Leopoldo Bianconi

Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study.

OBJECTIVES Our aim was to evaluate the benefits and risks of administering propafenone before electrical defibrillation for chronic atrial fibrillation. BACKGROUND In this context, an antiarrhythmic drug-although potentially useful in preventing early recurrence of arrhythmia-could adversely affect the defibrillation threshold and reduce the cardioversion success rate. METHODS We randomly assigned 100 patients with chronic atrial fibrillation to oral treatment with either placebo (51 patients) or 750 mg/day of propafenone (49 patients) for 48 h before administration of direct current shock. After successful cardioversion, all patients received propafenone therapy and were followed up for 48 h. RESULTS Before defibrillation, three patients in the propafenone group (6.1%) had reversion to sinus rhythm and one had sustained ventricular tachycardia. Shock efficacy (82.4% vs. 84.4%) and the cumulative effective energy (395 +/- 258 vs. 421 +/- 236 J) were not different between the placebo and propafenone groups. In the propafenone group, 11 patients had their arrhythmia transformed into atrial flutter and required a lower energy level for arrhythmia conversion than did the other patients with continued atrial fibrillation (245 +/- 197 vs. 493 +/- 215 J, p < 0.01); the latter patients showed a trend (p < 0.10) toward higher energy requirements than that of patients who received placebo. The incidence of asymptomatic bradyarrhythmias was higher in the propafenone group (28.9% vs. 7.1%, p < 0.02), but more patients who received placebo had early recurrence of atrial fibrillation (16.7% vs. 0%, p < 0.02). Two days after cardioversion, more patients given propafenone (73.5% vs. 52.9%, p < 0.05) were discharged from the hospital with sinus rhythm. During the in-hospital stay, propafenone was withdrawn from six patients (6.6%) because of side effects. CONCLUSIONS Propafenone, given before electrical cardioversion for chronic atrial fibrillation does not affect the mean defibrillation threshold or the rate of successful arrhythmia conversion. It decreases the recurrence of atrial fibrillation early after shock, thus allowing more patients to be discharged from the hospital with sinus rhythm.

n-3 Polyunsaturated fatty acids for the prevention of arrhythmia recurrence after electrical cardioversion of chronic persistent atrial fibrillation: a randomized, double-blind, multicentre study

AIMS Persistent atrial fibrillation (AF) often recurs after direct current electrical cardioversion (ECV). As several experimental and clinical studies suggest that n-3 polyunsaturated fatty acids (PUFAs) may have antiarrhythmic properties even at the atrial level, we aimed to evaluate whether oral supplementation with PUFAs, in addition to conventional antiarrhythmic drugs, could reduce the recurrence rate of the arrhythmia after ECV of persistent AF. METHODS AND RESULTS Two hundred and four patients (mean age 69.3 years, 33% females) with persistent AF were randomly assigned to receive 3 g/day of PUFAs until ECV and 2 g/day thereafter (104 patients) or placebo (100 patients) for 6 months, beginning at least 1 week before ECV. Selection of conventional antiarrhythmic prophylaxis was left to local medical advice. The cardiac rhythm was assessed by both trans-telephonic monitoring and clinical visits. Primary end-point was the recurrence rate of AF. Sinus rhythm was restored, either spontaneously or after ECV, in 187 patients (91.7%); 95 patients (91.4%) on PUFAs and 92 patients (92.0%) on placebo (P=not significant). AF relapsed in 56 (58.9%) of the PUFAs patients and in 47 (51.1%) of the placebo patients (P=0.28). The mean time to AF recurrence was 83±8 days in the PUFAs group and 106±9 days in the placebo group (P=0.29). CONCLUSION Our results do not support the hypothesis that, in patients undergoing ECV of chronic persistent AF, supplementation with PUFAs in addition to the usual antiarrhythmic treatment reduces recurrent AF.

