Coved ST-segment Elevation Research Articles

Non-invasive cardiac activation mapping and identification of severity of epicardial substrate in Brugada Syndrome: a case report

IntroductionIt has recently been shown that electrocardiographic imaging (ECGi) can be employed in individuals undergoing an ajmaline test who have Brugada Syndrome (BrS), to evaluate the extent of substrate-involved arrhythmia in the right ventricular overflow tract (RVOT). For the first time, we stratify the risk of sudden cardiac death (SCD) in BrS during ajmaline testing using the dST-Tiso interval (a robust predictor of the inducibility of ventricular arrhythmias (VAs) in the presence of drug-induced BrS type-1 pattern) in combination with ECGi technology.Case presentationWe studied a 48-year-old man with BrS ECG type-2 pattern and presence of J-wave without a family history of SCD but with a previous syncope. Transthoracic echocardiography and cardiac magnetic resonance imaging were performed, showing normal results. The ECG was performed to assess the novel ECG marker “dST-Tiso interval.” The 3D epicardial mapping of the RVOT surface was performed with the support of a non-contact cardiac mapping system in sinus rhythm during ajmaline infusion. The examination of the propagation map unveiled the presence of multiple conduction blocks in this pathologic epicardial region, and the conduction blocks were identified within the central part and/or near the boundary separating the normal and slow conduction areas.ConclusionThe dST-Tiso interval, which lies between the onset and termination of the coved ST-segment elevation and serves as a robust predictor of VA inducibility in cases of drug-induced BrS type-1 pattern, was utilized in conjunction with ECGi technology (employed for the non-invasive confirmation and identification of the pathological substrate area). This combined approach was applied to stratify the risk of SCD in BrS during ajmaline testing, alongside clinical scores.

Predicting ventricular arrhythmia inducibility in ajmaline-induced brugada type I pattern: validation of the dST-Tiso interval

Abstract Background The dST-Tiso is the interval between the onset of the coved ST-segment elevation and its termination at the isoelectric line in V1 and V2 electrocardiographic (ECG) leads during manifest Brugada (BrS) type I pattern. A dST-Tiso >300 ms was proposed as a predictor of ventricular arrythmia (VA) inducibility in patients with ajmaline-induced pattern. Purpose The aim of this study was to validate this criterion in an independent data set. Methods Consecutive patients with a BrS type I ECG pattern found after ajmaline administration underwent programmed ventricular stimulation (PVS). dST-Tiso was measured in all patients and tested as a predictor of positive VA inducibility. Results In our institution, a total of 128 patients (median age 43 years, 59% male) with drug-induced BrS Type I ECG pattern underwent PVS between January 2021 and December 2022. Thirty-two patients (25.0%) had VA inducibility that required defibrillation. Compared to non-inducible subjects, those with positive PVS were more frequently male (81% vs 51%, p=0.003), had longer PQ (165 vs. 160 ms, p=0.016) and dST-Tiso (310 vs 230 ms, p<0.001) intervals, and shorter QT interval (412 vs. 420 ms, p=0.022). The figure shows the distribution of dST-Tiso intervals for patients with not inducible and inducible VA. As a continuous variable, dST-Tiso confirmed significant association with VA inducibility with an adjusted odds ratio of 1.02 (95% CI 1.01-1.03, p<0.001) for each 1 ms increase in duration. A dST-Tiso interval >300 ms yielded a sensitivity of 75%, a specificity of 86%, positive and negative predictive values of 69% and 91%, respectively. Conclusion The validation of the estimation model based on the dST-Tiso interval >300 ms confirmed its high accuracy in predicting VA inducibility in drug-induced BrS type I pattern. This simple ECG marker might be related to the extent of the electrical substrate of the disease.Distribution of dST-Tiso intervals

SCN5A mutation is associated with a higher Shanghai Score in patients with type 1 Brugada ECG pattern.

