Asymptomatic versus symptomatic episodes in patients with paroxysmal atrial fibrillation via long-term monitoring with implantable loop recorders.

BACKGROUND: The presentation of atrial fibrillation (AF) varies remarkably, from totally asymptomatic to symptomatic patients, while the same individual may present symptomatic and asymptomatic episodes. We aimed to identify electrocardiographic differences between symptomatic and asymptomatic episodes and to find parameters related to the appearance of symptoms. METHODS: Thirty consecutive patients (age 66.9±10years) with paroxysmal AF received an implantable loop recorder. Three types of episodes were defined: asymptomatic (ASx), symptomatic (Sx), and mixed asymptomatic-symptomatic (AS-Sx). The heart rate (HR) and heart rate variability (HRV) were recorded during the first 2min of each ASx or Sx episode, and during the first 2min of both the symptomatic and asymptomatic periods in AS-Sx. RESULTS: Eighty-two episodes from twenty-five patients were evaluated. Mean HR was 142.48±25.84bpm for Sx and 95.71±19.29bpm for ASx (p<0.001). Mean HRV was 92.62±42.29ms for Sx and 150.06±49.68ms for ASx (p<0.001). In AS-Sx, mean HR was 102.91±24.54bpm for the asymptomatic and 141.88±23.43bpm for the symptomatic period (p<0.001). Mean HRV was 173.55±61.30ms for the asymptomatic and 87.33±30.65ms for the symptomatic period (p=0.003). There were no significant correlations between patients' characteristics and the clinical presentation of the arrhythmia. CONCLUSIONS: The ASx were characterized by a lower HR and higher HRV compared to Sx. In As-Sx, the asymptomatic period was characterized by a lower HR and higher HRV compared to the symptomatic. These findings suggest a possible contribution of variations in the autonomic nervous system activity to the perception of the arrhythmia.

The role of the post-cardioversion time course of hs-CRP levels in clarifying the relationship between inflammation and persistence of atrial fibrillation.

OBJECTIVES: Although recent studies suggest that inflammation is involved in the pathogenesis of atrial fibrillation (AF), it remains controversial whether it is a consequence or a cause of the arrhythmia. DESIGN: Prospective study. SETTING: Tertiary referral centre. PATIENTS AND INTERVENTIONS: In 52 patients with persistent AF lasting >3 months, high-sensitivity C-reactive protein (hs-CRP) was measured before and after electrical cardioversion. MEASUREMENTS AND RESULTS: All patients were successfully cardioverted to sinus rhythm (SR), but the recurrence rate was 23% at 1 month. Baseline hs-CRP was higher in patients with AF recurrence than in those who remained in SR (0.5 (SD 0.18) mg/dl vs 0.29 (SD 0.13) mg/dl, respectively, p<0.001). Similarly, arrhythmia recurrence was associated with greater left atrial diameters (45.4 (SD 3.3) mm vs 40.7 (SD 3.1) mm, respectively, p<0.001). However, logistic regression analysis showed that hs-CRP was the only independent predictor for AF recurrence (p<0.001). Additionally, patients who were in SR on final evaluation had significantly lower hs-CRP levels than at baseline (0.10 (SD 0.06) mg/dl vs 0.29 (SD 0.13) mg/dl, respectively, p<0.001), while those who experienced AF recurrence had similar values on final and on initial evaluation (0.56 (SD 0.24) mg/dl vs 0.50 (SD 0.18) mg/dl, respectively, p = 0.42). CONCLUSION: High levels of hs-CRP are associated with an increased risk of AF recurrence after cardioversion. The restoration and maintenance of SR result in a gradual decrease of hs-CRP while AF recurrence has a different effect, suggesting that inflammation is a consequence, rather than a cause, of AF.

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.

QT dispersion in patients with mitral valve prolapse is related to the echocardiographic degree of the prolapse and mitral leaflet thickness.

