bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling a hide side of the athlete's heart: a CMR focus on the left atrium.
Authors: Monosilio S , Ferrera A , Ortolina D , Di Gioia G , Prosperi S , Lemme E , Netti L , Mango R , Tonti G , Pedrizzetti G , Gualdi G , Pelliccia A , Squeo M R , Maestrini V
Published: October 2024

Background

cardiac magnetic resonance (CMR) is the gold standard to evaluate cardiac chambers’ dimensions and function, but data on left atrium (LA) dimensions and function among elite athletes are lacking.

Objective

to describe LA size and function among a cohort of elite athletes and evaluate eventual differences based on sports discipline and gender.

Methods

We enrolled 120 Olympic athletes with un-remarkable cardiovascular pre-participation screening tests (mean age 25±5 years, 50% males, 25% skill, 25% power, 25% mixed, 25% endurance). All the athletes underwent CMR without contrast administration. LA dimensions, in terms of absolute and indexed area and volume, were computed using 4- and 2-chamber steady state precession cine-sequences. LA ejection fraction (LAEF) and LA coupling index (LACI index, as the ratio between LA and LV end-diastolic volumes) were calculated. Cine-images were also used to analyse atrial deformation with a dedicated offline software to measure LA global longitudinal strain. LA dimensions and function were compared between males and females and athletes of different sports categories based on European classification.

Results

Among the entire cohort, endurance athletes showed the greatest remodelling in terms of LA and LV dimensions (Table). There were no significant differences in LAEF and LV-EF between athletes of different sport categories (p=0.121 and p=0.679). A trend in increasing LA volumes and decreasing LA strain consistent with a growing cardiovascular demand was observed, but the only statistically significant difference was between skill athletes and all the other groups for LA volumes (p<0.001), while there were no significant differences in LA strain (p=0.170). LACI did not differ between athletes of different sports categories (p=0.170). Female athletes showed higher LAEF and LA strain than males (respectively 55±5 vs 52±6% p=0.012 and 35±7 vs 32±7%, p=0.009) while LACI did not differ based on gender (19±5% for both females and males, p=0.385).

Conclusion

Among our cohort of Olympics, LA remodelling was observed in all athletes, being less evident in skill group, as for the LV. Thus, the ratio between LA and LV did not differ between sport categories. LAEF and LA strain were not significantly different between athletes of different sports categories although LA strain was slightly lower in endurance. Female athletes showed higher LAEF and LA strain than males, while LACI was not different based on gender.
Increased risk of cardiovascular events in the weeks following hospitalised COPD exacerbations: the EXACOS-CV French nationwide case-crossover study
Authors: Aboyans V , Nordon C , Poccardi N , Fabry-Vendrand C , Rhodes K , Rey A , Bretin O , Collin C , Zysman M
Published: October 2024

Introduction

Previous studies indicate that in people living with chronic obstructive pulmonary disease (COPD), the risk of myocardial infarction (MI), heart failure (HF) decompensation, arrhythmias and ischemic stroke increases following a COPD exacerbation. This association has not been explored for detailed types of cardiovascular events (CVE), namely for different types of myocardial infarction.

Objective

To quantify the risk of CVE following a COPD exacerbation overall, and by detailed type of CVE.

Methods

A case-crossover study was conducted using the French national hospital discharge database (Programme de Médicalisation des Systèmes d'Information, PMSI). Case-patients: (i) were aged≥40 years with a COPD diagnosis; (ii) hospitalised in 2018-2019 for CVE; (iii) experienced the CVE within 24 weeks of a hospitalised exacerbation of COPD. Hospitalisation date for CVE was index date. Conditional logistic regression models estimated the association between a hospitalised exacerbation and CVE (overall and by type of CVE) – expressed as odds ratios (OR) – comparing the odds of a hospitalised COPD exacerbation during the risk period (4 weeks prior to index date) versus control periods (9-24 weeks prior to index date).

Results

Among 122,172 patients with COPD hospitalised for a severe CVE in 2018-2019, 9,840 (8%) had a hospitalised exacerbation of COPD in the prior 24 weeks and qualified as case-patients. Mean age was 76.8 years (SD 10.7); 6,496 (66%) were male. The most frequent CVE were decompensated heart failure (n=5,888, 60%) and acute coronary syndrome (n=1,070, 11%); in-hospital death in the 24 weeks following an exacerbation of COPD occurred in 950 (10%) patients. Median time elapsed between hospitalised exacerbation and CVE (any type) was 43 days (Figure 1); the shortest delays were observed for non-STEMI (24 days) and resuscitated cardiac arrest (28 days). Risk of CVE in the 4 weeks following a hospitalised COPD exacerbation was 3-times the risk in the 9-24 weeks post-exacerbation (OR 3.0; 95%CI 2.9-3.2 – Figure 2). This increase in risk was observed for each individual type of CVE. The highest effect size was observed for non-STEMI (OR 5.3; 95%CI 4.5-6.3).

