Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial.

AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS: During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION: Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses.

BACKGROUND: Only few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood. OBJECTIVES: To study the potential of flecainide to terminate acutely induced AF of short duration (≥ 15 minutes), to examine flecainide-induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length, and ventricular depolarization and repolarization. ANIMALS: Nine Standardbred horses. Eight received flecainide, 3 were used as time-matched controls, 2 of which also received flecainide. METHODS: Prospective study. The antiarrhythmic and electrophysiologic effects of flecainide were based on 5 parameters: ability to terminate acute pacing-induced AF (≥ 15 minutes), and drug-induced changes in atrial effective refractory period, AF duration, AF vulnerability, and ventricular depolarization and repolarization times. Parameters were assessed at baseline and after flecainide by programmed electrical stimulation methods. RESULTS: Flecainide terminated all acutely induced AF episodes (n = 7); (AF duration, 21 ± 5 minutes) and significantly decreased the AF duration, but neither altered atrial effective refractory period nor AF vulnerability significantly. Ventricular repolarization time was prolonged between 8 and 20 minutes after initiation of flecainide infusion, but no ventricular arrhythmias were detected. CONCLUSIONS AND CLINICAL IMPORTANCE: Flecainide had clear antiarrhythmic properties in terminating acute pacing-induced AF, but showed no protective properties against immediate reinduction of AF. Flecainide caused temporary prolongation in the ventricular repolarization, which may be a proarrhythmic effect.

Percutaneous left atrial appendage occlusion for stroke prevention in atrial fibrillation: an update.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice. One of its most devastating complications is the development of thromboembolism leading to fatal or disabling stroke. Oral anticoagulation (OAC, warfarin) is the standard treatment for stroke prevention in patients with AF with an increased stroke risk. However, there are several obstacles to long-term OAC therapy, including the risk of serious bleeding, several drug-drug interactions and the need for frequent blood testing. Although newer oral anticoagulants have been developed, these drugs also face issues of major bleeding and non-compliance. Therefore, alternative treatment options for stroke prevention in patients with AF with a high stroke risk are needed. Percutaneous left atrial appendage (LAA) occlusion is an evolving therapy, which should be taken into consideration in those patients with non-valvular AF with a high stroke risk and contraindications for OAC. This article aims to discuss the rationale for LAA closure, the available LAA occlusion devices and their clinical evidence until now. Moreover, we discuss the importance of proper patient selection, the role of various imaging techniques and the need for a more tailored postprocedural antithrombotic therapy.

Antidepressant use and risk of out-of-hospital cardiac arrest: a nationwide case-time-control study.

Treatment with some types of antidepressants has been associated with sudden cardiac death. It is unknown whether the increased risk is due to a class effect or related to specific antidepressants within drug classes. All patients in Denmark with an out-of-hospital cardiac arrest (OHCA) were identified (2001-2007). Association between treatment with specific antidepressants and OHCA was examined by conditional logistic regression in case-time-control models. We identified 19,110 patients with an OHCA; 2,913 (15.2%) were receiving antidepressant treatment at the time of OHCA, with citalopram being the most frequently used type of antidepressant (50.8%). Tricyclic antidepressants (TCAs; odds ratio (OR) = 1.69, confidence interval (CI): 1.14-2.50) and selective serotonin reuptake inhibitors (SSRIs; OR = 1.21, CI: 1.00-1.47) were both associated with comparable increases in risk of OHCA, whereas no association was found for serotonin-norepinephrine reuptake inhibitors/noradrenergic and specific serotonergic antidepressants (SNRIs/NaSSAs; OR = 1.06, CI: 0.81-1.39). The increased risks were primarily driven by: citalopram (OR = 1.29, CI: 1.02-1.63) and nortriptyline (OR = 5.14, CI: 2.17-12.2). An association between cardiac arrest and antidepressant use could be documented in both the SSRI and TCA classes of drugs.

Prolonged signal-averaged P wave duration after elective cardioversion increases the risk of recurrent atrial fibrillation.

