[Current management of atrial fibrillation: rhythm or rate control and thoughts about a new treatment paradigm]. / Thérapeutiques actuelles de la fibrillation atriale, rythme et fréquence, réflexion sur un nouveau paradigme de prise en charge.

Over the past 30 years, treatment paradigms for atrial fibrillation (AF) patients have changed dramatically. Before 1989, and the publication of the CAST trial results, the primary objective was to maintain or restore sinus rhythm. In the following 20 years, the management of AF patients has focused on the prevention of thrombo-embolic events (with the confrontation of aspirin and oral anticoagulants), and on the debate between rhythm control and rate control. In 2010, the objectives are to reduce symptoms and improve quality of life, to prevent thrombo-embolic complications, and, if possible, to reduce mortality. New anticoagulants will soon be available. Ablative techniques are becoming current practice in selected patients, and the new antiarrhythmic agent dronedarone has shown remarkable clinical results in the ATHENA trial. Overall, ablative techniques can be used in younger patients with paroxysmal or persistent AF refractory to medical treatment a rate control strategy is appropriate in permanent AF, or as second line treatment in patients with other forms of AF.

[Management of atrial fibrillation in France: the observational FACTUEL study]. / Fibrillation atriale, description de la prise en charge par les cardiologues, étude observationnelle. Résultats de l'étude Factuel.

OBJECTIVES: To describe the management of patients with atrial fibrillation (AF) and to study consistency with guidelines on management of AF. PATIENTS AND METHODS: Observational study on a random sample of cardiologists from a French national database. Each cardiologist had to recruit the first five patients meeting inclusion criteria (patients diagnosed with AF between January 2004 and one month before inclusion and accepting the collection of their medical data). RESULTS: Between December 2006 and January 2207, 1789 patients aged 71 on average have been recruited by 481 cardiologists. Fifty-one percent were diagnosed with paroxysmal, 15% with persistent and 33% with permanent AF. Restoration of sinus rhythm was preferred in forms considered as paroxysmal or persistent forms whereas control of the ventricular rate was more frequent in AF considered as permanent. Overall, therapeutic guidelines are applied in practice, despite a frequent use of amiodarone in patients with no associated heart disease. Prevention of thromboembolism was observed in 88% of the patients. CONCLUSIONS: FACTUEL is the biggest observational study on AF ever conducted in France. The therapeutic strategies used by the cardiologists are consistent with the objectives of preventing thromboembolism and controlling heart rhythm and/or rate. In most cases, the treatment used is consistent with the therapeutic guidelines.

[Atrial fibrillation: challenge of antithrombotic treatment]. / Les enjeux du traitement antithrombotique.

Antithrombotic treatment is a crucial challenge in the management of patients with atrial fibrillation (AF). It is the only treatment which can decrease mortality in relation with AF. It can also prevent the first cause of dependency in elderly: stroke. Vitamin K antagonists are the more potent drugs to reduce the risk of ischemic stroke in patient with AF. Aspirin, unfractioned heparine or low molecular weight heparin and thienopyridine can also play a role in the antithrombotic therapy in special situations.

[Implantable cardioverter defibrillators in pediatric patients: results in a series of 33 cases]. / Le défibrillateur automatique implantable chez l'enfant et l'adolescent: indications, complications et résultats à propos d'une étude multicentrique française de 33 cas.

UNLABELLED: Implantable defibrillator is the recognized treatment of sudden cardiac death. Miniaturization of the devices allows implantation in children. METHODS: This multicentric retrospective study analyzed data of 33 children aged 18 years and less who were implanted from 1990 to 2005. RESULTS: Age of patients are 10 to 18 years, 20 patients were implanted after a resuscitation of sudden death, 10 after a syncope, 2 after a ventricular tachycardia and 1 in a prophylactic way. Tachycardias on primary electrical disease are most frequent (46%). Hypertrophic cardiomyopathy accounts for 22%, DAVD for 14%, congenital cardiopathies for 12%. Seventeen patients received appropriate shocks and 14 patients had inappropriate shocks. There were two unexplained deaths. Five leads fractures and two device infections were noted. CONCLUSION: Implantable defibrillator is an effective treatment for children high-risk of sudden death. Occurrence of inappropriate shocks due to sinusal tachycardia, infections and leads fractures are frequent.

