Echocardiographic Findings in Children of Patients Diagnosed with PRKAG2 Syndrome. / Achados Ecocardiográficos em Crianças de Pacientes com Diagnóstico de Síndrome do PRKAG2.

BACKGROUND: PRKAG2 syndrome typically manifests in adolescence and early adulthood, progressing with left ventricular hypertrophy, arrhythmias, and risk of sudden death. Findings of echocardiographic markers before clinical manifestation in children of patients affected by the disease can facilitate prevention strategies and therapeutic planning for this patient group. OBJECTIVE: To identify the existence of echocardiographic findings that manifest early in children of parents affected by PRKAG2 syndrome, while they are still asymptomatic. METHODS: In this cross-sectional observational study, 7 participants who were children of parents with established diagnosis of PRKAG2 syndrome, between the ages of 9 months and 12 years, with proven genetic diagnosis, underwent conventional and advanced echocardiography. Their findings were compared to those of a control group composed of 7 age- and sex-matched volunteers who were healthy from a cardiovascular point of view. P values < 0.05 were considered significant. RESULTS: Conventional echocardiography showed statistically significantly higher values in the case group for left atrium, interventricular septum, left ventricular posterior wall, indexed ventricular mass, and relative wall thickness (p < 0.05). Global longitudinal systolic strain on 2-dimensional echocardiography did not show statistical significance between the case and control groups. None of the parameters on 3-dimensional echocardiography showed statistical significance between groups. CONCLUSION: Children diagnosed with PRKAG2 showed echocardiographic findings indicative of a tendency toward cardiac hypertrophy. Echocardiography can be a useful tool in the evaluation and follow-up of this patient group before the onset of clinical manifestations.

FUNDAMENTO: A síndrome do PRKAG2 tipicamente se manifesta na adolescência e início da idade adulta, cursando com hipertrofia ventricular esquerda, arritmias e risco de morte súbita. O achado de marcadores ecocardiográficos antes da manifestação clínica nos filhos de pais acometidos pela doença pode facilitar a estratégia de prevenção e planejamento terapêutico para esse grupo de pacientes. OBJETIVO: Identificar a existência de achados ecocardiográficos que se manifestem precocemente nos filhos de pais acometidos por síndrome do PRKAG2, enquanto ainda assintomáticos. MÉTODOS: Estudo observacional transversal em que sete participantes, filhos de pais com diagnóstico estabelecido de síndrome do PRKAG2, com idades entre 9 meses e 12 anos e diagnóstico genético comprovado, foram submetidos à ecocardiografia convencional e por técnicas avançadas, tendo seus achados comparados aos de grupo controle composto por sete voluntários pareados por sexo e idade, hígidos do ponto de vista cardiovascular. Um valor de p < 0,05 foi considerado significante. RESULTADOS: A ecocardiografia convencional mostrou valores aumentados com significância estatística no grupo caso para átrio esquerdo, septo interventricular, parede posterior do ventrículo esquerdo, massa ventricular indexada e espessura relativa da parede (p < 0,05). O strain sistólico longitudinal global obtido pelo ecocardiograma bidimensional não mostrou diferença estatisticamente significativa entre os grupos caso e controle. Nenhum dos parâmetros ao ecocardiograma tridimensional apresentou significância estatística entre os grupos. CONCLUSÃO: Crianças diagnosticadas com PRKAG2 demonstraram achados ecocardiográficos indicativos de tendência à hipertrofia cardíaca. A ecocardiografia pode ser uma ferramenta útil na avaliação e seguimento desse grupo de pacientes, antes do início de manifestações clínicas.

Wolff-Parkinson-White Syndrome in the Preterm Neonate.

Wolff-Parkinson-White (WPW) syndrome is a rare cardiac condition arising from abnormal embryologic development of the annulus fibrosus in combination with the cardiac conduction system. The abnormality results in the development of accessory pathways and preexcitation changes which can provoke episodes of tachyarrhythmias. The most common presentation of WPW syndrome is supraventricular tachycardia. Beyond customary abortive therapy, chronic management strategies vary based upon timing and clinical severity of the initial disease presentation. Prompt diagnosis and rate control have a dramatic impact on the outcomes of morbidity and mortality. The purpose of this article is to present a case study of a preterm infant who manifested with WPW syndrome. Additionally, the article will explore the pathophysiology of WPW syndrome and the timing and presentation of common clinical manifestations of the disease, along with current diagnostic and treatment strategies to achieve optimal patient outcomes in the neonatal population.

