The inheritance of premature ventricular excitation syndrome and the evolution of its clinical course according to prospective studies

Interest for the problem of inheritance of premature ventricular excitation syndrome (PVES) has grown significantly in the recent years due to an increase in the prevalence of paroxysmal supraventricular tachycardia and atrial fibrillation in the general population. Appearance of such cardiac arrhythmias in young people makes it necessary to include PVES in diagnostic search program. At the same time, the clinical picture of the disease may change with age and appearance of various cardiovascular pathology. A prospective study including 240 patients was undertaken to study the evolution of the clinical course of PVES. A 30-year observation showed that in 88% of PVES patients the number of forms and the degree of the severity of cardiac arrhythmias tended to grow. By the end of the study the prevalence of paroxysmal supraventricular tachycardia had decreased significantly, while the number of patients with atrial fibrillation had increased. Attacks of atrial fibrillation occurred in PVES at older age than paroxysmal tachycardia, and it was observed much more often in cases where PVES was combined with other heart diseases. Thus, the studies show that paroxysms of atrial fibrillation in PVES patients occur more often in the presence of different cardiovascular diseases, and that clinical manifestations of PVES are determined by the evolution of the associated diseases as well.     

Pathogenesis of cardiac conduction disorders in children genetic and histopathologic aspects

Fetal dysrhythmias are usually transient. Abnormal fetal rates and rhythms during labor are "functional." Fetal dysrhythmias may be associated with congenital heart disease and fetal hydrops. Bradycardia is usually related to fetal distress; supraventricular tachycardia, atrial flutter, and atrial fibrillation may be associated with severe congestive heart failure. Ventricular fibrillation is rare in the fetus and infant and is usually associated with myocardial necrosis with perimembranous septal defect; the nonbranching atrioventricular (AV) bundle may have an aberrant position and result in cardiac arrhythmia. Wolff-Parkinson-White syndrome with conduction abnormalities and left ventricular hypertrophy (LVH) is due to an accessory pathway that bypasses the AV sulcus and results in faster conduction. Carnitine deficiency may be primary or secondary and may result in cardiac arrhythmia. Histiocytoid cardiomyopathy is characterized by cardiomegaly, incessant ventricular tachycardia, and frequently sudden death. Arrhythmogenic right ventricular dysplasia (ARVD) results in ventricular tachycardia and left bundle branch block. Noncompaction of the left ventricle predisposes to potentially fatal arrhythmias. Long Q-T syndromes (LQTS) are a heterogeneous group of disorders with many genetic mutations. Brugada syndrome is an autosomal dominant trait with right bundle branch block and ST elevation. Barth syndrome is an X-linked disorder with dilated cardiomyopathy, cyclic neutropenia and skeletal myopathy. Hypertrophic cardiomyopathy in infancy may be related to metabolic diseases, particularly glycogen storage diseases; the familial form predisposes to sudden death. Arrhythmias following cardiac surgery may occur after closure of a ventricular septal defect (VSD) or damage to the conduction system.     

Pathological analysis of myocardial cell under ventricular tachycardia and fibrillation based on symbolic dynamics.

Ventricular fibrillation (VF) is one of the most serious malignant arrhythmias usually resulting from immediate degeneration of ventricular tachycardia (VT). In order to analyse the nonlinear dynamics of the cardiac micro-mechanism under VT and VT rhythm, at the cellular level, myocardial cell action potentials are investigated under different rhythm, normal sinus rhythm, VT and VT. On the basis of nonlinear chaotic theory and symbolic dynamics, we put forward new definitions, complexity rate, etc, and obtained some useful properties for cellular electrophysiological analysis. The results of the experiments and computation show that the myocardial cellular signals under VT and VF rhythm are different kinds of chaotic signals in that the cardiac chaos attractor under VF is higher than that under VT. The analytical complexity theory has been promising in the clinical application.     

Pathological analysis of myocardial cell under ventricular tachycardia and fibrillation based on symbolic dynamics

Ventricular fibrillation (VF) is one of the most serious malignant arrhythmias usually resulting from immediate degeneration of ventricular tachycardia (VT). In order to analyse the nonlinear dynamics of the cardiac micro-mechanism under VT and VF rhythm, at the cellular level, myocardial cell action potentials are investigated under different rhythm, normal sinus rhythm, VT and VF. On the basis of nonlinear chaotic theory and symbolic dynamics, we put forward new definitions, complexity rate, etc, and obtained some useful properties for cellular electrophysiological analysis. The results of the experiments and computation show that the myocardial cellular signals under VT and VF rhythm are different kinds of chaotic signals in that the cardiac chaos attractor under VF is higher than that under VT. The analytical complexity theory has been promising in the clinical application.     

