bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arrhythmias caused by mutations in SCN5A in children
Authors: Polyakova E , Shcherbakova N 
Published: October 2021

Abstract

Pathogenic genetic variants of the sodium channel alpha-subunit gene (SCN5A) is the leading cause of familial bradyarrhythmias. These diseases often manifest with syncope, have family segregation, and needs antiarrhythmic devices implantation, even in children. However, phenotypically these mutations can manifest as sick sinus syndrome (SSS), atrial fibrillation (AF), Brugada syndrome, and long QT syndrome. There are no studies on the prevalence of SCN5A mutations in children with arrhythmias.
The aim is to study phenotypic and electrocardiographic manifestations of SCN5A-mutations in children with bradyarrhythmias.

Methods
We analyzed the data of 26 patients with bradyarrhythmias, who underwent genetic testing, from the database of the Russian Pediatric Arrhythmia Center. Seventeen were the probands, and nine - family members. The average age was 15.4±4.5 (from 2 to 17). Whole-exome sequencing was performed for 18 patients, cardiovascular panels for others.

Results
Variants of the sodium channel gene were detected in 3 family cases of arrhythmias and one sporadic case. In total, variants in SCN5A gene were found in 9 patients out of 26 (35%).
In the first family, two sisters aged 6 and 17 have two biallelic variants of unknown significance in SCN5A gene. Both girls periodically have a Brugada marker on their ECG. The sisters both had syncope before the implantation of defibrillators. The girls' parents and older sister are clinically healthy, but the father previously had syncope. In the second family, a boy with a binodal disease, syncope, and an implanted pacemaker has two biallelic likely pathogenic variants in SCN5A gene. The boy's sister inherited only the mother's of SCN5A variant, showed a normal ECG in the first year of life, but then developed bradycardia within one year, and then joined the AVB of the 1st degree. Both parents had no clinical manifestations and no complaints. The third family included a mother and daughter with SSS and the heterozygous missense variant of unknown significance in SCN5A gene. Both of them do not need pacemaker implantation. The 12-year-old girl with two heterozygous variants of unknown significance in SCN5A gene had SSS, AF and underwent pacemaker implantation.

Conclusion
Genetic variants of SCN5A were detected in 35% of patients with bradyarrhythmias. Electrocardiographic manifestations of arrhythmias in our patients with SCN5A variants are diverse – SSS, Brugada syndrome, atrial fibrillation. Phenotypic variability in the manifestation of the SCN5A mutation requires a more thorough study of bradyarrhythmias' genetic causes in children.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Clinical Research Institute of Pediatrics named after acad. Y.E.Veltishev at the Pirogov Russian National Research Medical University, Moscow, Russia
VT recurrence and predictors in patients with VT inducibility at the end of VT ablation
Authors: Nakasone K , Fukuzawa K , Kiuchi K , Takami M , Takemoto M , Sakai J , Nakamura T , Yatomi A , Sonoda Y , Takahara H , Yamamoto K , Suzuki Y , Tani K , Hirata K 
Published: October 2021

Abstract

Background
A successful Radiofrequency (RF) ablation of ventricular tachycardia (VT) can prevent VT recurrence. It has been reported that VT non-inducibility at the end of RF ablation is associated with less likely VT recurrence in ischemic cardiomyopathy (ICM) and non-ICM (NCIM). However, it is not clear whether we should use VT non-inducibility as routine end point in RF ablation of VT.

Purpose
The aim of this study was to evaluate VT recurrence in patients who couldn't be achieved VT non-inducibility at the end of RF ablation and the factors attributed to VT recurrence in ICM and NICM patients.

Methods
Between January 2009 and April 2020, 84 consecutive patients (ICM: 34, NICM: 50) underwent RF ablation for drug-resistant VT in our hospital. VT non-inducibility was defined as any ventricular tachy-arrhythmia, including clinical VT, non-clinical VT, and VF, was not induced by programed stimuli at the end of session. Non-inducibility was achieved in 37 patients but it was not achieved in 47 patients (ICM: 18, NICM: 29). To evaluate the validity of “non-inducibility” as an end point of VT ablation, 47 patients (male: 40, mean age: 66±15 years) in whom non-inducibility of any ventricular tachyarrhythmia was not achieved were studied. The primary endpoint was recurrence of any sustained VT and VF during follow up period (mean follow-up period was 1.4 (range, 0.0, 2.0) years.)

