient characteristicsFigure 1.Gene expression levels
A systematic review and meta-analysis reveals a consensus transcriptional signature highlighting neutrophil degranulation as a preserved and critical biological process in atrial fibrillation
Authors: Gomez Ochoa S , Mohn M M , Lanzer J D L , Levinson R T L
Published: November 2023

Background

Atrial fibrillation (AF) is the most frequent persistent arrhythmia, and is associated with a high burden of disease, especially when co-occurring with other cardiovascular pathologies. Despite significant advances in the understanding of its pathophysiology through transcriptomic studies, there are marked differences in the identified key AF genes between studies, potentially due to specific sociodemographic and clinical characteristics of the populations evaluated. Therefore, the transcriptional signature that is common to AF, regardless of the specific context, is currently unclear.

Purpose

To provide a consensus transcriptional signature of AF by comprehensively analyzing the studies comparing the gene expression patterns in patients with AF and controls in Sinus Rhythm (SR).

Methods

Four literature databases were searched to identify studies reporting gene expression patterns in atrial myocardial tissue from patients diagnosed with AF and comparing them with those of controls reportedly in SR. We excluded studies reporting results from in vitro experiments or those that provided incomplete information regarding the methodology for sample collection of bioinformatic analysis. After an initial descriptive analysis of the included studies, we manually curated and processed all the available datasets. At first, gene coverage was evaluated to assess the comparability of the included data, followed by meta-analysing the suitable datasets to obtain the consensus gene signature. Finally, we estimated the activities of relevant transcription factors and pathways by using biological prior knowledge bioinformatic tools (DoRothEA, and PROGENy, respectively).

Results

38 studies were included, from which seven related datasets consisting of 262 AF and 86 SR control samples fulfilled the selection criteria for meta-analysis (Figure). We observed a high heterogeneity in the marker genes reported across the studies, however, disease signatures were conserved across the included studies. Gene ranking revealed a significant enrichment of fibrosis and myocyte degeneration-related gene sets; however, enriched pathways, transcription factors, and microRNAs related to neutrophil activity gene signatures, specifically those related to the degranulation process, occupied an outstanding position in the top positions of the ranking (Table).

Conclusion

Despite high heterogeneity amongst studies, a conserved and identifiable molecular signature in AF is present. The high relevance of neutrophil activity in this signature is consistent with previous studies performed in AF and other cardiovascular diseases, such as ischemic heart failure. The identification of a consensus transcriptional footprint is a feasible approach that provides valuable information to better understand the common molecular mechanisms underlying the different disease patterns in AF.Figure.Table.
Androgen deprivation therapy for prostate cancer, measures of adiposity and strength, and adverse cardiovascular outcomes: observations from 3000 men in 5 countries in the RADICAL PC study
Authors: Leong D , Valle F , Delouya G , Fradet V , Violette P , Niazi T , Higano C , Shayegan B , Nain P , Hajjar L , Iakobishvili Z , Oliveira G , Avezum A , Selvanayagam J , Pinthus J
Published: November 2023

Background

Androgen deprivation therapy (ADT) is prescribed to nearly half of patients with prostate cancer (PC). ADT is associated with weight gain, reduced muscle strength and increased cardiovascular (CV) risk. However, no PC study has examined the relationship between these physical characteristics, their change with ADT and cardiovascular outcomes.

Purpose

In men with PC:

To compare 1-year changes in physical measures in those receiving versus not receiving ADT

To evaluate the relationship between physical measures and adverse CV outcomes

Methods

We prospectively studied 3080 men with PC from 37 sites in 5 countries (mean age 68 years), 41% on ADT. Inclusion criteria were one of: PC diagnosed in the past 12 months; started ADT within the past 6 months; or plan to start ADT in the next month. Weight, waist and hip circumference, handgrip strength and get-up-and-go time were recorded at baseline and 1 year. Change in measurements were adjusted for age, education, race, tobacco and alcohol use, baseline cardiovascular disease and renal function. Participants were followed for a median 3 years from enrolment to document adverse CV outcomes associated with adiposity: myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism and atrial fibrillation. The relationship between baseline physical measures and outcomes was evaluated by Cox proportional hazards models adjusted for age, diabetes, hypertension, total cholesterol, tobacco use and physical activity levels.

