Influence of Atropine on Fractal and Complexity Measures of Heart Rate Variability

Background: Measurement of short‐term fractal‐like correlation properties of heart rate dynamics has been shown to be a useful prognostic indicator of adverse events in cardiac patients. Complexity measurements of heart rate variability (HRV) have already provided important information in many cardiac conditions. However, data on the physiological background of these newer nonlinear measures of HRV are limited. Methods: Nine healthy subjects (aged from 22 to 35 years, 6 males, 3 females) had an electro‐cardiographic (ECG) recording during controlled breathing in supine position. HRV was analyzed for 5 min periods before and after intravenous injection of 0.6 mg of atropine using conventional HRV measures and newer nonlinear HRV measures including the short‐term scaling exponent (a,) and approximate entropy (ApEn). Results: The short‐term scaling exponent a₁ increased significantly after atropine injection (1.01 ± 0.23 vs 1.43 ± 0.19, P = 0.001). There was no significant difference between ApEn values before and after atropine injection (0.87 ± 0.17 vs 0.70 ± 0.31, respectively, P = 0.27). At baseline before atropine administration, a₁ had a significant negative correlation with SDNN, RMSSD, and HF (r = ‐0.70, ‐0.76, ‐0.67, respectively, P <0.05 for all), and a significant positive correlation with heart rate (r = 0.76, P < 0.05). After atropine injection, a, did not have significant correlation with any of the HRV parameters or heart rate. There were no significant correlations between ApEn and any of the HRV measures or heart rate either before or after atropine administration. Conclusions: Vagal tone has an important influence on the values of the short‐term scaling exponent a,. However, vagal modulation is not a major determinant of the values of ApEn. A.N.E. 2002;7(4):326–331     

Measuring the Complexity of Atrial Fibrillation Electrograms

AF Electrogram Complexity. Introduction: Complex fractionated atrial electrograms (CFAE) have been identified as targets for atrial fibrillation (AF) ablation. Robust automatic algorithms to objectively classify these signals would be useful. The aim of this study was to evaluate Shannon's entropy (ShEn) and the Kolmogorov‐Smirnov (K‐S) test as a measure of signal complexity and to compare these measures with fractional intervals (FI) in distinguishing CFAE from non‐CFAE signals. Methods and Results: Electrogram recordings of 5 seconds obtained from multiple atrial sites in 13 patients (11 M, 58 ± 10 years old) undergoing AF ablation were visually examined by 4 independent reviewers. Electrograms were classified as CFAE if they met Nademanee criteria. Agreement of 3 or more reviewers was considered consensus and the resulting classification was used as the gold standard. A total of 297 recordings were examined. Of these, 107 were consensus CFAE, 111 were non‐CFAE, and 79 were equivocal or noninterpretable. FIs less than 120 ms identified CFAEs with sensitivity of 87% and specificity of 79%. ShEn, with optimal parameters using receiver‐operator characteristic curves, resulted in a sensitivity of 87% and specificity of 81% in identifying CFAE. The K‐S test resulted in an optimal sensitivity of 100% and specificity of 95% in classifying uninterpretable electrogram from all other electrograms. Conclusions: ShEn showed comparable results to FI in distinguishing CFAE from non‐CFAE without requiring user input for threshold levels. Thus, measuring electrogram complexity using ShEn may have utility in objectively and automatically identifying CFAE sites for AF ablation. (J Cardiovasc Electrophysiol, Vol. 21, pp. 649‐655, June 2010)     

Time- and frequency-domain characteristics of atrial electrograms during sinus rhythm and atrial fibrillation

