Cardiac Syncope Research Articles

XGBoost machine learning algorithm for differential diagnosis of pediatric syncope

Abstract. The search for new methods of differential diagnosis of syncope types will allow to improve the diagnosis of vasovagal syncope (VVS), syncope due to orthostatic hypotension (OH) and cardiac syncope (CS) in childhood in order to make timely adequate diagnostic and therapeutic decisions. The aim of the study was to develop an effective machine learning model for the differential diagnosis of VVS, syncope due to OH and CS in children. Materials and Methods. 140 patients with syncope, aged 8-17 years, were examined: 92 children with a diagnosis of VVS, 28 children with syncope due to OH and 20 children with CS. A machine learning model was built using XGBoost algorithm for multiclass classification based on input clinical, laboratory and instrumental patient data. Results. The developed machine learning model based on the XGBoost algorithm is effective in the differential diagnosis of VVS, syncope due to OH and CS, which is confirmed by the metrics of accuracy (0.93), precision (0.93 for VVS; 1.00 for syncope due to OH; 0.80 for CS), recall (0.96 for VVS; 1.00 for syncope due to OH; 0.67 for CS), f1 (0.95 for VVS; 1.00 for syncope due to OH; 0.73 for CS), ROC AUC (0.95 for VVS; 1.00 for syncope due to OH; 0.89 for CS), PR AUC (0.96 for VVS; 1.00 for syncope due to OH; 0.79 for CS),Cohen’s Kappa (0.85), and Matthews correlation coefficient (0.85). The most informative parameters of the syncope types differential diagnosis model are OH, paroxysmal supraventricular tachycardia, Hildebrandt coefficient, Calgary Syncope Seizure Score, vitamin B6, average duration of the P-Q interval during 24 hours, duration of tachycardia during 24 hours, stroke index, homocysteine, heart volume, and systolic blood volume. Conclusions. The proposed machine learning model has sufficient efficiency and can be used by pediatricians and pediatric cardiologists for the differential diagnosis of VS, syncope due to OH, and CS in childhood.

Lamin A/C cardiomyopathy in children

Abstract Background Lamin A/C gene (LMNA) variants cause familial dilated cardiomyopathy (DCM) with a malignant cardiac phenotype characterized by atrioventricular (AV) block and supraventricular and ventricular arrhythmias, often preceding cardiac dilatation and dysfunction. Current guidelines recommend genetic and clinical screening of family members, starting at 10-12 years of age. However, children with LMNA variants are underrepresented in research publications and data are lacking on both the onset of a cardiac phenotype and the prevalence of cardiac events in this population. Purpose The study aimed to investigate the prevalence of cardiac events in LMNA genotype positive children and penetrance of LMNA cardiac phenotype in genotype positive paediatric relatives. Methods We conducted a longitudinal cohort study including consecutive genotype-positive LMNA patients and genotype positive relatives, all ≤18 years of age, followed between 2009 and 2022. The patients were examined by electrocardiography, Holter monitoring, and echocardiography. A cardiac phenotype was defined as the presence of either atrioventricular (AV) block, prolonged sinus arrest, atrial fibrillation/ flutter (AF), ventricular tachycardia (VT), or echocardiographic DCM. Cardiac events were defined as AF, VT, cardiac syncope, sudden cardiac arrest (SCA) or heart transplantation (Htx). Childhood-onset disease was defined as the presence of a cardiac phenotype ≤12 years of age. Results Among 44 LMNA genotype-positive children (age 10.4 [IQR 6.5-12.9] years, 34 relatives), 12 (27 %) became phenotype-positive at a median age of 12.8 [IQR 7.9-14.1] years, of which 7 (58 %) had childhood-onset disease (Figure 1). Nine (18 %) of the children experienced a cardiac event and 44 % of these were ≤12 years of age (Figure 2). Three children had AF, 5 had VT, and one had cardiac syncope. Htx was performed in two unrelated children, at 6 and 8 years of age, respectively. Among the 34 genotype-positive paediatric relatives, 21 % (n=7) became phenotype-positive at a median age of 10.9 [IQR 7.5-15.1] years, of which 57 % (n=4) had childhood-onset disease. Conclusions In a cohort of LMNA genotype children, there was a high prevalence of cardiac events and 44 % of these occurred in children ≤12 years of age. The penetrance of LMNA cardiac phenotype in genotype positive paediatric relatives was 21 %, highlighting the importance of early family screening and cardiological follow-up.

