Double-blind placebo-controlled trial of digoxin in symptomatic paroxysmal atrial fibrillation.

BACKGROUND: Digoxin is commonly prescribed in symptomatic paroxysmal atrial fibrillation (AF) but has never been evaluated in this condition. METHODS AND RESULTS: From a multicenter registry, 43 representative patients with frequent symptomatic AF episodes were recruited into a randomized, double-blind crossover comparison of digoxin (serum concentration, 1.29+/-0.35 nmol/L) and placebo. The study end point was the occurrence of 2 AF episodes (documented by patient-activated monitors), censored at 61 days. The median time to 2 episodes was 13.5 days on placebo and 18.7 days on digoxin (P<0. 05). The relative risk (95% CI) of 2 episodes (placebo:digoxin) was 2.19 (1.07 to 4.50). A similar effect was seen on the median time to 1 episode: increased from 3.5 to 5.4 days (P<0.05), relative risk 1. 69 (0.88 to 3.24). The mean+/-SD ventricular rates during AF recordings during placebo and digoxin treatment were 138+/-32 and 125+/-35 bpm, respectively (P<0.01). Twenty-four-hour ambulatory ECG recordings did not show significant differences in the frequency or duration of AF or in ventricular rate. CONCLUSIONS: Digoxin reduces the frequency of symptomatic AF episodes. However, the estimated effect is small and may be due to a reduction in the ventricular rate or irregularity rather than an antiarrhythmic action.

Efficacy and tolerability of transvenous low energy cardioversion of paroxysmal atrial fibrillation in humans.

OBJECTIVES: This study investigated the efficacy and tolerability of low energy shocks for termination of atrial fibrillation in patients, using an endocardial electrode configuration that embraced both atria. BACKGROUND: In animals, low energy biphasic shocks delivered between electrodes in the coronary sinus and right atrium have effectively terminated atrial fibrillation. If human defibrillation thresholds are sufficiently low, atrial defibrillation could be achieved in conscious patients using an implanted device. METHODS: Twenty-two consecutive patients with stable atrial fibrillation were studied during electrophysiologic testing. Biphasic R wave synchronous shocks were delivered between large surface area electrodes in the coronary sinus and high right atrium, using a step-up voltage protocol starting at 10 or 20 V and increasing to a maximum of 400 V. Patients were conscious at the start of the study and were asked to report on symptoms but were sedated later if shocks were not tolerated. RESULTS: Cardioversion was achieved in all 19 patients who completed the study, with a mean (+/- SD) leading-edge voltage of 237 +/- 55 V (range 140 to 340) and mean energy of 2.16 +/- 1.02 J (range 0.7 to 4.4). The mean maximal shock delivered without sedation was 116 +/- 51 V (range 60 to 180). No proarrhythmia or mechanical complications occurred. CONCLUSIONS: The delivery of biphasic R wave synchronous shocks between the high right atrium and coronary sinus can terminate atrial fibrillation with very low energies. General anaesthesia is not required, and a minority of fully conscious patients are able to tolerate this method of cardioversion.

Multicenter low energy transvenous atrial defibrillation (XAD) trial results in different subsets of atrial fibrillation.

OBJECTIVES: This prospective, multicenter trial was aimed at defining efficacy and safety of low energy shocks during atrial fibrillation in a diverse cohort of patients. BACKGROUND: Experimental studies in sheep and preliminary data in humans have suggested that low energy internal shocks delivered between right atrial and coronary sinus electrode catheters may terminate atrial fibrillation. METHODS: Biphasic 3/3-ms R wave synchronous shocks were delivered between two electrode catheters in the right atrium and coronary sinus. The defibrillation protocol started with a test shock of 20 V, and shocks increased in 40-V steps until restoration of sinus rhythm or a maximum of 400 V. Shock delivery was withheld after short RR intervals. In 141 patients with atrial fibrillation, the protocol was carried out under sedation in case the shock was associated with discomfort. The atrial arrhythmia was paroxysmal (< or = 7 days) in 50 patients, chronic (> 30 days) in 53, intermediate (> 7 days, < or = 30 days) in 18 and induced in 20. Underlying heart disease was present in 88 patients (62%). RESULTS: Paroxysmal atrial fibrillation was successfully terminated in 46 (92%) of 50 patients, chronic atrial fibrillation in 37 (70%) of 53, intermediate in 16 (89%) of 18 and induced in 16 (80%) of 20. Mean conversion threshold was 1.8 J (213 V) in the induced group, 2.0 J (229 V) in the paroxysmal group, 2.8 J (272 V) in the intermediate group and 3.6 J (311 V) in the chronic group. The conversion voltage was significantly (p < 0.001) higher in the chronic group than in the other groups of atrial fibrillation and increased significantly with the duration of atrial fibrillation and with left atrial size (p < 0.05). Of 1,779 R wave synchronized shocks delivered with a mean (+/-SD) preceding RR interval of 676 +/- 149 ms, no ventricular arrhythmia was induced. The latter may occur after unsynchronized shocks. CONCLUSIONS: Low energy transvenous shocks in patients with atrial fibrillation are effective and safe, provided that shocks are properly synchronized to R waves with preceding RR intervals that meet appropriate cycle length criteria. This study provides data that may be useful in the development of an implanted atrial defibrillator.

