bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex disparities in bystander defibrillation for out-of-hospital cardiac arrest
Authors: Paratz E , Nehme E , Heriot N , Sundararajan V , Page G , Fahy L , Rowe S , Anderson D , Stub D , La Gerche A , Nehme Z 
Published: October 2024

Abstract

Background
Previous studies have suggested that females experiencing out-of-hospital cardiac arrest (OHCA) receive lower rates of both bystander cardiopulmonary resuscitation (CPR) and defibrillation compared to males. Whether this disparity has improved over time is unknown.

Purpose
To investigate rates of bystander CPR and defibrillation in a sex-disaggregated manner over the last two decades.

Methods
A state-wide OHCA registry in Victoria, Australia collected data over twenty years (2002-2021) regarding rates of bystander interventions in OHCA. Characteristics and outcomes of each OHCA were compared with logistic regression according to sex and time (defined in two-year periods).

Results
32,502 OHCAs were included (69.7% male). Both bystander CPR and defibrillation rates increased for females over time (p&lt;0.0001). There was no sex disparity in receipt of bystander CPR after adjustment for baseline differences. Females were less likely than males to receive bystander defibrillation, with sex disparity increasing from 2010 onwards (adjOR 0.26 (95%CI 0.09-0.80) in 2020-21 for females compared to males).

Conclusion
Initiatives to increase bystander CPR and defibrillation have resulted in higher overall rates of bystander interventions in the last two decades and no significant sex differences in provision of bystander CPR. However, females receive less bystander defibrillation than males, and sex disparity is increasing. Strategies to promote bystander defibrillation in females experiencing OHCA with a shockable rhythm should be a priority.
Sex differences in cancer incidence amongst people with cardiovascular disease: a large British population study
Authors: Thuemmler R , Pana T A , Mamas M A , Myint P K 
Published: October 2024

Abstract

Background
Studies have shown that patients with cardiovascular disease (CVD) have an incremental risk of death due to noncardiac causes. This is especially attributable to cancer developments during long term follow up. The two diseases share pathophysiological mechanisms that extend beyond traditional risk factors. With well-established sex disparities in CVD, it becomes imperative to investigate whether similar sex-based differences exist in both the incidence of cancer and cancer-related mortality, in participants with CVD vs those without CVD.

Purpose
We aim to analyse the sex differences in incident cancer and cancer-related mortality between people with and without CVD.

Methods
Participants were drawn from a large British population based prospective cohort study and followed up for a median of 26.2 years. Participants were stratified by sex and whether they developed CVD over the study follow-up. The cumulative incidence of cancer, excluding non-melanoma skin cancers were calculated. Sex-specific lifetime risks were determined accounting for competing risks of death. Cause-specific hazard ratios were determined using Royston-Parmar models. Models were adjusted for ethnicity and time-updated covaries, including material deprivation, CV risk factors, lifestyle factors, comorbidities, and medication. Participants’ CVD status was time-updated over the study follow-up as this was diagnosed.

Results
Out of a total of 22, 534 participants, free of cancer at baseline, 53.7% were women. Mean (standard deviation) age was 58.6 (9.3) for women and 59.5 (9.3) for men, at baseline. Men were older and had more comorbidities. Hypertension and obesity were risk factors more prevalent amongst men, while women were more likely to be smokers at baseline. Participants with CVD had more comorbidities, were more likely to smoke, have higher HbA1cs and be obese than those without CVD. The adjusted lifetime risks of incident cancer in participants with CVD at age 75 were higher in men (13.9%) compared to women (10.1%). This translates into a cause-specific hazard ratio (cHR) (99% confidence interval) for incident cancer (men vs. women) of 1.41 (1.27 - 1.55). Similar findings were demonstrated in participants with no CVD (10.2% for men and 8.2% for women), corresponding to a cHR of 1.27 (1.15 - 1.40). Furthermore, men had a higher risk of cancer-related mortality compared to women in participants with CVD 1.54 (1.33 - 1.78), as well as among participants without CVD 1.34 (1.17 - 1.53).

