[Autonomic dysfunction and orthostatic intolerance].
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Autonomic Nervous System Diseases↗
Biomedical subjects
T Klingenheben
Publications and source records attributed to T Klingenheben.
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 patient's 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.
Adrenergic beta-Antagonists↗
Rate-dependence of QT dispersion and the QT interval: comparison of atrial pacing and exercise testing.
OBJECTIVES: The study was done to determine whether variables of QT dispersion from the 12-lead electrocardiogram (ECG) are dependent on heart rate. BACKGROUND: The dispersion of the QT interval is under evaluation as a risk marker in patients at risk for ventricular arrhythmias. Assuming that a similar rate correction is necessary as for the QT interval itself, investigators have frequently reported QTc-dispersion values utilizing the Bazett formula. It is not known whether there is a physiologic basis for such a rate correction in the human heart. METHODS: In 35 patients referred for evaluation of ventricular arrhythmias, digital 12-lead ECGs recorded at various heart rates during submaximal exercise testing and again during atrial pacing upon electrophysiologic testing were submitted to computerized interactive analysis of several ECG dispersion variables. RESULTS: Data from 11 patients were excluded due to incomplete high-quality analysis possible at all heart rates. From the remaining 24 patients, a total of 193 ECG recordings at various heart rates (ranging from 76 +/- 17 beats/min to 117 +/- 14 beats/min during atrial pacing and from 78 +/- 18 beats/min to 110 +/- 14 beats/min during exercise testing) were available. A highly significant linear relationship with heart rate was found for both the QT interval and the Q-to-T-peak interval. By contrast, standard QT interval dispersion (QTmax - QTmin), the T-peak-to-T-end interval, and the average area under the T wave did not change with increasing heart rates. CONCLUSIONS: Dispersion of the QT interval and other ECG variables of dispersion of ventricular repolarization are independent of heart rate. Therefore, it is not necessary to rate-correct these measurements.
Electrocardiography↗
Analysis of 12-lead T-wave morphology for risk stratification after myocardial infarction.
BACKGROUND: The 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 RESULTS: In 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, beta-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. CONCLUSIONS: Computerized 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.
Analysis of Variance↗
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.
Arrhythmias, Cardiac↗
[Postural orthostatic tachycardia syndrome (POTS): etiology, diagnosis and therapy].
BACKGROUND: Since the renaissance of tilt table testing in clinical cardiology some 15 years ago, the syndromes of autonomic dysfunction with orthostatic intolerance underwent improved differentiation and classification. In the present review a variant of autonomic dysfunction with orthostatic intolerance--POTS (postural orthostatic tachycardia syndrome)--will be discussed. DIAGNOSIS AND TREATMENT: The affected patients present with orthostatic intolerance, postural tachycardia, exercise intolerance, fatigue, dizziness and in some cases with other dysautonomic symptoms such as gastrointestinal or sudomotor dysfunction. Together with the clinical history, tilt table testing is the cornerstone of diagnostic evaluation by which the syndrome can be distinguished from typical neurocardiogenic disorders. POTS is characterized by different subtypes; accordingly, therapy for relief of symptoms is variable and includes beta blockers for patients with the hyperadrenergic type and alphamimetics for those with partial dysautonomia. CONCLUSION: Although it is now possible to differ POTS from other forms of autonomic dysfunction, further research is warranted to clarify the pathophysiology of this syndrome and its subtypes and to improve therapeutic interventions.
Adrenergic Agents↗
Association between atrial fibrillation and appropriate implantable cardioverter defibrillator therapy: results from a prospective study.