Localization of accessory pathways from the 12-lead electrocardiogram using a new algorithm.

A new algorithm (St. George's algorithm), based on the polarity and morphology of QRS complexes rather than delta waves, was developed for localizing accessory pathways to 1 of 9 sites on the atrioventricular annuli. This was compared with algorithms previously proposed by Skeberis et al (localizing to 1 of 7 sites) and Milstein et al (localizing to 1 of 4 sites). The preexcited 12-lead electrocardiograms recorded during sinus rhythm in 106 consecutive patients (including 60 retrospectively analyzed patients and 46 prospectively analyzed patients) who underwent successful radiofrequency catheter ablation of a single accessory pathway were analyzed by 3 blinded observers using all 3 algorithms. The results were compared with the actual localization of accessory pathways as derived from endocardial mapping during catheter ablation. In all 106 patients, the accuracy of the 3 algorithms for 4 sites on the atrioventricular annuli (as considered by Milstein's method) was 72%, 79%, and 92% for Milstein's, Skeberis', and St. George's algorithms, respectively. For 7 sites (as considered by Skeberis' method), the accuracy was 65% (Skeberis' algorithm) and 88% (St. George's algorithm), and for 9 sites (as considered by our method) the accuracy was 86% (St. George's algorithm). In 46 prospectively analyzed patients, the accuracy of the 3 algorithms for 4 sites was 70% (Milstein's), 67% (Skeberis'), and 87% (St. George's); for 7 sites the accuracy was 61% (Skeberis') and 85% (St. George's), and for 9 sites the accuracy was 85% (St. George's). The reproducibility of St. George's and Skeberis' methods was better than that of Milstein's method.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of fast heart rate episodes during paroxysmal atrial fibrillation.

OBJECTIVE: To investigate the defibrillator waiting time (time between the recognition of atrial fibrillation and the actual shock) by studying paroxysmal atrial fibrillation episodes with RR intervals shorter than a certain limit (that is, episodes during which defibrillation should not be attempted). METHODS: Long term 24 hour Holter recordings from a digoxin v placebo crossover study in patients with paroxysmal atrial fibrillation were analysed. In all, 23 recordings with atrial fibrillation episodes of at least 1000 ventricular cycles and with < 20% Holter artefacts or noise were used (11 recorded on placebo and 12 on digoxin). For each recording, the mean ("mean waiting time") and maximum ("maximum waiting time") duration of continuous sections of atrial fibrillation episodes with all RR intervals shorter than a certain threshold were evaluated, ranging the threshold from 400 to 1000 ms in 10 ms steps. For each threshold, the mean and maximum waiting times were compared between recordings on placebo and on digoxin. RESULTS: Both the mean and maximum waiting times increased exponentially with increasing threshold. Practically acceptable mean waiting times less than one minute were observed with thresholds below 600 ms. There were no significant differences in mean waiting times and maximum waiting times between recordings on placebo and digoxin, and only a trend towards shorter waiting times on digoxin. CONCLUSIONS: Introduction of a minimum RR interval threshold required to deliver atrial defibrillation leads to practically acceptable delays between atrial fibrillation recognition and the actual shock. These delays are not prolonged by digoxin treatment.

Low energy internal cardioversion of atrial fibrillation resistant to transthoracic shocks.