Ablation and Spectral Characteristics of Fibrillation. Background: Complex fractionated atrial electrograms (CFAE) have been considered to be helpful during catheter ablation of atrial fibrillation (AF). The purpose of this study was to analyze the characteristics of CFAEs recorded during sinus rhythm (SR) and AF, and to determine their relationship to perpetuation of AF and clinical outcome. Methods and Results: Antral pulmonary vein isolation (APVI) was performed in 34 consecutive patients (age = 59 ± 10 years) with paroxysmal AF who presented in SR. Time‐ and frequency‐domain characteristics of electrograms recorded from the same sites in the coronary sinus (CS) were analyzed during SR and AF, before and during isoproterenol infusion. There was a modest correlation in fractionation index (FI: change in the direction of depolarization, r = 0.40, P = 0.001) and complexity index (CI: change in the polarity of depolarization, r = 0.41, P = 0.001), but not in the dominant frequency (DF) between SR and AF. There was no relationship between the DF and CI or FI during AF. Isoproterenol was associated with an increase in DF during AF (6.6 ± 0.9 vs 5.1 ± 0.6 Hz, P < 0.001) but had no effect on CI or FI (P = 0.6). A higher CI (58.3 ± 21.0/s vs 38.0 ± 21.0/s, P < 0.01), and FI (123.5 ± 44.8/s vs 75.6 ± 44.6/s, P < 0.01) during AF were associated with a lower likelihood of termination of AF during APVI and a higher probability of recurrent AF after ablation. Ratio of FI during AF to SR was also higher when AF persisted than terminated after APVI (29.7 ± 12.4 vs 19.1 ± 9.7, P = 0.002). However, time‐ or frequency‐domain parameters during SR were not predictive of termination or clinical outcome. Conclusions: Structural and functional properties of the atrial myocardium during AF contribute to electrogram complexity, which may indicate the presence of extra‐PV mechanisms of AF that are not eliminated by APVI. Mapping of complex electrograms in SR is not likely to be sufficient to identify drivers of AF. (J Cardiovasc Electrophysiol, Vol. 22, pp. 851‐857, August 2011)     

The effect of head‐up tilt upon markers of heart rate variability in patients with atrial fibrillation

Background

Heart rate variability (HRV) analysis is uncommonly undertaken in patients with atrial fibrillation (AF) due to an assumption that ventricular response is random. We sought to determine the effects of head‐up tilt (HUT), a stimulus known to elicit an autonomic response, on HRV in patients with AF; we contrasted the findings with those of patients in sinus rhythm (SR).

Methods

Consecutive, clinically indicated tilt tests were examined for 207 patients: 176 in SR, 31 in AF. Patients in AF were compared to an age‐matched SR cohort (n = 69). Five minute windows immediately before and after tilting were analyzed using time‐domain, frequency‐domain and nonlinear HRV parameters. Continuous, noninvasive assessment of blood pressure, heart rate and stroke volume were available in the majority of patients.

Results

There were significant differences at baseline in all HRV parameters between AF and age matched SR. HUT produced significant hemodynamic changes, regardless of cardiac rhythm. Coincident with these hemodynamic changes, patients in AF had a significant increase in median [quartile 1, 2] DFA‐α2 (+0.14 [?0.03, 0.32], p < .005) and a decrease in sample entropy (?0.17 [?0.50, ?0.01], p < .005).

Conclusion

In the SR cohort, increasing age was associated with fewer HRV changes on tilting. Patients with AF had blunted HRV responses to tilting, mirroring those seen in an age matched SR group. It is feasible to measure HRV in patients with AF and the changes observed on HUT are comparable to those seen in patients in sinus rhythm.

     

Reproducibility and Gender‐Related Differences of Heart Rate Variability during All‐Day Activity in Young Men and Women

Background : Only few data are available on reproducibility over time in healthy young men and women and the corresponding gender‐related changes of heart rate variability (HRV) measurements. Methods : We studied temporal and spectral HRV indices obtained from 24‐hour Holter recordings in 32 healthy volunteers (14 men and 18 women, mean age 29 ± 3 years) during 2 days of their usual all‐day activity. Results : Time‐domain measures and the spectral low‐frequency (LF) and high‐frequency (HF) components as well as the LF/HF ratio were comparable on both test days. Significantly higher values on test day 2 were observed only for the spectral very‐low‐frequency (VLF) component and for the resulting total power. Compared to men, women had higher day‐ and nighttime vagus‐associated HRV indices, including root mean square of successive differences (RMSSD), pNN50 (NN50 count divided by the total number of all NN intervals), and HF power, and lower day‐ and nighttime VLF and LF power with lower LF/HF ratio and total power. Conclusions : Temporal indices and the LF and HF spectral HRV measures are reproducible over usual all‐day activity in young healthy subjects. Young women have higher day‐and nighttime vagal tone than men with similar age range.     

Approximate Entropy of Heart Rate Variability: Validation of Methods and Application in Heart Failure

Nonlinear analysis of heart rate variability (HRV) can give additional information about the autonomic control of heart rate. This study applied the method of approximate entropy (ApEn) in a heart failure population (CHF). The influence of time series length and of adding noise on approximate entropy was examined. The method was applied to study HRV of a healthy population (N = 21) and an end stage heart failure population (N = 21). One-hour recordings during day and night were used. Regular signals showed ApEn values of 0, while adding noise increased ApEn values. Brownian noise (1/f²-noise) seemed to have the least influence on ApEn. Both heart failure patients and the control group showed no circadian difference in ApEn. Heart failure patients showed a loss of circadian variation in time and frequency domain HRV indices. ApEn was higher in the CHF population during the night. We present values of approximate entropy of heart failure patients. Heart failure results in loss of circadian variation. Higher values of ApEn in the CHF population indicate a more erratic heart rate.     

