bluuebunny/crossref_metadata_2025_split huggingface dataset:
ECG as a screening tool for detection of significant functional mitral regurgitation in patients with left bundle branch block
Authors: Andrei D O , Calin A , Barbu F S , Oprean L V , Musat D L 
Published: October 2024

Abstract

Background
Functional mitral regurgitation (FMR) may occur in the left bundle branch block (LBBB) due to mechanical left ventricular (LV) dyssynchrony, by the imbalance between the tethering and the closing forces exerted on the mitral apparatus1-3. Progressive FMR and LV remodeling result in a reciprocal worsening downward spiral and worse clinical outcomes1-3. Therefore, timely screening and follow-up of these patients to prevent the irreversible progression of FMR is required. To date, only LBBB morphology and QRS duration have been proven predictors of FMR4.

Purpose
This study aimed to assess the relationship between ECG parameters of LV dyssynchrony and the severity of FMR in patients with LBBB.

Methods
We retrospectively included 154 consecutive patients with LBBB, in sinus rhythm, who had an echocardiogram, with no more than mild organic valvular heart disease. We measured the following intraventricular dyssynchrony markers: LV activation times (LVAT), intrinsicoid deflection (ID) in lateral and aVF leads and a newly defined marker – the difference (Diff) between aVL and aVF ID’s (Diff_IDaVL_aVF). These two leads record the electrical activation of the two opposing myocardial segments adjacent to the posteromedial and anterolateral papillary muscles, respectively5 (Figure 1). Based on the severity of FMR, the patients were divided into two groups: no/mild FMR (grade II or less) (61%), and significant FMR (grade III and IV) (39%).

Results
In patients with significant FMR, the LVAT measured in lateral leads, the IDaVL and Diff_IDaVL_aVF were significantly longer, but IDaVF was significantly shorter compared to patients with no/mild FMR (p&lt;0.001). Of all studied ECG parameters, the Diff_IDaVL_ aVF was the parameter that had the strongest correlation with significant FMR (r correlation coefficient 0.82, p &lt; 0.001). In multivariable analysis the Diff_IDaVL_aVF (p = 0.010) was the only parameter independently correlated with significant FMR. On ROC analysis the best cut-off for significant FMR prediction was 55 ms (AUC of 0.99, sensitivity 90% and specificity 97%) (Figure 2).

Conclusions
In LBBB, a simple intraventricular dyssynchrony ECG parameter can provide insights into FMR severity. A 55 msec Diff_IDaVL_aVF identifies significant FMR that may benefit from early medical or CRT treatment to avoid progression and worse prognosis.
Clopidogrel versus aspirin monotherapy for secondary prevention after percutaneous coronary intervention - a nationwide population-based study
Authors: Cho J H 
Published: October 2024

Abstract

Background
After percutaneous coronary intervention (PCI), patients are maintained on single antiplatelet therapy (SAPT) for secondary cardiovascular prevention after completing the guideline-recommended duration of DAPT for a period of time. We sought to compare the efficacy and safety of clopidogrel versus aspirin monotherapy for secondary prevention in patients who undergoing PCI in a population-based cohort study using the database from the National Health Insurance Service (NHIS) in Korea.

Methods
Of those who underwent PCI from 2009 to 2020, 133,343 patients were selected for analysis. (aspirin 65,802 patients, clopidogrel 67,653 patients). To balance between aspirin and clopidogrel users for the comparison of efficacy and safety, we applied the inverse probability of treatment weighting (IPTW) of propensity score method.
The primary effectiveness outcome was major cardiovascular events (MACEs) as the composite of cardiovascular death, myocardial infarction (MI) or stroke. The primary safety outcome was any bleeding.
We divided the short DAPT user (&lt; 6 months of DAPT in patients with CCS or &lt; 12 months of DAPT in patients with ACS) and long DAPT user (≥ 6 months of DAPT in patients with CCS or ≥ 12 months of DAPT in patients with ACS) by DAPT duration.

