Arrhythmic risk stratification after myocardial infarction using ambulatory electrocardiography signal averaging

Ambulatory ECG had been proposed to examine the amplified high resolution signal-averaged electrocardiogram (SAECG). Clinical investigations are required to confirm the predictive value of such a high resolution technique in arrhythmic risk stratification. The prognostic value of ambulatory Holter SAECG was evaluated in 108 postinfarction patients for the purpose of predicting the occurrence of serious arrhythmic (SARR) events (sudden cardiac death [SCD], VT, or VF) in comparison with classical real-time SAECG. During the 42+/-8 months of follow-up, the sudden cardiac death mortality was 4.6% (five deaths), six (5.6%) patients had VT, and one (0.9%) VF. QRSd was found to be the most predictive parameter using ROC curves analysis for SAAR + outcome (W = 0.833 and W = 0.803 for 25-250 Hz and 40-250 Hz filters, respectively) followed by RMS (W = 0.766 and W = 0.721) and LAS (W = 0.759, W = 0.709) (all P < 0.01). Abnormal Holter SAECG for 25 and 40-Hz LP filter were significant predictors of SARR+ by log-rank test (P < 0.01, P < 0.05, respectively). This study confirms that valuable prognostic information can be obtained from the ambulatory high resolution ECG technique and that Holter SAECG may predict arrhythmic risk in a postinfarction population.     

A Critical Appraisal of Quantitative Spectro-Temporal Analysis of the Signal-Averaged ECG: Predicting Arrhythmic Events After Myocardial Infarction

The objective of this study was to determine if spectra-temporal analysis of the signal-averaged ECG (SAECG) predicts spontaneous sustained ventricular tachyarrhythmias and sudden death in patients prospectively followed after myocardial infarction (MI). A SAECG was recorded in 177 patients 9 ± 5 days after MI. Spectro-temporal analysis of the SAECG involved incrementing a Hanning window every 3 ms beginning 20 ms before the end of the QRS complex and extending into the ST segment. Quantitative analysis was performed using a cross-correlation function to create a normality factor. A normality factor < 0.3 was deemed abnormal. The SAECG was abnormal in 41 % of patients using time-domain analysis and 44% of patients using spectra-temporal analysis. There was no correlation between an abnormal SAECG in the time domain and the frequency domain. Patients with inferior wall MI were more likely to have an abnormal spectra-temporal map (odds ratio 2.26, P < 0.05). Time-domain analysis of the SAECG (relative risk (RE) 2.6) was a statistically significant univariate predictor of arrhythmic events. Spectra-temporal analysis of the SAECG was only weakly (RR 1.8) and not significantly (P = 0.15) associated with the spontaneous occurrence of these arrhythmias. When both time-domain analysis and spectra-temporal analysis of the SAECG were abnormal, the relative risk for an arrhythmic event was increased by 3.3-fold. Quantitative spectra-temporal analysis of high frequency signals within the SAECG cannot by itself predict the occurrence of spontaneous ventricular arrhythmias in patients after MI.     

Prognostic Implications of Loss of Late Potentials Following Acute Myocardial Infarction