Results

Changes in physical measures are displayed in Table. ADT recipients gained 5x more weight than non-recipients. Weight gain was distributed evenly between waist and hips, resulting in no difference in waist:hip ratio. Muscle strength decreased in both groups but with 43% larger decrease among ADT recipients. The ratio of strength to body weight fell twice as much in ADT recipients as non-recipients. Gait speed slowed by 13% after 12 months’ ADT.

We observed 144 adverse CV events. There was a continuous relationship between handgrip strength and CV events. Each quartile reduction in strength was associated with adjusted hazard ratio (95% CI) 1.24 (1.01-1.52). There was no detectable association between other physical measures and CV events.

Conclusion

ADT use is associated with increased adiposity and reduced muscle strength. Low muscle strength, reflected by low handgrip strength is a better predictor of adverse CV outcomes than increased adiposity. These findings may explain help the association between ADT use and adverse CV outcomes.Table
SGLT2 i Dapagliflozin reduces NF-kB expression in heart and kydneys of preclinical models exposed to doxorubicin through MYd-88 and NLRP3 pathways: an hystological study
Authors: Maurea N , Bisceglia I , Iovine M , Paccone A , Florio F , Grimaldi S , Giordano V , Palma G , Luciano A , Bruzzese F , Zito F M , Montella M , Franco R , Scherillo M , Quagliariello V
Published: November 2023

Background

Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to be of therapeutic value in patients with type 2 diabetes, chronic kidney disease, and heart failure with reduced ejection fraction (HFrEF), conditions that commonly coexist and are interrelated pathophysiologically.

Purpose

We hypothesized that Dapagliflozin (an SGLT2i), administered during doxorubicin, could improve cardiac function in preclinical models

Methods

Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), DAPA at 12 mg/kg (DAPA, n=6) or doxorubicin combined to DAPA (DOXO-DAPA, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100) , pAMPK, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified through ELISA and western blot methods.

Results

DAPA improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88, DAMPs and NF-kB in cardiac tissues was seen in DOXO-DAPA group compared to DOXO mice (p<0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with DAPA indicating anti-inflammatory properties. Expression of pAMPK was strongly enhanced in DAPA-DOXO compared to DOXO group. Levels of Calgranulin S100 and galectine-3 were strongly enhanced in DOXO group; on the other hand their expression were reduced by 47.7 and 52.3% in DAPA-DOXO group vs DOXO (p<0.005). Hystology evaluation indicate reduction NF-kB expression in myocardial and renal tissue in DOXO-DAPA vs DOXO. Radial strain (RS) is 38.8% in DAPA-DOXO vs 14.1% in DOXO groups (P < 0.05); longitudinal strain (LS) is – 23.4 % in DAPA-DOXO vs – 10.5% in DOXO groups (P < 0.001)

Conclusion

In this preclinical study, DAPA is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. The overall picture of the study pushes the use of DAPA in prevention of cardiomyopathies induced by anthracyclines in cancer patients.
Risk of bleeding in patients with and without cancer on antiplatelet therapy following myocardial infarction: a study in primary care
Authors: Van Den Berg P F , Ow K W , Tyrer F , Rutherford M J , Lambert P C , Peake M D , Kadam U T , Adlam D A
Published: November 2023

Background

Antithrombotic medication and antiplatelet therapy (ATPL) are used in the treatment and prevention of thrombotic disorders, especially in patients following a myocardial infarction (MI). However, the risk reduction of future ischaemic events must be balanced against the potential bleeding risk. Co-morbidities may predispose individuals to bleeding events. Cancer influences risk of bleeding either directly through bleeding of fragile cancer-associated blood vessels or by indirectly increasing the risk of bleeding remote from the cancer site. In patients with cancer, bleeding risk may be increased due to ATPL given for concomitant cardiovascular disease.

Purpose

To investigate the association between pre-existing cancer and risk of bleeding in patients on ATPL after myocardial infarction in a primary care population.

