Long-term clinical outcomes of patients with drug-induced type 1 Brugada electrocardiographic pattern: A nationwide cohort registry study.

BACKGROUND: There are limited real-world data on the extended prognosis of patients with drug-induced type 1 Brugada electrocardiogram (ECG). OBJECTIVE: We assessed the clinical outcomes and predictors of life-threatening arrhythmias in patients with drug-induced type 1 Brugada ECG. METHODS: This multicenter retrospective study, conducted at 21 Italian and Swiss hospitals from July 1997 to May 2021, included consecutive patients with drug-induced type 1 ECG. The primary outcome, a composite of appropriate ICD therapies and sudden cardiac death, was assessed along with the clinical predictors of these events. RESULTS: A total of 606 patients (mean age 49.7 ± 14.7 years; 423 [69.8%] men) were followed for a median of 60.3 months (interquartile range 23.0-122.4 months). Nineteen patients (3.1%) experienced life-threatening arrhythmias, with a median annual event rate of 0.5% over 5 years and 0.25% over 10 years. The SCN5A mutation was the only predictor of the primary outcome (hazard ratio 4.54; P = .002), whereas a trend was observed for unexplained syncope (hazard ratio 3.85; P = .05). In patients who were asymptomatic at presentation, the median annual rate of life-threatening arrhythmias is 0.24% over 5 years and increases to 1.2% if they have inducible ventricular fibrillation during programmed ventricular stimulation. CONCLUSION: In patients with drug-induced type 1 Brugada ECG, the annual risk of life-threatening arrhythmias is low, with the SCN5A mutation as the only independent predictor. Unexplained syncope correlated with worse clinical outcomes. Ventricular fibrillation inducibility at programmed ventricular stimulation significantly increases the median annual rate of life-threatening arrhythmias from 0.24% to 1.2% over 5 years.

Opportunities and drawbacks of the subcutaneous defibrillator across different clinical settings.

INTRODUCTION: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an established therapy for the prevention of sudden cardiac death (SCD) and an alternative to a transvenous implantable cardioverter-defibrillator system in selected patients. Beyond randomized clinical trials, many observational studies have described the clinical performance of S-ICD across different subgroups of patients. AREAS COVERED: Our review aimed to describe the opportunities and drawbacks of the S-ICD, focusing on their use in special populations and across different clinical settings. EXPERT OPINION: The choice to implant S-ICD should be based on the patient's tailored approach, which takes into account the adequate S-ICD screening at rest or during stress, the infective risk, the ventricular arrhythmia susceptibility, the progressive nature of the underlying disease, the work or sports activity, and the risk of lead-related complications.

New Psychoactive Substances Intoxications and Fatalities during the COVID-19 Epidemic.

In January 2020, the World Health Organization (WHO) issued a Public Health Emergency of International Concern, declaring the COVID-19 outbreak a pandemic in March 2020. Stringent measures decreased consumption of some drugs, moving the illicit market to alternative substances, such as New Psychoactive Substances (NPS). A systematic literature search was performed, using scientific databases such as PubMed, Scopus, Web of Science and institutional and government websites, to identify reported intoxications and fatalities from NPS during the COVID-19 pandemic. The search terms were: COVID-19, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019, intox*, fatal*, new psychoactive substance, novel psychoactive substance, smart drugs, new psychoactive substance, novel synthetic opioid, synthetic opioid, synthetic cathinone, bath salts, legal highs, nitazene, bath salt, legal high, synthetic cannabinoid, phenethylamine, phencyclidine, piperazine, novel benzodiazepine, benzodiazepine analogue, designer benzodiazepines, tryptamine and psychostimulant. From January 2020 to March 2022, 215 NPS exposures were reported in Europe, UK, Japan and USA. Single NPS class intoxications accounted for 25, while mixed NPS class intoxications represented only 3 cases. A total of 130 NPS single class fatalities and 56 fatalities involving mixed NPS classes were published during the pandemic. Synthetic opioids were the NPS class most abused, followed by synthetic cathinones and synthetic cannabinoids. Notably, designer benzodiazepines were frequently found in combination with fentalogues. Considering the stress to communities and healthcare systems generated by the pandemic, NPS-related information may be underestimated. However, we could not define the exact impacts of COVID-19 on processing of toxicological data, autopsy and death investigations.

Subcutaneous versus transvenous implantable cardioverter-defibrillator among drug-induced type-1 ECG pattern Brugada syndrome: a propensity score matching analysis from IBRYD study.