Brugada syndrome (BrS) is an inherited arrhythmic disease characterized by a coved ST-segment elevation in the right precordial electrocardiogram leads (type 1 ECG pattern) and is associated with a risk of malignant ventricular arrhythmias and sudden cardiac death. In order to assess the predictive value of the Shanghai Score System for the presence of a SCN5A mutation in clinical practice, we studied a cohort of 125 patients with spontaneous or fever/drug-induced BrS type 1 ECG pattern, variably associated with symptoms and a positive family history. The Shanghai Score System items were collected for each patient and PR and QRS complex intervals were measured. Patients were genotyped through a next-generation sequencing (NGS) custom panel for the presence of SCN5A mutations and the common SCN5A polymorphism (H558R). The total Shanghai Score was higher in SCN5A+ patients than in SCN5A- patients. The 81% of SCN5A+ patients and the 100% of patients with a SCN5A truncating variant exhibit a spontaneous type 1 ECG pattern. A significant increase in PR (P = 0.006) and QRS (P = 0.02) was detected in the SCN5A+ group. The presence of the common H558R polymorphism did not significantly correlate with any of the items of the Shanghai Score, nor with the total score of the system. Data from our study suggest the usefulness of Shanghai Score collection in clinical practice in order to maximize genetic test appropriateness. Our data further highlight SCN5A mutations as a cause of conduction impairment in BrS patients.

Use, misuse, and pitfalls of the drug challenge test in the diagnosis of the Brugada syndrome.

The diagnosis of Brugada syndrome (BrS) requires the presence of a coved (Type 1) ST segment elevation in the right precordial leads of the electrocardiogram (ECG). The dynamic nature of the ECG is well known, and in patients with suspected BrS but non-diagnostic ECG at baseline, a sodium channel blocker test (SCBT) is routinely used to unmask BrS. There is little doubt, however, that in asymptomatic patients, a drug-induced Brugada pattern is associated with a much better prognosis compared to a spontaneous Type 1 ECG. The SCBT is also increasingly used to delineate the arrhythmogenic substrate during ablation studies. In the absence of a "gold standard" for the diagnosis of BrS, sensitivity and specificity of the SCBT remain elusive. By studying patient groups with different underlying diseases, it has become clear that the specificity of the test may not be optimal. This review aims to discuss the pitfalls of the SCBT and provides some directions in whom and when to perform the test. It is concluded that because of the debated specificity and the overall very low risk for future events in asymptomatic individuals, patients should be properly selected and counseled before SCBT is performed and that SCBT should not be performed in asymptomatic patients with a Type 2 Brugada pattern and no family history of BrS or sudden death.

BRUGADA-LIKE ECG PATTERN AND TUMORS INVOLVING RIGHT VENTRICULAR OUTFLOW TRACT - CASE SERIES AND LITERATURE REVIEW.

Mechanical heart compression, including that from mediastinal tumor, may cause Brugada-like ECG pattern. Such ECG pattern might also be observed in intracardiac tumor obstructing the right ventricular out"ow tract (RVOT). Eight cases with Brugada-like ECG and tumors involving RVOT have been described so far; 4 growing in the mediastinum (with one example of in"ammatory mass), 3 with intracardiac location, and 1 being an organized pericardial hematoma. The authors present other 3 cases of intracardiac metastatic tumors in RVOT and Brugada-like ECG pattern with coved ST-segment elevation in the right precordial leads. All patients had negative history of cardiovascular disease or familiar malignant arrhythmia occurrence. ECG were done routinely; none of the patients had chest pain or an increased level of cardiac troponins. In all patients, neoplastic disease was at advanced stage. A 76-year-old male, had a history of four neoplasms: bladder cancer was being treated with chemotherapy, while prostate, tongue, and lung cancers had been resected years ago and no signs of local relapse were found. A 78-year-old female, was diagnosed with colon cancer 1 month after an episode of venous thromboembolism. Six months after the resection of cancer, second focus of adenocarcinoma was found in the rectum. Third patient, a 65-year-old-male had undergone nephrectomy for renal cancer a year before cardiac metastasis diagnosis.

