[Ablation of atrial fibrillation: by who, where and at what cost?].
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Atrial Fibrillation↗
Biomedical subjects
F Extramiana
Publications and source records attributed to F Extramiana.
[Value and limitations of programmed ventricular stimulation].
The electrocardiogramme and methods of prolonged ECG recording are sufficient for diagnosing most cardiac arrhythmias. They also provide some prognostic information and allow evaluation and follow-up of treatment. However, in some situations, endocavitary electrophysiological investigations are required when the diagnosis is uncertain, that more prognostic information is required or interventional techniques (endocavitary ablation) are envisaged. The aim of this report is to summarise the value and limitations of programmed ventricular stimulation. Many of its indications have been abandoned in terms of rhythm stratification in the face of more robust parameters, in particular the left ventricular ejection fraction. However, it retains a potential utility in terms of prognosis in arrhythmogenic right ventricular dysplasia, the Brugada syndrome and operated Tetralogy of Fallot. In any event, it is important to remember that studies resulting in diagnostic or therapeutic recommendations were performed with strict protocols of stimulation in selected patients and that these recommendations can only be applied when the evaluation protocols are respected. The indications of programmed ventricular stimulation will increase in the therapeutic field with the development of new techniques of 3D mapping, new systems of catheter guiding which should extend the indications of endocavitary ablation.
Arrhythmias, Cardiac↗
[Primary anomalies of ventricular repolarisation].
The duration of repolarisation is the main determinant of the refractory period and therefore plays a major electrophysiological role. Ventricular repolarisation can be influenced or modified by very many extrinsic factors responsible for so-called secondary changes or anomalies. On the contrary, primary anomalies of ventricular repolarisation correspond to intrinsic anomalies of ionic conduction which in turn affect repolarisation. Primary anomalies of ventricular repolarisation are the consequences of vascular disease, which is the origin of both electrocardiographic anomalies and rhythm disorders, and which can result in sudden death from ventricular fibrillation. Three clinical syndromes correspond with these definitions: long QT syndrome, short QT syndrome, and Brugada syndrome. Much of the experimental work seems to show that arrhythmogenic action results mostly from an increase in the heterogeneity of the refractory periods, whether this involves a prolonged, short or even normal repolarisation time. The various experimental models also give a better understanding of the repolarisation changes observed on the electrocardiogram. Knowledge of the mechanisms responsible for arrhythmias due to primary anomalies of ventricular repolarisation could provide a model for secondary anomalies.
Action Potentials↗
[Recent concepts of the Brugada syndrome, the long QT syndrome and adrenergic ventricular tachycardias].
The clinical syndromes responsible for sudden death have benefited from spectacular advances in recent years. The authors propose a brief review of the genetic, electrophysiological, physiopathological and clinical characteristics of the long QT syndrome, Brugada's syndrome, adrenergic ventricular tachycardias and the short QT syndrome. The initial concept of one gene responsible for one pathology has uncovered new zones of complexity within diseases considered to be monogenetic in origin. These new findings have impacted on diagnostic and therapeutic strategies of these conditions. However, the assessment of the arrhythmic risk and the choice of treatment in individual cases still remain almost exclusively the domain of clinical judgement. Similarly, the better understanding of the mechanisms of the arrhythmias in these syndromes has opened up new specific therapeutic approaches which require validation by clinical trial.
Bundle-Branch Block↗
[Ventricular extrasystoles].
Ventricular extrasystoles result from premature excitation of the heart from a site beyond the bifurcation of the bundle of His, at the level of the conductive tissue or myocardial cells. In practice they represent a daily problem for cardiologists due to their frequent occurrence. They can be detected in symptomatic patients and also in asymptomatic subjects, for example during routine health checks. It is therefore important to distinguish benign ventricular extrasystoles from those which are potentially serious, so that a useless or even dangerous treatment is not undertaken and severe anxiety is not caused in patients who have become 'medicalised'. The decision about treatment is only made following electrocardiographic and echographic clinical investigation, with the presence of cardiopathy being one of the major deciding factors.
Adrenergic beta-Antagonists↗
New insights into septal anterior wall motion velocities at end-systole in normal and hypertrophied left ventricles.