Methods

We performed a matched cohort analysis using data from the Clinical Practice Research Datalink (CPRD) and linked Hospital Episodes Statistics (HES) in England. People with an MI between 2006–2017 were matched to patients without an MI at a 1:5 ratio. Four groups: patients with both MI and cancer (breast, digestive tract, lung, prostate at baseline [within 1-year prior to MI]), patients with only cancer or MI; and patients without either condition. Using flexible parametric methods, hazard ratios were calculated to determine the association between patient group and risk of bleeding, as well as between APTL-regimen after MI and bleeding risk during 1-year of follow-up after MI. All data were processed using STATA/SE16, using a significance level of ≤0.05.

Results

We included 58,951 patients with an average (mean) age of 74±10 years (66% male). Of all patients, 12,526 (21%) patients had cancer, and 9,942 (17%) had an MI; numbers per subgroup are presented in Figure 1. A bleeding event was observed in 1,193 (2%) patients. The vast majority (N=56,148 [95%]) of patients did not take ATPL. Of those who did receive ATPL, aspirin was the most common (N=2,359 [4%]). In a multivariable model (adjusted for age, gender, ethnicity, prior bleeding, diabetes, renal disease, smoking status, drug, hypertension, hypercholesteraemia and cancer), people with MI had a risk (hazard) of bleeding of 2.52 (95% CI 2.23-2.86), p<0.001. For people with cancer only, the risk of bleeding was 1.26 (95% CI 1.10-1.44), p<0.001.

Conclusion(s)

Bleeding risks are higher in people with cancer after an MI than those with MI or cancer alone. More research is needed on individual anti-platelet therapies for people with cancer who have a MI to minimize the risk of bleeding and future cardiovascular events.Figure 1
The prognostic power of two-dimensional strain-derived left ventricular myocardial work for all-cause mortality in pancreatic ductal adenocarcinoma patients receiving cancer therapy
Authors: Liu Y , Liu P Y , Yen C J , Shan Y S
Published: November 2023

Background

Left ventricular (LV) myocardial work (MW) is a relatively novel parameter derived from the integration of LV global longitudinal strain (GLS) and LV pressure. MW may provide additive information beyond LV ejection fraction (EF) and GLS. However, the clinical implication of MW in pancreatic ductal adenocarcinoma (PDAC) patients receiving cancer therapy is still unclear.

Purpose

We conducted this prospective cohort study to investigate the clinical implication and the prognostic valve of LV MW in PDAC patients receiving cancer therapy.

Methods

We prospectively enrolled a total of 234 newly diagnosed PDAC patients (65.1±11.1 years old, 51% male). We did echocardiographic study at the following timepoints: before chemotherapy and 3 months after cancer therapy. MW parameters, including global work index (GWI), global constructive work (GCW), global waste work (GWW) and global work efficiency (GWE), would be determined from the pressure-strain loop. A ≥15% reduction in absolute GLS value from baseline was defined as signifying cancer therapy–related cardiac dysfunction (CTRCD). The primary outcome was defined as all-cause mortality.

Results

A total of 185 patients (64.7±11.3 years old, 49% male) were included for analysis. We excluded 49 cancer patients who did not have echocardiographic studies at 3 months after cancer therapy. Over a median follow-up of 8 months, twenty-six (14.1%) patients had CTRCD and sixty (32.4%) patients were dead. There was no significant difference of baseline demographic and echocardiographic parameters between the survivors and the mortality patients. At 3 months after cancer therapy, compared to the survivors, the mortality patients had lower LV EF (survivor vs. death: 68.6±6.5% vs. 63.5±11.3%, p=0.002) and lower GLS (survivor vs. death: -18.8±2.2% vs. -17.3±3.4%, p=0.003). Moreover, the mortality group had lower GWI (survivor vs. death: 1984.2±376.0 mmHg% vs. 1746.8±495.1 mmHg%, p=0.002) and GCW (survivor vs. death: 2307.0±405.6 mmHg% vs. 2125.1±493.9 mmHg%, p=0.02). After adjusting for age, gender, LVEF (at 3-month), GLS and CTRCD, GWI <1700 mmHg% was independently associated with all-cause mortality (hazard ratio 2.35, 95% confidence interval 1.37–4.03, p<0.001; Figure).