The prognosis of patients following myocardial infarction is adversely affected by the finding of late potentials at the time of hospital discharge. Loss of late potentials has been previously reported during seriai testing during the first year after infarction, but it is not known whether such patients remain at risk of arrhythmic events. This study prospectively followed 243 patients after myocardial infarction. Late potentials were observed in 92 patients (group 1) at the time of hospital discharge. Of these patients, 23 no longer had late potentials at G-week follow-up and 8 had had an arrhythmic event (sudden death or ventricular tachycardia). In patients with loss of late potentials, overall QRS duration had decreased from 109 ± 11 msec at discharge to 104 ± 11 msec (P < 0.01), terminal QRS voltage rose from 15 ± 4 μV to 31 ± 9 μV (P = 0.001), and late potential duration fell from 42 ± 6 msec to 28 ± 6 msec (P = 0.001) at the 6-week study. Predictors of loss of late potentials were: initial duration of the QRS duration (P < 0.001) and terminal voltage (P < 0.005); non-Q wave infarction (P < 0.001); and being a male (P < 0.05). After the 6-week assessment, 11 additional arrhythmic events occurred during median follow-up of31 months. The risk of arrhythmic events was similar in patients with loss of late potentials and those who retained late potentials in group I (9% vs 11%, P - NS) but significantly greater than palients with no late potentials at discharge (group II, 2%). Of those patients with events beyond 6 weeks, a normal signal-averaged ECG (either lost late potentials or group II) was observed in 6/11 (55%) patients on at least one occasion prior to the occurrence of the event. Hence, a significant number of arrhythmic events occurring ≥ 6 weeks after myocardial infarction occur in palients with a normal signal-averaged ECG even when late potentials are initially present. “Loss’ of late potentials does not necessarily confer an improved prognosis in terms of risk of arrhythmic events.     

QRS duration in high-resolution methods and standard ECG in risk assessment after first and recurrent myocardial infarctions

Background: Prolonged QRS duration (QRSd) is associated with increased mortality after myocardial infarction (MI). Only little data exist about its predictive ability and relationships to clinical variables in the present era of active treatment of myocardial ischemia and cardiac dysfunction. We investigated whether QRSd in high-resolution methods and standard ECG predict arrhythmic events and cardiac death in post-infarction patients with cardiac dysfunction and how it relates to clinical variables, with a special emphasis on history of previous MI.
Methods and Results: Patients (n = 158) with acute MI and cardiac dysfunction had magnetocardiography (MCG), signal-averaged ECG (SAECG), and ECG registered at discharge. Patients with a previous MI had significantly longer QRSd although their left ventricular function was almost similarly impaired. During the mean follow-up of 50 ± 15 (range 1–72) months, 32 patients died and 17 (53%) of the deaths were classified as cardiac. Eighteen patients had an arrhythmic event. QRSd >121 ms in MCG and >114 ms in SAECG were significant predictors of arrhythmic events and cardiac death, whereas QRSd in ECG predicted only cardiac death. In multivariate analysis, QRSd in MCG (hazard ratio (HR) = 3.6, P = 0.007) and SAECG (HR = 4.6, P = 0.016) predicted only arrhythmic events, whereas QRSd in ECG was an independent predictor of cardiac death.
Conclusions: Prolonged QRSd in MCG and SAECG are powerful indicators of the arrhythmia substrate in post-infarction patients with cardiac dysfunction, whereas prolonged QRSd in standard ECG associates with increased risk of cardiac death.     

Prolonged QRS duration increases QT dispersion but does not relate to arrhythmias in survivors of acute myocardial infarction

QT dispersion has been suggested and disputed as a risk marker for ventricular arrhythmias after myocardial infarction. Delayed ventricular activation after myocardial infarction may affect arrhythmic risk and QT intervals. This study determined if delayed activation as assessed by (1) QRS duration in the 12-lead ECG and by (2) late potentials in the signal-averaged ECG affects QT dispersion and its ability to assess arrhythmic risk after myocardial infarction. QT duration, JT duration, QT dispersion, and JT dispersion were compared to QRS duration in the 12-lead ECG and to late potentials in the signal-averaged ECG recorded in 724 patients 2-3 weeks after myocardial infarction. Prolonged QRS duration (> 110 ms) and high QRS dispersion increased QT and JT dispersion by 12%-15% (P < 0.05). Presence of late potentials, in contrast, did not change QT dispersion. Only the presence of late potentials (n = 113) was related to arrhythmic events during 6-month follow-up. QT dispersion, JT dispersion, QRS duration, and QRS dispersion were equal in patients with (n = 29) and without arrhythmic events (QT disp 80 +/- 7 vs 78 +/- 1 ms, JT disp 80 +/- 6 vs 79 +/- 2 ms, mean +/- SEM, P > 0.2). In conclusion, prolonged QRS duration increases QT dispersion irrespective of arrhythmic events in survivors of myocardial infarction. Presence of late potentials, in contrast, relates to arrhythmic events but does not affect QT dispersion. Therefore, QT dispersion may not be an adequate parameter to assess arrhythmic risk in survivors of myocardial infarction.     