Right ventricular global longitudinal strain is associated with cardiovascular outcome in left ventricular non-compaction phenotype

Abstract Introduction Speckle-tracking echocardiography is an increasingly important tool for assessing left ventricular non-compaction (LVNC) phenotype. This study aims to analyse right (RV) and left (LV) ventricular global longitudinal strain (GLS) in patients with LVNC and explore their association with CV outcome during long-term follow-up. Methods From our prospective LVNC cohort study, 40 patients were identified with a comprehensive echocardiographic examination including strain analysis of both ventricles. Strain was determined using TomTec ImageArena v.4.6. A combined endpoint (CV event) was defined to include: atrial flutter/fibrillation, sustained ventricular arrhythmias, cardiac syncope, thromboembolic event, heart failure progression, aborted cardiac arrest, cardiovascular death or heart transplantation. Results Over a median follow-up duration of 8 [6–10] years, 23 (58%) of the patients experienced one or more CV event (event group); while the rest (17 [42%]) did not (no event group). Baseline clinical characteristics of the two groups were comparable except for a significantly older age (P<0.01) and a higher BMI (P=0.033) in the event group. RVGLS (Figure 1) was significantly lower in the event group (-13.9[-17.1 – -10.3]%) compared to no-event group (-17.3[-18.8 – -15.1]%, P=0.019). While LVGLS did not show a significant difference (P=0.112), LVEF was significantly lower (P=0.011) in the event group. Other echocardiographic parameters were comparable between the groups. RVGLS > -14.3% (sens. 61%, spec. 88%, AUC 72%; P = 0.010) was applied as cut-off to identify patients with a higher risk of CV events during follow-up. Kaplan-Meier curves revealed a higher probability of CV events when RVGLS was > -14.3% (ꭓ2 = 10.28, P = 0.001; Figure 2). Univariable regression models showed that RVGLS (HR 1.10; P = 0.013), LVGLS (HR 1.23; P = 0.045), and LVEF (HR 0.95; P = 0.005) were associated with an increased risk of CV events. The association of RVGLS (OR 1.19, P = 0.047) remained independent of LV GLS and LVEF in a multivariable logistic regression analysis. When RVGLS was included to the LV function model, a significant improvement was noted (ꭓ2 from 7.31 to 11.58; ANOVA P = 0.009). Conclusions RVGLS differentiated LVNC patients suffering a CV event from those who did not and provided incremental value to the association of LV function (LVEF and LVGLS) with an increased risk of CV events. These findings highlight the potential value of RVGLS for evaluating long-term outcome during follow-up of LVNC patients.

Clinical value of insertable loop recorder: single centre experience

Abstract Background The aetiology of syncope can be challenging to undermine because of its sporadic nature. Implantable loop recorders (ILR) are recommended to be used early in undetermined syncope to establish a symptom – rhythm correlation if cardiac syncope is suspected. Real world diagnostic yield of ILR is not well established. Purpose To evaluate the diagnostic yield of ILR devices in patients with undetermined syncope. Methods This single centre, retrospective study, reviewed the electronic medical records of all patients, who underwent ILR insertion for syncope from January 2017 to June 2022. Abnormal rhythm strips on ILR were reviewed by a cardiac physiologist and cardiology consultant to determine its significance. Primary outcome was to determine the total number of cardiac implantable electronic devices (CIEDs) inserted due to ILR findings. Secondary outcomes included (1) a baseline characteristics comparison between the group of patients who had an arrhythmia detected on ILR and patients who had detected no arrhythmia, and (2) the total number of clinical significant events (CSEs), defined as a symptomatic arrhythmia, an asymptomatic arrhythmia deemed clinically related to the patients’ history of syncope, and the absence of an arrhythmia when the patient experienced syncope. Complications of ILR insertion were recorded. Given that normality was not assumed, a non-parametric analysis was utilised to compare baseline characteristics. Results A total of 215 patients were included in this study, of which 43 (20%) had a CIED inserted due to ILR findings. Baseline characteristics were similar between the groups except age (Table 1). 103 (47.9%) of the patients had a CSE (Figure 1). Symptomatic arrhythmias were the most common clinically significant events, out of which a sinus pause of greater than 6 seconds was most prevalent arrhythmia. There were no complications that required early explant of the ILR in this cohort. Conclusion ILR detected a clinically significant arrhythmia and the absence of an arrhythmia in 42.7% and 5.1% of patients with undetermined syncope, respectively. ILR use is a valuable diagnostic tool in this cohort of patients. Further studies looking at cost-effectiveness would be beneficial.Baseline characteristicsCSE and arrhythmias

Abstract 17871: Heterozygous Carriers of KCNQ1 Variants Associated With the Jervell-Lange-Nielsen Syndrome Have a Better Outcome When Compared to Other Type 1 LQTS Patients