Effect of regional differences in cardiac cellular electrophysiology on the stability of ventricular arrhythmias: a computational study

Re-entry is an important mechanism of cardiac arrhythmias. During re-entry a wave of electrical activation repeatedly propagates into recovered tissue, rotating around a rod-like filament. Breakdown of a single re-entrant wave into multiple waves is believed to underlie the transition from ventricular tachycardia to ventricular fibrillation. Several mechanisms of breakup have been identified including the effect of anisotropic conduction in the ventricular wall. Cells in the inner and outer layers of the ventricular wall have different action potential durations (APD), and support re-entrant waves with different periods. The aim of this study was to use a computational approach to study twisting and breakdown in a transmural re-entrant wave spanning these regions, and examine the relative role of this effect and anisotropic conduction. We used a simplified model of action potential conduction in the ventricular wall that we modified so that it supported stable re-entry in an anisotropic model with uniform APD. We first examined the effect of regional differences on breakdown in an isotropic model with transmural differences in APD, and found that twisting of the re-entrant filament resulted in buckling and breakdown during the second cycle of re-entry. We found that breakdown was amplified in the anisotropic model, resulting in complex activation in the region of longest APD. This study shows that regional differences in cardiac electrophysiology are a potentially important mechanism for destabilizing re-entry and may act synergistically with other mechanisms to mediate the transition from ventricular tachycardia to ventricular fibrillation.     

Cardiac arrhythmias in aluminium phosphide poisoning studied by on continuous holter and cardioscopic monitoring

Variable incidences of cardiac arrhythmias (based on isolated 12 lead ECG records) have been reported in patients of aluminium phosphide (ALP) poisoning. We did continuous holter and cardioscopic monitoring in ICU in 30 patients of acute ALP poisoning. Supraventricular and ventricular ectopics were recorded in each and every patient. Life threatening ventricular tachycardia was recorded in 40% cases and ventricular fibrillation in 23.3% cases. Supraventricular tachycardia and atrial flutter/fibrillation occurred in 46.7% and 20% patients, respectively. ST-T changes simulating myocardial ischaemia were also present in all patients (S-T depression in 90%, S-T elevation in 10%). One-third of the patients developed variable degrees of heart block, IV amiodarone/xylocard could revert dangerous ventricular arrhythmias to sinus rhythm in 4 cases. Toxic myocarditis produced by phosphine seems to be responsible for the development of these arrhythmias.     

Reversible cardiac conduction block and defibrillation with high-frequency electric field

Electrical impulse propagation is an essential function in cardiac, skeletal muscle, and nervous tissue. Abnormalities in cardiac impulse propagation underlie lethal reentrant arrhythmias, including ventricular fibrillation. Temporary propagation block throughout the ventricular myocardium could possibly terminate these arrhythmias. Electrical stimulation has been applied to nervous tissue to cause reversible conduction block, but has not been explored sufficiently in cardiac tissue. We show that reversible propagation block can be achieved in cardiac tissue by holding myocardial cells in a refractory state for a designated period of time by applying a sustained sinusoidal high-frequency alternating current (HFAC); in doing so, reentrant arrhythmias are terminated. We demonstrate proof of concept using several models, including optically mapped monolayers of neonatal rat ventricular cardiomyocytes, Langendorff-perfused guinea pig and rabbit hearts, intact anesthetized adult rabbits, and computer simulations of whole-heart impulse propagation. HFAC may be an effective and potentially safer alternative to direct current application, currently used to treat ventricular fibrillation.     

Studies on faint attack due to arrhythmias with Holter electrocardiogram

Out of 1,400 Holter ECGs, 15 records revealed arrhythmias which would be responsible for faint attack, including 8 sick sinus syndrome with cardiac arrest, 4 non-sustained ventricular tachycardia (VT), 2 paroxysmal atrial fibrillation and 1 paroxysmal supraventricular tachycardia. All of cardiac arrest corresponding to faint attack lasted for longer than 4 sec, and an averaged duration of the arrest was 5.8 +/- 2.3 sec. This was significantly longer than that with no subjective symptoms, 3.4 +/- 0.7 sec. Duration and rate of VT did not show any significant relationship with faint attack. The result suggests that cardiac arrest is mostly responsible for arrhythmia-induced involvement of cerebral circulation and faint attack. It is also suggested that cardiac arrest longer than 4 sec should be extensively treated including pacemaker implantation.     