Noninvasive Arrhythmia Risk Stratification in Idiopathic Dilated Cardiomyopathy: Design and First Results of the Marburg Cardiomyopathy Study

The Marburg Cardiomyopathy Study (MACAS) is a prospective, observational study designed to determine the value of the following potential noninvasive arrhythmia risk predictors in at least 200 patients with idiopathic dilated Cardiomyopathy (IDC) over a 5-year follow-up period: NYHA-class, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, left bundle branch block and atrial fibrillation on ECG, QT/JT dispersion on 12-lead ECG, signal-averaged ECG, ventricular arrhythmias and heart rate variability (HRV) on 24-hour Hotter ECG, baroreflex sensitivity, and microvolt T wave alternans during exercise. This article describes the findings among the first 159 patients with IDCs enrolled in MACAS until May 1998 (40 women, 119 men;age:49 ± 12 years; LVEF: 32 ± 10%). Twenty-nine patients (18%) had atrial fibrillation and 130 patients (82%) were in sinus rhythm. Patients with sinus rhythm were further stratified according to LVEF < 30% (n = 54) versus LVEF ≥ 50% (n = 76). Compared to patients with LVEF ≥ 30%, patients with LVEF < 30% more often had left bundle branch block (43% vs 25%, P < 0.05), nonsustained VT (44% vs 22%, P < 0.05), decreased HRV (SDNN: 95 ± 39 vs 128 ± 42 ms, P < 0.01), decreased baroreflex sensitivity (5.6 ± 4 vs 8.3 ± 6 ms/mmHg, P < 0.01), and T wave alternans (59% vs 37%, P < 0.05). The prognostic significance of these findings will be determined by multivariate Cox analysis at the end of a 5-year follow-up. Primary endpoints in MACAS are overall mortality and arrhythmic events (i.e., sustained VT or VF, or sudden cardiac death).     

The Role of Parasympathetic Modulation of the Reentrant Arrhythmic Substrate in the Genesis of Sustained Ventricular Tachycardia

The influence of parasympathetic activity on the reentrant arrhythmic substrate in the genesis of sustained ventricular tachycardia remains unclear. To assess this influence, we studied the heart rate variability in 59 patients referred for invasive electrophysiological testing. In addition, the presence of late potentials and high grade ventricular ectopy, and the left ventricular ejection fraction was determined. The 28 patients with inducible sustained ventricular tachycardia were found to have lower heart rate variability by time- and frequency-domain measurements over 24 hours when compared to the 31 subjects who were noninducible. PNN50 was 4% in the inducible patients, whereas it was 9% in the subjects who were noninducible (P = 0.03). Similarly, HFP24H was 9 and 14 msec, respectively (P = 0.02). MAXHFP1H also differed (20 vs 27 msec [P = 0.04]) but not MINHFP1H (5 vs 6 msec). There was no association between heart rate variability and late potentials, degree of ventricular ectopy, or left ventricular ejection fraction. Thus, vagal tone does not appear to correlate with the presence of late potentials, ventricular ectopy, or left ventricular dysfunction. Low mean as well as maximal vagal tone, in contrast to minimal vagal tone, predicts inducibility of sustained ventricular tachycardia. Our data suggest that the inability to modulate parasympathetic tone appears to be an important determinant in the genesis of reentrant sustained ventricular tachycardia.     