Background: KCNQ1 mutations are associated with a risk of life-threatening torsade de Pointes. In the most common presentation, the mutation is heterozygous (type 1 LQTS). The homozygous expression causes type 1 Jervell-Lange-Nielsen syndrome (JLNS) with deafness and higher risk of sudden cardiac death. Hypothesis: Heterozygous carriers of JLN mutations would have different phenotype expression than patients carrying other KCNQ1 variants. Aims: To evaluate QTc duration and incidence of LQTS-related cardiac events according to genetic presentation. Methods: All patients with class 4 or 5 KCNQ1 variants for LQT1 or JLNS followed in our center (September 1993 to January 2023) were included. Lifelong Severe Cardiac events (ACA, SCD, appropriate shocks) and cardiac events (severe event + cardiac syncope) were collected.Quantitative data were compared between groups by ANOVA. Kaplan-Meier survival curves with the log-rank test were used to compare survival between the groups. Results: Three groups were identified among 741 LQT1 patients (55.3% female, age at diagnosis 25.2 years); 30 JLNS (group 1), 557 LQT1 carrying heterozygous mutations not found in the JLNS population (group 2), and 154 heterozygous carriers of mutations found in the JLNS population (group 3). QTc interval duration was different between groups (548±60ms, 467±36ms and 450±31ms in group 1, 2, 3 respectively, p<0.001).Patients carrying heterozygous JLN mutations (group 3) had a lower risk for cardiac events than patients with heterozygous non JLN mutations (group2) (HR 0.36 [0.23-0.57]; p<0.01) (Figure). Four parameters were independently associated with cardiac events: QTc (HR 1.01 [1.01-1.01]; p<0.01, haploinsufficiency (HR 0.57 [0.36-0.92]; p<0.05), pore localization (HR 1.63 [1.16-2.30]; p<0.01), and group (HR 0.50 [0.32-0.81]; p<0.01). Conclusion: Heterozygous carriers of JLNS variants have a lower risk of cardiac arrhythmic events that other type 1 LQTS patients.

Paroxysmal Throbbing Pain Precipitated by Swallowing, Followed by Syncope, are Fatal Processes of Glossopharyngeal Neuralgia

Glossopharyngeal neuralgia is not a simple disease with just sensory neurodynia, which could be followed by fatal cardiac syncope.

Unveiling The Diagnostic Pitfall: Complete Heart Block Presenting in Acute Coronary Syndromes Without Chest Pain and Non-Ischemic Electrocardiography in A Young Adult

Background: The majority of studies indicate that the asymptomatic or atypical presentation of acute coronary syndrome (ACS) as a significant manifestation of coronary artery disease (CAD) is associated with a poor prognosis. The purpose of this study was to characterize the clinical characteristics and management of ACS patients who presented without chest pain and non-ischemic electrocardiogram (ECG). Case Illustration: A 31 years old man with syncope was brought to our hospital. ECG revealed total AV block (TAVB) without ST segment changes. First, he was diagnosed with cardiac syncope because his ECG showed no ischemic sign. He had a strong familial history of CAD, so we examined his cardiac enzymes and found an increase in serial cardiac enzymes. Then, he was diagnosed with non-ST elevation myocardial infarction (NSTEMI). Early invasive strategy with chronic total occlusion (CTO) at osteal right coronary artery (RCA) and acute total occlusion at mid RCA with implantation of 1 DES at osteal-proximal RCA was selected for this patient. After five days of hospitalization, he discharged home with medicines. Conclusion: In order to significantly lower their morbidity and mortality, this group of high-risk patients needs to receive improved early diagnostic and treatment choices. Keyword: Acute Coronary Syndrome, Chest Pain, Heart Block.