OBJECTIVE: To assess the risk of atrial fibrillation (AF) recurrence after elective cardioversion of AF in relation to the signal-averaged P wave duration (SAPWD), clinical characteristics of the patient, and the duration of the AF disease. DESIGN: We studied 131 consecutive patients (88 men, 43 women), median age 67 years (range 29-87 years), after elective cardioversion of AF into sinus rhythm. The SAPWD was measured on inclusion, and the follow-up period was 1 month. Recurrent AF within the first month after cardioversion was regarded as endpoint. RESULTS: AF recurred in 73 patients (56%). Multiple logistic regression analysis showed that prolonged SAPWD above 160 ms was the only significant risk factor for recurrent AF, OR=2.22 (95% CI 1.07-4.60), p=0.03. There was no significant effect of age, diagnosed hypertension, diagnosed congestive heart failure, dilated left atrium, or long duration of AF on the risk of AF relapse. CONCLUSION: Prolonged SAPWD above 160 ms is a risk factor for recurrent AF after elective cardioversion of persistent AF.

The optimal oesophageal pacing technique--the importance of body position, interelectrode spacing, electrode surface area, pacing waveform and intra-oesophageal local anaesthesia.

In order to improve the technique of transoesophageal atrial stimulation (TAS), the effects of body position, interelectrode spacing and electrode surface area on pacing threshold were assessed in two substudies. The effects of intra-oesophageal local anaesthesia and of two different pacing wave configurations on pacing threshold and discomfort were also assessed. Substudy I comprised 16 subjects (3 patients with a history of paroxysmal supraventricular tachycardia and 13 healthy volunteers) and substudy II comprised 16 healthy volunteers. TAS was performed using a hexapolar luminal prototype oesophageal electrode catheter. In substudy I bipolar pacing was performed in the semi-supine and left decubitus body positions for different pulse durations (20, 10, 6 and 2 ms), interelectrode pole distances (10 to 24 mm) and electrode pole surface areas (0.22 to 0.66 cm2). In substudy II TAS was performed with square wave and triangular waveform pulses after intra-oesophageal saline and lidocaine 20 mg/ml. These solutions were given in random order. Neither the interelectrode distance nor electrode surface areas had any significant influence on pacing thresholds. Stimulation thresholds were not affected by body position. Intraoesophageal lidocaine did not affect the discomfort experienced. Peak pacing thresholds using a triangular waveform were significantly higher than thresholds using a square waveformn (p < 0.001). The optimal pacing technique for TAS remains to be defined. The TAS-induced pain is probably not generated from the oesophageal mucous membrane. There is a significant difference in pacing thresholds between triangular and square waveforms.

[Right bundle branch block, ST segment elevation and sudden cardiac death. A clinical and electrocardiographic syndrome--Brugada syndrome]. / Højresidigt grenblok, ST-segment-elevation og pludselig hjertedød. Et klinisk og elektrokardiografisk syndrom-Brugadas syndrom.

The association of an abnormal electrocardiogram (ecg) consisting of right bundle branch block and ST segment elevation in leads V1-V3 and sudden arrhythmic death has been described in patients with no demonstrable structural heart disease. A patient with these ecg findings and aborted sudden death is presented. The patient had no structural heart disease and received an implantable cardioverter-defibrillator which seems to be the treatment of choice.

Non-invasive assessment of the atrial cycle length during atrial fibrillation in man: introducing, validating and illustrating a new ECG method.

OBJECTIVES: Atrial fibrillation (AF) in man has previously been shown to include a wide variety of atrial activity. Assessment of the characteristics of this arrhythmia with a commonly applicable tool may therefore be important in the choice and evaluation of different therapeutic strategies. As the AF cycle length has been shown to correlate locally with atrial refractoriness and globally with the degree of atrial organization, with, in general, shorter cycle length during apparently random AF compared to more organized AF, we have developed a new method for non-invasive assessment of the AF cycle length using the surface and the esophagus (ESO) ECG. METHODS AND RESULTS: From the frequency spectrum of the residual ECG, created by suppression of the QRST complexes, the dominant atrial cycle length (DACL) was derived. By comparison with multiple intracardiac simultaneously acquired right and left AF cycle lengths in patients with paroxysmal AF, we found that the DACL in lead V1, ranging from 130 to 185 ms, well represented a spatial average of the right AF cycle lengths, whereas the DACL in the ESO ECG, ranging from 140 to 185 ms, reflected both the right and the left AF cycle length, where the influence from each structure depended on the atrial anatomy of the individual, as determined by MRI. In patients with chronic AF, the method was capable of following changes in the AF cycle length due to administration of D,L-sotalol and 5 min of ECG recording was sufficient for the DACL to be reproducible. CONCLUSIONS: We conclude that this new non-invasive method, named 'Frequency Analysis of Fibrillatory ECG' (FAF-ECG), is capable of assessing both the magnitude and the dynamics of the atrial fibrillation cycle length in man.