Within- and Between-Patient Variation of the Signal-Averaged P Wave in Coronary Artery Disease

Objectives: To estimate interobserver, within-patient and between-patient variation of the signal-averaged P wave. To determine whether demographic, clinical, conventional ECG information, and coronary angiographic data are associated with the signal-averaged P wave duration in patients with documented coronary artery disease. Background: A prolonged signal-averaged P wave may indicate the presence of a substrate for atrial tachyarrhythmias and may predict subsequent development of atrial fibrillation. However, information on variation, reproducibility, and determinants of the signal-averaged P wave are sparse. Methods: One hundred ninety-three patients with angiographically documented coronary artery disease underwent two consecutive procedures of signal-averaging of P waves (SAECG1 and SAECG2). Interobserver, within-patient, and between-patient variation of the signal-averaged P wave was estimated (coefficient of variation: SD/mean). Multiple linear regression analysis was applied to identify parameters independently associated with signal-averaged P wave duration (SA-P). Atrial late potentials were considered if SA-P > 140 ms, and logistic regression analysis was applied to identify parameters associated with the presence of atrial late potentials. Results: The interobserver, within-patient, and between-patient coefficients of variation for the signal-averaged P wave duration were 7.5%, 6.0%, and 8.4%, respectively. The signal-averaged P wave duration correlated significantly with standard ECG P wave duration and height of the patient (r = 0.59). Forty-nine percent of the patients had atrial late potentials. P wave duration in the standard ECG correctly classified 73% (140/188) of the patients with respect to atrial late potential positivity or negativity. The sensitivity was 67% and the specificity was 78%. Agreement on the presence or absence of atrial late potentials between two observers was present in 71% (136/193) of the patients, and in 78% (151/193) between SAECG1 and SAECG2. Conclusions: The signal-averaged P wave has limited reproducibility in patients with coronary artery disease, and a normal or abnormal signal-averaged P wave can be predicted from the conventional ECG with high accuracy. It is recommended that the signal-averaged P wave be compared with the standard ECG P wave duration in follow-up studies with the aim of predicting atrial fibrillation.     

Signal-Averaged Electrocardiography in Elderly Subjects With and Without Heart Disease

Prevalence of abnonnal signal-averaged electrocardiography in normal populations ap pears to be low, but has not been studied previously in an asymptomatic elderly population. To study the prevalence of abnormal ventricular late potentials in an elderly population, a group of 51 subjects with no evidence of cardiac disease and ranging In age from 62 to 102 years underwent signal-averaged electrocardiography. Results were compared to a group of 179 patients similar in age but with complex ventricular arrhythmias, and to a group of 25 asymptomatic volunteers under the age of 50. The prevalence of an abnormal signal-averaged ECG was 14% in the normal elderly subjects, and 31 % in the patients (P = 0.01), and 4 % in the young subjects (P = NS). We conclude that the prevalence of abnormal ventricular late potentials in elderly patients without heart disease is similar to levels reported in other populations of normal controls, but elderly patients with cardiac disease have a significantly higher prevalence of abnormal signal-averaged ECG studies than the normals.     

Quality-of-Life Six Months After CABG Surgery in Patients Randomized to ICD Versus No ICD Therapy: Findings from the CABG Patch Trial

ICDs can affect a patient's perceived quality-of-life (QOL). This article describes the QOL in patients who participated in The CABG Patch Trial. This trial evaluated the potential benefit of empiric ICD implantation in patients with an increased risk of arrhythmic cardiac death as determined by reduced ejection fraction (<0.36) and an abnormal signal-averaged ECG. Patients were randomized to control (no ICD) or treatment (ICD) limbs. QOL was measured using the SF-36 and other measures among 490 (68%) of 719 patients available at 6-month follow-up. Analysis was performed on 228 control patients (those without ICDs) and 262 patients with ICDs. RESULTS: Six months after having CABG surgery, patients in the ICD group had lower levels of psychological well-being than those in the control group. In addition, compared to controls, patients whose ICDs had delivered therapy reported feeling less healthy, had reduced physical and emotional role functioning, and had lower levels of psychological well-being. CONCLUSION: Strategies aimed at easing patients' adjustment to ICDs should be developed and tested for efficacy in the setting of ICD prophylaxis.     

