Circadian and Sex-Dependent QT Dynamics

The dynamic QT relationship between the QT and RR intervals in normal individuals, including sex differences, has not been well examined. The aim of this Holter monitor-based study was to assess circadian and sex-related variations in QT dynamics in healthy subjects. The study population consisted of 50 healthy volunteers (mean age = 32 ± 6 years, 25 men), in whom 24-hour digital Holter monitoring and QT interactive, beat-by-beat analyses were performed. The mean lengths of QT and RR intervals were measured from the 24-hour recordings. In order to assess QT dynamics, QT/RR linear regression was performed, and the slope was calculated over 24 hour and for day and night periods, and both genders separately. In the whole population, the mean QT interval was 356.5 ± 19.2 ms and RR interval was 785.9 ± 80.7 ms. The mean value of the slope over 24 hour was 0.17 ± 0.03, though significantly steeper during the day (0.13 ± 0.03) than at night (0.09 ± 0.03, P < 0.001). The analysis of QT/RR dynamics over 24 hour revealed a significantly steeper slope in women (0.18 ± 0.03) than in men (0.16 ± 0.03, P = 0.006), as well as during daytime (0.14 ± 0.03 vs 0.12 ± 0.03, P = 0.04). Circadian variations and sex differences were observed in QT dynamics. The latter may explain the greater susceptibility of women to torsades de pointes during treatment with drugs that prolong repolarization.     

Sympathovagal Balance Prior to Onset of Repetitive Monomorphic Idiopathic Ventricular Tachycardia

Repetitive monomorphic idiopathic (RMI) ventricular tachycardia (VT) occurs typically in patients without structural heart disease, originates in most cases from the right ventricular outflow tract, and can often be induced by exercise or isoproterenol. This study analyzed the dynamic changes in autonomic tone immediately before the spontaneous onset of RMIVT using frequency-domain heart rate variability (HRV) indices. We analyzed the ambulatory electrocardiographic recordings from 6 men and 8 women (mean age: 43 ± 18 years; mean number of VT runs per day: 134 ± 213; mean VT rate: 194 ± 40 bpm; median VT run length: 4 cycles) with RMIVT. A total of 36 clusters of nonsustained episodes of RMIVT preceded by ≥1 hour of sinus rhythm without VT were analyzed (25 minutes before the onset of RMIVT divided into five 5-minute periods; 8 minutes before onset of RIMVT divided into eight 1-minute periods). During 25 minutes preceding the onset of VT, the mean RR interval decreased from 767 ± 118 to 723 ± 105 ms (P = 0.015) and the low-frequency (LF)/high-frequency (HF) ratio increased from 2.24 ± 0.79 to 2.49 ± 1.0 (P = 0.03). During the 8 minutes before VT onset, the mean RR interval decreased from 745 ± 118 to 718 ± 102 ms (P = 0.001) and the LF components increased from 205 ± 72 to 253 ± 113 ms (P = 0.014). No change in HF components was observed during the 25 or 8 minutes periods preceding the RMIVT onset. The changes in HRV indices suggest a strong time-dependent primary activation of sympathetic tone prior to the occurrence of RMIVT. Withdrawal of vagal tone does not appear essential to the initiation of RMIVT clusters.     

Role of Sympathovagal Balance in the Initiation of Idiopathic Ventricular Tachycardia Originating from Right Ventricular Outflow Tract

VT originating from the right ventricular outflow tract (RVOT) is prone to occur when sympathetic nervous activity is increased. β-Blockade is, therefore, effective in suppressing this VT. The purpose of this study was to determine the role of sympathovagal balance assessed by heart rate variability (HRV) in the spontaneous initiation of repetitive premature ventricular contractions (PVCs) and VT (five or more consecutive PVCs) arising from RVOT in seven patients without structural heart diseases. Frequency-domain measures of HRV were determined by analyzing 24-hour Holter electrocardiographic recording with the maximum entropy method over α 1,280-second period immediately before the onset of 35 single PVCs, 26 episodes of 2-4 consecutive PVCs, and 21 episodes of VT. High frequency component (HF: 0.15–0.40 Hz) was used as an index of parasympathetic activity, and the ratio of low frequency component (LF: 0.04–0.15 Hz) to HF (LF/HF ratio), as an index of sympathovagal balance. NN50(%), a time-domain variable of parasympathetic activity, was also determined. Mean RR interval and any measures of HRV did not change significantly before single PVCs. Mean RR interval shortened and HF decreased prior to repetitive PVCs and VT. The LF/HF ratio, however, increased only before the onset of VT. NN50(%) tended to decrease before repetitive PVCs and decreased significantly before VT. With propranolol (30–60 mg/day), frequency of repetitive PVCs was suppressed from 2,048 ± 1,201 to 746 ± 658/day and VT was totally abolished, but frequency of single PVCs did not change significantly. In conclusion, sympathetic predominance plays an important role in the initiation of repetitive PVCs and VT originating from RVOT in patients without structural heart diseases.     