Rare Variant in MRC2 Associated With Familial Supraventricular Tachycardia and Wolff-Parkinson-White Syndrome.

BACKGROUND: Accessory pathways are a common cause of supraventricular tachycardia (SVT) and can lead to sudden cardiac death in otherwise healthy children and adults when associated with Wolff-Parkinson-White syndrome. The goal of this study was to identify genetic variants within a large family with structurally normal hearts affected by SVT and Wolff-Parkinson-White syndrome and determine causality of the gene deficit in a corresponding mouse model. METHODS: Whole exome sequencing performed on 2 distant members of a 3-generation family in which multiple members were affected by SVT or Wolff-Parkinson-White pattern (preexcitation) on ECG identified MRC2 as a candidate gene. Serial electrocardiograms, intracardiac electrophysiology studies, echocardiography, optical mapping studies, and histology were performed on both Mrc2 mutant and WT (wild-type) mice. RESULTS: A rare HET (heterozygous) missense variant c.2969A>G;p.Glu990Gly (E990G) in MRC2 was identified as the leading candidate gene variant segregating with the cardiac phenotype following an autosomal-dominant Mendelian trait segregation pattern with variable expressivity. In vivo electrophysiology studies revealed reentrant SVT in E990G mice. Optical mapping studies in E990G mice demonstrated abnormal retrograde conduction, suggesting the presence of an accessory pathway. Histological analysis of E990G mouse hearts showed a disordered ECM (extracellular matrix) in the annulus fibrosus. Finally, Mrc2 knockdown in human cardiac fibroblasts enhanced accelerated cell migration. CONCLUSIONS: This study identified a rare nonsynonymous variant in the MRC2 gene in individuals with familial reentrant SVT, Wolff-Parkinson-White ECG pattern, and structurally normal hearts. Furthermore, Mrc2 knock-in mice revealed an increased incidence of reentrant SVT and bypass tract formation in the setting of preserved cardiac structure and function.

A case of Williams syndrome with Wolff-Parkinson-White syndrome.

INTRODUCTION: Williams syndrome (WS) cases have been reported to have with 25-100 times greater increased risk of sudden cardiac death (SCD). SCD has been reported in cases without any evidence of structural cardiovascular anomalies. Wolff-Parkinson-White (WPW) syndrome is characterized by short PR interval and delta wave. Ventricular preexcitations can develop paroxysmal reentrant tachycardia through Kent bundle or less frequent atrial fibrillation and in some cases with accessory pathway effective refractory period (APERP) under 250 ms considered as risky and may lead to SCD. WS associated with WPW has not been reported before. CASE REPORT: An 11-year-old male who had been followed up with WS was referred to pediatric cardiology outpatient clinic with the complaint of palpitation. Electrocardiographic examination showed short PR interval and delta wave in the ECG consistent with WPW. He underwent electrophysiological study (EPS). Basic measurements were performed, and APERP was found at 280 ms cycle atrial pacing. RF energy was delivered using a 4 mm tip nonirrigated radiofrequency (RF) ablation catheter where the best ventriculoatrial (VA) signals were received and the AP was abolished within few seconds. DISCUSSION AND CONCLUSIONS: Although, WPW cases are usually asymptomatic or related to SVT, the risk of SCD should not be ignored. Thus, all patients with WPW deserve an EPS for assessing the AP conduction properties. Due to the increased risk of SCD in patients with WS compared to general population, in the presence of concomitant WPW, these patients should be evaluated with EPS even if they do not have symptoms.

Is this an anteroseptal accessory pathway?