Results
Mean left ventricular ejection fraction (LVEF) was 36±13%. Epicardial ablation was required in 8 patients. 32 patients had electrical storm at the time of ablation. Among them, 21 patients had VT recurrence and 26 patients had non-VT recurrence during follow-up period. VT recurrence rate was significantly lower in patients with LVEF≥35% than those with LVEF&lt;35% (HR=0.31, 95% CI 1.25–9.92). Multivariate survival analysis identified LVEF≥35% (HR=0.34, 95% CI 0.10–0.98) and ablation of VT isthmus (HR=0.18, 95% CI 0.02–0.78) as independent predictors of non-VT recurrence.

Conclusions
Even if non-inducibility of any ventricular tachyarrhythmia wasn't achieved at the end of ablation, the patients with LVEF≥35% or who had ablated of VT isthmus might prevent VT recurrence. The validity of non-inducibility of any ventricular tachyarrhythmia should be evaluated in each patient's background.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Abbott, Medtronic
Ventricular tachycardia ablation in nonischemic cardiomyopathy
Authors: Nascimento Matos D , Cavaco D , Cavaco D , Carmo P , Carmo P , Carvalho M.S , Carvalho M.S , Rodrigues G , Rodrigues G , Carmo J , Carmo J , Galvao Santos P , Galvao Santos P , Costa F.M , Costa F.M , Mendes M , Mendes M , Morgado F , Morgado F , Adragao P , Adragao P 
Published: October 2021

Abstract

Introduction
Catheter ablation outcomes for drug-resistant ventricular tachycardia (VT) in nonischemic cardiomyopathy (NICM) are suboptimal when compared to ischemic cardiomyopathy. We aimed to analyse the long-term efficacy and safety of percutaneous catheter ablation in this subset of patients.

Methods
Single-center observational retrospective registry including consecutive NICM patients who underwent catheter ablation for drug-resistant VT during a 10-year period. The efficacy endpoint was defined as VT-free survival after catheter ablation, while safety outcomes were defined by 30-days mortality and procedure-related complications. Independent predictors of VT recurrence were assessed by Cox regression.

Results
In a population of 68 patients, most were male (85%), mean left ventricular ejection fraction (LVEF) was 34±12%, and mean age was 58±15 years. All patients had an implantable cardioverter-defibrillator. Twenty-six (38%) patients underwent epicardial ablation (table 1). Over a median follow-up of 3 years (IQR 1–8), 41% (n=31) patients had VT recurrence and 28% died (n=19). Multivariate survival analysis identified LVEF (HR= 0.98; 95% CI 0.92–0.99, p=0.046) and VT storm at presentation (HR=2.38; 95% CI 1.04–5.46, p=0.041) as independent predictors of VT recurrence. The yearly rates of VT recurrence and overall mortality were 21%/year and 10%/year, respectively. No patients died at 30-days post-procedure, and mean hospital length of stay was 5±6 days. The complication rate was 7% (n=5, table 1), mostly in patients undergoing epicardial ablation (4 vs 1 in endocardial ablation, P=0.046).

Conclusion
LVEF and VT storm at presentation were independent predictors of VT recurrence in NICM patients after catheter ablation. While clinical outcomes can be improved with further technical and scientific development, a tailored endocardial/epicardial approach was safe, with low overall number of complications and no 30-days mortality.

Funding Acknowledgement
Type of funding sources: None.
Prodromal symptoms of out-of-hospital cardiac arrest among patients calling emergency and non-emergency medical help services
Authors: Zylyftari N , Lee C.J.-Y , Gnesin F , Moeller A.L , Mills E.H.A , Moeller S.G , Jensen B , Ringgren K.B , Christensen H.C , Blomberg N.F , Tan H.L , Folke F , Koeber L , Gislason G.H , Torp-Pedersen C 
Published: October 2021

Abstract

Background
Early identification of individuals at risk of out-of-hospital cardiac arrest (OHCA) remains difficult. Little is known about symptoms presented when contacting a medical helpline prior to OHCA.