AIMS: It was two-fold (1) to define tissue Doppler echocardiographic characteristics of the end-systolic septal anterior motion: passive due to heart translation, or active motion free of translational effects, substantiated by a myocardial velocity gradient. (2) to specify the temporal features of this septal anterior motion on normal and hypertrophied left ventricles since it occurs while the posterior wall contracts during late ejection. METHODS AND RESULTS: Myocardial velocity gradient was calculated during the anterior motion in simultaneously colour M-mode imaged septal and posterior walls of 21 controls (49+/-12 years) and 17 patients (49+/-13 years) with left ventricle hypertrophy. Timings of septal motion were compared with flow and posterior wall motion. In controls, septal anterior motion started prior to, and overlapped the end of subaortic flow and that of the posterior wall anterior motion. Myocardial velocity gradient was found, exceeding that at the posterior wall (2.5+/-1.6 vs 0.9+/-0.5s(-1), P=0.001). In patients, septal myocardial velocity gradient was lower than in controls (1.2+/-1.04 s(-1)P=0.006). The anterior motion had a longer duration than in controls (75+/-37 vs 50+/-17ms, P=0.003). Myocardial velocity gradient and duration were correlated with septal thickness (P=<0.01). CONCLUSIONS: The septal anterior motion was active. Patients showed a decreased myocardial velocity gradient, while wall asynchrony increased. Unusual higher septal than posterior wall systolic velocities at tissue Doppler echocardiography may suggest a relaxation pattern, in spite of its end-systolic onset.
Adult↗
[Brugada syndrome].
The Brugada syndrome is characterised clinically by the occurrence of syncope or sudden death due to ventricular arrhythmias in patients with structurally normal hearts and electrocardiographic signs of right bundle branch block and ST elevation in the right precordial leads (V1 to V3). The transmission of the condition is autosomal dominant with variable penetration. Mutations have been identified in a gene coding for the alpha sub-unity of the sodium channel (SCN5A) on chromosome 3 in only 30% of cases. This mutation is responsible for a reduction of the density of the sodium current and explains the aggravation of the electrocardiographic anomalies by antiarrhythmic drugs which block the sodium channels. The prognosis is poor in symptomatic patients and depends on the prevention of sudden death by the implantation of an automatic defibrillator. The therapeutic decision is much more difficult in asymptomatic patients without a family history. The authors propose a decisional algorithm. The management may have to be modified in the months or years to come depending on advances in the understanding of this syndrome.
Algorithms↗
[Indications for implantable automatic defibrillators: critical analysis].
The implantable automatic defibrillator (IAD), invented in 1980, has revolutionised the management of patients with malignant ventricular arrhythmias resistant to medical treatment or ablation procedures. The number of devices implanted continues to increase in the industrialised countries and, based on the results of clinical trials, the indications for IAD are now well codified and increase as new clinical studies are published. However, the absolute number of implantations in France remains low (about 1200 to 2000, about 20 per million population) for a number of reasons: cost of IAD, absence of reimbursement by the health service which has restrained the implantation to public hospitals, and information of cardiologists for whom IAD may seem to be reserved for a few exceptional cases. Several factors suggest that the number of implantations will increase in the near future. First of all, the procedures of implantation have become much more simple due mainly to technical improvements. Then, the results of recent studies have validated prophylactic implantations of these devices in primary prevention in the post-infarction period (MADIT, MUSTT, MADIT II studies) and have demonstrated the superiority of IAD over antiarrhythmic drug therapy in terms of global survival in patients with severe ventricular arrhythmias (AVID, CIDS, CASH studies).
Arrhythmias, Cardiac↗
[Bidirectional ventricular tachycardias].
Bidirectional tachycardias are rare arrhythmias. Nevertheless in the sixties and seventies these arrhythmias prompted much work relating to their mechanism. Discussions about the supposed supra-ventricular origin of certain bidirectional tachycardias essentially rested on presumptive arguments based on electrocardiographic analysis. All the electrophysiological investigations which could be performed in tachycardia showed a ventricular origin. The current hypotheses concerning the electrophysiological mechanism favour non-unifocal mechanisms as well as a very diverse aetiology: an automatic focus, or the triggered activities being associated with alternating conduction, or re-entry between the left hemibranches. Although the classic context is of excess digitalis with advanced cardiopathy, readily in atrial fibrillation with a poor prognosis as a corollary, the most recent description of catecholergic ventricular tachycardias with the very characteristic appearance of bidirectional tachycardias justifies updating the understanding of these unusual tachycardias.
Electrocardiography↗
[Endocavitary ablation for arrhythmias. New modalities of radiofrequency applications. New energy types].