Incidence of T Wave Alternation After Acute Myocardial Infarction and Correlation with Other Prognostic Parameters: Results of a Prospective Study

Tachycardia induced alternation of the T wave (TWA) has been associated with arrhythmia morbidity in mixed patient populations. However, less is known concerning the general incidence of TWA and its usefulness in risk stratification early after acute myocardial infarction (MI). TWA was prospectively and systematically assessed in 140 consecutive patients 15 +/- 6 days after acute MI and prior to discharge. Results of TWA measurements were compared to other noninvasive risk markers, LV function, and coronary angiography. Sustained TWA was present at rest or inducible during exercise in 27% of patients. The patient-specific heart rate for the onset of TWA was 98 +/- 9 beats/min. After multivariate analysis, TWA correlated with age (P = 0.02) and LV function (P = 0.002) and occurred more often in patients after nonanterior MI (P = 0.03). Acute results of Holter monitoring, late potentials by signal-averaged ECG, and heart rate variability were unrelated to the TWA status. During follow-up (451 +/- 210 days) two major arrhythmic events occurred. The incidence of TWA early after MI is about 25%. TWA is related to age and LV function but not to other common arrhythmia markers. Although TWA does not appear to be related to excessive cardiac morbidity, evaluation of the prognostic significance of TWA requires further study.     

Epsilon Wave in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Background: Epsilon wave is a major criteria for arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C). We sought to study systematically characteristics of Epsilon wave in ARVD/C patients from the southern Chinese population.
Methods: The population included 49 patients with ARVD/C meeting the diagnostic criteria. They were analyzed for the value of different electrocardiogram (ECG) criteria including Epsilon wave, the ones of 24-hour Holter recording, signal-averaged ECG, and echocardiography to learn the correlation between Epsilon wave and other variability with the use of nonparametric test. A probability value of ≤0.05 was considered significantly different.
Results: It shown that the detection rate of Epsilon wave was significantly higher in probands (65%) than involved family members (22%), P = 0.03. In the conventional as well as Fontaine leads, its detection rate were 18 (37%) and 28 (57%), respectively. The prevalence of diffuse right ventricle involvement, T-wave inversion and signal-averaged ECG are significantly different between the ARVD/C patients with Epsilon wave and without Epsilon wave.
Conclusion: It is significantly correlated between Epsilon wave and the progressive ARVD/C.     

Heart Rate Variability and Major Arrhythmic Events in Patients with Idiopathic Dilated Cardiomyopathy

This prospective study of 71 patients with idiopathic dilated cardiomyopathy (IDC) and preserved sinus rhythm was designed to evaluate the relation between heart rate variability (HRV) and subsequent major arrhythmic events. Standard time- and frequency-domain HRV parameters were obtained from analysis of 24-hour Holter ECG recordings. During a mean follow-up of 15 ± 5 months, major arrhythmic events including sustained ventricular tachycardia, ventricular fibrillation, and sudden cardiac death occurred in 10 of the 71 study patients (14%). Neither time- nor frequency-domain indices of HRV differed significantly between patients with and patients without subsequent major arrhythmic events. However, there was a trend toward a lower standard deviation of the average normal RR interval for all 5-minute segments of the 24-hour recording (68 ± 17 ms vs 80 ± 31 ms; P = 0.06) in patients with major arrhythmic events. In addition, the percentage of adjacent normal RR intervals differing > 50 ms over the recording period tended to be lower in patients with major arrhythmic events (6%± 3% vs 9%± 6%; P = 0.08). Our results indicate a tendency toward attenuated parasympathetic activity in IDC patients with subsequent major arrhythmic events compared to arrhythmia-free patients. Larger studies with longer follow-up periods are necessary to clarify the role of HRV measurements for arrhythmia risk prediction in patients with IDC.     