Conclusion

The risk of CVE substantially increases following a hospitalised exacerbation of COPD overall and for all types of CVE (acute ischemic events, arrhythmias, and heart failure decompensation). The first month following a hospitalised exacerbation is a period of vulnerability for people living with COPD, with some variability in the magnitude and temporality of risk increase according to the type of CVE. These results stress the need for immediate and sustained monitoring of exacerbating COPD patients to prevent a subsequent severe cardiac event. In addition, exacerbations prevention is an essential target of COPD treatment.
Prolonged ventricular repolarization acts as an independent predictor of sepsis prognosis: a cohort study and insights into intracardiac electrophysiology
Authors: Liu W , Shao R , Jin L , Zhang S , Liu R , Xiong N , Chen P , Ma H , Chen W , He B
Published: October 2024

Background

Sepsis-induced myocardial injury is a serious complication of sepsis, which requires identification in the early stage. The abnormality of ventricular repolarization is related to myocardial injury in a group of heterogeneous disorders. Prolongation of QT interval (QTP) is a proarrhythmic status reflecting the increased ventricular activation duration. However, the study on the clinical value of QT prolongation in sepsis and their potential mechanism is limited.

Purpose

We aimed to investigate the clinical characteristics, predictors of new-onset QT prolongation in sepsis and its relationship with outcomes in a multicenter cohort study, and exploration of the underlying mechanism of changes of ventricular repolarization in sepsis-induced myocardial injury.

Methods

Electrocardiograms were collected from septic patients after exclusion of QT-influencing medications and electrolyte abnormalities. The characteristics and predictive factors of QT prolongation (QTc>450ms) were analyzed, and so was its impact on prognosis. Ventricular depolarization and repolarization were observed in lipopolysaccharide-treated mice with optical mapping. Bulk-RNA sequencing of septic myocardium and pathway enrichment were also performed. The ion channel-related gene expression was thereafter determined.

Results

QT prolongation occurred in 235/1024 (22.9%) patients from 4 centers. The majority demonstrated similar pattern as type I long QT syndrome. Patients with QT prolongation had a higher 15-day and 30-day in-hospital mortality (P<0.001), which was demonstrated as an independent predictor for prognosis (P=0.044) after multivariate analysis. History of coronary artery disease (P=0.001), septic shock (P=0.008), acute respiratory (P<0.001), heart (P=0.021) and renal dysfunction (P=0.013) were independent predictors of QT prolongation in sepsis. Optical mapping demonstrated longer QT interval and global action potential duration in lipopolysaccharide-treated mice without an increase in its dispersion within the ventricles. Sequencing of septic myocardium revealed significant downregulation of multiple potassium channel genes, consistent with the results of quantitative PCR.

Conclusion

New-onset QT prolongation in sepsis was associated with increased mortality as well as atrial and ventricular arrhythmias, which was predicted by disease severity and organ dysfunction. The prolongation of ventricular repolarization can be explained by the downregulation of potassium channel-related genes and the subsequent lengthening of activation potential duration.Graphic Abstract
Treatment of Post-COVID-19 POTS by inhibiting FcRn: a phase 2 randomized, placebo controlled, double-blind, proof of concept study with efgartigimod
Authors: Chung T H , Vernino S , Raj S , Fedorowski A , Konig M F , Rohane P , Ulrichts P , Van Middendorp J , Azar A
Published: October 2024

Background

While the underlying pathophysiology is unknown, post–COVID-19 postural orthostatic tachycardia syndrome (POTS) may be related to immune dysfunction and autoimmunity precipitated by SARS-CoV-2 infection. Various autoantibodies, including those targeting G-protein coupled receptors (GPCRs), have been observed in patients with POTS. Binding of these autoantibodies to adrenergic receptors, which are prototypical GPCRs, has been hypothesized to modulate receptor activity, increase sympathetic tone, and cause tachycardia. Moreover, IgG anti-GPCR autoantibodies, acting as partial agonists, are thought to decrease the effect of peripheral vasomotor control, leading to an increased sympathetic response to upright posture that can result in postural tachycardia in the absence of hypotension.

Purpose

We hypothesize that a reduction in autoantibody levels by efgartigimod, a FcRn-antagonist, will ameliorate the underlying immune-mediated pathogenesis and lead to clinical improvements in patients who developed POTS following COVID-19 infection. We propose a phase II multicenter, randomized, placebo-controlled, double-blind, proof-of-mechanism study initiated to evaluate the safety and efficacy of efgartigimod in adults with post–COVID-19 POTS.

Methods

Adult patients diagnosed with new-onset of POTS following SARS-CoV-2 infection are eligible for participation in the study. Prior COVID-19 must be confirmed by documentation of historical PCR test, and POTS diagnosis must meet consensus criteria. Study subjects must have moderate to severe autonomic symptoms (COMPASS-31 score ≥ 35 points at screening). Approximately 42 patients will be randomly allocated (2:1) to receive weekly intravenous efgartigimod or placebo for 24 weeks. At the end of the treatment period, participants who complete the study may roll over into an open-label extension (OLE).

The co-primary endpoints are change from baseline to week 24 in the COMPASS-31 and Malmo POTS Symptom Score as well as safety and tolerability outcomes. Key secondary endpoints include assessments of disease activity, fatigue, cognitive function, walking capacity and quantitative autonomic testing. Additional exploratory endpoints include intraepidermal small fiber densities (optional), sudomotor innervation (optional) and peripheral blood biomarkers to define histopathological and immune determinants associated with treatment response.

