bluuebunny/crossref_metadata_2025 huggingface dataset:
PCSK9 inhibitors and incidence of arrhythmias in clinical practice: a phase IV multicentric study
Authors: Stronati G , Parente E , Nazziconi M , Brugiatelli L , Bastianoni G , Rago A , Comune A , Sfredda S , Costamagna M , Gironella P , Maurizi K , Finori L , Dello Russo A , Russo V , Guerra F
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

PCSK9 inhibitors (PCSK9i) are a novel drug class indicated for the treatment of dyslipidaemia. PCSK9i have been shown to remarkably reduce cardiovascular events in patients at high risk, but little data is currently available regarding the incidence of atrial fibrillation, no reports exist on ventricular events or other cardiac arrhythmias, and is not documented if this drug class is safe regarding arrhythmias as a potential side effect.

Purpose

To study the incidence of arrhythmias in patients before and after treatment with PCSK9i.

Methods

All consecutive patients starting treatment with PCSK9 inhibitors, either evolocumab or alirocumab, were consecutively enrolled in two high-volume Italian arrhythmia centres. All patients were treated according to ESC guidelines for primary and secondary prevention. All patients failed to achieve the recommended LDL goals with standard treatment before the introduction of PCSK9i. Patients with familial hypercholesterolemia were excluded. All arrhythmic endpoints were collected in a one-year time frame before and after the first dose of PCSK9i.

Results

191 patients were enrolled (mean age 63±15 years, 76.6% males) and followed up for one year. 13.2% were labelled as "statin-intolerant" and were treated only with ezetimibe, all the others had PCSK9i prescription on top of both statin and ezetimibe. The recommended LDL threshold was reached in 45.1% of patients at very high-risk and 76.7% at high-risk. 14.9% of all patients had a history of PACs and 15.6% had a history of PVCs. 7.8% had a previous diagnosis of atrial fibrillation, 2.1% of TRNAV and 6.4% of sustained ventricular arrhythmias. These 6.4% all had an ICD implanted for secondary prevention, while another 0.9% had a primary prevention indication. The total number of PACs in 24 hours decreased from 1260 to 800, although the difference was not statistically significant (p=0.058). Similar results were noted for PVCs (from 271 to 195 in 24 hours; p=0.089). The one-year incidence was 6.1% for atrial fibrillation, 2.3% for TRNAV and 3.8% for sustained ventricular arrhythmias, with no difference between the year before (all p=NS). Of all patients with an ICD and a history of appropriate ICD therapies (n=11, 5.7%) only one experienced appropriate therapies in the year after PCSK9i started.

Conclusions

The treatment with PCSK9 inhibitors does not significantly modify the risk of supraventricular or ventricular arrhythmias in patients with non-familial hypercholesterolemia. Preliminary data support the safety of this class of drug also regarding arrhythmic events.
Sudden death in sports. 2018-2020. Argentine Registry
Authors: Gant Lopez J , Cueto A F , Peidro R M , Colque F , Fitz Maurice M D , Cilio M , Sansalone R A , Speranza R , Meiller F , Guillen R H , Medesani L A
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

The prevalence of Sudden Death in Sports (SDS) is low in relation to other forms of death in the general population. There is little current data about this problem in Argentina.

Objectives

Obtain information about the characteristics of these events in order to recommend effective prevention measures.

Methods

A specific mailbox was created to receive SDS case reports. The study was presented in academic, health and social media institutions. The information received was analyzed and investigated with direct contact with professionals or people related to the event.

Results

From January 2018 to February 2020, 26 months, 35 cases of SDS were surveyed. 89% of the male sex pts, 68% over 35 years. SDS occurred mainly in: Football, 11 pts, Gymnastics, 10 pts and marathon 9 pts. 68% of the athletes were amateurs and 52% during high performance practices. Assistance received: 29 athletes received assistance, 19 pts Basic Cardiopulmonary Resuscitation (CPR) and 10 pts advanced CPR with automatic or manual defibrillation in 9 cases. Of the 21 pts that were transferred, 9 pts entered and 8 exited alive. The survival rate was 23% and all graduated in functional class I. A forensic autopsy was performed in only 8 cases. Associated pathologies: 8 pts with coronary heart disease, 7 pts dilated cardiomyopathy, 3 pts, unspecified heart disease, 1 pt with toxic medication, 1 pt died from commotio cordis and 15 pts without diagnosis.

Conclusions

The number of reported cases of SDS was low, with an approximate incidence of 0.25% / 100,000.hab / year, 1 to 2 cases per month. SDS episodes occurred mainly in football, gymnasia and marathon, with an adequate level of on-site assistance and greater use of defibrillation therapy compared to previous reports. High mortality persists (77%). The use of autopsy is low showing cardiomyopathy or unknown origin in young people and coronary disease in adults
Atrial fibrillation detection using the ECG signal in the left in ear region: validation study on patients electively admitted for DC cardioversion
Authors: De Lucia R , Parollo M , Barletta V , Di Cori A , Segreti L , Viani S , Canu A , Mazzocchetti L , Zucchelli G
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Early detection of atrial fibrillation is a major opportunity for mobile health, as portable devices nowadays available can detect multiple-lead electrocardiogram (ECG). The study aims to validate the in-ear region as a new anatomical site for ECG signal detection in patients (pts) affected by atrial fibrillation (AF).