Focal Onset Seizures: New Treatment Options in The Clinical Practice

This symposium took place during the 2023 Congress of the European Academy of Neurology (EAN). Mar Carreño, Director, Epilepsy Unit, Hospital Clínic and Instituto Clavel, Barcelona, Spain, presented the definition of drug-resistant epilepsy (DRE), and stressed that uncontrolled epilepsy does not necessarily indicate DRE. Before a diagnosis of DRE is made in a patient not responding to medication, questions should be asked regarding the initial epilepsy diagnosis. Carreño discussed paroxysmal events that may mimic epilepsy, and presented three cases of misdiagnosed DRE that were subsequently correctly identified as cardiac syncope, a psychogenic event, and use of inappropriate medication in a patient with generalised epilepsy. The second part of Carreño’s presentation focused on patients with confirmed DRE. They outlined the complications of DRE, including sudden unexpected death in epilepsy (SUDEP), which should be discussed with the patient. Carreño finished their lecture with a discussion of comorbid conditions, including neuropsychiatric comorbidities, which affect one in three patients with epilepsy. Bernhard J. Steinhoff, Medical Director, Kork Epilepsy Center, Kehl, Germany, then discussed the clinical approach to patients with DRE, including treatment options, the range of anti-seizure medications (ASM), and the reasons for failure of first-line treatment, noting that the probability of achieving seizure freedom decreases with each failed ASM. Steinhoff explored the options of substitution monotherapy or combination therapy after failure of the first ASM, before describing cenobamate (CNB) add-on therapy. A randomised, placebo-controlled, dose-response trial showed that adjunctive CNB reduced focal (partial)-onset seizure frequency in a dose-related fashion. Several papers have been published providing real-world evidence to show that adjunctive CNB therapy is associated with improved seizure outcomes, and that the number of concomitant ASMs could be reduced. The symposium concluded with a question and answer session.

Definitive aetiology of unexplained syncope after cardiovascular autonomic tests in a tertiary syncope unit.

Syncope is a common condition with many possible causes, ranging from benign to life-threatening aetiologies. Establishing a diagnosis can be difficult, and specialized syncope units, using cardiovascular autonomic tests (CATs), including a head-up tilt test, can increase the diagnostic yield. However, up to one-fifth of examined patients have inconclusive CAT results. The aim of the present study was to investigate the predictive value of history, and clinical findings for unexplained syncope after CAT and characterize the group with negative results. Consecutive syncope patients [n = 2663, 61% women, median age 52 (32-69) years] were evaluated and CAT explained aetiology of syncope in 79% of cases, whereas 21% remained unexplained. Predictors of negative CAT were older age at first syncope (+8% higher odds per 10-year increment, P = 0.042), higher supine heart rate (HR; +12% per 10 b.p.m.; P = 0.003), absence of prodromes (+48%; P < 0.001), hypertension (+45%; P = 0.003), diabetes (+82%; P < 0.001), heart failure (+98%; P = 0.014), and coronary artery disease (+51%; P = 0.027). Compared with vasovagal syncope, patients with negative CAT were older, reported more often the absence of prodromes, and had a higher burden of cardiovascular comorbidities. A cardiovascular autonomic test established the cause of syncope in 79% of patients evaluated in a syncope unit. Syncope without prodromes and cardiovascular comorbidities were significant predictors of failure to reveal an aetiology from assessment by CAT. These are known risk factors for cardiac syncope and patients with inconclusive CAT warrant further investigation.

Clinical analysis of sixty-nine children with anomalous aortic origin of the coronary artery

We aimed to analyse the clinical characteristics of children with different types of anomalous aortic origin of the coronary artery (AAOCA) at different ages, and to discuss the factors related to myocardial ischaemia. In this retrospective study, we included 69 children diagnosed with AAOCA using CT coronary angiography; we classified the participants based on the type of AAOCA, age, and high-risk anatomy. The clinical characteristics of the different AAOCA types and age groups were compared, and the correlation between manifestations and high-risk anatomy was analysed. Anomalous origin of the left coronary artery from the right coronary artery sinus, anomalous origin of the right coronary artery from the left coronary artery sinus, and a coronary artery origin without coronary sinuses was found in 10 (14.5%), 57 (82.6%), 2 (2.9%) patients, respectively. There were no significant differences in sex, clinical manifestations, percentage of positive myocardial injury markers, electrocardiogram, transthoracic echocardiography, or proportion of high-risk anatomy among the groups with different AAOCA types. According to age group, the proportion of asymptomatic infants and pre-schoolers was the highest (p < 0.001). Forty-three patients (62.3%) had high-risk anatomy and were more likely to present with severe symptoms and cardiac syncope (p < 0.05). Conclusion: There were no significant differences in the proportions of high-risk anatomy and clinical characteristics among children with different AAOCA types. We found a relation between the severity of AAOCA clinical symptoms and anatomical risk.What is Known:• Clinical symptoms in children with AAOCA are varied and the results of routine cardiological examinations lack specificity.• High-risk anatomical features, exercise, cardiac symptoms, and ALCA are risk factors for the occurrence of SCD in patients with AAOCA.What is New:• Compared the clinical characteristics of different types of AAOCA and ages.• Analysed the correlation between symptoms and high-risk anatomical features.

Investigation of cardiac arrhythmia events in patients treated with lamotrigine: FDA adverse event reporing system analysis.

