Brugada phenocopy associated with multiple psychotic drugs.

Brugada phenocopy (BrP) is a clinical condition characterized by transient ECG changes of Brugada syndrome (BrS), which can be due to various clinical conditions. We describe a case report of BrP due to psychotic drugs.

Captagon-induced Brugada phenocopy: A report of two cases.

Brugada phenocopies (BrP) represent electrocardiogram changes identical to those of true congenital Brugada syndrome but are induced by reversible clinical conditions. Previous cases have been reported in patients following recreational drug use. This report presents two cases of type 1B BrP associated with Fenethylline abuse, a recreational drug known by its trade name, Captagon.

T-Peak to T-End Interval for Prediction of Positive Response to Ajmaline Challenge Test in Suspected Brugada Syndrome Patients.

BACKGROUND: Brugada syndrome (BrS) is diagnosed in patients with ST-segment elevation with coved-type morphology in the right precordial leads, occurring spontaneously or after provocative drugs. Due to electrocardiographic (ECG) inconsistency, provocative drugs, such as sodium-channel blockers, are useful for unmasking BrS. Ajmaline is superior to flecainide and procainamide to provoke BrS. Prolonged T-peak to T-end (TpTe) is associated with an increased risk of ventricular arrhythmia and sudden cardiac death in Brugada syndrome patients. OBJECTIVE: This study aimed to investigate the predictive value of T-peak to T-end interval and corrected T-peak to T-end interval for predicting the positive response of the ajmaline challenge test in suspected Brugada syndrome patients. METHODS: Patients who underwent the ajmaline test in our center were enrolled. Clinical characteristics and electrocardiographic parameters were analyzed, including TpTe, corrected TpTe, QT, corrected QT(QTc) interval, and S-wave duration, compared with the result of the ajmaline challenge test. RESULTS: The study found that TpTe and corrected TpTe interval in suspected BrS patients were not significantly associated with a positive response to the ajmaline challenge test. CONCLUSIONS: The T-peak to T-end interval and corrected T-peak to T-end interval could not predict the positive response of the ajmaline challenge test in suspected Brugada syndrome patients.

The assessment of cardiac risk in patients taking lamotrigine; a systematic review.

OBJECTIVE: The Food and Drug Administration (FDA) warned about lamotrigine's arrhythmogenicity based on in vitro data. This systematic review investigates lamotrigine's effect on cardiac conduction and risk of sudden cardiac death (SCD) in individuals with and without cardiovascular disease. METHODS: We searched Web of Science and PubMed from inception through August 2021. We included studies measuring electrocardiogram (ECG) changes, laboratory abnormalities, or SCD among patients taking lamotrigine. Studies examining sudden unexpected death in epilepsy were excluded for scope. Two reviewers assessed articles and extracted data. We used the Effective Public Healthcare Panacea Project tool to evaluate confidence in evidence. RESULTS: Eight randomized controlled trials, 9 nonrandomized observational studies, and 24 case reports were identified, with >3054 total participants, >1606 of whom used lamotrigine. One randomized trial of older patients found an average QRS increase of 3.5 +/- 13.1 ms. Fifteen studies reported no changes in ECG parameters. Case reports documented QRS widening (13), Brugada syndrome (6), QTc prolongation (1) and SCD (2), though many ingested toxic quantities of lamotrigine and/or other medications. CONCLUSIONS: Evidence is insufficient to support the breadth of the FDA warning concerning lamotrigine's cardiac risk. Lamotrigine at therapeutic doses may be associated with modest, non-dangerous QRS widening.

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.

Lithium-induced ECG modifications: navigating from acute coronary syndrome to Brugada syndrome.

Lithium is frequently used in the treatment of bipolar disorders and is known to induce ECG alterations. This case study describes various patterns of lithium-induced ECG modifications in a patient with acute-on-chronic lithium intoxication. Clinicians should be familiar with this problem as it can have life-threatening consequences and lead to important changes in patient's management. Our patient was admitted for acute delirium with an ECG showing atrial fibrillation with wide QRS and ST-segment elevation. These modifications were first mistaken for an acute myocardial infarction and a diagnosis of Brugada syndrome was finally reached. Treatment after the acute phase implied changes in the therapeutic modality and required frequent monitoring.

Electrophysiological Study Prognostic Value and Long-Term Outcome in Drug-Induced Type 1 Brugada Syndrome: The IBRYD Study.