Radiofrequency remains the reference energy type for catheter ablation of rhythm disorders. In the classic indications, which are atrial flutter or tachycardia, nodal re-entry and Wolff-Parkinson-White syndrome, this energy source has the best cost-efficiency-safety ratio, subject to strict conditions of use. Some new modalities of application have further improved performance, especially active irrigation of the electrode which allows induction of deeper lesions which is very useful for the ablation of difficult atrial flutters, epicardial fascicles of Kent and ischaemic ventricular tachycardias. The only emerging alternative energy type, in the framework of classical ablation, is cold, for which the principal advantages are the homogenous and slightly thrombogenic character for the lesion involved, and the possibility of reversible applications tests which are especially useful in the ablation of structures at risk. The situation is more open-ended concerning research on ablation for atrial fibrillation or the so-called new energy types, such as ultrasound and laser, whilst recognising a renewal in interest, especially for circumferential ablation of the pulmonary veins to isolate the ectopic venous foci. Mechanical energy such as luminous energy is emitted across a catheter balloon deployed at the orifice of the vein, perpendicular to its axis, aiming to reach a continuous circumferential lesion with a minimum of applications. Equally radiofrequency has been undergoing significant evolution for this application, such as by the development of porous catheter balloons with a liquid electrode, as well as by the development of deployable circumferential catheters. Ablation is use for atrial fibrillation, by endocavity atrial segmentation remains a field of research in which radiofrequency retains an important place. It is delivered via multi-electrode catheters according to the new application modalities, either pulsed or by phase interval, which secure better efficacy by better continuity of the line of block. Research is equally underway on the use of microwaves and cold in this application.
Atrial Fibrillation↗
[Role of antiarrhythmics in the treatment of paroxysmal atrial fibrillation].
Atrial fibrillation is not a homogenous entity. Numerous parameters affect its cause, its continuation, and the arrest of an attack. The presence or absence of cardiopathy and left ventricular dysfunction play a major role via the electrophysiological and haemodynamic consequences and the repercussions on the state of the autonomic nervous system, and finally on the effect of anti-arrhythmics themselves. This shows the importance of taking into account all of these parameters together in order to adapt the therapeutic approach. Equally, this underlines the difficulty in interpreting clinical studies comparing pharmacological treatments when the populations treated are poorly defined or very heterogenous. Most often, one drug is not more or less effective than another, it is more or less suited to the patients treated. The frequency of recurrences of AF despite anti-arrhythmic treatment (on average 50% to 60% at one year) means that in paroxysmal AF the goal of anti-arrhythmic treatment is relatively modest: essentially reducing the frequency, duration and severity of AF attacks, allowing an improvement in the quality of life. The consequences in daily practice are clear: one must ensure good patient compliance and minimise the risks of treatment: side effects of and pro-arrhythmic effects of anti-arrhythmics.
Anti-Arrhythmia Agents↗
[Homozygotous mutation of the SCN5A gene responsible for congenital long QT syndrome with 2/1 atrioventricular block].
Long QT syndrome is characterized by a prolongation of the QT interval on the surface ECG. This clinically and genetically heterogeneous cardiac disease is potentially lethal due to ventricular polymorphic tachyarrhythmias leading to syncope or sudden death. It is transmitted according to different mendelian modes due to mutations in several genes coding for cardiac ion channels. Heterozygous mutations in KCNQ1, HERG, SCN5A, KCNE1 and KCNE2 genes are responsible for the dominant form without deafness whereas homozygous mutations in KCNQ1 and KCNE1 are responsible for the recessive form (Jervell and Lange-Nielsen syndrome) associated with congenital deafness. We report the case of a 5 year-old boy referred for syncope with a prolongation of the QTc interval (526 ms) and a 2/1 Atrio-Ventricular (AVB) block on the surface ECG. Under beta-blocking therapy, the sinus rate decreased and the 2/1 AVB disappeared. Electrophysiological study evidenced an infra-hisian block and a unipolar ventricular endocardial pacemaker was implanted. A V1777M missense mutation was identified in the C-terminal part of SCN5A, cardiac sodium channel gene, at the homozygous state in the proband and at the heterozygous state in both parents and 2 sibblings. Only the proband had a severe phenotype with syncope and AV conduction anomalies. All other genetically affected subjects were asymptomatic. This study provides evidence for the involvement of homozygous LQT3 forms in "functional" AVB.