The ECG of a patient during sinus rhythm shows preexcited QRS pattern, with rS pattern in lead V1, transition in lead V2, and positive inferior leads. Following the stepwise algorithms, the location of accessory pathway (AP) was identified at anteroseptal region. However, the precordial transition in lead V2 indicates mid-septal or posteroseptal AP. The mismatch suggested multiple APs and 5 APs were identified by electrophysiologic study. This case highlights the importance of detailed analysis of ECG in order to achieve adequate ablation.

Evaluation of T-wave memory after accessory pathway ablation in pediatric patients with Wolff-Parkinson-White syndrome.

BACKGROUND: T-wave memory (TWM) is a rare cause of T-wave inversion (TWI). Alterations in ventricular activation due to abnormal depolarization may cause repolarization abnormalities on the ECG, even if myocardial conduction returns to normal. These repolarization changes are defined as TWM. In our study, we aimed to determine the frequency of TWM development and the predictors affecting it in the pediatric population who underwent accessory pathway (AP) ablation due to Wolff-Parkinson-White (WPW) syndrome. METHODS: The data of patients with manifest AP who underwent electrophysiological studies and ablation between 2015 and 2021 were retrospectively analyzed. The study included 180 patients who were under 21 years of age and had at least one year of follow-up after ablation. Patients with structural heart disease, intermittent WPWs, recurrent ablation, other arrhythmia substrates, and those with less than one-year follow-up were excluded from the study. The ECG data of the patients before the procedure, in the first 24 h after the procedure, three months, and in the first year were recorded. The standard ablation technique was used in all patients. RESULTS: Postprocedure TWM was observed in 116 (64.4%) patients. Ninety-three patients (51.7%) had a right-sided AP, and 87 patients (48.3%) had a left-sided AP. The presence of posteroseptal AP was found to be significantly higher in the group that developed TWM. Of these patients, 107 (93.1%) patients showed improvement at the end of the first year. Preprocedural absolute QRS-T angle, postprocedural PR interval, and right posteroseptal pathway location were identified as predictors of TWM. CONCLUSION: The development of TWM is particularly associated with the right-sided pathway location, especially the right posteroseptal pathway location. The predictors of TWM are the preprocedural QRS-T angle, the postprocedural PR interval, and the presence of the right posteroseptal AP.

Ablation of accessory pathways in different anatomic locations using focal pulsed field ablation.

BACKGROUND: Ablation of accessory pathways (APs) is the cornerstone for treatment of patients with Wolff-Parkinson-White syndrome and manifestation of atrioventricular reentrant tachycardia. Pulsed field ablation (PFA) is a new type of nonthermal energy source delivered to the underlying tissue via the ablation catheter and used for ablation of arrhythmic substrates. OBJECTIVE: The purpose of this study was to determine the efficiency and long-term outcome of ablation of APs of different localizations using a focal pulsed electrical field. METHODS: Electrophysiological study was performed in patients with indication for AP ablation. An ablation catheter was used to map the position of AP insertion. Pulsed electric field was delivered through a standard ablation catheter. In left-sided APs, the first ablation attempt was within the coronary sinus (CS). Patient follow-up was scheduled 1-3 months after the ablation. Additional check-up was performed after 6 and 12 months. RESULTS: Fourteen 14 patients (3 pediatric) were treated. Termination of AP conduction was achieved in all procedures. The cohort consisted of 3 right free wall, 3 posteroseptal, and 8 left-sided APs. Ablation through CS was successfully used in 7 of 8 patients with left-sided APs. No complications were reported. Median follow-up was 5.5 months. Conduction recurrence through AP was documented in 1 patient. CONCLUSION: Focal PFA for AP shows promising results in terms of efficacy and safety. A high rate of successful termination of left-sided APs by ablation within CS may represent a new standard approach. The safety and efficacy profile of PFA seems to be transferable to the pediatric population.

EPM algorithm: A stepwise approach to accessory pathway localization in ventricular pre-excitation.