OBJECTIVE: To investigate the efficacy of internal cardioversion using low energy shocks delivered with a biatrial electrode configuration in chronic atrial fibrillation resistant to transthoracic shocks. METHODS: Low energy internal cardioversion was attempted in 11 patients who had been in atrial fibrillation for 233 (SD 193) days and had failed to cardiovert with transthoracic shocks of 360 J in both apex-base and anterior-posterior positions. Synchronised biphasic shocks of up to 400 V (approximately 6 J) were delivered, usually with intravenous sedation only, between high surface area electrodes in the right atrium and the left atrium (coronary sinus in nine, left pulmonary artery in one, left atrium via patent foramen ovale in one). RESULTS: Sinus rhythm was restored in 8/11 patients. The mean leading edge voltage of successful shocks was 363 (46) V [4.9 (1.2) J]. Higher energy shocks induced transient bradycardia [time to first R wave 1955 (218) ms]. No proarrhythmia or other acute complications were observed. CONCLUSIONS: Low energy internal cardioversion of atrial fibrillation can restore sinus rhythm in patients in whom conventional transthoracic shocks have failed.

Critical noise level reduction for correct identification of late potentials: an illustrative case report.

The precision of detection of late potentials (LPs) on signal-averaged electrocardiography (SAECG) depends on the degree of noise reduction. The recommended low-noise endpoint is 0.3 microV. We describe a patient with sustained ventricular tachycardia after myocardial infarction with very low amplitude LPs in whom a noise level lower than 0.3 microV was necessary in order to obtain an abnormal result of the SAECG. The presence of LPs was confirmed by spectral temporal mapping of the SAECG.

Non-pharmacological treatments for atrial fibrillation. A critical perspective on the status quo.

In a proportion of patients with atrial fibrillation, antiarrhythmic drugs are either ineffective, unsafe, or poorly tolerated. Accordingly, a variety of non-pharmacological treatments have been developed. This article critically reviews these modalities. (i) For ventricular rate control, catheter ablation of the atrioventricular node with pacemaker implantation is commonplace. An alternative is atrioventricular node modulation using a procedure similar to "slow pathway" ablation. (ii) For restoration of sinus rhythm, internal cardioversion using low energy shocks is highly effective; this has prompted the development of atrial and dual chamber defibrillators. (iii) To eliminate the atrial fibrillation substrate, a number of surgical procedures have been developed, of which the most effective is the "Maze" operation. The efficacy of this operation cannot be reproduced by conventional catheter ablation, and current research is concentrating on simplified procedures using new catheter designs for linear ablation. (iv) Finally, pacemakers and catheter ablation may be used to suppress the triggers for atrial fibrillation episodes. A number of atrial algorithms are under investigation for overdrive suppression of ectopy, and the use of multisite atrial pacing to alter the atrial response to ectopy has shown promising results. Catheter ablation has shown considerable success in preventing "focal" atrial fibrillation that is triggered or driven by ectopy arising usually from the pulmonary veins. To date, there are few data regarding the long-term efficacy and safety of these techniques, and their effects on quality of life. However, ongoing multicentre trials addressing these issues are expected to report over the next few years.

[Reproducibility of signal-averaged electrocardiography]. / Reproductibilité immédiate de l'électrocardiogramme à haute amplification et moyennage.

The reproducibility of the parameters defining the presence of late potentials on the signal-averaged electrocardiogram is one of the limiting factors of the method. The authors studied the coefficients of correlation and reproducibility of these parameters in patients with coronary artery disease. In addition, they tried to determine which parameter was most often responsible for changing a diagnostic conclusion (i.e., presence or absence of late potentials). Two signal-averaged ECGs were recorded one after the other in 127 patients. The presence of late potentials was defined as the presence of a least two of the following criteria: total amplified and averaged QRS duration (tQRS) > 114 ms: duration of the last signal of under 40 microV (LAS) > 38 ms, and root mean square of the amplitude of the last 40 ms (RMS) < 20 microV. The correlation coefficients were 0.98, 0.96 and 0.94 for the duration of tQRS, LAS and RMS respectively (p < 0.0001). The coefficients of reproducibility were 7.0 ms. 7.0 ms and 16.1 microV respectively. Late potentials were present in 22% of patients. A change in diagnosis between the first and second recording was observed in 10 subjects (8% of the population). A combined change in LAS and RMS was responsible for 6 of these revised diagnoses, a change in LAS alone in 2 cases, of the RMS alone in 1 case and the tQRS alone in 1 case. In patients with coronary artery disease, the immediate reproducibility of the diagnosis of late potentials is affected by changes in LAS and RMS. The tQRS is only rarely responsible for a change in diagnosis. This study suggests that the result of the signal-averaged ECG should be interpreted with caution when the LAS or RMS are near their threshold values.