Methods

We performed the ECG using KardiaMobile 6L device on 40 patients affected by AF and admitted to our hospital for elective electrical cardioversion. All the digital ECGs were detected in a modified modality or using the left in-ear region instead of the right hand. All the recorded ECGs were analyzed by the device and the results checked by two cardiologists.

Results

We successfully collected all 40 modified digital ECGs performed on the group of 40 pts: age 69.4 ± 9.4 years; male 28 (70)%; medium HR 95±25.4bpm; 26 (65%) affected by hypertension; 2 (5%) affected by diabetes mellitus; 37 (92,5%) in NOACs. In all cases, the KardiaMobile 6L automatic diagnosis of the ECG detected by this modified modality was correct in 100% of cases.

Conclusion

The in-ear region could be a reliable novel anatomical site for ECG signal detection in patients affected by atrial fibrillation. These data could support the development of new portable mobile ECG devices using the left in ear region and so leaving at least one hand free.
Deep learning to diagnose left ventricular hypertrophy from standard, 12-lead ECG signals: a proof-of-concept study
Authors: Pantelidis P , Oikonomou E , Souvaliotis N , Spartalis M , Lampsas S , Bampa M , Bakogiannis C , Antonopoulos A , Siasos G , Vavuranakis M , Papapetrou P
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Although several sets of voltage and non-voltage criteria have been employed to detect left ventricular hypertrophy (LVH) in 12-lead electrocardiogram (ECG) signals, their accuracy has been proven suboptimal, while their use is limited by the lack of expertise of most non-specialised caregivers. Deep learning (DL) can be employed as an integrated, automated solution, yielding high predictive power for this task.

Purpose

To train a DL model to diagnose LVH from 12-lead ECG signals and evaluate its diagnostic performance.

Methods

A total of 21,837 previously annotated ECG samples were retrieved from the PTB-XL database. Of them, 2,137 (9.8%) had a diagnosis of LVH, while the remaining 90.2% presented with other abnormalities, including non-specific ST changes and conduction disturbances. After applying discrete wavelet transformation to denoise signals (remove the baseline drift and fine noise), we applied a dedicated convolutional, time-series-dedicated neural network (InceptionTime), which we trained on 90% of the data. We reserved the remaining 10% of "unseen" samples for testing its performance and quantifying its recall (sensitivity), precision, F1-score (harmonic mean of recall and precision) and area under the curve (AUC). We employed k-fold cross-validation and repeated the same procedure 10 times, to obtain distributions for each metric score.

Results

The 10 training/testing iterations yielded a median recall of 0.78 (interquartile range, IQR: 0.70-0.91) and a median precision of 0.78 (IQR: 0.75-0.87), indicating the predictive power of the model to both correctly detect LVH when it exists and also not falsely overdiagnose it, missing less than 1 out of 4 cases, in both scenarios. The obtained F1-score was 0.8 (IQR: 0.76-0.83) and the median AUC was 0.86 (IQR: 0.83-0.91).

Conclusions

Although a proof-of-concept study, this attempt demonstrates the potential of DL approaches to accurately detect heart abnormalities, such as LVH, from standard ECG recordings. Such strategies can not only support non-specialist physicians in picking diagnoses hidden "in plain sight", but they can also offer high diagnostic performance, given that attempts are made to optimize them. Toward this direction, our concept work shows that even a simple DL approach, without rigorous optimization, can display high predictive power, misdiagnosing less than 22% of the cases, paving the way for the improvement of such techniques and their integration in clinical practice.
Improved patient selection for primary prevention ICD implantation by predicting ICD non-benefit using artificial intelligence
Authors: Kolk M Z H , Ruiperez-Campillo S , Deb B , Bekkers E J , De Vos B D , Van Der Lingen A C J , Allaart C P , Isgum I , Rogers A J , Clopton P , Wilde A A M , Knops R E , Narayan S M , Tjong F V Y
Published: May 2023

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO Rubicon (452019308)

Amsterdam Cardiovascular Sciences

Background

Left Ventricular Ejection Fraction (LVEF) is suboptimal as a sole marker for predicting sudden cardiac death (SCD) or benefit from an ICD. Machine (ML) and deep (DL) learning provide new opportunities for personalised predictions using complex, multi-modal physiological data.

Objective

We hypothesise that risk stratification for ICD implantation can be improved by ML and DL models that combine clinical variables with time series features from 12-lead electrocardiograms (ECG).

Methods

We present a multicentre study of 1010 patients with an ischaemic, dilated or non-ischaemic cardiomyopathy and LVEF≤35% implanted with an ICD between 2007 and 2021 for primary prevention of SCD (64.9 ±10.8 years, 73.2% male) in two academic hospitals. For each patient, raw 12-lead, 10-second ECG-recordings obtained <90 days before ICD implantation and clinical details were collected. Supervised ML and DL models were trained and validated using stratified k-fold cross-validation (5 repeats, k=10) on a development cohort (n=550) from Hospital A. We used this model to predict ICD non-benefit defined as mortality without prior appropriate ICD-therapy on an external dataset from Hospital B (n=460). Kaplan-Meier survival analysis stratified by high vs. low predicted probability using Youden's J statistic as cut-off was performed.