INTRODUCTION: Atrial fibrillation (AF) is associated with significant morbidity and mortality that may be related to hemodynamic 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. METHODS AND RESULTS: Consecutive patients with indication for an implantable cardioverter defibrillator (ICD) were classified for the presence or absence of persistent AF at the time of device implantation. Incidence of device therapy, stored electrograms, and clinical events during follow-up were evaluated prospectively. Two hundred fifty patients were included. During follow-up (20+/-14 months), patients in AF experienced appropriate device therapy for recurrent ventricular arrhythmias more frequently compared with patients in sinus rhythm (SR) (63% vs 38%, P = 0.01). On multivariate analysis, AF was an independent predictor of appropriate ICD therapy (relative risk 1.8; 95% confidence interval [CI] 1.2 to 2.9) and inappropriate device therapy (relative risk 2.3; 95% CI 1.2 to 4.5). Predefined clinical events (cluster endpoint: death, syncope, and hospitalizations) were observed more frequently in AF than in SR patients (55% vs 31%, P = 0.01). Analysis of device-stored electrograms revealed a higher incidence of short-long-short cycles preceding ventricular arrhythmias in AF compared with SR patients (50% vs 16%, P = 0.002). Baseline heart rate preceding ventricular arrhythmias did not differ between the two groups. CONCLUSION: AF is an independent predictor of recurrent ventricular arrhythmias in ICD recipients. The underlying electrophysiologic mechanism seems to be irregular rather than rapid ventricular activation, with a high incidence of short-long-short sequences preceding ventricular tachyarrhythmias in AF patients.
Aged↗
Adenosine-induced atrial fibrillation.
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Adenosine↗
[Microvolt level T wave alternans: a new marker for noninvasive risk stratification].
Prospective identification of patients with structural heart disease who could profit from prophylactic ICD therapy is hampered by the low predictive power of the currently available risk stratification parameters. Microvolt T wave alternans measured noninvasively is a new promising parameter to assess impaired ventricular repolarization which has been associated with an increased incidence of ventricular tachyarrhythmias. T wave alternans is rate-dependent; to induce alternans, heart rate may be increased by atrial stimulation during invasive EP testing or noninvasively by exercise stress testing. The first clinical validation with respect to prediction of inducibility of ventricular tachyarrhythmias and of arrhythmic events during follow-up in patients undergoing invasive EP testing was reported in 1994. Subsequently, a good concordance between the results of invasive and noninvasive assessment of T wave alternans was demonstrated by our group. The first prospective evaluation of the noninvasive alternans measurement using submaximal exercise testing was performed in patients surviving prehospital ventricular fibrillation or sustained ventricular tachycardia referred to our institution. The occurrence of T wave alternans in this patient population was predictive of future tachyarrhythmic events with subsequent appropriate ICD therapy. The results of the currently performed prospective trials in various patient populations will help to establish the utility of T wave alternans assessment as a risk stratifier in clinical practice.
Action Potentials↗
[Cardiac autonomic tone in risk stratification after myocardial infarct: results of a prospective long-term study of 411 consecutive patients].
Prognosis of patients surviving acute myocardial infarction has substantially improved over the last two decades. However, stratification of patients at risk for death due to arrhythmic events remains a clinical challenge. Due to the important role of the autonomic nervous system in the genesis of sudden death, autonomic markers such as heart rate variability and baroreflex sensitivity have recently gained attention as risk stratification parameters. The present study reports the results of noninvasive risk stratification in 411 consecutive postinfarction patients treated due to contemporary therapeutical guidelines with a high proportion of patients discharged with a patent infarct related artery. The diagnostic arsenal of risk parameters comprised heart rate variability, baroreflex sensitivity, and more traditional markers such as non-sustained ventricular tachycardia, left ventricular ejection fraction, and ventricular late potentials. Patients were followed for a mean of 33 +/- 21 months. Stepwise logistic regression analysis revealed that left ventricular function, both autonomic markers, and the patency of the infarct related artery were independent predictors of the prospectively defined primary study endpoint, i.e., all-cause mortality plus ventricular tachyarrhythmic events. With respect to the secondary endpoint (ventricular tachyarrhythmic events), left ventricular function, heart rate variability, and infarct vessel patency were independent predictors. Ventricular late potentials and nonsustained ventricular tachycardia had no predictive value with respect to ventricular tachyarrhythmic events. These findings from a large prospective long-term study demonstrate the value of markers of cardiac autonomic tone in identifying infarct survivors at risk for malignant ventricular tachyarrhythmias and sudden death.
Adult↗
[Syndromes of autonomic insufficiency associated with orthostatic intolerance: classification, diagnostic and therapeutic approach].
