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Background: Atrial tachyarrhythmias (ATAs) are the primary cause of inappropriate implantable cardioverter-defibrillator (ICD) therapy in patients with idiopathic ventricular fibrillation (IVF) and are associated with decreased quality of life and increased mortality. Nonetheless, the incidence of ATAs in IVF cases has not been clarified. Objective: The study sought to determine the incidence and clinical significance of ATAs in patients with IVF compared with those with Brugada syndrome (BrS). Methods: Patients diagnosed with IVF or BrS and receiving ICDs in 6 hospitals were enrolled between February 1997 and July 2020 to compute data regarding the incidence of ATAs, appropriate/inappropriate ICD therapy frequency, and independent predictors of ATAs. Results: Overall, 137 patients (51 in the IVF group and 86 in the BrS group) were enrolled. ATAs were detected in 22 (43.1%) patients in the IVF group and 17 (19.8%) in the BrS group (P = .006). Inappropriate ICD therapies due to ATAs were more frequently observed in the IVF group than in the BrS group (12 [23.5%] vs 7 [8.1%]; P = .020). Conversely, there was no significant difference in appropriate ICD therapies between the IVF and BrS groups (14 [27.5%] vs 23 [27.1%]; P = 1.000). Cox regression analysis revealed no predictive factors for the development of ATAs in the IVF group. Conclusion: ATA events were observed more frequently in patients with IVF than in those with BrS, and ATAs led to inappropriate ICD therapy in patients with IVF. Clinicians need to consider the recurrence of not only ventricular arrhythmias, but also the development of atrial arrhythmias for better management of IVF cases.

Idiopathic ventricular fibrillation is diagnosed in survivors of sudden cardiac death that has been caused by ventricular fibrillation without known structural or electrical abnormalities, even after extensive investigation. It is a common cause of sudden death in young adults. Although idiopathic ventricular fibrillation is a diagnosis of exclusion, in many cases only a partial investigation algorithm is performed. The aim of this review is to present a comprehensive diagnostic evaluation algorithm with a focus on diagnostic assessment of inherited arrhythmic syndromes and genetic background. [ABSTRACT FROM AUTHOR]

Energy drinks potentially can trigger life-threatening cardiac arrhythmias. It has been postulated that the highly stimulating and unregulated ingredients alter heart rate, blood pressure, cardiac contractility, and cardiac repolarization in a potentially proarrhythmic manner. The purpose of this study was to describe our experience regarding sudden cardiac arrest (SCA) occurring in proximity to energy drink consumption in patients with underlying genetic heart diseases. The electronic medical records of all SCA survivors with proven arrhythmias referred to the Mayo Clinic Windland Smith Rice Genetic Heart Rhythm Clinic for evaluation were reviewed to identify those who consumed an energy drink before their event. Patient demographics, clinical characteristics, documented energy drink consumption, and temporal relationship of energy drink consumption to SCA were obtained. Among 144 SCA survivors, 7 (5%; 6 female; mean age at SCA 29 ± 8 years) experienced an unexplained SCA associated temporally with energy drink consumption. Of these individuals, 2 had long QT syndrome and 2 had catecholaminergic polymorphic ventricular tachycardia; the remaining 3 were diagnosed with idiopathic ventricular fibrillation. Three patients (43%) consumed energy drinks regularly. Six patients (86%) required a rescue shock, and 1 (14%) was resuscitated manually. All SCA survivors have quit consuming energy drinks and have been event-free since. Overall, 5% of SCA survivors experienced SCA in proximity to consuming an energy drink. Although larger cohort studies are needed to elucidate the incidence/prevalence and quantify its precise risk, it seems prudent to sound an early warning on this potential risk. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sixty-six patients with non-ischaemic sudden cardiac arrest without LV structural disease. • A genetic variant of interest was found in 1/3 of tested patients. • Most patients had no phenotypic clues, but genetic testing was still profitable. • Many had channelopathies and arrhythmogenic RV cardiomyopathy-associated genes. • 1/3 of variants were (likely) pathogenic, so useful for family screening. With the development of advanced sequencing techniques, genetic testing has emerged as a valuable tool for the work-up of non-ischaemic sudden cardiac arrest (SCA). To evaluate the effectiveness of genetic testing in patients with unexplained SCA, according to clinical phenotype. All patients who underwent molecular genetic testing for non-ischaemic SCA with no left ventricular cardiomyopathy between 2012 and 2021 in two French university hospitals were included. Of 66 patients (mean age 36.7 ± 11.9 years, 54.5% men), 21 (31.8%; 95% confidence interval 22.4–45.3%) carried a genetic variant: eight (12.1%) had a pathogenic or likely pathogenic (P/LP) variant and 13 (19.7%) had a variant of uncertain significance (VUS). Among 37 patients (56.1%) with no phenotypic clues, genetic testing identified a P/LP variant in five (13.5%), mainly in RYR2 (n = 3) and SCN5A (n = 2), and a VUS in nine (24.3%). None of the nine patients with phenotypic evidence of channelopathies had P/LP variants, but two had VUS in RYR2 and NKX2.5. Among the 20 patients with suspected arrhythmogenic cardiomyopathy, three P/LP variants (15.0%) and two VUS (10.0%) were found in DSC2 , PKP2 , SCN5A and DSG2 , TRPM4 , respectively. Genetic testing was performed sooner after cardiac arrest (P < 0.001) and results were obtained more rapidly (P = 0.02) after versus before 2016. This study highlights the utility of molecular genetic testing with a genetic variant of interest identified in one-third of patients with unexplained SCA. Genetic testing was beneficial even in patients without phenotypic clues, with one-fourth of patients carrying a P/LP variant that could have direct implications. [ABSTRACT FROM AUTHOR]