Conclusion
Our study showed an association between CVD and the lifetime cancer risk in both sexes after extensive adjustment. Furthermore, we show that men have a higher risk of cancer incidence and cancer-related mortality than women, regardless of comorbid CVD. However, these associations, were stronger in participants with CVD. It is vital to identify driving forces of such disparities to achieve health equity.
Mitochondrial Oxidative Stress and Cardiac Dysfunction in TERT Knockout Mice
Authors: Zhou Z , Zhang Y , Zhao R , Liu D , Xie B , Zhang Q , Tse G , Wang F , Liu T 
Published: October 2024

Abstract

Background
Heart failure (HF) is a major cause of hospitalization in the elderly, with its incidence increasing due to aging and associated risk factors like hypertension, diabetes, and myocardial fibrosis. Aging-related myocardial fibrosis, characterized by alterations in the extracellular matrix and myocardial structure, impairs cardiac function. Mitochondrial oxidative stress plays a pivotal role in cardiac electrical and structural remodeling, necessitating a deeper understanding of its involvement in aging-related heart failure.

Purpose
The purpose of this study is to investigate the mechanisms of aging-related ventricular electrical and structural remodeling by constructing an aging mouse model. This research aims to provide potential therapeutic targets for heart failure associated with aging.

Methods
We developed a third-generation homozygous telomerase reverse transcriptase (TERT) knockout mouse model. Comparing third-generation homozygous TERT knockout mice (F3 group) with age-matched wild-type males (WT group). The study encompassed blood pressure measurement, electrocardiographic analysis, echocardiography, ELISA for cardiac biomarkers, ventricular tissue electrophysiology, fibrosis assessment through staining, transcriptomic profiling via RNA-seq, and electron microscopy of ventricular mitochondria.

Results
Compared to the WT group, the F3 group demonstrated increased P53 and P16 protein expression. Decreased LVEF and FS, along with increased interventricular septum thickness, left ventricular diameter, and left ventricular volume. Elevated serum NT-pro-BNP and troponin I (cTnI) levels, with prolonged QRS duration. Decreased left and right ventricular conduction velocity, accompanied by increased conduction dispersion. Notable elevation in COLI, TGFβ, and α-SMA gene transcription and protein expression in ventricular tissue. Significant differences in mitochondrial oxidative stress signal pathways via RNA-seq analysis. Elevated serum MDA levels and decreased SOD levels, with up-regulated Mn-SOD gene transcription and protein expression, and down-regulated MFN2 and Drp1 gene transcription and protein expression in ventricular tissue. Electron microscopy revealed mitochondrial abnormalities such as loose arrangement, decreased number, swelling, vacuolation, and myofilament disintegration or breakage in the F3 group.

Conclusion
Third-generation TERT-/- senescent mice exhibit notable cardiac impairments, including electrical remodeling, structural changes, and mitochondrial dysfunction. These findings suggest a potential link between mitochondrial oxidative stress and aging-related heart failure, indicating novel therapeutic opportunities targeting mitochondrial dysfunction for managing such conditions.
The Mutscore metapredictor: a new application of artificial intelligence in cardiogenetics
Authors: Porretta A , Fressart V , Denjoy I , Morgat C , Surget E , Messali A , Algalarrondo V , Vedrenne G , Pruvot E , Quinodoz M , Rivolta C , Leenhardt A , Extramiana F 
Published: October 2024

Abstract

Introduction
The rapid development of high-throughput next generation sequencing has shifted the limits of genetic knowledge from variant sequencing to variant interpretation. The current standards recommend that sequence variants are interpreted according to a comprehensive analysis including, among others, computational data. The two major types of in-silico predictive tools encompass those predicting the theoretical variant effect on splicing and algorithms predicting the potential damage of missense variants. However, overall for missense variants, prediction accuracy is often limited and results are sometimes inconsistent between software programs.

Purpose
We aimed at testing the predictive performance of a new predictive algorithm (Mutscore) for missense variants based on a machine learning approach, in our cohort of families referred for hereditary cardiac diseases.

Methods
We retrospectively reviewed DNA sequencing results from 230 families (from 01.07.2014 till 01.07.2023) addressed to our center for channelopathy or hereditary cardiomyopathy. Missense variants were identified and evaluated according to the current standards of the American College of Medical Genetics and Genomics. Variants were analysed with the commonly used in-silico tools CADD, Polyphen, Alpha-missense and Revel. We further applied the Mutscore, a new metapredictor integrating 16 existing predictive tools to data on variant topographical location.