[Use of PTCA in a gastroepiploic aortocoronary graft]. / PTCA gastroepiploického aortokoronárního stepu.

The use of the gastroepiploic inferior artery as an aortocoronary graft is at present a method of third choice after the mammary artery and venous grafts in revascularizations of the heart muscle. The results are comparable with those obtained with the mammary artery. With regard to the increasing number of operations are more plentiful on the development of atherosclerosis of the above mentioned graft. This dumps the initial enthusiasm that in this artery atherosclerosis does not develop. Reports on PTCA, when this artery is affected, are so far rate. The authors performed a successful PTCA of this graft in a patient with complete affection of the coronary circulation where alternative possibilities of revascularization of the heart muscle were practically exhausted. To improve the technique a suitable type of catheter must be developed which will make it possible to overcome technical problems associated with cannulation of artery and its dilatation.

Gentamicin induced ototoxicity during treatment of enterococcal endocarditis: resolution with substitution by netilmicin.

Enterococcal endocarditis can be very difficult to eradicate, requiring prolonged treatment with a combination of a penicillin and an aminoglycoside. In this patient with a pacemaker associated enterococcal endocarditis, ototoxicity occurred due to total gentamicin dose despite plasma concentrations consistently within the treatment range. Substitution with netilmicin, without a break in aminoglycoside treatment, resulted in a rapid improvement in hearing and allowed the required course of aminoglycoside to be completed. The risk factors for ototoxicity with gentamicin are reviewed, in particular the dangers of increasing age and of multiple and prolonged courses. Close treatment monitoring does not totally avoid this risk, especially when prolonged aminoglycoside treatment is required. This case emphasises the need for prompt investigation and adequate, definitive treatment of enterococcal endocarditis to avoid the increased risk consequent on repeated courses of antibiotics. The resolution of the ototoxicity with netilmicin is consistent with other reports of lower cochleotoxicity than with other aminoglycosides.

Current concepts in atrial fibrillation.

The mechanism of atrial fibrillation has recently become clearer, and is understood in terms of multiple irregular wavelets of excitation. This understanding allows a simple model to be proposed which unites the various aetiologies and treatments of atrial fibrillation.

Recurrent syncope due to complete atrioventricular block, a rare presenting symptom of otherwise silent coronary artery disease: successful treatment by PTCA.

A patient presented with recurrent syncope and episodes of AV block preceded by asymptomatic ST segment elevation on ambulatory monitoring. Coronary angiography revealed a severe stenosis in the midsegment of the right coronary artery (RCA). Successful PTCA and stent insertion abolished further episodes of syncope.

Identification of atrial fibrillation episodes in ambulatory electrocardiographic recordings: validation of a method for obtaining labeled R-R interval files.

Current systems for analyzing ambulatory electrocardiograms (ECGs) are unable to distinguish precisely between sinus rhythm and atrial fibrillation (AF) episodes, and are unable to produce RR interval listings that distinguish AF from sinus rhythm on a beat-to-beat basis. We describe a method for obtaining such a computerized listing ("Composite Rhythm" file) from ambulatory recordings containing episodes of AF. The file lists the rhythm of each beat, its real time, and the QRS complex morphology. A visual inspection is made of a full printout of the recording to identify the precise time of onset and termination of each episode of AF. These times are entered into a computer and identified with the corresponding beats on a conventional RR interval file generated by Holter analysis. The method was validated using 1-hour segments from 20 ambulatory ECGs containing 145 episodes of AF. These were visually identified by four independent observers with a mean sensitivity of 99.1%. The first beat of AF was identified concordantly in 96% of episodes, with a discrepancy of < or = 3 beats in the other episodes. The times of 200 selected QRS complexes were then entered into the computer by each observer; 91.1% of these complexes were identified exactly and 100% were identified to within one beat. The Composite Rhythm files have several potential applications for testing AF detection algorithms and studying the mode of onset of AF.

Effect of digoxin on the ventricular rate variability during paroxysmal atrial fibrillation.