Stimulated by the widespread use of tilt table testing, disorders of autonomic function with orthostatic hypotension have recently gained attention by clinical cardiologists. At the same time, improved characterization of the underlying circulatory responses have led to a reclassification of these syndromes. In particular, three subgroups of chronic primary dysautonomia have been defined such as Pure Autonomic Dysfunction, Multiple System Atrophy, and the Postural Orthostatic Tachycardia Syndrome. On the other hand, acute dysautonomias represent a rare yet clinically sometimes dramatic form of autonomic disorders. Several diseases as well as enzymatic disorders, and pharmacological drugs may cause secondary dysautonomia. The clinical correlate of all these forms of dysautonomia is orthostatic hypotension and syncope. Thus, a careful history forms the basis of a successful diagnostic workup of the underlying cause of syncope. This review summarizes the current knowledge of autonomic disorders, their classification and diagnostic and therapy strategies.
Autonomic Nervous System Diseases↗
[T-wave alternans in microwave frequency as a new indicator of disordered ventricular repolarization: pathophysiology, methodology, clinical results].
Primary prevention of sudden cardiac death is hampered by the inability to accurately identify high risk patients. Various noninvasive methods such as determination of left ventricular function or heart rate variability as well as invasive electrophysiologic testing are currently used for risk stratification. Noninvasive measurement of microvolt T wave alternans (TWA) is a promising new method to assess repolarization abnormalities; in experimental studies, TWA was associated with an increased incidence of ventricular tachyarrhythmias. Since the occurrence of TWA is heart rate-dependent, it is measured either during atrial pacing or during exercise stress testing. The first clinical validation of the method was performed in patients undergoing invasive EP testing to assess prediction of inducibility of ventricular tachyarrhythmias. A first prospective validation of the noninvasive method was performed in patients surviving out-of-hospital cardiac arrest fitted with an ICD. Further studies have shown a good concordance between invasive and noninvasive TWA determination. The occurrence of TWA in this population was of predictive value with respect to arrhythmia recurrence. Recently published data confirm the value of TWA assessment with respect to identification of patients with congestive heart failure at high risk of malignant ventricular tachyarrhythmias. The use of this method in post myocardial infarction risk stratification is currently under prospective evaluation.
Cardiac Pacing, Artificial↗
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.
Adult↗
First worldwide clinical experience with a new dual chamber implantable cardioverter defibrillator. Advantages and complications. The Ventak AV II DR investigators.
AIMS: The need for physiological pacing and for improving the ability to discriminate atrial from ventricular tachyarrhythmias has prompted the development of dual chamber implantable cardioverter/defibrillators (ICDs). METHODS: Fifty-two patients were implanted with a newly developed dual-chamber ICD providing rate-responsive physiological pacing (Ventak AV II DR). The device possesses two new arrhythmia detection algorithms ('atrial fibrillation rate threshold' and 'ventricular to atrial rate relationship') in addition to commonly used features such as 'onset' and 'stability'. During implantation, the atrial and ventricular lead impedances and pacing thresholds were determined together with the defibrillation threshold. Prior to discharge, attempts were made to induce both atrial and ventricular tachyarrhythmias in order to test those new detection criteria. All patients were followed for at least 3 months. RESULTS: The device was successfully implanted in all 52 patients. Placement of the atrial lead was successful in 50/52 patients (96%; P-wave 3.2 +/- 1.4 mV; impedance 576 +/- 123 omega; atrial pacing threshold 1.2 +/- 0.9 V). Prior to discharge, 32 episodes of atrial fibrillation (AF) alone, 38 episodes of AF with ventricular fibrillation and 10 episodes of AF with monomorphic ventricular tachycardia were induced in 33/50 patients (66%) and all were appropriately classified by the detection algorithm. During the 3 months follow-up, 12 patients (23%) had appropriate and successful therapies for ventricular arrhythmias, while four patients (8%) experienced inappropriate ICD therapies. Although all these episodes were detected correctly as supraventricular arrhythmias by the device, therapy was delivered because of incorrect or incomplete programming. In all cases reprogramming of the device resolved the problem. CONCLUSION: Implantation of dual chamber ICDs is feasible and appears to improve discrimination of supraventricular from ventricular tachyarrhythmias. In addition, patients with tachyarrhythmias and concomitant bradyarrhythmias may benefit from simultaneous physiological pacing. However, implantation and follow-up of such patients should be performed at experienced centres since both surgical handling and programming of these devices is more difficult and complex than conventional ICDs.
Algorithms↗
Prospective evaluation of a two-step therapeutic strategy in neurocardiogenic syncope: midodrine as second line treatment in patients refractory to beta-blockers.