No real-world data are available about the complications rate in drug-induced type 1 Brugada Syndrome (BrS) patients with an implantable cardioverter-defibrillator (ICD). Aim of our study is to compare the device-related complications, infections, and inappropriate therapies among drug-induced type 1 BrS patients with transvenous- ICD (TV-ICD) versus subcutaneous-ICD (S-ICD). Data for this study were sourced from the IBRYD (Italian BRugada sYnDrome) registry which includes 619 drug-induced type-1 BrS patients followed at 20 Italian tertiary referral hospitals. For the present analysis, we selected 258 consecutive BrS patients implanted with ICD. 198 patients (76.7%) received a TV-ICD, while 60 a S-ICD (23.4%). And were followed-up for a median time of 84.3 [46.5-147] months. ICD inappropriate therapies were experienced by 16 patients (6.2%). 14 patients (7.1%) in the TVICD group and 2 patients (3.3%) in S-ICD group (log-rank P = 0.64). ICD-related complications occurred in 31 patients (12%); 29 (14.6%) in TV-ICD group and 2 (3.3%) in S-ICD group (log-rank P = 0.41). ICD-related infections occurred in 10 patients (3.88%); 9 (4.5%) in TV-ICD group and 1 (1.8%) in S-ICD group (log-rank P = 0.80). After balancing for potential confounders using the propensity score matching technique, no differences were found in terms of clinical outcomes between the two groups. In a real-world setting of drug-induced type-1 BrS patients with ICD, no significant differences in inappropriate ICD therapies, device-related complications, and infections were shown among S-ICD vs TV-ICD. However, a reduction in lead-related complications was observed in the S-ICD group. In conclusion, our evidence suggests that S-ICD is at least non-inferior to TV-ICD in this population and may also reduce the risk of lead-related complications which can expose the patients to the necessity of lead extractions.

Lights and shadows of subcutaneous implantable cardioverter-defibrillator in Brugada syndrome.

Currently the cornerstone of therapy for ventricular arrhythmic complications and sudden cardiac death prevention in Brugada syndrome (BrS) is an implantable cardioverter-defibrillator (ICD). BrS patient population differs from the majority of patients with an ICD implanted for structural heart disease, and as widely known, transvenous ICD (TV-ICD) systems have been associated with high complication rates in patients with BrS. Technological evolution of these devices has certainly reduced complications due to the device itself, but a careful preimplant screening of these patients is still essential. To date, criteria for an adequate screening process to select suitable candidates for a subcutaneous implantable cardioverter-defibrillator (S-ICD) from patients with BrS are sometimes nonstandardized and often lack important precautions that are instead fundamental to select the most suitable type of ICD for these patients. To better select suitable candidates for an S-ICD from patients with BrS, a full screening process should include screening during or immediately after an exercise test and after a drug provocation challenge test. We report an analysis of the "lights and shadows" of S-ICD for a correct use of this device in patients with BrS.

Cardiac electrophysiology and pacing educational and training needs among early-career cardiologists: a national survey of the Young Committee of the Italian Association of Arrhythmology and Cardiac Pacing.

BACKGROUND: Over the past three decades, cardiac electrophysiology and pacing, including device therapy and catheter ablation of arrhythmias, has rapidly developed as a subspecialty in cardiology. Currently, there is no clear perception about the needs in cardiac electrophysiology and pacing among early-career cardiologists. METHODS: To address these concerns, the Young Committee of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC) carried out a survey among those under the age of 40 years to obtain detailed information on practical activities and formal lessons during the fellowship in cardiology and their satisfaction and proficiency level at the end of the fellowship. RESULTS: We obtained 334 answers to the survey. In invasive cardiac electrophysiology and pacing, the percentage of participants attending the activity for a longer time (3-6 months) is lower compared with those in noninvasive subspecialties. About 40% of participants did not receive lessons on interventional cardiology, cardiac electrophysiology and pacing. On the contrary, 71% of participants received an adequate number of lessons on clinical arrhythmology. The vast majority of the participants expressed satisfaction for the education received in the echocardiographic, cardiac interventional laboratories and clinical arrhythmology, but about half of the participants were unsatisfied with the education received in cardiac electrophysiology and pacing. In interventional arrhythmology, the majority of the participants declare their lack of proficiency with two peaks for more complex procedures, namely interventional electrophysiology procedures (82%) and cardiac resynchronization therapy (CRT) procedures (76%). CONCLUSION: The present survey among Italian early-career cardiologists suggests that the majority of participants consider themselves not confident in performing cardiac electrophysiology and pacing procedures. Due to the complexity of the treatment for heart rhythm disorders and the long learning curve, structured additional training in cardiac electrophysiology and pacing procedures is required after cardiology fellowship.

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.

Intensive care and anesthetic management of patients with Brugada syndrome and COVID-19 infection.

Coronavirus disease 2019 (COVID-19) spreads across the world, and the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic viral infection. Rapid diagnosis, isolation, and intensive clinical management are very important for all patients with COVID-19, especially for those with cardiac diseases as Brugada syndrome (BrS). BrS is an arrhythmogenic disease reported to be one among the leading causes of sudden cardiac death. In these patients, episodes of lethal arrhythmias may be induced by several factors or situations, and for this reason management during ICU permanence or anesthesia must provide some precautions, avoiding factors that are known to have the potential to worsen the probability to induce arrhythmias. For ICU practitioners, management of acute respiratory failure, hemodynamics, and cardiovascular complications certainly are the key for the best treatment of these patients but to date specific data on supportive ICU care for these patients are lacking, and current recommendations are based on existing evidence from other viral infections and general intensive care management. We want to focus on some general rules, resulted from cases series and clinical practice, to be followed during the ICU management of patients with BrS and concomitant COVID-19 infection.

