Idiopathic Ventricular Fibrillation Patients Research Articles

Impact of sympathetic innervation on recurrent life-threatening arrhythmias in the follow-up of patients with idiopathic ventricular fibrillation

Idiopathic ventricular fibrillation (IVF) is defined as VF in the absence of any identifiable structural or functional cardiac disease. The underlying pathophysiological mechanisms are unknown. This study was performed to investigate the potential impact of sympathetic dysfunction, assessed by (123)I-meta-iodo-benzylguanidine scintigraphy ((123)I-MIBG SPECT), on the long-term prognosis of patients with IVF. (123)I-MIBG SPECT was performed in 20 patients (mean age 37+/-13 years) with IVF. Mean follow-up of patients after study entry was 7.2+/-1.5 years (range 4.9-10.5 years). Ten patients (five men, five women; mean age 43+/-12 years; p=NS versus study group) with medullary carcinoma of the thyroid gland served as an age-matched control group. Abnormal (123)I-MIBG uptake was observed in 13 patients (65%). During follow-up, 18 episodes of VF/fast polymorphic ventricular tachycardias occurred in four IVF patients with abnormal (123)I-MIBG uptake whereas only two episodes of monomorphic ventricular tachycardia (and no VF) occurred in a single IVF patient with normal (123)I-MIBG uptake. Impairment of sympathetic innervation may indicate a higher risk of future recurrent episodes of life-threatening ventricular tachyarrhythmias in patients with IVF. Studies in larger cohorts are required to validate the significance of (123)I-MIBG SPECT during the long-term follow-up of these patients.

Repolarization Dynamics in Patients with Idiopathic Ventricular Fibrillation

The electrocardiographic parameters relating occurrence of ventricular fibrillation (VF) episodes in patients with idiopathic VF (IVF) are still unknown. The aim of this study was to clarify efficacy of pharmacological therapy in patients with IVF with respect to repolarization dynamics. The study group consisted of 8 men (age 43.6 +/- 9.1 years) with IVF (Brugada type 5 patients, prominent J wave in the inferior leads 3 patients) who had documented spontaneous episodes of VF, 7 of whom had implantable cardioverter defibrillators. The relation between QT and RR interval was analyzed from 24-hour Holter ECG using an automatic analyzing system before and after pharmacological therapy (bepridil 5 and disopyramide 3). From QT-RR linear regression lines, QT intervals were determined at RR intervals of 0.6 second [QT(0.6)], 1.0 second [QT(1.0)], and 1.2 seconds [QT(1.2)]. Pharmacological therapy increased the slope of QT-RR regression line from 0.105 +/- 0.020 to 0.144 +/- 0.037 (P < 0.05). Accordingly, QT(1.0) and QT(1.2) became longer after drug therapy [QT(1.0), 0.382 +/- 0.016 seconds vs 0.414 +/- 0.016 seconds (P < 0.01); QT(1.2), 0.403 +/- 0.017 seconds vs 0.442 +/- 0.021 seconds (P < 0.01)]. However, QT(0.6) did not change after drug administration. Before drug therapy the average episodes of VF were 5.5 +/- 5.8 (range 1 to 17) during the observation period of 19.3 +/- 17.6 months (range 6 to 60 months). After drug therapy, 6 patients had no episode of VF for 24 to 120 months (66.0 +/- 38.5 months). Two patients had a single episode of VF for 12- and 96-month follow-ups. Pharmacological therapy decreased the frequency of VF episodes in association with prolongation of QT intervals at slower heart rates. Not only J wave and ST elevation but also shorter QT intervals at slower heart rates may represent an electrophysiological substrate for development of VF episodes in these specific IVF patients.

Proposed Diagnostic Criteria for the Brugada Syndrome

Asyndrome characterized by ST-segment elevation in right precordial leads (V1 to V3) that is unrelated to ischemia, electrolyte disturbances, or obvious structural heart disease was reported as early as 1953,1 but was first described as a distinct clinical entity associated with a high risk of sudden cardiac death in 1992.2–4⇓⇓ The Brugada syndrome is a familial disease that displays an autosomal dominant mode of transmission, with incomplete penetrance and an incidence ranging between 5 and 66 per 10 000. In regions of Southeast Asia where it is endemic, the clinical presentation of Brugada syndrome is distinguished by a male predominance (8:1 ratio of male:female) and the appearance of arrhythmic events at an average age of 40 years (range: 1 to 77 years).2,5⇓ Although a number of candidate genes are considered plausible, thus far the syndrome has been linked only to mutations in SCN5A , the gene encoding for the α subunit of the sodium channel.6 A number of ambiguities exist concerning the diagnosis of Brugada syndrome. The electrocardiographic signature of the syndrome is dynamic and often concealed, but can be unmasked by potent sodium channel blockers such as flecainide, ajmaline, and procainamide,7 although the specificity of this effect for uncovering patients at risk for sudden death has been an issue of concern. A recent report by Remme et al8 has shown that the number of idiopathic ventricular fibrillation patients diagnosed as having Brugada syndrome is a sensitive function of the diagnostic criteria applied. What are the proper diagnostic criteria for identifying Brugada syndrome? A definitive answer to this question has been out of reach and is the reason for the establishment of a special Arrhythmia Working Group of the European Society of Cardiology that met from August 31 to …

