bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity of device-measured activity in patients with an implantable cardioverter-defibrillator
Authors: Kolk M Z H , Frodi D M , Langford J , Price E , Andersen T O , Niels Risum N , Jacobsen P K , Tan H L , Svendsen J H , Knops R E , Diederichsen S Z , Tjong F V Y 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Horizon

Introduction
There is a growing interest in the use of accelerometers and sensors embedded in implantable cardioverter-defibrillators (ICDs) for monitoring patient activity. Despite evidence regarding the potential clinical value of device-measured activity (D-PA), the validity of these measurements has not yet been established.

Objective
To assess the validity of device-measured activity against a research-grade, widely validated wearable accelerometer.

Methods
This is a subanalysis of the ongoing multicenter, prospective SafeHeart study. Raw accelerometry data was continuously sampled at 50Hz from a wrist-worn accelerometer (GENEActiv) during 12 months. Days with at least 22 hours of wear time were used to create summary measures of time in activity, daily active volume and total slow walking steps. These measures were compared to D-PA harmonised as percentage of active time per day, from four different ICD vendors’ remote transmission data, using linear mixed effect models.

Results
Wearable and device-measured activity data in 51 ICD patients rendered 1228 days (mean 24 days ±19) with both wearable and device-measured activity data. There were significant differences between wearable and device-measured accelerometery in the average time active per day (Table 1). For two vendors significant associations between D-PA, daily active volume, and total slow walking steps were observed. Also, associations between D-PA and daily active time and moderate vigorous physical activity were found in a third vendor. For the fourth vendor no association between any wearable activity metric and D-PA was found. Inter-patient differences accounted for 73.1% of the total variance in D-PA.

Conclusion
Results demonstrate substantial differences in device-measured activity measurements compared to research-grade activity data. This has implications for the utility and generalizability of D-PA as clinical parameter.
Developing a patient-centric remote monitoring platform for heart failure: a usability and feasibility pilot
Authors: Kaza N , Sakatsume R , Bachtiger P , Noar A , Miyazawa A , Fudge M , Shun-Shin M J , Keene D 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Implantable cardiac devices can invasively measure physiological markers. Although it was anticipated that these markers could help predict worsening heart failure, results have been conflicting1. However, the Triage-HF Plus study has shown that combining device-derived measures with telephone-based symptom assessment markedly increased sensitivity for detecting worsening heart failure to 98.6%2. Nevertheless, telephone assessment increases clinician workload and is dependent on patient availability. The Care Information Exchange is the largest integrated patient-facing digital care portal in the NHS and is a tool which could be employed in remote monitoring of patient symptoms. We aimed to assess the usability and feasibility of using the Care Information Exchange digital platform for symptom data collection amongst heart failure patients with Heart Failure Risk Score-enabled devices and identify barriers preventing its use so that this could be addressed in the future.

Methods and Results
A digital readiness questionnaire was conducted at enrolment. Weekly symptom questionnaires were sent using the Care Information Exchange platform for up to 5 weeks. Afterwards, semi-structured interviews on the usability and feasibility of the platform were conducted.
Of 131 eligible patients, 87 were successfully contacted, of which 56% enrolled. Reasons for declining to participate included: disinterest (45%), illness (18%) or no device ownership (18%). 53% of those enrolled successfully engaged in one to five symptom questionnaire and the mean weekly adherence rate for the symptom questionnaires was 68% amongst patients who had activated their Care Information Exchange account. Amongst those who engaged, 96% of patients agreed that the digital platform was easy to navigate and 100% agreed that they would be willing to use the platform again for health-related questionnaires. 77% of patients who never engaged did not have activated Care Information Exchange accounts due to barriers such as lack of assistance, technological problems and time constraints.