[Clinical evolution of patients following investigation of atrial vulnerability after a first cerebral ischaemic accident]. / Evolution clinique des patients ayant eu une recherche de vulnérabilité atriale après un premier accident ischémique cérébral.

Atrial vulnerability reflects the ability of the atrium to fibrillate. ISAV (Ischemic stroke and atrial vulnerability) is a French epidemiological registry whose main goal is to assess the evolution modalities of patients in whom an electrophysiological study of the atrium has been performed. A group of 269 patients with a history of non elucidated ischemic stroke and an electrophysiological study of the atrium performed in a mean delay of 3 months after the stroke has been included. Their mean age at the time of the stroke was 55 +/- 15.8 years. The electrophysiological study has measured the effective refractory period of the atrium, the locoregional right intra-atrial conduction time, the index of latent atrial vulnerability and assessed the inductibility. The mean delay between the date of the stroke and the date of the last news was 4.4 +/- 2.8 years. We observed 12 deaths and 11 patients presented during the follow up a spontaneous atrial arrhythmia and 17 a recurrence of stroke. If we consider the occurrence of the 28 combined events (atrial arrhythmia and/or stroke), it is not correlated with the presence of an atrial septal defect nor with the existence of an atrial vulnerability. On the contrary this occurrence is correlated with tobacco consumption and/or arterial hypertension; 82% of patients have these risk factors versus 54% of patients without events (p = 0.004). This association is not significant in patients younger than 55 years.

Post-operative use of heparin increases morbidity of pacemaker implantation.

AIMS: The objective of this study is to characterize the incidence of peri-operative severe adverse events (AEs) related to the post-operative use of heparin in patients undergoing pacemaker surgery. METHODS AND RESULTS: We retrospectively compared the outcome of 38 patients with mechanical valves (MVs) and 76 patients with atrial fibrillation (AF) with control cases matched for gender, age, and surgical details. Heparin was systematically used post-operatively in MV patients, but left to clinical judgment in AF patients. The relative risk for severe haemorrhagic AEs was 11 (CI 1.5-81.1, P < 0.01) in the MV group when compared with matched controls and 8 (CI 1.0-62.5, P < 0.05) in the AF group. Overall, the relative risk of heparin use in the post-operative period was 14 (CI 1.88-104, P = 0.0006) and the post-operative stay was prolonged from 7 days in this group when compared with control cases (P < 0.0001).The variables associated with haemorrhage were the delay to restart heparin after surgery and the presence of an MV. CONCLUSION: Post-operative use of heparin increases morbidity of pacemaker implantation. A different approach to management of these patients is possible.

Cardiac resynchronisation therapy reduces functional mitral regurgitation during dynamic exercise in patients with chronic heart failure: an acute echocardiographic study.

OBJECTIVES: To assess non-invasively the acute effects of cardiac resynchronisation therapy (CRT) on functional mitral regurgitation (MR) at rest and during dynamic exercise. METHODS: 21 patients with left ventricular (LV) systolic dysfunction and functional MR at rest, treated with CRT, were studied. Each patient performed a symptom-limited maximal exercise with continuous two dimensional Doppler echocardiography twice. The first exercise was performed with CRT; the second exercise was performed without CRT. Mitral regurgitant flow volume (RV), effective regurgitant orifice area (ERO) and LV dP/dt were measured at rest and at peak exercise. RESULTS: CRT mildly reduced resting mitral ERO (mean 8 (SEM 2) v 11 (2) mm(2) without CRT, p = 0.02) and RV (13 (3) v 18 (3) ml without CRT, p = 0.03). CRT attenuated the spontaneous increase in mitral ERO and RV during exercise (1 (1) v 9 (2) mm(2), p = 0.004 and 1 (1) v 8 (2) ml, p = 0.004, respectively). CRT also significantly increased exercise-induced changes in LV dP/dt (140 (46) v 479 (112) mm Hg/s, p < 0.001). CONCLUSION: Attenuation of functional MR, induced by an increase in LV contractility during dynamic exercise, may contribute to the beneficial clinical outcome of CRT in patients with chronic heart failure and LV asynchrony.