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 QT_ec (time interval between the onset of QRS and the end of the T wave) and QT_ac (time interval between the onset of the QRS and the peak of the T wave) were calculated, with their standard deviations (SDQT_e and SDQT_a) taken as indices of QT variability. The slopes of the regression line for the QT_e and QT_a 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. QT_ac was significantly longer in group A than in group R (321 ± 20 vs 312 ± 22, P < 0.0001) and SDQT_a was significantly lower (2.8 ± 1.2 vs 4.7 ± 3.7, P < 0.03). There were no significant differences in QT_ec, SDQT_e, QTe/RR and QT_a/RR before and after the episodes. Our data indicate that in patients with HCM, the averaged QT_ac is significantly longer and the QT_a variability significantly lower before episodes of nonsustained VT.     

Acute Testing of the Rate-Smoothed Pacing Algorithm for Ventricular Rate Stabilization

We evaluated the capability of a new pacemaker-based rate-smoothing algorithm (RSA) to reduce the irregular ventricular response of AF. RSA prevents sudden decreases in rate using a modified physiological band and flywheel feature. Twelve patients (51 ± 21 years) with hemodynamically tolerated AF of 4 months to 20 years duration were studied. Atrial and ventricular leads were connected to the external pacemaker device in the electrophysiology laboratory. Consecutive RR intervals during AF were measured at baseline and after ventricular pacing with RSA ON. Ventricular pacing with the rate smoothing algorithm reduced maximum RR intervals (1,207 ± 299 vs 855 ± 148 ms, P = 0.0005), with no significant change in the minimum RR interval (401 ± 55 vs 393 ± 74 ms, P = 0.292). A small shortening of the mean RR interval (634 ± 153 vs 594 ± 135 ms, P = 0.007) was seen with no change in the median RR interval (609 ± 153 vs 595 ± 143 ms, P = 0.388). There was a 43% reduction in RR standard deviation (145 ± 52 vs 82 ± 28, P = 0.0005), 49% reduction in mean absolute RR interval difference (MAD) (152 ± 64 vs 77 ± 34, P = 0.0005) and MAD/mean RR ratio (0.23 ± 0.05 vs 0.13 ± 0.04, P = 0.0005). We conclude that rate-smoothed pacing effectively reduces RR variability of AF in the acute setting.     

The Role of the Selective Serotonin Re‐Uptake Inhibitor Sertraline in Nondepressive Patients with Chronic Ischemic Heart Failure: A Preliminary Study

Background: Selective serotonin re‐uptake inhibitors (SSRIs) have been associated with better psychiatric status, functional capacity, and fewer arrhythmias in depressive patients with heart failure (HF). In this study, we tested the impact of sertraline (an SSRI) on patients with HF, but not clinical depression. Methods: We studied 62 clinically stable, nondepressive patients with ischemic HF (New York Heart Association class: I‐II), and implantable cardioverter‐defibrillator (ICD). Following psychiatric evaluation and quality of life (QoL) assessment, 24‐hour electrocardiogram recordings including heart rate variability (HRV) and ICD interrogation were performed every 4 months for 1 year. Ventricular effective refractory period (ERP) at 600‐, 500‐, and 400‐ms cycle length and the inducibility of ventricular tachycardia (VT) were assessed via the ICD. After that, sertraline 50 mg/day was administered for 12 months and the whole evaluation was repeated. Results: Sertraline was associated with fewer ventricular extrasystoles per 24 hours and a significant change in HRV (increase in mean R‐R, 5‐minute standard deviation of RR intervals, and root mean‐square difference of successive RR intervals, and reduction in ultra and very low frequency). It was also followed by an improvement in patients’ QoL. A trend toward a decrease was observed in the number of recalled nonsustained VTs. The episodes of sustained VT were not significantly reduced. Ventricular ERPs and VT inducibility remained unaltered. Conclusion: In clinically stable, nondepressive patients with ischemic HF and ICD, sertraline is associated with reduced ventricular extrasystoles, better QoL, and a possible improvement in some HRV indexes. This suggests that SSRIs may have a favorable clinical impact on these patients, independent of the improvement in depressive symptoms. (PACE 2010; 33:1217–1223)     