Background: Idiopathic ventricular fibrillation (iVF) is a rare cause of sudden cardiac arrest and, by definition, a diagnosis of exclusion. Due to the rarity of the disease, previous and current studies are limited by their retrospective design and small patient numbers. Even though the incidence of iVF has declined owing to the identification of new disease entities, an important subgroup of patients remains. Aim: To expand the existing Dutch iVF Registry into a large nationwide cohort of patients initially diagnosed with iVF, to reveal the underlying cause of iVF in these patients, and to improve arrhythmia management. Methods: The Dutch iVF Registry includes sudden cardiac arrest survivors with an initial diagnosis of iVF. Clinical data and outcomes are collected. Outcomes include subsequent detection of a diagnosis other than 'idiopathic', arrhythmia recurrence and death. Non-invasive electrocardiographic imaging is used to investigate electropathological substrates and triggers of VF. Results: To date, 432 patients have been included in the registry (median age at event 40 years (interquartile range 28–52)), 61% male. During a median follow-up of 6 (2–12) years, 38 patients (9%) received a diagnosis other than 'idiopathic'. Eleven iVF patients were characterised with electrocardiographic imaging. Conclusion: The Dutch iVF Registry is currently the largest of its kind worldwide. In this heterogeneous population of index patients, we aim to identify common functional denominators associated with iVF. With the implementation of non-invasive electrocardiographic imaging and other diagnostic modalities (e.g. echocardiographic deformation, cardiac magnetic resonance), we advance the possibilities to reveal pro-fibrillatory substrates. [ABSTRACT FROM AUTHOR]

Aims Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. Methods and results This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579). Conclusion A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) in children is a devastating event, often linked to primary electrical diseases (PED) of the heart. PEDs, often referred to as channelopathies, are a group of genetic disorders that disrupt the normal ion channel function in cardiac cells, leading to arrhythmias and sudden cardiac death. This paper investigates the unique challenges of risk assessment and stratification for channelopathy-related SCD in pediatric patients—Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, idiopathic ventricular fibrillation, long QT syndrome, Anderson–Tawil syndrome, short QT syndrome, and early repolarization syndrome. We explore the intricate interplay of genetic, clinical, and electrophysiological factors that contribute to the complex nature of these conditions. Recognizing the significance of early identification and tailored management, this paper underscores the need for a comprehensive risk stratification approach specifically designed for pediatric populations. By integrating genetic testing, family history, and advanced electrophysiological evaluation, clinicians can enhance their ability to identify children at the highest risk for SCD, ultimately paving the way for more effective preventive strategies and improved outcomes in this vulnerable patient group. [ABSTRACT FROM AUTHOR]

Background: Early repolarization pattern (ERP) has been associated with idiopathic ventricular fibrillation (IVF) and with cardiovascular mortality in the general population. As there is limited data about long- term outcome of IVF, the aim of our study was to observe ventricular arrhythmia (VA) recurrences in these patients and to identify a possible correlation of VA with ECG markers of early repolarization. Methods and results: We investigated 56 consecutive IVF patients who received an implantable cardioverter-defibrillator for secondary prevention. ERP was defined as a J-point elevation ≥ 0.1 mV in two or more contiguous inferior or lateral leads. Markers of early repolarization were present in 32.1% of cases with a preponderance of QRS slurring (77.8%). During a mean follow-up of 41.2 months, 11 patients (19.6%) received in total 18 adequate ICD-therapies. VF was most the common cause for ICDtherapy (61.1%) but monomorphic VT also occurred in four patients. Presence of ERP was associated with a significant trend towards arrhythmia recurrences. 38.9% patients with ERP received appropriate ICD-therapies whereas only 10.5% of patients without ERP had arrhythmia recurrence (p = 0.05). Inappropriate ICD-therapies occurred in seven patients (12.5%) with a non-significant trend towards a higher incidence in patients with a transvenous ICD (p = 0.15). Conclusion: A significant correlation between ERP and VA recurrences in patients with IVF could be observed. Though monomorphic VA also play a role in the studied IVF-population, our data support the use of the S-ICD in this collective. [ABSTRACT FROM AUTHOR]

Idiopathic ventricular fibrillation is diagnosed in survivors of sudden cardiac death that has been caused by ventricular fibrillation without known structural or electrical abnormalities, even after extensive investigation. It is a common cause of sudden death in young adults. Although idiopathic ventricular fibrillation is a diagnosis of exclusion, in many cases only a partial investigation algorithm is performed. The aim of this review is to present a comprehensive diagnostic evaluation algorithm with a focus on diagnostic assessment of inherited arrhythmic syndromes and genetic background.