[AFFIRM: what we have learned ... and pending issues]. / AFFIRM: ce que nous avons appris ... et les questions en suspens.

During these last years, several therapeutic strategies trials have been performed in atrial fibrillation: the goal was to compare the rhythm control strategy (restoration and maintenance of sinus rhythm) to the rate control strategy (slowing of heart rate in atrial fibrillation). The most important of these different trials is the AFFIRM study. The main conclusion of this trial is that rate control can be chosen in first intention and not only in case of failure of the rhythm control strategy. These results can not be applied to 2 categories of patients: on one hand patients with heart failure and on the other hand young patients without cardiopathy in whom the strategy of rhythm control and sinus rhythm maintenance, mainly by class I antiarrhythmic drugs, remains the better choice.

[New concepts of anticoagulant therapy of atrial fibrillation]. / Nouveautés dans le traitement anticoagulant de la fibrillation auriculaire.

The news concerning anticoagulant therapy is very rich. It was also keenly awaited in view of the real imperfection of antivitamin K drugs on which the present strategy of prevention of thromboembolic risk related to atrial fibrillation is based. The new anticoagulants have differing targets identified from the physiological mechanism of coagulation and the physiopathology of thrombosis.

Local symptoms at the site of pacemaker implantation indicate latent systemic infection.

BACKGROUND: To determine whether local complications at the site of pacemaker implantation indicate infection of the intravascular part of the lead as well as of the pacemaker pocket. METHODS: 105 patients admitted for local inflammatory findings, impending pacemaker or lead exteriorisation, frank pacemaker or lead exteriorisation, or overt infection were studied prospectively. After systematic lead extraction, the initial clinical presentation was related to the results of lead cultures. RESULTS: Regardless of the initial presentation, the intravascular parts of the leads gave positive cultures in 79.3% of patients. Additionally, 91.6% of the cultures of the extravascular lead segments were positive, in contrast to 38.1% positivity for wound swab cultures. No clinical observations or laboratory investigations permitted identification of patients with negative lead cultures. In a subgroup of 50 patients with manifestations strictly limited to the pacemaker implantation site, cultures of intravascular lead segments were positive in 72%. Infection recurred in 4/8 patients without complete lead body extraction (50%) v 1/97 patients (1.0%) whose leads were totally extracted (p < 0.001). CONCLUSIONS: Local complications at the site of pacemaker implantation are usually associated with infection of the intravascular part of the leads, with a risk of progressing to systemic infection. Such local symptoms should prompt the extraction of leads even in the absence of other infectious manifestations.

Tissue Doppler echocardiography in patients with long QT syndrome.

BACKGROUND: Congenital long QT syndrome (LQTS) is a well-defined clinical entity associated with a high mortality among untreated patients. Tissue Doppler (TD) echocardiography that has been recently introduced, facilitates wall motion analysis. Therefore, to further characterize myocardial velocity abnormalities associated with LQTS, using TD and conventional echocardiography, we compared control subjects and LQTS patients. METHODS AND RESULTS: Ten patients with mild LQTS and 14 control subjects were examined with standard and TD echocardiography. We studied myocardial velocities in basal and mid-segments of the septal, lateral, inferior and anterior walls. Peak velocity and time intervals were measured in each segment. We confirmed previously described M-mode abnormalities, demonstrated by an increase of the wall thickening time index. TD analysis demonstrated increased systolic and diastolic peak velocities for all segments in LQTS patients. Regional isovolumic relaxation time and systolic velocity half time (VHT) were significantly longer in LQTS group associated with a prolonged late systolic phase, resulting in a plateau morphology. CONCLUSION: We demonstrated that TD allows the characterization of myocardial velocity abnormalities in LQTS patients. TD measurements could become part of the routine clinical evaluation for patients potentially affected by the LQTS as a new phenotypic marker.

[Complications of permanent cardiac pacing]. / Complications de la stimulation cardiaque définitive.

