Idiopathic Ventricular Fibrillation Survivors Research Articles

Evolution of the ECG in idiopathic ventricular fibrillation survivors: results from a single-centre UK registry

Abstract Background Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion in subjects with an unexplained cardiac arrest and no evidence of overt structural or electrical cardiac abnormalities (1). It can be associated with an early repolarisation pattern (ERP)(2). Data on the evolution of the ECG in this population are lacking. Purpose To compare the baseline ECG characteristic of idiopathic VF survivors and age and gender matched controls, and investigate if the presence of an ERP at ECG is a predictor of risk. Methods Forty-nine subjects with idiopathic VF evaluated in our tertiary centre from 1997 to 2022, and followed-up for at least 3 months were included in this study. The first representative ECG available after cardiac arrest was evaluated and compared with that of an age and gender matched control with no symptoms, family history of sudden cardiac death and normal cardiac tests; moreover, comparison was made with a follow-up ECG off antiarrhythmic medications (quinidine, amiodarone and verapamil). Medical notes were reviewed to investigate the presence of events at f-up (SCD/appropriate ICD shock). Results The mean age at presentation was 33±7 years; 63% of patients were males, and 16% had previous syncope. Twelve cases (24%) and 6 controls (12%) showed ERP on the resting ECG (P=NS). Only resting heart rate (HR) and QRS duration differed between the two groups (Table 1). Follow-up ECGs in 46 idiopathic VF survivors indicated that resting HR, QRS axis and QTc values were significantly different compared to the baseline ECG. In addition, 4 subjects with ERP at baseline did not exhibit it on the most recent ECG, and 6 subjects without ERP at baseline showed it on the most recent ECG. Over a median follow-up of 3.3 years (IQR 6), 13 subjects experienced appropriate ICD shocks. Kaplan-Meyer survival estimates showed no differences in events between subjects showing ERP or not (log rank p=0.092). Conclusions Subjects with idiopathic VF show baseline ECGs similar to those of age and gender matched healthy controls from the general population. ECG parameters tend to change only slightly over long-term follow up. The ERP in idiopathic VF survivors is dynamic and thus its relationship with events may be underestimated.Table 1 Table 2

Ventricular Conduction Stability Noninvasively Identifies an Arrhythmic Substrate in Survivors of Idiopathic Ventricular Fibrillation.

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.

Prevalence of Inherited Cardiac Conditions in Pediatric First-Degree Relatives of Patients with Idiopathic Ventricular Fibrillation.

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 55months (IQR 27.0-87.0months); 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.

Medium-term outcomes of idiopathic ventricular fibrillation survivors and family screening: a multicentre experience.

Early repolarization (ER) has been linked to poorer outcomes in idiopathic ventricular fibrillation (IVF). The role of family screening in IVF is not clear. Our aim was to review predictors for poorer outcomes and evaluate the role of family screening in IVF. This was a retrospective multicentre cohort study including all patients diagnosed with IVF. Data were collected on baseline characteristics, ECG findings, and recurrence of ventricular arrhythmia (VA) during follow-up. Electrocardiogram findings were reviewed in first-degree relatives that were screened. A total of 66 patients were included with male predominance (42/66, 64%) and Caucasian ethnicity (47/66, 71%). Mean age at cardiac arrest was 38 years ± 11. Thirty-one patients had ER (47%) predominantly with J-point amplitude ≥2 mm and horizontal ST segments (18/31, 58%). Recurrent VA was seen in 13 patients (20%). Horizontal ST segments were associated with increased rates of VA recurrence (OR 11, 95% CI 2.7-43.7; P = 0.0007). Early repolarization was seen in 20% of the 72 first-degree relatives and was more common if the proband had persistent ER pattern (OR 10.7, 95% CI 2.2-51.5; P = 0.003). Ventricular arrhythmia recurrence was lower than previously reported. Early repolarization was common in this IVF cohort, and horizontal ST segments were suggestive predictor for poorer outcomes. Persistent ER in proband was associated with ER in first-degree relatives. With better understanding of its predictive value and the relationship to IVF, this information could potentially be used to guide family screening and identify new mutations using family members with persistent ER.