Value of Heart Rate Variability to Predict Ventricular Arrhythmias in Recipients of Prophylactic Defibrillators with Idiopathic Dilated Cardiomyopathy

GRIMM, W., et al. : Value of Heart Rate Variability to Predict Ventricular Arrhythmias in Recipients of Prophylactic Defibrillators with Idiopathic Dilated Cardiomyopathy. This study investigated the relation between heart rate variability (HRV) measured as standard deviation of normal to normal RR intervals (SDNN) on baseline 24-hour ambulatory electrocardiogram (ECG) and subsequent appropriate implantable cardioverter defibrillator (ICD) interventions in 70 patients with idiopathic dilated cardiomyopathy (IDC) in whom ICDs were implanted prophylactically in the presence of a low left ventricular ejection fraction (LVEF). During   43 ± 26   months of follow-up, 26 of 70 (37%) study patients with IDC received one or more appropriate ICD interventions for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) documented by electrograms stored in the ICD. Mean SDNN at ICD implant was   94 ± 33 ms   . No difference was found between patients with   (90 ± 25 ms)   versus without   (96 ± 37 ms)   appropriate ICD interventions for VT or VF during follow-up. Multivariate Cox regression analysis of baseline clinical characteristics including age, gender, LVEF, NYHA functional class, nonsustained VT on Holter, history of syncope, left bundle branch block, baseline medication and HRV revealed LVEF as the only significant predictor of arrhythmia. These findings do not support the use of HRV measured as SDNN on 24-hour ambulatory ECG to select patients with IDC for prophylactic ICD therapy. (PACE 2003; 26[Pt. II]:411–415)     

Arrhythmia Risk Prediction in Idiopathic Dilated Cardiomyopathy Based on Heart Rate Variability and Baroreflex Sensitivity

This study examined the relation between heart rate variability (HRV) and baroreflex sensitivity (BRS) and subsequent major arrhythmic events (MAE), defined as sustained VT, VF or sudden death, in 263 patients with idiopathic dilated cardiomyopathy (IDC) in sinus rhythm. The predefined measure of HRV was the standard deviation of all normal-to-normal RR intervals (SDNN) on baseline 24-hour ambulatory ECG. BRS was determined by the phenylephrine method. Over 52 ± 21 months of follow-up, MAE occurred in 38 patients (14%). SDNN at baseline 24-hour ambulatory ECG (106 ± 46 vs 109 ± 45, ns) and BRS (7.9 ± 5.5 vs 7.7 ± 5.3 ms/mmHg, ns) were both similar in patients with versus without MAE during follow-up. In contrast, left ventricular ejection fraction was significantly lower in patients with versus without MAE (24%± 7% vs 31%± 10%, P < 0.019. Conclusions: Neither HRV nor BRS predicted MAE in patients with IDC.     

Abnormal Nocturnal Heart Rate Variability and QT Dynamics in Patients with Brugada Syndrome