BACKGROUND: Ventricular arrhythmias are common in patients with mitral valve prolapse (MVP). Previous studies have provided evidence that a higher degree of systolic mitral valve displacement and the presence of a thickened anterior mitral leaflet are related to an increased incidence of complex ventricular arrhythmias and risk of sudden death in these patients. The aim of our study was to investigate whether QT dispersion in patients with MVP is associated with the echocardiographic degree of the prolapse and mitral leaflet thickness. METHODS: QT and JT intervals and dispersions were measured in 89 patients with primary mitral valve prolapse (26 men and 63 women with mean age 39 +/- 14 years). All patients underwent a full echocardiographic examination and a scoring system was used to determine the degree of MVP. Anterior mitral leaflet thickness was also measured. Twenty-four hour Holter monitoring was used to assess ventricular arrhythmogenesis. RESULTS: According to their echocardiographic score. patients were divided into three groups (Group A. B and C) reflecting the different degrees of the prolapse. QT dispersion in patients with the highest degree of MVP, i.e. Group C was significantly greater (65 +/- 13 ms) than that of the other two groups (Group A: 38 +/- 14 ms, P<0.005 and Group B: 45 +/- 12 ms, P<0.005). Similar differences between groups were also found for JT dispersion. Multiple regression analysis revealed that among the demographic and clinical variables that were tested, only the echocardiographic degree of the prolapse and anterior mitral leaflet thickness were independently associated with QT dispersion. Holter monitoring showed that the incidence of complex ventricular arrhythmias was also higher in patients with more severe MVP. CONCLUSIONS: Our results indicate that QT and JT dispersions are related to the echocardiographic degree of MVP and mitral leaflet thickness. The echocardiographic assessment of the severity of the prolapse may help to identify a subgroup of patients at increased risk of life-threatening arrhythmias.

Atrial defibrillation threshold in humans minutes after atrial fibrillation induction; "A stitch in time saves nine".

AIMS: To assess the effects of atrial fibrillation duration on the defibrillation threshold in atrial fibrillation patients seconds or minutes after initiation of the arrhythmia. METHODS AND RESULTS: Nineteen patients with recurrent symptomatic atrial fibrillation were evaluated. After programmed induction of atrial fibrillation, the defibrillation threshold was assessed after two sequential periods of arrhythmia in the same patient: an "ultrashort" period of 30 s duration and a "short" period, which lasted 10 min. After the specified period, internal cardioversion was attempted using a balloon-guided catheter that allows the delivery of biphasic shocks between one electrode array placed in the left pulmonary artery and a proximal electrode array on the lateral right atrial wall. The defibrillation threshold was assessed with energy steps of 0.5 J with a starting level of 0.5 J. Mean time from induction to successful defibrillation was 92+/-30 s after the "ultrashort" period of atrial fibrillation and 910+/-86 s after the short period. The defibrillation threshold was significantly greater after 10 min of atrial fibrillation than after 30 s of arrhythmia (2.32+/-0.61 J vs 1.31+/-0.66 J, P<0.001). Clinical data were not found to affect the defibrillation threshold. CONCLUSIONS: Prolongation of atrial fibrillation over minutes in patients with paroxysmal arrhythmia increases the energy requirements for successful defibrillation.

Sinus pacemaker function after cardioversion of chronic atrial fibrillation: is sinus node remodeling related with recurrence?

INTRODUCTION: The objective of this study was to investigate the temporal changes in sinus node function in postcardioversion chronic atrial fibrillation (AF) patients and their possible relation with the recurrence rates of AF. METHODS AND RESULTS: In 37 chronic AF patients, internally cardioverted to sinus rhythm, corrected sinus node recovery time (CSNRT), and the pattern of corrected return cycle lengths were assessed 5 to 20 minutes and 24 hours after conversion. The last 20 consecutive patients also were evaluated after autonomic blockade. Twenty subjects with normal atrial structure and no history of AF served as the control group. Patients were followed-up for 1 month for recurrence, and the density of supraventricular ectopic beats per hour was obtained during the first 24 hours after conversion. Fifteen patients (40.5%) relapsed during follow-up. CSNRT values at 600 msec (371 +/- 182 msec) and 500 ms (445 +/- 338 msec) were significantly higher than those of control subjects (278 +/- 157 msec, P = 0.050, and 279 +/- 130 msec, P = 0.037, respectively). Significant temporal changes in CSNRT also were observed during the first 24 hours after conversion (600 msec: 308 +/- 120 msec, P = 0.034; 500 msec: 340 +/- 208 msec, P = 0.017). No significant interaction and temporal effects were observed with regard to corrected return cycle length pattern. Similar data regarding CSNRT and corrected return cycle length pattern were obtained after autonomic blockade. Patients with abnormal CSNRT after cardioversion had higher recurrence rates (50%) than those with normal function (37%; P = NS). Patients who relapsed had a higher density of supraventricular ectopic beats per hour (159 +/- 120) compared with those who did not (35 +/- 37; P = 0.001). CONCLUSION: Depressed sinus node function is observed after conversion of chronic AF. Recovery from this abnormality and its independence from autonomic function suggest that AF remodels the sinus node. Our data do not support a causative role of sinus node function in AF recurrence, but they do indicate such a role for the density of atrial ectopic beats.

