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.     

Influence of Filtering Techniques on the Time-Domain Analysis, Diagnosis, and Clinical Use of Signal-Averaged Electrocardiogram

In order to investigate the effect of different filtering techniques on the time-domain analysis of signal-averaged electrocardiogram (SAECG), recordings of 1,192 subjects were analyzed using Butterworth and Del Mar filters, both set at 40–250 Hz high and low pass frequencies. The recordings were taken from six clinically defined groups: (a) survivors of acute myocardial infarction (n = 553); (b) patients with sustained symptomatic postinfarction ventricular tachycardia (n = 89); (c) patients with hyperthropic cardiomyopathy (n = 219); (d) patients with dilated cardiomyopathy (n = 76); (e) direct relatives of patients with dilated cardiomyopathy (n = 170); and (f) normal healthy volunteers (n = 85). The study investigated differences between the SAECG results reported with both filters in three individual aspects: (l) numerical values of individual time-domain SAECG variables; (2) differences in SAECG findings of patients with postinfarction ventricular tachycardia and pair matched patients with uncomplicated follow-up after acute infarction; and (3) the power of SAECG findings to predict high risk of arrhythmic complication (sudden death and/or sustained ventricular tachycardia) among survivors of acute myocardial infarction. Compared with the Butterworth filter, the Del Mar filter led to a systematic difference of + 8% in total QRS duration, was equally powerful in distinguishing between the pair matched patients with and without postinfarction ventricular tachycardia, and was statistically significantly more powerful in identifying those survivors of acute infarction who were at high risk of arrhythmic complications. The study concludes that the use of different filters may produce discordant results of SAECG analysis. Normal and abnormal values for various types of SAEGG recording and analysis have to be established individually for different equipment and different software settings. These optimal cut-offs of SAEGG variables should also take into account the clinical characteristics of patient groups.     

Long Runs of Non-Sustained Ventricular Tachycardia on 24-Hour Ambulatory Electrocardiogram Predict Major Arrhythmic Events in Patients with Idiopathic Dilated Cardiomyopathy

This study examined the prognostic significance of the rate and length of non-sustained (NS) ventricular tachycardia (VT) on 24-hour ambulatory electrocardiograms (ECG) recorded in 343 patients with idiopathic dilated cardiomyopathy (IDC) in the prospective Marburg Cardiomyopathy study. NSVT was defined as ≥3 consecutive ventricular premature beats at >120 bpm. During 52 ± 21 months of follow-up, major arrhythmic events defined as sustained VT, VF, or sudden cardiac death occurred in 46 of 343 patients (13%). Patients with 3–4 beat runs of NSVT had a similar arrhythmia-free survival as patients without NSVT on baseline 24-hour ambulatory ECG. The incidence of major arrhythmic events during follow-up increased significantly from 2% per year in patients without NSVT, to 5% per year in patients with 5–9 beat runs of NSVT, to 10% per year in patients with ≥10 beat runs of NSVT (P < 0.05). Unlike the length, the rate of NSVT was similar in patients with versus without subsequent major arrhythmic events (163 ± 23 vs 160 ± 24 bpm). Thus, the length but not the rate of NSVT on 24-hour ambulatory ECG was a predictor of major arrhythmic events in patients with IDC. The presence of NSVT with ≥10 beat runs on ambulatory ECG was associated with a particularly high risk of major arrhythmic events.     