Background: In Brugada syndrome (BSY), most of the ventricular arrhythmic events are nocturnal, suggesting an influence of the autonomic nervous system.
Methods: In 46 patients (mean age = 41 ± 14 years, 43 men) with electrocardiograms (ECG) consistent with BSY and structurally normal hearts, we measured heart rate variability (HRV) and QT dynamics (QT/RR slopes) on 24-hour ambulatory ECG. Type 1 BSY-ECG was spontaneous in 23 (50%) and induced in 23 patients.
Results: History of syncope was present in 23 patients (50%). Programmed ventricular stimulation induced ventricular tachyarrhythmias (VTA) in 13 patients (28%). A single patient developed ventricular tachycardia during a mean follow-up of 34 months. Compared to a control group matched for age and sex, HRV was decreased over 24 hours and during nighttime in patients with BSY (SDNN 122 ± 44 vs 93 ± 36 ms, P = 0.0008 and SDANN 88 ± 39 vs 54 ± 24 ms, P < 0.0001). QTend /RR slopes were decreased over 24 hours in patients with BSY (0.159 ± 0.05 vs 0.127 ± 0.05, P = 0.003) and particularly at night (0.123 ± 0.04 vs 0.089 ± 0.04, P = 0.0001). QTend /RR slopes were significantly decreased during nighttime in patients with spontaneous versus provoked BSY-ECG patterns. By contrast, HRV and QT/RR slopes were similar in symptomatic and asymptomatic patients, whether VTA were induced or not.
Conclusions: Patients with a BSY-ECG pattern had lower HRV and QT/RR slopes than control subjects during nighttime. High-risk patients with spontaneous BSY-ECG patterns had the lowest nocturnal QTend/RR slopes. These unique repolarization dynamics might be related to the frequent nocturnal occurrence of VTA in BSY.     

Congestive Heart Failure and VVI Pacing Mode: Dynamic Behavior of the Dispersion of Ventricular Repolarization

Dynamic Behavior of the Dispersion of Ventricular Repolarization. The aim of this study was to evaluate the circadian variation in the spatial dispersion of ventricular repolarization in continuously paced patients with congestive heart failure (CHF). Fourteen patients (10 males, 4 females, aged 65 ± 5 years) with CHF due to dilated cardiomyopathy (DCM) and an echocardiographic ejection fraction of 28%± 3% were studied. All patients underwent AV functional RF ablation and permanent pacemaker implantation for drug refractory chronic atrial fibrillation (AF). Patients were evaluated at 1 month postimplant with a three-channel 24-hour Holter monitor, using the three plane Frank orthogonal leads (X, Y, and Z), in VVI pacing mode at 70 beats/min. For each hour, the mean value of spike-T interval dispersion of the first five beats was measured. The control group consisted of 20 patients without structural heart disease, but with AF and complete AV block, continuously paced in WI mode at 70 beats/min. The dispersion of the spike-T interval had a circadian behavior in the study population, with higher values at night and lower during the daytime. During the daytime, the mean value of spike-T interval dispersion was 39 ± 5 ms and during the nighttime it was 45 ± 7 ms (P = 0.003). Such a difference between day and night was not found in the control group (38 ± 6 ms and 40 ± 8 ms, respectively, P = NS), In the daytime period the mean value of spike-T interval dispersion of our study population was comparable to that of the control group (P = NS), while during the nighttime it was significantly higher (P = 0.0004). In conclusion, by evaluating the dispersion of ventricular repolarization in two dimensions, space and time, a circadian variation was found in paced patients with CHF due to DCM. The increased QT dispersion in these patients during the nighttime period was attributed to different effects of vagal activity in normal and abnormal myocardial areas.     

Heart Rate Variability and Sudden Infant Death Syndrome

PERTICONE, F., ET AL.: Heart Rate Variability and Sudden Infant Death Syndrome. The sudden infant death syndrome (SIDS) is the most common cause of death in infancy. The pathophysiological mechanism leading to SIDS is still obscure. In the QT hypothesis, the mechanism must be an arrhythmogenic sympathetic imbalance: the infants die suddenly of cardiac arrhythmia. Recently, it has been suggested that analysis of heart rate variability (HRV), expressed as standard deviation or variance analysis, can provide adequate information on sympathovagal interaction. We studied 150 newborns enrolled in a previous prospective electrocardiographic study to evaluate the predictive value of QT interval for SIDS. We analyzed the ECGs recorded with infants alert on the fourth day of life and after 2 months. For each ECG, the HRV was calculated using the first standard deviation of of RR intervals (ms) measured for 1 minute. The average RR interval was 441 ± 71 ms at the fourth day and 420 ± 39 ms at the second month. The QT_c and HRV mean values were 396 ± 23 and 23 ± 12 ms at the fourth day, 412 ± 19 and 15 ± 7 msec at the second month. Therefore, the SD values of heart rate were correlated with QT_cin order to assess a possible relationship between the two variables. The correlation coefficient and regression equation were: -0.639 and y = 423.67 - 2.18*× (P < 0.002) at the fourth day, -0.146 and y = 418.09 - 0.37*× (NS) at the second month. In conclusion, our data seems to confirm a delayed maturation or impaired fuctioning of the autonomic nervous system in the first weeks of life, reflecting a direct correlation with QT prolongation.     