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.

Aortic atherosclerotic lesions in the thoracic aorta detected by multiplane transesophageal echocardiography as a predictor of coronary artery disease in elderly patients.

BACKGROUND: The presence of atherosclerotic lesions in the thoracic aorta by transesophageal echocardiography (TEE) appears to be a marker for the presence of significant coronary artery disease (CAD) in the general population. HYPOTHESIS: We investigated whether atherosclerotic lesions in the thoracic aorta, by multiplane TEE, could be a marker for CAD in elderly patients. METHODS: In all, 127 patients (67 men, 60 women, aged 68 +/- 13 years), underwent a TEE study with imaging of the thoracic aorta and cardiac catheterization with coronary angiography. The presence of a distinct, linear, or focal, highly echogenic mass protruding into the vessel lumen was the criterion for the diagnosis of atherosclerotic plaque. RESULTS: Atherosclerotic lesions were found in 30 of 36 patients (83.3%) with and in 20 of 91 (22%) without CAD. Of the 41 patients > or = 70 years, atherosclerotic lesions were detected in 14 of 17 (82.3%) with and in 13 of 24 patients (54%) without CAD. The sensitivity, specificity, and positive and negative predictive values in this group were 82.3, 46, 52, and 78.6%, respectively. Multivariate logistic regression analysis revealed that in patients aged > or = 70 years only advanced atherosclerotic lesions were independent predictors of significant CAD. However, the high negative predictive value of the method indicates that the absence of aortic plaque is a strong predictor of the absence of CAD. CONCLUSIONS: The presence of atherosclerotic lesions in the thoracic aorta is a strong predictor of CAD only in patients < 70 years old. However, the negative predictive value of the method is high for all patients regardless of age.

Relation of autonomic modulation to recurrence of atrial fibrillation following cardioversion.

The aim of this study was to investigate the time course of changes in autonomic nervous system activity in patients with long-standing atrial fibrillation (AF) following internal electrical conversion to sinus rhythm and to look for differences between patients who do and do not relapse. Time-domain indexes of heart rate variability were calculated from 24-hour Holter recordings on the day of conversion and 1 day and 1 month afterward for 22 patients with chronic (> 3 months) AF. Ten healthy subjects served as a control group. During the day of cardioversion the mean RR interval and its circadian variation differed significantly between controls and patients. The mean values of successive RR intervals that deviated by > 50% from the prior RR interval and the root-mean-square of successive RR interval differences--indexes of vagal modulation--were initially significantly higher in patients than in controls but showed a decrease (p < 0.05) by the second day (from 12.4 +/- 7% to 8.1 +/- 5% to 7.3 +/- 5% and from 49 +/- 9 to 39 +/- 12 to 41 +/- 11 ms, respectively) to levels similar to those of the controls (7.6 +/- 5% and 40 +/- 17 ms, respectively). Only these 2 indexes contained significant prognostic information about relapse: patients who later relapsed had higher initial values than those who did not, and these values remained high during the 2 days after conversion. In conclusion, this study provides data confirming that spontaneous chronic AF in humans results in a significant increase in vagal tone that is reversed with time after restoration of sinus rhythm. Persistently higher values of vagal tone are observed in patients who relapse, and are probably a predictor for recurrence.

Left ventricular diastolic filling pattern predicts cardiopulmonary determinants of functional capacity in patients with congestive heart failure.