Prediction of Arrhythmic Events After Acute Myocardial Infarction Using Two Methods for Late Potentials Recording

One hundred consecutive patients recovering from an acute myocardiai infarction underwent, prior to home discharge, signal-averaged electrocardiography (ECG), left ventriculography. and 24-hour Holter ECG recording. The signal-averaged ECG was recorded and analyzed using two procedures: the orthogonal bipolar XYZ lead configuration with a bidirectional filter: and a precordial unipolar lead configuration with a uonrecursive digital filter. An abnormal signal-averaged ECG was seen in 40% of patients with the XYZ system and in 30% of patients in the precordial method, abnormal ejection fraction (< 40%) in 24% of patients and high grade ectopy activity in 22%. During the 24-month follow-up period, 12 patients (12%) had an arrhythmic event defined as either sudden death (11 patients) or sustained ventricular tachycardia (1 patient). Neither the signal-averaged ECG with the XYZ configuration, the abnormal ejection fraction, nor the high grade ectopy were able to statistically predict a higher arrhythmic event rate. The signal-averaged ECG with the precordial configuration was able to statistically predict a higher arrhythmic event rate, P < 0.03; odds ratio = 3.96. The combination of the orthogonal XYZ configuration signal-averaged ECG with the ejection fraction (P < 0.01, odds ralio = 7.33), or with ejection fraction and Holter monitoring (P < 0.06. odds ratio = 6.17) was able to predict a higher arrhythmic event rate. The combination of the precordial configuration signal-averaged ECG with the ejection fraction (P < 0.002, odds ratio = 14.4), or with ejection fraction and Holter monitoring (P < 0.06. odds ratio =10) was able to better predict a higher arrhythmic event rate. The combination of a normal or abnormal signal-averaged ECG and ejection fraction gave a sensitivity, specificity, positive, or negative value prediction of arrhythmic events of 60%, 90.6%, 37.5%, and 96%, respectively. It must be emphasized that the number of arrhythmic events during the 2-year follow-up was small and further study is required to determine the true predictive value of each method for arrhythmic events.     

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.     

Heart Rate Variability in Myocardial Infarction With and Without Malignant Arrhythmias: Comparison with Heart Transplant Recipients and Normal Subjects

Myocardial autonomic denervation occurs after acute MI. This process is followed by a reduction of heart rate variability (HRV) and an increase of malignant ventricular arrhythmias and sudden death. This study investigated whether there are any significant differences in HRV among the population of MI who did and did not have malignant ventricular arrhythmias (MVAs), normal subjects and heart transplant recipients, the paradigm of the denervated heart. We studied 25 subjects aged 42 ± 17 years, with normal clinical and cardiac noninvasive evaluation (group A); 70 patients aged 57 ± 14 years, who had MI hut no arrhythmic event in 36 months of follow-up (group B); 13 patients with MI aged 65 ± 9 years, who had had sustained VT, VF, or sudden death (group C); and 16 cardiac transplant recipients aged 35 ± 14 years (group D). The ECG was sampled for 256 seconds. We calculated, in time and frequency domain, the standard deviation of the RR cycle length and the spectral component's very low frequency (< 0.05 Hz), low frequency (0.05–0.15 Hz), and high frequency (0.15–0.35 Hz). The values of HRV in group A were significantly greater than in groups B, C, and D (P < 0.001) and greater in group B than in groups C and D (P < 0.001). Groups C and D did not differ (P = 0.610). These data indicate that HRV of patients who have had an MI and MVAs is very similar to that of heart transplant recipients. This is an indirect evidence that myocardial autonomic denervation may play an important role in the genesis of malignant arrhythmic events.     

Proarrhythmic Response to Antiarrhythmic Drug as a Risk Factor for Sudden Cardiac Death in Patients with Ischemic Heart Disease

The prognostic significance of arrhythmogenicc response to an antiarrhythmic drug was studied. In 782 palients with ischemic heart disease (IHD) and frequent and/or complex ventricular premature boats (VPBs), 1,041 drug tests guided by 24-hour Holter monitoring were conducted. The following drugs were assessed: beta blockers, disopyramide, mexiletine, amiodarone. Proarrhythmia was defined as: (1) > 4-fold increase in VPBs, (2) > 10-fold increase in repetitive forms, or (3) new occurrence of ventricular tachycardia or ventricular fibrillation (VT/VF). During a follow-up of 1–49 months fmean 22) patients were treated with anfiarrhythmic drugs found to be safe in control Holter monitoring, Proarrhythmic effects were observed in 8.4% of patients. No drug was completely free of this type of reaction. In long-term observation, cardiac death and sudden death occurred in 5.3 and 32 patients, respectively. With actuarial analysis (Kaplan-Meier method, log-rank test) there was a significant difference in cardiac death (P < 0.01) and sudden death rate (P < 0.05) of proarrhythmia (+) compared with proarrhythmia (-) patients at 1 year (11% vs 4%, 7% vs 3%) and 3 years (24% vs 11%, 16% vs 7%). Proarrhythmic response was an independent risk factor apart from myocardial infarction, VT/VF, ejection fraction < 40% and QT_c > 440 msec. Arrhythmogenic response to antiarrhythmic drugs seems to be en additional predictor of sudden death in IHD.     