Results

At 3-year follow-up, 16.0% of patients had died of whom 72.8% met the criteria for ICD non-benefit. Extreme gradient boosting models identified subjects with ICD non-benefit with an area under the receiver operator curve (AUROC) of 0.897 ±0.05 during internal validation (Figure 1, solid line). In the external cohort, the AUROC was 0.793 (95% CI 0.75-0.84) (Figure 1, dashed line). Survival analysis for low vs. high predicted risk indicated ICD non-benefit rates of 6.0% versus 30.3% at 3-year follow-up, respectively (Figure 2).

Conclusion

A ML model that combined clinical with ECG features better predicted ICD non-benefit at 3-years in a primary prevention population than currently available risk scores such as the MADIT-ICD score. This approach may provide new tools to support personalized decision making for ICD therapy. Prospective validation is needed to assess the real-world clinical performance of the model.
The European TeleCheck-AF project on remote app-based management of atrial fibrillation: ablation outpatient clinic experience
Authors: Hermans A N L , Gawalko M , Verhaert D V M , Duncker D , Manninger M , Scherr D , Sultan A , Steven D , Lodzinski P , Gupta D , Vernooy K , Sohaib A , Pluymaekers N A H A , Hendriks J M , Linz D
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

TeleCheck-AF is a multicentre international project initiated to implement remote care delivery for patients with atrial fibrillation (AF) through teleconsultations supported by an on-demand photoplethysmography (PPG)-based heart rate/rhythm monitoring app.

Purpose

The current sub-study of the TeleCheck-AF project aimed to provide the first real-world dataset on feasibility and patient experience of this standardized mobile health (mHealth) infrastructure in the clinical setting of follow-up after catheter ablation.

Methods

This sub-study included consecutive patients in each centre who have undergone catheter ablation. In the post-ablation period, at the 3-, 6- or 12-month visit, patients were provided with the app and were instructed to perform 60-second heart rate/rhythm recordings three times daily and in case of symptoms for seven consecutive days prior to teleconsultation. Recurrences of AF were documented by PPG-based app (FibriCheck®). Motivation was defined as number of days in which the expected number of measurements (≥three/day) were performed per number of days over the entire prescription period. Adherence was defined as number of performed measurements per number of expected measurements over the entire prescription period. Patients’ experience was based on a survey sent to each patient via e-mail.

Results

Data from 588 patients (median age 63 [56-70] years, 39% female) from eight centres from six European countries were analysed. Patients with both optimal motivation (100%) and adherence (≥100%) constituted 158 (29%) of the study population and had more often previously undergone an ablation for AF (77% vs 62%), P=0.005) and had a higher number of AF PPG recordings (mean 1.9 vs 0.8, P=0.017). The app gave patients a safe feeling (70%) and automated reminders were useful (68%). Patients agreed that the app was easy to use (97%), easy to install (89%) and that they would like to use the app in the future (70%).

In 95 (16%) patients, AF was detected by the app. There was no statistically significant difference between patients with (vs without) app-based detected AF, except a higher prevalence of prescribed three or more cardiovascular drugs (65% vs 53%, P=0.032) and beta-blockers (64% vs 52%, P=0.033). Patients with (vs without) app-based detected AF had higher optimal adherence (66% vs 41%, P<0.001).

Conclusion

The TeleCheck-AF approach is feasible and associated with high adherence as well as motivation to use the app and with optimal patient experience. Whether this approach can replace conventional rhythm follow-up after catheter ablation required further study.
The association between adherence to a systematic atrial fibrillation screening program and clinical outcomes: a subanalysis from the STROKESTOP study
Authors: Van Der Velden R , Engdahl J , Crijns H , Friberg L , Kemp-Gudmundsdottir K , Linz D , Svennberg E
Published: May 2023

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): Stockholm County Council, the Swedish Heart & Lung Foundation

Introduction

Screening for atrial fibrillation (AF) in older adults and high-risk patients may be beneficial in preventing clinical outcomes such as stroke. Studies on clinical outcomes in screening-detected AF have highlighted difficulties in getting the population at highest risk to participate in screening programs. Whether the risk of clinical outcomes differs among individuals depending on the level of adherence to the screening program instructions, is currently unknown.

Purpose

To explore associations between different levels of adherence consistency of and adherence to systematic screening, consisting of measurements using a handheld ECG device, and clinical outcomes.

Methods

Half of all 75- and 76-year old inhabitants of two Swedish regions were invited to participate in an AF screening program (STROKESTOP I study). Participants in whom AF was not diagnosed previously or during the baseline visit, were asked to perform 30-seconds recordings using a handheld ECG device twice daily for a period of two weeks. The total screening period consisted of 13 days. Adherence was defined as the total number of recordings performed divided by the total number of recordings asked, whereas adherence consistency was defined as the number of screening days on which the asked number of recordings was performed. Based on the thresholds when 90% of AF cases were detected, the participants were divided into low (<73%), moderate (73-99%) and optimal (≥100%) adherence and low (10 days), moderate (11-12 days) and optimal (13 days) adherence consistency groups.

