Stereotactic arrhythmia radioablation and its implications for modern cardiac electrophysiology: results of an EHRA survey.

Stereotactic arrhythmia radioablation (STAR) is a treatment option for recurrent ventricular tachycardia/fibrillation (VT/VF) in patients with structural heart disease (SHD). The current and future role of STAR as viewed by cardiologists is unknown. The study aimed to assess the current role, barriers to application, and expected future role of STAR. An online survey consisting of 20 questions on baseline demographics, awareness/access, current use, and the future role of STAR was conducted. A total of 129 international participants completed the survey [mean age 43 ± 11 years, 25 (16.4%) female]. Ninety-one (59.9%) participants were electrophysiologists. Nine participants (7%) were unaware of STAR as a therapeutic option. Sixty-four (49.6%) had access to STAR, while 62 (48.1%) had treated/referred a patient for treatment. Common primary indications for STAR were recurrent VT/VF in SHD (45%), recurrent VT/VF without SHD (7.8%), or premature ventricular contraction (3.9%). Reported main advantages of STAR were efficacy in the treatment of arrhythmias not amenable to conventional treatment (49%) and non-invasive treatment approach with overall low expected acute and short-term procedural risk (23%). Most respondents have foreseen a future clinical role of STAR in the treatment of VT/VF with or without underlying SHD (72% and 75%, respectively), although only a minority expected a first-line indication for it (7% and 5%, respectively). Stereotactic arrhythmia radioablation as a novel treatment option of recurrent VT appears to gain acceptance within the cardiology community. Further trials are critical to further define efficacy, patient populations, as well as the appropriate clinical use for the treatment of VT.

[Therapeutic strategy for totally thoracoscopic repeat mitral valve surgery under moderate hypothermia-induced ventricular fibrillation].

Objective: To examine the therapeutic strategy and its impacting factors by analyzing the perioperative outcomes of total thoracoscopic repeat mitral valve surgery under moderate hypothermia-induced ventricular fibrillation with cardiopulmonary bypass. Methods: This study is a retrospective case series. Totally 63 patients who underwent repeat mitral valve surgery by the same surgeon from January 2021 to December 2023 in Department of Cardiovascular Surgery, the First Medical Center of People's Liberation Army General Hospital were retrospectively enrolled. There were 28 males and 35 females with an age of (58.3±15.9) years (range: 13 to 84 years). Surgery was performed using a totally thoracoscopic approach under moderate hypothermia-induced ventricular fibrillation. Mitral valvuloplasty was completed in 32 cases and mitral valve replacement in 31 cases. Preoperative baseline data and perioperative outcomes of the patients were collected and Logistic regression was used to analyze independent influencing factors of premature ventricular contractions in the early postoperative period. Results: The intraoperative cardiopulmonary bypass time was (191.5±50.9) minutes (range: 95 to 286 minutes), and the hypothermic ventricular fibrillation time was (99.0±39.8) minutes (range: 34 to 203 minutes). The anal temperature before the start of cardiopulmonary bypass was (36.3±0.5) ℃ (range: 35.2 to 38.0 ℃), the lowest intraoperative anal temperature was (27.3±1.3) ℃(range: 23.7 to 30.1 ℃), and the anal temperature at the time of the cessation of cardiopulmonary bypass was (36.3±0.4) ℃ (range: 35.2 to 37.0 ℃), and excessive rewarming was observed in 33 cases. Six cases applied the artificial heart assist device. Seventeen cases developed premature ventricular contractions in the early postoperative period. Two cases developed neurologic complications. Five cases developed respiratory complications. One case developed urological systemic complications. Six cases were mechanically ventilated for more than 3 days, and the duration of ICU stay in 16 cases was more than 3 days and the postoperative discharge time of (M(IQR)) 8.0 (3.5) days (range: 3 to 26 days). Two cases died or were discharged voluntarily. Logistic regression results showed that persistent preoperative atrial fibrillation (OR=11.424, 95%CI: 1.477 to 144.564, P=0.033) and excessive rewarming (OR=15.249, 95%CI: 1.357 to 279.571, P=0.038) were independent risk factors for the appearance of premature ventricular contractions in the early postoperative period. Conclusions: The technique of total thoracoscopic surgery under induced moderate hypothermic ventricular fibrillation with cardiopulmonary bypass could be applied to repeated mitral valve surgeries with less trauma and faster recovery. Persistent preoperative atrial fibrillation and excessive rewarming are independent risk factors for the occurrence of premature ventricular contractions in the early postoperative period.

Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.

Primary electrical heart diseases, often considered channelopathies, are inherited genetic abnormalities of cardiomyocyte electrical behavior carrying the risk of malignant arrhythmias leading to sudden cardiac death (SCD). Approximately 54% of sudden, unexpected deaths in individuals under the age of 35 do not exhibit signs of structural heart disease during autopsy, suggesting the potential significance of channelopathies in this group of age. Channelopathies constitute a highly heterogenous group comprising various diseases such as long QT syndrome (LQTS), short QT syndrome (SQTS), idiopathic ventricular fibrillation (IVF), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and early repolarization syndromes (ERS). Although new advances in the diagnostic process of channelopathies have been made, the link between a disease and sudden cardiac death remains not fully explained. Evolving data in electrophysiology and genetic testing suggest previously described diseases as complex with multiple underlying genes and a high variety of factors associated with SCD in channelopathies. This review summarizes available, well-established information about channelopathy pathogenesis, genetic basics, and molecular aspects relative to principles of the pathophysiology of arrhythmia. In addition, general information about diagnostic approaches and management is presented. Analyzing principles of channelopathies and their underlying causes improves the understanding of genetic and molecular basics that may assist general research and improve SCD prevention.

Temporal Association Between Vaping and Risk of Cardiac Events.

OBJECTIVE: To describe our early observations with sudden cardiac arrest (SCA) and sudden death (SD) in patients using vape products. PATIENTS AND METHODS: A retrospective analysis of Mayo Clinic's Windland Smith Rice Genetic Heart Rhythm Clinic and Sudden Death Genomics Laboratory was performed on all SCA survivors and decedents who presented between January 1, 2007, and December 31, 2021, to identify patients/decedents with a history of vaping. Data abstraction included patient demographics, clinical characteristics, and documented use of vape products. RESULTS: Among 144 SCA survivors and 360 SD victims, there were six individuals (1%; 3 females) with unexplained SCA (n=4) or SD (n=2) that was temporally associated with vaping use with a mean age at sentinel event of 23±5 years. The SCA survivors include a 19-year-old male who was resuscitated from documented ventricular fibrillation 40 minutes after vaping and a 19-year-old male who was resuscitated from ventricular fibrillation a few hours post vaping. The first SD victim was a 19-year-old female with exercise-induced asthma who died in her sleep after vaping that evening. Autopsy results showed eosinophilic infiltrates in the lung tissue and death was attributed to bronchial asthma. The second vaping-associated death involved a 26-year-old male whose autopsy attributed the death to acute respiratory distress syndrome. CONCLUSION: We have identified six young individuals with a history of vaping who experienced a near fatal episode or a tragic SD. Although larger cohort studies are needed to quantify the actual risk of SD, it seems prudent to sound an early warning about vaping's potential lethality.

Life-Threatening Electrical Storm Following Liver Transplantation: A Case Report.

BACKGROUND Electrical storm is a rare but potentially life-threatening syndrome characterized by recurrent ventricular arrhythmias. Liver transplant recipients are at increased risk of developing electrical storms due to conditions that prolong QT intervals, such as cirrhotic cardiomyopathy. However, limited information exists on electrical storms in this specific population. This case report presents a patient who experienced 13 cardiac arrests during ventricular fibrillation following liver transplantation. CASE REPORT A 61-year-old woman with a medical history of diabetes, obesity, and cirrhosis due to non-alcoholic fatty liver disease underwent liver transplantation using a deceased donor's liver. Following the procedure, she developed a deterioration in her respiratory function, necessitating orotracheal intubation. Approximately 21 hours post-surgery, she experienced cardiac arrest during ventricular fibrillation, which was rapidly reversed with electrical defibrillation. However, the patient entered a state of electrical storm. Management involved antiarrhythmic medications and temporary transvenous cardiac pacing. She remained stable for 40 hours, but a dislodgment of the device triggered another episode of ventricular fibrillation, leading to her death. CONCLUSIONS This case report highlights the clinical presentation and challenges in managing electrical storms in liver transplant recipients. We hypothesize that cirrhotic cardiomyopathy could be the cause of her recurrent ventricular arrhythmias. Further studies are needed to better understand the underlying mechanisms and risk factors of this life-threatening syndrome in this population, which may enhance risk stratification and enable earlier intervention.