Prediction of paroxysmal atrial fibrillation using nonlinear analysis of the R-R interval dynamics before the spontaneous onset of atrial fibrillation.

BACKGROUND: New methods based on nonlinear theory have been developed to give more insight into complex heart rate (HR) dynamics. This study was designed to test the hypothesis that altered HR dynamics, as analyzed with complexity and fractal measures, may precede the spontaneous onset of paroxysmal atrial fibrillation (PAF). Secondly, the difference in the temporal change of these measurements between the different types of atrial fibrillation (AF) was assessed. METHODS AND RESULTS: From 105 Holter tapes in which PAF was recorded, 44 PAF (>or=5 min) episodes in 33 patients (22 men, 58 +/- 12 years), preceded by sinus rhythm for more than 1 h, were selected and submitted to time-and frequency-domain HR variability analyses, along with detrended fluctuation analysis, approximate entropy (ApEn) and sample entropy (SampEn). The 60 min before the onset of AF were divided into 6 10-min periods and studied using repeated measures ANOVA. PAF episodes were divided into 3 subgroups: an increased HF component and decreased L/H ratio (vagal type, n=20); increased L/H ratio and decreased HF component (sympathetic type, n=14); and non-related type (n=10). None of the time- or frequency-domain parameters showed any significant change before AF in any type of AF. The alpha(1) showed a tendency to decrease before the onset of AF and the change in alpha(1) was divergent according to the AF type. The ApEn decreased before the onset of AF (1.005+/-0.046, 60-50 min before AF to 0.894+/-0.052, 10-0 min before AF; p=0.032). The SampEn also decreased progressively before the start of AF (1.165 +/- 0.085, 60-50 min before AF to 0.887 +/- 0.077, 10-0 min before AF, p=0.003). The decrease in both the ApEn and SampEn was irrespective of the AF type. CONCLUSIONS: A reduction in the ApEn and SampEn, which reflects the nonlinear complexity of HR variability, is a hallmark of altered HR dynamics preceding the spontaneous onset of AF.     

Predictive value of heart rate variability for the recurrence of chronic atrial fibrillation after electrical cardioversion

BACKGROUND: The relation between heart rate variability (HRV) and occurrence of atrial fibrillation (AF) in paroxysmal AF has been well studied, but there are controversial observations regarding the relation of HRV parameters to the recurrence of chronic AF after cardioversion. HYPOTHESIS: The present study compared HRV parameters of patients with chronic AF on the second day of cardioversion with a healthy control group and investigated their predictive value for AF recurrence. METHODS: Forty-one patients with chronic AF (> 3 months), who had various underlying cardiovascular disorders, were enrolled to the study. Of these, 31 patients were successfully cardioverted by external direct current shock, but 27 patients fulfilled the entry criteria. Twenty healthy subjects served as a control group. On the second day of restoration of sinus rhythm, 24-h Holter recording was obtained and the following time-domain indices of HRV were measured: SDNN (the standard deviation of the mean RR interval expressed in ms), SDANN (the SD of the averages of RR intervals in all 5-min segments of the 24-h recording), rMSSD (the root mean square of differences of successive RR intervals), and pNN50 (the percentage of adjacent RR intervals that differed by more than 50 ms). Patients were followed-up for 6 weeks for recurrence of AF. RESULTS: After cardioversion, SDNN and SDANN were found to be significantly lower in the AF group than in the control group (86.4 +/- 31.7 ms vs. 142.1 +/- 40.2 ms, and 57 +/- 17.4 ms vs. 124.4 +/- 37.7 ms, p < 0.001 and p < 0.001, respectively). The indices of vagal modulation of heart rate (rMSS and pNN50) were not different between the AF group and the control group. Recurrence of AF was observed in 15 patients. In these patients, all HRV parameters were significantly depressed compared with those with maintained sinus rhythm. Logistic regression analysis revealed that only decreased pNN50 was an independent predictor of AF relapse (relative risk = 1.5, p = 0.02, 95% confidence interval 1.1-2.2). There was also a trend toward a shortened SDNN as a predictor of AF recurrences. CONCLUSION: Suppressed HRV parameters and decreased vagal tone are probably a risk factor for AF recurrences after cardioversion to sinus rhythm in a specific subset of patients with chronic AF.     