Heart Rate Variability Used as an Arrhythmia Risk Stratifier After Myocardial Infarction

Heart rate variability (HRV) is considered to represent a noninvasive tool to assess cardiac autonomic tone at the level of the sinus node. It has been shown to have predictive power for risk assessment in patients surviving acute myocardial infarction. For this purpose, HRV should be assessed from 24-hour Holter recordings obtained 7–10 days following the infarction. Although there is some recovery of HRV during the first 3 months after infarction, HRV remains reduced in postinfarction patients compared to values obtained in healthy individuals. Compared to assessment of left ventricular function as a risk marker, HRV is superior with respect to prediction of arrhythmic events and sudden death whereas both parameters yield comparative power for prediction of total cardiac mortality. Since the predictive power of HRV analysis alone is relatively low, the combined use of HRV measurements together with traditional risk markers (such as ventricular ectopic beats, signal-averaged ECG, or left ventricular function) results in improved risk prediction with positive predictive accuracy in the range of 30%–50%.     

Variability of Holter electrocardiographic findings in patients fulfilling the noninvasive MADIT criteria. Multicenter Automatic Defibrillator Implantation Trial

In the MADIT study, a selected group of postinfarction patients with asymptomatic nonsustained ventricular tachycardia (NSVT) has been shown to benefit from prophylactic ICD treatment. The present study analyzed the variability of NSVT in a patient population fulfilling the non-invasive MADIT criteria. Three consecutive Holter ECGs were performed in weekly intervals in 68 postinfarction patients with an LVEF < or = 0.35. Patients with NSVT underwent programmed ventricular stimulation (PVS); patients were implanted with an ICD if sustained VT or VF was inducible. If NSVT was found in at least two recordings, the arrhythmia was defined as reproducible. In 28 (41%) of the 68 patients, NSVT was found in at least one recording. Seventeen patients revealed NSVT in the first, the remaining 11 in the second registration; no patient had NSVT only in the third Holter. Of the patients with NSVT, 50% had only one, 39% had two, and 11% had three positive recordings. Thus, reproducible NSVT was found in only 50% of the patients with NSVT. Predictors for reproducibility were LVEF > 0.27, NYHA Class I, absence of digitalis therapy, and > 2 NSVT per 24-hour period. Reproducible NSVT was not associated with risk factors such as elevated mean heart rate, reduced heart rate variability, late potentials, or inducibility of sustained VT during PVS. During 17 +/- 9 months of follow-up, seven (10%) patients experienced arrhythmic events: two without and five with previously documented NSVT. In the latter patients, first occurrence of NSVT was consistently in the first Holter; only two of them had reproducible NSVT. In postinfarction patients, the risk factor NSVT exhibits marked spontaneous variability, especially in those with a low number of NSVT per 24-hour period, LVEF < 0.27 or NYHA III, which limits its clinical value as a selection criterion for PVS. Reproducibility of NSVT itself does not seem to be an independent risk factor.     

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.     