Ventricular fibrillation in the Wolff-Parkinson-White syndrome.

To examine the risk of ventricular fibrillation in patients with the Wolff-Parkinson-White syndrome, we compared patients who had this syndrome and a history of ventricular fibrillation related to preexcitation with patients who had the syndrome without this history. Ventricular fibrillation occurred during atrial fibrillation, with rapid conduction over the accessory pathway, and these patients had a higher prevalence of both reciprocating tachycardia and atrial fibrillation (14 of 25 vs. 18 of 73, P = 0.004) and multiple accessory pathways (five of 25 vs. four of 73, P = 0.012). The shortest preexcitation R-R interval during atrial fibrillation was less in the group with ventricular fibrillation (mean shortest R-R, 180 vs. 240 milliseconds, P less than 0.0001) as was the average R-R interval (mean average R-R, 269 vs 340 milliseconds, P less than 0.0001). Patients with Wolff-Parkinson-White syndrome who are most susceptible to ventricular fibrillation have a history of atrial fibrillation and reciprocating tachycardia, demonstrate rapid conduction over an accessory pathway during atrial fibrillation and have multiple accessory pathways.     

Cardiac rhythm in healthy elderly subjects

Summary To study the normal cardiac rhythm in elderly subjects we performed 24-h Holter monitoring on 94 subjects aged over 70 years. We had previously discarded those with cardiac disease by using history, physical examination, electrocardiography (ECG), chest X-radiography and Doppler echocardiography. The maximum, average and minimum heart rates were 113, 79 and 62, respectively, during the day, and 90, 64 and 53 during the night. Supraventricular and ventricular arrhythmias were frequent (91% and 89.4% respectively). Some 50% of the subjects had complex ventricular arrhythmias. Two subjects presented with sinus pauses of more than 2 s, and 4 had Wenckebach second-degree atrioventricular (AV) block. During a follow-up averaging 20.8 months, there were no deaths or symptoms of an arrhythmic origin.Abbreviations ECG electrocardiogram - AV atrioventricular - HBP hypertension - AT atrial tachycardia - FC functional class - VT ventricular tachycardia - bpm beats per minute - SVE supraventricular extrasystoles - AF atrial fibrillation - VE ventricular extrasystole - W-AVB Wenckebach atrioventricular block     

Detection of life-threatening cardiac arrhythmias using the wavelet transformation

Time-frequency wavelet theory is used for the detection of life threatening electrocardiography (ECG) arrhythmias. This is achieved through the use of the raised cosine wavelet transform (RCWT). The RCWT is found to be useful in differentiating between ventricular fibrillation, ventricular tachycardia and atrial fibrillation. Ventricular fibrillation is characterised by continuous bands in the range of 2–10 Hz; ventricular tachycardia is characterised by two distinct bands: the first band in the range of 2–5 Hz and the second in the range of 6–8 Hz; and atrial fibrillation is determined by a low frequency band in the range of 0–5 Hz. A classification algorithm is developed to classify ECG records on the basis of the computation of three parameters defined in the time-frequency plane of the wavelet transform. Furthermore, the advantage of localising and separating ECG signals from high as well as intermediate frequencies is demonstrated. The above capabilities of the wavelet technique are supported by results obtained from ECG signals obtained from normal and abnormal subjects.     

Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation

Small conductance Ca²⁺-activated K⁺ channels (SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca²⁺  (Ca²⁺_i)  with membrane potential. We have recently reported the functional existence of SK2 channels in human and mouse cardiac myocytes. Moreover, we have found that the channel is predominantly expressed in atria compared to the ventricular myocytes. We hypothesize that knockout of SK2 channels may be sufficient to disrupt the intricate balance of the inward and outward currents during repolarization in atrial myocytes. We further predict that knockout of SK2 channels may predispose the atria to tachy-arrhythmias due to the fact that the late phase of the cardiac action potential is highly susceptible to aberrant excitation. We take advantage of a mouse model with genetic knockout of the SK2 channel gene. In vivo and in vitro electrophysiological studies were performed to probe the functional roles of SK2 channels in the heart. Whole-cell patch-clamp techniques show a significant prolongation of the action potential duration prominently in late cardiac repolarization in atrial myocytes from the heterozygous and homozygous null mutant animals. Morover, in vivo electrophysiological recordings show inducible atrial fibrillation in the null mutant mice but not wild-type animals. No ventricular arrhythmias are detected in the null mutant mice or wild-type animals. In summary, our data support the important functional roles of SK2 channels in cardiac repolarization in atrial myocytes. Genetic knockout of the SK2 channels results in the delay in cardiac repolarization and atrial arrhythmias.     