Results
After IPTW matching, overall the mean age of participants was 63.8±16.3 and the median SAPT duration was 3.3 (1.3 – 6.2). During period, the overall primary effectiveness outcome occurred in 4.1% in aspirin group and 2.8% in clopidogrel group (hazard ratio [HR], 0.684; 95% CI, 0.656 – 0.712; p-value &lt;0.0001) (Figure 1-A). the overall primary safety outcome occurred in 2.4% in aspirin group and 2.1% in clopidogrel group (HR, 0.945; 95% CI, 0.899 – 0.994; p-value, 0.0287) (Figure 1-B). In short DAPT group, clopidogrel reduced the risk of MACE (HR, 0.761; 95% CI, 0.715 – 0.811; p-value, &lt;0.0001) but did not reduce the risk of bleeding (HR, 0.973; 95% CI, 0.893 – 1.056; p-value, 0.5067) comaped with aspirin. However, in the long DAPT group, clopdiogrel reduced both MACE (HR, 0.633; 95% CI, 0.600 – 0.669; p-value &lt;0.0001) and bleeding risk (HR, 0.931; 95% CI, 0.873 – 0.992; p-value, 0.028) compared with aspirin. (Figure 2)

Conclusion
Clopidogrel monotherapy, compared with aspirin monotherapy during the chronic maintenance period after PCI reduced the risk of MACEs and bleeding. As shown in randomized controlled trials, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future clinical adverse events in real-world bid database.
Evaluating off-target drug effects seen in RCTs using proteomics and mendelian randomisation
Authors: Brody J A , Sitlani C M , Ye T , Bis J C , Davies N M , Floyd J S 
Published: October 2024

Abstract

Introduction
Serious adverse drug effects are often not detected until late in drug development after thousands of patients have been exposed to an investigational drug in long and costly clinical trials. More efficient approaches are desirable. Proteomics-informed Mendelian randomisation (MR) can identify potential molecular mechanisms underlying off-target effects of pharmaceuticals and drug repurposing opportunities.

Purpose
As a demonstration of this approach, we used findings from a previous plasma proteomics study nested within a clinical trial of torcetrapib, which was terminated early because of an increased risk of cardiac events and mortality, in which 200 plasma proteins significantly increased (n=68) or decreased (n=132) after three months of torcetrapib use. We surveyed potential plasma protein-mediated causal effecs of torcetrapib on a wide array of relevant phenotypes in three broad domains: cardiovascular(n=10), immunological(n=9) and cancer(n=4), representing major categories of adverse outcomes that were more common in the treatment arm.

Methods
We performed three-sample MR on torcetrapib-associated proteins. First, we identified independent cis-pQTL instruments for these proteins in the Atherosclerosis Risk in Communities (ARIC) Study. Then, we used pQTL effect estimates from the deCODE study, to reduce the potential for bias due to winner’s curse and to increase precision. Lastly, we conducted MR analyses on disease-relevant phenotypes using a debiased-IVW estimator and summary results from the largest available GWAS on these phenotypes: coronary artery disease, ischaemic stroke, blood pressure, lipids, heart rate, QT interval, eGFR, serious infections, blood cell counts, immune cell fractions, and several cancers. The significance level for causal protein-phenotype associations was p=1.85E-5 (0.05/(104*26)), correcting for the 104 proteins with valid instruments and the 26 tested outcomes.

Results
Thirty-three proteins had evidence of a causal association with at least one phenotype. Seventeen proteins were associated with cardiovascular outcomes, including 8 for blood pressure and 9 for lipid levels. We identified more proteins, 25, associated with immune-related phenotypes. One protein was associated with cancer. Of note, 9 proteins had pleiotropic effects across several domains.