Non-invasive assessment of magnitude and dispersion of atrial cycle length during chronic atrial fibrillation in man.

AIMS: Atrial fibrillation cycle lengths can be assessed from right precordial ECG leads and the unipolar oesophageal ECG using a non-invasive method called Frequency Analysis of Fibrillatory ECG. The purpose of this report is to present the results from application of this method in a large group of patients with long-term atrial fibrillation and to examine the differences between patients with 'coarse' and 'fine' atrial fibrillation. METHODS AND RESULTS: Simultaneous 15 min recordings from V1, V2 and an oesophageal lead at a position behind the posterior atrium were obtained in 28 patients, aged 41 to 78 years, with long-term (> 1 month) atrial fibrillation. In each lead, using the time averaging technique, the QRST complexes were suppressed. Thereafter, the frequency distribution of the residual ECG was estimated by means of Fast Fourier Transform. In the 3-12 Hz range of each lead, the dominant atrial cycle length, the power maximum and the spectral width were calculated. In 26 patients (93%), frequency spectra in the 3-12 Hz range could be obtained. The dominant atrial cycle length ranged from 120 to 175 ms, mean 150+/-16 (SD) ms in V1, and from 120 to 190 ms, mean 150+/-16 in an oesophageal lead (ns). The absolute difference in the dominant atrial cycle length between V1 and the oesophageal lead was 10.4+/-7.7 ms. There was no significant difference in the dominant atrial cycle length in V1 between patients with coarse and fine atrial fibrillation. The power maximum in V1 was significantly greater in patients with coarse compared to fine atrial fibrillation (P=0.01). The spectral widths ranged from 10 to 55 ms and demonstrated significantly higher mean values in lead V2 compared to V1 (P=0.001). Compared to V1, the mean values tended to be smaller in the oesophageal lead (P=0.05). CONCLUSIONS: Using the Frequency Analysis of Fibrillatory ECG method, the dominant atrial cycle length, power maximum and spectral width can be estimated from the frequency spectra in the majority of patients with atrial fibrillation. Spatial dispersion of the dominant atrial cycle length occurs in some patients and may be an important proarrhythmic marker. The distinction between coarse and fine atrial fibrillation cannot be used as a marker of the atrial cycle length.

Signed value of monophasic action potential duration difference. A useful measure in evaluation of dispersion of repolarization in patients with ventricular arrhythmias.

AIMS: To evaluate the usefulness of the signed value of monophasic action potential duration difference in analysing the cause of dispersion of ventricular repolarization. METHODS AND RESULTS: Monophasic action potentials were simultaneously recorded from the right ventricular apex and outflow tract during programmed stimulation in 36 patients with ventricular arrhythmias. The time difference between the ends of repolarization on the two monophasic action potentials was used as a measure of the dispersion of ventricular repolarization, and the signed value of the monophasic action potential duration difference was used to specify the contributions of the activation time difference and the monophasic action potential duration difference to the dispersion of ventricular repolarization. During right ventricular pacing, single and double programmed stimulation and at the induction of ventricular arrhythmias, the dispersion of ventricular repolarization and the signed value of monophasic action potential duration difference were markedly greater in the 11 patients with polymorphic ventricular tachycardia/ventricular fibrillation induced than in the 13 patients with monomorphic ventricular tachycardia induced, and in the 10 patients with clinical polymorphic ventricular tachycardia/ventricular fibrillation/cardiac arrest than in the 12 patients with sustained monomorphic ventricular tachycardia. This disclosed that the increased dispersion of ventricular repolarization was caused by increases in both the activation time difference and the monophasic action potential duration difference in the former, but mainly by an increased activation time difference in the latter groups. CONCLUSION: The signed value of monophasic action potential duration difference can specify whether an increased dispersion of ventricular repolarization is caused by inhomogeneous repolarization, inhomogeneous conduction or both, and thereby it is useful in study of the mechanism of ventricular arrhythmias.