BACKGROUND: Abnormalities of diastolic function are an important determinant of exercise intolerance in patients with heart failure. However, the relation between left ventricular filling pattern and cardiopulmonary exercise performance has not been adequately studied. METHODS: Thirty-one patients with idiopathic (n = 14) or ischemic (n = 17) dilated cardiomyopathy, demonstrated by coronary angiography, and radionuclide ejection fraction 30.5% +/- 9% underwent cardiopulmonary exercise testing with a modified Naughton protocol and a complete echocardiographic study. Patients were subdivided into restrictive and nonrestrictive groups according to their Doppler transmitral flow pattern. Gas exchange data were measured during exercise testing. The relation of left ventricular filling pattern to cardiopulmonary parameters was assessed in both groups. RESULTS: Exercise duration was similar in the restrictive and nonrestrictive groups but significant differences were found in oxygen consumption (VO(2)) at peak exercise (14.3 +/- 2.4 vs 20.4 +/- 4.7 mL/kg per minute; P <.001) and at the anaerobic threshold (VO(2AT)) (13 +/- 2.2 vs 17.3 +/- 3 mL/kg per minute; P <.001). Simple linear regression analysis revealed that both peak VO(2) and VO(2AT) were significantly correlated with the ratio of peak early (E wave) to late (A wave) transmitral filling velocity, early filling deceleration time, atrial filling fraction, and A-wave velocity but not with left ventricular ejection fraction. Multivariate regression analysis gave only the peak A-wave velocity as an independent predictor for both peak VO(2) and VO(2AT). CONCLUSIONS: In patients with heart failure, abnormalities of diastolic function are the most important determinant of exercise intolerance. A restrictive transmitral flow pattern by Doppler echocardiography is a marker of diminished cardiopulmonary exercise performance in these patients.

Changes in atrial electrical properties following cardioversion of chronic atrial fibrillation: relation with recurrence.

OBJECTIVE: To study the reversibility of atrial electrical remodeling and its relation with recurrence in post-conversion chronic atrial fibrillation (CAF) patients. METHODS: In 28 drug-free CAF patients (mean AF duration 41+/-39 months) electrically converted to sinus rhythm effective refractory period (ERP) at 500 ms, monophasic action potential at 90% of repolarization (MAPd90) at five cycle lengths (CL, 350, 400, 450, 500, 600 ms), and P wave duration were measured three times: within the interval 5-20 min post-conversion, 24 h and 1 month later. Fifteen subjects with no history of AF and normal atrial structure served as a control group. Patients were followed up for recurrence for 1 month; 12 relapsed. RESULTS: ERP changed from 205+/-20 to 243+/-31 to 241+/-24 ms (P<0. 001), attaining a level comparable to that of the controls (238+/-21 ms) within 24 h. MAPd90 significantly (P<0.001) increased (from 175+/-11 to 190+/-19 to 191+/-10 ms at CL 350 ms and 201+/-12 to 234+/-20 and 233+/-23 ms at CL 600 ms) also reaching control levels within 24 h. MAPd90 exhibited an abnormal adaptation to rate only in the first evaluation. P wave duration was prolonged (137+/-33 ms) and exhibited a slower course of shortening (130+/-32 to 123+/-27 ms, P<0.001), reaching control levels within 1 month. Patients with higher values of MAPd90 at CL 350 in the immediate post-conversion period were more likely to relapse (P<0.005). CONCLUSIONS: ERP and repolarization shortening as a result of CAF are reversed within 24 h after conversion, while P wave duration reduces more slowly. Post-conversion MAPd90 values contain prognostic information for recurrence.

Impact of chronic DDD pacing on time-domain indexes of heart rate variability in patients with hypertrophic obstructive cardiomyopathy.