Conclusions
Our approach of using Mendelian randomisation to investigate the causal effects of plasma proteins impacted by medication with known off-target adverse effects revealed several novel causal relationships, highlighting the role of immune function in the development of cardiovascular disease. These results support the use of intermediate omics evaluation to identify potential biomarkers for safety monitoring for drug development and reveal avenues of investigation for drug repurposing.
Development of a cardiotoxicity evaluation system using a Heart-on-a-Chip Microdevice with aligned fiber device
Authors: Murata K , Takamura K , Abulaiti M , Nagagaki Y , Kato K , Masumoto H 
Published: October 2024

Abstract

Background and Purpose
Cardiovascular cells differentiated from human induced pluripotent stem (iPS) cells, such as cardiomyocytes, are expected to be useful for evaluating cardiac pharmacology and toxicity in humans. In recent years, myocardial damage caused by anticancer drugs has begun to attract attention. Being able to evaluate human cardiotoxicity early in the development of novel drugs like anticancer agents confers advantages in terms of cost and development speed. The aim of this study was to develop a highly sensitive bioassay system that can evaluate the physiological function of the human heart, and to validate the efficacy of the system toward detection of cardiotoxicity of drugs.

Methods
We differentiated human iPS cells into cardiovascular cells (cardiomyocytes, endothelial cells and mural cells) and applied dynamic culture training to generate vascularized microtissues (VCM) with vascular network structures. By integrating this VCM with a microfluidic chip containing microchannels, we developed a heart-on-a-chip microdevice (HMD) specialized for evaluating cardiac function (Figure 1). Furthermore, through a collaborative study with the Stem Cell & Device Laboratory (SCAD), application of their aligned fiber device improved throughput and stability, allowing development of a SCAD-HMD capable of evaluating longer-term cardiotoxicity.

Results
SCAD-HMD can quantify physiological parameters of VCM such as ejection volume and force based on displacement of particles within the microchannels. Our results showed that SCAD-HMD not only exhibited pharmacological responses to representative circulatory stimulants, but also reproduced clinical events occurring in actual practice, demonstrating that the anticancer drug trastuzumab, commonly used for breast cancer treatment, causes myocardial disfunction when combined with doxorubicin.

Conclusions
This study demonstrated that SCAD-HMD can stably evaluate the toxicity of drugs on the human heart. In the future, establishing SCAD-HMD using iPS cells derived from individual patients and assessing responses to specific drugs may enable "individualized cardiotoxicity assessment systems" that can preemptively avoid cardiac complications associated with anticancer drugs and other pharmacological agents.
Cardiac rehabilitation ambassadors - a new model to enhance patient participation
Authors: Kevill J , Cacavas G , Hooper S 
Published: October 2024

Abstract

Introduction
Participation in outpatient Cardiac Rehabilitation (CR) is considered an integral part of secondary treatment of heart disease. Despite being considered standard care, participation remains low internationally. Encouraging patients to enrol in CR during their hospital stay is linked to higher participation. [1] This study was conducted at a hospital that provides acute cardiac and rehabilitation services in Australia.

Purpose
As a provider of cardiac care, we identified that increasing nurses’ knowledge of the of CR would improve their capacity to promote CR during patient’s hospital stay.

Methods
Utilising a quality improvement methodology, the Cardiac Ambassador Initiative was developed with key stakeholders working on cardiac units in 2022.
The program consisted of an immersion experience for cardiac nurses to shadow CR nurses working in a specialist rehabilitation centre providing best practice CR for patients with a variety of cardiac conditions.
To evaluate the impact of the program, cross-sectional surveys and individual interviews were conducted with participants and Nurse-Unit-Managers (NUMs). Key outcomes included: ambassadors’ knowledge and confidence to promote CR participation to their patients on the wards and NUM's perceptions of the impact of the program.

Results
The program was run over two years. The NUMs and CR-coordinator selected a total of 13 nurses to participate. In 2022 4 participants attended a total of 5 days each. Following evaluation, the program was modified to 3 days for participants in 2023, which enabled 9 participants to attend.
All participants described not fully understanding the nature of CR and its impact on patients until they attended a program. Prior to attendance, 100% of participants considered it was important or somewhat important for patients to attend CR. Following attendance 100% of participants consider it essential or important for patients to attend. They also reported feeling more confident to discuss CR with patients and colleagues and encourage patient participation following the immersion experience. Pre-attendance 100% of participants felt either not at all confident or somewhat confident to discuss CR with their patients and this improved post program with 100% feeling very confident. 100% of participants also indicated that their confidence and skill in discussing CR with patients greatly improved and recommended that others should participate in the CR Ambassador program.
Nurse Unit Managers reported that the CR Ambassadors were a valuable resource for both staff and patients on the cardiac unit and that they had identified a need to review the accessibility of CR information and referral documentation available on their wards.

