Amiodarone versus propafenone for conversion of chronic atrial fibrillation: results of a randomized, controlled study.

OBJECTIVES: The purpose of this study was to investigate the efficacy and safety of amiodarone and propafenone in the conversion of chronic atrial fibrillation in a prospective, randomized, placebo-controlled study. BACKGROUND: The effectiveness of amiodarone and propafenone in the treatment of patients with chronic atrial fibrillation has not been adequately studied. METHODS: One hundred one patients (48 men, mean age 64 +/- 9 years) with atrial fibrillation lasting >3 weeks participated in the study. Thirty-four patients received amiodarone (300 mg intravenously over 1 h, followed by 20 mg/kg over the next 24 h plus 600 mg orally, in three doses, for 1 week, then 400 mg/day orally, for three weeks), 32 received propafenone (2 mg/kg intravenously over 15 min, followed by 10 mg/kg over 24 h and then 450 mg/day orally, for one month) and the remaining 35 served as control subjects. All patients received digoxin and anticoagulant treatment as indicated (International Normalized Ratio 2 to 3). RESULTS: Conversion to sinus rhythm was achieved in 16 (47.05%) patients who received amiodarone, in 13 (40.62%) who received propafenone and in none of the control subjects (p < 0.001 for both groups vs. control subjects). Those who converted had smaller atria than those who did not and atrial fibrillation of shorter duration in both the amiodarone and propafenone groups. Treatment was discontinued in one patient of the propafenone group because of significant QRS widening. CONCLUSIONS: Amiodarone and propafenone appear to be safe and equally effective in the termination of chronic atrial fibrillation. Left atrial diameter and arrhythmia duration are independent predictors of conversion.

Myocardial perfusion in patients with permanent ventricular pacing and normal coronary arteries.

OBJECTIVES: The purposes of this study were to test the specificity of dipyridamole myocardial perfusion scintigraphy in patients with permanent ventricular pacing (PVP) and to evaluate coronary blood flow and reserve in these patients. BACKGROUND: Permanent ventricular pacing is associated with exercise perfusion defects on myocardial scintigraphy in the absence of coronary artery disease (CAD). On the basis of studies in patients with left bundle brunch block, coronary vasodilation with dipyridamole has been proposed as an alternative to exercise testing for detecting CAD in paced patients, but this approach has never been tested. METHODS: Fourteen patients with a PVP and normal coronary arteries underwent stress thallium-201 scintigraphy and cardiac catheterization. In these patients and in eight control subjects, coronary flow velocities were measured in the left anterior descending coronary artery (LAD) and in the dominant coronary artery before and after adenosine administration. RESULTS: In the paced patients, coronary flow velocities in the LAD and in the dominant coronary artery were significantly lower than those in the control subjects. In addition, seven patients showed perfusion defects on dipyridamole thallium-201 single-photon emission computed tomography, with a specificity of 50% for this test. The defect-related artery in these patients had lower coronary flow reserve (2.6 +/- 0.5) as compared with those without perfusion defects (3.9 +/- 1.0, p < 0.05) or the control group (3.5 +/- 0.5, p < 0.05). CONCLUSIONS: Permanent ventricular pacing is associated with alterations in regional myocardial perfusion. Furthermore, abnormalities of microvascular flow, as indicated by reduced coronary flow reserve in the defect-related artery, are at least partially responsible for the uncertain specificity of dipyridamole myocardial perfusion scintigraphy.

Efficacy of amiodarone for the termination of persistent atrial fibrillation.

The efficacy and safety of amiodarone in the conversion of persistent atrial fibrillation (AF) were investigated in a prospective, randomized, controlled study. Of 67 consecutive patients (32 men, mean age 64+/-9 years) with AF lasting >48 hours, 33 received amiodarone and 34 received placebo. Baseline clinical characteristics were similar in the 2 groups. Patients randomized to amiodarone received 300 mg intravenously for 1 hour and then 20 mg/kg for 24 hours. They were also given 600 mg/day orally, divided into 3 doses, for 1 week and thereafter 400 mg/day for 3 weeks. Patients randomized to placebo received an identical amount of saline IV over 24 hours and then oral placebo for 1 month. Conversion to sinus rhythm was achieved in 16 of the 33 patients (48.5%) who received amiodarone and in none of the 34 patients in the placebo group (p <0.001). None of the patients converted to sinus rhythm within the first 3 days. Those who converted had smaller atria than those who did not (diameter 41.9+/-7.2 vs 50.4+/-5.7 mm, p <0.001). Sex, age, baseline heart rate, left ventricular ejection fraction, and the duration of AF did not differ significantly between patients who converted and those who did not. No side effects requiring discontinuation of treatment were observed in either group. Amiodarone, administered both intravenously and orally, appears to be safe and effective in the termination of persistent AF. Left atrial diameter is the sole independent predictor of conversion.