Aim
To examine the registered prodromal symptoms when patients phoned to seek medical help prior to OHCA.

Methods
OHCA patients (≥18 years) were identified from the Danish Cardiac Arrest Registry (2014–2018) and linked with calls to the non-emergency (1813-Medical Helpline) and Emergency Medical Services 1–1-2 (112). We examined (1) symptoms registered within 30 days before OHCA, categorized into eight groups and stratified by time-period and call-type; (2) hospital diagnoses and medical prescriptions according to symptom groups within 180 days before these calls.

Results
Among 974 OHCA patients who called in total within 30 days before OHCA, 816 OHCA patients (males 57%, median age 76 years [Q1-Q3: 65–84]) had a registered symptom and some of them called more than once (1,145 calls by 816 patients). Overall, the most reported group of symptoms was “Other” (29%), containing a diverse group of prodromal symptoms registered by the caregiver that did not fit into the other categories (Figure), followed by breathing problems (15%). When stratified by time-period (Figure) the most common symptom group remained “Other”. This was followed by symptoms related to the Central Nervous System (CNS)/Unconsciousness (17%) for the time-period within 0–7 days before OHCA, and by breathing problems (19%) and trauma/exposure (17%) for the time-period within 8–30 days before OHCA (Figure). When stratified by call-type, most patients (60.8%) called the 1813-Medical Helpline, where “Other” (35%) and abdominal/back/urinary (14%) symptom groups were the most common. While breathing problems (24%) and CNS/Unconsciousness (21%) were highly reported among calls to 112. Within 180-days before contact with the medical helpline, independently of the symptom group presented, respiratory-related hospital diagnoses and antibiotic medications were common.

Conclusions
Patients with OHCA who called emergency and non-emergency medical helpline 30 days before OHCA had diverse prodromal symptoms; the largest category were “Other” symptoms, followed by breathing-related symptoms.

Funding Acknowledgement
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 under the ESCAPE-NET program;Helsefonden Figure 1. Classification of the prodromal symptoms among patients that called for medical assistance. Stratified by the time-period within 0–7 days and 8–30 days before OHCA. The number of calls within 0–7 days before OHCA = 471 (399 patients), and the number of calls within 8–30 days before OHCA = 674 (500 patients).
The frequency of electrodes replacement in patients undergoing cardiac resynchronizaton therapy during long term follow up
Authors: Jedrzejczyk-Patej E , Mazurek M , Sokal A , Kotalczyk A , Gumprecht J , Szulik M , Pruszkowska-Skrzep P , Kowalski O , Lenarczyk R , Kalarus Z 
Published: October 2021

Abstract

Background
Cardiac resynchronization therapy (CRT) is an effective method of treatment in patients with HF, but as complex device with three electrodes, it is prone to electrode dysfunctions and the need to replace them. However little is known about the frequency of need for leads replacement in subjects undergone CRT in a very long-term follow up.

Aim
To determine the frequency of leads replacement in patients undergoing CRT during long term follow-up.

Methods
Study population consisted of 1059 consecutive patients with CRT implanted between 2002 and 2019 in tertiary care university hospital, in a densely inhabited, urban region of Poland. The data about lead replacement was collected.

Results
During the median follow-up of 1661 days (IQR: 815–2792) for non-infectious reasons (dislocation, dysfunction, fracture etc.) a total of 324 leads in 251 patients (23.7%) were replaced. Median time from CRT implantation to the first lead replacement was 359 days (42–1413). The electrode replacement within first year after CRT implantation was performed in 126 subjects (50.2%), in the rest of patients (49.8%) the leads were replaced after one year of device implantation. In patients with above ten years of follow up (n=143; 13.5%) 67 subjects (46.8%) had one or more lead replacement during follow up.
Patients with electrode replacement during follow-up were younger (63 vs 66 years, P&lt;0.001), more often with nonischemic cardiomyopathy (52.6% vs 41.6%, P=0.002), less often with permanent atrial fibrillation (12.4% vs 24.4%, P&lt;0.001) and had higher left ventricle end-diastolic diameter (68 vs 67 mm, P=0.02). The duration of the first CRT device implantation were longer with higher fluoroscopy time in comparison with patients without lead replacement during follow up (135 vs 120 min, P&lt;0.001 and 20.5 vs 16 min, P&lt;0.001, respectively) and these were an independent predictors of lead replacement during FU (HR 1.002, 95% CI 1.000–1.006, P=0.03 and HR 1.005, 95% CI 1.002–1.008, P&lt;0.001, respectively).