Pharmacological therapy of neurocardiogenic syncope is often limited by the relatively low response rate to such treatment. In particular, response to beta-blocker treatment has been reported to average 50%. Therefore, a two-step protocol, with metoprolol being the drug of first choice, was developed and prospectively evaluated in consecutive patients with a history of repeated syncopal attacks and a positive tilt table test indicative of neurocardiogenic syncope. Patients not responding to the beta-blocker were switched to the alpha-adrenoceptoragonist midodrine. Acute drug efficacy was assessed by repeated tilt table testing. The incidence of syncope recurrence rate was determined during a 7-month follow-up. In 16 of 30 (53%) patients, metoprolol was primarily effective; this was also the case in 7 of 11 patients receiving midodrine. Thus, the overall efficacy rate could be increased to 77% by the treatment protocol (P = 0.009, as compared to beta-blocker treatment alone). During follow-up, only 1 of 27 patients (4%) had a syncopal event. Thus, the two-step treatment protocol presented in this study proved to be safe and to improve significantly patients clinical symptoms, as well as results of repeated tilt table testing as compared to beta-blocker treatment alone.
Adrenergic alpha-Agonists↗
Assessment of QT dispersion for prediction of mortality or arrhythmic events after myocardial infarction: results of a prospective, long-term follow-up study.
BACKGROUND: Risk stratification by means of analysis of QT dispersion (QTD) in the 12-lead surface ECG is under intense investigation in various patient populations. The aim of the present prospective study was to evaluate the prognostic value of QTD and other ECG variables reflecting dispersion of ventricular repolarization in comparison with established risk stratifiers during long-term follow-up in a large cohort of post-myocardial infarction patients treated according to contemporary therapeutic guidelines. METHODS AND RESULTS: In 280 consecutive infarct survivors, the 12-lead ECG was optically scanned and digitized for analysis of QTD (QTmax-QTmin) and 25 other repolarization variables, including recently developed and validated parameters such as the T peak-to-T end interval and the area under the T wave. In addition, a variety of established risk stratifiers were assessed. After a mean follow-up period of 32+/-10 months, 30 patients reached one of the prospectively defined study end points (death, ventricular tachycardia, or resuscitated ventricular fibrillation). Comparisons between event and nonevent patients by means of Kaplan-Meier event probability analyses revealed that none of the ECG dispersion variables were of discriminative value. In contrast, variables such as left ventricular ejection fraction (P=0.007), mean 24-hour heart rate (P=0.022), or heart rate variability (P=0.007) proved to be potentially useful risk stratifiers in this patient population. On multivariate analysis, only LVEF, heart rate variability, and a history of thrombolysis were independent predictors of outcome. CONCLUSIONS: Determination of QTD from the surface ECG even when performed with the best available methodology failed to predict subsequent risk in this large series of infarct survivors.
Adult↗
[Brief analysis of heart rate variability in for determining prognosis in the post-myocardial infarct period: methodologically reliable alternative to long-term ECG?].
Heart rate variability (HRV) has been established as an important risk parameter in patients surviving myocardial infarction. Recently, analysis of HRV-particularly of the standard deviation of NN intervals (SDNN)--from short term ECG recordings has been proposed as an alternative to that from 24 hour Holter monitorings. The present study is the first to compare SDNN from short term recordings to that from 24 hour recordings with respect to risk stratification after myocardial infarction. In 60 patients at the time of discharge from the hospital, SDNN from Holter monitoring averaged 93 +/- 30 ms compared to 39 +/- 18 determined from short term recordings. Patients with a prospectively defined clinical endpoint differed significantly from those with an uneventful course with respect to age, left ventricular ejection fraction, mean RR interval from Holter recording (753 +/- 153 vs 921 +/- 132 ms), mean RR from short term recording (783 +/- 153 vs 914 +/- 163 ms), and SDNN from the Hotler recording (71 +/- 27 vs 97 +/- 29 ms; p < 0.001). However, patients with and without a clinical event could not be separated by means of SDNN measured from short term ECG registrations (35 +/- 22 vs 41 +/- 19 ms; p = NS). Thus, SDNN measured from short term ECG recordings does not seem to be useful regarding risk stratification of patients after myocardial infarction. Analysis of HRV should be performed using 24 hour Holter monitoring, which provides more information and reflects circadian fluctuation in autonomic tone.
Adult↗
QT dispersion as a marker of risk in patients awaiting heart transplantation?
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Electrocardiography↗