A practical reconstructed phase space approach for ECG arrhythmias classification

Abstract

Atrial and ventricular arrhythmias are symptoms of the main common causes of rapid death. The severity of these arrhythmias depends on their occurrence either within the atria or ventricles. These abnormalities of the heart activity may cause an immediate death or cause damage of the heart. In this paper, a new algorithm is proposed for the classification of life threatening cardiac arrhythmias including atrial fibrillation (AF), ventricular tachycardia (VT) and ventricular fibrillation (VF). The proposed technique uses a simple signal processing technique for analysing the non-linear dynamics of the ECG signals in the time domain. The classification algorithm is based upon the distribution of the attractor in the reconstructed phase space (RPS). The behaviour of the ECG signal in the reconstructed phase space is used to determine the classification features of the whole classifier. It is found that different arrhythmias occupy different regions in the reconstructed phase space. Three regions in the RPS are found to be more representative of the considered arrhythmias. Therefore, only three simple features are extracted to be used as classification parameters. To evaluate the performance of the presented classification algorithm, real datasets are obtained from the MIT database. A learning dataset is used to design the classification algorithm and a testing dataset is used to verify the algorithm. The algorithm is designed to guarantee achieving both 100% sensitivity and 100% specificity. The classification algorithm is validated by using 45 ECG signals spanning the considered life threatening arrhythmias. The obtained results show that the classification algorithm attains a sensitivity ranging from 85.7–100%, a specificity ranging from 86.7–100% and an overall accuracy of 95.55%.     

The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity

The purpose of this study is to test the role that parasympathetic postganglionic neurons could play on the adaptive electrophysiological changes produced by physical training on intrinsic myocardial automatism, conduction and refractoriness. Trained rabbits were submitted to a physical training protocol on treadmill during 6 weeks. The electrophysiological study was performed in an isolated heart preparation. The investigated myocardial properties were: (a) sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c) atrial, conduction system and ventricular refractoriness. The parameters to study the refractoriness were obtained by means of extrastimulus test at four different pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200 and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular fibrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 μM), in order to block cholinergic receptors. Cholinergic receptor blockade did not modify either the increase in sinus cycle length, atrioventricular conduction and refractoriness (left ventricular and atrioventricular conduction system functional refractory periods) or the decrease of DF of VF. These findings reveal that the myocardial electrophysiological modifications produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.     

Variants in NAA15 cause pediatric hypertrophic cardiomyopathy

The NatA N‐acetyltransferase complex is important for cotranslational protein modification and regulation of multiple cellular processes. The NatA complex includes the core components of NAA10, the catalytic subunit, and NAA15, the auxiliary component. Both NAA10 and NAA15 have been associated with neurodevelopmental disorders with overlapping clinical features, including variable intellectual disability, dysmorphic facial features, and, less commonly, congenital anomalies such as cleft lip or palate. Cardiac arrhythmias, including long QT syndrome, ventricular tachycardia, and ventricular fibrillation were among the first reported cardiac manifestations in patients with NAA10‐related syndrome. Recently, three individuals with NAA10‐related syndrome have been reported to also have hypertrophic cardiomyopathy (HCM). The general and cardiac phenotypes of NAA15‐related syndrome are not as well described as NAA10‐related syndrome. Congenital heart disease, including ventricular septal defects, and arrhythmias, such as ectopic atrial tachycardia, have been reported in a small proportion of patients with NAA15‐related syndrome. Given the relationship between NAA10 and NAA15, we propose that HCM is also likely to occur in NAA15‐related disorder. We present two patients with pediatric HCM found to have NAA15‐related disorder via exome sequencing, providing the first evidence that variants in NAA15 can cause HCM.     

Sustained arrhythmias in hypertrophic obstructive cardiomyopathy

Patients with hypertrophic obstructive cardiomyopathy are subject to syncope and sudden death. Ambulatory monitoring discloses frequent and complex ventricular ectopy in many of these patients, and the occurrence of ventricular tachycardia suggests an increased risk of sudden death. We prospectively evaluated whether induced sustained arrhythmia could explain episodes of cerebral dysfunction in hypertrophic cardiomyopathy. Seven consecutive symptomatic patients (six of whom had an intraventricular gradient of 40 to 130 mm Hg) were subjected to atrial and ventricular stimulation. An electrophysiologic abnormality that would explain the symptoms was identified in every patient: supraventricular tachycardia was present in two, sustained ventricular tachycardia in three, ventricular fibrillation in one, and a prolonged QT interval and dispersion of ventricular refractoriness in one. Antiarrhythmic drugs were selected on the basis of the response to electrophysiologic testing. There has been no recurrence of symptoms in 120 patient-months of follow-up. This experience suggests that arrhythmias are the principal cause of syncope or sudden death in obstructive cardiomyopathy and that electrophysiologic study may be useful in selecting prophylactic therapy.     