The aim of this study was to examine whether DDD pacing affects time-domain indexes of heart rate variability (HRV) in patients with hypertrophic obstructive cardiomyopathy (HOCM). We studied 11 patients (7 men, age 52 +/- 8 years) with HOCM refractory to drugs. In all patients a DDD pacemaker was implanted and the atrioventricular delay was programmed to ensure a full ventricular activation sequence. Time-domain indexes of HRV (mean NN, SDANN, SDNN, SD, rMSSD, pNN50) were determined from 24-hour Holter recordings 3 days before and 1 year after pacemaker implantation. The pacemaker was turned off during the second recordings. The same indexes were determined in ten healthy controls at the same time points. The controls showed no significant differences in any of the measured parameters between the two time points. The HOCM patients showed an increase in SD (from 27 +/- 13 to 41 +/- 13 ms, P < 0.001), rMSSD (from 18 +/- 5 to 32 +/- 8 ms, P < 0.001), and pNN50 (from 1.03 +/- 1.06 to 8.52 +/- 4.84%, P < 0.0001). As a result, the values of these three parameters, which were lower in the HOCM patients than in the controls before pacing, were restored to normal levels by the end of the study. In conclusion, our findings indicate that long-term pacing in HOCM patients restores the sympathovagal balance in the heart by increasing vagal activity.

The effect of DDD pacing on ergospirometric parameters and neurohormonal activity in patients with hypertrophic obstructive cardiomyopathy.

This study examined the acute and long-term effects of DDD pacing on ergospirometric parameters and neurohormonal activity in patients with hypertrophic obstructive cardiomyopathy (HOCM). We studied eight patients (five males), aged 56 +/- 7 years, with HOCM refractory to drugs. In all patients a DDD pacemaker was implanted and programmed with an atrioventricular (AV) delay that insured full ventricular activation. The patients underwent echocardiographic examination and exercise stress testing before and 3 days, 3 months, and 12 months after pacemaker implantation. Oxygen consumption was measured at the anaerobic threshold (VO2AT) and peak exercise (pVO2). Atrial natriuretic peptide (ANP) and cyclic adenosine monophosphate (c-AMP) levels were measured concomitantly. Left ventricular outflow tract (LVOT) pressure gradient decreased significantly from 70 +/- 18 to 25 +/- 12 mmHg (P < 0.05) 3 days after pacing and remained unchanged at 3 and 12 months. pVO2 and VO2AT increased significantly, from 20.1 +/- 3 to 23.4 +/- 3 mL/kg/min and from 16 +/- 3 to 17.8 +/- 2 mL/kg/min, respectively (P < 0.05). This improvement continued up to 3 months, and then remained stable until the end of the 12-month follow-up period. ANP levels decreased at 3 days from 85.4 +/- 5.7 to 75.4 +/- 7.3 fmol/mL (P < 0.05), and remained unchanged over the 12 months. c-AMP levels did not change significantly after the onset of pacing. DDD pacing in patients with HOCM not only reduces the LVOT pressure gradient but also causes a significant early and long-term improvement in exercise capacity and neurohormonal profile.

QT variability before and after episodes of nonsustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

This study examined the changes in QT dynamics occurring during 5-minute intervals sampled immediately before and 1 hour after episodes of nonsustained ventricular tachycardia (VT) in patients with hypertrophic cardiomyopathy (HCM). Twenty-four hour Holter recordings were performed in 10 patients with HCM in the absence of antiarrhythmic medications and processed by the ELA Medical QT analysis software. All sinus complexes were averaged over 30-second segments and 2,880 templates were created. For each template, a mean corrected QTec (time interval between the onset of QRS and the end of the T wave) and QTac (time interval between the onset of the QRS and the peak of the T wave) were calculated, with their standard deviations (SDQTe and SDQTa) taken as indices of QT variability. The slopes of the regression line for the QTe and QTa against the corresponding RR also were calculated. Forty 5-minute segments were analyzed immediately before (sample A) and 1 hour after (sample B) 20 episodes of nonsustained VT. QTac was significantly longer in group A than in group B (321 +/- 20 vs 312 +/- 22, P < 0.0001) and SDQTa was significantly lower (2.8 +/- 1.2 vs 4.7 +/- 3.7, P < 0.03). There were no significant differences in QTec, SDQTe, QTe/RR and QTa/RR before and after the episodes. Our data indicate that in patients with HCM, the averaged QTac is significantly longer and the QTa variability significantly lower before episodes of nonsustained VT.

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.

Effects of long-term digoxin therapy on heart rate variability, baroreceptor sensitivity, and exercise capacity in patients with heart failure.