Center-Level Variation in Failure to Rescue After Pediatric Cardiac Surgery.

BACKGROUND: Although failure to rescue (FTR) is increasingly recognized as a quality metric, studies in congenital cardiac surgery remain sparse. Within a national cohort of children undergoing cardiac operations, we characterized the presence of center-level variation in FTR and hypothesized a strong association with mortality but not complications. METHODS: All children undergoing congenital cardiac operations were identified in the 2013 to 2019 Nationwide Readmissions Database. FTR was defined as in-hospital death after cardiac arrest, ventricular tachycardia/fibrillation, prolonged mechanical ventilation, pneumonia, stroke, venous thromboembolism, or sepsis, among other complications. Hierarchical models were used to generate hospital-specific, risk-adjusted rates of mortality, complications, and FTR. Centers in the highest decile of FTR were identified and compared with others. RESULTS: Of an estimated 74,070 patients, 1.9% died before discharge, at least 1 perioperative complication developed in 43.0%, and 4.1% experienced FTR. After multilevel modeling, decreasing age, nonelective admission, and increasing operative complexity were associated with greater odds of FTR. Variations in overall mortality and FTR exhibited a strong, positive relationship (r = 0.97), whereas mortality and complications had a negligible association (r = -0.02). Compared with others, patients at centers with high rates of FTR had similar distributions of age, sex, chronic conditions, and operative complexity. CONCLUSIONS: In the present study, center-level variations in mortality were more strongly explained by differences in FTR than complications. Our findings suggest the utility of FTR as a quality metric for congenital heart surgery, although further study is needed to develop a widely accepted definition and appropriate risk-adjustment models.

Etiologies, Mechanisms, Management, and Outcomes of Electrical Storm.

Electrical storm (ES) is characterized by three or more discrete sustained ventricular tachyarrhythmia episodes occurring within a limited time frame (generally ≤ 24 h) or an incessant ventricular tachyarrhythmia lasting > 12 h. In patients with an implantable cardioverterdefibrillator (ICD), ES is defined as three or more appropriate device therapies, separated from each other by at least 5 min, which occur within a 24-h period. ES may constitute a medical emergency, depending on the number arrhythmic episodes, their duration, the type, and the cycle length of the ventricular arrhythmias, as well as the underlying ventricular function. This narrative review was facilitated by a search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other clinically relevant studies. The search was limited to English-language reports published between 1999 and 2023. ES was searched using the terms mechanisms, genetics, channelopathies, management, pharmacological therapy, sedation, neuraxial modulation, cardiac sympathetic denervation, ICDs, and structural heart disease. Google and Google scholar as well as bibliographies of identified articles were reviewed for additional references. This manuscript examines the current strategies available to treat ES and compares pharmacological and invasive treatment strategies to diminish ES recurrence, morbidity, and mortality.

[Development of Human Vital Signs and Body Posture Monitoring and Positioning Alarm Systems].

In view of the high incidence of malignant diseases such as malignant arrhythmias in the elderly population, accidental injuries such as falls, and the problem of no witnesses when danger occurs, the study developed a human vital signs and body posture monitoring and positioning alarm system. Through the collection and analysis of electrocardiogram (ECG), respiration (RESP) and acceleration (ACC) signals, the system monitors human vital signs and body posture in real time, automatically judges critical states such as malignant arrhythmias and accidental falls on the local device side, and then issues alarm information, opens the positioning function, and uploads physiological information and patient location information through 4G communication. Experiments have shown that the system can accurately determine the occurrence of ventricular fibrillation and falls, and issue position and alarm information.

Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties.

AIMS: The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts. METHODS AND RESULTS: We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. CONCLUSION: We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.

Comparison of amiodarone and esmolol for prevention of reperfusion ventricular fibrillation in individuals undergoing heart valve or aortic surgery: a study protocol for a randomized controlled clinical trial.

BACKGROUND: Amiodarone and esmolol can help to prevent and treat post-cardiac surgery reperfusion ventricular fibrillation. However, the relative efficacies of these two drugs remain unknown. The aim of the current trial is to compare the performances of amiodarone and esmolol for preventing reperfusion ventricular fibrillation following open heart surgery. METHODS/DESIGN: This is a single-center, prospective, double-blind, controlled clinical trial. A total of 260 patients undergoing heart valve or aortic surgery will be assigned randomly to treatment with prophylactic esmolol (intervention group) or amiodarone (control group). The main outcome is the incidence of reperfusion ventricular fibrillation following aortic opening during extracorporeal circulation. The secondary outcomes are the rate of automatic cardiac resuscitation, energy and frequency of electrical defibrillation, number of electrical defibrillations, and pacemaker use in the two groups of patients. Information on the patients' general condition and the durations of anesthesia, extracorporeal circulation, aortic occlusion, and operation time will be recorded. We will also compare the heart rate, mean arterial pressure, and central venous pressure between the two groups of patients at induction of anesthesia (T1), start of surgery (T2), start of extracorporeal circulation (T3), aortic block (T4), aortic opening (T5), after opening for 10 (T6), 20 (T7), and 30 min (T8), at cessation of extracorporeal circulation (T9), and at the end of surgery (T10) and compare blood gas analysis results at T1, T5, T9, and T10. DISCUSSION: This study will determine if prophylactic esmolol is more effective than amiodarone for reducing the incidence of reperfusion ventricular fibrillation in patients undergoing heart valve or aortic surgery. TRIAL REGISTRATION: China Clinical Trials Registry ChiCTR1900026429. Registered on 2019.10.9.

Low-energy defibrillation using a base-apex epicardial electrode.

BACKGROUND: Current implantable cardioverter defibrillators (ICDs) require electric conduction with high voltage and high energy, which can impair cardiac function and induce another malignant arrhythmia. As a result, there has been a demand for an ICD that can effectively operate with lower energy to mitigate the risks of a strong electric shock. METHODS: A pair of sheet-shaped electrodes covering the heart were analyzed in three configurations (top-bottom, left-right, and front-back) using a heart simulator. We also varied the distance between the two electrodes (clearance) to identify the electrode shape with the lowest defibrillation threshold (DFT). We also investigated the ICD shock waveform, shock direction, and the effect of the backside insulator of the electrode. RESULTS: The DFT was high when the clearance was too small and the DFT was high even when the clearance was too large, suggesting that an optimal value clearance. The top-bottom electrodes with optimal clearance showed the lowest DFT when the biphasic shocks set the top electrode to a high potential first and then the bottom electrode was set to a high potential. An interval between a first shock waveform and a second shock waveform should be provided for low-energy defibrillation. Because the insulator prevents unnecessary current flow to the backside, the DFT of the electrodes with insulators is less than those without insulators. CONCLUSION: Painless defibrillation using sheet-shaped electrodes on the epicardium is predicated on the basis of results using a heart simulator.

Excision of left atrial myxoma under perfused ventricular fibrillation with hypothermia after coronary artery bypass grafting.