OBJECTIVES: This study aimed to retrospectively assess long-term outcome and the prognostic role of electrophysiological study (EPS) for risk stratification of drug-induced type 1 Brugada syndrome (BrS) patients. BACKGROUND: BrS is a hereditary cardiac disease, predisposing to sudden cardiac death. Few real-world data are available on long-term outcomes of drug-induced type 1 BrS patients, and questions about risk stratification still remain unanswered. METHODS: The IBRYD (Italian Brugada Syndrome) study is a multicenter observational retrospective study. A total of 226 drug-induced type 1 BrS patients were enrolled from 9 Italian tertiary referral institutions. Primary endpoint was a composite of appropriate implantable cardioverter-defibrillator (ICD) therapy and sudden cardiac death. The authors further assessed clinical predictors to ICD implantation, as well as for arrhythmia induction at EPS, along with EPS as potential risk factor for the outcomes of interest. RESULTS: 142 patients (62.8%) received an ICD due to syncope and/or inducible ventricular tachyarrhythmias at EPS. During a median follow-up of 106 months, 11 patients (4.9%) experienced primary outcome events. The ICD therapy median annual incidence over 8 years was 0.38% (interquartile range: 0% to 1.47%). Ventricular tachyarrhythmia inducibility during EPS was not predictive of arrhythmic events in ICD recipients versus non-ICD patients and in symptomatic versus asymptomatic subgroups, showing a low positive predictive value (9.6% and 8.9%, respectively) versus a high negative predictive value (96.6% and 95%, respectively). The authors reported 29 ICD-related complications and 4.9% inappropriate shocks. CONCLUSIONS: Drug-induced type 1 BrS patients have a very low arrhythmic risk. Clinical decision for implantation is supported by syncope and/or EPS positivity, though they fail to stratify high-risk patients. A better risk-to-benefit ratio should be pursued, considering both arrhythmic risk and ICD-related complications.

Frequency of Irritable Bowel Syndrome in Patients with Brugada Syndrome and Drug-Induced Type 1 Brugada Pattern.

Irritable bowel syndrome (IBS) is one of the most widely recognized functional bowel disorders (FBDs) with a genetic component. SCN5A gene and SCN1B loci have been identified in population-based IBS cohorts and proposed to have a mechanistic role in the pathophysiology of IBS. These same genes have been associated with Brugada syndrome (BrS). The present study examines the hypothesis that these two inherited syndromes are linked. Prevalence of FBDs over a 12 months period were compared between probands with BrS/drug-induced type 1 Brugada pattern (DI-Type 1 BrP) (n = 148) and a control group (n = 124) matched for age, female sex, presence of arrhythmia and co-morbid conditions. SCN5A/SCN1B genes were screened in 88 patients. Prevalence of IBS was 25% in patients with BrS/DI-Type 1 BrP and 8.1% in the control group (p = 2.34 × 10-4). On stepwise logistic regression analysis, presence of current and/or history of migraine (OR of 2.75; 95% CI: 1.08 to 6.98; p = 0.033) was a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. We identified 8 putative SCN5A/SCN1B variants in 7 (12.3%) patients with BrS/DI-Type 1 BrP and 1 (3.2%) patient in control group. Five out of 8 (62.5%) patients with SCN5A/SCN1B variants had FBDs. In conclusion, IBS is a common co-morbidity in patients with BrS/DI-Type 1 BrP. Presence of current and/or history of migraine are a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. Frequent co-existence of IBS and BrS/DI-Type 1 BrP necessitates cautious use of certain drugs among the therapeutic options for IBS that are known to exacerbate the Brugada phenotype.

Lacosamide induced Brugada I morphology in the setting of septicemia: A case report.

INTRODUCTION: Brugada syndrome may be unmasked by non-antiarrhythmic pharmaceuticals or drugs. Lacosamide is an antiepileptic agent with a novel mechanism of sodium channel inhibition and has the potential to cause cardiac sodium channel blockade. PATIENT CONCERNS: In this report, we describe the case of patient with a history of a seizure disorder who presented with Brugada I electrocardiogram morphology in the setting of septicemia. DIAGNOSIS: Brugada I electrocardiogram morphology was unmasked by lacosamide antiepileptic monotherapy. INTERVENTIONS: Lacosamide therapy was discontinued. OUTCOMES: Normalization of the electrocardiogram and resolution of Brugada morphology occurred on hospital day 1. CONCLUSION: Caution should be exercised in the use of lacosamide in those at risk for conduction delay, or in combination therapy with medications that impair renal clearance, metabolism of lacosamide, or that display inherent sodium channel blocking properties.