Results

In total, 6436 participants (3585 females (55.7%)) were included in the analysis. Participants with low adherence consistency were at higher risk of ischemic stroke (hazard ratio (HR) 1.7 (95% confidence interval (CI) 1.2-2.3), p=0.001), systemic embolism (HR 1.7 (1.3-2.4), p=<0.001), dementia (HR 1.7 (1.3-2.2), p<0.001), and a composite endpoint of stroke, systemic embolism, bleeding leading to hospitalisation, and all-cause death (HR 1.3 (1.1-1.5), p=0.001), as well as the composite endpoint with the addition of cardiovascular hospitalisation (HR 1.2 (1.1-1.4), p=0.001) compared to patients in the optimal group (Figure 1). In addition, participants with low adherence were at higher risk of the composite endpoint with cardiovascular hospitalisation (HR 1.3 (1.0-1.7), p=0.018), as well as of the individual endpoints dementia (HR 2.5 (1.7-3.6), p<0.001) and cardiovascular death (HR 2.1 (1.3-3.6), p=0.004).

Conclusion

Low adherence and adherence consistency in systematic screening for AF were associated with a higher risk of adverse cardiovascular and cerebral outcomes.
Telemedicine: the future of personalised atrial fibrillation care in a post pandemic world?
Authors: Kotb A , Armstrong S , Koev I , Antoun I , Vali Z , Barker J , Panchal G , Mavilakandy A , Chin S H , Lazdam M , Ibrahim M , Sandilands A , Somani R , Ng G A
Published: May 2023

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): The pilot phase of the Virtual Ward was funded by Leicester, Leicestershire and Rutland Clinical Commissioning Group and supported by a Digital Healthcare Partnership Award from NHS Innovation (now Transformation Directorate).

Background

The current model of care for patients with atrial fibrillation (AF) is born out of legacy physician-centred care models. The development and acceptance of digital technology have enabled the advent of novel telemedicine-based models for patients with fast AF.

Purpose

A virtual AF ward was implemented as a proof-of-concept care model for patients with AF and rapid ventricular response.

Methods

Patients presenting acutely with AF or Atrial flutter (AFL) to the hospital were onboarded to the virtual ward and managed remotely at home, after being given access to a single-lead ECG device (Kardia), a blood pressure monitor and pulse oximeter with instructions to record daily ECGs, blood pressure, oxygen saturations and complete an online AF symptom questionnaire. Data were uploaded to a digital platform (Dignio) for daily review by the clinical team. Primary outcomes included admission avoidance, re-admission avoidance, and patient satisfaction. Patient satisfaction was assessed using the NHS Friends and Family test (FFT) in addition to narrative feedback.

Results

There were 50 admissions to the virtual ward between January and August 2022. Twenty-four initial hospital admissions were avoided with patients instead directly enrolled from the outpatient setting and a further 25 re-admissions were appropriately prevented during virtual surveillance, avoiding a total of 49 admissions to hospital beds. Most admissions were in AF 78% (n=39) or AFL 18% (n=9), with two admissions frequently alternating between sinus rhythm and AF 4% (n=2). Mean HR at the time of admission and discharge was 122 ± 26 and 82 ± 27 bpm, respectively. FFT response rate was 90% (n=45), with 100% positive responses. Only one patient declined using the service due to technology related anxiety. None of the patients demanded to unilaterally terminate the monitoring, or stopped using the online platform before being discharged from the virtual ward.

Conclusion

This is a first real-world experience of an AF virtual ward that demonstrates a potential for reducing the healthcare burden imposed by AF admissions, while providing the holistic and personalised care that AF needs. Work is ongoing to further confirm safety and cost-effectiveness upon progress in a larger patient cohort.
Adherence to a mobile health-based atrial fibrillation screening program: a subanalysis from STROKESTOP I and II
Authors: Van Der Velden R , Engdahl J , Crijns H , Friberg L , Kemp-Gudmundsdottir K , Linz D , Svennberg E
Published: May 2023

Funding Acknowledgements

Type of funding sources: Other. Main funding source(s): Stockholm County Council, the Swedish Heart & Lung Foundation

Introduction

Atrial fibrillation (AF) is associated with an increased risk of stroke, which may be reduced through timely and adequate treatment initiation. Consequently, early detection of AF is important. In a recent European Heart Rhythm Association practical guide on the use of digital devices, systematic screening for AF of those ≥75 years is recommended.

Purpose

To 1) evaluate adherence and adherence consistency to a handheld electrocardiography (ECG)-based device for AF screening and 2) evaluate factors associated with optimal adherence and adherence consistency.

Methods

In STROKESTOP I and II, half of the 75- and 76-year old population in up to two regions in Sweden were invited to an AF screening program. Participants without previously known AF and without AF during baseline visit, were asked to perform 30-seconds recordings using a handheld ECG-based device for a period of two weeks twice daily in STROKESTOP I and four times a day in STROKESTOP II. Adherence was defined as the number of recordings performed per number of recordings that were asked from the participant over the entire screening period. Adherence consistency was defined as full screening days, i.e. the number of screening days on which the asked number of recordings was performed. Since baseline date was excluded from analysis, the total screening period consisted of 13 days.