Conclusions

This phase II study of efgartigimod will evaluate the effect of FcRn inhibition on disease pathology and the potential for therapeutic benefit in patients with post–COVID-19 POTS.
The association between mammographic breast density, epicardial adipose tissue volume and coronary artery disease
Authors: Aldous E , Goel V , Yeong C , Vasanthakumar S , Tu H , Salib A , Xu E , Nerlekar N
Published: October 2024

Background

Dysfunctional adipose tissue is strongly linked to cardiometabolic disease. Epicardial adipose tissue (EAT) which is measurable on cardiac computed tomography (CT) is well correlated with cardiovascular disease (CVD), however it is not reported clinically. Breast mammography mandates reporting of breast density (BD), which is also a marker of breast adipose tissue quantity with less dense breasts indicating greater adipose tissue volume. Given the widespread use of screening mammography, this presents an opportunity to employ BD as a possible surrogate for CVD risk.

Purpose

To evaluate the correlation between BD, EAT and coronary artery disease (CAD).

Methods

Single-centre, retrospective, cross-sectional study, including women who had both clinically indicated coronary computed tomography angiogram (CCTA) and mammography. Epicardial adipose tissue volume (EATv) was quantified using semi-automated software (QFAT 2.0). BD was visually assessed by standard 4-level Breast Imaging-Reporting and Data System (BI-RADS) grade with grade A-B representing low density, and C-D representing high density. CAD was categorised as presence/absence of any coronary artery plaque, and CAD severity was quantified using the Coronary Artery Disease Reporting and Data Systems (CAD-RADS) score, with CAD-RADS 1-2 representing mild disease, CAD-RADS 3 moderate disease and CAD-RADS 4 severe disease. CAD analyses were adjusted for modifiable (hypertension, dyslipidaemia, diabetes, body mass index) and non-modifiable (age, past smoking, family history, breast cancer) risk factors. Logistic regression was performed with results presented as Odds Ratio (OR) and [95% Confidence Intervals].

Results

Among 153 patients (mean age 62±10), 103 (67.3%) had low BD (high breast adiposity). Compared with high BD, low BD patients were older, had greater rates of hypertension, had significantly higher mean EAT (106.6 ± 43.0 vs 81.0 ± 31.6ml, p<0.001) (Figure 1), and body mass index (30.5 ± 6.3 vs 26.4 ± 5.4kg/m², p<0.001). Adjusted for age and hypertension, EATv remained independently predictive of low BD (OR:1.02 [1.01-1.03], p=0.006). Low BD made up a higher proportion of mild (76.5%), moderate (73.9%) and severe (80.0%) disease. Low BD was strongly associated with presence of CAD (prevalence 75% vs 48%, OR 3.21 [1.58-6.53], p=0.001) independent of EATv (p=0.25), and independent of modifiable (OR: 2.69 [1.24-5.92], p=0.012) and non-modifiable (OR: 2.42 [1.04-5.85], p=0.047) risk factors (Figure 2).

Conclusions

Low breast density is associated with higher EATv and independently associated with CAD presence beyond EATv and other risk factors. Consequently, mammographic breast density may act as an early risk identification tool for CAD in women.
First-in-human study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of RBD4059, a GalNAc-siRNA drug targeting coagulation factor XI (FXI), in healthy subjects
Authors: Gabrielsen A , Feng Z , Fu J , Ueckert S , Egnell L , Wikstrom J , Wei W , Chen G , Friend R , Zhan H , Liang Z , Gao S , Gan L
Published: October 2024

Background

Patients at risk of thrombosis/thromboembolism, require effective and safe anti-coagulation with high compliance. Inhibiting FXI has emerged as a promising strategy with potential for lower bleeding risk compared to currently approved anti-coagulants. Here we report on the safety, PK and PD effects of the GalNAc-conjugated siRNA RBD4059, specifically targeting and repressing FXI protein synthesis in the liver.

Purpose

Investigate safety, PK, and PD of first-in-human dosing of RBD4059 in healthy subjects.

Methods

A randomized, single-blind, placebo-controlled, single ascending dose (SAD) phase I study in healthy subjects (NCT05653037), in cohorts of eight randomized 3:1 to receive escalating doses of RBD4059 (50, 150, and 400 mg) or placebo administered subcutaneously.

Results

As of January 25, 2024, 24 subjects (with follow-up to week 24) with demographics and baseline clinical characteristics shown in Table 1 were enrolled. RBD4059 was well tolerated (Table 2), all related AEs were grade 1. There was no evidence of any clinically relevant bleeding events. Plasma exposure of RBD4059 tended to increase in proportion to the dose. Maximum concentration in plasma (Cmax) was reached in 2 to 4 h and then declined in line with one-compartment kinetics. The mean plasma half-life (t1/2) ranged from 3.2 to 7.0 h. RBD4059 treatment resulted in dose dependent and sustained reductions in FXI activity and FXI antigen (Figure 1A, B, D). Observed mean maximum percentage change from baseline in FXI activity from the 50 mg, 150 mg, and 400 mg SAD cohorts were 67.5%, 81.0%, and 85.8%, respectively, recovering with a maintained effect observed on D141 (50mg: 50.6% inhibition; 150mg: 68.2% inhibition). The reduction in FXI antigen showed a very similar pattern as the reduction in FXI activity, and reductions were accompanied by a concomitant increase in APTT. (Figure 1C, D). PKPD modelling supports that RBD4059 may be dosed every 3 months or less frequent with a >90% FXI reduction throughout the dosing interval, and will be tested in the upcoming phase 2 study.