Quantitative Assessment of the Effects of Therapeutic Hypothermia on Early Repolarization in Idiopathic Ventricular Fibrillation Survivors

Background— The early repolarization (ER) pattern on ECG is associated with an increased risk of idiopathic ventricular fibrillation (ID-VF). Hypothermia is known to result in similar electrocardiographic changes. In this retrospective cohort study, we examine the impact of therapeutic hypothermia on ER in survivors of cardiac arrest attributed to ID-VF and draw comparisons with a control group who experienced coronary artery disease–related VF (CAD-VF). Methods and Results— All patients who had cardiac arrest and were treated with therapeutic hypothermia over a 7-year period were considered for inclusion in the study. Forty-three patients were identified with ID-VF or CAD-VF arrest. ECGs were obtained during cooling and again after rewarming. ECGs were digitized and assessed for the presence of ER by 2 independent observers. Cooling significantly increased the prevalence (74% during cooling versus 51% at baseline temperature; P =0.044) and mean amplitude (0.78±0.10 mV during cooling versus 0.56±0.09 mV at baseline temperature; P =0.038) of ER in the overall cohort. During cooling, ER was more common among survivors of ID-VF than of CAD-VF (100% versus 67%; P =0.043). ER magnitude was significantly greater among ID-VF survivors than CAD-VF survivors both during cooling (1.16±0.18 versus 0.70±0.11 mV; P =0.044) and at baseline temperature (1.02±0.21 versus 0.42±0.09 mV; P =0.005). Conclusions— Hypothermia increases both the prevalence and magnitude of ER in cardiac arrest survivors. Despite the association of ER with ID-VF, therapeutic hypothermia only increases ER amplitude in CAD-VF survivors.

The investigation of sudden arrhythmic death syndrome (SADS)—the current approach to family screening and the future role of genomics and stem cell technology

SADS is defined as sudden death under the age of 40 years old in the absence of structural heart disease. Family screening studies are able to identify a cause in up to 50% of cases-most commonly long QT syndrome (LQTS), Brugada and early repolarization syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT) using standard clinical screening investigations including pharmacological challenge testing. These diagnoses may be supported by genetic testing which can aid cascade screening and may help guide management. In the current era it is possible to undertake molecular autopsy provided suitable samples of DNA can be obtained from the proband. With the evolution of rapid sequencing techniques it is possible to sequence the whole exome for candidate genes. This major advance offers the opportunity to identify novel causes of lethal arrhythmia but also poses the challenge of managing the volume of data generated and evaluating variants of unknown significance (VUS). The emergence of induced pluripotent stem cell technology could enable evaluation of the electrophysiological relevance of specific ion channel mutations in the proband or their relatives and will potentially enable screening of idiopathic ventricular fibrillation survivors combining genetic and electrophysiological studies in derived myocytes. This also could facilitate the assessment of personalized preventative pharmacological therapies. This review will evaluate the current screening strategies in SADS families, the role of molecular autopsy and genetic testing and the potential applications of molecular and cellular diagnostic strategies on the horizon.

Early repolarization: A sword in the haystack?

Much has been written over the past few years regarding the early repolarization syndrome. Works by Gussak and Antzelevitch,1 Haissaguerre et al,2 Rosso et al,3 and others have redefined this electrocardiogram (ECG) finding as a risk factor for idiopathic ventricular fibrillation (VF), a dramatic change for a common ECG abnormality that was once believed to be a benign variant. Collectively, these studies have demonstrated an increased prevalence of early repolarization, as described as J-point elevation in a notching or slurring pattern in the inferior or lateral leads, in idiopathic VF survivors vs matched controls.