Assessment of atrial functional remodeling in patients with atrioventricular nodal reentrant tachycardia with and without drug-induced type 1 Brugada pattern: A case-control study.

PURPOSE: The time interval between the onset of the P-wave on electrocardiogram (ECG) and peak A' velocity of the lateral left atrial wall assessed by tissue Doppler imaging (PA-TDI interval) determine total atrial conduction time (TACT) which reflects atrial remodeling and arrhythmic substrate. In this retrospective study, we aimed to assess TACT in patients with atrioventricular nodal reentrant tachycardia (AVNRT) with and without drug-induced type 1 Brugada electrocardiogram ECG pattern (DI-Type 1 BrP) and control subjects. METHODS: Study population consisted of 62 consecutive patients (46 women; mean age 44 ± 12 years) undergoing electrophysiological study and ablation for symptomatic, drug-resistant AVNRT, and 42 age-matched and sex-matched control subjects. All patients and control subjects underwent ajmaline challenge test and tissue Doppler imaging. RESULTS: A DI-Type 1 BrP was uncovered in 24 of 62 patients with AVNRT (38.7%). PA-TDI interval was similar among AVNRT patients with and without DI-Type 1 BrP (124 ± 12 ms vs 119 ± 14 ms, respectively, P = .32), but significantly longer in patients with AVNRT with as well as without DI-Type 1 BrP than in control subjects (124 ± 12 ms and 119 ± 14 ms vs 105 ± 11 ms, respectively, P < .001). CONCLUSION: The TACT assessed by PA-TDI interval is longer in patients with AVNRT with and without DI-Type 1 BrP than in age-matched and sex-matched healthy control subjects.

Acacetin suppresses the electrocardiographic and arrhythmic manifestations of the J wave syndromes.

BACKGROUND: J wave syndromes (JWS), including Brugada (BrS) and early repolarization syndromes (ERS), are associated with increased risk for life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently very limited. Here, we evaluate the effects of the natural flavone acacetin. METHODS: The effects of acacetin on action potential (AP) morphology and transient outward current (Ito) were first studied in isolated canine RV epicardial myocytes using whole-cell patch clamp techniques. Acacetin's effects on transmembrane APs, unipolar electrograms and transmural ECGs were then studied in isolated coronary-perfused canine RV and LV wedge preparations as well as in whole-heart, Langendorff-perfused preparations from which we recorded a 12 lead ECG and unipolar electrograms. Using floating glass microelectrodes we also recorded transmembrane APs from the RVOT of the whole-heart model. The Ito agonist NS5806, sodium channel blocker ajmaline, calcium channel blocker verapamil or hypothermia (32°C) were used to pharmacologically mimic the genetic defects and conditions associated with JWS, thus eliciting prominent J waves and provoking VT/VF. RESULTS: Acacetin (5-10 µM) reduced Ito density, AP notch and J wave area and totally suppressed the electrocardiographic and arrhythmic manifestation of both BrS and ERS, regardless of the experimental model used. In wedge and whole-heart models of JWS, increasing Ito with NS5806, decreasing INa or ICa (with ajmaline or verapamil) or hypothermia all resulted in accentuation of epicardial AP notch and ECG J waves, resulting in characteristic BrS and ERS phenotypes. Phase 2-reentrant extrasystoles originating from the RVOT triggered VT/VF. The J waves in leads V1 and V2 were never associated with a delay of RVOT activation and always coincided with the appearance of the AP notch recorded from RVOT epicardium. All repolarization defects giving rise to VT/VF in the BrS and ERS models were reversed by acacetin, resulting in total suppression of VT/VF. CONCLUSIONS: We present experimental models of BrS and ERS capable of recapitulating all of the ECG and arrhythmic manifestations of the JWS. Our findings provide definitive support for the repolarization but not the depolarization hypothesis proposed to underlie BrS and point to acacetin as a promising new pharmacologic treatment for JWS.

Recognition and clinical implications of high prevalence of migraine in patients with Brugada syndrome and drug-induced type 1 Brugada pattern.