Neurohumoral activation and ventricular arrhythmias in patients with decompensated congestive heart failure: role of endothelin

Patients with congestive heart failure (CHF) have a high incidence of ventricular arrhythmias and sudden arrhythmic death. CHF entails profound and complex abnormalities in humoral responses that are thought to promote arrhythmic events. However, it is unknown which of the many endogenous mediators that accumulate as part of neurohormonal activation is important in arrhythmogenesis in the setting of CHF. The study included 83 patients admitted to the hospital for treatment of decompensated CHF. Neurohormonal and cytokine activation was assessed by measuring plasma renin activity, aldosterone, norepinephrine, endothelin-1, tumor necrosis factor-alpha, and interleukin-6 levels. Atrial and ventricular arrhythmic events were assessed by 24-hour Holter monitoring. In a univariate analysis, a highly significant, positive relationship was found between plasma endothelin-1 levels and the average hourly total premature ventricular beats (P = 0.003), the frequency of ventricular pairs (P = 0.0003), and the frequency of ventricular tachycardia episodes (P = 0.001). After inclusion of clinical variables, drug therapies, neurohormones, and cytokine levels in a multivariate analysis, the positive relationship between plasma endothelin-1 level and the average hourly total premature ventricular beats (P = 0.008), the frequency of ventricular pairs (P = 0.007), and ventricular tachycardia episodes (P = 0.009) remained independent. No association between other neurohormones or cytokines and arrhythmic events was demonstrated. The results of the present study suggest that increased endothelin-1 concentrations may be involved in promoting the occurrence of ventricular ectopy in patients with decompensated CHF. Proarrhythmic effects may account, in part, for the poor outcome associated with increased endothelin-1 levels in patients with decompensated CHF.     

Role of Programmed Electrical Stimulation of the Heart in Risk Stratification Post-Myocardial Infarction

Programmed electrical stimulation (PES) of the heart was evaluated as a method of identifying patients at risk of sudden death post-myocardial infarction (post-MI). Eighty-four patients (mean age, 56 +/- 10 years) underwent PES 6 to 8 weeks post-MI. PES was performed at the right ventricular apex at twice diastolic threshold. Prior to stimulation patients were studied with exercise stress testing, 24-hour Holter monitoring and radionuclide ejection fraction. The patients were placed into two groups, according to their responses to electrical stimulation. Group 1:65 patients in whom no arrhythmias were induced or who had repetitive responses that lasted less than six cycles; Group 2:19 patients in whom ventricular tachycardia was induced. At the end of follow-up (20 +/- 9 months) six patients from Group 1 had died. Complex ventricular ectopy and ventricular tachycardia were more frequently detected on Holter in Group 2 (9/19) than in Group 1 (14/65) (p less than 0.03). The results of exercise testing and radionuclide ejection fraction did not correlate with the response to PES. However all but one of the patients who died had a left ventricular ejection fraction (LVEF) under 40% and four out of six patients had ventricular tachycardia on Holter monitor. We draw the conclusion that PES did not contribute to the identification of high-risk patients post-MI, as none of the 19 patients in whom ventricular tachycardia was induced died during follow-up. In addition, high-risk patients were characterized by poor ventricular function and complex ventricular arrhythmias on Holter recording.     

Evolution of QRS duration after myocardial infarction: clinical consequences

The natural history of late potentials after acute myocardial infarction (AMI) has been studied in the first 2 years following myocardial infarction (MI). The purpose of the study was to assess the influence of some time delays since MI, including a time delay longer than 2 years on signal-averaged ECG (SAECG). SAECG was recorded at 40-Hz high pass filtering in 40 patients 10 days after acute MI (SAECG 1), then repeated 6-12 months later (mean 9 +/- 3 months) (SAECG 2), and then, 2-4 years later (mean 3 +/- 2 years) (SAECG 3). QRS duration, root mean square voltage of the last 40 ms of QRS (RMS 40), and low amplitude signal duration (LAS) were measured at the first (1), second (2), and third recording (3). Results: (***P < 0.001) [table: see text] The analysis of individual results showed a lengthening QRS duration at the third recording only in patients who had a decreased left ventricular ejection fraction (LVEF) at the third recording. In 12 patients with LVEF > 40%, QRS duration did not change at the first and third recording (104 +/- 15 vs 101 +/- 12 ms). In all 28 patients, but one with LVEF < 40%, QRS duration increased from 107 +/- 12 to 128 +/- 18 ms***. There was no correlation between QRS duration and LVEF at the second recording and no correlation between QRS duration increase at the third recording and the presence or not of late potentials at the first recording. QRS duration lengthening at the third recording was significantly correlated with a left ventricular (LV) dilatation occurrence at the two-dimensional echocardiogram. All arrhythmic events, but two, occurred in patients who developed a QRS duration prolongation and were significantly correlated (P < 0.01) to a mean longer QRS duration (132 +/- 20 ms) than in patients without arrhythmic events (113 +/- 17 ms). In conclusion, the patients with a LV impairment, and who developed a LV dilatation several months after AMI, presented a delayed lengthening of QRS duration noted only at least 2 years after infarction. These patients are at risk of arrhythmic events.     