Increased sympathetic nervous system activity as cause of exercise-induced ventricular tachycardia in patients with normal coronary arteries

In this prospective study, we set out to determine whether analysis of heart rate variability (HRV) in patients with exercise-induced ventricular tachycardia (EIVT) and normal coronary arteries would reveal increased sympathetic nervous system activity. From January 1996 to December 2001, we compared 16 patients with EIVT and normal coronary arteries with an age- and sex-matched control group. Analysis of HRV showed that parameters indicative of parasympathetic activity were lower in our study group than in our control group: standard deviation of the mean of qualified NN intervals (SDNN), 81.6 +/- 14.5 vs 139.3 +/- 11.0, P <0.001; root mean square of successive differences (RMSSD), 22.3 +/- 4.8 vs 36.3 +/- 6.6, P <0.001; number of NN intervals that differed by more than 5 ms from the adjacent interval, divided by the total number of NN intervals (PNN50), 4.8 +/- 1.5 vs 10.2 +/- 3. 1, P <0.001; and high-frequency component (HF), 28.7 +/- 2.5 vs 32.4 +/- 3.9, P <0.05. Conversely, parameters indicative of sympathetic activity were higher in patients with EIVT: low-frequency component (LF), 71.2 +/- 5.0 vs 52.0 +/- 5.8, P <0.001; and absolute low/high frequency component ratio (LF/HF), 2.7 +/- 0.2 vs 1.6 +/- 0.2, P <0.001. There was a positive correlation between EIVT and LF (r=0.79, P <0.001) and between EIVT and LF/HF (r=0.81, P <0.001). Our results suggest the presence of increased sympathetic and decreased parasympathetic tone in patients with EIVT. We conclude that EIVT is associated with an imbalance in the autonomic nervous system.     

The Relationship Between Heart Rate Recovery and Heart Rate Variability in Coronary Artery Disease

Background: Reduced heart rate recovery (HRR) in coronary artery disease (CAD) is predictive of increased cardiovascular mortality and is related to reduced parasympathetic tonus. Objective: To investigate HRR and heart rate variability (HRV) measured at steady state condition and the relationship between these two parameters in CAD. Materials and Methods: In our study, we enrolled 33 (28 males, mean age 52.4 ± 9.6 years) patients with CAD who did not have heart failure, atrial fibrillation, pacemaker, and any disease state that could affect the autonomic functions and 38 age‐matched healthy subjects (21 males, mean age 48.3 ± 7.8 years). All the patients underwent submaximal treadmill exercise testing (Bruce protocol). HRR was calculated by subtracting the heart rate values at the 1st, 2nd, and 3rd minutes of the recovery phase from the peak heart rate (HRR₁, HRR₂, HRR₃). Before exercise testing, short‐term steady state HRV analyses of all subjects were obtained with the time‐ and frequency‐domain methods and were correlated to HRR. For frequency‐domain analysis, low‐frequency HRV (LF, 0.004–0.15 Hz), high‐frequency HRV (HF, 0.15–0.5 Hz), and LF/HF ratio were measured for 5 minutes in the morning. For time‐domain analysis, standard deviation of the normal‐to‐normal NN intervals (SDNN), square root of the mean squared differences of successive N‐N intervals (RMSSD), and proportion derived by dividing the number of interval differences of successive N‐N intervals greater than 50 ms by the total number of N‐N intervals (pNN50) were obtained. Only HRR₃ was used for the correlation analysis. Results: In CAD groups, the HF, an indicator of parasympathetic activation, was significantly reduced, whereas the LF and LF/HF values, which are indicators of sympathetic activity, were increased (P = 0.0001 for each parameter). The time‐domain parameters SDNN, RMSSD, and pNN50 were significantly reduced in the patient group (P = 0.0001, P = 0.009, and P = 0.0001, respectively). Similar to the HRV parameters, the HRR₁, HRR₂, and HRR₃ values were significantly reduced in the patient group (P = 0.0001 for each parameter). We observed a significant negative correlation between HRR₃ and LF (r =?0.67, P = 0.0001) and between HRR₃ and LF/HF (r =?0.62, P < 0.0001), while there was a significant positive correlation between HRR₃ and HF, SDNN, RMSSD, and pNN50 (r = 0.69, P = 0.0001; r = 0.41, P = 0.0001; r = 0.31, P = 0.008; and r = 0.44, P = 0.0001). Conclusions: HRR and HRV are significantly reduced in CAD. The reduction in HRR is parallel to the changes in HRV parameters. HRR, which can be measured easily in the recovery phase of exercise testing, can be used to detect the depression of parasympathetic tonus and to evaluate the basal autonomic balance in this patient group.     