Conclusion
The immersion experience represents a feasible and sustainable approach to establishing CR ambassadors on acute cardiac wards with the skills needed to promote CR participation to colleagues and patients.
Quantifying cardiac tissue heterogeneity using high-density grid catheter: validation in porcine model
Authors: Ronda Rute L , Ramirez E , Ruiperez-Campillo S , Millet J , Castells F , Hejc J 
Published: October 2024

Abstract

Background and Objectives
Characterizing cardiac substrate is crucial for diagnosing and treating cardiac arrhythmias due to its association with the presence of fibrotic tissue. Omnipolar Electrogram (EGM) technology provides orientation-independent signal generation and instantaneous propagation direction determination. Although traditionally, the amplitude of the bipolar signal has been the most used metric, it alone does not suffice for comprehensive tissue characterization. Recently, a novel metric has been developed to quantify the degree of directional propagation disorganization within cardiac tissue, defined as Vector Field Heterogenity (VFH)[1] that can provide additional insights to the tissue characterization. Due to the presence of tissues with varying impedance, changes in the direction of propagation of cardiac electrical signals can occur. Therefore, the objective of this study is to characterize how the presence of fibrotic or necrotic tissue can influence the disorganization of electrical activity propagation, and thus assess the effectiveness of the heterogeneity metric in characterizing these tissues.

Method
We worked with a database of a female swine records of the left atrium. These records include data pre and post-ablation by electroporation. From the unipolar signals available in the database, we have calculated the Omnipolar EGMs in cross configuration. From the omnipolar signals, we calculated the propagation direction. On this propagation direction, we applied the heterogeneity metric for each catheter position along all the left atrium. This metric has a normalized range between 0 and 1, 0 describing the minimum disorganization and 1 the maximum. These calculations have been applied in the same way in the registers pre and post-ablation to evaluate the differences.

Results
Pre-procedure bipolar peak-to-peak voltages averaged 2.7591mV (SD = 3.4257), decreasing post-procedure to 0.754mV (SD = 1.1666), (p&lt; 0.0001) indicating a significant decrease in bipolar amplitude following ablation. Heterogeneity scores increased post-ablation (mean = 0.3753, SD = 0.21218; post: mean = 0.53526, SD = 0.1320, p&lt;0.0001. This indicates that after ablation, not only does the signal amplitude decrease, but also the level of disorganization of electrical propagation increases. These findings are visually depicted in Figure 1.

Conclusion
The ablation procedure led to reduced tissue electrical activity, manifested by decreased amplitude and increased propagation heterogeneity, indicative of tissue disorganization. Transitioning from homogeneous to heterogeneous conduction post-ablation suggests the presence of necrotic tissue, hindering uniform wave propagation. This highlights the significance of heterogeneity scoring in evaluating tissue health and ablative intervention outcomes.Figure 1.Catheter HD Grid
A prehabilitation programme is feasible and acceptable for mild-to-moderately frail patients undergoing cardiac surgeries
Authors: Li P W C , Yu D S F 
Published: October 2024

Abstract

Background
Preoperative frailty is a strong prognostication in cardiac surgical patients to predict poorer health outcomes. Intervening at the preoperative stage through prehabilitation is gaining increasing research attention. Previous studies tested a single frailty-reversing strategy, either nutritional or exercise, the exercise protocols were mainly aerobic-focused, which deviates from the exercise prescription principles suggested for frailty management, rendering an effective prehabilitation intervention is yet to be developed in cardiac surgical patients.

Purpose
This study aimed to examine the preliminary effects and explore the feasibility of a multi-component frailty-specific prehabilitation programme for mild-to-moderately frail patients undergoing cardiac surgeries/procedures. We hypothesised that compared with patients who receive usual care, patients awaiting cardiac surgeries who participate in the prehabilitation programme would have improved functional capacity, frailty status, quality of life and psychological outcomes, increased serum albumin and reduced C-reactive protein.