Ventricular tachyarrhythmias in patients receiving an implantable cardioverter-defibrillator for primary versus secondary prophylaxis indications

Introduction: Data on the mechanisms of sudden cardiac death are limited and may be biased by delays in rhythm recording and selection bias in survivors. As a result, the relative contributions of monomorphic ventricular tachycardia (VT) (cycle length [CL] > 260 ms), monomorphic fast VT (FVT) (CL ≤ 260 ms), and polymorphic VT (PMVT)/ventricular fibrillation (VF) have not been well characterized nor compared in patients with and without prior arrhythmic events. Methods: A retrospective cohort study of implantable cardioverter‐defibrillator (ICD) recipients with primary or secondary implant indications was used to evaluate intracardiac electrograms (EGMs) for the first spontaneous VT/VF resulting in appropriate ICD therapy. EGMs were categorized into VT, FVT, and PMVT/VF based on CL and morphologic criteria. Results: Of 616 implants, 145 patients (58 [40%] primary indications) received appropriate ICD therapy for VT/VF over mean follow‐up of 3.8 ± 3.2 years. Primary implants had more diabetes (28% vs 12%; P = 0.02) and less antiarrhythmic use (15% vs 33%; P = 0.02). In those patients with spontaneous arrhythmia, PMVT/VF occurred in 20.7% of primary versus 21.8% of secondary implants, FVT in 19.0% versus 21.8%, and VT in 60.3% versus 56.4%, respectively (P = 0.88). Spontaneous VT CL was similar regardless of implant indication (284 ± 56 [primary] vs 286 ± 67 ms [secondary]; P = 0.92). Conclusions: Monomorphic VT is the most common cause of appropriate ICD therapy regardless of implant indication. These results provide insight into the mechanisms of sudden cardiac death and have implications for the use of interventions designed to limit ICD shocks. (PACE 2011; 34:571–576)     

Filtered QRS duration on signal-averaged electrocardiography predicts inducibility of ventricular tachycardia in arrhythmogenic right ventricle dysplasia

Treatment of arrhythmogenic right ventricular dysplasia (ARVD) is mostly based on the prevention of sudden cardiac death that results from arrhythmias. A clinical history suggestive of ARVD requires careful evaluation including electrophysiological study. The potential ability to identify those patients who will have inducible VT with electrophysiological study will enable better risk stratification and selection of vulnerable patients for electrophysiologically guided therapy. The purpose of the study was to evaluate the predictive ability of signal-averaged electrocardiography (SAECG) to predict inducibility of VT in patients with ARVD. The patient population consisted of 31 ARVD patients diagnosed with McKenna's criteria who underwent electrophysiological study. Electrophysiological study was considered positive if sustained monomorphic VT was induced. The sensitivity, specificity, and predictive accuracy of various SAECG criteria for inducibility of sustained monomorphic VT were also calculated. Twenty-one patients had inducible VT. The filtered QRS duration (fQRS), duration of signal <40 uV (LAS40), and root mean square voltage in the last 40 ms of QRS duration (RMS40) in ARVD patients induced versus noninduced were 122 +/- 21 and 103 +/- 8 ms (P=0.007), 45 +/- 20 and 28 +/- 14 ms (P=0.02), 19 +/- 19 and 32 +/- 22 uV (0.03), respectively. The ejection fractions were comparable in both groups. fQRS duration > or =110 ms had sensitivity of 91%, specificity of 90%, and a total predictive accuracy of 90% in predicting inducibility of VT in these patients. Filtered QRS duration on SAECG is predictive of electrophysiological study outcome in ARVD. Further studies will be needed to determine if SAECG results can predict the development of ventricular arrhythmias during follow-up.     