Aims During the diagnostic work-up of patients with idiopathic ventricular fibrillation (VF), next-generation sequencing panels can be considered to identify genotypes associated with arrhythmias. However, consensus for gene panel testing is still lacking, and variants of uncertain significance (VUS) are often identified. The aim of this study was to evaluate genetic testing and its results in idiopathic VF patients. Methods and results We investigated 419 patients with available medical records from the Dutch Idiopathic VF Registry. Genetic testing was performed in 379 (91%) patients [median age at event 39 years (27–51), 60% male]. Single-gene testing was performed in 87 patients (23%) and was initiated more often in patients with idiopathic VF before 2010. Panel testing was performed in 292 patients (77%). The majority of causal (likely) pathogenic variants (LP/P, n = 56, 15%) entailed the DPP6 risk haplotype (n = 39, 70%). Moreover, 10 LP/P variants were found in cardiomyopathy genes (FLNC , MYL2 , MYH7 , PLN (two), TTN (four), RBM20), and 7 LP/P variants were identified in genes associated with cardiac arrhythmias (KCNQ1 , SCN5A (2), RYR2 (four)). For eight patients (2%), identification of an LP/P variant resulted in a change of diagnosis. In 113 patients (30%), a VUS was identified. Broad panel testing resulted in a higher incidence of VUS in comparison to single-gene testing (38% vs. 3%, P < 0.001). Conclusion Almost all patients from the registry underwent, albeit not broad, genetic testing. The genetic yield of causal LP/P variants in idiopathic VF patients is 5%, increasing to 15% when including DPP6. In specific cases, the LP/P variant is the underlying diagnosis. A gene panel specifically for idiopathic VF patients is proposed. [ABSTRACT FROM AUTHOR]

Aims Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. Methods and results This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing–based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3 , MYH7 , DSP , and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Conclusion Next-generation sequencing–based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy. [ABSTRACT FROM AUTHOR]

Aims Calmodulinopathy due to mutations in any of the three CALM genes (CALM1–3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. Methods and results The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM -positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5–19]), 97 index cases and 43 family members. CALM -LQTS and CALM -CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P =.001) and sudden death (9% vs. 27%; P =.008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM -LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. Conclusion Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter–defibrillator. [ABSTRACT FROM AUTHOR]

Short-coupled ventricular fibrillation (SCVF) is a distinct phenotype among individuals with unexplained cardiac arrest accounting for 7% to 14% of cases of idiopathic ventricular fibrillation (IVF). VF is typically initiated by a trigger premature ventricular contraction with a short-coupling interval of less than 350 milliseconds. In the absence of specific electrocardiographic features or provocative tests, the diagnosis remains challenging and requires documentation of VF onset. Most cases are diagnosed during follow-up at the time of VF recurrence. SCVF is characterized by a high risk of VF recurrence. Insertion of an implantable cardioverter-defibrillator and quinidine are the keystones of SCVF management. [ABSTRACT FROM AUTHOR]

Calcium release deficiency syndrome (CRDS) is a newly described form of inherited arrhythmia caused by damaging loss-of-function variants in the cardiac ryanodine receptor (RyR2). Unlike the prototypical RyR2 gain-of-function channelopathy, known as catecholaminergic polymorphic ventricular tachycardia, patients with CRDS are predisposed to sudden death usually in the absence of any electrical abnormalities at rest or during stress electrocardiography. This makes diagnosis incredibly challenging, however, an invasive electrophysiologic test appears to be effective in unmasking the phenotype, called the long-burst, long-pause, short-coupled ventricular extra-stimulus protocol. Optimal therapies for patients with CRDS remain unestablished, although flecainide appears to be a promising candidate drug. [ABSTRACT FROM AUTHOR]

Unexplained cardiac arrest (UCA) is a working diagnosis that should be replaced by a final diagnosis once evaluation is completed. Complete evaluation of UCA should include high-yield tests like cardiac magnetic resonance imaging, exercise treadmill test, and sodium-channel blocker challenge to identify latent causes of UCA. If no clear etiology is revealed after complete evaluation, idiopathic ventricular fibrillation may be diagnosed, and the strength of its diagnosis can be divided into definitive, probable, and possible based on the number of high-yield tests performed. Care should be provided by a multidisciplinary team with expertise in this area. [ABSTRACT FROM AUTHOR]

Ventricular fibrillation (VF) is a life-threatening arrhythmia that usually happens in patients with structural heart diseases. However, fever-induced ventricular fibrillation in structurally normal hearts was reported, and the four main diseases associated with these cases were Brugada syndrome, long QT syndrome, idiopathic ventricular fibrillation, and non-cardiovascular diseases. In this review, we analyzed this phenomenon and its clinical characteristics.