A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome

Mutations in the human cardiac Na + channel α subunit gene ( SCN5A) are responsible for Brugada syndrome, an idiopathic ventricular fibrillation (IVF) subgroup characterized by right bundle branch block and ST elevation on an electrocardiogram (ECG). However, the molecular basis of IVF in subgroups lacking these ECG findings has not been elucidated. We performed genetic screenings of Japanese IVF patients and found a novel SCN5A missense mutation (S1710L) in one symptomatic IVF patient that did not exhibit the typical Brugada ECG. Heterologously expressed S1710L channels showed marked acceleration in the current decay together with a large hyperpolarizing shift of steady-state inactivation and depolarizing shift of activation. These findings suggest that SCN5A is one of the responsible genes for IVF patients who do not show typical ECG manifestations of the Brugada syndrome.

Spatial features in body surface potential maps of patients with ventricular tachyarrhythmias with or without coronary artery disease

Body surface potential maps (BSPM) from patients with coronary artery disease or no structural heart disease were analyzed with respect to their spatial features and QT/QT c dispersion in order to determine whether BSPM allows identification of patients with ventricular fibrillation. QRST integral maps and QT/QT c dispersion were acquired from simultaneous recordings of 62 ECG leads during sinus rhythm in patients with idiopathic ventricular fibrillation ( n=13), ventricular fibrillation and coronary artery disease ( n=22), coronary artery disease without ventricular fibrillation ( n=21) and healthy controls ( n=18). The Karhunen-Loève transformation was applied to reduce the dimensionality of the data matrix of the QRST map to eight coefficients. Linear discriminant analysis allowed discrimination between idiopathic ventricular fibrillation patients and controls with high sensitivity (85%) and specificity (89%). However, discrimination between coronary artery disease patients with or without ventricular fibrillation was poor (68% and 67%, respectively). QT c dispersion calculated from BSPM was longer in idiopathic ventricular fibrillation patients than in controls (99±30 ms vs 70±14 ms, P=0.009) in contrast to QT c dispersion taken from 12-lead ECG (53±21 ms vs. 47±12 ms, P=n.s.). No significant difference was noted for coronary artery disease patients with or without ventricular fibrillation. In conclusion, repolarization disturbances detected by BSPM allow identification of ventricular fibrillation patients without structural heart disease. However, our results do not suggest a major impact of QT/QT c dispersion or QRST integral mapping for identification of ventricular fibrillation patients with coronary artery disease.

Genetic basis and molecular mechanism for idiopathic ventricular fibrillation.

Ventricular fibrillation causes more than 300,000 sudden deaths each year in the USA alone. In approximately 5-12% of these cases, there are no demonstrable cardiac or non-cardiac causes to account for the episode, which is therefore classified as idiopathic ventricular fibrillation (IVF). A distinct group of IVF patients has been found to present with a characteristic electrocardiographic pattern. Because of the small size of most pedigrees and the high incidence of sudden death, however, molecular genetic studies of IVF have not yet been done. Because IVF causes cardiac rhythm disturbance, we investigated whether malfunction of ion channels could cause the disorder by studying mutations in the cardiac sodium channel gene SCN5A. We have now identified a missense mutation, a splice-donor mutation, and a frameshift mutation in the coding region of SCN5A in three IVF families. We show that sodium channels with the missense mutation recover from inactivation more rapidly than normal and that the frameshift mutation causes the sodium channel to be non-functional. Our results indicate that mutations in cardiac ion-channel genes contribute to the risk of developing IVF.

Adjustment for QRS duration and improving QT correction for heart rate

The presence of J waves on ECGs is related to idiopathic ventricular fibrillation (VF).The purpose of this study was to investigate the pathophysiology of J waves by assessing risk markers that reflect electrophysiologic abnormalities.The study enrolled 22 idiopathic VF patients (17 men and 5 women; mean age 36 ± 13 years). Patients were divided into two groups according to the presence or absence of J waves. The following risk stratifiers were assessed: late potentials (LPs; depolarization abnormality marker) for 24 hours using a newly developed signal-averaging system, and T-wave alternans and QT dispersion (repolarization abnormality markers). Frequency-domain heart rate variability (HRV), which reflects autonomic modulation, also was assessed. The results were compared to those of 30 control subjects with J waves and 30 with no J wave, matched for age and gender to the idiopathic VF patients.J waves were present in 7 (32%) idiopathic VF patients. The incidence of LP in the idiopathic VF J-wave group was higher than in the idiopathic VF non–J-wave group (86% vs 27%, P = .02). In contrast, repolarization abnormality markers did not differ between the two groups. In the idiopathic VF J-wave group, dynamic changes in LP parameters (fQRS, RMS40, LAS40) were observed and were pronounced at nighttime; this was not the case in the idiopathic VF non–J-wave group and the control J-wave group. High-frequency components (vagal tone index) on frequency-domain HRV analysis were associated with J waves in idiopathic VF patients (P < .05).Idiopathic VF patients with J waves had a high incidence of LP showing circadian variation with night ascendancy. J waves may be more closely associated with depolarization abnormality and autonomic modulation than with repolarization abnormality.