In October 2020 and March 2021, the U.S. Food and Drug Administration (FDA) classified lamotrigine as a class IB antiarrhythmic, announcing an increased risk of heart rhythm problems. We sought to investigate the nature of the arrhythmia signal with lamotrigine use compared to anticonvulsants with sodium-blocking and non-sodium-blocking mechanisms. This retrospective pharmacovigilance case-non-case study used disproportionality analysis to detect signals of adverse reaction of interest reported with lamotrigine to the FDA Adverse Event Reporting System (FAERS) between 1998 and 2022. Our regression model adjusted for interacting concomitant medications. Sensitivity analyses included stratifying by indication and publication date. Overall, 2917 cases of heart rhythm problems with anticonvulsants were analyzed (1557 female [58.4%] and 1109 male [41.6%]). The mean age ± standard deviation (SD) was 43 ± 19, the groups did not differ significantly by age. Forty cases (7.91%) in the epileptic indication included more than one concomitant medication that influences cardiac conduction. The disproportionality signal for cardiac arrest did not differ for lamotrigine compared with other anticonvulsants, adjusted reporting odds ratio (adj.ROR, .88; 95% CI, .59-1.29) in the epileptic indication. A significantly lower reporting risk for bradyarrhythmia was identified with lamotrigine users in the epileptic population, (adj.ROR, .45; 95% confidence interval [CI], .29-.68). The psychiatric indication demonstrated a sixfold reporting risk for cardiac arrest compared to the epileptic indication. Concomitant medications that affect cardiac conduction, as well as reports on overdose and suicide attempts, were significant variables in psychiatric patients (ROR, 2.45; 95% CI, 2.21-2.71) and (ROR, 1.44; 95% CI, 1.34-1.55), respectively. Our results do not support a significant difference in the reporting risk for cardiac arrest, syncope, tachyarrhythmia, and bradyarrhythmia with lamotrigine in the epileptic indication. Signals of cardiac arrest in lamotrigine could be explained by confounding factors in the psychiatric indication, such as greater concomitant use of medications with cardiac adverse events, and greater reports on overdose and suicide attempts. We recommend that patients with polypharmacy undergo clinical and electrocardiographic monitoring. We illustrate the importance of examining signals for separate indications.

Comment On: Serum Vitamin D Levels in Children and Adolescents with Vasovagal Syncope, Syncope due to Orthostatic Hypotension, and Cardiac Syncope.

Comment On: Serum Vitamin D Levels in Children and Adolescents with Vasovagal Syncope, Syncope due to Orthostatic Hypotension, and Cardiac Syncope.

Syncope and Traffic Crash: A Population-Based Case-Crossover Analysis

BackgroundAmong individuals with recent syncope, recurrence of syncope while driving might incapacitate a driver and cause a motor vehicle crash. Current driving restrictions assume that some forms of syncope transiently increase crash risk. We evaluated whether syncope is associated with a transient increase in crash risk. MethodsWe performed a case-crossover analysis of linked administrative health and driving data from British Columbia, Canada (2010 to 2015). We included licensed drivers who visited an emergency department with "syncope and collapse" and who were involved as a driver in an eligible motor vehicle crash, both within the study interval. Using conditional logistic regression, we compared the rate of emergency visits for syncope in the 28 days before crash (the "pre-crash interval") with the rate of emergency visits for syncope in 3 self-matched 28-day control intervals (ending 6, 12, and 18 months before the crash). ResultsAmong eligible crash-involved drivers, 47 of 3026 pre-crash intervals and 112 of 9078 control intervals had emergency visits for syncope, indicating syncope was not significantly associated with subsequent crash (1.6% vs 1.2%; adjusted odds ratio [OR], 1.27; 95% confidence interval [CI], 0.90-1.79; P = 0.18). There was no significant association between syncope and crash in subgroups at higher risk for adverse outcomes after syncope (eg, age > 65 years, cardiovascular disease, cardiac syncope). ConclusionsIn the context of prevailing modifications of driving behaviour after syncope, an emergency department visit for syncope did not transiently increase the risk of subsequent traffic collision. Overall crash risks after syncope appear to be adequately addressed by current driving restrictions.