Background: The genetic risk haplotype DPP6 has been linked to familial idiopathic ventricular fibrillation (IVF), but the associated long-term outcomes are unknown. Methods: DPP6 risk haplotype-positive family members (DPP6 cases) and their risk haplotype-negative relatives (DPP6 controls) were included. Clinical follow-up data were collected through March 2023. Implantable cardioverter-defibrillator (ICD) indication was divided in primary or secondary prevention. Cumulative survival and event rates were calculated. Results: We included 327 DPP6 cases and 315 DPP6 controls. Median follow-up time was 9 years (interquartile range: 4–12). Of the DPP6 cases, 129 (39%) reached the composite endpoint of appropriate ICD shock, sudden cardiac arrest or death, at a median age of 45 years (range: 15–97). Median overall survival was 83 years and 87 years for DPP6 cases and DPP6 controls, respectively (p < 0.001). In DPP6 cases, median overall survival was shorter for males (74 years) than females (85 years) (p < 0.001). Of the DPP6 cases, 97 (30%) died, at a median age of 50 years. With a prophylactic ICD implantation advise based on risk haplotype, sex and age, 137 (42%) of DPP6 cases received an ICD, for primary prevention (n = 109) or secondary prevention (n = 28). In the primary prevention subgroup, 10 patients experienced a total of 34 appropriate ICD shocks, and there were no deaths during follow-up. DPP6 cases with a secondary prevention ICD experienced a total of 231 appropriate ICD shocks. Conclusion: Patients with the DPP6 risk haplotype, particularly males, are at an increased risk of IVF and sudden cardiac death. Using a risk stratification approach based on risk haplotype, sex and age, a substantial proportion of patients with a primary prevention ICD experienced appropriate ICD shocks, showing the benefit of prophylactic ICD implantation with this strategy. [ABSTRACT FROM AUTHOR]

Ventricular fibrillation (VF) can be initiated by ventricular premature depolarizations (VPDs) in the absence of obvious structural abnormalities. The purpose of this study was to determine the prevalence of 12-lead electrocardiographic (ECG) sinus rhythm reduced QRS amplitude, QRS fractionation (QRSf), and early repolarization (ER) pattern, and the outcome of catheter ablation and VPD anatomic distribution in patients with VPDs initiating VF. We compared a cohort with no apparent structural heart disease and VPDs initiating VF (group 1; n = 42) to a reference cohort (group 2; n = 61) of patients with no structural heart disease and symptomatic unifocal VPDs. A reduced QRS amplitude (<0.55 mV) in aVF (59% vs 10%; P <.001), QRSf in ≥2 contiguous leads (50% vs 16%; P <.001), and ER pattern (21.4% vs 1.6%; P =.01) were more common in group 1 than in group 2. At least 1 abnormal ECG finding was present in 34 group 1 patients (81%) vs 17 group 2 patients (28%) (P <.001). VPD origin included right ventricular and left ventricular distal Purkinje system and moderator band/papillary muscles in 83% of group 1 patients vs 18% of group 2 patients (P <.001). VF was eliminated with a single ablation procedure in 77% of group 1 patients with at least 2 years of follow-up. A reduced QRS amplitude (<0.55 mV) in aVF, QRSf in ≥2 contiguous leads, and/or an ER pattern are frequently observed in patients with VPDs initiating VF. VPDs initiating VF typically originate from the distal Purkinje system and papillary muscles and can be successfully eliminated with catheter ablation. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic ventricular fibrillation (IVF) is mainly associated with and triggered by short‐coupled (R‐on‐T) ventricular ectopics. However, little is known about the risk of VF associated with long‐coupled premature ventricular complexes (LCPVCs). Objective: To examine the prevalence and characteristics of IVF patients presenting with LCPVCs. Methods: Consecutive patients with IVF and PVCs from five arrhythmia referral centers were reviewed. We included patients presenting LCPVCs, defined as PVCs falling after the end of the T wave, with a normal QTc interval. We evaluated demographics, medical history, and clinical circumstances associated with PVCs and VF episodes. The origin of PVCs was determined by invasive mapping. Results: Seventy‐nine patients with IVF were reviewed. Among them, 12 (15.2%) met the inclusion criteria (8 women, age 36 ± 14 years). Eleven patients had documented LCPVCs initiating repetitive PVCs or sustained VF, whereas 1 had only documented isolated PVCs. In 10 of 12 patients, PVCs were recorded showing both long and short coupling intervals of 418 ± 46 and 304 ± 33 ms, respectively. Mapping showed that PVCs originated from the left Purkinje in 10 patients, from the right Purkinje in 1 patient, and both in 1 patient. Compared to other patients from the initial cohort, IVF with LCPVCs was associated with a left‐sided origin of PVCs (92% in long‐coupled IVF vs. 46% of left Purkinje PVCs in short‐coupled IVF, p =.004). Conclusion: Long‐coupled fascicular PVCs, traditionally recognized as benign, can be associated with IVF in a subset of patients. They can induce IVF by themselves or in association with short‐coupled PVCs. [ABSTRACT FROM AUTHOR]