Heart rate variability in arrhythmogenic right ventricular cardiomyopathy correlation with clinical and prognostic features

The identification of subjects with arrhythmogenic right ventricular cardiomyopathy (ARVC) at higher risk for sudden death is an unresolved issue. An influence of the autonomic activity on the genesis of ventricular arrhythmias was postulated. Heart rate variability (HRV) analysis provides a useful method to measure autonomic activity, and is a predictor of increased risk of death after myocardial infarction. For these reasons, the aim of the study was to evaluate HRV and its correlations with ventricular arrhythmias, heart function, and prognostic outcome in patients with ARVC. The study included 46 patients with ARVC who were not taking antiarrhythmic medications. The diagnosis was made by ECG, echocardiography, angiography, and endomyocardial biopsy. Exercise stress test and Holter monitoring were obtained in all patients. Time-domain analysis of HRV was expressed as the standard deviation of all normal to normal NN intervals (SDNN) detected during 24-hour Holter monitoring. Thirty healthy subjects represented a control group for HRV analysis. The mean follow-up was 10.8 +/- 1.86 years. SDNN was reduced in patients with ARVC in comparison with the control group (151 +/- 36 vs 176 +/- 34, P = 0.00042). Moreover, there was a significant correlation of this index with the age of the patients (r = - 0.59, P < 0.001), with the left (r = 0.44, P = 0.002) and right (r = 0.47, P = 0.001) ventricle ejection fraction, with the right ventricular end diastolic volume (r = - 0.62, P < 0.001), and with the ventricular arrhythmias, detected during the same Holter record used for HRV analysis (patients with isolated ventricular ectopic beats < 1,000/24 hours, 184 +/- 34; patients with isolated ventricular ectopic beats > 1,000/24 hours and/or couplets, 156 +/- 25; patients with repetitive ventricular ectopic beats (> or = 3) and/or ventricular tachycardia, 129 +/- 25; P < 0.001). During follow-up two patients showed a transient but significant reduction of SDNN and a concomitant increase of the arrhythmic events. In eight patients an episode of sustained ventricular tachycardia occurred, but the mean SDNN of this subgroup did not differ from the mean value of the remaining patients (152 +/- 15 vs 150 +/- 39; P = NS). Only one subject died after heart transplantation during follow-up (case censored). Time-domain analysis of HRV seems to be a useful method to assess the autonomic influences in ARVC. A reduction of vagal influences correlates with the extent of the disease. The significant correlation between SDNN and ventricular arrhythmias confirmed the influences of autonomic activity in the modulation of the electrical instability in ARVC patients. However, SDNN was not predictive of spontaneous episodes of sustained ventricular tachycardia.     

Signal-averaged electrocardiography: a new noninvasive test to identify patients at risk for ventricular arrhythmias

Signal-averaged electrocardiography (ECG) is a new noninvasive test for identifying patients at risk for ventricular arrhythmias. This computerized method of analyzing standard ECGs identifies particular microvolt-level signals called late potentials. Late potentials have been correlated with clinical ventricular tachycardia, are predictive of ventricular tachycardia inducibility at the time of electrophysiologic testing, and are predictive of arrhythmic events after myocardial infarction. In this review, we describe late potentials, the method of obtaining and processing the signal-averaged ECG, and clinical studies in various patient groups that have assessed the predictive value of the signal-averaged ECG for identification of patients at risk for subsequent ventricular arrhythmias.     