Results

In total, 6436 participants from STROKESTOP I (3585 females (55.7%)) and 3712 participants from STROKESTOP II (2218 females (59.8%)) were included in the current analysis. Median adherence was 100% [92-100%] and 90% [75-98%] in STROKESTOP I and II, respectively. The median number of full screening days was 12 [11-13] in STROKESTOP I and 8 [3-11] in STROKESTOP II. In STROKESTOP I, female sex, region of inclusion, income in 1st to 3rd quartile and no university or college education were factors independently associated with both optimal adherence and adherence consistency (Figure 1). In addition, no previous stroke or transient ischemic attack and the use of beta blockers were associated with optimal adherence, whereas no diabetes and low alcohol index were associated with optimal adherence consistency. In STROKESTOP II, socioeconomic factors were not available at the time of the current analysis. Other associations (female sex, absence of diabetes) were comparable to STROKESTOP I.

Conclusions

In this screening program for AF, median adherence was optimal in case of twice daily measurements, and nearly optimal in case of measurements four times a day. Several demographic and socioeconomic factors, as well as low alcohol index and the absence of diabetes and previous stroke were associated with optimal adherence and/or adherence consistency.
The economic impact of remote control in patients with implantable cardioverter defibrillators or cardiac resynchronization therapy defibrillators: single center experience
Authors: Marini M , Videsott L , Dalle Fratte C F , Francesconi A , Bonvicin E , Quintarelli S , Martin M , Guarracini F , Coser A , Benetollo P , Bonmassari R , Boriani G
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Introduction

Remote monitoring (RM) technologies have the potential to improve patient care by increasing compliance, providing early indications of heart failure (HF) decompensation, and potentially allowing for optimization of therapy to prevent HF admissions. The aim of this observational, retrospective study was to assess the clinical and economic consequences of RM vs standard monitoring (SM) through in-office cardiology visits, in patients carrying an implantable cardioverter defibrillator (ICD) or a cardiac resynchronization therapy defibrillator (CRTD).

Methods

Clinical and resource consumption data of this retrospective analysis were extracted from the Electrophysiology Registry of our Cardiology Unit, which has been systemically collecting patient information from January 2011 to February 2022. From a clinical standpoint, survival analysis was conducted, and incidence of CV-related hospitalizations was measured. From an economic standpoint, direct costs of RM and SM patients were collected to compare the cost per treated patient over a 2-year time horizon. Propensity score matching (PSM) was used to reduce the effect of confounding biases and the unbalance of patient characteristics at baseline.

Results

In the enrollment period, N=402 patients carrying ICD/CRTD met the inclusion criteria and were included in the analysis (N=189 patients -47.0%- followed through SM; N=213 patients -53.0%- followed through RM). After PSM, comparison was limited to N=191 patients in each arm (Figure 1). After a follow-up of 2 years since ICD/CRTD implantation, mortality rate for any cause was 1.6% in the RM group and 19.9% in the SM group (log-rank test, p<0.0001). Also, a lower proportion of patients in the RM group (25.1%) were hospitalized for CV-related reasons, compared to the SM group (51.3%; p<0.0001, two-sample test for proportions). Overall, the implementation of the RM program in our territory was cost-saving in both payer and hospital perspectives. The investment required to fund RM (a fee for service in the payer perspective, and staffing costs for hospitals), was more than offset by the lower rate of hospitalizations for CV-related disease. RM adoption generated savings of -€4,771 and -€6,752 per patient in 2 years, in the payer and hospital perspective, respectively (Figure 2).

Conclusion

RM of patients carrying ICD/CRTD improves short-term (2-year) morbidity and mortality risks, compared to SM (based on the traditional in-office visit approach) and finally reduces direct management costs for both hospitals and healthcare services
The relationship between high dominant frequency and low voltage areas in patients with atrial fibrillation: digital twin study
Authors: Lim B , Kwon O S , Jin Z , Yang S , Kim D , Park J W , Yu H T , Kim T H , Uhm J S , Joung B , Lee M H , Hwang C , Pak H N
Published: May 2023

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): a grant [2022R1I1A1A0106342211] from the Basic Science Research Program run by the National Research Foundation of Korea (NRF) which is funded by the Ministry of Science, ICT & Future Planning (MSIP)

Background

It has been suggested that the high dominant frequency (DF) site plays an atrial fibrillation (AF) driver, but its relationship with the atrial substrate voltage map (Vm) in the entire chamber AF map has yet to be studied. We explored the relationship between the DF site during AF and Vm in the entire chamber maps by applying the human left atrial (LA) electroanatomical map (EAM) to the digital twin AF map.

Methods

We acquired LA substrate Vm (at sinus rhythm, >800 points bipolar electrograms) of 110 patients with persistent AF (male 72.7%, 58.7±9.8 years old) who underwent AF catheter ablation. We applied EAM to digital twins (0.4 million nodes), reflecting anatomy, histology, and electrophysiology. We evaluated the highest 10% DF areas for 6 sec after inducing virtual AF. The correlation between the highest 10% DF and the low Vm areas (<0.2mV) was evaluated in the LA region of 10 segments.

Results

The mean voltage of the entire LA area was 1.96±0.85 mV (2.19±0.82 mV extra-PV area, 1.33±0.93 mV PV area) in 110 patients. The correlation between low Vm and high DF areas was not significant in the entire LA (r=0.106, p<0.001), extra-PV (r=0.157, p<0.001), and PV (r=0.079, p=0.097) areas. In the LA 10 segment regional analysis, 72 patients (65.5%) showed the co-localization of the highest DF in the region with the lowest Vm, and 14 patients (12.7%) had the lowest Vm segment in the region with the highest DF. The mean voltage where high DF appeared was 0.69±1.35 mV, and the mean voltage of the region where high DF did not appear was 0.59±1.15 mV (p=0.171).