Conclusion

Approximate 14% of PDCA patients receiving cancer therapy had CTRCD. Lower values of LV GWI (<1700 mmHg%) was independently associated with increased all-cause mortality at a median follow-up of 8 months. LV GWI showed the better performance for mortality prognostic power compared to LVEF and LV GLS in PDCA patients receiving cancer therapy.
Acute and long-term outcomes of acute coronary syndrome in patients with hematological malignancies
Authors: Lange S A , Schliemann C , Makowski L , Engelbertz C , Feld J , Gerss J , Droege P , Ruhnke J , Guenster T , Reinecke H , Koeppe J
Published: November 2023

Background

Coronary heart disease (CHD) and cancer are the leading causes of death. Treatment outcomes have improved significantly for both disease groups. In particular, patients with hematologic malignancies (HM) have an improved prognosis. However, knowledge of the interaction between acute coronary syndrome (ACS) and HM remains poor.

Objective

This analysis aimed to clarify how acute coronary syndrome affects the prognosis of HM patients.

Results

Between January 1, 2010, and December 31, 2018, 439,716 patients with ACS insured by AOK Germany were identified, of whom 2,104 (0.5%) also had HM. Myelodysplastic/myeloproliferative disorders, lymphocytic leukemias, and plasmacytomas predominated. These patients were approximately 6 years older and more likely to have had a myocardial infarction without ST-segment elevation. These patients had more concomitant cardiovascular disease and worse NYHA stage. They were less likely to receive coronary angiography and percutaneous coronary intervention (PCI), although the number of bleeding events was not significantly increased. Hospital stay was longer. All-cause mortality was increased regardless of age. After adjustment for patient risk profile, HM was associated with worse outcomes for all endpoints studied.

Conclusion

Survival is lower in ACS with HM, possibly due to the fact that these patients are less likely to undergo invasive diagnostics.Mortality, MACE and re-infarctionSurvival after STEMI and NSTEMI
Metabolomics to characterise adaptations in cellular metabolism for the stages of atrial fibrillation
Authors: Wijdeveld L F J M , Pool L , Van Weeghel M , Schomakers B V , De Groot N M S , Houtkooper R H , Brundel B J J M
Published: November 2023

Background

Atrial fibrillation (AF) is a highly prevalent, progressive cardiac arrhythmia associated with high cardiovascular comorbidity. Current treatments targeting electropathophysiology have high recurrence rates, prompting researchers to uncover alternative molecular mechanisms underlying AF, aiming to find novel targets for diagnostics and treatment. Highly relevant to several cardiovascular diseases, adaptations in cellular metabolism have gained interest in AF. However, changes in the metabolome across various AF stages have not yet been studied.

Aim

The study aims to identify leads for potential biomarkers and treatment targets by gaining more insight in metabolic adaptation and mechanisms in atrial fibrillation.

Methods

From the HALT&REVERSE biobank, 60 atrial appendage samples were selected [controls (SR=21), paroxysmal (ParAF=16), persistent (PerAF=11) and longstanding-persistent AF (Ls-PerAF=12)]. Metabolomics, a large-scale semi-quantitative method based on mass-spectrometry, was performed. Comparisons were made SR vs. AF, and SR vs. AF stages by Mann-Whitney U and Kruskal Wallis statistical tests with a Benjamini-Hochberg correction (FDR=0,10) for multiple testing.

Results

Comparing SR and AF, fructose-1,6-diphosphate (F1,6DP) was decreased (p<0.001), whilst CDP (p<0.001) and UMP were increased (p<0.01). Comparing the AF stages, in SR vs. ParAF CDP was significantly increased. Regarding the AF stages, SR and LsperAF show the biggest differences in metabolites, presenting as decreases glycolysis and nicotinamide metabolites. Overall, metabolites associated with the glycolysis, nicotinamide, and carnitine metabolism show decreases in AF patients, whilst metabolites involved with pyrimidine metabolism are increased AF patients.

Conclusion

CDP, F1,6DP and UMP were strongly correlated with AF samples in univariate analyses and therefore should be further investigated in serum for their biomarker potential, specifically CDP which was already strongly increased in ParAF. F1,6DP and similar energy metabolites in the glycolysis and nicotinamide pathways are decreased in AF and therefore could be as a therapeutic target through supplementation. Leads from this analysis should be validated and further investigated in mechanistic studies of these metabolic pathways.