Effects of sulfonylurea hypoglycemic agents and adenosine triphosphate dependent potassium channel antagonists on ventricular arrhythmias in patients with decompensated heart failure

Hypoglycemic sulfonylureas block cardiac ATP-sensitive potassium channels (K(ATP)). The opening of these channels in cardiomyocytes can induce arrhythmias. In animal studies, sulfonylureas exert an antiarrhythmic effect on the ischemic myocardium, but data on human arrhythmic events are lacking. The study population included 207 patients (age 61 +/- 14 years) admitted for decompensated CHF. The severity of ventricular arrhythmias was assessed by 24-hour Holter monitoring. None of the patients were on parenteral vasoactive therapy or antiarrhythmics during Holter recording. Diabetic patients comprised 48% of the study population, and 34% of diabetic patients were prescribed sulfonylureas. The mean hourly ventricular pairs (3.6 +/- 0.5 vs 1.8 +/- 0.3, P = 0.03), the mean hourly repetitive ventricular beats (5.7 +/- 1.0 vs 2.6 +/- 0.1, P = 0.03), and the frequency of ventricular tachycardia episodes per 24 hours (4.7 +/- 0.8 vs 2.2 +/- 0.4, P = 0.03) were significantly lower in patients with diabetes who were receiving sulfonylureas compared with nondiabetics. No significant difference occurred between patients with diabetes who were not receiving sulfonylureas and nondiabetic patients. Multivariate regression revealed a negative independent relationship between sulfonylurea therapy and hourly ventricular pairs (P = 0.03), the mean hourly repetitive ventricular beats (P = 0.03), and ventricular tachycardia episodes (P = 0.04). In a multiple logistic regression, sulfonylurea therapy was a negative predictor of repetitive ventricular beats (P = 0.01, adjusted OR, 0.31; 95% CI, 0.12-0.78). Concomitant sulfonylurea therapy may reduce the occurrence of complex ventricular ectopy in the setting of severe CHF. These results suggest that cardiac K(ATP) channel activation may be involved in the genesis of ventricular arrhythmias in CHF.     

Continuous Holter telemetry of atrial electrograms and marker annotations using a common Holter recording system: impact on Holter electrocardiogram interpretation in patients with dual chamber pacemakers

The impact of continuous telemetry of atrial electrogram and marker annotations on Holter ECG interpretation was assessed in 98 patients with bipolar dual chamber pacemakers (VDD pacemakers n = 29, DDD(R) systems n = 69). Atrial electrogram and marker annotations were continuously sampled by a telemetry coil that was externally positioned on the pacemaker pocket, amplified, and transduced to a three-channel Holter ECG recorder in addition to an ECG recording. Holter tapes were analyzed by two experienced investigators for quality of P wave recognition and episodes suspicious of pacemaker dysfunction. Initially, only the ECG channel was analyzed. Thereafter, results were compared to those achieved on the basis of the complete recording including atrial electrogram and marker annotations. Recognition of atrial rhythm was markedly improved by Holter telemetry. During 99.3% of recording time telemetry showed a satisfying quality, whereas ECG alone allowed a reliable P wave recognition only during 84.4% of recording time (P < 0.001). One hundred twenty-nine episodes suspicious of pacemaker malfunction occurred in 17 of 98 patients. By analysis of ECG, only 78.3% of episodes were concordantly classified by the investigators. However, 98.4% of all episodes were properly identified when atrial electrogram and marker annotations were added to the analysis (P < 0.001). In particular, discrimination between atrial undersensing, sinus bradycardia, and atrial sensed events within the refractory periods was facilitated. Holter telemetry of atrial electrogram and marker annotations facilitates the analysis of Holter ECGs in pacemaker recipients and improves the detection of pacemaker dysfunctions.