Conclusion

High DF site, a parameter representing a localized focal source, had statistically significant but very poor correlations with LA extra-PV voltage substrate in patients with persistent AF.
Clinical factors that influence the onset of atrial fibrillation or worsen its course after infection with Covid - 19
Authors: Stasyshena O V , Sychov O S , Romanova O M , Talaeva T V , Sribna O V , Deyak S I , Mikhalieva T V , Ilchyshyna O I A , Getman T V
Published: May 2023

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): In. of cardiology

Introduction

It is known that atrial fibrillation (AF) is not only one of the most common arrhythmias, but also a frequent rhythm disturbance in patients who have undergone SARS-CoV-2 infection. This arrhythmia often develops in the post-covid period.

Purpose

to determine clinical factors associated with the onset or worsening of the course of atrial fibrillation in patients with coronavirus disease (COVID-19).

Materials and methods

The study included 187 patients aged 62.5±0.9 years (47% men, 53% women). The vast majority of patients (89%) had arterial hypertension (II stage – 80%, III stage – 9%). Chronic forms of coronary heart disease were diagnosed in 53% of patients. The first three groups formed 116 patients who had AF and underwent coronavirus infection (CI). The first group (G1) consisted of 36 patients who did not have AF before CI. The second group (G2) was represented by 25 patients in whom the transition of the paroxysmal form of AF into persistent, or persistent AF into its permanent form occurred. The third group (G3) consisted of 55 patients in whom the form of AF did not change, but in 35 of them the frequency or duration of AF paroxysms increased (subgroup 3a), and in 20 people the frequency or duration of AF paroxysms did not change (subgroup 3b). Two control groups were also formed: K1 - 49 patients with AF who did not have a history of HF, and K2 - 22 patients with extrasystole who experienced HF, but who did not develop AF.

The results. G1 patients were older than those in K2 (63.6±0.64 years vs. 50.7±1.1 years, respectively; p<0.001). At the same time, G2 patients at the time of inclusion in the study were older than those in G3 (66.5±1.04 years vs. 62.9±1.12 years, respectively; p<0.05). Women more often occurred in G1 than in K1 (51.7% vs. 30.6%, respectively; p<0.001), as well as in the combined group of G2-G3 compared to K1 (53.7% vs. 30.6% ,respectively; p<0.001). Concomitant hypertension was associated with an increase in the frequency and duration of AF paroxysms after COVID-19. Thus, group 2, compared to group 3, was characterized by more frequent detection of both stage II hypertension (72% vs. 65.5%; p<0.05) and its stage III (12% vs. 3.6%, p<0 ,05). Similarly, patients with chronic forms of CAD were more frequent in group 2, in contrast to group 3 (72.0% vs. 50%, p<0.001). In addition, the frequency of detection of patients with chronic forms of coronary heart disease was higher in subgroup 3a, compared to subgroup 3b (54.3% vs. 45.0%; p<0.005).

Conclusion

Older age, female sex, hypertension, and coronary heart disease were clinical factors associated with the occurrence of AF or worsening of previously diagnosed AF in patients with COVID-19.
PITX2c impairment electrical remodeling increases susceptibility to atrial fibrillation
Authors: Mun D S , Kang J Y , Chun Y M , Park D S , Kim H E , Yun N R , Joung B Y
Published: May 2023

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT), the Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korea government

Background

Functional mutations in the PITX2 (Paired-like homeodomain transcription factor 2) gene cause genetically inherited atrial fibrillation (AF). PITX2 is known to plays a pivotal role in regulating the expression of distinct ion channels, beta-adrenergic stimulation, cell-cell coupling and resulting in AF due to abnormal calcium abnormalities and electrical remodeling. However, the pathophysiological mechanisms linking impaired PITX2 with AF are still to be explored. This study was performed to generate PITX2c knockout human iPSC atrial cardiomyocytes (hiPSC-atrial CM), which are useful tools for arrhythmia modeling, and evaluate the mechanism of PITX2 deficiency leading to AF.

Methods

We generated a PITX2 knock-out iPSC line using a CRISPR/Cas9-based genome editing system. hiPSCs were electroporated with Cas9/sgRNA ribonucleoprotein (RNP) complexes. PITX2c knock-out hiPSC-CMs differentiated into atrial cardiomyocytes based on the manipulation of retinoic acid signaling. For the three-dimensional (3D) culture model, cells were plated in the spherical plate 5D. Electrophysiological properties and oxidative stress were assessed in PITX2c-deficient cardiomyocytes. Proarrhythmic effects of the PITX2c knock-out were quantified with AP morphology, AP duration (APD) restitution, wavelength (WL) and conduction velocity (CV) restitution using microelectrode arrays (MEA).