Does heart rate identify sudden death survivors? Assessment of heart rate, QT interval, and heart rate variability

The objective was to test whether the circadian variability of several electrocardiographic variables distinguishes sudden cardiac death survivors from heart disease patients without a history of cardiac arrest and from normal subjects. Heart rate, heart rate variability, and QT interval have been reported to identify survivors of sudden cardiac death. Computer-assisted continuous QT measurement and heart rate variability analysis were performed on 24-hour Holter records for three groups: (1) 14 sudden death survivors; (2) 14 control patients with diagnosis and therapy matched to survivors; and (3) 14 healthy subjects. There were no significant differences in 24-hour mean RR and QT intervals between groups. However, heart rate was significantly different between the three groups at night but not during the day because the expected nighttime decline was markedly blunted in survivors and somewhat blunted in control patients. The QT interval and frequency domain heart rate variability measures followed a similar circadian pattern. The mean QTc was significantly longer in control patients. The QTc had a wide range in all groups, but less in sudden death survivors. Of ten common time and frequency domain heart rate variability indices, only SDANN and SDNN were significantly lower in sudden death survivors. Reduced circadian variation of heart rate, with marked blunting of the nighttime heart rate decline, identifies sudden cardiac death survivors as well as does SDANN and SDNN, and, in contrast to heart rate variability measures, can easily be obtained from a Holter report without complex calculations.     

Evolution of Cardiac Autonomic Nervous Activity Indices in Patients Presenting with Transient Left Ventricular Apical Ballooning

Backround: Transient left ventricular (LV) apical ballooning (AB) is characterized by a rapidly reversible, acute LV systolic dysfunction, triggered by physical or emotional stress. Despite observations strongly suggesting catecholamine-mediated myocardial stunning due to enhanced sympathetic activity, the early time course of heart rate variability (HRV) has not been described.
Methods: We prospectively enrolled 39 consecutive patients (median age = 68 years, range 35–85 years, 38 women) with LV AB. Indices of HRV were extracted from 24-hour ambulatory electrocardiograms on the day of hospital admission, on days 2 and 3, and 3 months after the hospitalization.
Results: Within 48 hours after hospital admission, the indices of HRV were markedly depressed (standard deviation of normal-to-normal [NN] intervals [SDNN] 89.6 ± 19.9 ms; mean standard deviation of NN intervals for 5-minute segments [SDNNi] 37.8 ± 6.2 ms; root mean square of consecutive difference of normal-to-normal intervals [rMSSD] 23.0 ± 9 ms; standard deviation of the averages of NN intervals for all 5-minute segments [SDANN] 70.1 ± 18.0 ms; geometric triangular index [TI] 23.7 ± 5.9 ms), recovered in the subacute phase and had normalized at 3 months follow-up (SDNN 124.7 ± 24 ms; SDNNi 47.1 ± 5.7 ms; rMSSD 31.1 ± 10.5 ms; SDANN 118.5 ± 27 ms; TI 31.2 ± 8 ms; all P < 0.05). Mean RR-interval increased from 845 ± 121 ms on day 1, to 929 ± 84 ms at 3 months (P = 0.06).
Conclusions: A marked depression of cardiac parasympathetic activity was observed in the acute phase of LV AB, followed by recovery of autonomic modulation between the subacute and the chronic phases. The rapid return of parasympathetic function may partially explain the favorable outcomes of patients presenting with LV AB.     