Low-dose amiodarone versus sotalol for suppression of recurrent symptomatic atrial fibrillation.

To compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation (AF), 70 patients were entered into a randomized, double-blind study. Of these, 35 received amiodarone and 35 sotalol. There were no significant differences in baseline clinical characteristics between groups. Patients with ejection fraction < 40% or clinically significant heart disease were excluded. Patients randomized to amiodarone began with 800 to 1,600 mg/day for 7 to 14 days orally. After the initial loading phase, the drug dose was tapered to maintenance levels over 7 to 12 days; thereafter, therapy was generally maintained at a dosage of 200 mg/day. The sotalol dosage was 80 to 360 mg twice daily, as tolerated. Follow-up clinical evaluations were conducted at 1, 2, 4, 6, 9, and 12 months. The proportion of patients remaining in sinus rhythm on each agent was calculated for the 2 groups using the Kaplan-Meier method. Ten of the 35 patients who were taking amiodarone developed AF during the 12-month observation period, compared with 21 of the 35 who were taking sotalol (p = 0.008). No significant effect of sex, age, left atrial size, or type of AF could be detected that increased the risk of development of AF. We conclude that both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with recurrent symptomatic AF but that amiodarone is the more effective of the 2 drugs for this purpose.

Effect of pericardial pressure on human coronary circulation.

A 52-year-old patient underwent percutaneous balloon pericardiotomy because of rapid fluid accumulation. During the procedure, we calculated the amount of blood flow to the nondiseased left anterior descending coronary artery while pericardial pressure was gradually increased by the infusion of warmed normal saline solution. Coronary vasodilator reserve was assessed by intracoronary adenosine. With increasing pericardial pressure, there was a continuous decline in coronary blood flow, due to an increase in coronary vascular resistance, and an unaffected hyperemic response throughout. The maximal hyperemic flow was far less under increased pericardial pressure than at normal pressure, which implies an augmented susceptibility to myocardial ischemia.

Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study.

STUDY OBJECTIVES: To investigate the efficacy and safety of amiodarone administered as the drug of first choice in the conversion of atrial fibrillation, regardless of its duration. DESIGN: : Prospective, randomized, controlled clinical study. SETTING: : Tertiary cardiac referral center. PATIENTS: Two-hundred eight consecutive patients (102 men; mean [+/- SD] age, 65 +/- 10 years) with atrial fibrillation. INTERVENTIONS: One-hundred eight patients received amiodarone, and 100 patients received placebo treatment. Patients randomized to amiodarone received 300 mg IV for 1 h, and then 20 mg/kg for 24 h. They were also given 600 mg/d orally, divided into three doses, for 1 week, and thereafter 400 mg/d for 3 weeks. Patients randomized to placebo treatment received an identical amount of saline solution IV over 24 h, and oral placebo treatment for 1 month. MEASUREMENTS AND RESULTS: Baseline clinical characteristics were similar in the two groups. Conversion to sinus rhythm was achieved in 87 of 108 patients (80.05%) who received amiodarone, and in 40 of 100 patients (40%) in the placebo group (p < 0.0001). Statistical analysis showed that the duration of the arrhythmia and the size of the left atrium affected both the likelihood of conversion to sinus rhythm and the time to conversion in both groups. No side effects requiring discontinuation of treatment were observed in either group. CONCLUSIONS: Amiodarone appears to be safe and effective in the termination of atrial fibrillation. However, extreme cases with a large left atrium and long-lasting arrhythmia need long-term therapy.

Left atrial appendage function during DDD and VVI pacing.