Background Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion following normal cardiac investigations. We sought to determine if exercise‐induced changes in electrical substrate could distinguish patient groups with various ventricular arrhythmic pathophysiological conditions and identify patients susceptible to VF. Methods and Results Computed tomography and exercise testing in patients wearing a 252‐electrode vest were combined to determine ventricular conduction stability between rest and peak exercise, as previously described. Using ventricular conduction stability, conduction heterogeneity in idiopathic VF survivors (n=14) was compared with those surviving VF during acute ischemia with preserved ventricular function following full revascularization (n=10), patients with benign ventricular ectopy (n=11), and patients with normal hearts, no arrhythmic history, and negative Ajmaline challenge during Brugada family screening (Brugada syndrome relatives; n=11). Activation patterns in normal subjects (Brugada syndrome relatives) are preserved following exercise, with mean ventricular conduction stability of 99.2±0.9%. Increased heterogeneity of activation occurred in the idiopathic VF survivors (ventricular conduction stability: 96.9±2.3%) compared with the other groups combined (versus 98.8±1.6%; P=0.001). All groups demonstrated periodic variation in activation heterogeneity (frequency, 0.3–1 Hz), but magnitude was greater in idiopathic VF survivors than Brugada syndrome relatives or patients with ventricular ectopy (7.6±4.1%, 2.9±2.9%, and 2.8±1.2%, respectively). The cause of this periodicity is unknown and was not replicable by introducing exercise‐induced noise at comparable frequencies. Conclusions In normal subjects, ventricular activation patterns change little with exercise. In contrast, patients with susceptibility to VF experience activation heterogeneity following exercise that requires further investigation as a testable manifestation of underlying myocardial abnormalities otherwise silent during routine testing.

Introduction: Idiopathic ventricular fibrillation triggered by short-coupled premature ventricular contractions has been studied for years; recently, it has been proposed as a new phenotype called short-coupled idiopathic ventricular fibrillation (sc-IVF). Objective: To describe the clinical and electrocardiographic evolution of patients with sc-IVF. Method: A descriptive study on patients with sc-IVF was carried out. Patients with other diseases that could cause ventricular fibrillation (such as channelopathies and specific electrical diseases) were excluded. Short-coupled premature ventricular contraction was defined as a coupling interval of less than or equal to 300 ms, located on the ascending branch or top of the T wave, or on its descending branch, and some cases with “not-so-short” intervals were also considered. Results: Twelve subjects suffering from sc-IVF, without structural heart disease demonstrated by conventional methods, were studied. The average age was 37.9 years (minimum 15, maximum 60), with 6 patients were female and 6 male patients. The onset in all cases was sudden death due to ventricular fibrillation, and in six patients, torsades de pointes were also associated. The location of the ventricular extrasystole could vary in the same patient; the lowest value was taken, and it prevailed in the ascending branch or at the top of the T wave (66.6%, minimum value 220 ms). There were four cases exhibiting “not-so-short” coupling intervals. Two patients died, both without an implantable cardioverter-defibrillator. Conclusions: Idiopathic ventricular fibrillation triggered by short-coupled premature ventricular contractions constitutes a new phenotype within the spectrum of malignant ventricular arrhythmias. Shorter intervals are associated with higher malignancy. The association with torsades de pointes is frequent. [ABSTRACT FROM AUTHOR]

Deterioration of atrial fibrillation into ventricular fibrillation has frequently been described in patients with pre-excitation of the ventricles. We report two cases of atrial fibrillation without pre-excitation leading to rapid ventricular tachycardias and recurrent implantable cardioverter defibrillator therapy in young idiopathic ventricular fibrillation patients. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) in children is a devastating event, often linked to primary electrical diseases (PED) of the heart. PEDs, often referred to as channelopathies, are a group of genetic disorders that disrupt the normal ion channel function in cardiac cells, leading to arrhythmias and sudden cardiac death. This paper investigates the unique challenges of risk assessment and stratification for channelopathy-related SCD in pediatric patients—Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, idiopathic ventricular fibrillation, long QT syndrome, Anderson–Tawil syndrome, short QT syndrome, and early repolarization syndrome. We explore the intricate interplay of genetic, clinical, and electrophysiological factors that contribute to the complex nature of these conditions. Recognizing the significance of early identification and tailored management, this paper underscores the need for a comprehensive risk stratification approach specifically designed for pediatric populations. By integrating genetic testing, family history, and advanced electrophysiological evaluation, clinicians can enhance their ability to identify children at the highest risk for SCD, ultimately paving the way for more effective preventive strategies and improved outcomes in this vulnerable patient group.

Life-threatening ventricular arrhythmias (VA) may occur in patients with unknown cardiac disease. A sizable part of them remains labeled as Idiopathic VA and limited data is available regarding their natural history. Our aim was to evaluate the long-term clinical outcomes of survivors of an idiopathic life-threatening VA. Patients who survived an idiopathic life-threatening VA referred to an ICD were included and followed for a median follow-up of 7 years. Clinical and device data were collected and a comparison between genders was made. A total of 29 patients, 41% female, mean age of 50 (19) years were studied; all were implanted with an ICD at index hospitalization. At follow-up, an etiological diagnosis was established in 38% of patients. Genetic testing improved the diagnosis and allowed the identification of a distinct clinical entity in 60% of patients (p=0.04, OR = 7.0), especially in women. Regarding ICD data, 31% received appropriate therapies with a median time to first appropriate shock of 39 months (IQR 12-46 months). Men had a significantly higher prevalence of appropriated shocks (50% vs 8%, p=0.04), with a similar time to the first arrhythmic event between genders. Two of the patients died, both from non-arrhythmic causes. Etiologic diagnosis and recurrence prediction in patients with idiopathic VA is challenging, even with long-term follow-up and sophisticated diagnostic evaluation. Genetic testing significantly improved the diagnostic yield, especially in women. Arrhythmia recurrence occurred in about one-third of patients and is significantly higher in men, underscoring the importance of ICD implantation.