The implantation of a pacemaker is an everyday medical procedure. New indications are under evaluation. However, it should be recalled that this is a surgical intervention with implantation of a prosthesis with possible complications. This should, therefore, be a considered decision. There are early complications which occur in the first 6 weeks after implantation. Their incidence is underestimated (up to 7%) as is their seriousness. There are late complications. Some are responsible for pacemaker dysfunction, the risk of which is proportional to the dependence of the patient on permanent cardiac pacing. The migration of a pacing catheter or the fracture of an Accufix catheter expose the patient to much greater risk. Venous complications are overlooked as they are usually asymptomatic. The superior vena cava syndrome is, however, a serious complication of cardiac pacing. Two recent studies (MOST and DAVID) underline the deleterious haemodynamic effects of unnecessary right ventricular pacing. This right ventricular pacing may have a pro-arrhythmic effect on the ventricles and be responsible for sudden death. It may also cause atrial arrhythmia even if atrio-ventricular synchronisation is preserved. Infectious complications are also under-reported, partially because of the difficulty of diagnosis. They may be life-threatening and require extraction of the implanted material. In conclusion, it is wrong to think that even if a patient does not benefit from his implanted device this cannot have deleterious consequences. Pacemakers should be adjusted especially to avoid inappropriate right ventricular stimulation.

[Use of semi-automatic defibrillators outside the hospital]. / Utilisation extrahospitalière du défibrillateur semi-automatique.

With an annual incidence of 1 to 2@1000 and a rate of survival without complication of 2%, sudden death outside hospital constitutes a serious public health problem in France. Ventricular fibrillation (VF) is responsible for more than three quarters of these deaths. The rate of survival is inversely proportional to the duration of VF making early defibrillation a strong link in the chain of survival. The chances of survival are much greater if the cardio-respiratory arrest occurs with a witness, basic first aid is started rapidly, diagnosis of VF is made quickly and the first shock is delivered as soon as possible. These last two criteria are being met more often since the advent of the semi-automatic defibrillator (SAD) and its availability to first line rescuers. The SAD is a light and compact defibrillator capable of automatic analysis of the electrocardiographic trace, charging if it detects ventricular tachycardia (VT) or VF. By analysing the QRS amplitude, its slope, its morphology, its spectral density and the duration of the isoelectric line, the SAD is capable of recognising VF with a sensibility of 98% and a specificity of 93%. The shock, however, is only delivered with a manoeuvre from the operator. The SAD memorizes both the rhythmic event treated and certain parameters relating to its use. During the last decade, the SAD has benefited from the technological evolutions of the implantable automatic defibrillator, with the introduction of a biphasic shock. The use of a biphasic shock allows reduction in the minimal defibrillation charge and thus lightens the apparatus and increases the number of shocks which the SAD can deliver on a charged battery. In authorizing paramedics by statute to use the SAD, it has been possible to reduce the interval from alert to first delivered shock to 8 minutes although it would be 10 minutes if the medical team was awaited, and to obtain a survival rate without complication of 6.3%. The progress achieved by the use of the SAD in the chain of survival cannot be denied. However, to surpass automatic defibrillation and widen the use of defibrillators to an informed and motivated public would certainly bring our results closer to those obtained in America where the survival rate reaches 30% in the best cases; subject to widespread first aid training for the population.

[Contribution of the implantable ECG monitor in the etiologic diagnosis of syncope and unexplained recurrent syncopal attacks. Initial experience with 32 patients]. / Apport du moniteur ECG implantable pour le diagnostic étiologique des syncopes et lipothymies récidivantes inexpliquées. Expérience initiale à propos de 32 patients.