Results
Among our 230 families, we detected 252 missense variants (class I-II 2.4%, class III 62.3%, class IV and V 15.9% and 19.4% respectively). We observed a significant positive correlation (r = 0.59, p=0.000) between the Mutscore and the interpretation of variants according to standards. The Mutscore had a better predictive performance than Polyphen (AUC 0.83 vs 0.67, p=0.007), Alpha-missense (AUC 0.87 vs 0.79, p=0.047) and CADD (AUC 0.87 vs 0.70, p=0.0001). Compared to Revel, the Mutscore had a comparable predictive performance (0.89 vs 0.87, p=NS), but a better sensitivity (75% vs 66%) at the maximum tolerated false positive rate of 10%. Figure 1. Focusing on variants of uncertain significance (VUS), we applied Mutscore cut-off values which were identified to reclassify variants in our previous study (1). Importantly, the Mutscore reclassified 45% of VUS into likely benign/pathogenic variants. Figure 2.

Conclusions
The Mutscore, through its metaprediction approach integrating data on variant topographical location, improves the accuracy of pathogenicity prediction as compared to three out of four algorithms commonly used in clinical practice, and seems to represent a valuable tool contributing to VUS disambiguation.
Cardiovascular outcomes in pregnant women with congenital heart disease
Authors: Kanigalpula S P R , Ali Z , Mufarrih S A , Pothuru S 
Published: October 2024

Abstract

Background
Individuals with congenital heart disease (CHD) are at increased risk of cardiovascular complications. There is limited available data on burden of acute cardiovascular complications in pregnant women with CHD.

Purpose
To study the acute cardiovascular complications in pregnant women with CHD.

Methods
We conducted a retrospective observational analysis using the Nationwide Inpatient Sample (NIS) database. Using ICD-9 and ICD-10-CM codes, we identified pregnant women aged 18 years or older with and without CHD hospitalized between January 1st, 2010, and December 31st, 2019. The outcomes of the study were peripartum cardiomyopathy, hypertensive disorders of pregnancy (gestational hypertension, pre-eclampsia, and eclampsia), acute myocardial infarction, cardiac arrhythmias, cardiac arrest, stroke or transient ischemia, and in hospital mortality.

Results
During the study period, there were a total of 41,114,105 hospitalizations for pregnancy. Of these, 43,131 (0.1%) had CHD. The mean age of the population was 28 years in both CHD and non-CHD groups. The majority were white patients, followed by black patients and then Asians in both groups. There was a higher proportion of white patients in the CHD group compared to the non-CHD group. Comorbidities including diabetes mellitus, chronic pulmonary disease, chronic kidney disease, hyperlipidemia, smoking, depression, and drug abuse were higher in the CHD group compared to the non-CHD group (Table 1). Pregnant women with CHD had a significantly higher incidence of peripartum cardiomyopathy (1905 vs 89 per 100,000 pregnancy hospitalizations; p&lt;0.001), hypertensive disorders of pregnancy (9332 vs 7802 per 100,000 pregnancy hospitalizations ; p&lt;0.001), acute coronary syndrome (253 vs 12 per 100,000 pregnancy hospitalizations; p&lt;0.001), cardiac arrhythmias (3480 vs 176 per 100,000 pregnancy hospitalizations; p&lt;0.001), cardiac arrest (127 vs 6 per 100,000 pregnancy hospitalizations; p&lt;0.001), stroke or transient ischemic attack (1648 vs 32 per 100,000 pregnancy hospitalizations; p&lt;0.001), and venous thromboembolism (816 vs 124 per 100,000 pregnancy hospitalizations; p&lt;0.001) (Table 2). Similarly, pregnant women with CHD had significantly higher in hospital mortality compared to pregnant women with no CHD (116 vs 11 per 100,000 pregnancy hospitalizations; p&lt;0.001).

Conclusion
Pregnant women with CHD are at significantly increased risk of acute cardiovascular complications compared to those without CHD. Our study underscores the importance of close monitoring and specialized care for this high-risk population during pregnancy and delivery. Further research is warranted to better understand the risks associated with these complications and to optimize management strategies for pregnant women with CHD.Baseline CharacteristicsOutcomes
Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy and future perspectives
Authors: Pay L , Cetin T C , Dereli S D , Kadi H K , Yumurtas A C Y , Cinar T C , Hayiroglu M I H 
Published: October 2024

Abstract

Background/Introduction
The fact that hypertrophic cardiomyopathy (HCM) is associated with sudden cardiac death (SCD) due to malignant ventricular arrhythmias underlies its clinical importance (1). SCD in patients with HCM is often an unpredictable event, occurring without previous warning signs or symptoms, and is most common in the young middle-aged group (2). The greatest dilemma in the management of HCM patients is to identify the high-risk population for SCD. The HCM risk- SCD model provides a useful convenience in determining the risk of SCD in patients with HCM even though some patients with low-risk scores still remain at risk of SCD (3). These results have increased the interest in additional strategies to improve the existing risk model.