Background: Sodium channel blocker (SCB) infusion is used to unmask the electrocardiographic pattern of Brugada syndrome. The test may also induce premature ventricular complexes (PVCs) in individuals without Brugada pattern, the clinical relevance of which is little known.Objective: The purpose of this study was to describe the prevalence of short-coupled (Sc) PVCs induced by ajmaline or flecainide in patients with suspected or documented severe ventricular arrhythmias.Methods: We reviewed the SCB tests performed in 335 patients with suspected ventricular arrhythmias and structurally normal hearts in 9 centers. ScPVCs were defined as frequent and repetitive PVCs with an R-on-T pattern on SCB tests. Repeated SCB tests were performed in 7 patients and electrophysiological mapping of ScPVCs in 9.Results: Sixteen patients (8 men; mean age 36 ± 11 years) showed ScPVCs and were included. ScPVCs appeared 229 ± 118 seconds after the initiation of infusion and displayed coupling intervals of 288 ± 28 ms. ScPVC patterns were monomorphic in 12 patients, originating from the Purkinje system in mapped patients. Repetitive PVCs were induced in 15 patients (94%) including polymorphic ventricular tachycardias in 9 (56%). SCB infusion was repeated 45 (interquartile range 0.6-46) months later and induced identical ScPVC in all. SCB test was the only mean to reveal the malignant arrhythmia in 6 patients. Catheter ablation was performed in 9 patients, resulting in arrhythmia elimination in 8 with a follow-up of 6 (interquartile range 2-9) years.Conclusion: SCB can induce ScPVC, mostly from Purkinje tissue, in a small subset of patients with idiopathic ventricular arrhythmias. Its high reproducibility suggests a distinct individual mechanism. [ABSTRACT FROM AUTHOR]

Competing Interests: Disclosures The author has no conflicts of interest to disclose.