UNLABELLED: Following an exhaustive aetiological investigation, 10 to 26% of syncopal attacks remain unexplained. In these cases the correlation between symptoms and rhythm is a deciding step for the aetiological diagnosis. We report our initial experience using an implantable electrocardiographic monitor, a new diagnostic tool in patients suffering from syncope and recurrent unexplained syncopal attacks. RESULTS: The study included 32 patients (average age 55 +/- 22 years; 23 males) suffering from syncope and/or recurrent syncopal attacks remaining unexplained following an exhaustive aetiological investigation. The average follow up was 10.2 +/- 2.5 months. No case of sudden death was registered, and the device was removed in only one patient due to poor tolerance. During follow up, 21 recordings were memorized and analysed in 15 patients (45%), giving an average of 1.4 recordings per patient. The average interval for recurrence of symptoms after implantation was from 84 +/- 104 days, 75% of the episodes coming in the first 2 months following implantation. An arrhythmia was detected on 10 occasions: a malignant ventricular arrhythmia in 2 patients, a non-sustained ventricular tachycardia in 1 patient, a junctional tachycardia in 1 patient, entry into paroxysmal atrial fibrillation in 4 patients, a sinus bradycardia in 1 patient, and a sinus pause for 19 seconds in 1 patient. In one patient ST segment depression was documented following anterior chest pain. The tracing was normal with sinus rhythm recorded on 10 occasions, representing the only documented information in 4 patients. In total, an aetiology was found in 11 of the 32 patients evaluated (34%). Once the aetiological diagnosis was established and a specific treatment initiated, all the patients became asymptomatic. CONCLUSIONS: Our preliminary results underline the significance of the implantable ECG monitor in the diagnostic approach to recurrent unexplained syncopal attacks. The exact place of this tool in the decisional algorithm for syncope remains to be defined with further studies.

Long-term follow-up of children and adolescents with syncope; predictor of syncope recurrence.

BACKGROUND: Previous studies have shown that investigation by tilt testing is very appropriate in paediatrics, but the characteristics of children and adolescents who are at high risk of recurrent syncope, once the diagnosis is established, remain unclear. This study was set up to analyse the risk factors attributed to syncope recurrence in paediatric patients. METHODS: One hundred and one children and adolescents aged 7 to 18 years, undergoing a tilt test for recurrent syncope, were studied. They were subsequently followed-up in clinic visits with a final interview at the clinic or by telephone at the end of the follow-up period. RESULTS: A head-up tilt test elicited syncope or pre-syncope in 67 children. The positive responses included vasovagal syncope in 58 patients and psychogenic syncope in nine patients. Gender, age, number of pre-tilt test syncopal episodes or duration of symptoms made no difference to children with positive or negative tilt test results. Following the tilt test, 43 of 67 children with a positive tilt test were treated empirically. No treatment was prescribed for the remaining 24 with a positive test, or for those with a negative tilt test. There were no differences between treated and untreated children with respect to the number of pre-tilt test syncopes, duration of symptoms and duration of follow-up. Follow-up data were available in 97 children. During a mean follow-up of 46+/-28 months, syncope recurred in 31 children (32%). The recurrence rate was similar between positive and negative tilt test groups (22/66 vs 9/31, respectively; P=ns), as well as between treated and untreated children (14/43 vs 8/23, respectively; P=ns). When comparing syncope-free children at follow-up in a univariate analysis, children with recurrent syncope reported a greater number of historical syncopal spells (7+/-8 vs 3+/-3, P=0.01). In addition linear correlation (r=0.6, 95% CI 0.47 to 0.72, P<0.0001) was significant between the number of historical syncope episodes and the risk of recurrent syncope. CONCLUSIONS: These findings suggest that the risk of syncope recurrence for children and adolescents with such a history is not correlated to the tilt test result or prophylactic treatment. The number of historical syncopal spells is, however, predictive.

[Value of an implantable EKG monitor for the diagnosis of arrhythmic syncope in children]. / Intérêt d'un moniteur ECG implantable pour le diagnostic de syncopes rythmiques chez l'enfant.

The value of an implantable ECG monitor (Reveal TM Plus) is reported in a 12 year old child with unexplained syncopal episodes despite extensive investigations. Twenty-seven days after the implantation, ventricular tachycardia at 450/min was recorded at the first recurrence. This case shows that this type of monitoring can be particularly useful when an arrhythmia is thought to be the cause of syncope in a child and the initial investigation is negative.

Prospective evaluation of a simplified approach for common atrial flutter radio frequency ablation with only two catheters.