Conclusion(s)

RBD4059 demonstrated favorable safety, predictable PK, and pronounced durable PD effect in the dose range of 50 mg - 400 mg. This first-in-human SAD study supports the further development of RBD4059 as an anticoagulant that can maintain a high level of PD effect with a once every 3 month or less frequent dosing regimen, with potential for enhanced compliance in chronic anti-coagulant therapy.Table 1 & Table 2Figure 1.Panels A-D
Integrity of central nervous autonomous tracts is associated with cardiac function, cardiovascular risk factors, organ damage and major adverse cardiovascular events
Authors: Nolde J , Hosp J A , Weiss J , Rau A , Reisert M
Published: October 2024

Background

Alterations in the central autonomic nervous system have been linked to the pathogenesis of cardiovascular (CV) risk and disease. Moreover, these conditions are treatable by pharmacological or interventional modification of the activity of the autonomic nervous system.

Purpose

The UK Biobank enables the investigation of the relationship between changes in the CAN and CV function or disease within a large population. Microstructural integrity of the CAN was assessed for associations with cardiac function, CV risk and damage representations, and major adverse cardiovascular events (MACE).

Method

Microstructural diffusion metrics for 7 CAN tracts were estimated using a Bayesian approach, which determines the three components of a standard white matter-based tissue model: 1. the free water fraction (CSF); 2. the fraction within neuronal processes, i.e. axons and dendrites (INTRA); and 3. the fraction outside of axons or dendrites (EXTRA), representing the cellular compartment and the extracellular matrix. Volume fractions of the three microstructural components were analysed for associations with cardiac index, blood pressure, CV target organ damage (arterial stiffness, left ventricular mass, and wall thickness), and MACE, using covariate-adjusted regression models that corrected for multiple comparisons.

Results

Analysis of cardiac function in 26,302 participants revealed significant associations between cardiac index and CAN regions in the cortical and subcortical networks. Arterial stiffness was significantly associated with markers of microstructural integrity in the cortical networks only (n=22,491), while systolic (n=34,114) and diastolic blood pressure (n=34,130), left ventricular mass (n=22,491) and wall thickness (n=22,491) showed extensive associations with the cortical and subcortical CAN. MACE (n=33,444) was associated with cortical markers of microstructural integrity of the CAN in limbic pathways (significant CANs all p<0.002) and the CAN pathways connecting cortical areas (significant CANs left all <0.001, right=0.001). The observed pattern of microstructural metrics suggests that the integrity of neural connections (intra-fraction) positively correlates with adverse outcomes, while an increase in free fluid (CSF) volume was typically associated with a negative impact.

Conclusion

In this analysis, markers of CAN integrity and degradation showed extensive associations with indicators of CV function, risk factors, damage parameters, and outcomes. This evidence supports the crucial role of autonomic regulation in cardiovascular disease. Future research is needed to determine whether these associations indicate harmful processes, such as neuroinflammation, contributing to cardiovascular (CV) risk and disease development, or if they are consequences of pre-existing elevated risk factors or events.CANs associated with MACEAssociations of CAN with CV organ damage
Interethnic validation of an artificial intelligence algorithm for prediction of atrial fibrillation using sinus rhythm electrocardiogram
Authors: Lee J H , Choi J , Kim J , Cho Y , Oh I
Published: October 2024

Background

Previous research has demonstrated acceptable diagnostic accuracy of artificial intelligence (AI)-enabled sinus rhythm (SR) electrocardiogram (ECG) interpretation for identifying paroxysmal atrial fibrillation (AF). However, interethnic validations of the AI algorithms have not been widely conducted.

Purpose

We aimed to develop our own AI model for the identification of paroxysmal AF based on SR ECGs in the Korean population and to validate its diagnostic performance in Brazilian citizens.

Methods

We trained a Transformer-based vision network on 90% of a dataset comprising 808,194 ECGs from 121,282 patients at Seoul National University Bundang Hospital (2003-2020). The remaining 10% of the dataset was used for internal validation. The model was trained to compute a risk score for paroxysmal AF or new-onset AF within 2 years. External validation was conducted using non-AF ECGs from the CODE 15% dataset provided by the Telehealth Network of Minas Gerais, Brazil.

Results

In internal validation, our AI model achieved an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.911 (95% CI: 0.902 - 0.921), with a sensitivity of 78.1% and a specificity of 89.0%. Subgroup analyses showed an AUROC of 0.893 (95% CI: 0.876 - 0.909) for patients in routine health checkups or outpatient settings, and 0.854 for patients with "Normal ECG" interpretations. In external validation with the CODE 15% dataset, the AI model exhibited an AUROC of 0.884 (95% CI: 0.869-0.900), which increased to 0.906 (95% CI: 0.893-0.919) when adjusted for age and sex (Figure 1). In the subset of patients with "Normal ECG" interpretations, the AUROC was 0.826 (95% CI: 0.769-0.883), increasing to 0.861 (95% CI: 0.814-0.908) after applying the same adjustments.