Conclusion
For the current generation of heart failure patients with devices, feasibility is limited for the digital platform symptom assessment, but the platform was usable in those who engaged. As both clinical services and research trials seek to expand the scope of information which can be collected digitally and remotely, these findings may be used to highlight the steps needed to ensure equitable delivery in making digital health interventions accessible to all patients.
Exosome-mediated targeted delivery of NOX4 siRNA ameliorates angiotensin II-induced atrial fibrillation in mice
Authors: Kang J Y , Mun D S , Chun Y M , Park D S , Kim H E , Yun N R , Joung B Y 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Research Foundation of Korea

Background
Exosomes have gained attention as nanocarrier; however, the poor targeting ability after systemic administration restrict exosomes' clinical application. The targeting ability of exosomes can be improved by surface modifications. Recently, the popular method is the cell engineering technique, but cell engineering processes are complex, high-cost, time-consuming, and labor-intensive. To resolve this problem, several previous reports demonstrated exosomes are directly modified by chemical reactions (e.g., biochemical conjugation or hydrophobic insertion). However, few studies have modified exosomes with targeting ligands for atrial fibrillation.

Purpose
This study aimed to develop exosomes endowed with heart-targeting properties using a fast and easy chemical modification method to serve as a promising therapeutic tool for atrial fibrillation.

Methods
We firstly generated heart-targeted delivery system (CTP-Exo) by engineering the surface of exosomes with cardiac targeting peptide (CTP) using bio-orthogonal copper-free click chemistry. Next, we loaded NOX4 siRNA into CTP-Exo, and NOX4 siRNA-mediated cardioprotective effects were examined in angiotensin II (Ang II)-treated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and mice.

Results
CTP-Exo had typical exosome properties, such as ~ 150 nm rounded or cup-shaped morphology, and the presence of marker proteins. Compared with unmodified-Exo, CTP-Exo specifically accumulated in the heart (P &lt; 0.05). In addition, NOX4 siRNA-loaded CTP-Exo (siNOX4/CTP-Exo) exerted strong cardioprotective effects with excellent heart-targeting ability. In Ang II-treated iPSC-CMs, siNOX4/CTP-Exo exhibited the reduced the peak-to-peak interval variability, beating frequency, and Ca2+ transient amplitude. After intravenous injection of siNOX4/CTP-Exo in Ang II-treated mice, there was a significant improvement in cardiac function (P &lt; 0.05) with reduced fibrosis and arrhythmia inducibility.

Conclusion
Taken together, our results suggest that CTP-Exo function as efficient vehicles for heart-targeted delivery of siRNA, which in turn may potentially be used for the treatment of atrial fibrillation.
Genetic background of sinus node dysfunction requiring permanent pacemaker implantation after atrial fibrillation catheter ablation
Authors: Park J W , Hong M H , Kim D H , Yu H T , Kim T H , Uhm J S , Joung B Y , Lee M H , Hwang C , Pak H N 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Atrial fibrillation catheter ablation (AFCA) improves sinus node function and may defer a permanent pacemaker (PPM) implantation. We explored the clinical and genetic characteristics of the patients with AF and sinus node dysfunction (SND) who eventually needed PPM implantation after AFCA.

Methods
Among 2,732 AF patients with genome-wide association study (GWAS, PMRA, Thermofisher scientific, MA, USA) data who underwent the first AFCA, 244 patients (65.0, IQR [59.0, 72.0] years, male 58.2%, paroxysmal AF 79.5%) had underlying SND before AFCA (class I indication for PPM). We retrospectively investigated clinical factors, single-nucleotide polymorphisms (SNPs), and their polygenic risk score (PRS) associated with PPM-AFCA. We defined the cut-off of PRS using the Youden index.

Results
During median 37.9 (IQR 20.3-77.9) months follow-up, 36 out of 244 patients (16.1%) with underlying SND eventually underwent PPM implantation after AFCA (PPM-AFCA). PPM-AFCA group a had a higher body mass index (p=0.013) and large left atrial (LA) dimension (p=0.006) than their counterpart. Among 44 SNPs related to AF and SND, the rs3922844 (p=0.003) near SCN5A and rs9320841 (p=0.011) and rs1015451 (p=0.046) near CJA1 were significantly associated with PPM-AFCA. The rate of PPM-AFCA implantation was significantly higher in the high PRS group (≥1.175, 25.6%) compared to the low PRS group (&lt;1.175, 9.38%, p=0.002, Log-rank p=0.002). LA dimension (adjusted HR 1.06, 95% CI [1.00-1.13], p=0.044) and PRS (adjusted HR 2.69, 95% CI [1.68-4.31], p&lt;0.001) were associated with a higher risk for PPM-AFCA after adjusting clinical factors including age, sex, AF type, beta blocker, and antiarrhythmic drugs after AFCA.