Brugada Syndrome

Brugada syndrome (BrS) is an "inherited" condition characterized by predisposition to syncope and cardiac arrest, predominantly during sleep. The prevalence is ∼1:2,000, and is more commonly diagnosed in young to middle-aged males, although patient sex does not appear to impact prognosis. Despite the perception of BrS being an inherited arrhythmia syndrome, most cases are not associated with a single causative gene variant. Electrocardiogram (ECG) findings support variable extent of depolarization and repolarization changes, with coved ST-segment elevation ≥2 mm and a negative T-wave in the right precordial leads. These ECG changes are often intermittent, and may be provoked by fever or sodium channel blocker challenge. Growing evidence from cardiac imaging, epicardial ablation, and pathology studies suggests the presence of an epicardial arrhythmic substrate within the right ventricular outflow tract. Risk stratification aims to identify those who are at increased risk of sudden cardiac death, with well-established factors being the presence of spontaneous ECG changes and a history of cardiac arrest or cardiogenic syncope. Current management involves conservative measures in asymptomatic patients, including fever management and drug avoidance. Symptomatic patients typically undergo implantable cardioverter defibrillator insertion, with quinidine and epicardial ablation used for patients with recurrent arrhythmia. This review summarizes our current understanding of BrS and provides clinicians with a practical approach to diagnosis and management.

The Cove in Coronavirus Disease 2019

Brugada pattern is characterized by coved ST-segment elevation found in more than one of the precordial leads V1 through V3. In the emergence of coronavirus disease 2019 (COVID-19) pandemic, transient occurrence of these patterns is rarely observed in patients with severe acute respiratory syndrome coronavirus 2 infections. Whether these electrocardiographic findings develop due to fever or a direct effect of the infection itself is a matter that deserves further investigation. We present a young female and an elderly male with Brugada patterns on electrocardiograms when febrile due to COVID-19. After defervescence, these patterns disappeared and both patients progressively improved. We found nine similar articles, all involving male patients. Thus, our case of the young female patient may be the first reported case. It is worth noting that fever was not entirely simultaneous with the appearance of Brugada patterns in the other reports suggesting the possibility that COVID-19 itself with its unique pathogenic mechanism could directly underlie these electrocardiographic abnormalities.

DST-Tiso Interval, a Novel Electrocardiographic Marker of Ventricular Arrhythmia Inducibility in Individuals With Ajmaline-Induced Brugada Type I Pattern

The aim of this study was to investigate the reliability of a novel electrocardiographic (ECG) marker in predicting ventricular arrhythmia (VA) inducibility in individuals with drug-induced Brugada syndrome (BrS) type I pattern. Consecutive patients with drug-induced type I BrS pattern underwent programmed ventricular stimulation (PVS) and, according to their response, were divided into 2 groups. Clinical characteristics and 12-lead ECG intervals before and after ajmaline infusion were compared between the 2 groups. A novel ECG marker named dST-Tiso interval consisting in the interval between the onset of the coved ST-segment elevation and its termination at the isoelectric line was also evaluated. Our cohort included 76 individuals (median age 44 years, 75% male). Twenty-five (32.9%) had VA inducibility requiring defibrillation. As compared with not inducible subjects, those with VA inducibility were more frequently male (92% vs 65%, p=0.013), had longer PQ interval (basal: 172 vs 152 ms, p=0.033; after ajmaline: 216 vs 200 ms, p=0.040), higher J peak (0.6 vs 0.5 mV, p=0.006) and longer dST-Tiso (360 vs 240 ms, p < 0.001). The dST-Tiso showed a C-statistics of 0.90 (95% confidence interval: 0.82 to 0.99) and an adjusted odds ratio for VA of 1.03 (1.01 to 1.04, p < 0.001). A dST-Tiso interval >300 ms yielded a sensitivity of 92.0%, a specificity of 90.2%, positive and negative predictive values of 82.1% and 95.8%. In conclusion, the dST-Tiso interval is a powerful predictor of VA inducibility in drug-induced BrS type I pattern. External validation is needed, but this marker might be useful in the clinical counseling process of these individuals before invasive PVS.

Inherited Arrhythmia Syndromes.

Inherited Arrhythmia Syndromes.

Brugada Syndrome: Clinical Features, Risk Stratification, and Management.