Dispersion of repolarization following double and triple programmed stimulation. A clinical study using the monophasic action potential recording technique.

To study the dispersion of ventricular repolarization following double and triple programmed stimulation and its correlation with the inducibility of ventricular arrhythmias, monophasic action potentials were simultaneously recorded from the right ventricular apex and outflow tract during programmed stimulation in 12 patients with ventricular arrhythmias and a normal QT interval. The time difference between the ends of the two monophasic action potentials were used as a measure of the dispersion of ventricular repolarization, which consists of the activation time difference and the monophasic action potential duration difference. During double and triple programmed stimulation, the dispersion of ventricular repolarization increased significantly with the shortening of the coupling interval but decreased slightly with the shortening of the preceding interval. The induction of the ventricular arrhythmias in these patients was invariably associated with a marked increase in the dispersion of ventricular repolarization. The maximal dispersion of ventricular repolarization was significantly larger in the seven patients with polymorphic ventricular tachycardia and/or ventricular flutter/fibrillation induced than in the four patients with monomorphic ventricular tachycardia induced. Analysis of the two components of the dispersion of ventricular repolarization revealed that the increased dispersion of ventricular repolarization was mainly caused by an increase in the activation time difference in the monomorphic ventricular tachycardia subgroup, and by increases in both the activation time difference and monophasic action potential duration difference in the polymorphic ventricular tachycardia/fibrillation subgroup. These findings suggest that increased dispersion of ventricular repolarization is one of the underlying mechanisms accounting for the myocardial vulnerability to ventricular arrhythmias and that repolarization disturbance is important for the genesis of polymorphic ventricular tachycardia/fibrillation.

Clinical value of transesophageal atrial stimulation and recording in patients with arrhythmia-related symptoms or documented supraventricular tachycardia--correlation to clinical history and invasive studies.

The main objective of the present study was to evaluate the clinical applicability of transesophageal atrial stimulation (TAS) and recording with regard to inducibility of supraventricular tachycardia (SVT) in patients with either an ECG-documented paroxysmal SVT or a clinical history of palpitations suggesting this disease. A further objective was to assess the inducibility of SVT and to compare the inducibility by TAS with that obtained by an invasive electrophysiologic study (EPS). A total of 64 patients (aged 13-74 years) with ECG-documented paroxysmal SVT (n = 50) or only a history of palpitations (n = 14) was referred for TAS. Preexcitation was present in 35 patients. The study protocol included single and double extrastimuli delivered at a basic paced interval of 500 ms, and incremental atrial stimulation until a cycle length of 275 ms or a second-degree AV block appeared. In 10 patients atropine intravenously was required for induction. The same protocol was used in 34 of the patients who also underwent invasive EPS. TAS was completed in 56 of 64 patients (88%). In this group SVT was induced during TAS in 84% (47/56). Of patients with ECG-documented tachycardia, clinical tachycardia was induced in 90% (35/39) with ECG-documented regular paroxysmal SVT and in 67% of patients (4/6) with ECG-documented atrial fibrillation. In patients without ECG-documented atrial fibrillation. In patients without ECG-documented tachycardia, clinically relevant arrhythmia was induced in 73% (8/11). In 30 of 32 patients (94%) with an inducible tachycardia during invasive EPS, it was also possible to induce the tachycardia by TAS.(ABSTRACT TRUNCATED AT 250 WORDS)

[The diagnostic value of esophageal ECG and transesophageal atrial stimulation in paroxysmal supraventricular tachycardia]. / Den diagnostiske vaerdi af esophagus-ekg og transøsofageal atrial stimulation ved paroksystisk supraventrikulaer takykardi.