Amino Acid Sequence↗
Homozygous SCN5A mutation in long-QT syndrome with functional two-to-one atrioventricular block.
Heterozygous mutations in genes encoding cardiac ionic channel subunits KCNQ1, HERG, SCN5A, KCNE1, and KCNE2 are causally involved in the dominant form of long-QT syndrome (LQTS) while homozygous mutations in KCNQ1 and KCNE1 cause LQTS with or without congenital deafness. In addition, two homozygous HERG mutations have been associated with severe LQTS with functional atrioventricular conduction anomalies in young children. A 2:1 atrioventricular block (AVB) with a major QTc prolongation (526 ms) was evidenced in a 5-year-old boy referred for syncope and seizure. LQTS was diagnosed and beta-blocking therapy initiated leading to normal atrioventricular conduction. Electrophysiological study provided support that location of the AVB was infra-Hisian. DNA analysis was performed in the proband and in asymptomatic family members. A novel missense mutation, V1777M, in the early C-terminal domain of SCN5A was identified. The proband was homozygous while the parents and two siblings were heterozygous carriers. Homozygote and heterozygote expression of the mutant channels in tsA201 mammalian cells resulted in a persistent inward sodium current of 3.96+/-0.83% and 1.49+/-0.47% at -30 mV, respectively, which was dramatically reduced in the presence of tetrodotoxin. This study provides the first evidence for a homozygous missense mutation in SCN5A and suggests that LQTS with functional 2:1 AVB in young children, a severe phenotype associated with bad prognosis, may be caused by homozygous or heterozygous compound mutations not only in HERG but also in SCN5A. The full text of this article is available at http://www.circresaha.org.
Amino Acid Sequence↗
Autonomic influences on ventricular repolarization in congestive heart failure.
We studied the QT interval rate-dependence in patients with congestive heart failure (CHF). The long-term autonomic nervous function was investigated by separate analysis of diurnal and nocturnal periods. For this purpose, QTm rate-dependence was determined from Holter recordings. Twelve patients with stable CHF (mean age 63 +/- 2 years) and 15 healthy subjects (mean age 59 +/- 4 years) were included in the study. CHF patients showed an increased nocturnal QTm rate-dependence when compared to normal subjects (0.150 [95% confidence interval (CI) 0.114 to 0.186] versus 0.106 [95% CI 0.080 to 0.133], P < .05). In contrast, QTm rate-dependence was not significantly different between the 2 groups during the day (0.177 [95% CI 0.149 to 0.210] in the CHF group versus 0.194 [95% CI 0.158 to 0.231] in the control group). It was also not significantly different between day and night for the CHF group, thus showing a loss of the circadian modulation in these patients. Thus, ventricular myocardial properties are altered by changes in the autonomic nervous system in CHF, as observed at the atrial level. These modifications may be related to the increased susceptibility to ventricular arrhythmias.
Aged↗
[New markers for the risk of sudden death: analysis of ventricular repolarization].
The identification of patients at high risk of sudden cardiac death is one of the greatest challenges for cardiologists. Non-invasive methods have, characteristically, low predictive sensitivities and specificities. The role of abnormalities of ventricular repolarisation (QT interval) in the genesis of ventricular arrhythmias has been well established by experimental data. For this reason, parameters of ventricular repolarisation on the surface electrocardiogram have been proposed. However, taken in isolation, these markers are limited in terms of arrhythmic risk stratification. This report analyses the value of the different parameters of ventricular repolarisation in the identification of high risk: QT dispersion, QT dynamics and T wave alternans. The dispersion of the QT interval is a marker of unhomogenous ventricular depolarisation. This concept must be applied differently in such pathologically dissimilar diseases such as myocardial infarction, cardiomyopathy or the long QT syndrome. Moreover, methodological problems make the interpretation of many experimental studies very delicate. Frequency dependence of the QT helps select high risk patients after myocardial infarction or with dilated cardiomyopathy. A common feature of pathological ventricular myocardium is the more pronounced frequency-dependency of the QT interval. The predictive value of this new index should be evaluated and compared with other non-invasive risk factors in prospective trials. Studies of T wave alternans in selected high risk populations, essentially patients with coronary artery disease and dilated cardiomyopathy, have shown this parameter to be predictive of arrhythmia. The predictive value requires confirmation in much larger populations at lower levels of risk of arrhythmia and sudden death in prospective trials. A new field of research has opened up in the study of ventricular repolarisation. Many studies have been undertaken on the duration of the QT interval, the morphology of the QT (including T wave alternans and post-pause changes) and, finally, the dynamics of the QT interval. By regrouping, analysing and using these data correctly, we should be able to identify new markers of high arrhythmic risk.