Sympathetic Overactivity in Patients with Pulmonary Stenosis and Improvement after Percutaneous Balloon Valvuloplasty

Objective : Percutaneous balloon valvulotomy (PBV) is the procedure of choice for the treatment of valvular pulmonary stenosis (PS) with similar results comparable to surgical valvotomy but less invasive. . Methods and Results : Twenty‐seven consecutive patients with PS being evaluated for PBV were enrolled in the study. Peak instantaneous transvalvular gradient, right ventricle (RV) diameter, mean atrial pressures, RV systolic pressure (RVSP), pro‐brain natriuretic peptide (proBNP) levels significantly decreased immediately after PBV. Regarding heart rate variability (HRV) parameters, mean HR (heart rate), LF (low frequency) day and night, LF/HF day and night significantly decreased and standard deviation of all NN intervals (SDNN), root mean square of successive differences (RMSSD), P number of NN intervals that differed by more than 50 ms from adjacent interval divided by the total number of all NN intervals (PNN50), HF (High frequency) day and night significantly increased 1 day after PBV and these changes were shown to be preserved at the first month. The increase in SDNN was correlated with the decrease in right atrial pressure (RAP) (r =?0.5, P = 0.04); the increase in standard deviation of the 5‐minute mean RR intervals (SDANN) was correlated with the decrease in proBNP (r =?0.4, P = 0.03). Conclusions : Sympathetic overactivity and increased proBNP levels were associated with the symptomatic status of patients with PS. Associated with a decrease in atrial pressures and proBNP levels, PBV yielded a decrease in adrenergic overactivity in the patients with PS.     

Relationship Between Myocardial Beta‐Adrenergic Sensitivity and Heart Rate Variability

Background: In congestive heart failure, despite activation of the sympathetic nervous system, heart rate variability parameters reflecting sympathetic modulation on sinus node are decreased. Our goal was to assess the role of beta‐adrenergic sensitivity in the modulation of heart rate variability (HRV) in patients with valvular heart diseases. Methods and results: Ten patients with aortic stenosis, 10 patients with heart failure, and 12 controls were included. Baroreflex sensitivity was calculated by the sequency method. Noradrenaline plasma levels were assayed by HPLC. HRV was studied using 24‐hour Holter monitoring. Cardiac beta‐adrenergic receptivity was assessed by the chronotropic response to dobutamine. Right auricular samples were obtained for determination of beta‐adrenergic receptor density by binding study with [¹²⁵I]‐iodocynaopindolol, and beta 1 and beta 2 densities, measured by competition between ¹²⁵ICP binding by isoprenaline. In multivariate analysis, the dose of dobutamine that increases basal heart rate for 25 beats/min (ED25) is correlated with a parameter of global HRV: SDNN (r = 0.6, P < 0.001) and with indexes reflecting rather sympathetic modulation of HRV: SDANN (r = 0.62, P < 0.001) or SD (r = 0.47, P < 0.0001). All these relations were independent from mean NN, spontaneous baroreflex sensitivity, and noradrenaline plasma levels. No significant correlation existed between dobutamine ED25 and HRV indexes reflecting parasympathic tone. No relationship existed between HRV and beta‐adrenergic receptor‐binding characteristics. Conclusion: Cardiac beta‐adrenergic sensitivity explored by dobutamine ED25 is an important determinant of HRV independent from mean NN, spontaneous baroreflex sensitivity, and noradrenaline plasma levels.     

Effects of cigarette smoking on the circadian rhythm of heart rate variability

BACKGROUND: The effects of cigarette smoking on the circadian rhythm of heart rate variability (HRV) are not known. METHODS: We studied the effects of cigarette smoking on the circadian rhythm of HRV in 24 smoking and 21 non-smoking healthy subjects. Twenty-four hour ambulatory electrocardiograms were recorded and time domain parameters of HRV (SDNN [standard deviation of all R-R intervals], SDANN [standard deviation of the averages of R-R intervals in all 5-minute segments of the entire recording], RMSSD [the square root of the mean of the sum of the squares of differences between adjacent R-R intervals]) were determined for the entire 24-hour period and for each 3-hour period. RESULTS: In total, SDNN and SDANN were significantly lower in smokers than non-smokers (116 +/- 26 vs 136 +/- 27, p < 0.05 for SDNN, 109 +/- 25 vs 121 +/- 24, p < 0.05 for SDANN). However, there were no statistical differences between smokers and non-smokers in heart rate (81 +/- 9 vs 76 +/- 10, p > 0.05) and RMSSD (32 +/- 12 vs 37 +/- 18, p > 0.05). These HRV parameters showed a circadian variation: they increased at night and decreased during the day in both groups. The parameters were lower in smokers than non-smokers during daytime (especially, between 8-14 hours). However, no differences were detected during night-time. CONCLUSIONS: Time domain parameters of HRV (SDNN, SDANN and RMSSD) in both smoking and non-smoking healthy subjects have a circadian rhythm. SDNN and SDANN were lower in smokers than non-smokers during daytime.     