Conclusions

Our AI-powered SR ECG interpretation model demonstrated excellent diagnostic performance in predicting paroxysmal AF, with valid performance in the Brazilian population as well. This suggests that the model has potential for broad application across different ethnic groups.Figure 1
Prospective evaluation of an AI algorithm for real-time LVEF assessment in acute coronary syndrome using left coronary angiograms: the CathEF multicenter study
Authors: Perrin N P , Theriault-Lauzier P , Sarshoghi A , Ly S , Knafo M , Grandchamp A , Xu Y A N X U , Lessard M G , Corbin D , Tastet O , Gallo R , So D , Marquis-Gravel G , Tanguay J F , Avram R
Published: October 2024

Background

Acute assessment of Left Ventricular Ejection Fraction (LVEF) is critical at time of percutaneous coronary intervention to optimize clinical management. The CathEF artificial intelligence algorithm offers a novel approach for real-time, intra-procedural LVEF assessment using routinely obtained left coronary artery angiograms without additional dye use[1]. Our objective was to evaluate the real-time application of the CathEF algorithm for LVEF measurement during coronary angiogram procedures in patients with acute coronary syndrome (ACS) and to compare its performance with transthoracic echocardiography (TTE) and left ventriculography.

Methods

The CathEF study is a prospective multi-center study that recruited ACS patients undergoing coronary angiography at two institutions from July 2022 to July 2023. Using the CathEF algorithm and the PACS-AI software, we analyzed 2 to 4 left coronary angiogram videos per procedure for LVEF assessment to compare to ventriculography (if indicated) and echocardiography performed during the same hospitalization. Operators were blinded to the CathEF AI-generated results. The primary measure was the algorithm's area under the receiving-operating characteristic curve (AUC) in identifying LVEF <40% or ≥40% compared to TTE-LVEF.

Results

240 patients (32% female, average age 66 ± 12 years) were enrolled, with 207 undergoing TTE during index hospitalization (coronary angiogram to TTE mean delay of 0.8±6.3 days). The CathEF algorithm analyzed 881 coronary angiogram videos, averaging 3.12±1.66 per patient. Indications for angiography included unstable angina (18%), NSTEMI (47%), and STEMI (35%). The algorithm took under one minute to apply. CathEF’s performance yielded an AUC of 0.90 (95% CI, 0.840-0.96) and an MAE of 6.81% ± 0.43, with a Spearman correlation of 0.52.

Conclusions

This study provides proof-of-concept for prospective deployment of an AI algorithm at point-of-care with reliable LVEF measurement in real-time during ACS. This innovation holds the potential to ensure all ACS patients can receive prompt and appropriate care based on their LVEF.CathEF algorithm applied to an angiogramPACS-AI : Platform used to apply CathEF
Interpretable artificial intelligence-based transthyretin amyloid cardiomyopathy detection in patients with severe aortic stenosis
Authors: Shiri I , Balzer S , Bernhard B , Nakase M , Tomii D , L Leib Z , Dobner S , Rominger A , Caobelli F , Valenzuela W , Lanz J , Pilgrim T , Windecker S , Stortecky S , Graeni C
Published: October 2024

Background

The concurrent presence of transthyretin amyloid cardiomyopathy (ATTR-CM) in candidates for transcatheter aortic valve implantation (TAVI) with severe aortic stenosis (AS) is frequently observed.

Objective

This study aims to develop a multimodal artificial intelligence-based model for ATTR-CM detection in patients with severe AS.

Methods

A total of 263 prospectively enrolled (57% males, 83±4.6 years) patients with severe AS were enrolled. All underwent DPD-scintigraphy, and coexisting ATTR-CM was confirmed in 27 (10.3%). 4D-cardiac computed tomography (CT), electrocardiogram, echocardiography, angiography, clinical, and laboratory data were assessed. Specifically, in the 4D-CT, LV myocardial radiomics features as well as global- and segmental myocardial strain. All features underwent z-score normalization, and those with high correlation were eliminated. Different feature selection and machine learning (ML) techniques were used for classification in single- and multimodality scenarios. Eighty percent of the dataset was used for pre-processing, feature extraction, and tuning, with the remaining 20% for evaluating the final model. The model's effectiveness was assessed with accuracy, F1 score, and ROC-AUC across 100 random seeds to establish a reliable classifier. The SHAP (SHapley Additive exPlanations) model is used to interpret the output of ML models.

Results

Among the different algorithms used, Logistic Regression offers the most effective detection of ATTR-CM, surpassing other models with AUC scores of 0.85. CT strain (AUC: 0.85), Radiomics (AUC: 0.76), and clinical features (AUC: 0.70) alone and in combination yielded the highest performance (i.e., AUC: >70), while the remaining modalities had AUC scores ranging from 0.52 to 0.56.

Conclusion

The study shows that AI is effective for non-invasively detecting ATTR-CM in severe aortic stenosis patients, offering a potential alternative to costly DPD-scintigraphy or invasive biopsy.
Impact of a clinician-to-clinician electronic consultation program in heart failure patients with previous hospitalization. Implications for heart failure multidisciplinary management
Authors: Garcia Vega D , Mazon-Ramos P , Portela-Romero M , Rodriguez-Manero M , Rey-Aldana D , Sestayo-Fernandez M , Cinza-Sanjurjo S , Gonzalez-Juanatey J R
Published: October 2024

Background

A clinician-to-clinician electronic consultation (e-consultation) programme may not only improve the accessibility to care but may also impact patient outcomes, particularly in heart failure (HF) patients with a previous episode of hospitalization (HFH), group of patients associated with a worse outcome.