Link between Brugada phenocopy and myocardial ischemia: Results from the International Registry on Brugada Phenocopy.

BACKGROUND: Brugada phenocopies clinical entities that have indistinguishable electrocardiographic (ECG) patterns from true congenital Brugada syndrome. However, they are induced by other clinical circumstances such as myocardial ischemia. The purpose of our study was to examine the clinical features and pathogenesis of ischemia-induced Brugada phenocopy (BrP). METHODS: Data from 17 cases of ischemia-induced BrP were collected from the International Registry (www.brugadaphenocopy.com). Data were extracted from these publications and authors were contacted to provide further insight into each case. RESULTS: Of the patients included in this study, 71% were male. Mean age was 59 ± 11 years (range: 38-76). Type-1 Brugada ECG pattern occurred in 15/17 (88%) of the cases, while a type-2 Brugada ECG pattern was observed in the other 2/17 (12%). In all cases, the Brugada ECG pattern resolved upon correction of the ischemia, indicating ischemia as the inducing circumstance. No arrhythmic events have been detected acutely or during the follow-up. Reported time to resolution ranged from 2 minutes to 5 hours. Provocative challenges using sodium channel blocking agents were performed in 7/17 cases (41%), and all failed to induce a Brugada ECG pattern (BrP Class A). The remaining 10/17 cases (59%) did not undergo provocative testing due to various clinical reasons. CONCLUSIONS: Myocardial ischemia is a commonly reported etiology of BrP. Importantly, this study found no association between BrP induced by myocardial ischemia and sudden cardiac death or malignant ventricular arrhythmias.

Relation of the Brugada Phenocopy to Hyperkalemia (from the International Registry on Brugada Phenocopy).

Brugada phenocopies (BrPs) are clinical entities that differ in etiology from true congenital Brugada syndrome but have identical electrocardiographic (ECG) patterns. Hyperkalemia is known to be one of the causes of BrP. The aim of this study was to determine the clinical characteristics and evolution of hyperkalemia-induced BrP. Data from 27 cases of hyperkalemia-induced BrP were collected from the International Registry at www.brugadaphenocopy.com. Data were extracted from publications. Of the 27 patients included in the analysis, 18 (67%) were male; mean age was 53 ± 15 years (range 31 to 89). Mean serum potassium concentration was 7.45 ± 0.89 mmol/L. Type-1 Brugada ECG pattern was observed in 21 cases (78%), whereas 6 cases (22%) showed a type-2 Brugada ECG pattern. The Brugada ECG pattern resolved once the hyperkalemia was corrected, with no arrhythmic events. Estimated time to resolution was 7 ± 3 hours. In 4 cases (16%), a concurrent metabolic abnormality was detected: 3 (11%) presented with acidosis, 2 (7%) with hyponatremia, 1 (4%) with hypocalcaemia, 1 (4%) with hyperphosphatemia, and 1 (4%) with hyperglycemia. In 7 cases (26%), provocative testing using sodium channel blockers was performed, and all failed to reproduce a BrS ECG pattern (BrP class A). Additionally, no sudden cardiac death or malignant ventricular arrhythmias were detected. Hyperkalemia was found a common cause of BrP in our International Registry. The Brugada ECG pattern appears to occur at high serum potassium concentrations (>6.5 mmol/L). The ECG normalizes within hours of correcting the electrolyte imbalance. Importantly, hyperkalemia-induced BrP has not been associated with sudden cardiac death or ventricular arrhythmia.

Anesthetic and Perioperative Management of Patients With Brugada Syndrome.

Brugada syndrome (BrS) is an arrhythmogenic disease reported to be one among the leading causes of cardiac death in subjects under the age of 40 years. In these patients, episodes of lethal arrhythmias may be induced by several factors or situations, and for this reason, management during anesthesia and surgery must provide some precautions and drugs restrictions. To date, it is difficult to formulate guidelines for anesthetic management of patients with BrS because of the absence of prospective studies, and there is not a definite recommendation for neither general nor regional anesthesia, and there are no large studies in merit. For this reason, in the anesthesia management of patients with BrS, the decision of using each drug must be made after careful consideration and always in controlled conditions, avoiding other factors that are known to have the potential to induce arrhythmias and with a close cooperation between anesthetists and cardiologists, which is essential before and after surgery. In conclusion, given the absence of large studies in literature, we want to focus on some general rules, which resulted from case series and clinical practice, to be followed during the perioperative and anesthetic management of patients with BrS.

Recurrent in-stent restenosis, certainty of its origin, uncertainty about treatment.

Treatment of recurrent in-stent restenosis is a real brainteaser for the interventional cardiologist who cannot resort to the guidelines to have indications about the type of treatment to be preferred. The use of intracoronary imaging may provide insights into the underlying mechanisms of this complication and use of drug-coated balloons may be a valid alternative and especially a thoughtful treatment when the repeated and perseverant use of drug-eluting stents clearly fails. In this setting, we present a review of the literature about this interesting topic, going deep into the heart of the problem, its origin and possible treatment options.