Nikos E. Igoumenidis

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.

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.

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.

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 internals 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 parasympa‐thetic 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.

Amiodarone, Sotalol, or Propafenone in Atrial Fibrillation: Which Is Preferred to Maintain Normal Sinus Rhythm?

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.

Intravenous Propafenone Versus Intravenous Amiodarone in the Management of Atrial Fibrillation of Recent Onset: A Placebo-Controlled Study

The efficacy and safety of intravenous propafenone, amiodarone, or placebo were compared in the treatment of atrial fibrillation (AF) of recent onset (duration ≤ 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 IV 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.

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 ≊ 0.012). When the duration of the atrial fibrillation was ≤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 ≊ 0.004). None of the patients with atrial fibrillation lasting ≤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.

Peripheral monocytes from diabetic patients with coronary artery disease display increased bFGF and VEGF mRNA expression

BackgroundMacrophages can produce vascular endothelial growth factor (VEGF) in response to hypoxia, transforming growth factor β1 (TGF-β1), angiotensin II, basic fibroblast growth factor (bFGF), and interleukin-1. These factors have been found in the serum of coronary artery disease (CAD) patients as well as in atherosclerotic lesions. The aim of the present study was to test the hypothesis that the expression of VEGF, TGF-β1 and bFGF in peripheral monocytes and lymphocytes is related to CAD.MethodsHuman Mononuclear cells and lymphocytes from peripheral blood were isolated from 53 donors undergoing angiography. Seventeen were found to be healthy and 36 were diagnosed with CAD. The respective mRNAs were extracted and quantified.ResultsThe statistical analysis revealed a significant increase of the basal level expression for macrophage VEGF and bFGF in the CAD SA (stable angina) patient group compared to the noCAD (control) (p = 0.041 and p = 0.022 respectively) and CAD UA (unstable angina) (p = 0.024 and p = 0.005 respectively) groups, which was highly dependent on the diabetic status of the population. Furthermore, we demonstrated with an in vitro cell culture model that the levels of VEGF and bFGF in monocytes of healthy donors are not affected by short term exposure to increased glucose levels (usually observed in the diabetic patients) and/or statin.ConclusionOur findings display a statistically significant association of the increased VEGF and bFGF levels in peripheral monocytes, with stable angina and diabetes in coronary artery disease. The results give new insight to CAD and the impaired collateral vessel formation in diabetics.

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 (HR V) 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. AII 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.

Electrocardiographic appearance of old myocardial infarction in paced patients.

KOCHIADAKIS, G.E., et al.: Electrocardiographic Appearance of Old Myocardial Infarction in Paced Patients. This study evaluated the possibility of diagnosing chronic myocardial infarction in the presence of the pacing electrocardiogram. Forty‐five patients with known myocardial infarction (anterior 23, inferior 22) and 26 healthy controls were studied. After coronary angiography, pacing was applied from the right ventricular apex, and the sensitivity, specificity, and average diagnostic accuracy of five criteria on the paced electrocardiogram were assessed: (1) Notching 0.04 second in duration in the ascending limb of the S wave of leads V3, V4, or V5 (Cabreras sign); (2) Notching of the upstroke of the R wave in leads I, aVL, or V6 (Chapmans sign); (3) Q waves > 0.03 second in duration in leads I, aVL, or V6; (4) Notching of the first 0.04 second of the QRS complex in leads II, III, and aVF; (5) Q wave > 0.03 second in duration in leads II, III, and aVF. The most sensitive criteria, for anterior and inferior myocardial infarctions were Cabreras and Chapmans (91.1 and 86.6%, respectively). All criteria had low specificity (range 42.3–69.2%). The combination of Cabreras and Chapmans sign decreased the sensitivity to 77.7%, but increased specificity to 82.2%. The sensitivity and specificity of all the criteria were independent of the myocardial infarction site. In paced patients, the application of electrocardiographic criteria, and especially the combination of Cabrera and Chapman, provides useful clinical information in recognizing prior myocardial infarction but not in assigning the specific infarct site.