OBJECTIVE: To examine, using transoesophageal echocardiography, the possible disturbances of left atrial appendage function during VVI and DDD pacing in patients with a normal atrium paced with a dual chamber system. DESIGN: Randomised controlled trial. SETTING: Tertiary care centre. PATIENTS: 22 patients (mean age 68 (SD 6) years) who had been paced with dual chamber pacemakers for at least six months. Exclusion criteria were valvar disease, cardiomyopathy, hypertension, and diabetes mellitus. INTERVENTIONS: All patients underwent a transoesophageal echocardiographic evaluation of left atrial appendage function under DDD and VVI modes in random order. Measurements were made after at least two months' pacing in each mode. MAIN OUTCOME MEASURES: Echocardiographic indices of left atrial appendage flow under both pacing modes. RESULTS: All 22 patients had higher emptying and filling flow velocities under DDD than under VVI mode. The filling and emptying flow velocity integrals were also significantly higher under DDD mode (P < 0.001, P = 0.019). CONCLUSIONS: Left atrial appendage function, as reflected in indices of emptying and filling assessed by transoesophageal echocardiography, is significantly different with DDD than with VVI pacing. This may explain the higher incidence of thromboembolic episodes in patients paced under VVI mode.

Spectral analysis of heart rate variability during tilt-table testing in patients with vasovagal syncope.

Spectral analysis of heart rate variability was used to assess changes in autonomic function in 44 patients with vasovagal syndrome and 20 normal controls before and during postural tilt and to attempt to relate such changes to specific types of haemodynamic response to tilt. Frequency domain measurements of the high (HF) and low (LF) frequency bands and the ratio LF/HF were derived from Holter recordings, computed by Fast Fourier Analysis for 4 min intervals immediately before tilt testing, immediately after tilting and just before the end of the test. In the syncopal patients the mean values of LF and HF decreased significantly in response to tilting, while the LF/HF ratio remained constant. All parameters showed a statistically significant increase just before the onset of syncope. In the control group there was an increase in the LF and LF/HF ratio and a decrease in the HF immediately after tilting. The three subgroups of patients had similar patterns of changes in autonomic activity. The results of this study show that syncopal patients have a different pattern of response to the tilting test. The pathological mechanism leading to vasovagal syncope appears to be independent of the specific type of haemodynamic response to tilt testing.

Electrocardiographic diagnosis of acute myocardial infarction in the presence of ventricular paced rhythm.

ST-segment deviation was recently described as the only ECG finding that was useful in the diagnosis of acute myocardial infarction during right ventricular pacing. This report shows that the same sign may also indicate the amount of myocardium in jeopardy and the coronary artery responsible.

Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study.

OBJECTIVE: To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation. DESIGN: Prospective, randomised, single blind, placebo controlled study. SETTING: Tertiary cardiac referral centre. PATIENTS: 186 consecutive patients (97 men, 89 women; mean (SD) age, 63 (10) years) with recurrent, symptomatic atrial fibrillation. INTERVENTIONS: 65 patients were randomised to amiodarone, 61 to sotalol, and 60 to placebo. Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase. The sotalol dose was 160-480 mg daily, as tolerated. MAIN OUTCOME MEASURES: Recurrence of atrial fibrillation or side effects. RESULTS: In the amiodarone group, 31 of the 65 patients developed atrial fibrillation after an average of six months, while 15 (11 in sinus rhythm and four in atrial fibrillation) experienced significant side effects after an average of 16 months. In the sotalol group, relapse to atrial fibrillation occurred in 47 of the 61 patients after an average of eight months; three experienced side effects during the titration phase. In the placebo group, 53 of the 60 patients developed atrial fibrillation after an average of four months (p < 0.001 for amiodarone and sotalol v placebo; p < 0.001 for amiodarone v sotalol). CONCLUSIONS: Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation. Amiodarone is more effective but causes more side effects.

Reproducibility of tilt table testing in patients with vasovagal syncope and its relation to variations in autonomic nervous system activity.

To assess the variability of head-up tilt table testing, 35 patients with vasovagal syncope, shown by a positive tilt table test, underwent a second test 1 week later. Also, on the day before each test, spectral and time-domain indexes of heart rate variability were derived from Holter recordings to examine the stability of autonomous nervous system activity in these patients. Fifteen healthy volunteers served as a control group and also underwent two tilt table tests with prior Holter monitoring. Twenty-one (60%) of the 35 patients had a second positive test. None of the patients in the control group experienced syncope during either of the tests. The heart rate variability measures in the control group varied slightly from 1 day to the other, in contrast to the syncopal patients, where only low frequency spectral power and the mean of all 5-minute standard deviations of RR intervals showed comparable behavior. The indexes which reflect parasympathetic activity exhibited significant fluctuations in the syncopal patients. These fluctuations were due entirely to the patients who did not reproduce the outcome of the tilt table test, where high parasympathetic tone was associated with the positive test and normal parasympathetic tone with the negative test. In contrast, the patients with two positive tests had high parasympathetic tone during both test periods, with low individual variability. In conclusion, patients with vasovagal syncope show variations in vagal autonomic tone and appear to be more prone to syncope when their parasympathetic tone is elevated.