Value of Heart Rate Variability Parameters for Prediction of Serious Arrhythmic Events in Patients with Malignant Ventricular Arrhythmias

Heart rate variability (HRV) assesses the electrical stability of the heart and can identify patients at risk of sudden cardiac death (SCD). The value of 10 HRV parameters from 24 hour ECG (in both time and frequency domain) to predict serious arrhythmic events (SAE) in a group of 56 patients with ventricular tachycardia and/or ventricular fibrillation of different etiologies not due to acute myocardial infarction was explored. Eighteen patients had low left ventricular ejection fractions (LVEF). During follow-up (6–46 months, mean = 24) 8 SCD and 12 recurrences of malignant ventricular arrhythmias or ICD discharges were recorded. Proportional hazard analysis (Cox model) for SAE revealed that the mean of all 5 minute standard deviation of RR intervals (SD) and the amplitude of low frequency spectrum (L) were independent risk factors of SAE (P < 0.05). The best models were: SD+EF and L+EF where predictive values were high (sensitivity approximately 60%, specificity over 95%, positive predictive value over 90% and negative predictive value approximately 80%). Event-free survival curves revealed a significantly shorter survival in patients with EF < 40%: 47% vs. 92%, SD < 43 ms; 56% vs. 92% and L < 16 ms; 56% vs. 89% (all P < 0.001) after 2 years. The subgroup with low EF and SD < 43 ms revealed a significantly shortened survival (27% vs 83% at 2 years, P < 0.01). Some HRV parameters, SD from the time and L from the frequency domain, were predictive of a fatal outcome in VT/VF patients. Combined SD +EF and L +EF values are powerful predictors of serious arrhythmic events.     

Excessive increase in QT interval and dispersion of repolarization predict recurrent ventricular tachyarrhythmia after amiodarone

Although chronic amiodarone has been proven to be effective to suppress ventricular tachycardia (VT) and ventricular fibrillation (VF), how we predict the recurrence of VT/VF after chronic amiodarone remains unknown. This study evaluated the predictive value of the QT interval, spatial, and transmural dispersions of repolarization (SDR and TDR) for further arrhythmic events after chronic amiodarone. Eighty-seven leads body surface ECGs were recorded before (pre) and one month after (post) chronic oral amiodarone in 50 patients with sustained monomorphic VT associated with organic heart disease. The Q-Tend (QTe), the Q-Tpeak (QTp), and the interval between Tpeak and Tend (Tp-e) as an index of TDR were measured automatically from 87-lead ECG, corrected Bazett's method (QTce, QTcp, Tcp-e), and averaged among all 87 leads. As an index of SDR, the maximum (max) minus minimum (min) QTce (max-min QTce) and standard deviation of QTce (SD-QTce) was obtained among 87 leads. All patients were prospectively followed (15 +/- 10 months) after starting amiodarone, and 20 patients had arrhythmic events. The univariate analysis revealed that post max QTce, post SD-QTce, post max-min QTce, and post mean Tcp-e from 87-lead but not from 12-lead ECG were the significant predictors for further arrhythmic events. ROC analysis indicated the post max-min QTce > or = 106 ms as the best predictor of events (hazard ratio = 10.4, 95%, CI 2.7 to 40.5, P = 0.0008). Excessive QT prolongation associated with increased spatial and transmural dispersions of repolarization predict the recurrence of VT/VF after amiodarone treatment.     

Prediction of short- and long-term outcomes by electrocardiography in survivors of out-of-hospital cardiac arrest