Background: Current cohorts of patients with idiopathic ventricular fibrillation (IVF) primarily include adult-onset patients. Underlying causes of sudden cardiac arrest vary with age; therefore, underlying causes and disease course may differ for adolescent-onset vs adult-onset patients., Objective: The purpose of this study was to compare adolescent-onset with adult-onset patients having an initially unexplained cause of VF., Methods: The study included 39 patients with an index event aged ≤19 years (adolescent-onset) and 417 adult-onset patients from the Dutch Idiopathic VF Registry. Data on event circumstances, clinical characteristics, change in diagnosis, and arrhythmia recurrences were collected and compared between the 2 groups., Results: In total, 42 patients received an underlying diagnosis during follow-up (median 7 [2-12] years), with similar yields (15% adolescent-onset vs 9% adult-onset; P = .16). Among the remaining unexplained patients, adolescent-onset patients (n = 33) had their index event at a median age of 17 [16-18] years, and 72% were male. The youngest patient was aged 13 years. In comparison with adults (n = 381), adolescent-onset patients more often had their index event during exercise (P <.01). Adolescent-onset patients experienced more appropriate implantable cardioverter-defibrillator (ICD) therapy during follow-up compared with adults (44% vs 26%; P = .03). Inappropriate ICD therapy (26% vs 17%; P = .19), ICD complications (19% vs 14%; P = .41), and deaths (3% vs 4%; P = 1) did not significantly differ between adolescent-onset and adult-onset patients., Conclusion: IVF may occur during adolescence. Adolescent-onset patients more often present during exercise compared with adults. Furthermore, they are more vulnerable to ventricular arrhythmias as reflected by a higher incidence of appropriate ICD therapy., Competing Interests: Disclosures Dr Yap is a consultant for Boston Scientific; and has received lecture fees and research grants from Medtronic, Biotronik, and Boston Scientific. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Idiopathic ventricular fibrillation (IVF) is an unrefined diagnosis representing a heterogeneous patient group without a structural or genetic definition. IVF treatment is not mechanistic-based due to the lack of experimental patient-models. We sought to create a methodology to assess cellular arrhythmia mechanisms for IVF as a proof-of-concept study. Using IVF patient-specific induced pluripotent stem cell-derived cardiomyocytes, we integrate electrophysiological optical mapping with computational modeling to characterize the cellular phenotype. This approach flips the traditional paradigm using a biophysically detailed computational model to solve the problem inversely. Insight into the cellular mechanisms of this patient's IVF phenotype could also serve as a therapeutic testbed., Competing Interests: Funding Support and Author Disclosures This work was supported by NIH R01HL170521 (LLE, EG), NIH R01HL163987 (Dr Eckhardt), NIH R01HL139738 (Dr Eckhardt), 2R01HL141214 (Dr Glukhov), AHA846898, and AHA 24SCEFIA1255230 (Dr Lang), 24CDA1258695 (Dr Ni). This work was also funded in part by the Gary and Marie Weiner Professor in Cardiovascular Medicine Research (Dr Eckhardt). All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts., Objectives: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates., Methods: This was a multicenter collaboration study. At 32 centers, we selected patients with an initial diagnosis of IVF and recurrent arrhythmia at follow-up without antiarrhythmic drugs, in whom mapping demonstrated Purk or MiCM substrate. We analyzed variables related to previous ectopy, sinus rate preceding VF, trigger, and initial VF cycle lengths. Logistic regression with cross validation was used to evaluate the performance of criteria to discriminate Purk or MiCM substrates., Results: Among 95 patients (35 women, age 35 ± 11 years) meeting the inclusion criteria, IVF was associated with MiCM in 41 and Purk in 54 patients. A total of 117 arrhythmia recurrences including 91% VF were recorded on defibrillator. Three variables were mostly discriminant. Sinus tachycardia (≤570 ms) was more frequent in MiCM (35.9% vs 13.4%, P = 0.014) whereas short-coupled (<350 ms) triggers were most frequent in Purk-related VF (95.5% vs 23.1%, P = 0.001), which also had shorter VFCLs (182 ± 15 ms vs 215 ± 24 ms, P < 0.001).The multivariable combination provided the highest prediction (accuracy = 0.93 ± 0.05, range 0.833-1.000), discriminating 81% of IVF substrates with a high probability (>80%). Ectopy were inconsistently present before VF., Conclusions: Characteristics of arrhythmia recurrences on implantable cardioverter- defibrillator provide phenotypic markers of the distinct and hidden substrates underlying IVF. These findings have significant clinical and genetic implications., Competing Interests: Funding Support and Author Disclosures Dr Haissaguerre has received grant support from Biosense Webster. Dr Marijon has received grant support and consulting fees from Medtronic, Boston Scientific, Abbott, Microport, Biotronik, and Zoll. Pr Gandjbakhch has received lecture fees from Biotronik; and consulting fees from Medtronic, Microport, and Abbott. Dr Tilz is a consultant for Boston Scientific, Biotronik, Biosense Webster, and Abbott Medical; has received speaker honoraria from Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and Lifetech; and has received research grants from Abbott, Biosense Webster, and Lifetech. Dr Roten has received research grants from Medtronic, the Swiss National Foundation, the Swiss Heart Foundation, the Immanuel and Ilse Straub Foundation, and the Sitem Insel Support Fund, all for work outside the submitted study; and has received speaker/consulting honoraria from Abbott and Medtronic. Dr Reichlin has receivedresearch grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Sitem Insel support funds, Biotronik, Boston-Scientific, and Medtronic, all for work outside the submitted study; and has received speaker/consulting honoraria or travel support from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic, all for work outside the submitted study. Support for his institution’s fellowship program from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic for work outside the submitted study. Dr Sacher has receivedspeaking honorarium from Abbott, Boston Scientific, and Biosense Webster; and equity from InHeart. Dr Nogami has received lecture fees from Abbott; and endowments from Medtronic. Dr Massoullié has received lecture fees from Boston Scientific, Biosense Webster, and Abbot. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Idiopathic ventricular fibrillation is a rare cause of sudden cardiac arrest and a diagnosis by exclusion. Unraveling the mechanism of ventricular fibrillation is important for targeted management, and potentially for initiating family screening. Sudden cardiac arrest survivors undergo extensive clinical testing, with a growing role for multimodality imaging, before diagnosing "idiopathic" ventricular fibrillation. Multimodality imaging, considered as using multiple imaging modalities as diagnostics, is important for revealing structural myocardial abnormalities in patients with cardiac arrest. This review focuses on combining imaging modalities (echocardiography, cardiac magnetic resonance and computed tomography) and the electrocardiographic characterization of sudden cardiac arrest survivors and discusses the surplus value of multimodality imaging in the diagnostic routing of these patients. We focus on novel insights obtained through electrostructural and/or electromechanical imaging in apparently idiopathic ventricular fibrillation patients, with special attention to non-invasive electrocardiographic imaging. [ABSTRACT FROM AUTHOR]