Sinus rate and QRS duration on lead V1 predict major events in Brugada syndrome

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Ministère de la Santé Française Background Arrhythmic risk stratification remains a major challenge in asymptomatic Brugada patients. Many studies have evaluated risk stratification performance based on a single or a few ECG-derived parameters measured manually. We aimed to assess the predictive value of multi ECG parameters measured automatically in patients with Brugada syndrome. Materials and Methods We performed a prospective, multicenter cohort study including Brugada patients with at least one available type 1 ECG (either spontaneously or drug-induced) between January 2005 and November 2021. Paper ECG were first digitized and then automatically analyzed using the Glasgow and Bravo algorithms (included in the logiciel CalECG). Clinical data and Brugada related events at diagnosis and during follow-up were collected. Sudden cardiac death, aborted cardiac arrest and appropriate ICD therapy in the VF zone were considered as major events. The predictive value of clinical and ECG parameters for symptomatic status was assessed using uni- and multivariate Cox models. Results ECGs from 301 Brugada patients (77% male, mean age at diagnosis 43 years, follow-up 7±5.6 years) were analyzed. Brugada-related symptoms (cardiac syncope or major event) occurred in 23% of patients before diagnosis and 11% during follow-up (incidence: 1.57%/year). After multivariate Cox analysis, only 2 baseline ECG (without Ajmaline) parameters were significantly associated with major events: RR interval (HR=1.01 (95%CI [1-1.01]), p=0.002) and QRS duration in lead V1 (HR=1.04 (95%CI [1-1.07]), p=0.038). QRS prolongation in lead V1 &amp;gt;113 ms (AUROC 0.69 (95% CI [0.58-0.8])) was associated with a 3-fold increased risk of major event (HR =3.49 (95% CI [1.72-7.09]), p=0.001). Conclusion Many previously described ECG parameter were not associated with major event in Brugada patients after multi-parameter evaluation. Sinus rate and QRS duration on lead V1 were independent risk factor. These results need to be validated on an external cohort. The predictive value of ECG parameters in Brugada syndrome should be assessed using automated multiparametric quantification.

Genotype-phenotype correlation of rare variants in the SCN5A gene in children population

Abstract Funding Acknowledgements Type of funding sources: None. Background Rare variants in the SCN5A gene have been associated with Brugada syndrome (BS), long QT syndrome type 3 (LQTS3), and other conduction disorders that can lead to life-threatening arrhythmias. Variable expressivity, incomplete penetrance and other modifying factors make it difficult to establish a genotype-phenotype correlation, especially in paediatric patients. This, together with the finding of variants of uncertain significance (VUS), makes the genetic diagnosis of arrhythmogenic syndromes challenging. Purpose To describe the phenotypes associated with rare variants in the SCN5A gene in children. Methods This is a retrospective, single-centre descriptive analysis of the phenotypes found in patients (≤18 years of age at diagnosis) carriers of rare variants in the SCN5A gene. Sixty-four children (75% male, median age 8 years – IQR: 3-13 years) from 41 families were included. The variants were classified according to the recommendations of the American College of Medical Genetics. Results 82.8% of patients harboured pathogenic (P) or likely pathogenic (LP) variants and 17.2% VUS. 89.1% was diagnosed with BS, 6.3% with LQTS3, and one family presented atrial fibrillation. Two patients died before the first year of life. Of the patients, 41.9% had symptoms: 21.9% cardiac events (cardiac syncope, resuscitated sudden death, ventricular fibrillation and ventricular tachycardia), 7.9% conduction disorders (sinus node dysfunction, atrioventricular block, bifascicular block) and 4.7% supraventricular arrhythmias (supraventricular tachycardia, atrial fibrillation, flutter). Non-cardiac phenotypes included: epilepsy (10.9%) and febrile seizures (7.8%). 58.1% of patients remained asymptomatic during follow-up (median follow-up 5 years – IQR: 2.25-6). In total, 39 variants were identified, 87.2 were classified as P/LP. Segregation studies allowed the reclassification of 28.2% of VUS as P/LP, 12.8% of the variants remained as VUS. 53.8% of the variants were located in the cytosolic region (Figure 1). Conclusions The presence of rare variants in the SCN5A gene is associated with arrhythmic phenotypes that can trigger cardiac events and lead to sudden death. The most common cardiac symptom in children is syncope. Patients may present with neurological symptoms such as epilepsy and febrile seizures. Identified VUS should be considered and not discarded until a definitive classification is made. VUS segregation can help to clarify the meaning of these variants, but should not be used to identify individuals at risk in the family, nor in clinical decisions. The high number of asymptomatic patients may be explained by the fact that these are diseases in which the onset of symptoms usually occurs in adolescence and later. Most of the variants were found in mutational hot spots, mainly located in the cytosolic and extracellular region of the protein.