BACKGROUND: Redo heart surgery has become increasingly common but involves additional high surgical risk, especially redo surgery after coronary artery bypass grafting (CABG). CASE PRESENTATION: In this study, we report the case of a 57-year-old Chinese male with left atrium myxoma who had previously undergone CABG. Common surgical methods usually include aortic cross-clamping, administering cold cardioplegia perfusion to protect the myocardium, opening the heart, and then removing the tumor. However, for patients with previous CABG, redo thoracotomy and ascending aortic cross-clamping present a greater risk of damage to the grafted vessels. In this study, we chose a right lateral mini-thoracotomy incision and hypothermia-induced ventricular fibrillation to minimize damage and avoid any adverse effects on the bridge vasculature. The patient recovered uneventfully and was discharged seven days after surgery. CONCLUSIONS: For patients with previous CABG, minimally invasive right thoracotomy under perfused ventricular fibrillation with hypothermia is safe and reliable and can prevent potential damage to the ascending aorta and graft.

Ventricular Fibrillation Is a Sign of Life.

Ventricular fibrillation (VF) is a deadly rhythm problem. With asystole, it represents one of the most extreme emergencies that may engage vital prognosis within only few minutes if appropriated treatment is not instituted. It is learned in all medical schools worldwide that VF is not compatible with consciousness and sustained life. Moreover, at 37°C, and without restauration of cardiac flow, VF may be responsible for severe and most often irreversible brain damage after 3 minutes.

New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.

Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be benign, typical, threatening, ultimately fatal, occurs in clinical practice, patients on digitalis, anaesthesia or acute myocardial infarction. Both traditional and genetic animal models are: In-vitro: Isolated ventricular Myocytes, Guinea pig papillary muscles, Patch-Clamp Experiments, Porcine Atrial Myocytes, Guinea pig ventricular myocytes, Guinea pig papillary muscle: action potential and refractory period, Langendorff technique, Arrhythmia by acetylcholine or potassium. Acquired arrhythmia disorders: Transverse Aortic Constriction, Myocardial Ischemia, Complete Heart Block and AV Node Ablation, Chronic Tachypacing, Inflammation, Metabolic and Drug-Induced Arrhythmia. In-Vivo: Chemically induced arrhythmia: Aconitine antagonism, Digoxin-induced arrhythmia, Strophanthin/ouabain-induced arrhythmia, Adrenaline-induced arrhythmia, and Calcium-induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Arrhythmia through programmed electrical stimulation, sudden coronary death in dogs, Exercise ventricular fibrillation. Genetic Arrhythmia: Channelopathies, Calcium Release Deficiency Syndrome, Long QT Syndrome, Short QT Syndrome, Brugada Syndrome. Genetic with Structural Heart Disease: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Atrial Fibrillation, Sick Sinus Syndrome, Atrioventricular Block, Preexcitation Syndrome. Arrhythmia in Pluripotent Stem Cell Cardiomyocytes. Conclusion: Both traditional and genetic, experimental models of cardiac arrhythmias' characteristics and significance help in development of new antiarrhythmic drugs.

Management of a complex acetabular fracture following defibrillation for ventricular fibrillation cardiac arrest.

In this case report, we describe the first case of a patient who sustained a complex acetabular fracture following defibrillation for ventricular fibrillation cardiac arrest in the context of acute myocardial infarction. The patient was unable to undergo definitive open reduction internal fixation surgery due to the need to continue dual antiplatelet therapy following coronary stenting of his occluded left anterior descending artery. Following multidisciplinary discussions, a staged approach was opted for, with percutaneous closed reduction screw fixation of the fracture performed while the patient was maintained on dual antiplatelet therapy. The patient was discharged with a plan to perform definitive surgical management when safe to discontinue dual antiplatelets. This is the first confirmed case of defibrillation causing an acetabular fracture. We discuss the various aspects that need to be considered when patients are being worked up for surgery while on dual antiplatelet therapy.

