George E. Kochiadakis

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.

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.

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.

Phasic coronary flow pattern and flow reserve in patients with left bundle branch block and normal coronary arteries.

OBJECTIVES The purpose of this study was to determine whether scintigraphic myocardial perfusion defects in patients with left bundle branch block (LBBB) and normal coronary arteries are related to abnormalities in coronary flow velocity pattern and/or coronary flow reserve. BACKGROUND Septal or anteroseptal defects on exercise myocardial perfusion scintigraphy are common in patients with LBBB and normal coronary arteries. METHODS Thirteen patients (7 men, age 61+/-8 years) with LBBB and normal coronary arteries underwent stress thallium-201 scintigraphy and cardiac catheterization. In all patients and in 11 control subjects coronary blood flow parameters were calculated from Doppler measurements of flow velocity in the left anterior descending coronary artery (LAD) before and after adenosine administration. RESULTS The time to maximum peak diastolic flow velocity was significantly longer both for the seven patients with (134+/-19 ms) and for the six without (136+/-7 ms) exercise perfusion defects than for controls (105+/-12 ms, p < 0.05), whereas the acceleration was slower (170+/-54, 186+/-42 and 279+/-96 cm/s2, respectively, p < 0.05). Coronary flow reserve in the patients with exercise perfusion defects (2.7+/-0.3) was significantly lower than in those without (3.7+/-0.5, p < 0.05) or in the control group (3.4+/-0.5, p < 0.05). CONCLUSIONS Patients with LBBB have an impairment of early diastolic blood flow in the LAD due to an increase in early diastolic compressive resistance resulting from delayed ventricular relaxation. Furthermore, exercise scintigraphic perfusion defects in these patients are associated with a reduced coronary flow reserve, indicating abnormalities of microvascular function in the same vascular territory.

Mechanisms, Risk Factors, and Management of Acquired Long QT Syndrome: A Comprehensive Review

Long QT syndrome is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram and is associated with precipitation of torsade de pointes (TdP), a polymorphic ventricular tachycardia that may cause sudden death. Acquired long QT syndrome describes pathologic excessive prolongation of the QT interval, upon exposure to an environmental stressor, with reversion back to normal following removal of the stressor. The most common environmental stressor in acquired long QT syndrome is drug therapy. Acquired long QT syndrome is an important issue for clinicians and a significant public health problem concerning the large number of drugs with this adverse effect with a potentially fatal outcome, the large number of patients exposed to these drugs, and our inability to predict the risk for a given individual. In this paper, we focus on mechanisms underlying QT prolongation, risk factors for torsades de pointes and describe the short- and long-term treatment of acquired long QT syndrome.

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.

The influence of premedication on heart rate variability

Analysis of heart rate variability has been used to study the effects of midazolam, morphine and clonidine on the autonomic nervous system, when administered to patients for premedication. Ninety‐five patients were studied 60 min before and 60 min after premedication. Normal saline (n = 25), midazolam 0.08 mgkg−1 (n = 24), morphine 0.15 mgkg−1 (n = 23), or clonidine 2 μgkg−1 (n = 23) were administered intramuscularly by random allocation. A Holter device was connected to the patient during the study period. Using power spectral analysis the low‐frequency and high‐frequency components were calculated from the Holter recordings. These are markers for sympathetic and parasympathetic activity respectively; the low‐ to high‐frequency ratio was also calculated, a ratio of >1 signifying sympathetic dominance. A significant reduction was noticed in both low‐frequency and high‐frequency power in the three premedicated groups, whereas no changes were observed in the normal saline group. In the case of midazolam, both the low and high frequencies were decreased but the low‐ to high‐frequency ratio did not change significantly. Morphine and clonidine depressed the low‐frequency component more than the high‐frequency component and the low‐ to high‐frequency ratio was decreased, suggesting parasympathetic dominance. We conclude that heart rate variability may be a useful tool for investigating the effect of drugs on the autonomic nervous system.

Autonomic Nervous System Activity During Tilt Testing in Syncopal Patients, Estimated by Power Spectral Analysis of Heart Rate Variability

Spectral analysis of heart rate variability (HRV) was used to assess changes in autonomic function before and during postural tilt in 28 syncopal patients: 14 (group A) with positive and 14 (group B) with negative tilting test, and 14 normal controls (group C). 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‐minute intervals immediately before tilt testing, immediately after tilting, and just before the end of the test. In group A, the mean values of LF and HF decreased slightly in response to tilting while the LF/HF ratio increased, though these changes were not statistically significant. All parameters showed a statistically significant increase just before the onset of syncope. In group B, there were no significant changes in the parameters measured throughout the test. In group C. there was an increase in the LF and LF/HF ratio and a decrease in the HF immediately after tilting. There were no further significant changes in any of the parameters during the test. Syncopal patients have a different pattern of response to the orthostatic stimulus, in that they do not show the increase in sympathetic tone observed in normal individuals immediately after tilting. In the patients with a positive tilt test, there is a shift in the balance of ANS activity towards the sympathetic system shortly before the onset of syncope. (PACE 1997; 20[Pt. I]:1332‐1341)

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.