Transthoracic DC Shock May Represent a Serious Hazard in Pacemaker Dependent Patients

External defibrillation is widely used for the termination of various atrial and ventricular tachyarrhythmias, including pacemaker patients. Our study was intended to evaluate the effects of DC shocks in 36 patients with unipolar pacemakers implanted in the right pectoral region (25 DDD, 10 VVI, 3 AAI). The shocks were delivered with paddles on the anterior surface of the thorax, as far as possible away from the pacemaker. The pacing output was programmed at 0.5 msec and 5 V (25 patients), 4 V (1 patient), and 2.5 V (10 patients). Transient loss of capture occurred in 18 patients (50%). These patients, compared with those without capture failure, received higher peak and cumulative shock energies, respectively, 216 ± 99 versus 123 ± 50 joules (P < 0.002) and 352 ± 62 versus 147 ± 98 joules (P < 0.004) and had a lower pacemaker pulse amplitude (4.0 ± 1.2 vs 4.6 ± 1.0 V, P = 0.11). Failure to capture lasted from 5 seconds to 30 minutes (mean 157 sec). In 15 patients the ventricular stimulation threshold was measured before and serially after cardioversion. A six‐fold threshold increase was observed 3 minutes after the shock (P < 0.004) with gradual recovery to nearly baseline values at 24 hours. Transient sensing failure occurred in 7 of the 17 patients in whom it could be evaluated (41%). Furthermore, three cases of shock induced pacemaker malfunctions were observed requiring replacement of the stimulator in two patients. In conclusion, the incidence of loss of capture in pacemaker patients subjected to electrical cardioversion/defibrillation is high. The phenomenon is due to an abrupt rise in stimulation threshold, caused by the electrical shock, and may represent a serious hazard in pacemaker dependent patients. The risk of pacing failure could be reduced by utilizing low shock energies when possible, and by programming the pacemaker at its maximal output before cardioversion.

Local Capture by Atrial Pacing in Spontaneous Chronic Atrial Fibrillation

BACKGROUND Atrial fibrillation (AF) is considered to be maintained by multiple reentrant circuits without or with a very short excitable gap. However, the possibility of local atrial capture has been shown recently in experimental AF or induced AF in humans. METHODS AND RESULTS This study was undertaken to evaluate the feasibility of atrial capture-suggestive of an excitable gap-in spontaneous chronic AF. Decremental pacing was performed in 47 right atrial sites in 14 patients with chronic AF, not taking antiarrhythmic drugs. A Franz catheter (for pacing and monophasic action potential recording) and a recording quadripolar catheter positioned about 10 mm apart were used. Local capture was achieved in 41 (87.2%) sites for a total of 100 captures. In 71 episodes the capture was lost within 15 seconds, while in the remaining 29, pacing was stopped after 15 seconds of stable capture. AF types immediately before capture were type 1 in 83 and type 2 in 17 episodes. Type 3 AF was never captured. Pacing cycle at capture was 175.7 +/- 20.9 ms. The baseline atrial interval (FF) was 185.4 +/- 24.5, significantly longer than the FF recorded during pacing immediately before capture (176.0 +/- 19.8 ms) (P < .02). CONCLUSIONS During spontaneous chronic AF in humans, (1) local capture by atrial pacing is possible up to at least 15 mm from the pacing site, (2) regional entrainment is possible during type 1 and type 2 AF but not type 3 AF, and (3) pacing before capture accelerates AF, probably by transient or local capture. These findings suggest that an excitable gap is present in chronic AF, therefore supporting the hypothesis that leading circle reentry is not the unique electrophysiological mechanism maintaining the arrhythmia.

Comparison between propafenone and digoxin administered intravenously to patients with acute atrial fibrillation

In recent-onset atrial fibrillation, intravenous propafenone has been shown to effectively restore sinus rhythm, whereas the efficacy of intravenous digoxin has been questioned. We directly compared these 2 drugs and placebo in acute atrial fibrillation. One hundred twenty-three patients with atrial fibrillation lasting <72 hours were randomized to a 10-minute intravenous infusion of either propafenone (2 mg/kg, 41 patients) or digoxin (0.007 mg/kg, 40 patients) or placebo (42 patients). After 1 hour, nonconverted propafenone or digoxin patients were switched to the alternative drug, while nonconverted placebo patients were randomized to either propafenone or digoxin. The observation time ended 1 hour later. By 1 hour, conversion rates were 49% in the propafenone group, 32% in the digoxin group (p = 0.12), and 14% in placebo group (p <0.001 vs propafenone, p = 0.08 vs digoxin). After crossover, digoxin converted 5% of propafenone patients, while propafenone converted 48% of digoxin patients (p <0.05). In the 36 nonconverted placebo patients, sinus rhythm was obtained in 53% of cases with propafenone, and in 5% with digoxin (p < 0.05). Globally, among the 116 patients who received a drug as first treatment, 30 of 60 patients (50%) were converted by propafenone versus 14 of 56 (25%) by digoxin (p <0.01) (odds ratio 2.0, 95% confidence interval 1.19 to 3.36). In nonconverters, the ventricular rate reduction was faster (15 vs 45 minutes) and more prominent (-24% vs -14%) with propafenone than with digoxin. In conclusion, intravenous propafenone terminates atrial fibrillation more effectively than either placebo or intravenous digoxin. In addition, in nonconverted patients, it obtains a more rapid and marked control of the ventricular rate.