Recent progress in electrocardiography

Recent advances in electrocardiography (ECG) have revealed new and useful information concerning the electrophysiologic properties of the normal and diseased heart. 1) Evaluation of the frequency of ventricular premature contractions (VPCs) as a function of underlying heart rate with Holter ECG recordings is a useful approach to elucidate the mechanisms of ventricular arrhythmias and to predict the response of ventricular arrhythmias to antiarrhythmic agents. 2) Decreased heart rate variability, presence of late potential, prolonged QT interval, increased QT interval dispersion, and T wave alternans indicate lethal ventricular tachyarrhythmias and sudden cardiac death. 3) The multiple reentrant wave hypothesis has been widely accepted for the mechanism of atrial fibrillation (AF). Recently, spontaneous initiation of AF by ectopic beats originating from the superior vena cava and the pulmonary veins has been reported. Radiofrequency ablation of the focal source of AF completely prevented the recurrence of AF.     

EMBASE search strategies for identifying methodologically sound diagnostic studies for use by clinicians and researchers

Background

The recurrence of cardiac events in patients with idiopathic ventricular fibrillation (VF) excluding patients with the Brugada syndrome is unclear since this entity remains present in previous studies.

Methods

Since 1992, 18 patients (72% male) with idiopathic VF out of 455 ICD implants were treated with an implantable cardioverter defibrillator (ICD). The mean age at first ICD implantation was 42 ± 14 years. Brugada syndrome, as well as other primary electrical diseases (e.g. long QT), were systematically excluded in all patients by the absence of the typical electrocardiogram (ST elevation in the right precordial leads) at rest and/or after pharmacological tests (ajmaline, flecainide, or procainamide). Recurrence of cardiac events was prospectively assessed.

Results

During a mean follow-up period of 41 ± 27 months, VF recurrence with appropriate shock occurred in 7 patients (39%) covering a total of 27 shocks. The median time to first appropriate shock was 12 ± 9 months. There were no deaths. In the electrophysiological study, 39% of patients were inducible, but inducibility failed to predict subsequent arrhythmic events. Forty-four percent of patients suffered 21 inappropriate shocks, which were caused by sinus tachycardia, atrial arrhythmias or lead malfunction.

Conclusion

Idiopathic ventricular fibrillation patients have a high recurrence rate of potentially fatal ventricular arrhythmias, excluding patients with the Brugada syndrome or other known causes. ICD prevents sudden cardiac death but inappropriate shocks remained a major issue in this young and active population.     

Is there a role for long-chain ω3 or oil-rich fish in the treatment of atrial fibrillation?

Atrial fibrillation is the most common cardiac arrhythmia in Europe and north America, and recently it was described as an epidemic. Treatment and management of this arrhythmia consists of using drugs, external electrical cardioversion and in extreme cases, internal electrical pacing. Despite treatment, this arrhythmia continues to impact on morbidity and mortality. The possible benefit from dietary interventions in relation to the primary and secondary prevention of atrial fibrillation have largely been overlooked. Our hypothesis is that increasing the intake of long-chain polyunsaturated omega3 fatty acids (LCn3) from eating a diet containing moderate amounts of oil-rich fish, will benefit people with persistent atrial fibrillation. A number of possible anti-arrhythmic actions from LCn3 have been found from animal and laboratory studies, mainly on ventricular arrhythmias. These include reducing pro-arrhythmic eicosanoids and inhibiting sodium and calcium currents. If found to be beneficial to these patients, dietary advice to eat more oil-rich fish, or take LCn3 supplements, could be part of a package of care for people with this arrhythmia. We have currently started a randomised controlled trial to test our hypothesis.     

Assessment of RR-Intervalogram Instability

The series of cardiac intervals is a dynamic chaotic deterministic process. Transition from regular to chaotic process is characterized by self-organized critical organization. This transition is accompanied by flicker noise. The RR-intervalogram spectrum is a diagnostic symptom for ventricular fibrillation, ventricular tachycardia, and atrial fibrillation.