Time to Cardioversion of Recurrent Atrial Arrhythmias After Catheter Ablation of Atrial Fibrillation and Long‐Term Clinical Outcome

Introduction: It is unclear whether early restoration of sinus rhythm in patients with persistent atrial arrhythmias after catheter ablation of atrial fibrillation (AF) facilitates reverse atrial remodeling and promotes long‐term maintenance of sinus rhythm. The purpose of this study was to determine the relationship between the time to restoration of sinus rhythm after a recurrence of an atrial arrhythmia and long‐term maintenance of sinus rhythm after radiofrequency catheter ablation of AF. Methods and Results: Radiofrequency catheter ablation was performed in 384 consecutive patients (age 60 ± 9 years) for paroxysmal (215 patients) or persistent AF (169 patients). Transthoracic cardioversion was performed in all 93 patients (24%) who presented with a persistent atrial arrhythmia: AF (n = 74) or atrial flutter (n = 19) at a mean of 51 ± 53 days from the recurrence of atrial arrhythmia and 88 ± 72 days from the ablation procedure. At a mean of 16 ± 10 months after the ablation procedure, 25 of 93 patients (27%) who underwent cardioversion were in sinus rhythm without antiarrhythmic therapy. Among the 46 patients who underwent cardioversion at ≤30 days after the recurrence, 23 (50%) were in sinus rhythm without antiarrhythmic therapy. On multivariate analysis of clinical variables, time to cardioversion within 30 days after the onset of atrial arrhythmia was the only independent predictor of maintenance of sinus rhythm in the absence of antiarrhythmic drug therapy after a single ablation procedure (OR 22.5; 95% CI 4.87–103.88, P < 0.001). Conclusion: Freedom from AF/flutter is achieved in approximately 50% of patients who undergo cardioversion within 30 days of a persistent atrial arrhythmia after catheter ablation of AF.     

Autonomic Dysfunction and New‐Onset Atrial Fibrillation in Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: A CARISMA Substudy

Predicting New‐Onset AF. Background: Atrial fibrillation (AF) increases morbidity and mortality in patients with previous myocardial infarction and left ventricular systolic dysfunction. The purpose of this study was to identify patients with a high risk for new‐onset AF in this population using invasive and noninvasive electrophysiological tests. Methods: The study included 271 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with an acute myocardial infarction (AMI) and left ventricular ejection fraction ≤40% without previous AF at enrollment. Within 21 days after the AMI, an implantable loop recorder was inserted and used to diagnose AF over the 2‐year study duration. The following tests were performed: heart rate variability (HRV) and turbulence (HRT) analyses from repeated 24‐hour Holter recordings, 2‐dimensional (2D)‐echocardiograms, exercise test, and programmed electrophysiologic stimulation. Results: A total of 101 patients (37%) developed AF during the study. Predictive measures included several indexes of HRV including reduced low‐frequency (LF) power from spectral HRV analysis (adjusted HR = 1.6, P = 0.034), HRT slope ≤2.5 (HR = 1.6, P = 0.032) and Detrended Fluctuation Analysis (DFA1) from HRV analysis (HR = 1.8, P = 0.011); all are measures of cardiac autonomic nervous system dysfunction. Combined with age >60 years, low values for LF, HRT slope, and DFA1 provided a powerful risk score for prediction of new‐onset AF (1–2 points: HR = 4.3, P = 0.001, 3–4 points: HR = 7.0, P < 0.001). Conclusion: Abnormal HRV and HRT parameters, which are associated with disturbances in the cardiac autonomic regulation, are associated with increased risk of new‐onset AF independently of conventional clinical risk variables. (J Cardiovasc Electrophysiol, Vol. 21, pp. 983‐990, September 2010)     

Left atrial radiofrequency ablation during cardiac surgery in patients with atrial fibrillation