Cardiac syncope in an elderly patient: a clinical case from practice

Syncope is the most important, frequently occurring, and difficult to diagnose problem in modern clinical medicine. Often, syncope in the elderly is the first and only symptom of life-threatening arrhythmias and, if not diagnosed in time, increases the risk of sudden cardiac death. The presence of concomitant pathology, primarily cardiological and neurological, makes it difficult to differentiate syncope in elderly and old patients. The combination of the patient’s complaints about transient short-term loss of consciousness and electrocardiographic signs of bifascicular heart block makes the cardiac – arrhythmic cause of syncope to be more probable. The article is devoted to the possibility of diagnosing arrhythmic causes of syncope in elderly and old patients with polymorbid pathology.

Value of programmed electrical stimulation in Brugada Syndrome: a cohort study

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Prognostic value of programmed electrical stimulation (PES) in Brugada Syndrome (BrS) remains controversial. Substantial controversy exists regarding usefulness of PES in identifying BrS patients at risk of sudden cardiac death (SCD). Implantation of an implantable cardioverter-defibrillator is the only reliable form of SCD prevention in this specific population Purpose To determine if induction of sustained ventricular arrhythmia (VA) in PES is a predictor of cardiac events (CE), defined as the composite of SCD, appropriate ICD therapy for VA or unexplained syncope. Methods A retrospective analysis of 34 patients with spontaneous or pharmacologically induced type 1 Brugada pattern, submitted to electrophysiology study with PES between 2015 and 2019 in a Portuguese Center, was performed. Patients were followed for 24 months. Hospital records and monitoring data from cardiac devices were consulted. The Mann-Whitney U test was used for median comparison between groups. Binary logistic regression through the stepwise method was performed to evaluate categorical features. Results 35% (n=12) and 27% (n=9) had spontaneous type 1 and type 2 Brugada pattern in basal electrocardiography, respectively. 23% (n=8) had VA induced by PES. The mean age was 51,2±12,3 years. 71% (n=24) were male. 15% (n=5) had history of cardiac syncope, and 27% (n=9) had a family history of SCD. 9% (n=3) were carriers of a SNC5A mutation. Mean AH time and HV time were, respectively, 105±31,9, and 49±8,5ms. During the 24 months of follow-up, 9% (n=3) suffered a CE (2 unexplained syncope and 1 SCD). None of the patients who suffered CE had VA inducible at PES study. There was no statistical significance in the occurrence of cardiac events when comparing both groups (VA induced in PES vs. no induced arrhythmia) (p=0,49, OR 0,89, IC 95% 0,70;1,02). Through binary logistics, adjusted for potential confounders (gender, history of syncope, history of family SCD and identification of a genetic variant), patients with spontaneous type 1 Brugada pattern in basal electrocardiography were 2,2 times more likely to have a CE (IC 95% 0,12;40,2). Conclusion In this population, VA induced by PES was not a predictor of CE during the follow-up period, which highlights the difficulty of risk stratification in patients with BrS. New risk-stratification tools are urgently needed to select those patients at higher-risk of SCD, which are candidates for prophylactic ICD implantation.

Severity of Brugada syndrome disease manifestation and risk of new-onset depression or anxiety: a Danish nationwide study.

Reduced psychological health is associated with adverse patient outcomes and higher mortality. We aimed to examine if a Brugada syndrome (BrS) diagnosis and symptomatic disease presentation were associated with an increased risk of new-onset depression or anxiety and all-cause mortality. All Danish patients diagnosed with BrS (2006-2018) with no history of psychiatric disease and available for ≥6 months follow-up were identified using nationwide registries and followed for up to 5 years after diagnosis. The development of clinical depression or anxiety was evaluated using the prescription of medication and diagnosis codes. Factors associated with developing new-onset depression or anxiety were determined using a multivariate Cox proportional hazards regression model. Disease manifestation was categorized as symptomatic (aborted cardiac arrest, ventricular tachycardia, or syncope) or asymptomatic/unspecified at diagnosis. A total of 223 patients with BrS and no history of psychiatric disease were identified (72.6% male, median age at diagnosis 46 years, 45.3% symptomatic). Of these, 15.7% (35/223) developed new-onset depression or anxiety after BrS diagnosis (median follow-up 5.0 years). A greater proportion of symptomatic patients developed new-onset depression or anxiety compared with asymptomatic patients [21/101 (20.8%) and 14/122 (11.5%), respectively, P = 0.08]. Symptomatic disease presentation (HR 3.43, 1.46-8.05) and older age (lower vs. upper tertile: HR 4.41, 1.42-13.63) were significantly associated with new-onset depression or anxiety. All-cause mortality in this group of patients treated according to guidelines was low (n = 4, 1.8%); however, 3/4 developed depression or anxiety before death. Approximately, one-sixth of patients with BrS developed new-onset depression or anxiety following a diagnosis of BrS. Symptomatic BrS disease manifestation was significantly associated with new-onset depression or anxiety.