This study investigated whether the irregularity of ventricular cycle length during atrial fibrillation (AF) is affected by digoxin. Patients (n = 41) with paroxysmal AF enrolled in a randomized crossover comparison of digoxin and placebo underwent 24-hour ambulatory monitoring during each treatment. Tapes containing AF episodes lasting at least 2 minutes were selected (24 recordings on placebo and 17 on digoxin). The mean (mRR) and standard deviation (SDRR) of RR intervals was calculated for each 30-second segment of AF. The resulting SDRR values were clustered according to bins of mRR values ranging from 350-650 ms in 25-ms steps. In each bin, the SDRR values of all placebo and all digoxin recordings were statistically compared for the top 5, 10, and 15 percentiles of each bin which represented the extremes of ventricular cycle length irregularity during AF. There were no significant differences between the total data of SDRR values in individual bins of mRR. However, the top 5, 10, and 15 percentiles of SDRR values corresponding to mRR values from 350-550 ms were significantly reduced by digoxin (P < 0.0001). The study concludes that although digoxin does not influence the mean variability of RR cycles during AF paroxysms, it suppresses episodes in which a fast ventricular response is associated with extreme variability of RR periods.

Graphical representation of complex data--diurnal patterns of initiations of atrial fibrillation episodes.

A construction of a purpose designed graphical display is demonstrated in a study investigating the circadian distribution of patterns of RR interval sequences preceding episodes of paroxysmal atrial fibrillation (PAF). Based on a comparison with a (80%, 120%) range around the median of preceding 10 RR intervals, each RR interval is classified as normal, short, or long. Classifications of RR intervals in n-tuplets (n = 1, ...,5) preceding PAF episodes are used to compute probabilities of individual types of sequences occurring within 4-hour periods of the day (between 1 am, 5 am, 9 am, 1 pm, 5 pm, and 9 pm). Graphical representation of the data is proposed using a hierarchy of bar graphs. The graphical system has been filled with data of 327 atrial fibrillation episodes recorded in 46 24-hour ECGs in PAF patients. The graphical analysis supports a link between PAF initiation and cardiac autonomic status.

A new pacing algorithm for overdrive suppression of atrial fibrillation. Chorus Multicentre Study Group.

Constant rapid pacing may suppress arrhythmias, but it is usually poorly tolerated in the long term. We report a pilot study of a new pacing algorithm for overdrive suppression of atrial premature complexes (APCs) and atrial fibrillation (AF), which prevents postextrasystolic pauses and varies the pacing rate in response to the frequency of APCs. The algorithm was tested in a multiple crossover study for 24 hours in dual chamber pacemakers implanted in 70 patients. Comparison was made on ambulatory recordings between the number of atrial arrhythmias commencing with the algorithm active and inactive. In all cases, the algorithm functioned as designed. No patient was aware of its operation, and no malignant arrhythmias were induced. The 36 recordings that showed atrial arrhythmia were included for analysis. The effects of the algorithm were: APCs (estimated from pacemaker statistics) reduced in 18 patients, increased in 8 (P = 0.02); atrial salvos reduced in 12, increased in 4 (P = 0.041); and AF reduced in 11, increased in 8 (P = NS). In all patients with frequent AF (> 5 episodes in total), fewer episodes occurred when the algorithm was active. We conclude that the algorithm is safe and well tolerated, reduces atrial ectopic activity, and may reduce the frequency of sustained atrial fibrillation.

Circadian variation in atrial fibrillation in patients with frequent paroxysms.

Determinants of the duration of episodes of atrial fibrillation (AF) in patients with paroxysmal atrial fibrillation (PAF) are poorly understood. However, autonomic tone shows circadian variation and is known to affect atrial electrophysiology. We therefore compared the duration of episodes of AF with an onset during the day (08:00-22:00) to those with an onset during the night in a database of 24-hour ECG recordings in patients with frequent symptomatic PAF. The heart rate in the 30 seconds prior to AF onset was also compared. From 42 recordings, 296 episodes of AF > 30 seconds duration and preceded by > 60 seconds sinus rhythm were identified. The 165 nocturnal episodes tended to be shorter (median = 1.15 min) than the 131 diurnal episodes (median = 1.5 min) and the distribution of nocturnal and diurnal durations was significantly different (P = 0.007; Kolgomorov-Smirnov test). This was also true in recordings containing at least 1 diurnal and at least 1 nocturnal episode. The mean heart rate prior to AF onset was lower at night (62.2 +/- 11.8 vs 75.6 +/- 16.4 beats/min; P < 0.0001 Wilcoxon test). These findings suggest that in patients with frequent symptomatic PAF, autonomic influences affect the duration of episodes of AF and has pathphysiological and therapeutic implications.