Introduction: Intraoperative left atrial radiofrequency (RF) ablation recently has been suggested as an effective surgical treatment for atrial fibrillation (AF). The aim of this study was to verify the outcome of this technique in a controlled multicenter trial. Methods and Results: One hundred three consecutive patients (39 men and 65 women; age 62 ± 11 years) affected by AF underwent cardiac surgery and RF ablation in the left atrium (RF group). The control group consisted of 27 patients (6 men and 21 women; age 64 ± 7 years) with AF who underwent cardiac surgery during the same period and refused RF ablation. Mitral valve disease was present in 89 (86%) and 25 (92%) patients, respectively (P = NS). RF endocardial ablation was performed in order to obtain isolation of both right and left pulmonary veins, a lesion connecting the previous lines, and a lesion connecting the line encircling the left veins to the mitral annulus. Upon discharge from the hospital, sinus rhythm was present in 65 patients (63%) versus 5 patients (18%) in the control group (P < 0.0001). Mean time of cardiopulmonary bypass was longer in the RF group (148 ± 50 min vs 117 ± 30 min, P = 0.013). The complication rate was similar in both groups, but RF ablation‐related complications occurred in 4 RF group patients (3.9%). After a mean follow‐up of 12.5 ± 5 months (range 4–24), 83 (81%) of 102 RF group patients were in stable sinus rhythm versus 3 (11%) of 27 in the control group (P < 0.0001). The success rate was similar among the four surgical centers. Atrial contraction was present in 66 (79.5%) of 83 patients in the RF group in sinus rhythm. Conclusion: Endocardial RF left atrial compartmentalization during cardiac surgery is effective in restoring sinus rhythm in many patients. This technique is easy to perform and reproducible. Rare RF ablation‐related complications can occur. During follow‐up, sinus rhythm persistence is good, and biatrial contraction is preserved in most patients. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1289‐1295, December 2003)     

原发性高血压合并2型糖尿病患者心率变异性与心脏变时功能不全的特点及相关性

目的 探讨原发性高血压合并2型糖尿病患者的心率变异性和心脏变时功能不全特点. 方法 原发性高血压合并2型糖尿病患者与健康人各40例,行24 h动态心电图检查,计算心脏变异性指标SDNN、SDANN、RMSSD、PNN50;行平板运动试验检查,计算运动中最大心率、心脏变时指数、心率储备率,分析心脏变时指数和心率储备率与SDNN、SDANN、RMSSD、PNN50的相关性. 结果 原发性高血压合并2型糖尿病患者SDNN、SDANN 、RMSSD、PNN50均较健康者降低（P〈0.01）.最大心率、心脏变时指数、心率储备率明显低于健康者（P〈0.01）;SDNN、SDANN、RMSSD及PNN50与心脏变时指数（r=0.522、0.472、0.337、0.321）和心率储备率（r=0.541、0.480、0.351、0.285）均存在明显正相关. 结论 原发性高血压合并2型糖尿病患者心脏自主神经受损明显,表现为迷走神经功能减退和交感神经兴奋性增高.     

Impact of heart rhythm status on registration accuracy of the left atrium for catheter ablation of atrial fibrillation

Introduction: Registration accuracy is of crucial importance to the successful use of image integration technique to facilitate atrial fibrillation (AF) ablation. It is well known that a patient's heart rhythm can switch from sinus rhythm (SR) to AF or vice versa during an AF ablation procedure. However, the impact of the heart rhythm change on the accuracy of left atrium (LA) registration has not been studied. Methods: This study included 10 patients who underwent AF ablation. Prior to the ablation procedure, the patients had contrast‐enhanced cardiac CT scan obtained during SR (n = 7) or AF (n = 3). Using an image integration system (CartoMerge, Biosense Webster Inc.), LA CT surface reconstruction was registered to the real‐time mapping space represented by the LA electroanatomic map. To determine the effect of rhythm change on registration accuracy, LA registration was performed during both SR and AF in each study subject. The distance between the surface of the registered LA CT reconstruction and multiple real‐time LA electroanatomic map points (surface‐to‐point distance) was used as an index for LA registration error. The position error after rhythm change was defined as the surface‐to‐point distance between the surface of the LA CT reconstruction registered in the initial rhythm and the LA electroanatomic map points sampled during the second rhythm. Results: A total of 90 ± 12 and 92 ± 9.5 LA electroanatomic map points were sampled for registration during SR and AF, respectively. No significant difference was found in surface‐to‐point distance when comparing SR with AF as the underlying rhythm during registration (1.91 ± 0.24 vs 1.84 ± 0.38 mm, P = 0.60). The position error after rhythm change was not different from the surface‐to‐point distance of LA registration conducted during the initial rhythm (2.05 ± 0.39 vs 1.96 ± 0.29 mm, P = 0.4). The surface‐to‐point distance did not differ when comparing LA registration conducted during the same versus different rhythm from that during CT imaging (1.96 ± 0.29 vs 1.79 ± 0.32 mm, P = 0.13). Conclusions: Registration error did not differ between LA registrations conducted during the same versus different rhythm as was present during CT imaging. Rhythm changes between SR and AF did not introduce significant error to the LA registration process for catheter ablation of AF. These findings are reassuring and suggest that reregistration is not needed if a patient's rhythm changes from SR to AF or vice versa during an ablation procedure.     