The Use of the Block Cycle Length as a Safe and Efficient Means of Interrupting Sustained Ventricular Tachycardia and Its Pharmacological Modification

In nine patients who had inducible monomorphic sustained ventricular tachycardia (VT), rapid pacing was performed in 11 episodes of morphologically distinct VT at progressively shorter cycle lengths and VT was interrupted at a critical cycle length. The VT interrupting critical cycle length was defined as the block cycle length (BCL) and the effect of Class I antiarrhythmic drugs were examined. Both the VT cycle length (VTCL) and the BCL were prolonged after administration of either drug. The overall mean ratio of the BCL to the VTCL was unchanged after procainamide administration, but increased after the use of mexiletine. The ratio, however, varied in individual VTs and the BCL after treatment with Class I antiarrhythmic drugs could not be predicted from the ratio baseline value, although the ratio was always > 60% and the hazard of VT acceleration might be avoided if the BCL is used.     

Relationship Between QT Interval Duration and Electrical Induction of Ventricular Tachycardia

The relation of inducible ventricular tachycardia (VT) to QT interval duration of ventricular paced rhythm has not been evaluated. To clarify this relation we measured corrected QT interval duration (QT_C) during sinus rhythm and QT interval duration during ventricular paced rhythm (QT-V) in patients with coronary artery disease without (non-VT group = group B) and with inducible VT (VT group = group A). Duration of QT-V was greater in the VT group (n = 20) compared with non-VT group (n = 20) during ventricular pacing at cycle lengths of 600 ms (424 ± 26 vs 396 ± 19 ms, P < 0.01), of 500 ms (407 ± 20 vs 383 ± 21 ms, P < 0.01), and of 400 ms (390 ± 21 vs 362 ± 17 ms, P < 0.001). During sinus rhythm the mean values of QT_C were similar in both groups (408 ± 25 vs 413 ± 20 ms, NSJ. During ventricular stimulation the percentage of patients with values of QT-V exceeding 380 ms was 35% in non-VT group and 95% in VT group (P <0.01) at cycle length of 500 ms and 5% versus 60%, respectively, (P < 0.01), at cycle length of 400 ms. Thus, a trend toward longer QT values of ventricular paced rhythm exists in patients with inducible VT.     

The Mean Ventricular Fibrillation Cycle Length: A Potentially Useful Parameter for Programming Implantable Cardioverter Defibrillators

In programming the implantable cardioverter defibrillator (ICD), the ventricular tachycardia (VT) detection cycle length (CL) is based on the CL of the documented tachycardia but the ventricular fibrillation (VF) detection CL is set arbitrarily. Appropriate programming of VF detection may not only reduce the incidence of inappropriate ICD shocks for non-VF rhythms but can also avoid the fatal underdetection of VF. The mean VFCL may provide a useful parameter for optimal ICD programming for VF detection if it is reproducible. This study examined the intrapatient reproducibility and interpatient variation of the mean VFCL in 30 ICD patients (25 men and 5 women, mean age 63 ± 13 years). A total of 210 VF episodes (7 ± 4 per patient, range 3–17) induced by T-wave shocks (166) or AC (44) at the ICD implant (30 patients) and the predischarge test (12 of 30 patients) were analyzed. The mean VFCL was calculated from the stored V-V intervals in the ICDs. Although the mean VFCL varied significantly from 171 ± 6 to 263 ± 11 ms (P < 0.01) among different patients, it was reproducible among different VF episodes in an individual patient (maximal variation 4–50 ms, P > 0.05). The mean VFCL was not significantly different between patients with and without antiarrhythmic drugs (210 ± 32 vs 210 ± 23 ms, P > 0.05) and was correlated with the ventricular effective refractory period (r = 0.5, P < 0.05). The mean VFCL varies greatly among different patients but remains reproducible in an individual patient, suggesting that the mean VFCL may serve as a reference for ICD programming of VF detection.     

Association Between Stimulated QT Interval and Ventricular Rhythm Disturbances: Influence of Autonomic Nervous System