Conclusions
The need for leads replacement due to non-infectious reasons reaches almost 25% of patients with CRT within 4.5 years. Half of the patients have lead replacement within one year after CRT implantation and the other half during long term follow up. The duration of the first procedure (CRT device implantation) is strong predictor of lead replacement during follow up.

Funding Acknowledgement
Type of funding sources: None.
Low level transcutaneous vagus nerve stimulation reverses cardiac dysfunction and changes left ventricular gene expression in a rat model of heart failure with preserved ejection fraction
Authors: Niewiadomska M , Elkholey K , Morris L , Houser J , Flor Ramirez M , Humphrey M.B , Stavrakis S 
Published: October 2021

Abstract

Introduction
Heart failure with preserved ejection fraction (HFpEF) has become a major public health concern, accounting for approximately half of all heart failure patients. Despite normal or near normal left ventricular ejection fraction, HFpEF is associated with increased morbidity and mortality. The complex pathophysiology of HFpEF is not yet fully understood. Inflammation and fibrosis play a central role in the development of HFpEF. We have previously shown that low-level transcutaneous vagus nerve stimulation (LLTS) is anti-inflammatory. The goal of this study was to determine the effect of chronic intermittent LLTS on cardiac fibrosis, diastolic dysfunction, and left ventricular (LV) gene expression in a rat model of HFpEF.

Methods
Dahl salt-sensitive (DSS) rats were randomized into high salt (HS, 8% NaCl) or low salt (LS) diet (0.3% NaCl) at 7 weeks of age. The animals were monitored for the development of HFpEF on a daily basis. After 6 weeks of LS or HS diets, HS rats were randomized into 4 groups: HS active LLTS (n=50), HS sham LLTS (n=48), HS plus olmesartan (n=14) and HS active LLTS plus methyllycaconitine (MLA) (n=36), a specific blocker of the α7-nicotinic acetylcholine receptor (a7nAChR), which mediates the anti-inflammatory effects of LLTS. Stimulation was delivered for 30 min daily (20Hz, 3mA) for 4 weeks. Echocardiography was performed at 13 weeks (baseline) and 17 weeks (endpoint). At endpoint, LV histology and gene expression were examined.

Results
After 6 weeks of diets, HS rats developed hypertension and LV hypertrophy compared to LS rats. At endpoint, LLTS significantly attenuated blood pressure elevation, prevented the deterioration of diastolic function and improved LV circumferential strain, compared to the HS sham LLTS group. LV fibrosis was decreased in the HS active LLTS compared to HS sham LLTS group. MLA attenuated this effect, suggesting that the anti-inflammatory effect of LLTS is necessary to prevent fibrosis in this model (Figure 1). RNA-seq analysis revealed that LLTS significantly changed the expression of genes involved in mitochondrial dysfunction, sitruin signaling pathway, and oxidative phosphorylation.

Conclusion
Autonomic modulation with LLTS attenuates the unfavorable changes of echocardiographic parameters and LV fibrosis induced by HS diet through its anti-inflammatory effects. The results support our hypothesis that inhibiting the anti-inflammatory effect of LLTS attenuates the antifibrotic effect. The obtained data suggest that LLTS may be used clinically as a novel non-invasive neuromodulation therapy for the treatment of HFpEF.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health (NIH)
The right ventricle: pairing structural with functional assessment
Authors: Rocha B , Cunha G , Strong C , Maltes S , Brizido C , Aguiar C , Mendes M 
Published: October 2021

Abstract

Background
Right Ventricular (RV) dysfunction is a well-recognized prognostic marker in the natural history of left-sided Heart Failure (HF). Common experience dictates that structural and functional evaluation are often seemingly discrepant. We aimed to evaluate the correlation between RV function by transthoracic echocardiography (TTE) and Right Heart Catheterization (RHC) parameters, and their prognostic value in patients with HF.