Methods
This study adopted a mixed-method design comprising a pilot randomised controlled trial and a qualitative study. Adult patients with a Clinical Frailty Scale score between 4 and 6, waiting for coronary artery bypass grafting surgery and/or valve repair/replacement, with at least 5 weeks of procedural waiting time and without contraindications for exercise were recruited. They were randomized in a 1:1 ratio to receive the prehabilitation programme or usual care. The programme comprised a structured preoperative education, nutritional optimization, stress management; and a multi-component exercise training with 3 sessions/week and 60 minutes/session. The exercise training lasted at least 4 weeks and maintained throughout the preoperative period.

Results
Twenty participants were randomized into the intervention (n = 11) or control (n = 9) group. The programme was feasible, acceptable and no severe adverse events were recorded. The lost to follow-up rate was 7.9%, and the overall attendance was 96%. The intervention group showed significantly greater improvement in functional capacity, frailty status and psychological outcomes than the control group at post-intervention. Participants gave positive comments about the programme and its delivery mode. They expressed that the one-on-one home-based practice enabled them greater confidence to overcome kinesiophobia. Two participants voiced out the preference for exclusive home-based training, rather than having hospital-based training in the first two weeks.

Conclusion(s)
The prehabilitation programme is feasible and acceptable for patients waiting for cardiac surgeries. It improves the functional performance, frailty status and psychological outcomes in these patients. A full-scale randomised controlled trial is warranted to investigate its longer-term and clinical effects.
Heart rate variability to predict 1-day atrial fibrillation episode onset using machine learning
Authors: Gregoire J M , Gilon C , Bersini H , Groben L , Nguyen T , Godart P , Carlier S 
Published: October 2024

Abstract

Background
Studies using AI assessment of 10-second 12-lead ECG suggest that it provides incremental identification of AF risk compared with clinical scores. However, it is not clear what preventive treatment should be given as the exact time of AF onset remains unknown. The use of machine learning (ML) with 2-lead Holter ECG allows the development of predictive models for paroxysmal AF within a short time window, potentially allowing an optimised pill-in-the-pocket (PITP)-like strategy.

Aim
To identify patients who are still in sinus rhythm but will develop an episode of AF in the next few hours using 24-hour Holter recordings and ML.

Materials and methods
We created a new database of 95871 Holter recordings that were manually analysed. We identified 1319 paroxysmal AF episodes from 872 patients. A total of 835 AF episodes from 506 recordings had more than 60 minutes of normal sinus rhythm (NSR) before AF onset and more than 10 minutes of AF after onset, and a total of 964 AF episodes had 30 minutes or more of NSR before AF onset. Patients were divided into five groups: all patients, patients younger than 60 years, 60-70 years, 70-80 years, and older than 80 years. A total of 365 recordings from 347 patients without rhythm abnormalities were identified and classified in our database, from which we took two ECG windows. We used a gradient-boosted decision tree model with heart rate variability (HRV) parameters as input.

Results
The most significant results were obtained from recordings with more than 5 minutes of AF with an AUROC of 0.919 (95% CI: 0.879-0.958) and an AUPRC of 0.919 (0.879-0.958) 15H08 ± 13H05 hours before the onset of AF (Figures 1 - 2). Using a threshold of 0.5, the accuracy was 84.5% (81.2-87.8), the sensitivity was 83.0% (79.5-86.4), the specificity was 86.6% (79.3-93.9), the PPV was 90.2% (85.5-94.9), the NPV was 78.4% (74.7-82.1) and the F1 score was 86.2% (83.5-89.0) for all patients.

Conclusion
These results suggest that the most important information for short-term prediction of AF onset is contained in HRV, allowing a preventive strategy. This could be exploited by wearables in mHealth allowing the use of a PITP-like preventive strategy to reduce the burden of AF. Prospective studies are needed to confirm the encouraging potential of these findings.AUROC of the XGBoost modelPrecision-recall curves