Purpose
Hence, the aim of our study was to assess the performance of HCM Risk-SCD in a large series of consecutive patients with HCM who had been followed up in a tertiary centre.

Methods
The study population consisted of 389 consecutive HCM patients who had been followed up between 2004 and 2021. Demographic and clinical characteristics estimated 5-year risk using the HCM Risk-SCD model were compiled and survival data were collected during follow-up. Patients were divided into 2 groups according to their long-term survival and HCM risk-SCD scores of these two groups were compared.

Results
The long-term mortality was observed in 47 patients out of 389 patients in the mean follow-up of 55.5 ± 12.7 months. The mean HCM Risk-SCD of surviving patients was significantly lower than that of non-survivors (1.8% vs. 3.0%, p&lt;0.001). The HCM Risk-SCD score was above 6% in 9 (2.6%) survivors and 9 (19.1%) non-survivors (p&lt;0.001). Considering the Kaplan-Meier curve based on the 6% HCM Risk-SCD score, patients at ≥6% risk also had a significantly higher long-term risk of death compared to those with &lt;6% (log-rank test value: 33.72, p&lt;0.001) (Figure 1). The ROC curve based on the HCM Risk-SCD score had 61% sensitivity and 61% specificity for risk for 2.0%, 38% sensitivity and 99% specificity for ≥4%, 17% sensitivity and 99% specificity for ≥6% (Figure 2).

Conclusion(s)
In conclusion, the current study demonstrates that the HCM risk-SCD model, while easily calculable and clinically useful, does not reliably identify a significant subset of patients with HCM who will potentially be at lifetime risk of SCD. Identifying patients with hypertrophic cardiomyopathy at high risk for SCD who deserve ICD therapy is a critical management priority. A new risk algorithm that can detect the SCD risk of HCM patients with higher sensitivity is needed.Figure 1Figure 2
Impact of chronic kidney disease on patients with Myocardial Infarction with Non Obstructive Coronary Arteries (MINOCA)
Authors: Gil Mancebo N , Mata Caballero R , Fraile Sanz A , Izquierdo Coronel B , Rodriguez Montes P , Martin Munoz M , Alvarez Bello M , Perela Alvarez C , Nieto Ibanez D , De La Serna Real De Asua M , Humanes Ybanez S , Olsen Rodriguez R , Espinosa Pascual M , Awamleh Garcia P , Alonso Martin J J 
Published: October 2024

Abstract

Background
Chronic kidney disease (CKD) in patients with myocardial infarction (MI) is associated with more advanced disease, a higher risk of complications and poorer prognosis, as well as increased mortality. The aim of this study is to assess the impact of CKD in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and its influence on the prognosis of these patients.

Methods
it was an observational, prospective and analytic study. We analyzed all consecutive patients with MI who underwent coronary angiography admitted to our Hospital between 2016 and 2023; MINOCA patients were classified following the 2023 ESC Guidelines definition. The patients were divided into two groups depending on whether they had CKD or not. Median follow-up was 43 months [20-71].

Results
we included 136 patients with MINOCA, of whom 11 (8.1%) had CKD. Patients with impaired kidney function were older and mostly male. They also exhibited a higher prevalence of classic cardiovascular risk factors such as hypertension, diabetes, or dyslipidemia. However, there were fewer smokers in this group. We did not find significant differences in coronary artery anatomy (smooth or small plaques) between both groups. Additionally, the majority of patients in both groups had preserved left ventricular function. Despite that, patients with CKD typically had ST segment elevation in the ECG and higher myocardial injury biomarkers’ levels as well as NT-proBNP.
During hospitalization, patients without renal dysfunction had more complications (11.2% vs 0%, p=0.062) such as inotropic requirements, stroke or cardiogenic shock, but overall there were very few. In terms of treatment, it was fairly similar in both groups, although patients with kidney disease received diuretics significantly more often.
Throughout the follow up, there were no significant differences in MACE (major adverse cardiovascular events) between death (27.3% vs 7.4%, p=0.06), readmission (10% vs 10.8%, p=1) or MI (0% vs 3.4%, p=1), but patients with CKD suffered more frequently from stroke (40% vs 4.2%, p&lt;0.01).