Yield of Genetic Screening in Inherited Cardiac Channelopathies

Background— Identification of mutations in cardiac ion channel genes concurs to the diagnosis of long-QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. However, because availability of genetic screening is still limited and reimbursement policies are lacking, there is a need of evidence-based criteria to prioritize access to genetic testing for these diseases. Methods and Results— We determined the yield of genetic testing and cost per positive genotyping in 1394 consecutive probands. Among the 546 patients referred for long-QT syndrome-genes screening, those with clinical diagnosis of long-QT syndrome had the highest yield (64%) and lowest cost (US $8418) for each positive genotyping. Among 798 individuals screened for mutation on the SCN5A gene, the highest yield was obtained in patients with type 1 Brugada syndrome ECG pattern (51 of 405; 13%) corresponding to a cost of US $21441 per positive genotyping. In conclusive Brugada syndrome patients the presence of atrioventricular block (odds ratio: 3.3, CI: 1.8 to 6.1; P =0.0001) increases the yield (23%) of genotyping and reduces its cost (US $ 11700). Among 175 patients screened on RyR2 gene, those with documented bidirectional ventricular tachycardia had the highest incidence (62%) of mutations and the lowest cost (US $5263) per positive genotyping. Genetic screening of unselected family members of sudden cardiac death victims and idiopathic ventricular fibrillation survivors is largely ineffective (yield of 9%) and costly (US $71430 per 1 positive genotyping). Conclusions— Genotyping can be performed at reasonable cost in individuals with conclusive diagnosis of long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia, and in patients with type I Brugada syndrome ECG with atrioventricular block. These patients should be given priority to access genetic testing.

Cost-Effectiveness of Genotyping in Inherited Arrhythmia Syndromes

Over the last decade, the identification of the diverse genetic basis of most important inherited arrhythmia syndromes has remarkably changed our attitude toward these life-threatening diseases. Just over 10 years ago, long-QT syndrome (LQTS) was considered one disease entity, Brugada syndrome (BrS) had just been described, and short-QT syndrome was not yet recognized. In addition to improved understanding of the pathophysiological basis of these disorders, these advances have added genetic testing to our diagnostic armentarium, providing new opportunities for patient management. Early (presymptomatic) identification and treatment of patients at risk of developing fatal arrhythmias is now a reality. More importantly, in particular in LQTS, gene-specific aspects of disease management have evolved, making gene testing highly desirable.1 Article see p 6 One of the difficult aspects of genetic testing, however, are the financial costs, which are considerable. Reimbursement policies dealing with this issue are lacking in almost every country in the (Western) world, a problem that has certainly contributed to prohibiting widespread dissemination. Priori and coworkers2 are applauded for tackling this issue and providing insight into the genotyping cost of the most important primary arrhythmia syndromes. Not unexpectedly, these costs are indeed considerable. They vary between $8418 (±Є6734) for LQTS with high clinical suspicion to $71430 (±Є57144) for idiopathic ventricular fibrillation survivors. In assessing these costs, the most important determinants were the prices of the commercial genotyping company, Familion, and the subdivision of patients on the basis of their clinical characteristics into groups for which affection by the disorder was considered conclusive versus possible.2 Positive genotyping was defined as “a mutation with high probability causative of the inherited cardiac ionchannelopathy.”2 All of these parameters need to be considered carefully. First, it should be noted that getting to a genetic diagnosis is not …

Early Repolarization in Survivors of Idiopathic Ventricular Fibrillation

Early repolarization is a common electrocardiographic finding that is thought to be benign. However, experimental evidence suggests that early

Distribution and Prognostic Significance of QT Intervals in the Lowest Half Centile in 12,012 Apparently Healthy Persons