Purpose

To evaluate the impact of an outpatient care management programme that includes a clinician-to-clinician e-consultation on delay time in care, hospital admissions, and mortality in a high-risk group of patients with heart failure (HF) and previous episodes of HF hospitalization (HFH).

Materials and methods

We selected 6444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4146 were attended in e-consultation, and 2230 had previous HFH (Fig 1a). Using an interrupted time series regression model, we analysed the impact of incorporating e-consultation into the healthcare model in the group of patients with HFH and evaluated the elapsed time to cardiology care, HF, cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). We performed a multivariate logistic regression for each of these outcomes in both groups.

Results

Patients with HFH had a higher prevalence of men (P < 0.001) but had a similar age (P = 0.267) compared to patients without HFH. Patients with HFH had a higher prevalence of diabetes (P < 0.001), ischaemic heart disease (P = 0.036), and peripheral arterial disease (P = 0.008) (Fig 1b). In the group of patients with HFH, the introduction of e-consult substantially decreased waiting times to cardiology care (8.6 [8.7] vs. 55.4 [79.9] days, P < 0.001) (Fig 2a). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [95%CI]: 0.837 [0.840–0.833]), 0.900 [0.862–0.949] for CV and 0.699 [0.678–0.726] for all-cause hospitalizations (Fig 2b). There was also lower mortality (iRR [95%CI]: 0.715 [0.657–0.798] due to HF, 0.737 [0.764–0.706] for CV and 0.687 [0.652–0.718] for all-cause) (Fig 2c). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH. The multivariate analyses showed a higher risk of hospitalizations in men, patients with HFH, and those who required more emergency department assistance (Fig 2d).

Conclusions

In patients with HFH, an outpatient care programme that includes an e-consultation significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year. Our results may have implications for optimize the heart failure care organization.Figure 1Figure 2
Distribution of microvascular endothelial function in different clinical and non-clinical settings in the united states and china
Authors: Naghavi M , Messahli L , Naghavi Y , Gul A , Gul M , Yen A , Tanaka H , Metcalfe R , Kleis S
Published: October 2024

Background

Despite the fact that microvascular (endothelial) dysfunction is associated with various diseases from cardiovascular to kidney, lung, liver, and other medical conditions, it has not been extensively studied in various clinical and non-clinical settings as blood pressure has. Digital Thermal Flowmetry (DTF) of microvascular endothelial function is a new and automated technique based on monitoring fingertip temperature fall and rebound during reactive hyperemia. Here we report distributions of microvascular function across (1) CVD patients, (2) wellness and internal medicine clinics, (3) college students, and (4) community-based healthy volunteers in China.

Methods

A total of 7,907 endothelial function test results were collected from various settings. Blood pressure and heart rate were measured before the tests. The tests were conducted using FDA-approved automated VENDYS devices (Endothelix Inc., Palo Alto, CA). Adjusted maximum temperature rebound was reported as Vascular Reactivity Index (VRI) and compared across different settings.

Results

VRI in CVD patients, wellness and internal medicine clinics, college students, and Chinese volunteers were (1.25±0.34) (1.53±0.5) (1.86±0.5) (1.95±0.44.) respectively P<0.01. Age was weakly correlated with VRI with the equation age=-0.01 VRI+2.01 (r=0.17 p<0.001)

Conclusions

To our knowledge, this is the largest database of finger-based endothelial function testing. VRI showed distinct distributions across various clinical and non-clinical settings with CVD patients exhibiting the lowest and Chinese healthy volunteers the highest values. The VRI trend mimics the statistically expected risk trend with CVD patients having the highest and Chinese healthy volunteers having the lowest CVD events risk.Figure 1.
The role of digital health intervention in improving physical activity in cardiac rehabilitation center: a randomised controlled trial
Authors: Kizilkilic S E , Ramakers W , Falter M , Scherrenberg M , Bonneux C , Xu L , Pieters Z , De Pauw M , Hansen D , Coninx K , Dendale P
Published: October 2024

Background

Physical activity plays a crucial role in cardiac rehabilitation for secondary prevention. Despite its importance, participation rates in cardiac rehabilitation programs remain low. Telemedicine, particularly telerehabilitation, presents a viable solution by offering remote access to cardiac rehabilitation services. This innovative approach has the potential to significantly enhance patient outcomes.

Purpose

This study aimed to assess the effectiveness of digital health intervention in improving physical activity in cardiac rehabilitation center.

Methods

A prospective randomised controlled trial was conducted, enrolling 80 eligible cardiac rehabilitation patients. Participants were 1:1 randomised into two groups: a 12-week center-based cardiac rehabilitation program (control group), and a 12-week center-based cardiac rehabilitation program combined with a digital health intervention (intervention group). This digital health intervention consists of smartphone, web, and tablet applications to monitor physical activity outside of rehabilitation sessions and motivate patients to engage in more physical activities.

