Thomas Klingenheben

Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure

Measurement of microvolt level T-wave alternans in the surface electrocardiogram is a novel way to assess the risk of ventricular arrhythmias. Seven tests of arrhythmic risk, including T-wave alternans, were undertaken in 107 consecutive patients with congestive heart failure and no history of sustained ventricular arrhythmias; the patients were followed up for arrhythmic events during the next 18 months. Of the patients with events, 11 had positive and two indeterminate T-wave alternans results; there were no arrhythmic events among patients with negative T-wave alternans results. Of the seven tests, only T-wave alternans was a significant (p=0.0036) and independent predictor of arrhythmic events.

Microvolt T-wave alternans physiological basis, methods of measurement, and clinical utility--consensus guideline by International Society for Holter and Noninvasive Electrocardiology.

This consensus guideline was prepared on behalf of the International Society for Holter and Noninvasive Electrocardiology and is cosponsored by the Japanese Circulation Society, the Computers in Cardiology Working Group on e-Cardiology of the European Society of Cardiology, and the European Cardiac Arrhythmia Society. It discusses the electrocardiographic phenomenon of T-wave alternans (TWA) (i.e., a beat-to-beat alternation in the morphology and amplitude of the ST-segment or T-wave). This statement focuses on its physiological basis and measurement technologies and its clinical utility in stratifying risk for life-threatening ventricular arrhythmias. Signal processing techniques including the frequency-domain Spectral Method and the time-domain Modified Moving Average method have demonstrated the utility of TWA in arrhythmia risk stratification in prospective studies in >12,000 patients. The majority of exercise-based studies using both methods have reported high relative risks for cardiovascular mortality and for sudden cardiac death in patients with preserved as well as depressed left ventricular ejection fraction. Studies with ambulatory electrocardiogram-based TWA analysis with Modified Moving Average method have yielded significant predictive capacity. However, negative studies with the Spectral Method have also appeared, including 2 interventional studies in patients with implantable defibrillators. Meta-analyses have been performed to gain insights into this issue. Frontiers of TWA research include use in arrhythmia risk stratification of individuals with preserved ejection fraction, improvements in predictivity with quantitative analysis, and utility in guiding medical as well as device-based therapy. Overall, although TWA appears to be a useful marker of risk for arrhythmic and cardiovascular death, there is as yet no definitive evidence that it can guide therapy.

Analysis of 12-Lead T-Wave Morphology for Risk Stratification After Myocardial Infarction

BackgroundThe stratification of post–myocardial infarction (MI) patients at risk of sudden cardiac death remains important. The aim of the present study was to assess the prognostic value of novel T-wave morphology descriptors derived from resting 12-lead ECGs. Methods and ResultsIn 280 consecutive post-MI patients, a 12-lead ECG was recorded before discharge, optically scanned, and digitized. For the present study, 5 T-wave morphology descriptors were automatically calculated after singular value decomposition of the ECG signal. The total cosine R-to-T (TCRT [describes the global angle between repolarization and depolarization wavefront]) and the T-wave loop dispersion were univariately associated (P =0.0002 and P <0.002, respectively, U test) with 27 prospectively defined clinical events in 261 patients (mean follow-up 32±10 months). Kaplan-Meier event probability curves for strata above and below the median confirmed the strong risk discrimination by TCRT and T-wave loop dispersion (P <0.003 and P <0.001, respectively, log-rank test). On Cox regression analysis, with the entering of age, left ventricular ejection fraction, heart rate, QRS width, reperfusion therapy, &bgr;-adrenergic–blocker treatment, and standard deviation of R-R intervals on 24-hour Holter monitoring, TCRT (P <0.03) yielded independent predictive value, whereas T-wave loop dispersion was of borderline independence (P =0.064). Heart rate (P <0.02), left ventricular ejection fraction (P <0.02), and reperfusion therapy (P <0.02) also remained in the final model. ConclusionsComputerized T-wave morphology analysis of the 12-lead resting ECG permits independent assessment of post-MI risk and an improved risk stratification when combined with other risk markers.

Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study

OBJECTIVES This study was designed to evaluate the ability of microvolt-level T-wave alternans (MTWA) to identify prospectively patients with idiopathic dilated cardiomyopathy (DCM) at risk of ventricular tachyarrhythmic events and to compare its predictive accuracy with that of conventional risk stratifiers. BACKGROUND Patients with DCM are at increased risk of sudden death from ventricular tachyarrhythmias. At present, there are no established methods of assessing this risk. METHODS A total of 137 patients with DCM underwent risk stratification through assessment of MTWA, left ventricular ejection fraction, baroreflex sensitivity (BRS), heart rate variability, presence of nonsustained ventricular tachycardia (VT), signal-averaged electrocardiogram, and presence of intraventricular conduction defect. The study end point was either sudden death, resuscitated ventricular fibrillation, or documented hemodynamically unstable VT. RESULTS During an average follow-up of 14 +/- 6 months, MTWA and BRS were significant univariate predictors of ventricular tachyarrhythmic events (p < 0.035 and p < 0.015, respectively). Multivariate Cox regression analysis revealed that only MTWA was a significant predictor. CONCLUSIONS Microvolt-level T-wave alternans is a powerful independent predictor of ventricular tachyarrhythmic events in patients with DCM.

Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope.

Background— Previous studies that assessed the effects of &bgr;-blockers in preventing vasovagal syncope provided mixed results. Our goal was to determine whether treatment with metoprolol reduces the risk of syncope in patients with vasovagal syncope. Methods and Results— The multicenter Prevention of Syncope Trial (POST) was a randomized, placebo-controlled, double-blind, trial designed to assess the effects of metoprolol in vasovagal syncope over a 1-year treatment period. Two prespecified analyses included the relationships of age and initial tilt-test results to any benefit from metoprolol. All patients had >2 syncopal spells and a positive tilt test. Randomization was stratified according to ages <42 and ≥42 years. Patients received either metoprolol or matching placebo at highest-tolerated doses from 25 to 200 mg daily. The main outcome measure was the first recurrence of syncope. A total of 208 patients (mean age 42±18 years) with a median of 9 syncopal spells over a median of 11 years were randomized, 108 to receive metoprolol and 100 to the placebo group. There were 75 patients with ≥1 recurrence of syncope. The likelihood of recurrent syncope was not significantly different between groups. Neither the age of the patient nor the need for isoproterenol to produce a positive tilt test predicted subsequent significant benefit from metoprolol. Conclusions— Metoprolol was not effective in preventing vasovagal syncope in the study population.

Open infarct artery, late potentials, and other prognostic factors in patients after acute myocardial infarction in the thrombolytic era. A prospective trial.

BACKGROUND Successful reperfusion of the infarct-related artery in patients with acute myocardial infarction has been shown to reduce in-hospital as well as 1-year mortality. Besides the thrombolysis-induced myocardial salvage, there is increasing evidence that an open infarct-related artery results in increased electrical stability of the heart and that this effect is at least in part responsible for the favorable long-term outcome of these patients. The exact incidence of arrhythmic events during the first year after myocardial infarction and the predictive value of different risk factors for these complications, however, have not been determined in patients in the thrombolytic era. METHODS AND RESULTS A total of 173 patients with acute myocardial infarction, 51% treated with thrombolysis, were prospectively entered into the study. At the time of hospital discharge, signal-averaged ECG, Holter monitoring, radionuclide angiography, coronary angiography, and levocardiography were performed in all patients. An open infarct-related artery was documented in 136 patients. The overall incidence of late potentials was 24% (41 patients). By multivariate analysis, an occluded infarct-related artery (P = .04) and the presence of regional wall motion abnormalities (P = .02) were the strongest independent predictors for the development of a late potential. Residual ischemia was treated by either percutaneous transluminal coronary angioplasty or surgery in 86 of 173 patients (50%). Seventy percent of the patients received beta-blocker therapy. During a mean follow-up of 12 +/- 5 months, 7 patients died suddenly or had ventricular fibrillation documented, while only 2 developed sustained monomorphic ventricular tachycardia. Overall 1-year mortality was 4.1%. Multivariate analysis revealed only an occluded infarct-related artery as an independent predictor of arrhythmic complications (P = .017). CONCLUSIONS In patients with acute myocardial infarction treated according to contemporary therapeutic guidelines, with a large proportion of individuals undergoing coronary artery revascularization, a low incidence of arrhythmic events, particularly of ventricular tachycardia, was observed in the first year after the index infarction. The presence or absence of an open infarct-related artery was the strongest independent predictor of these events, whereas other traditional risk factors, such as late potentials, were less helpful in identifying patients prone to sudden death. These findings emphasize the importance of the open artery hypothesis in patients recovering from acute myocardial infarction.