Conclusions
In AF patients with SND, 16% with the genetic background of SCN5A and CJA1 or large atrium eventually needed PPM implantation after AFCA.
ECG-patch assessment of atrial fibrillation during the very-early blanking predicts late blanking period recurrence: preliminary data from a prospective registry
Authors: Marques Antunes M , Silva Cunha P , Lacerda Teixeira B , Alves S , Portugal G , Valente B , Delgado A S , Bras M , Coutinho Cruz M , Paulo M , Lousinha A , Guerra C , Cruz Ferreira R , Martins Oliveira M 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Ablation of atrial fibrillation (AF) is a procedure that causes significant atrial tissue lesions, with transient, albeit significant tissue oedema and inflammation. These mechanisms may trigger early rhythm abnormalities that do not necessarily correlate with future arrhythmias, and, therefore, evaluation of AF recurrence is currently validated by routine ECG and ambulatory 24h Holter monitoring, only after a 3-month blanking period. However, recent data have shown that AF episodes occurring during the blanking period are common and may predict late AF recurrences. The E-Patch (Bio Tel Heart) is an innovative, thin single-use adhesive electrode with extended continuous ECG monitoring for up to 120h.

Aim
To assess if continuous extended monitoring in the very-early blanking period can be associated with event recorder data performed in the late blanking period after AF ablation.

Methods
Single-centre, prospective, longitudinal study, including consecutive patients (P) 24h after AF ablation, monitored with the E-patch. The effectiveness of the device in continuously recording within 5 days after ablation was analyzed, as well as the occurrence of AF episodes during an external 7- day loop-recorder, obtained in the 2nd-month post-ablation.

Results
A total of 30P were included (57% male, 63±8 years). AF ablation was performed with radiofrequency (RF) energy in 14P and with a balloon of cryoenergy in 16P. All P were in sinus rhythm at the beginning of the recording. The mean number of hours of recording was 113±16, with no discomfort complaints in the use of the device or interpretation artefacts. During the E-patch monitoring, a total of 10P (33%) presented AF (AF burden 6.8% of the recording, IQR 3.0-20%). All 30P underwent an external loop recorder for 7 days 2 months post-ablation, with 40% showing AF periods (&gt; 30 seconds duration). All 10P that had AF detection in the very-early E-patch recording had also recurrence in the 2 nd month of extended 7-day continuous recording. Very- early AF detection had a sensitivity of 83.3% and a specificity of 100% to detect late blanking period AF (ROC 0.916±0.06; 95%CI 080-1.0).

Conclusions
The use of the E-patch very-early after AF ablation is effective for AF detection and is highly predictive of AF recurrence in the late blanking period. These findings require validation in larger studies to assess the potential of very-early assessment in the determination of a higher risk for AF recurrence.
Artificial intelligence-estimated biological heart age using 12 lead electrocardiogram predicts mortality and cardiovascular outcomes
Authors: Baek Y , Lee D H , Jo Y S , Lee S C , Choi W I , Kim D H 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None. Main funding source(s): none

Background
There is a paucity of data on the artificial intelligence-estimated biological ECG heart age (AI ECG-heart age) for predicting cardiovascular outcomes as distinct from the chronological age (CA).

Purpose
We sought to investigate whether a deep learning-based algorithm to estimate the AI ECG-heart age using standard 12-lead ECGs predicted mortality and cardiovascular outcomes.

Methods
We trained and validated a deep neural network using raw ECG digital data from 425,051 12-lead ECGs acquired between January 2006 and December 2021. The network performed a holdout test using a separate set of 97,058 ECGs. Additionally, randomly age-sex matched patients with reduced and preserved ejection fraction (EF) were compared.