Sotalol vs metoprolol for ventricular rate control in patients with chronic atrial fibrillation who have undergone digitalization: a single-blinded crossover study.

AIMS: To compare the effects of sotalol and metoprolol on heart rate, during isotonic (ITE) and isometric (IME) exercise and daily activities, in digitalized patients with chronic atrial fibrillation. METHODS AND RESULTS: The study had a randomized, single-blinded, crossover design. Twenty-three patients with chronic atrial fibrillation received placebo for 4 weeks, followed by a 4-week period of treatment with sotalol and metoprolol in random order. At the end of each period, the patients were assessed with 24-h ECG monitoring, a cardiopulmonary exercise test and a handgrip manoeuvre. Both agents produced a lower heart rate than placebo at rest and at all levels of isotonic exercise (P < 0.001) without affecting oxygen uptake. Sotalol produced a lower heart rate than metoprolol only at submaximal exercise (116 +/- 9 bpm for sotalol vs 125 +/- 11 bpm for metoprolol, P < 0.001). During isometric exercise, sotalol produced a lower maximum heart rate than did metoprolol (113 +/- 22 vs 129 +/- 18 bpm, respectively). Both agents produced a lower mean heart rate than placebo over 24 h (P < 0.001 for all), while sotalol produced a lower mean heart rate than metoprolol during the daytime (P < 0.01). CONCLUSION: Sotalol is a safe and effective agent for control of heart rate in digitalized patients with atrial fibrillation. Sotalol is superior to metoprolol at submaximal exercise, resulting in better rate control during daily activities.

Autonomic nervous system activity before and during episodes of myocardial ischemia in patients with stable coronary artery disease during daily life.

Spectral analysis of heart rate variability (HRV) was used to assess changes in the autonomic nervous system (ANS) 10 minutes before, during, and 10 minutes after 110 ischemic episodes (IEs) in 38 patients (25 men, age 61 +/- 10 years) with stable coronary artery disease. In 26 of 77 diurnal IEs (07:00-22:59) there were no changes in the spectral indexes (LF and HF) during the study period. In the remainder there was an increase in the LF:HF ratio due to HF withdrawal that started before the onset of the IE. All 33 nocturnal episodes also showed an increase in the LF:HF ratio, which was due not only to HF withdrawal, but also to a simultaneous increase in LF. Although it is not the only cause, the ANS plays a significant role in triggering IEs during daily life in patients with stable coronary artery disease. The common factor in all such episodes is a gradual withdrawal of parasympathetic tone.

Amiodarone, sotalol, or propafenone in atrial fibrillation: which is preferred to maintain normal sinus rhythm?

UNLABELLED: This randomized study compared the efficacy and safety of amiodarone, propafenone and sotalol in the prevention of atrial fibrillation. METHODS: The population consisted of 214 consecutive patients (mean age 64 +/- 8 years, 106 men) with recurrent symptomatic atrial fibrillation. After restoration of sinus rhythm, patients were randomized to amiodarone (200 mg/day), propafenone (450 mg/day) or sotalol (320 +/- 20 mg/day). Follow-up evaluations were conducted at 1, 2, 4 and 6 months, and at 3-month intervals thereafter. The proportion of patients developing recurrent atrial fibrillation and/or experiencing unacceptable adverse effects was measured in the three groups by the Kaplan-Meier method. RESULTS: Recurrent atrial fibrillation occurred in 25 of the 75 patients treated with amiodarone compared to 51 of the 75 patients treated with sotalol and 24 of the 64 patients treated with propafenone. Fourteen patients treated with amiodarone, five with sotalol, and one with propafenone experienced adverse effects while in sinus rhythm, necessitating discontinuation of treatment (P < 0.001 for amiodarone and propafenone vs sotalol). The difference between amiodarone and propafenone was statistically nonsignificant when all events were included in the analysis. However, if the analysis was limited to recurrent atrial fibrillation events, amiodarone was more effective than propafenone (P < 0.05). CONCLUSIONS: Amiodarone and propafenone were superior to sotalol in maintaining long-term normal sinus rhythm in patients with atrial fibrillation. Amiodarone tended to be superior to propafenone, though its long-term efficacy was limited by adverse side effects.

Effect of acute atrial fibrillation on phasic coronary blood flow pattern and flow reserve in humans.