Effect of metoprolol and d,l-sotalol on microvolt-level T-wave alternans: Results of a prospective, double-blind, randomized study

OBJECTIVES The study evaluated the effects of metoprolol, a pure beta-blocker, and d,l-sotalol, a beta-blocker with additional class III antiarrhythmic effects, on microvolt-level T-wave alternans (TWA). BACKGROUND Assessment of TWA is increasingly used for purposes of risk stratification in patients prone to sudden death. There are only sparse data regarding the effects of beta-blockers and antiarrhythmic drugs on TWA. METHODS Patients with a history of documented or suspected malignant ventricular tachyarrhythmias were eligible. All patients underwent invasive electrophysiologic (EP) testing including programmed ventricular stimulation and determination of TWA at increasing heart rates using atrial pacing. Reproducibility of TWA at two consecutive drug-free baseline measurements was tested in a random patient subset. Following baseline measurements, all patients were randomized either to double-blind intravenous infusion of sotalol (1.0 mg/kg) or metoprolol (0.1 mg/kg). Results of TWA assessment at baseline and after drug exposure were compared. RESULTS Fifty-four consecutive patients were studied. In 12 patients, repetitive baseline measurement of TWA revealed stable alternans voltage (V(alt)) values (9.1 +/- 5.8 microV vs. 8.5 +/- 5.7 microV, p = NS). After drug administration, V(alt) decreased by 35% with metoprolol (7.9 +/- 6.0 microV to 4.9 +/- 4.2 microV; p < 0.001) and by 38% with sotalol (8.6 +/- 6.8 microV to 4.4 +/- 2.3 microV; p = 0.001). In eight patients with positive TWA at baseline, repeated measurement revealed negative test results. CONCLUSIONS In patients prone to sudden cardiac death, there is a reduction in TWA amplitude following the administration of antiadrenergic drugs. This result indicates that TWA is responsive to the pharmacologic milieu and suggests that, to assess a patients risk of spontaneous ventricular arrhythmia, the patient should be tested while maintaining the pharmacologic regimen under which the risk of arrhythmia is being assessed. This applies particularly for beta-blocker therapy.

Prevalence, Characteristics and Prognostic Value During Long-Term Follow-up of Nonsustained Ventricular Tachycardia After Myocardial Infarction in the Thrombolytic Era

OBJECTIVES The purpose of this study was to determine the prevalence, characteristics and the predictive value of nonsustained ventricular tachycardia (VT) for subsequent death and arrhythmic events after acute myocardial infarction (AMI). BACKGROUND Nonsustained VT has been linked to an increased risk for sudden death in coronary patients. It is unknown whether this parameter can be used for selection of high-risk patients to receive an implantable defibrillator for primary prevention of sudden death in patients shortly after AMI. METHODS In 325 consecutive infarct survivors, 24-h Holter monitoring was performed 10+/-6 days after AMI. All patients underwent coronary angiography, determination of left ventricular function and assessment of heart rate variability (HRV). Mean follow-up was 30+/-22 months. RESULTS There was a low prevalence (9%) of nonsustained VT shortly after AMI. Nonsustained VT together with depressed left ventricular ejection fraction (LVEF) was found in only 2.4% of patients. During follow-up, 25 patients reached one of the prospectively defined end points (primary composite end point of cardiac death, sustained VT or resuscitated ventricular fibrillation; secondary end point: arrhythmic events). Kaplan Meier event probability analyses revealed that only HRV, LVEF and status of the infarct-related artery were univariate predictors of death or arrhythmic events. The presence of nonsustained VT carried a relative risk of 2.6 for the primary study end point but was not a significant predictor if only arrhythmic events were considered. On multivariate analysis, only HRV, LVEF and the status of the infarct artery were found to be independently related to the primary study end point. CONCLUSIONS There is a low prevalence of nonsustained VT shortly after AMI. Only 2% to 3% of all infarct survivors treated according to contemporary guidelines demonstrate both depressed LVEF and nonsustained VT. The predictive value of nonsustained VT for subsequent mortality and arrhythmic events is inferior to that of impaired autonomic tone, LVEF or infarct-related artery patency. Accordingly, the use of nonsustained VT to select patients for primary implantable cardioverter/defibrillator prevention trials shortly after AMI appears to be limited.

Association Between Atrial Fibrillation and Appropriate Implantable Cardioverter Defibrillator Therapy:Results from a Prospective Study

Atrial Fibrillation and Appropriate ICD Therapy. Introduction: Atrial fibrillation(AF) is associated with significant morbidity and mortality that may be related to heniodynamic Impairment, thromboembolic events, or enhanced electrical instability of the ventricular myocardium. There is, however, a lack of data concerning the association of AF and ventricular tachyarrhythmias.

Age of first faint in patients with vasovagal syncope.

Introduction: Understanding whether vasovagal syncope is a lifelong disorder might shed insight into its physiology and affect management strategies. Accordingly, we determined the age of the first syncopal spell in adult patients who sought care for syncope.