BACKGROUND: Accurate estimation of accessory pathway (AP) localization in patients with ventricular pre-excitation or Wolff-Parkinson-White (WPW) syndrome remains a diagnostic challenge. Existing algorithms have contributed significantly to this area, but alternative algorithms can offer additional perspectives and approaches to AP localization. OBJECTIVE: This study introduces and evaluates the diagnostic accuracy of the EPM algorithm in AP localization, comparing it with established algorithms Arruda and EASY. METHODS: A retrospective analysis was conducted on 138 patients from Hospital São Paulo who underwent catheter ablation. Three blinded examiners assessed the EPM algorithm's diagnostic accuracy against the Arruda and EASY algorithms. The gold standard for comparison was the radioscopic position of the AP where radiofrequency ablation led to pre-excitation disappearance on the ECG. RESULTS: EPM showed a diagnostic accuracy of 51.45%, closely aligning with Arruda (53.29%) and EASY (44.69%). Adjacency accuracy for EPM was 70.67%, with Arruda at 66.18% and EASY at 72.22%. Sensitivity for EPM in distinguishing left vs. right APs was 95.73%, with a specificity of 74.33%. For identifying septal vs. lateral right APs, EPM sensitivity was 82.79% with a specificity of 46.15%. These measures were comparable to those of Arruda and EASY. Inter-observer variability was excellent for EPM, with Kappa statistics over 0.9. CONCLUSION: The EPM algorithm emerges as a reliable tool for AP localization, offering a systematic approach beneficial for therapeutic decision-making in electrophysiology. Its comparable diagnostic accuracy and excellent inter-observer variability underscore its potential clinical applicability. Future research may further validate its efficacy in a broader clinical setting.

Comparison of the Limb-lead Electrocardiogram to the 12-Lead Electrocardiogram for Identifying Conditions Associated with Sudden Cardiac Death in Youth Athletes.

The optimal screening strategy to prevent sudden cardiac death (SCD) in athletes remains unknown. Pre-participation screening with electrocardiogram (ECG) remains controversial. The utility and accuracy of limb-lead (LL) ECG alone in identifying cardiac abnormalities associated with SCD has not been studied. This study was a comparative secondary data analysis, comparing the interpretation accuracy of 4 physicians evaluating publicly available ECGs of the most common cardiac conditions associated with SCD in athletes. Each physician interpreted a total of 100 ECGs: 50 normal ECGs (25 LL and 25 standard 12L) and 50 abnormal ECGs (25 LL and 25 standard 12L). The agreement between LL ECGs and 12L ECGs was assessed by Cohen's kappa coefficient and the accuracy of identifying an abnormal ECG was compared across LL and 12L ECGs using a chi-squared test. Inter-rater reliability was assessed by estimating the Fleiss's kappa coefficient. The sensitivity of LL ECG and 12L ECG was identical at 86%. The specificity of LL ECG was 75% (95% CI = 65% to 83%) and 12L ECG was 82% (95% CI = 73% to 89%). Substantial agreement was seen between LL ECG and 12L ECG interpretation across all readers (k = 0.63; 95% CI = 0.49 to 0.77). Interpretation accuracy was 81% (95% CI = 74% to 86%) and 84% (95% CI 78% to 89%) using LL ECG and 12L ECG, respectively (p = 0.43). In conclusion, the accuracy, sensitivity, and specificity were high and comparable for both LL ECG and 12L ECG in identifying cardiovascular conditions associated with SCD. Agreement between LL ECG and 12L ECG was substantial.

The use of intravenous amiodarone in patients with atrial fibrillation and Wolff-Parkinson-White syndrome.