UNLABELLED: Intra-atrial conduction block within the inferior vena cava-tricuspid annulus isthmus (IVCT) has been shown to predict successful common atrial flutter ablation. However, its demonstration requires the use of several electrode catheters and mapping of the line of block. The aim of this study was prospectively to test the feasibility of a simplified ablation procedure using only two catheters. METHODS: Radio frequency (RF) ablation of common atrial flutter was performed in 30 patients with the sole use of a catheter for atrial pacing and a RF catheter. RF ablation lesions were created in the IVCT. Surface ECG criteria were used to monitor the conduction within the IVCT. The end point during low lateral atrial pacing was an increment in the interval between the pacing artefact and the peak of the R wave in surface lead II >50 ms and clockwise rotation of the P wave axis beyond -30 degrees and inferiorly. Then, the line of lesions was mapped during atrial pacing with the RF catheter. Additional RF lesions were applied if mapping disclosed a zone of residual conduction. Otherwise the procedure was stopped if mapping showed parallel double potentials all along the line. Finally, the block was reassessed with a 'Halo' catheter. RESULTS: Surface ECG criteria were met in 26 patients. Mapping the line of lesions showed a complete corridor of parallel double potentials in these 26 cases and in 3 of the 4 patients in whom ECG criteria were not met. Conduction evaluated with the Halo catheter showed bi-directional complete block in these 29 patients. After a follow-up of 16 +/- 4 months there was no recurrence of atrial flutter. CONCLUSION: Surface ECG criteria combined with mapping of the line of block demonstrate evidence of bi-directional IVCT block. This simplified RF ablation of common atrial flutter is feasible with a low recurrence rate.

[The ilio-femoral approach: an alternative for implanting permanent cardiac pacemakers. Three case reports]. / La voie ilio-fémorale: une alternative pour l'implantation de sondes de stimulation cardiaque définitives. A propos de trois cas.

Permanent endocavitary cardiac pacing is a widely used therapeutic method. The implantation of pacing catheters is usually performed by the supracardiac veins, the epicardial approach being the classical alternative. The ilio-femoral approach is a third possibility. The authors report three cases in which this approach was used. The implantations were performed under general anaesthesia with an abdominal pacemaker. In two cases, atrial and ventricular catheters were implanted. After an average of 19 months' follow-up, no short or long-term complications were observed: displacement or fracture of the pacing catheter, infection, venous thrombosis, threshold elevation. These results show that this is a safe and feasible alternative to implantation by the traditional or epicardial techniques when these approaches cannot be used.

Critical analysis of dual-chamber implantable cardioverter-defibrillator arrhythmia detection : results and technical considerations.

BACKGROUND: One of the perceived benefits of dual-chamber implantable cardioverter-defibrillators (ICDs) is the reduction in inappropriate therapy due to new detection algorithms. It was the purpose of the present investigation to propose methods to minimize bias during such comparisons and to report the arrhythmia detection clinical results of the PR Logic dual-chamber detection algorithm in the GEM DR ICD in the context of these methods. METHODS AND RESULTS: Between November 1997 and October 1998, 933 patients received the GEM DR ICD in this prospective multicenter study. A total of 4856 sustained arrhythmia episodes (n=311) with stored electrogram and marker channel were classified by the investigators; 3488 episodes (n=232) were ventricular tachycardia (VT)/ventricular fibrillation (VF), and 1368 episodes (n=149) were supraventricular tachycardia (SVT). The overall detection results were corrected for multiple episodes within a patient with the generalized estimating equations (GEE) method with an exchangeable correlation structure between episodes. The relative sensitivity for detection of sustained VT and/or VF was 100.0% (3488 of 3488, n=232; 95% CI 98.3% to 100%), the VT/VF positive predictivity was 88.4% uncorrected (3488 of 3945, n=278) and 78.1% corrected (95% CI 73.3% to 82.3%) with the GEE method, and the SVT positive predictivity was 100.0% (911 of 911, n=101; 95% CI 96% to 100%). CONCLUSIONS: A structured approach to analysis limits the bias inherent in the evaluation of tachycardia discrimination algorithms through the use of relative VT/VF sensitivity, VT/VF positive predictivity, and SVT positive predictivity along with corrections for multiple tachycardia episodes in a single patient.

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.