BACKGROUND: Programs focusing on early defibrillation have improved both short- and long-term survival of patients with VF out-of-hospital cardiac arrest (OHCA). Subsequent long-term management of survivors would be facilitated by a straight-forward, non-invasive method of identifying those at highest risk for recurrence. Therefore, we assessed the predictive value of the standard ECG to determine both short- and long-term outcomes in survivors of VF OHCA to assist in risk stratification of those patients at highest risk of sudden death. METHODS: All patients with an OHCA between November 1990 and December 2000 who received early defibrillation for VF in Olmsted County Minnesota (MN) were included. Cox proportional hazards modeling was used to examine ECG variables and subsequent ICD deployment and death. RESULTS: Two hundred patients presented in VF OHCA; of these 138 (69%) survived to hospital admission (seven died in the emergency department prior to admission) and 79 (40%) were discharged. The QRS duration (141 +/- 41ms in nonsurvivors, 123 +/- 35 in survivors, P = 0.004) was predictive of short-term mortality in patients who did not survive to hospital discharge. The ventricular rate, PR interval, presence of right or left bundle branch block, QTc, ST elevation myocardial infarction, and atrial fibrillation/flutter were nonpredictive. The average length of follow up for hospital dismissal survivors was 4.8 +/- 3.0 years. In univariate analysis, each 30 ms interval increase in the QRS width and PR interval was associated with increased mortality and ICD deployment hazard ratio of 1.6 (CI 1.1-2.5, P = 0.02) and 1.12 (CI 1.0-1.2, P = 0.05), respectively. In multivariate analysis accounting for admission ejection fraction, a PR > 200 ms [HR 4.5 (CI 1.7-11.8, P = 0.022)], QRS width increase greater than 30 ms [HR 1.9 (CI 1.3-2.8, P < 0.001)], and a QRS > 120 ms [HR 2.4 (CI 1.1-5.4, P = 0.032)] were predictive of long-term mortality and ICD shocks. CONCLUSION: Careful evaluation of the admitting and discharge ECG provides prognostic information for in-hospital and long-term outcomes, respectively in this cohort of out-of-hospital cardiac arrest survivors. The QRS duration on the dismissal ECG following VF OHCA provides prognostic information which might be useful to identify those at highest risk long-term, and who would benefit from more aggressive antiarrhythmic therapy and cardiac stabilization.     

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).     

Predictive Characteristics of Holter-Based Postinfarction Risk Stratifiers Appear Superior to Electrophysiological Testing

Prevalent low-frequency (PLF) oscillation of heart rate and turbulence slope (TS) are both powerful postmyocardial infarction (MI) risk factors. Abnormal composite risk stratifier (CRS) was defined as abnormal PLF or abnormal TS when PLF was not analyzable. We compared the predictive power of CRS with the previously published predictive value of conventional electrophysiological (EP) testing based on the presence of nonsustained ventricular tachycardia (NSVT) and inducibility of sustained ventricular tachycardia/fibrillation (VT/VF) during programmed ventricular stimulation (PVS). PLF and TS were calculated from baseline Holter recordings in the placebo population of European Amiodarone Infarction Myocardial Infarction Trial (EMIAT trial) (n = 633; LVEF ≤ 40%; 87 deaths; 22-month follow-up). Previously established cut-off values of PLF ≥ 0.1 Hz and TS ≤ 2.5 ms/RR were used. The clinical characteristics of the EMIAT population were similar to those of the Multicenter Unsustained Tachycardia Trial (MUSTT trial). Therefore, we compared the predictive power of CRS and conventional PVS using the values of 35% VT/VF inducibility during PVS in NSVT patients, and a 33% and 50% increase in all-cause and arrhythmic mortality, respectively, associated with VT/VF inducibility in MUSTT. Projecting the predictive power of PVS in MUSTT into the EMIAT population yielded a sensitivity of 13.8% and 14.0% and positive predictive value (PPV) of 27.9% and 14.0% for all-cause and arrhythmic mortality, respectively, whereas an abnormal CRS was associated with sensitivities of 46.0% and 46.5% and PPV of 37.4% and 18.7%. Compared with the noninvasive Holter-based CRS, invasive PVS appears inferior in the identification of high-risk post-MI patients with left ventricular dysfunction.     

Induced Sustained Ventricular Tachycardia in Nonischemic Dilated Cardiomyopathy: Dependence on Clinical Presentation and Response to Antiarrhythmic Agents