Paroxysmal supraventricular tachycardia (PSVT) includes a group of common arrhythmias. The diagnosis should be based on 12-lead ECG. Oesophageal ECG, which registers mainly left-sided posterior atrial activity may be of value for further assessment of the arrhythmic mechanism in determination of the time relationship between atrial and ventricular signals. A ventriculoatrial interval during PSVT measured by oesophageal ECG of under 70 ms is evidence of atrioventricular nodal re-entry tachycardia while an interval of over 70 ms suggests orthodromic reciprocating tachycardia with participation of an accessory atrioventricular pathway. Transoesophageal atrial stimulation (TAS) via an electrode catheter is possible in approximately 90% of the patients with PSVT. TAS requires greater quantities of energy than endocardial stimulation and is associated with slight to moderate retrosternal discomfort. The method renders possible both programmed stimulation with the object of inducing arrhythmia and in stopping the majority of cases PSVT, with the exception of atrial fibrillation. The method is relatively simple, non-invasive, requires few resources and can be carried out on outpatients.

Localization of cardiac arrhythmias: conventional noninvasive methods.

Noninvasive localization of the accessory pathway (AP) in patients with the Wolff-Parkinson-White syndrome and of the site of origin of ventricular tachycardia (VT) is reviewed. 12-lead electrocardiography (ECG) is the most readily available method for localization of both the AP and the site of VT origin. Many published ECG criteria are introduced. The application of body surface potential mapping, vectorcardiography, nuclear phase imaging, echocardiography, computed tomography, nuclear magnetic resonance, and signal-averaged ECG in the localization of these arrhythmogenic substrates is also described. We believe that ECG is the most sensitive noninvasive method for AP localization as well as being convenient and simple; it may be used as the only noninvasive method for the initial evaluation. The left lateral AP, which occurs with an incidence of more than 40%, could be localized preoperatively by noninvasive methods only. For localization of the site of VT origin, none of the noninvasive methods is accurate enough for guiding the surgical and catheter-mediated ablative therapies so far.

[Prognostic value of ECG on admission in patients with acute myocardial infarction]. / Prognostisk vaerdi af indlaeggelses-ekg hos patienter med akut myokardieinfarkt.

The initial ECG in acute myocardial infarction (AMI) was assessed in relation to the mortality during hospitalization and development of acute complications endangering life in 405 cases of AMI (345 patients) admitted during a period of three years. The initial ECG recordings were grouped as "positive" or "negative" according to meticulously defined criteria based on the morphology of the QRS complex, deviations of the ST segment and the polarity of the T waves. The ECG recordings were "positive" in 298 cases (86.4%) and "negative" in 47 cases (13.6%). The mortality during hospitalization in the group with "negative" ECG records was definitely lower than in the group with "positive" ECG records (p less than 0.001, chi 2 = 13.99). On the other hand, no definite differences were observed when the initial ECG was compared with the incidence of arrhythmias endangering life (ventricular fibrillation, ventricular tachycardia, asystoly and 3 degrees atrio-ventricular block) (0.10 less than p less than 0.20; chi 2 = 2.46). The authors thus cannot recommend that the initial ECG is given decisive value as to whether a patient with suspected AMI is to be observed in a coronary unit.

Effect of intraperitoneal instillation of 32% dextran 70 on postoperative adhesion formation after tubal surgery.

The intraperitoneal instillation of 32% dextran 70 (HyskonR, Pharmacia AB, Sweden) has previously been reported to prevent the formation of postoperative adhesions. Against this background, the present study was undertaken to evaluate the efficacy of HyskonR in counteracting peritoneal adhesions following tubal microsurgery. 105 infertile women were operated upon in a prospective, randomized, controlled, double-blind, multicenter study. The intra-abdominal adhesions present from the beginning were classified by means of a standardized scoring scale and the extent of adhesions was again evaluated at follow-up laparoscopy 4-10 weeks later. A reduction in the extent of the intra-abdominal adhesions (statistically highly significant) was revealed in both the Hyskon group and the saline control group. The extent of adhesions in the Hyskon group was not lesser than in the saline group, however. The pregnancy rates in the two groups were also similar.