Ventricular arrhythmias in patients with hypertrophic cardiomyopathy: Prevalence, distribution, predictors, and outcome.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) carries an increased risk of sudden cardiac death. Ventricular fibrillation (VF) is thought to be the common culprit arrhythmia. OBJECTIVE: The purpose of this study was to describe the incidence and predictors of sustained ventricular arrhythmias (VTAs) in HCM patients. METHODS: We retrospectively analyzed all patients with HCM and an implantable cardioverter-defibrillator (ICD) from a prospectively derived registry in 2 tertiary medical centers. Clinical, electrocardiographic, echocardiographic, ICD interrogation, and genetic data were collected and compared, first between patients with and without VTAs and then between patients with only VF and those with ventricular tachycardia (VT) with or without VF. RESULTS: Of the 1328 HCM patients, 207 (145 [70%] male; mean age 33 ± 16 years) were implanted with ICDs. Over a mean follow-up of 10 ± 6 years, 37 patients with ICDs (18%) developed sustained VTAs. These were associated with a family history of sudden cardiac death and a personal history of VTAs (P = .036 and P = .001, respectively). Sustained monomorphic VT was the most common arrhythmia (n = 26, 70%) and was linked to decreased left ventricular (LV) ejection fraction and increased LV end-systolic and end-diastolic diameters. Antitachycardia pacing (ATP) successfully terminated 258 (79%) of the 326 VT events. Mortality rates were comparable between patients with and without VTAs (4 [11%] vs 29 [17%]; P = .42) and between those with and without ICDs (24 [16%] vs 85 [20%]; P = .367). CONCLUSION: VT rather than VF is the most common arrhythmia in patients with HCM; it is amenable to ATP and is associated with lower LV ejection fraction and higher LV diameters. Therefore, ATP-capable devices may be considered in HCM patients with these LV features.

Early repolarization: Electrocardiographic cues to distinguish benign from malignant variants.

Historically, early repolarization (ER) has been considered a marker of good health as it is more prevalent in athletes, younger persons, and at slower heart rates. However, contemporary reports, largely based on data from resuscitated sudden cardiac arrest patients, suggest an association between ER and an increased risk for sudden cardiac death and the development of malignant ventricular arrhythmias. Therefore, after we present a brief-case presentation, we intend to review a challenging topic in recognition of malignant variants and propose a four-step comprehensive approach to simplify ECG discrimination when assessing ER changes.

[Mitral Valve Repair under Ventricular Fibrillation for Acute Mitral Valve Regurgitation in a Patient with Aortitis Syndrome].

A 73-year-old woman with a history of aortitis syndrome was referred to our hospital presenting with congestive heart failure caused by acute severe mitral regurgitation due to posterior leaflet prolapse. Upon admission, the patient fell into shock state while undergoing an examination. Medical treatment including mechanical ventilation could not alleviate circulatory collapse, so emergency surgery was performed on the day of admission. Severe calcification of the ascending aorta and severe stenosis or occlusion of the aortic arch vessels resulted from the patient's aortitis syndrome precluded aortic cannulation and aortic clamp. Therefore, mitral valve repair was performed under ventricular fibrillation at moderate hypothermia. Surgery was successful, and the patient recovered well without any cerebral complications after the surgery.

Subepicardial Cardiomyopathy: A Disease Underlying J-Wave Syndromes and Idiopathic Ventricular Fibrillation.

Brugada syndrome (BrS), early repolarization syndrome (ERS), and idiopathic ventricular fibrillation (iVF) have long been considered primary electrical disorders associated with malignant ventricular arrhythmia and sudden cardiac death. However, recent studies have revealed the presence of subtle microstructural abnormalities of the extracellular matrix in some cases of BrS, ERS, and iVF, particularly within right ventricular subepicardial myocardium. Substrate-based ablation within this region has been shown to ameliorate the electrocardiographic phenotype and to reduce arrhythmia frequency in BrS. Patients with ERS and iVF may also exhibit low-voltage and fractionated electrograms in the ventricular subepicardial myocardium, which can be treated with ablation. A significant proportion of patients with BrS and ERS, as well as some iVF survivors, harbor pathogenic variants in the voltage-gated sodium channel gene, SCN5A, but the majority of genetic susceptibility of these disorders is likely to be polygenic. Here, we postulate that BrS, ERS, and iVF may form part of a spectrum of subtle subepicardial cardiomyopathy. We propose that impaired sodium current, along with genetic and environmental susceptibility, precipitates a reduction in epicardial conduction reserve, facilitating current-to-load mismatch at sites of structural discontinuity, giving rise to electrocardiographic changes and the arrhythmogenic substrate.