Results

Of the initial 80 patients, 70 completed the study, and the results are presented in Table 1. In the intervention group, there was a statistically significant improvement in peak rate of oxygen consumption (VO2 peak) (p < 0.01) and peak power output (W peak) (p < 0.01), as measured by cardiopulmonary exercise testing between the end and the beginning of the study at the significance level of 0.05. Similar improvements were also observed in the control group (p = 0.0002 for VO2 peak and p < 0.01 for W peak). After 12 weeks of intervention, significant between-group differences were found: We observe a greater improvement in VO2 peak, on average 1.39 (95% CI: 0.23-2.54) ml/kg, and in W peak, on average, 12.29 (95% CI: 4.12-20.45), higher in the intervention group compared to the control group. Regarding physical activity, the intervention group showed a significant improvement in step count (P = 0.002), measured by an accelerometer, whereas no significant improvement was observed in the control group (P = 0.9714). There is a statistically significant difference in the change of step count between the intervention and control group at the significance level of 0.05. We observe a greater improvement, on average 14 788 steps (95% CI: 4 246 – 25 331), in the intervention group compared to the control group.

Conclusion

This study shows that a combination of a digital health intervention based telerehabilitation with a center-based cardiac rehabilitation is more effective in increasing patient’s exercise capacity and physical activity compared with a center-based cardiac rehabilitation.Table 1:results
Factors associated with non-publication of clinical trials in cardiovascular medicine: a cross-sectional analysis
Authors: Alawajneh M , Aljabai A , Theeb L , Badwan Z , Abd Alnabi A , Theeb H , Altibi A
Published: October 2024

Background/introduction

Cardiovascular medicine is the fourth most-funded area of clinical research as it received an estimate for 7% of the total research funding. Nearly 8% of all clinical trials are cardiovascular-related (1,2). Non-publication of the registered clinical trials wastes money and time, encourages dissemination bias, and creates a body of possibly inaccurate literature, all of which obstruct scientific advancement. (3)

Purpose

To study the factors associated with the non-publication of cardiovascular clinical trials between January 2000 and June 2022.

Methods

We performed a cross-sectional analysis using ClinicalTrials.gov to determine all completed, discontinued, published, and unpublished cardiovascular medicine clinical trials between January 2000 and June 2022. For each trial, data on the trial phase, funding source, intervention type, enrolment size, trial completion, and publication status were extracted and subjected to logistic regression to determine clinical trial publication predictor factors.

Results

Among 3946 trials in cardiovascular medicine registered in ClinicalTrials.gov, there were 3215 completed trials included in the analysis. Of these, 34.2% (n=1100) were unpublished. On multivariate logistic regression, triple-blinded and quadruple-blinded trials were less likely to be unpublished compared to open-label trials (odds ratio [OR] 0.622; 95% confidence interval [CI] 0.45-0.85; p=0.003) and (OR 0.54; CI 0.42-0.69; p<0.001), respectively. Enrolment of 100 participants or more was associated with a decreased likelihood of non-publication (OR 0.46; CI 0.39-0.55; p<0.001). In addition, randomised trials were less likely to be unpublished than non-randomised trials (OR 0.67; CI 0.50-0.88; p=0.004). There was no significant effect of the intervention type, phase of the trial, trial participants' age and gender, or the trial funding resource on the publication status of cardiovascular medicine clinical trials.

Conclusions

It is observed that a considerable number of clinical trials in cardiovascular medicine remain unpublished. This issue raises some concerns regarding the risks and discomfort participants may encounter during the trial, while no results are added to the literature. Blinding of the trials, enrolment size, and allocation methods are the main predictors of trial publication.Forest plot of logistic regression
Efficacy and safety of catheter ablation for idiopathic premature ventricular contraction in Japan: from the nationwide Japan Catheter Ablation Registry
Authors: Goto K , Miyazaki S , Tonegawa-Kuji R , Kanaoka K , Yamashita S , Sasano T , Iwanaga Y , Nakai M , Inoue K , Kusano K , Yamane T , Shimizu W
Published: October 2024

Introduction

Catheter ablation (CA) is a viable approach for managing frequent idiopathic premature ventricular contractions (PVCs) associated with PVC-related cardiomyopathy. However, the real-world outcomes and appropriate indications for CA need further clarification.

Methods

This is the first nationwide analysis focusing on the efficacy and safety of CA of idiopathic PVCs. We analyzed 6,751 patients (age 58 [45-70], 3,265 males [48.4%]) who underwent their first CA for idiopathic PVCs with a single origin (3,849 right ventricular [RV] outflow tract [OT], 614 other RV, 1,517 in left ventricular [LV]-OT, and 771 in other LV), based on the Japanese Catheter Ablation Registry between August 2017 and December 2020.

Results

Success at discharge (SAD) was achieved in 5,276 (78.1%) patients, while 238 patients experienced recurrence before discharge (4.3% of those with acute success). SAD was achieved in 3,236/3,849 (84.1%) RVOT, 379/614 (61.7%) other RV, 1,145/1,517 (75.5%) LVOT, and 516/771 (66.9%) other LV patients (P <0.001). Age <50 and females were independent predictors for SAD. Conversely, obesity, origins other than RVOT, and low-volume facilities were independently inversely related to SAD. 171 (2.5%) acute complications, including 125 cardiac tamponades (CTs) (1.9%), were reported. Age ≥60 and females were independent predictors for both total complications and CTs. Remarkably, females aged ≥80 with RVOT origins exhibited a 10.3% rate of CTs.