In 1992, the Brugada brothers published a patient series of aborted sudden death, who were successfully resuscitated from ventricular fibrillation (VF). These patients had a characteristic coved ST-segment elevation in the right precordial leads on their 12-lead electrocardiogram with no apparent structural heart abnormality. This disease was referred to as “right bundle branch block, persistent ST-segment elevation, and sudden death syndrome.” The term Brugada syndrome (BrS) was first coined for this new arrhythmogenic entity in 1996. BrS is more prevalent in Southeast Asian ethnic groups and was considered a familial disease due to the presence of syncope and/or sudden deaths in several members of the same family, however, the genetic alteration was only noted in 1998. The genetic characterization of BrS has proven to be challenging. The most common and well-established BrS genotype involves loss-of-function mutations in the SCN5A gene, but only represents between 15% and 30% of the diagnosed patients. Patients with BrS can present with a range of symptoms which can include syncope, seizures, and nocturnal agonal breathing due to polymorphic ventricular tachycardia or VF. If these arrhythmias are sustained, sudden cardiac death may result. Despite the significant progress on the understanding of BrS over the last two decades, there remain a number of uncertainties and challenges; we present an update review on the subject.

Clinical Presentation and Outcome of Brugada Syndrome Diagnosed With the New 2013 Criteria.

The 2013 HRS/EHRA/APHRS consensus statement recommends the use of V1 and V2 leads recorded in the second and third intercostal spaces (High-ICS) for diagnosis of Brugada syndrome (BrS) creating a new category of patients discovered only with modified leads. The clinical presentation and the arrhythmic risk in these patients are ill defined. This study was aimed at assessing the role of High-ICS in the analysis of BrS and the clinical profile of the patients diagnosed only when ECG leads are moved to upper intercostal spaces. We searched our Brugada syndrome registry and identified 300 subjects (age 36 ± 13 years), without a diagnostic coved ST-segment elevation in conventional V1 -V3 leads, both at baseline and after provocative drug challenge. Sixty-four subjects (21.3%, mean age at last follow-up 42 ± 11 years) were diagnosed with High-ICS. Diagnosis was possible at baseline only in 4 subjects while in 60 it was made after drug challenge with sodium channel blockers. Three subjects (4.7%) with spontaneous abnormal ECG experienced cardiac events with an annual event rate (0.11%) superimposable to that of the low risk category of BrS diagnosed in standard leads. This study demonstrates that the use of new diagnostic criteria for BrS allows increasing the diagnostic yield by 20% and that the arrhythmic risk is low when BrS can be established only in High-ICS. We also show that the prognostic value of spontaneous ECG pattern is confirmed in this subgroup.

Even a Pooled Analysis Does Not Resolve the Debate of Electrophysiology Testing in Brugada Syndrome

Since the first description,1 investigative work into the pathophysiology and clinical management of Brugada syndrome (BrS) has been active. Like other channelopathies, BrS is a cause of sudden cardiac arrest (SCA) in young, otherwise healthy, individuals. Initially attributed to the loss of sodium channel function, BrS has also been attributed to the loss of calcium channel function. Thus, the disease is not solely a sodium channelopathy, but rather related to an imbalance between inward and outward currents during phase 1 of the action potential. The hallmark ECG feature is a type 1 pattern of a coved ST-segment elevation of ≥2 mm followed by a negative T wave, present in >1 right precordial lead (V1 through V3), occurring either spontaneously or provoked with a sodium channel antagonist. However, the ECG in BrS can demonstrate type 1, 2, or 3 patterns, or be normal; and these changes can occur either spontaneously or be related to autonomic tone, physiological parameters (eg, fever), and ECG lead position. BrS, therefore, is a dynamic disease, influenced by ethnicity, sex, genotype, autonomic tone, regionally abnormal myocardium,2 and varied physiological and pharmacological stimuli. With this interplay of pathophysiology, risk stratification of patients with BrS ECG pattern is challenging. Programmed electric stimulation (PES) has been reported to be a useful tool for risk stratification; however, this recommendation is controversial.3–11 Article see p 622 In this issue of Circulation , Sroubek et al12 report on the relationship between inducible malignant ventricular arrhythmias with PES and future occurrence of the primary outcome, defined as SCA or appropriate implantable cardiac defibrillator (ICD) shock therapy. The database consists of multicenter pooled participant-level data from prospective studies identified from a literature search. Included patients were those who underwent PES, who had a spontaneous or sodium channel …