The presence of an abnormally short QT interval has been noted among survivors of idiopathic ventricular fibrillation and among close relatives of victims of unexplained sudden death. Most reported cases have had rate-corrected QT (QTc) intervals of <300 ms. The prevalence of such values in the community has not been documented. We reviewed the electrocardiograms (ECGs) of 12,012 subjects who underwent routine medical examinations for occupational reasons. The QT interval was measured by 2 physicians in all cases, and QTc interval was calculated. All ECGs with QTc values in the lowest 5% were reviewed by 2 cardiologists expert in QT analysis, and the QT measurement was corrected if necessary. Information about subsequent survival was obtained from the case file or from public records. In the lowest 1/2 centile, the distribution of QTc values continued to follow a normal pattern without evidence of a distinct subpopulation of low values. The shortest QTc encountered was 335 ms. Information about subsequent survival was available for 36 of the 60 subjects with the lowest 1/2 centile of QTc values. None of these subjects died during the 7.9 +/- 4.5 years subsequent to the ECG that demonstrated the short QT interval. In conclusion, a QTc interval of <or=330 ms is extremely rare in healthy subjects, and the presence of a QT interval in the lowest 1/2 centile of the normal range does not imply a significant risk of sudden death.

Psychological Stress Preceding Idiopathic Ventricular Fibrillation

Emotional stress is well established as a trigger of sudden death in the context of coronary heart disease (CHD), but its role in patients experiencing cardiac arrest with apparently normal hearts is unknown. This study sought to determine the role of psychosocial stress as a precipitant of cardiac arrest in patients with apparently normal hearts, so-called idiopathic ventricular fibrillation (IVF). We interviewed 25 IVF survivors (12 men, 13 women) and 25 matched comparison patients regarding life events during the 6 months and 24 hours preceding the cardiac event. The comparison group consisted of patients with an acute myocardial infarction or angina pectoris requiring angioplasty but without cardiac arrest. Judges independently rated written summaries of these interviews for psychosocial stress at each time point on a three-point scale (low, moderate, severe). During the 6 months before the cardiac event, 20 patients sustaining IVF had severe/moderate stress and five had low stress, whereas 10 comparison patients had severe/moderate stress and 15 had low stress (Fisher exact p = .008). During the preceding 24 hours, nine patients with IVF had severe/moderate stress and 16 had low stress, whereas two comparison patients had severe/moderate stress and 22 had low stress (Fisher exact p = .04) (one silent myocardial infarction could not be precisely dated). These data suggest that psychosocial stress is playing a role in otherwise unexplained cardiac arrest.

Late Outcome of Survivors of Idiopathic Ventricular Fibrillation

This report describes clinical, hemodynamic, and electrophysiologic characteristics of 18 consecutive survivors of sudden cardiac arrest due to idiopathic ventricular fibrillation (VF) between 1986 and 1996. Long-term data in relation to the prescribed therapy are presented. The mean age of the 18 patients was 48 ± 14 years (median 49). Electrophysiologic studies showed a low inducibility of sustained ventricular tachyarrhythmias in 4 patients (22%). Treatment consisted of class III agents, β blockers, or implantable cardioverter-defibrillators. Two patients were discharged without any therapy. Therapy control was undertaken either by serial drug testing or by the empirical approach. Serious complications of therapy occurred in 2 patients: 1 patient experienced a proarrhythmic effect of antiarrhythmic drug therapy, and the other patient received multiple inadequate defibrillator discharges due to a defect in the transvenous lead. All but 1 patient (94%) remained free of recurrences of sudden cardiac arrest during a follow-up time of 45 ± 29 months (median 41). One patient died 2 weeks after surviving cardiac arrest due to intractable VF while receiving sotalol treatment. Therapy guided by electrophysiologic studies did not have any impact on survival. Adverse effects or noncompliance led to discontinuation of drug therapy in 7 patients after a mean period of 31 ± 30 months. Without any treatment 9 patients remained without recurrences over 45 ± 33 months. Because of the absence of risk factors for arrhythmia recurrence and criteria to select therapy, randomized prospective studies are warranted to assess the optimal therapies in these young, ostensibly healthy patients.