We evaluated the effects of long-term digoxin therapy on exercise capacity and on physiological parameters reflecting autonomic tone in 23 patients with mild to moderate heart failure. Before and after maintenance digoxin treatment, all patients underwent cardiopulmonary exercise testing and indexes of heart rate variability (HRV) and baroreceptor sensitivity (BRS) were measured. Long-term digoxin therapy significantly (P < 0.05) increased time domain indexes (rMSSD, pNN50) which reflect parasympathetic activity (from 30 +/- 16 to 37 +/- 14 and from 8 +/- 9 to 12 +/- 7, respectively). High-frequency (HF) and low-frequency (LF) power spectral components also showed a significant increase (from 4.5 +/- 1 to 5.1 +/- 1 and from 5.4 +/- 1 to 5.8 +/- 1, respectively), but the ratio LF/HF decreased, indicating a predominance of vagal activity. The magnitude of these changes exhibited a strong negative Pearson correlation coefficient when compared with initial values before treatment. BRS increased from 2.95 +/- 1.2 to 5.32 +/- 3 ms/mmHg (P < 0.05). Oxygen consumption at peak exercise and at the anerobic threshold increased significantly (from 17 +/- 3 to 19 +/- 3 mL/kg/min and from 14.7 +/- 3 to 16.5 +/- 3 mL/kg/min, respectively). A persistent negative correlation was found between initial values of HRV and the magnitude of changes in exercise capacity. These findings show that long-term digoxin therapy increases vagal activity and improves exercise capacity in patients with mild to moderate heart failure and seems to exert a more marked therapeutic effect on patients with poorer initial autonomic function.

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.

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.

Assessment of autonomic function at rest and during tilt testing in patients with vasovagal syncope.

This study evaluated autonomic nervous system function in 30 patients with syncope and a positive tilt test result, 20 with a negative test result, and 20 healthy controls. Indexes of heart rate variability were measured during the intervals immediately before and after tilt, while all subjects were asymptomatic, and over a 24-hour period. There were no significant differences among the groups in any of the indexes of heart rate variability over the 24-hour period. In patients with a positive tilt result, tilting caused a decrease in low-frequency (LF) and high-frequency (HF) bands, although the LF/HF ratio did not significantly change. In patients with a negative tilt result there was a decrease in the HF band but no other significant changes. In the controls there was an increase in the LF band and LF/HF ratio and a decrease in the HF band. Our findings showed that patients with vasovagal syncope have no chronic differences from normal subjects in autonomic nervous system activity, but that these patients respond differently to the orthostatic stimulus.

Left ventricular diastolic filling changes during dipyridamole-induced ischaemia. An echo-Doppler study.

OBJECTIVE: To evaluate the usefulness of the Doppler assessment of left ventricular diastolic functioning during dipyridamole-induced ischaemia in patients with coronary artery disease (CAD). METHODS: We studied 28 patients with angiographically proven CAD [18 men, aged 62 +/- 7 years (mean +/- SD)] and 18 normal subjects (12 men, aged 59 +/- 7.5 years). Two-dimensional and transmitral flow Doppler echocardiography studies were performed at baseline and after intravenous administration of a high dose of dipyridamole (0.84 mg/kg during 10 min). Left ventricular wall motion was evaluated by two-dimensional Doppler echocardiography, with the left ventricle divided into a 16-segment model, whereas peak velocities of early and late diastolic flow, the early:late diastolic flow ratio and the deceleration rate of early diastolic flow were determined from transmitral flow Doppler echocardiography. RESULTS: Sixteen patients developed new wall-motion abnormalities (WMA), whereas the remaining 12 patients and the controls did not. Multivariate logistic regression analysis was performed to identify which of the parameters had independent diagnostic value for revealing CAD. WMA was entered at the first step and yielded a 57% sensitivity and 100% specificity; the changes in deceleration rate were entered as the second step, which improved the sensitivity to 85.5%, and reduced the specificity to 83% and raised the overall accuracy to 85% from 70% for WMA alone. More specifically, the sensitivity improved from 37.5, 63.5 and 65.5% to 62.5, 91 and 100%, respectively, for patients with one-, two- and three-vessel disease. The cut-off value of the change in deceleration rate was 7%. CONCLUSIONS: Patients could be classified as having CAD either if they developed new WMA or if the deceleration rate of early diastolic flow during dipyridamole-stress echocardiography increased by more than 7% compared with the rest value.