To examine the association between ventricular rhythm disturbances and changes in the pacemaker-induced stimulated T interval (STIM-T interval), we compared findings from monitoring of two patient groups. The first group consisted of 15 patients with QTX microprocessor pacemakers and the second group consisted of 198 patients with documented ventricular rhythm disturbances and coronary artery disease (CAD). In the first group, which was free of ventricular rhythm disturbances and manifest coronary artery disease, the STIM-T interval was measured every 4 hours over a 36-hour period at four pacemaker frequency settings (70, 80, 90, and 100) in order to observe the circadian variation of the STIM-T interval as a function of changes in autonomic nervous system (ANS) tone. The second group was comprised of patients with CAD and over 30 VES/hrs (Lown grade classification 1–5), and taking no antiarrhythmic medication. These patients were followed using 24-hour Holter monitoring over a minimum of 23 hours and with less than 5% artifact/recording. Information regarding mean hourly heart rate, total number of VES, VES pairs, VT runs, and ischemic episodes in this group was compared with changes in the STIM-T interval in the first group. The STIM-T interval was found to be shorter during the day and longer at night at all heart rate settings. The total frequency of VES, of VES pairs, VT runs, and ischemic episodes in the second group varies in a similar circadian fashion. The greatest total number of VES, of VES pairs, VT runs, and ischemic episodes was recorded in the waking hours, at the same time when the STIM-T interval is the shortest, while this number was significantly lower during sleep, when the STIM-T interval of the first group is the longest. This coincidence of circadian variation pattern between STIM-T interval in group I, and ventricular arrhythmias and ischemic episodes in group II, suggests that alterations in ANS tone reflected in the STIM-T interval may be an important factor in the occurrence of these untoward events.     

Amiodarone in the Management of Patients with Ventricular Tachycardia and Ventricular Fibrillation

Fifty-eight patients with symptomatic ventricular tachycardia (VT) or ventricular fibrillation (VF) were treated with amiodarone. All had clinical episodes of VT/VF or inducible VT during electropharmacologic testing despite treatment with maximumtolerated doses of conventional antiarrhythmic agents. Chronic treatment with amiodarone was begun at a dose of 800–1000 mg per day. Thirty-two patients were also treated with a previously ineffective conventional agent. Thirty patients underwent programmed ventricular stimulation after 2.6 ± 1.7 months (mean ± S. D.) of treatment with amiodarone at a mean daily dose of 588 ± 155 mg. VT was induced in 25 patients (sustained in 20, nonsustained in five). Seventeen patients had a recurrence of VT or VF after 0.5–9 months of treatment with amiodarone (fatal in seven, non-fatal in 10). Forty-one patients (71%) had no recurrence of symptomatic VT or VF while being treated with amiodarone (mean follow-up period, 17.1 ± 12.4 months). Among the 25 patients who had inducible VT with programmed ventricular stimulation while being treated with amiodarone, 19 patients (76%) have had no recurrence of symptomatic VT or VF overa follow-up period of 21.5 ± 7.3 months. Ambulatory electrocardiographic recordings obtained after one week of treatment with amiodarone were not helpful in predicting clinical response. Twenty-two patients (38%) developed ataxia and/or an intention tremor which improved with a decrease in the amiodarone dose. Amiodarone, either by itself or in combination with conventional antiarrhythmic drugs, has a significant therapeutic effect in high risk patients with refractory VT. The finding of inducible VT during electropharmacologic testing in patients taking amiodarone does not preclude a favorable clinical response. Neurologic toxicity is common in patients treated with 600–800 mg per day of amiodarone.     

Circadian Variation in Atrial Fibrillation in Patients with Frequent Paroxysms

Determinants of the duration of episodes of atrial fibrillation (AF) in patients with paroxysmal atrial fibrillation (PAF) are poorly understood. However, autonomic tone shows circadian variation and is known to affect atrial electrophysiology. We therefore compared the duration of episodes of AF with an onset during the day (08:00 - 22:00) to those with an onset during the night in a database of 24-hour ECG recordings in patients with frequent symptomatic PAF. The heart rate in the 30 seconds prior to AF onset was also compared. From 42 recordings, 296 episodes of AF > 30 seconds duration and preceded by > 60 seconds sinus rhythm were identified. The 165 nocturnal episodes tended to be shorter (median =1.15 min) than the 131 diurnal episodes (median =1.5 min) and the distribution of nocturnal and diurnal durations was significantly different (P = 0.007; Kolgomorov-Smirnov test). This was also true in recordings containing at least 1 diurnal and at least 1 nocturnal episode. The mean heart rate prior to AF onset was lower at night (62.2 ± 11.8 vs 75.6 ± 16.4 beats/min; P < 0.0001 Wilcoxon test). These findings suggest that in patients with frequent symptomatic PAF, autonomic influences affect the duration of episodes of AF and has pathphysiohgical and therapeutic implications.