Brugada Syndrome: an Update

More than 20 years have passed since the description of Brugada syndrome as a clinical entity. The original case series depicted patients who all had coved ST-segment elevation in the right precordial leads, associated with a high risk of sudden death and no apparent structural heart disease. As subsequent registry data were published, it became apparent that the spectrum of risk is wide, with the majority of patients classified as low risk. Two consensus documents have been published that will continue to be updated. Despite intense research efforts, many controversies still exist over its pathophysiology and the risk stratification for sudden death. Management continues to be challenging with a lack of drug therapy and high complication rates from implantable cardioverter defibrillators. In this review, we highlight the current state-of-the-art therapies and their controversies.

Brugada phenocopy: new terminology and proposed classification.

Brugada syndrome is a channelopathy characterized on ECG by coved ST-segment elevation (≥2 mm) in the right precordial leads and is associated with an increased risk of malignant ventricular arrhythmias. The term Brugada phenocopy is proposed to describe conditions that induce Brugada-like ECG manifestations in patients without true Brugada syndrome. An extensive review of the literature identified case reports that were classified according to their suspected etiological mechanism. Future directions to learn more about these intriguing cases is discussed.

Brugada Syndrome Unmasked by Febrile Illness in an Asymptomatic Child

4-year-old boy was admitted to the hospital for fever, cough, and chest pain in the last 2 days. Chest radiograph showed pneumonia of the lower left lobe, and antimicrobial medication was administered. Of note, an electrocardiogram (ECG) was performed while the patient had a fever, which revealed coved ST-segment elevation >2 mm in right precordial V1-V2 leads and incomplete right bundlebranch block, compatible with type 1 Brugada syndrome pattern (Figure). This ECG pattern disappeared as the patient’s fever subsided. Echocardiogram excluded structural anomalies. Family history revealed sudden death in a maternal 9-month-old sister and a 5-month-old cousin; no episodes of syncope or arrhythmia were referred. The whole family was screened for Brugada syndrome, and his mother resulted positive. Genetic analysis in the child excluded SCN5A gene mutations. No long-term treatment was started because the patient was asymptomatic and at low risk for sudden death, given his asymptomatic Brugada syndrome ECGpatternduringfeverandhisnegativehistoryforsyncope. Brugada syndrome accounts for 20% of sudden death in young adults, with a prevalence in children of 3 per 10000. 1 Brugada syndrome is inherited in an autosomal-dominant manner 2 and is attributable to cardiac sodium channel muta

Mexiletine Differentially Restores the Trafficking Defects Caused by Two Brugada Syndrome Mutations

The human cardiac sodium channel Nav1.5 encoded by the SCN5A gene plays a critical role in cardiac excitability and the propagation of action potentials. Nav1.5 dysfunctions due to mutations cause cardiac diseases such as the LQT3 form of long QT syndrome, conduction disorders, and Brugada syndrome (BrS). They have also recently been associated with dilated cardiomyopathy. BrS is characterized by coved ST-segment elevation on surface ECGs and lethal ventricular arrhythmias in an apparently structurally normal heart. Nav1.5 mutations that cause BrS result in a loss of channel function. Our aim was to functionally characterize two novel Nav1.5 mutations (A124D and V1378M) in BrS patients. Wild-type (WT) and mutant Nav1.5 channels were expressed in tsA201 cells in the presence of the β1-auxiliary subunit. The patch-clamp technique and immunocytochemistry approaches were used to study the mutant channels and their cellular localization. The two mutant channels displayed a dramatic reduction in current density but had normal gating properties. The reduction in current density was caused by the retention of channel proteins in the endoplasmic reticulum (ER). Mutant channel retention could be partially reversed by incubating transfected cells at 25°C and by treating them with mexiletine (for V1378M but not A124D), or with curcumin or thapsigargin, two drugs that target ER resident proteins. It is likely that the clinical phenotypes observed in these two BrS patients were related to a surface expression defect caused by ER retention.