New Antiarrhythmic Drugs for the Treatment of Atrial Fibrillation

Atrial fibrillation is the most common sustained cardiac arrhythmia. It is associated with a decrease in cardiac output with a fivefold increased risk of stroke and twofold increased mortality rate. Although the control of ventricular response is usually the first clinical concern, the restoration and maintenance of sinus rhythm would be the optimal therapy of the arrhythmia and could result in improved cardiac performance and a reduced risk of thromboembolic complications. The only drugs available for restoring and maintaining sinus rhythm have been Class IA antiarrhythmic agents (quinidine, procainamide, and disopyramide). Their use was limited by the frequent occurrence of systemic side effects and their efficacy in maintaining sinus rhythm did not exceed 50% on a yearly basis. Moreover, their safety has been questioned since the long-term treatment with quinidine was found to be associated with an increased mortality compared to placebo. Subsequently, other drugs pertaining to Classes IC and III have gradually gained acceptance for the chronic prophylaxis of the arrhythmia since they were better tolerated (propafenone and flecainide), more effective (amiodarone), and probably safer (all of them) than Class IA agents. Moreover, a high success rate in acute conversion of the recent onset atrial fibrillation was achieved with Class IC drugs. Nevertheless, the existing drugs were far from being ideal. Class IC drugs do not seem to be more effective than quinidine and have a depressant effect on myocardial contractility and conduction, while amiodarone, which does not have the same drawbacks, is burdened by a high incidence of systemic side effects when used long-term. In brief, it is clear that the safety and effectiveness of the current antiarrhythmic drugs are largely suboptimal and that drugs more effective and, most important, devoid of systemic and cardiac untoward effects are strongly desirable. The recent advances in understanding the electrophysiological basis of the arrhythmia have identified the short atrial refractory period associated with atrial fibrillation as the “vulnerable parameter” of the arrhythmia. On this basis, in the last decade, research has focused on the development of drugs specifically aimed at prolonging repolarization (the so-called “pure” Class III effect). A great deal of expectation was placed on these new compounds because they emerged as being virtually devoid of undesirable effects on cardiac contractility, excitability, and conduction, and this would allow their use even in patients in whom other antiarrhythmic drugs are precluded. The first of these novel compounds, ibutilide and dofetilide, are already clinically available and a number of other ones are going through different stages of preclinical and clinical development.

C-reactive protein and left atrial appendage velocity are independent determinants of the risk of thrombogenesis in patients with atrial fibrillation

BACKGROUND The association between inflammatory status and thrombosis in patients with atrial fibrillation (AF) is unclear. We studied the correlation between inflammation and the risk of thrombogenesis in patients with AF and the relationship of inflammation with other factors associated with thrombotic risk. METHODS We studied 150 consecutive patients (69 men, age 65+/-12 years) with persistent non-valvular AF who had transesophageal echocardiography prior to cardioversion. Patients underwent also measurements of high-sensitivity C-reactive protein, fibrinogen, D-dimer, and hematocrit levels. RESULTS Patients were divided into two groups according to the presence (n=52) or absence (n=98) of dense spontaneous echo contrast (SEC) in left atrium or left atrial appendage. The two groups were similar for age, sex, and major clinical risk factors. Patients with dense SEC had significantly larger left atrium diameter (p=0.007), lower left atrial appendage mean velocity (p<0.0001), and higher levels of C-reactive protein (p=0.003), D-dimer (p=0.008), and fibrinogen (p=0.006). At multivariate analysis, only left atrial appendage velocity (odds ratio: 19.11; 95% confidence interval 4.2-80.9) and C-reactive protein (odds ratio: 3.41; 95% confidence interval 1.2-9.8) were significantly associated with thrombus and/or dense SEC. However, there was no relationship between C-reactive protein levels and left atrial appendage velocity (p=0.24, r=-0.09). CONCLUSIONS Our results show that left atrial appendage velocity and C-reactive protein are independently associated with the risk of thromboembolism in AF. Thus, blood stasis and inflammation appear to constitute two major distinct components of thrombogenesis.