Results

We demonstrated that atrial-specific differentiated hiPSC-CMs expressed atrial-specific genes and the properties of action potentials were like those of human atrial cardiomyocytes. In addition, both 2D and 3D PITX2c knock-out atrial hiPSC-CMs showed signs of APD shortening and reduced wavelength (WL) and increased conduction velocity (CV) restitution (P<0.05). Next, a functional assessment of calcium homeostasis has shown that PITX2c causes atrial arrhythmias by impairing calcium handling genes (SERCA2a, RyR2, PLN). We then demonstrated that miR-374a-5p and miR-374b-5p could be involved in pathophysiological functions as therapeutic candidates when affinity for PITX2 was based on the upper context score percentile (> 99).

Conclusions

This study provides an understanding of electrical remodeling by PITX2c loss-of-function mutations and suggests the potential therapeutic candidates by miR-374a-5p and miR-374b-5p, thus helping to understand the mechanism of PITX2 deficiency leading to atrial fibrillation.
Soluble ST2 in predicting an adverse outcome of revascularization and the development of heart failure in patients with acute myocardial infarction with ST segment elevation
Authors: Kutya I , Rodionova I , Korytsya M , Hilova Y
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Objective

to study the relationship between the sST2 level and the degree of epicardial blood flow recovery and with the heart failure (HF) development or exacerbation in 6 month follow-up in patients with STEMI after PCI.

Materials and methods

The study involved 61 patients with STEMI — 51 (83.6%) males and 10 (16.4%) females, with average age of 59.85 ± 10.01 years. Standard clinical and biochemical parameters were determined, as well as sST2 level was measured by enzyme immunoassay using a reagent kit «Presage ST2 analysis, Critical Diagnosis» (USA) in all patients, on the first day of the disease. Patients were divided into two groups depending on the degree of blood flow recovery in a culprit artery (TIMI) The first group (n = 12) included patients with TIMI 0, I, II, the second group (n = 49) with TIMI III.

Results

The sST2 level was significantly higher in the first hours of the disease in the group with unrepaired or decreased epicardial blood flow (TIMI 0-II) after PCI (p = 0.003). ROC analysis showed that sST2 levels above 34.2 ng / ml, detected in the first hours of the disease, is an independent predictor of adverse revascularization (TIMI 0-II) in patients with STEMI with a sensitivity of 92.3% and a specificity of 62.5%; the area under curve (the AUC) is 0.8 (95% CI = 0.651 - 0.873; p = 0.001). When conducting a univariate (χ2 = 17.741; p = 0.04) and multivariate (χ2= 9.293; p = 0.004) logistic analyzes, sST2 was a significant predictor of the unfavorable outcome of epicardial vascular revascularization (TIMI 0-ІІ).

Conclusions

sST2 is highly associated with the degree of epicardial blood flow recovery in patients with STEMI and is of great clinical importance as prognostic marker.
Clinical and genetic characteristics and course of congenital long QT syndrome: A ten-year single center experience
Authors: Blich M , Kchoury A , Darawsha W , Eyal A , Suleiman M , Gepstein L , Boulos M
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Long QT syndrome (LQTS) is an inherited primary arrhythmia syndrome associated with life-threatening ventricular arrhythmia.

Objective

To report the clinical and genetic characteristics and outcome of LQTS patients in single center inherited arrhythmia clinic.

Methods

Retrospective review of patients diagnosed LQTS and evaluated by ECG, 12 lead holter, exercise test and genetic testing in inherited arrhythmia clinic from January 212 to January 2022.

Results

101 patients (32 families) were included, mean age 24.3± 17 years. Thirteen patients (12.8%) were diagnosed after previous cardiac arrest and six patients (6%) had syncope. Seventy (69.3%) were identified as having LQTS during family screening. 97 patients (97%) were confirmed to have a pathogenic mutation for LQTS genes. Beta blockers were recommended to 74 patients (73%), flecainide to 20 (19.8%). Nine patients (8.9%) received an ICD for secondary prevention and one patient (1%) for primary prevention. During 5.8 ± 2.7 years, dose of beta-blockers increased from propranolol 70 ±42 mg to 105 ±60.3 mg (p= 0.0004), QTC shortening (479 ± 36.9 to 466 ±30.1 msec, p=0.01) in ECG and maximal QTC measured in 12 lead holter (521± 43.9 to 505± 37.8 msec, p=0.01). Maximal heart rates measured in 12 lead holter and exercise test were reduced ( 130± 24.5 to 116 ± 20.2 beats/min p=0.0001 and 152.6±22 to 145± 20.58 beats/min, p=0.043). Seven patients (6.9%) experienced ventricular arrhythmia, five received appropriate ICD shock and two patients that declined beta blockers experienced syncope due to polymorphic ventricular tachycardia and cardiac arrest. The one patient that had the ICD for primary prevention, experienced polymorphic ventricular tachycardia that was successfully treated by the ICD.

Conclusions

Intensive clinical follow up and an optimal medical therapy in a specialized arrhythmia clinic is associated with a relatively low incidence of sudden cardiac death and a low rate of ICD utilization in LQTS patients.
Risk stratification of severe ventricular arrhythmias in Brugada syndrome
Authors: Nguyen Khiem T H A O , Truong Thanh V I E N , Pham Thanh B I N H , Phan Nhu N G O C , Vu Xuan Q U A N G , Vu Tran Dinh H U Y , Ngo N M T A M , Mazur W , Chung E U G E N E , Ton That M I N H
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Predicting likelihood of severe ventricular arrhythmias in Brugada syndrome (BrS) patients is challenging due to conflicting evidence.