心房颤动患者心房纤维化分子基础的临床研究

目的研究风湿性心脏瓣膜病(风心病)心房颤动(房颤)患者心房组织中胶原、基质金属蛋白酶2(matrixmetalloproteinases2,MMP2)及其内源性抑制剂金属蛋白酶组织抑制因子(tissueinhibitorsofmetalloproteinases,TIMPs)的基因转录,探讨房颤患者心房纤维化的分子机制及其在房颤发生、持续中的作用。方法73例风心病接受换瓣手术者分为三组,其中窦性心律组34例,阵发性房颤组9例,持续性房颤组30例。于术中获取右心耳组织,应用半定量逆转录聚合酶链反应(RT PCR)方法,测定心房组织中Ⅰ型胶原、Ⅲ型胶原、MMP2、TIMP1、TIMP2、TIMP3、TIMP4的mRNA水平。结果与窦性心律组比较,Ⅰ型胶原、MMP2的mRNA在阵发性房颤患者(均为P<0.05)、持续性房颤患者(均为P<0.01)心房组织中的表达均明显增加。房颤患者Ⅲ型胶原的mRNA表达虽有增加,但无统计学意义(P>0.05)。持续性房颤组TIMP1、TIMP2、TIMP3的mRNA表达明显下调(均为P<0.01)。TIMP4的mRNA表达水平在各组中差异无统计学意义(P>0.05)。Ⅰ型胶原的mRNA表达水平与左心房内径(r=0.336,P=0.004)、房颤持续时间(r=0.339,P=0.003)呈正相关;MMP2的mRNA表达水平与TIMP2的mRNA表达水平呈负相关(r=-0.326,P=0.006),与Ⅰ型胶原(r=0.322,P=0.006)、左心房内径(r=0.300,P=0.011)、房颤持续时     

Preoperative alterations in correlation properties and complexity of R-R interval dynamics predict the risk of atrial fibrillation after coronary artery bypass grafting in patients with preserved left ventricular function

Introduction: We evaluated whether there are constant preoperative alterations in nonlinear R–R interval dynamics that associate with the risk of postoperative atrial fibrillation in patients with preserved left ventricular function. Methods: We analyzed mean normal‐to‐normal R–R intervals, short‐term scaling exponent of detrended fluctuation analysis (DFA α₁), approximate entropy and entropy of symbolic dynamics (SymDyn En) from 10‐minute ECG recordings during rest, paced breathing, and passive tilt performed 1 day before surgery in 67 elective coronary artery bypass grafting patients. Results: Nineteen patients developed postoperative atrial fibrillation. The preoperative DFA α₁ was constantly lower in patients developing postoperative atrial fibrillation than in patients remaining in sinus rhythm (P = 0.016); during spontaneous breathing, the DFA α₁ was 0.93 ± 0.33 in patients with atrial fibrillation and 1.13 ± 0.24 in patients with sinus rhythm. The entropy of symbolic dynamics was higher during the spontaneous breathing in patients with atrial fibrillation than in patients with sinus rhythm (4.72 ± 0.51 vs 4.36 ± 0.51, P = 0.012). Higher short‐term scaling exponent of detrended fluctuation analysis during the spontaneous breathing period reduced the risk of postoperative atrial fibrillation (OR 0.31 for an interquartile increase in DFA α₁, 95% CI 0.13–0.78), while higher entropy of symbolic dynamics increased it (OR 3.16 for an interquartile increase in SymDyn En, 95% CI 1.23–8.10), independently of age and clinical risk factors. Conclusion: The preoperatively altered nonlinear R–R interval dynamics were independent predictors of postoperative atrial fibrillation and might become a useful tool for the risk assessment of atrial fibrillation.