Idiopathic ventricular fibrillation (IVF) is diagnosed in out-of-hospital VF survivors after comprehensive investigations have excluded structural heart disease or inherited channelopathies. Current guidelines recommend clinical screening of first-degree relatives of IVF survivors, but this approach has not been validated in children. This study aimed to assess the yield of clinical cardiac screening in child first-degree relatives of IVF victims. A retrospective observational study was conducted of all consecutive pediatric first-degree relatives of IVF patients referred to our center between December 2007 and April 2020. Patients underwent systematic evaluation including medical and family history; 12-lead resting, signal-averaged, and ambulatory electrocardiogram (ECG); echocardiogram; exercise testing; cardiac magnetic resonance imaging; and ajmaline provocation testing. Sixty child first-degree relatives of 32 IVF survivors were included [median follow-up time of 55 months (IQR 27.0–87.0 months); 30 (50%) females]. Eight patients (13.3%) from 6 families (18.8%) received a cardiac diagnosis: long QT syndrome (n = 4); Brugada syndrome (n = 3); and dilated cardiomyopathy (n = 1). There were no deaths during follow-up. This study demonstrates a high yield of clinical screening for inherited cardiac disease in child first-degree relatives of IVF survivors. These findings highlight the variable expression of inherited cardiac conditions and the importance of comprehensive clinical evaluation in pediatric relatives, even when extensive investigations in the proband have not identified a clear etiology. Moreover, our results support the validity of the investigations proposed by current guidelines in family relatives of IVF survivors. [ABSTRACT FROM AUTHOR]

In some cases with idiopathic ventricular fibrillation, short-coupled premature ventricular contractions (PVCs) initiate fatal arrhythmia, which has recently been proposed as short-coupled ventricular fibrillation (SCVF). In the present case of SCVF, catheter ablation for trigger PVCs originating from the His-Purkinje system in both ventricles caused transient complete atrioventricular block, and a combination of quinidine and verapamil suppressed ventricular tachyarrhythmia. < Learning objective: In some cases with short-coupled ventricular fibrillation, a combination of quinidine and verapamil can suppress fatal ventricular tachyarrhythmia.> [ABSTRACT FROM AUTHOR]

The article presents the discussion on short or long‐coupled idiopathic ventricular fibrillation. Topics include arrhythmias originated from the left posterior fascicle, the left anterior fascicle and presumably the right ventricular moderator band; and performing with the high suspicion where syncope being related to aborted malignant tachyarrhythmias.

Background Idiopathic ventricular fibrillation (IVF) is diagnosed in patients with ventricular fibrillation of which the origin is not identified after extensive evaluations. Recent studies suggest an association between mitral annulus disjunction (MAD), mitral valve prolapse (MVP), and ventricular arrhythmias. The prevalence of MAD and MVP in patients with IVF in this regard is not well established. We aimed to explore the prevalence of MAD and MVP in a consecutive cohort of patients with IVF compared with matched controls. Methods and Results In this retrospective, multicenter cohort study, cardiac magnetic resonance images from patients with IVF (ie, negative for ischemia, cardiomyopathy, and channelopathies) and age‐ and sex‐matched control subjects were analyzed for the presence of MAD (≥2 mm) and MVP (>2 mm). In total, 72 patients (mean age 39±14 years, 42% women) and 72 control subjects (mean age 41±11 years, 42% women) were included. MAD in the inferolateral wall was more prevalent in patients with IVF versus healthy controls (7 [11%] versus 1 [1%], P=0.024). MVP was only seen in patients with IVF and not in controls (5 [7%] versus 0 [0%], P=0.016). MAD was observed in both patients with (n=4) and without (n=3) MVP. Conclusions Inferolateral MAD and MVP were significantly more prevalent in patients with IVF compared with healthy controls. The authors advocate that evaluation of the mitral valve region deserves extra attention in the extensive screening of patients with unexplained cardiac arrest. These findings support further exploration of the pathophysiological mechanisms underlying a subset of IVF that associates with MAD and MVP.

Abstract During an initial diagnosis of IVF, an arrhythmic substrate may be missed for several reasons such as lack of information; thus, a careful follow‐up is important. A three‐dimensional mapping may identify a possible missed arrhythmic substrate in IVF.

We report 3 cases (mean age 48.3 ± 11.6 years) of idiopathic ventricular fibrillation (IVF), in which a triggering premature ventricular complex leading to IVF could not be identified. All patients underwent posterior fascicle transection with empirical linear ablation of the mid-Purkinje potentials identified along the left ventricular interventricular inferior septum, and no ventricular fibrillation recurrence was documented in any of the patients. (Level of Difficulty: Advanced.)

Idiopathic ventricular fibrillation is responsible for ≈5%-7% of aborted cardiac arrest, mainly striking subjects in their forties. Syncope caused by short-coupled rapid polymorphic ventricular tachycardia is frequently noted in a patient's past history. However, a diagnosis of neurally mediated syncope, the most frequent cause of syncope in the young, is often erroneously made. Clinical clues suggest that syncope has an arrhythmic rather than a neurally mediated origin. In addition, the presence of premature ventricular contractions on an electrocardiogram recorded shortly after a syncopal event has utmost importance in establishing the cause of syncope. Although such extrasystoles are frequently benign, especially when associated with a long coupling interval, they also may suggest a malignant origin when closely coupled to the preceding complex with short coupling intervals (usually <350 ms). These arrhythmias mainly originate from the Purkinje system (usually the right ventricle in men and the left ventricle in women) and favorably respond to quinidine as well as to ablation therapy targeting Purkinje-fibers ectopic activity. [ABSTRACT FROM AUTHOR]

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Background: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule., Objectives: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation., Methods: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed., Results: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively., Conclusions: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)