Thirty-one patients with nonischemic dilated cardiomyopathy either idiopathic or due to regurgitant valvular disease were studied in the cardiac electrophysiology lab. The indications for study were sustained ventricular tachycardia (VT) in 26, ventricular fibrillation (VF) in 11, and syncope of unknown etiology in 4. Sustained VT was reproducibly induced in 17 patients, including 12 with a history of sustained VT, 2 with VF and 3 with syncope. Of 15 patients undergoing serial antiarrhythmic drug studies, sustained VT was rendered noninducible or nonsustained in 23. Three had recurrent arrhythmic events while on therapy predicted to be effective. One of 2 patients discharged on a regimen predicted to be ineffective had a recurrence of sustained VT that resulted in cardiac arrest. Of 14 patients in whom sustained VT could not he reproducibly induced, 2 subsequently had spontaneous occurrences of sustained VT, and 2 experienced aborted sudden death. These results suggest the following; (1) the induction of sustained VT in the setting of nonischemic dilated cardiomyopathy is dependent on the clinical presentation; (2) antiarrhythmic drugs frequently render sustained VT noninducible or nonsustained; (3) antiarrhythmic drug suppression of inducible sustained VT predicts long-term prevention of spontaneous recurrences; and (4) noninducibility of sustained VT in the baseline state does not predict freedom from subsequent episodes of VT or sudden death.     

Electrophysiologic studies of patients with hypertrophic cardiomyopathy presenting with syncope of undetermined etiology

Patients with hypertrophic cardiomyopathy (HC) have a high risk of sudden death. The best clinical predictors of sudden death from HC are young age, strong family history of sudden death, ventricular tachycardia (VT), and progression of symptoms such as syncope. We performed 24-hour Holter monitoring and electrophysiologic studies (EPS) on 26 patients with HC, some with the obstructive form of the disease and some with syncope, in order to predict their vulnerability to syncope and to potentially malignant arrhythmias. Holter monitoring demonstrated supraventricular tachycardia (SVT) in 9/26 patients whereas atrial programmed electrical stimulation induced SVT in 17/26 patients. Of the 17 patients, nine had symptomatic hypotension with SVT while lying supine. Holter monitoring demonstrated nonsustained VT in 7/26 patients whereas ventricular programmed electrical stimulation induced VT or ventricular fibrillation (VF) in 6/26 patients. The patient who had the longest run of nonsustained VT on Holter had VF induced by ventricular programmed electrical stimulation. He was cardioverted to normal sinus rhythm with no untoward effects. We found that atrial programmed electrical stimulation induced SVT with hypotension best predicted a history of syncope in these patients. Although one patient required direct current cardioversion, EPS was conducted safely in all patients. Further long-term studies are needed to demonstrate the value of clinical decisions based upon EPS in patients with HC.     

Time-Domain Signal-Averaged Electrocardiogram in Nonischemic Ventricular Tachycardia

The prevalence of late ventricular potentials (LVPs) detected by signal averaged ECG (SAECG) is variable in nonischemic heart diseases. In idiopathic dilated cardiomyopathy, the prevalence increases from about 25% to 70%-90% in cases of spontaneous sustained ventricular tachycardia (VT), is not significantly correlated with hemodynamic and Holter data, and has a good positive predictive value for induced and spontaneous sustained VT. However, its predictive value for cardiac death has not been established. In primary hypertrophic cardiomyopathy, LVPs are rare (about 10%), not correlated to hemodynamic data, enhanced in cases of spontaneous sustained VT (up to 77%), and have a good predictive value of induced VT. LVP-SAECG are frequent in arrhythmogenic right ventricular dysplasia (ARVD) (70%-80%). They can identify patients with VT and an unapparent or limited form of this disease, or ARVD with few ventricular arrhythmias. The prevalence (26%-37%) of LVPs in mitral valve prolapse is clearly higher than in normal individuals or in other valvular diseases and is enhanced in cases of spontaneous and induced VT. Its significance remains speculative. After surgical repair of tetralogy of Fallot, LVPs can identify a group of patients with higher probability of induced and spontaneous risk of VT. The usefulness and significance of LVPs in other nonischemic cardiac diseases have not to date been established. In "true" idiopathic VT, without proved structural cardiac disease, the prevalence of LVPs does not exceed that observed in normal individuals (0%-5%), but in "apparent" idiopathic VT the prevalence of LVPs rises to 20%-40%. In these latter cases more invasive techniques must be used to discover a limited form of myocardiopathy.