Results
The deep neural network was trained to estimate the AI ECG-heart age (the mean absolute error 5.8 ± 3.9 years and R squared of 0.7 (r=0.84, p&lt;0.0001) (Fig 1A). In the Cox proportional-hazards models after adjusting for relevant co-morbidity factors, the subjects with an AI ECG-heart age of seven years older than the chronological age had higher all-cause mortality (HR 1.62 [1.43-1.84]) and major adverse cardiovascular events (MACEs) (HR 1.92 [1.65-2.23]), while those under seven years had an inverse relationship (HR 0.86 [0.77-0.95] for all-cause mortality; HR 0.73 [0.63-0.84] for MACEs) (Fig 2). Subjects with a reduced EF had a substantially higher mean AI ECG heart-age, QRS duration, and corrected QT intervals than those with a preserved EF (all p&lt;0.001) (Fig 1B).

Conclusion
The biological heart age estimated by AI had a significant impact on mortality and MACE. Those data suggested that the AI ECG-heart age might facilitate the primary prevention and health care for cardiovascular outcomes.
Prolonged electrocardiographic monitorization with a wearable system after an embolic stroke of undetermined source
Authors: De Castro D , Jorge Toquero J T R , Diego Jimenez D J S , Eusebio Garcia-Izquierdo E G I , Victor Castro-Urda V C U , Cristina Aguilera-Agudo C A A , Daniel Garcia-Rodriguez D G R , Fernando Hernandez-Terciado F H T , Paula Vela-Martin P V M , Paloma Remior P R P , Andrea Matutano A M M , Ramon Garrido-Gonzalez R G G , Daniel Escribano Garcia D E G , Sergio Garcia-Gomez S G G , Ignacio Fernandez-Lozano I F L 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Embolic cerebrovascular events that remain of unknown etiology after careful diagnostic evaluation are known as Embolic Strokes of Undetermined Source (ESUS). Subclinical atrial fibrillation (AF) is an important cause of ESUS.

Purpose
Our aims were to analyze the global diagnostic yield of a prolonged cardiac monitoring wearable system (PCMw) after an ESUS to detect AF and factors associated with it, including the time frame from the ESUS event to PCMw initiation.

Methods
We retrospectively analyzed 200 ECG recordings (3-leads, 30 days duration) by means of a PCMw in patients with an ESUS to detect AF lasting longer than 30 seconds, between 2017-2021.

Results
AF was detected in 21 patients (10,5 %). Patients with AF had more left atrial enlargement (OR=4,22 [1.59-6.85]; p=0.01) and atrial arrythmias in the initial 24-h Holter during hospitalization (OR=5,73 [2.03-16,49]; p=0.001). The detection of AF was significatively higher if the PCMw was worn within the first 30 days after the ESUS compared to beyond 30 days (17% vs 10,3%; p=0,002).

Conclusion
PCMw represents a feasible non-invasive device that could reliably detect subclinical AF episodes after an ESUS. Diagnostic yield was significatively higher when used within the first 30 days after the event, especially in selected patients.
BIOMONITOR III sensing dependency on Body Mass Index (BMi3 Study): Preliminary results
Authors: Domenichini G , Graf D , Le Bloa M , Teres Castillo C , Carroz P , Herrera-Siklody C , Porretta A P , Pascale P , Pruvot E 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): BIOTRONIK SE & Co. KG

Background
Published data on commercially available implantable cardiac monitors (ICMs) and the influence of body mass index (BMI) on the devices sensing performance are scarce. The BIOMONITOR III is an ICM equipped with a large sensing vector allowing to detect high quality subcutaneous ECG (sECG) signals.

Purpose
To evaluate the sensing performance of BIOMONITOR III in two groups of patients (pts) with different BMIs: the first group with BMI&gt;30 (group A) and the second group with BMI&lt;20 (group B).