Objectives

The goal of this study was to construct a prediction model of severe ventricular arrhythmias (VAs) for BrS patients.

Methods

Two hundred forty-two BrS patients were enrolled from 2008 to 2019 in a single-center cohort study. Those patients were followed up until December 2021. Clinical data and multiple ECG markers were collected and analyzed to determine the risk factors of severe VAs and sudden cardiac death (SCD). Multivariate logistic regression analysis was then used to develop a risk prediction model for adverse arrhythmic outcomes in BrS patients.

Results

During the follow-up (90.1 ± 45.8 months) of 242 BrS patients (mean age 42.3 ± 12 years; 94.6% male), 49 (20.2%) patients had syncope/pre-syncope due to VAs and 7 (2.9%) patients had aborted cardiac arrest. In multivariable analysis, epsilon wave, early repolarization sign, S wave duration in lead I, QRS duration in V2 and Tp-e duration were significant associated with adverse arrhythmic outcomes. A clinical model including these five significant predictors had a good performance to predict outcomes with balanced accuracy of 0.86 and area under curve of 0.93 (95% CI, 0.89-0.96, p < 0.001) indicating a good discriminative ability. Furthermore, the Hosmer–Lemeshow test and the calibration plot showed a good fit between the predicted and observed probabilities of the predictive model.

Conclusions

This study constructed a risk prediction model for severe VAs in BrS patients with a high predictive accuracy.
Interim evaluation of insertable cardiac monitor signal quality in the LUX-Dx PERFORM study
Authors: Richards M , Mahajan D , Simon T , Kupfer M , Rajan A , Herrmann K , Rogers J D , Garner J , Pokorney S
Published: May 2023

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Boston Scientific Corporation

Background

The LUX-Dx PERFORM Study is designed to evaluate safety and performance of the LUX-Dx Insertable Cardiac Monitor (ICM) in a general patient population. Although follow-up is ongoing, enrollment is complete, and at least half of the patients have completed 180 days of follow-up. The visibility (or absence) of P-waves in the ICM-recorded S-ECG is an important feature in the diagnosis of atrial arrhythmias.

Objective

Evaluate the visibility of P-waves in patients enrolled in the LUX-Dx PERFORM study.

Methods

P-wave visibility was evaluated from the first 356 patients enrolled in the LUX-Dx PERFORM study. The daily presenting S-ECGs (10 second rhythm) nearest to Day 7 (+/- 1) and Day 180 (+/- 7) after implant were blindly adjudicated by independent electrophysiologists to calculate the percentage of beats with clearly visible P-waves.

Results

Of 636 reviewed S-ECGs, 24 (3.7%) were excluded from analysis for presence of AF rhythm (11), or unavailable data (8 with insufficient adjudication and 5 with no detected R-waves from which to calculate the percentage of beats with visible P-waves). Figure 1 shows an example of a presenting S-ECG rhythm with clearly visible P-waves from the patient management system LATITUDE Clarity. The P-waves were found to be clearly visible in 89.1% of the total heart cycles (Day 7: 90.4%, Day 180: 87.8%). The average difference in percent visibility between Day 7 and Day 180 was approximately 2.2% (p=.248). At a patient level, 88% of patients had visible P-waves in at least one presenting ECG for more than 90% of beats, as shown in Figure 2. In addition, 69% of patients had visible P-waves in both presenting ECGs (Day 7 and Day 180) for at least 90% of beats.

Conclusion

The LUX-Dx showed consistent visibility of P-waves in the first half of patients enrolled in the LUX-Dx PERFORM study, which represents a general patient population. Adequate P-wave visibility is an important clinical feature in diagnosing atrial arrhythmias and may aid in analysis and clinic workflow efficiency.
Heart rate variability according to electrolyte changes during hemodialysis in patients with chronic kidney disease
Authors: Im S I , Shin H S
Published: May 2023

Funding Acknowledgements

Type of funding sources: None.

Background

Autonomic neuropathy commonly arises as a long-term complication in chronic kidney disease (CKD) and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings.

Purpose

There is limited data about HRV using real-time ECG according to electrolyte levels during hemodialysis (HD) in patients with CKD.

Methods

Total of 50 patients (62.1±10.7 years) with CKD underwent continuous real-time ECG monitor (237.4±15.3 mins) during HD for HRV using remote monitoring system and checked electrolyte levels before/after HD. And we compared HRV according to electrolyte levels.

Results

During the monitor, we checked total 2374 times of ECG and electrolyte level simultaneously of all patients. Both time and frequency domain HRV were higher when the patients had lower K+ level change before/after HD (<0.5mEq/L) as compared with those with higher K+ level change (>0.5mEq/L) in Table. In addition, there were higher incidence of arrhythmic events including atrial/ventricular premature complexes, even though no difference of mean heart rate in patients with lower K+ level change group (P<0.001).

Conclusions

Poor controlled K+ level during hemodialysis was independently associated with higher HRV in patients with CKD. This is further substantiated by independent continuous associations between real-time measures of K+ level and higher HRV. These data strongly suggest that cardiac autonomic dysfunction can be caused by lower change before/after hemodialysis alone.