Methods
We designed a retrospective single-centre study of patients with advanced HF referred to TTE and RHC as part of Heart Transplant candidacy evaluation, from 2010 to 2019. Pulmonary Hypertension (PH) was defined by a mean pulmonary artery pressure (mPAP) ≥25mmHg. Patients with PH other than Group II (WHO) PH were excluded. In appropriate cases, vasodilator challenge with inhaled NO was performed. The primary endpoint was a composite of death, heart transplant or HF hospitalization at 6 months.

Results
The cohort was comprised of 68 patients (mean age 56±11 years, 73.5% male, ischaemic HF 44.1%). Most patients had PH (n=61) and TTE evidence of RV dysfunction (n=46). The strongest correlations between RHC and TTE parameters were moderate at best – mPAP, pulmonary capillary wedge pressure and central venous pressure with E/A ratio (Pearson r 0,461, 0,533 and 0,543, respectively; p&lt;0.05); and RV stroke work index and mPAP with non-invasive estimated systolic pulmonary artery (PA) pressure (Pearson r 0,483 and 0,481, respectively; p&lt;0.05). Over a median follow-up of 26 (12–42) months, 53 patients had a primary endpoint event, of whom 36 within 6 months. The best model integrating data from structural and functional assessment to predict the primary endpoint included the systolic PA pressure to stroke volume ratio – i.e. PA elastance (HR per 0.10 units: 2.817; 95% CI 1.030–1.338; p=0.016) – and RV free wall longitudinal strain (HR per −1%: 0.792; 95% CI 0.656–0.956; p=0.015). ROC curve analysis disclosed the best cut-off values as follows: 1.3 (sensitivity 77.2%, specificity 65.6%) and −18% (sensitivity 10.7%, specificity 86.4%), respectively.

Conclusion
In a cohort of patients with advanced HF, who were potential candidates for heart transplantation, RV dysfunction was often noted. The model with highest accuracy to predict the primary outcome integrated RV structural with functional data. Additional studies are warranted to define well-validated scores useful in the algorithmic therapeutic decision of advanced HF.

Funding Acknowledgement
Type of funding sources: None.
Right ventricular remodeling and prognostic relevance after ST-segment elevation myocardial infarction in patients treated with primary percutaneous coronary intervention
Authors: Chimed S , Van Der Bijl P , Lustosa R , Hirasawa K , Yedidya I , Fortuni F , Montero J.M , Marsan N.A , Delgado V , Bax J.J 
Published: October 2021

Abstract

Background
ST-segment elevation myocardial infarction (STEMI) often involves changes in right ventricular (RV) function and size over time. However, the prognostic implications of RV remodeling after STEMI are unknown. The aim of current study was to characterize RV remodeling in post-STEMI patients and to investigate it's prognostic relevance.

Methods
RV remodeling in post-STEMI patients who underwent primary percutaneous coronary intervention (PCI) was defined by RV end-systolic area (RV ESA) change at 6 months after STEMI, compared to baseline. The optimal threshold of RV ESA change (≥40%) to define RV remodeling was derived from spline curve analysis (Figure 1A). The primary endpoint was the composite of all-cause mortality and heart failure (HF) hospitalization. Long term outcomes were compared between patients with and without RV remodeling by means of a log rank test.

Results
A total of 2280 patients were analyzed (mean age 60±11 years, 76% male) and RV remodeling was present in 320 patients (14%). After a median follow-up of 75 months (interquartile range 50–106 months), the composite endpoint of all-cause mortality and HF hospitalization occurred in 292 patients (13%). After adjustment for various risk factors, including tricuspid annular plane systolic excursion (TAPSE), post-STEMI RV remodeling was independently associated with a higher risk of all-cause mortality and HF hospitalization (HR=1.37, 95% CI 1.00–1.87, p=0.049. Finally, patients with RV remodeling were had a significantly lower event-free survival rate compared with patients without RV remodeling during follow-up (log-rank test p=0.009) (Figure 1B).

Conclusion
RV post-infarct remodeling is associated with mortality and HF hospitalization, independent of RV systolic function.

Funding Acknowledgement
Type of funding sources: None. Figure 1. A) Spline and B) Kaplan-Meier curve