Death, Sudden, Cardiac↗
Chronic amiodarone effects on epicardial conduction and repolarization in the isolated porcine heart.
Amiodarone is a potent antiarrhythmic agent with complex chronic effects, notably on repolarization and conduction, that are not fully understood. Its low arrhythmogenic potential has been related to a lack of increase in repolarization dispersion. Since its effects are not documented in pigs we conducted a mapping study of activation and repolarization in isolated perfused porcine hearts. Amio20 female pigs (n = 7) received amiodarone 20 mg/kg per day over 4 weeks while Amio50 female pigs (n = 7) received 50 mg/kg per day over 4 weeks. Concentrations of the drug encompassed values found in clinical studies. Then, activation patterns and activation-to-recovery intervals (ARI) were mapped epicardially from 128 unipolar electrograms in isolated perfused hearts in corroboration of epicardial action potential recordings. Mean ARI was longer in Amio20 experiments compared to the seven control hearts (325 +/- 11 ms vs 288 +/- 5 ms at 1,000 ms), whereas ARI dispersion was not different, being comprised between 7 and 11 ms and generating smooth gradients. In Amio50 experiments, mean ARI was further prolonged (390 +/- 10 ms at 1,500 ms) with an exaggerated reverse rate dependence concomitant with a depressant effect on the plateau of the action potential. Again, ARI dispersion did not differ from controls. Finally, the drug depressed the maximal rate of depolarization (Vmax) and slowed conduction in a rate dependent and concentration dependent fashion. In conclusion, chronic amiodarone induces Class I and Class III antiarrhythmic effects in ventricular porcine epicardium that are concentration dependent but does not affect dispersion of repolarization. This may partly explain its low arrhythmogenic potential.
Action Potentials↗
[Ventricular repolarization and Holter monitoring. Effect of sympathetic blockage on the QT/RR ratio].
Circadian variations of the QT interval and its heart rate dependency have been established. However, the respective roles of the sympathetic and parasympathetic nervous systems in their regulation are still undetermined. Eighteen healthy volunteers (average age 39 +/- 7 years, 10 men) were recruited and selected randomly to receive either placebo or atenolol (100 mg/day). The treatments were crossed after 7 days. The rate dependency of the QT was assessed by day and by night by 24 hour Holter ECG monitoring. The effects of atenolol on the rate dependency of the QT interval depend on the time of day. During the daytime, the QT rate dependency was reduced by atenolol (0.180 (0.162:0.198) versus 0.216 (0.195:0.236) with placebo, p < 0.01) whereas during the night, the QT rate dependency was the same in both groups. Therefore, the betablocker is associated with an inversion of the daily modulation of the QT rate dependency. The daytime rate-dependency of the QT interval in decreased with betablocker therapy. This result suggests a direct or indirect influence of the sympathetic nervous system on the rate dependency of ventricular repolarisation.
Adult↗
[Electrocardiographic changes and rhythm problems in the diabetic].
Diabetes is a cause of serious myocardial disease related to an increased incidence of coronary artery disease, probably aggravated by cardiac autonomic neuropathy (CAN). In its incipient form, CAN hardly changes the sinus rhythm with an increase in nocturnal heart rate but without an appreciable effect on the indices of variability. In more advanced forms, "CAN+", there are not only changes in the heart rate variability but also in ventricular repolarisation. It is classical to underline the value of the corrected QT interval but this index has little real value. The "QT dispersion", comparing the duration of ventricular repolarisation on the surface leads, is no better a marker from the theoretical point of view. The dynamics of ventricular repolarisation on the other hand seem to be much more indicative of ventricular myocardial disease. They are studied by evaluating the QT-heart rate relationship and its increase distinguishes clearly CAN diabetics from CAN+ diabetics. In addition, in the latter subjects, diurnal physiological increase in the heart rate dependency of the QT interval (QT/RR slope) disappears or even inverse. It is probably this phenomenon which is responsible for the traditionally increased risk of ventricular arrhythmias and particularly sudden death in diabetics with autonomic neuropathy.
Action Potentials↗