Methods
The BMi3 is a multicentre, prospective, non-randomized, observational study. The ICM data collection was performed at the implantation and then at 10-days and 3-month follow-up (f-up) visits. A patient questionnaire was conducted at each f-up. The primary end-point was an average R-wave amplitude at f-up end &gt; 0.5 mV in both groups.

Results
A total of 15 pts were included, 10 in group A (8 males, BMI 35.8±3.9) and 5 in group B (2 males, BMI 18.2±1.3). The main implant site was along the heart axis at 45° (70% of pts in group A and 60% of pts of group B), followed by a left parasternal position. The average R-wave amplitude was &gt; 0.5 mV at implant and at each f-up in both groups without significant differences between the groups (see Figure). The P-wave was visible on sECG in all group B pts and in 80% of group A pts. At 3-month f-up the noise burden (detected over the previous 24-h) was 2.6±1.8% in group A vs. 0.0% in group B (p=0.005). Device extraction was performed at the end of the study in 2 pts because of device migration associated to pending erosion (1 pt, group A) or discomfort (1 pt, group A), documented at the 3-months f-up. Overall, the device comfort was reported as "good" or "very good" by 89% of pts in group A vs. 67% of pts in group B (p = ns).

Conclusions
In the BMi3 study the BMI does not significantly affect the R-wave amplitude which remained stable and satisfactory during f-up in both groups. Conversely P-wave visibility on sECG can be reduced in obese pts. Noise is more frequently detected in BMIs &gt; 30 presumably because of difficulties in reaching an implant site allowing minimal device movements in these specific cases. Finally, both skinny and obese pts seem to be a higher risk to experience device migration compared to standard population but larger studies are required to confirm these preliminary observations.
Anatomical and electrophysiological factors involved in atrial cardiomyopathy identify remodeling discrepancies between paroxysmal and persistent atrial fibrillation
Authors: Huang T , Nairn D N , Arentz T A , Jadidi A J 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Progressive atrial fibrotic remodeling has been reported to be associated with atrial cardiomyopathy and the transition from paroxysmal to persistent atrial fibrillation(AF). We sought to identify the anatomical and electrophysiological factors involved in atrial remodeling that promote AF persistency.

Methods
Consecutive patients with paroxysmal(n=134) or persistent(n=136) AF who presented for their first AF ablation procedure were included. Patients underwent high-definition mapping (1835 ± 421 sites/map) during sinus rhythm and were randomized to training and validation sets for model development and evaluation. A total of 62 parameters from both electro-anatomical left atrial(LA) mapping and non-invasive baseline data were extracted encompassing four main categories: (1)LA size, (2)extent of low-voltage-substrate(LVS), (3)LA voltages and (4)bi-atrial conduction time as identified by the duration of amplified P-wave(APWD) in a digital 12-lead-ECG. Least absolute shrinkage and selection operator(LASSO) and logistic regression were performed to identify the factors that are most relevant to AF persistency in each category alone and all categories combined. The performance of the developed models for diagnosis of AF persistency was validated regarding discrimination, calibration and clinical usefulness.

Results
In training and validation sets, APWD (threshold 151ms), LA volume (threshold 94ml), bipolar LVS area &lt;1.0 mV (threshold 4.55cm2) and LA global mean voltage (GMV, threshold 1.66mV) were identified as best determinants for AF persistency in the respective category. Moreover, APWD (AUC 0.851 and 0.801) and LA volume (AUC 0.788 and 0.741) achieved better discrimination than LVS extent (AUC 0.783 and 0.682) and GMV (AUC 0.751 and 0.707). The integrated model (combining APWD and LAV, which were identified after selection among all 62 parameters) yielded the best discrimination performance between AF types (AUC 0.876 in training set and 0.830 in validation set). The calibration performance and clinical usefulness were also superior in APWD and LAV.

Conclusion
Among 62 electro-anatomical parameters, we identified APWD, LA volume, LVS extent and mean LA voltage as the four determinant electrophysiological and anatomical factors that are most indicative for AF persistency. Notably, the combination of APWD with LA volume enabled discrimination between paroxysmal and persistent AF with high accuracy, emphasizing their importance as underlying substrate of persistent AF.