INTRODUCTION: We have previously reported high 1-year prevalence of migraine in patients with atrial arrhythmias associated with DI-type 1 BrP. The present study was designed to determine the lifetime prevalence of migraine in patients with Brugada syndrome (BrS) or drug-induced type 1 Brugada pattern (DI-type 1 BrP) and control group, to investigate the demographic and clinical characteristics, and to identify clinical variables to predict underlying BrS/DI-type 1 BrP among migraineurs. METHODS AND RESULTS: Lifetime prevalence of migraine and migraine characteristics were compared between probands with BrS/DI-type 1 BrP (n = 257) and control group (n = 370). Lifetime prevalence of migraine was 60.7% in patients with BrS/DI-type 1 BrP and 30.3% in control group (p = 3.6 × 10-14 ). On stepwise regression analysis, familial migraine (odds ratio [OR] of 4.4; 95% confidence interval [CI]: 2.0-9.8; p = 1.3 × 10-4 ), vestibular migraine (OR of 5.4; 95% CI: 1.4-21.0); p = .013), migraine with visual aura (OR of 1.8; 95% CI: 1.0-3.4); p = .04) and younger age-at-onset of migraine (OR of 0.95; 95% CI: 0.93-0.98); p = .004) were predictors of underlying BrS/DI-type 1 BrP among migraineurs. Use of anti-migraine drugs classified as "to be avoided" or "preferably avoided" in patients with BrS and several other anti-migraine drugs with potential cardiac INa /ICa channel blocking properties was present in 25.6% and 26.9% of migraineurs with BrS/DI-type 1 BrP, respectively. CONCLUSION: Migraine comorbidity is common in patients with BrS/DI-type 1 BrP. We identify several clinical variables that point to an underlying type-1 BrP among migraineurs, necessitating cautious use of certain anti-migraine drugs.

Electrocardiographic findings of methanol toxicity: a cross-sectional study of 356 cases in Iran.

BACKGROUND: Methanol is widely used in industry; however, methanol poisoning is not common. In this regard, a number of outbreaks have been recently reported due to inappropriate processing of alcoholic beverages. Shiraz, a city located in the southern part of Iran, faced one of such outbreaks in 2020 during COVID-19 pandemic. There is no sufficient literature on the electrocardiographic findings in methanol toxicity. This study aimed to address this gap in the literature. METHOD: A total of 356 cases with methanol toxicity referred to Shiraz University of Medical Science Tertiary Hospitals (Faghihi and Namazi) in March and April, 2020. The clinical findings of blindness and impaired level of consciousness, lab data such as arterial blood gas, electrolytes, and creatinine, and the most common findings from ECGs were collected. RESULTS: The most common ECG findings were J point elevation (68.8%), presence of U wave (59.2%), QTc prolongation (53.2% in males and 28.6% in females), and fragmented QRS (33.7%). An outstanding finding in this study was the presence of myocardial infarction in 5.3% of the cases. This finding, to the best of our knowledge, has only been reported in a few case reports. Brugada pattern (8.1%) and Osborn wave (3.7%) were the other interesting findings. In multivariate analysis, when confounding factors were adjusted, myocardial infarction, atrioventricular conduction disturbances, sinus tachycardia, and the prolonged QTC > 500 msecond were four independent factors correlated with methanol toxicity severity measured with arterial blood PH on arterial blood gas measurements, with odds ratios of 12.82, 4.46, 2.32 and 3.15 (P < 0.05 for all), respectively. CONCLUSION: Electrocardiographic variations during methanol intoxication are remarkable and well-correlated with poisoning severity. Myocardial infarction was an egregious and yet a common concerning finding in this sample, which need to be ruled out in methanol toxicity.

Brugada phenocopy induced by consumption of yellow oleander seeds - A case report.

Brugada phenocopy is a brugada-like pattern in ECG seen in some diseases without an inherited channelopathy. The causes of brugada phenocopy are usually reversible. Once the reversible condition resolves, the ECG pattern disappears. There are many conditions that cause brugada phenocopy like myocardial infarction, hyperkalemia etc. Here we report a case of brugada phenocopy induced by consumption of yellow oleander seeds (T. Peruviana).

Unintentional Cocaine Exposure and Brugada Syndrome: A Case Report.

This case report describes a 16-month-old child with an accidental ingestion of cocaine. The clinical presentation, diagnostic reasoning, hospital course, and subsequent follow-up are discussed in this report. In 2018, there were 2.1 million human poison exposure calls to U.S. Poison Control Centers, with the highest incidence of calls for children aged 1-2 years. The substances with the largest number of deaths across all age groups included sedatives, sleeping medications, stimulants, street drugs, opioids, and alcohol. The child in this case report is a male who presented to the emergency department with altered mental status. When his urine drug screen resulted positive for cocaine, a social service consult was initiated, and the child was admitted to the intensive care unit for monitoring and supportive care. His electrocardiogram showed a Brugada rhythm. This case report highlights the incidence of accidental drug ingestions by children and a rare but potentially fatal cardiac arrhythmia.