BACKGROUND: It was reported that intravenous amiodarone might induce ventricular fibrillation for acute treatment in patients with atrial fibrillation (AF) and Wolff-Parkinson-White (WPW) syndrome. No study was done to assess its application comprehensively in this population. METHODS: This study was a retrospective analysis and undertaken by reviewing medical records and electronic databases to search for patients admitted with tachycardia resulting from WPW syndrome and AF, who have intravenously administrated amiodarone at the emergency department from January 2008 to June 2018. RESULTS: Thirty patients were involved in this study, of which 27 were males. The mean age of the patients was 47.8 ± 17.0 years. The mean systolic blood pressure and diastolic blood pressure were 111.9 ± 18.3 mmHg and 76.1 ± 14.6 mmHg, respectively. The mean heart rate was 171 (150-189) beats per minute. Half of the patients (53.3%) had no comorbidities, and only one had prior syncope. Nearly 17 patients (56.7%) started with a loading dose of 150 mg. No ventricular acceleration or VF developed. The incidence of hypotension was 3.3% (1/30). Eighteen patients (60.0%) restored to sinus rhythm by amiodarone with the conversion time of 486.0 (229.0-1278.0) minutes. CONCLUSIONS: Intravenous amiodarone might be an alternative for acute treatment of AF and WPW syndrome in patients characterized by stable hemodynamics, relatively low admission heart rate, few comorbidities, elder age, and no prior syncope. The loading dosage of 150 mg appeared to be preferred, and the maintenance period was better to less than 12 hours. Monitoring and electrolyte correction were also necessary. It is essential to keep a defibrillator nearby during pharmacologic cardioversion.

Change of Paradigm in the Management of Patients with Accessory Pathways over the Last Forty Years: Wolff-Parkinson-White Syndrome as an Electrophysiological Marvel at Risk of Extinction.

Over the last decades, the approach to the Wolff-Parkinson-White syndrome, as well as its treatment, has substantially changed, leading to improvement in the prognosis and quality of life of these patients. From the first diagnostic electrophysiologic studies to the most recent evaluations, important data on pathophysiologic and clinical aspects have been gathered, and this learning journey is still not concluded. This body of knowledge is a fundamental part of any cardiologists' armamentarium despite the fact that this syndrome is rarely observed in adult patients.

Accessory Pathway-Mediated Tachycardias: Precision Electrocardiology Through Standard and Advanced Electrocardiogram Recording Techniques.

An accessory pathway (AP) can be apparent during sinus rhythm if it depolarizes part of the ventricles ahead of the normal wave front from the conduction system. An AP can generate an anatomic circuit able to sustain a macroreentrant atrioventricular reentrant tachycardia. This arrhythmia can engage the normal conducting system in an antegrade direction or retrogradely, generating, respectively, a narrow or a wide complex tachycardia. The combined use of a standard electrocardiogram and an esophageal recording-pacing can be particularly useful in the first approach to patients with Wolff-Parkinson-White syndrome, further stratifying patients requiring electrophysiology study and transcatheter ablation.

Algorithms to Identify Accessory Pathways' Location on the 12-Lead Electrocardiogram.

The ability to estimate accessory pathway (AP) position enables pre-procedural planning, reduces mapping times, and improves risk estimates as part of the patient consent process. In this article, the nomenclature and important concepts of AP localization algorithms are outlined. An overview of three prominent algorithms is then provided. Each represents an era of invasive treatment of APs: surgical therapy, endocardial ablation, and contemporary electroanatomic mapping. In this manner, the premises, pitfalls, and evolution of AP localization algorithms are illustrated. In addition, the pertinent features of their work are distilled in a simplified topographic algorithm with the interventional electrophysiologist in mind.

Sudden Cardiac Death in Patients with Ventricular Preexcitation.

Patients with the Wolff-Parkinson-White syndrome may experience benign and malignant arrhythmias, the most common being atrioventricular reentrant tachycardias. This arrhythmia may degenerate into atrial fibrillation, which can be conducted over an accessory pathway capable of exceptionally fast conduction to the ventricles and degenerate into ventricular fibrillation, leading to sudden cardiac death. These life-threatening events generally affect symptomatic patients in their third or fourth decade. Although rare, ventricular fibrillation may be the first clinical manifestation in subjects who are asymptomatic or unaware of their conditions. Electrophysiologic study may be useful to identify subjects at high risk of sudden cardiac death.

Methodology of Typical Accessory Pathway Catheter Ablation.

Accessory pathways are abnormal electrical conductions between the atrial and ventricular myocardium, bypassing the atrioventricular node and as such are an important substrate for arrhythmias. Ablation is a curative treatment and should always be offered to symptomatic patients and asymptomatic patients with high risk professions. Adequate knowledge and understanding of different mapping and ablation techniques is pivotal to achieve successful outcomes.