Sinus rate and QRS duration on lead V1 predict major events in Brugada syndrome

Arrhythmic risk stratification remains a major challenge in asymptomatic Brugada patients. Many studies have evaluated risk stratification performance based on a single or a few ECG-derived parameters measured manually. We aimed to assess the predictive value of multi ECG parameters measured automatically in patients with Brugada syndrome. We performed a prospective, multicenter cohort study including Brugada patients with at least one available type 1 ECG (either spontaneously or drug-induced) between January 2005 and November 2021. Paper ECG were first digitized and then automatically analyzed using the Glasgow and Bravo algorithms. Clinical data and Brugada related events at diagnosis and during follow-up were collected. Sudden cardiac death, aborted cardiac arrest and appropriate ICD therapy in the VF zone were considered as major events. The predictive value of clinical and ECG parameters for symptomatic status was assessed using uni- and multivariate Cox models. ECGs from 301 Brugada patients (77% male, mean age at diagnosis 43 years, follow-up 7 ± 5.6 years) were analyzed. Brugada-related symptoms (cardiac syncope or major event) occurred in 23% of patients before diagnosis and 11% during follow-up (incidence: 1.57%/year). After multivariate Cox analysis, only 2 baseline ECG (without Ajmaline) parameters were significantly associated with major events: RR interval (HR = 1.01 [95%CI 1–1.01], P = 0.002) and QRS duration in lead V1 (HR = 1.04 [95%CI 1–1.07], P = 0.038). QRS prolongation in lead V1 > 113 ms (AUROC 0.69 [95%CI 0.58–0.8], Fig. 1) was associated with a 3-fold increased risk of major event [Fig. 2] (HR = 3.49 (95% CI [1.72–7.09], P = 0.001). Many previously described ECG parameter were not associated with major event in Brugada patients after multi-parameter evaluation. Sinus rate and QRS duration on lead V1 were independent risk factor. These results need to be validated on an external cohort. The predictive value of ECG parameters in Brugada syndrome should be assessed using automated multiparametric quantification.

PO-03-145 BETA BLOCKERS IN PATIENTS WITH LONG QT SYNDROME: MOVING AWAY FROM ONE-SIZE-FITS-ALL?

Experts in the field recommend using nadolol at 1mg/kg/day and propranolol at 2-3mg/kg/day for patients with long QT syndrome (LQTS), but there are no available studies defining the most effective dose. In our experience, most but not all patients tolerate beta blocker at full dose. To describe our institutional experience with utilizing exercise stress testing (EST) in the subset of LQTS patients who did not tolerate standard beta-blocker dosing. We queried our Inherited Arrhythmia Registry and identified patients with LQTS who were on "submaximal" nadolol/propranolol doses (defined as < 1mg/kg/day for nadolol and < 2mg/kg/day for propranolol) and who had at least one follow up appointment. For those patients, we have devised a practical approach for demonstrating sufficient beta blockade effect by assessing for heart rate (HR) blunting at maximal exercise, which was defined as at least 15-20% decrease from maximal HR. Of 166 patients with LQTS, 51 (53% females, 53% probands) were on “submaximal” beta blocker therapy at time of last follow up and formed our study cohort. Median age at diagnosis and QTc were 15.8 yrs (range: 0.1-50.9 yrs) and 484 ms (400-610 ms) respectively. In terms of LQTS type: 24 had LQT1, 22 had LQT2, 2 had LQT5, 1 had LQT1 + LQT2, 1 had LQT3, and 1 patient had a VUS in CALM3 gene. Cardiac events included: cardiac arrest in 4 (8%) prompting ICD implantation, bradycardia-induced Torsades de Pointes in 2 (4%) prompting pacemaker implantation, recurrent cardiac syncope prompting sympathectomy in 2 (4%) and cardiac syncope in 10 (20%). The distribution of beta blocker dose is shown in Figure 1A and % predicted peak HR on EST as a function of beta blocker dose is shown in Figure 1B. EST data was available in 37 (73%) patients and demonstrated that HR blunting can be achieved with “submaximal” doses. Over a median follow up of 6.3 years and while on intentional “submaximal” beta blocker therapy, 1 (2%) patient had recurrent appropriate ICD shocks prompting referral for sympathectomy, and no patient (0/34, 0%) with adequate HR blunting had a cardiac event. In our institutional LQTS experience, adequate heart rate blunting may be achieved with "submaximal" beta blocker dose. EST may be a useful modality to devise an individualized treatment plan and titrate beta blocker dose to effect, especially in those that cannot tolerate the recommended guideline directed dose.