Conclusions
1) Patients with MINOCA and CKD are typically older and predominantly male with a high prevalence of cardiovascular comorbidities (hypertension, diabetes, dyslipidaemia).
2) The severity of MI appears to be slightly higher in this group, as evidenced by more ST-segment elevation upon admission and higher hs Troponine T levels. However, they experience fewer cardiovascular complications and maintain normal left ventricular function.
3) Although we found no significant differences in major adverse cardiovascular events (MACE), patients with CKD were more likely to suffer from stroke.Table 1Table 1
Developing p21-activated kinase 1 (PAK1) activators to treat hypertrophic cardiomyopathy (HCM)
Authors: He Y , Bae J , Wang Y J , Watkins H , Lei M 
Published: October 2024

Abstract
Despite significant progress in comprehending the genetic and metabolic underpinnings of cardiomyocyte dysfunction, there is still a pressing need for targeted treatments to address hypertrophy and progressive remodelling (e.g., fibrosis), seen in HCM1 . PAK1, a regulator of ion channels and myofilaments in cardiomyocytes, has shown promise in curbing pathological hypertrophy2 . Our hypothesis centres on the potential therapeutic benefits of pharmacologically activating PAK1 in managing hypertrophy and adverse remodelling in HCM. First, we conducted virtual screening and kinase assays to identify potent small molecule PAK1 activators, which significantly increased PAK1 activity by 3 to 5-fold, with an EC50 range between 0.5 and 2.5 μΜ. We then evaluated these compounds on cellular hypertrophy in an in vitro model using neonatal rat cardiomyocytes exposed to isoprenaline (ISO). Among those, JB2020A not only prevented ISO-induced hypertrophy, but also reversed pre-existing cellular hypertrophy induced by ISO 24 hours earlier. Subsequently, we assessed the therapeutic potential of JB2020A in a well-characterised HCM mouse model (i.e., Actc1E99K) 3 , known for its rapid disease progression. We initiated a six-week oral treatment regime at 4 weeks of age, dosing at 10 mg/kg per day. Echocardiography and fibrosis evaluation confirmed that JB2020A led to a significant reduction in cardiac hypertrophy and fibrosis with preserved contractile function. Western blotting analysis revealed increased PAK1 phosphorylation and activation in JB2020A-treated E99K hearts, along with a reduction in pro-apoptotic CHOP expression and an upregulation of protective endoplasmic reticulum (ER) response (e.g., ATF4 and Xbp1), indicating an amelioration of ER stress in HCM. These findings underscore the therapeutic potential of small molecule PAK1 activators as a novel approach for addressing hypertrophy and progressive remodelling in HCM.
Experimental evidence on colchicine's mode of action in human carotid artery plaques
Authors: Von Ehr A , Steenbuck I D , Haefele C , Vico T A , Wolf D , Tholen S , Schilling O , Czerny M , Westermann D , Hilgendorf I 
Published: October 2024

Abstract

Background and aims
Atherosclerosis driven by inflammation is a major cause of cardiovascular events. Recent clinical trials have demonstrated the therapeutic potential of anti-inflammatory treatments. Consequently, colchicine is recommended in current guidelines as a second-line therapy for secondary prevention, although the drug's mechanism of action is not fully understood.

Methods
To this end, we performed a multiomic study of the effect of colchicine on human carotid plaques. Sections from endarterectomy specimens were exposed ex vivo to colchicine at concentrations of 2 ng/ml and 10 ng/ml for 24 hours and compared with untreated segments of the same plaque. Changes in gene expression were analyzed by RNA sequencing, and plaque secretomes were subjected to proteomic analysis by mass spectrometry. In situ cell proliferation was examined histologically.

Results
Our data suggest that colchicine primarily suppresses neutrophil and platelet degranulation, collagen degradation, and macrophage proliferation in atheromatous plaques in a dose-dependent manner, while stimulating myofibroblast activation.

Conclusion
Our study demonstrates multifactorial pathways by which colchicine, the first anti-inflammatory drug recommended by cardiovascular guidelines, acts on human atherosclerotic lesions. Targeting neutrophil and platelet degranulation, collagen degradation and macrophage proliferation could provide significant therapeutic benefit in atherosclerotic cardiovascular disease without the adverse side effects of colchicine.