Rhabdomyoma of the interventricular septum presenting as a Brugada phenocopy

Brugada syndrome is a channelopathy characterised electrocardiographically by distinctive coved ST-segment elevation in the right precordial leads and is associated with a predisposition for sudden death secondary to ventricular arrhythmias in otherwise healthy patients. Previously known as Brugada-like patterns, Brugada phenocopies include agents and conditions that mimic true Brugada syndrome, presenting with an acquired Brugada Type-1 ECG pattern. We describe the first reported case of a 17-month-old female with an asymptomatic rhabdomyoma of the interventricular septum that presented as a Brugada phenocopy.

Brugada Syndrome and SCN5A-Encoded Cardiac Sodium Channel Mutations in Singapore

Introduction:This study aims to characterize patients with Brugada syndrome (BrS) in Singapore, and its association with SCN5A-encoded cardiac sodium channel mutations.Methods:The study population consisted of 30 unrelated individuals (28 males, 93%) with either spontaneous or drug induced type 1 coved ST-segment elevation in leads V1–V3.Results:The mean age of symptom onset was 40.8 years (SD 13.5, min 11, max 72). The mean follow up duration was 3.6 years. Nine patients had an ICD implanted, none had appropriate ICD shocks.Mutation in the SCN5A gene was found in 5 out of the 30 individuals (16.7%). The PR interval in SCN5A mutation carriers was significantly prolonged (201.40 +/− 28.35 ms vs 168.92 +/− 27.67 ms, p=0.024). One individual had compound heterozygous mutation and presented with syncope and VT at the age of 11. A total of 6 mutations were identified, four of which were novel (67%).Conclusion:In this study, a mutation in the SCN5A gene was found in 16.7% of patients with BrS. The presence of a SCN5A mutation results in a longer PR interval. Compound heterozygosity in one individual appears to confer a more severe phenotype and an earlier onset of symptoms.

Risk Determinants in Individuals With a Spontaneous Type 1 Brugada ECG

Spontaneous coved ST-segment elevation ≥2 mm followed by a negative T-wave in the right precordial leads (type 1 Brugada ECG) is diagnostic of Brugada syndrome (BS), but there is a false-positive rate. Computer-processed analysis of a 12-lead ECG database containing 49,286 females and 52,779 males was performed to select patients with a spontaneous type 1 Brugada ECG for an examination of the association of this ECG characteristic with long-term prognosis. There were 185 patients with a spontaneous type 1 Brugada ECG and of these, 16 (15 males; mean age, 46.7±14.0 years) were diagnosed with BS and 15 patients (all males; mean age, 50.1±13.4 years) were undiagnosed. The PQ interval was significantly longer in the diagnosed patients than in the undiagnosed patients (187.4±28.3 ms vs. 161.2±21.5 ms; P=0.0073). The T-wave in lead V(1) was more negative in the diagnosed patients than in the undiagnosed patients (-170.2±174.6 µV vs. -43.2±122.3 µV, P=0.027). Multivariate analysis revealed that a PQ interval ≥170 ms and T-wave amplitude <105 µV in lead V(1) were independent risk stratifiers of life-threatening events. Survival analysis (mean follow-up, 78.6±81.8 months) showed that the PQ interval and a negative T-wave in lead V(1) were significantly associated with poor prognosis. Analysis of a standard 12-lead ECG can stratify the prognosis of patients with a spontaneous type 1 Brugada ECG.

Copenhagen city heart study: more mermaids than Brugada's patients in Copenhagen

This editorial refers to ‘The prevalence and relevance of the Brugada-type electrocardiogram in the Danish general population: data from the Copenhagen City Heart Study’ by R. Pecini et al. , on page 982 Since the initial identification of so-called Brugada syndrome by the Brugada brothers in 1992, this specific electrocardiographic pattern has focused attention because of the potential risk of sudden death identified in these patients.1 Progressively, considerable progress has been made in our understanding of this disease. As there can be a great deal of variation in the electrocardiographic (ECG) pattern and as the pattern of the ST-segment elevation is often not easy to analyse since there may be subtle variations from type 1 to type 2 or 3, the publication of the first and second consensus conferences has provided clarification of the diagnosis.2,3 Now, diagnosis of the syndrome can only be made when the typical type 1 ECG pattern is present, characterized by a coved ST-segment elevation of at least 2 mm (0.2 mV) followed by a negative T-wave in two right precordial leads (V1 to V3).3 These criteria are supposed to …