Effects of Oral Propafenone Therapy on Chronic Myocardial Pacing Threshold

The effects of oral propofenone therapy on pacing threshold were studied in 36 patients chronically paced for sick sinus syndrome or AV block. The pacemakers, all unipolar models and with noninvasive threshold measurement facilities, were: 9 VVI, 15 AAI, and 12 DDD. Each patient received an initial propafenone dose of 450 mg/day, that in 18 cases was increased to 900 mg/day. Threshold was tested at baseline and at each dosage after 7 days of therapy. With the lower propa/enone dosage the threshold, measured at 2.5 V, rose from 0.14 ± 0.10 to 0.21 ± 0.16 msec (+ 55%) in the atrium (P < 0.0001) and from 0.10 ± 0.08 to 0.15 ± 0.09 msec (+ 63%) in the ventricle (P < 0.0001). In the 18 patients who received both dosages, the mean atrial and ventricular threshold increased from 0.12 ± 0.10 to 0.17 ± 0.14 msec with the lower dose and to 0.27 ± 0.22 msec (+125%) with the higher dose (P < 0.0001) for both increments), With the 900 mg/day dose, a threshold increment ± 300% was observed in 15% of the stimulated chambers. A good linear correlation (r = 0.76) was found between the ventricular threshold increment and the drug induced QRS widening. In conclusion, treatment with oral propafenone increases atrial and ventricular stimulation threshold in pacemaker patients. Threshold increment is dose dependent and proportional to the drug induced QHS widening. In the majority of the cases the threshold increment is not clinically significant, but caution must be used in prescribing high doses of the drug to patients with high baseline threshold.

Postcardioversion atrial electrophysiologic changes induced by oral verapamil in patients with persistent atrial fibrillation

OBJECTIVES The aim of our study was to verify the effect of oral administration of verapamil on atrial electrophysiologic characteristics after cardioversion of persistent atrial fibrillation (AF) in humans. BACKGROUND Discordant findings have been reported regarding the efficacy of verapamil in preventing the electrical remodeling induced by AF. METHODS We determined the effective refractory periods (ERPs) at five pacing cycle lengths (300 to 700 ms) and in five right atrial sites after internal cardioversion of persistent AF (mean duration 238.1+/-305.9 days) in 19 patients. Nine patients received oral verapamil (240 mg/day) starting four weeks before the electrophysiologic study, whereas the other 10 patients were in pharmacologic washout. RESULTS The mean ERPs were 202.0+/-22.7 ms in the washout group and 189.3+/-18.5 ms in the verapamil group (p < 0.0001). The degree of adaptation of refractoriness to rate was similar in the two groups (mean slope value in the washout group and verapamil group: 0.07+/-0.03 and 0.08+/-0.05, respectively), showing a normal or nearly normal adaptation to rate in the majority of the paced sites in both groups. The mean ERP was slightly longer in the septum than in the lateral wall and in the roof, both in the washout and verapamil groups. CONCLUSIONS In patients with persistent AF, long-term administration of verapamil before internal cardioversion resulted in 1) shortening of atrial ERPs; 2) no change in refractoriness dispersion within the right atrium; and 3) no change in atrial ERP adaptation to rate.

Transcutaneous Cardiac Pacing for Termination of Tachyarrhythmias

ALTAMURA, G., ET AL.: Transcutaneous Cardiac Pacing for Termination of Tachyarrhythmias. Transcutaneous cardiac pacing (TCP) was used for interruption of tachyarrhythmias in 31 patients: 20 with ventricular tachycardia (VT); eight with atrioventricular reentrant tachycardia (AVRT) and three had atrioventricular nodal tachycardia (AVNT). The stimulators used (Pace Aid 50/52) allow pacing at programmable rates (50–160 ppm) and output (10–200 mA at 20‐msec pulse duration), when possible overdrive pacing was used. Short bursts of stimuli were delivered with increasing current intensity until interruption of the arrhythmia or to the maximum energy tolerated by the patient. VTs were interrupted in eight of the 20 patients: four of the six (67%) treated by overdrive pacing and four of the 14 (29%) were treated by underdrive pacing. Supraventricular tachycardias (SVT) were terminated in eight of the 11 patients: seven out of eight (88%) AVT, and one out of three AVNT (33%). We observed two cases of arrhythmia worsening: a VT acceleration and induction of ventricular fibrillation in a patient with AVNT. TCP was well tolerated by the majority of the patients. We conclude that TCP is an effective method for interruption of ventricular and supraventricular reentrant tachycardias, but the risk of arrhythmia worsening must be considered.