Conclusion

Female patients aged <50 with OT-PVC without obesity, demonstrated favorable efficacy. However, non-OT PVCs were independently inversely related to SAD. Special attention should be given to females aged ≥60 with RVOT origins.
VSIG4 inhibits the anti-inflammatory reaction of immune cells after cardiogenic shock
Authors: Erbe S , Kneuer J , Buettner P , Thiele H , Laufs U , Boeckel J N
Published: October 2024

Cardiogenic shock (CS) still has a mortality rate of approximately 50%. CS leads to a significant activation of the immune system. The aim of this study was to characterize the immune cell populations and the immune cell-specific changes in CS on admission to the clinic and after revascularization. We developed a web-based platform named 'IRCaS - Immune Cell Regulations in Cardiogenic Shock' to map the temporal course of immune cell-specific processes of CS after acute myocardial infarction (AMI) from admission to 3 days after revascularization. Our tool revealed an endogenous anti-inflammatory response after CS, which is inhibited by the cell-cell receptor VSIG4.

The web platform contains newly acquired single-cell sequencing data from patients with CS after AMI on admission and 24, 48, and 72 hours after revascularisation, as well as controls. In total, 171,962 immune cells derived from peripheral blood mononuclear cells (PBMCs) were individually sequenced. Analysis of the immune cell populations revealed, that 24 hours after revascularisation, monocytes increased to 62.4% (vs. 30.4% in controls), while T cells decreased from 46.3% to 25.0%. On the immune cell expression level, we observed an inflammatory response indicated by IL1B which continuously increased from 24 h (1.6+fold), over 48h (3.1+fold) to 72 h (3.5+fold) after revascularization. Interestingly, there was a significant anti-inflammatory response shortly after revascularization, as evidenced by a transient increase in the anti-inflammatory CD16+ monocyte subpopulation from 12.1% to 26.7% at 24 hours and an increase in THBS1 after revascularization, which was only short-lived. We identified a negative feedback in the increasing anti-inflammatory CD16+ cells caused by a subsequent VSIG4 (+5.2-fold) increase. Indeed, overexpression of VSIG4 in monocytes resulted in a significant decrease of anti-inflammatory CD16+ monocytes by 33.9% and a decrease in anti-inflammatory transcripts.

Our data show that in addition to the strong inflammatory response in CS, there is also an opposing anti-inflammatory response, which is however only short-lived, as it is attenuated by a negative feedback via an increase in VSIG4. In addition, our webplatform offers time-dynamic gene expression profiles of immune cells, allowing users to select and visualize specific genes during the course of CS after AMI.
Dysfunctional atrial fibroblast processing of filamin A in atrial fibrillation
Authors: Johnston A M , Yiu C H K , Moreira L A , Srivastava V , Sayeed R , Walcot N R H , Sastry P , Smart N , Reilly S
Published: October 2024

Background/Introduction

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with atrial structural remodelling, hallmarked by fibrosis. Atrial fibrosis is instigated by atrial fibroblasts (AFBs). It was previously uncovered the hormone calcitonin (CT) is produced in the heart and, via binding to the CT-receptors (CTR), inhibits atrial fibrogenesis and fibroblast profibrotic activity. [1] In AF, abnormally increased CTR internalisation causes loss of physiological surface CTR and prevents fibroblast activation by CT. The molecular mechanisms of this phenomenon in ACFs are unknown.

Aim

To explore the role of filamin A (FLNa), an actin cross-linking protein that was previously shown to interact with CTR, [2] in the regulation of CTR trafficking.

Methods

AFBs were enzymatically isolated from left atrial appendage biopsies collected from 30 patients in persistent AF or normal sinus rhythm (SR, controls) undergoing elective heart surgery. Immunostaining assessed the localisation of CTR and its overlap with the nucleus (stained with DAPI) and FLNa in AFBs. Co-localisation was quantified by the JACoP BIOP plugin for ImageJ. Target mRNA expression was assessed by RT-qPCR and protein levels by immunoblot. Immunoprecipitation (IP) then immunoblot (IB) validated protein-protein interactions. Calpain activity was assessed with a fluorescence-based assay. The effects of calpains on FLNa proteolytic processing was examined with calpain inhibitor calpeptin (10nM–100nM vs DMSO loading control).

Results

Immunostaining revealed aberrant, intracellular localisation of CTR in AF-AFBs (A) with increased nuclear localisation (p=0.03) and reduced co-localisation with FLNa (p=0.03). FLNa gene expression showed a trend towards reduction in AF (by 36%, p=0.06; B). Meanwhile, although full-length FLNa protein was unaltered in AF, there was a striking 67% reduction (p=0.02) in the expression of FLNa’s c-terminal fragment (FLNaCT), which contains the CTR binding domain (C). Co-immunoprecipitation confirmed a physical interaction between CTR and FLNaCT (D) in both SR and AF AFBs. FLNaCT is typically generated when FLNa is cleaved by the protease calpain 1, whose protein (F) but not mRNA (E), was significantly downregulated (71%, p<0.001) in AF. Puzzlingly, a ~70% loss of calpain 1 protein was associated with unchanged calpain activity (G) and FLNaCT levels in AFBs treated with calpain inhibitor calpeptin (H).

Conclusions

Persistent AF is associated with an aberrant CTR localisation and FLNa proteolytic processing, not attributable to altered calpain activity. Further characterisation of the molecular determinants of the altered CTR localisation may uncover novel and potentially druggable facets of structural remodelling in AF.