AIMS: To assess the effect of experimentally induced atrial fibrillation on coronary flow in humans. METHODS AND RESULTS: In 16 patients (10 men, mean age 43+/-13 years) with normal coronary vessels, baseline and hyperaemic blood pressure and Doppler phasic coronary flow velocity were measured, using a 0.014 inch intracoronary Doppler flow wire, during sinus rhythm, experimentally induced atrial fibrillation, and right atrial pacing at a similar heart rate to that during atrial fibrillation. Coronary flow velocity integral per minute increased significantly during both right atrial pacing and atrial fibrillation compared to sinus rhythm, but during right atrial pacing the increase was greater (85+/-43% vs 52+/-25%, P<0.001). This difference persisted even after correction for the product of heart rate and blood pressure (1.15+/-0.51 vs 0.97+/-0.46, respectively, P<0.02). In a further 12 paced patients (seven men, mean age 54+/-10 years) with complete atrioventricular block the induction of atrial fibrillation (atrial fibrillation with regular RR interval) caused no significant changes in coronary flow velocity variables. CONCLUSIONS: Acute atrial fibrillation in humans causes an increase in coronary flow that is, however, insufficient to compensate for the augmented myocardial oxygen demand, mainly because of the irregularity in the ventricular rhythm that exists during atrial fibrillation.

Conversion of atrial fibrillation to sinus rhythm using acute intravenous procainamide infusion.

The efficacy and safety of intravenous procainamide in the conversion of atrial fibrillation was investigated. A total of 114 patients without severe heart failure were randomized to receive either intravenous procainamide (1 g over 30 minutes, followed by an infusion of 2 mg/min over 1 hour) or placebo in a double-blind trial. Digoxin (0.5 mg intravenously) was administered to all patients who had not previously been receiving digoxin. Treatment was considered successful if sinus rhythm was restored within 1 hour after starting the infusion. Conversion to sinus rhythm was achieved in 29 (50.9%) of the 57 patients treated with procainamide and in 16 (28.1%) of the 57 who received placebo (P approximately 0.012). When the duration of the atrial fibrillation was < or = 48 hours, conversion to sinus rhythm was achieved in 29 (69%) of the 42 patients receiving procainamide and in 16 (38.1%) of those receiving placebo (P approximately 0.004). None of the patients with atrial fibrillation lasting > or = 48 hours converted to sinus rhythm in either group. Another factor that played a role in the restoration of sinus rhythm was the size of the left atrium: the smaller the left atrium, the larger the success rate. The results of the study suggest that intravenous procainamide is an effective and safe means for the rapid termination of atrial fibrillation of recent onset and that its success rate is inversely related to the size of the left atrium. However, the drug is ineffective in the conversion of atrial fibrillation lasting more than 48 hours.

Intravenous propafenone versus intravenous amiodarone in the management of atrial fibrillation of recent onset: a placebo-controlled study.

UNLABELLED: The efficacy and safety of intravenous propafenone, amiodarone, or placebo were compared in the treatment of atrial fibrillation (AF) of recent onset (duration < or = 48 hours). METHODS: 143 patients (77 men, mean age 63 +/- 12 years) were studied, of whom 46 received propafenone (2 mg/kg over 15 minutes followed by 10 mg/kg over the next 24 hours), 48 received amiodarone (300 mg intravenously over 1 hour, followed by 20 mg/kg over the next 24 hours, plus 1,800 mg/day orally, in 3 divided doses), and 49 received placebo (the equivalent amount of saline i.v. over 24 hours). Digoxin was administered to all patients who had not previously received it. RESULTS: Conversion to normal sinus rhythm occurred in 36 of 46 patients (78.2%) receiving propafenone, in 40 of 48 patients (83.3%) receiving amiodarone, and in 27 of the 49 (55.10%) controls (P < 0.02, drug vs placebo, between drugs NS). The mean time to conversion was 2 +/- 3 hours for propafenone, 7 +/- 5 hours for amiodarone, and 13 +/- 9 for placebo (P < 0.05). Patients who converted had smaller atria than those who did not (diameter: 42.7 +/- 5 vs 47.2 +/- 7 mm, P < 0.001 for all). Treatment was discontinued in one patient in the amiodarone group because of an allergic reaction and in two patients in the propafenone group because of excessive QRS widening. No side effects were observed in the placebo group. CONCLUSIONS: Both drugs tested intravenously were equally effective and safe for the rapid conversion of recent-onset atrial fibrillation to sinus rhythm. However, propafenone offered the advantage of more rapid conversion than amiodarone.