Biomedical subjects

T Klingenheben

Publications and source records attributed to T Klingenheben.

50 records · Page 3Linked to original sources

PubMed1994

Insights into the pathogenesis of sudden cardiac death from analysis of circadian fluctuations of potential triggering factors.

Sudden cardiac death continues to be a poorly understood event in terms of its underlying pathophysiological mechanisms. The observation of a circadian variability in the incidence of this catastrophic event with a prominent peak in the early morning hours provides an opportunity to study triggering factors that may play a causative role in the genesis of sudden cardiac death. As reviewed in this article, there is convincing evidence that transient disturbances in autonomic tone and the resulting consequences may predispose the heart to increased electrical vulnerability. This evidence is based for instance on circadian fluctuations of spontaneous ventricular ectopic activity and transient ischemia, which may serve as trigger factors for the genesis of sustained ventricular tachyarrhythmias. Analysis of heart rate variability provides further evidence of reduced vagal and elevated sympathetic tone during the morning hours particularly in patients with compromised left ventricular function. Diurnal variations in ventricular repolarization as indicated by QT interval changes in the surface ECG also support the concept of triggering factors in the genesis of sudden cardiac death. Therapeutic measures aiming at a reduction in sympathetic input to the heart have been successful in preventing ventricular fibrillation and thus indicate the importance of unbalanced sympathetic tone in patients prone to sudden cardiac death.

Arrhythmias, Cardiac↗

PubMed1994

Changes in autonomic tone following thrombolytic therapy for acute myocardial infarction: assessment by analysis of heart rate variability.

INTRODUCTION: Little data are available on changes in autonomic tone during the first 24 hours of acute infarction in patients undergoing thrombolytic therapy. Particularly, the association of changes in autonomic tone to reperfusion of the infarct-related artery has not been evaluated in man. Heart rate variability (HRV) is a noninvasive tool to assess cardiac autonomic tone, which carries prognostic information in postinfarction patients. METHODS AND RESULTS: To assess changes in autonomic tone with angiographically assessed success of thrombolysis in patients with acute infarction, the proportion of adjacent RR intervals different by greater than 50 msec (pNN50) was analyzed from 24-hour Holter monitoring initiated before the start of thrombolytic therapy in 103 consecutive patients. Mean heart rate (HR) and pNN50 were available in 95 of 103 patients and were separately analyzed for the first hour after initiation of thrombolysis (reperfusion phase) and the first 24 hours. As assessed by coronary angiography 90 minutes after start of thrombolysis, 74 patients (78%) had successful coronary artery reperfusion. HR averaged 72 +/- 13/min for the first hour in all 95 patients and 74 +/- 13/min for the first 24 hours. The respective values for pNN50 were 11.2% +/- 11.7% for the first hour and 9.7% +/- 9.2% for the first 24 hours. Patients with inferior myocardial infarction (MI) had a lower mean HR of 72 +/- 12/min versus 76 +/- 13/min (P = 0.11) and a higher pNN50 (11.2% +/- 9.8% versus 7.6% +/- 8.3%, P = 0.01) compared to patients with anterior MI. The mean HR correlated weakly with pNN50 (r = -0.33, P < 0.01). For patients with coronary artery patency after 90 minutes, mean HR was 70 +/- 12/min for the first hour compared to 80 +/- 13/min for patients without (P = 0.003). For the first 24 hours, these values were 72 +/- 12/min compared to 80 +/- 14/min (P = 0.02). For the first hour, pNN50 averaged 12.6% +/- 12.4% for patients with successful reperfusion compared to 6.6% +/- 7.3% for patients without (P = 0.024). For the first 24 hours, these values were 9.2% +/- 8.5% compared to 11.5% +/- 11.3% (P = NS). Patients with in-hospital ventricular fibrillation (n = 8) had a higher mean HR throughout the first 24 hours (88 +/- 16/min vs 73 +/- 12/min, P = 0.008) compared to patients with an uneventful course. Additionally, there was a trend toward a lower HRV in patients with ventricular fibrillation. CONCLUSION: Thrombolysis-induced reperfusion of the infarct-related artery results in a higher vagal tone during the early hours of MI as compared to failed reperfusion. This finding is independent from infarct location and associated with a trend toward a lower incidence of ventricular fibrillation during the acute phase of infarction.

Acute Disease↗

PubMed1994

Reflex versus tonic vagal activity as a prognostic parameter in patients with sustained ventricular tachycardia or ventricular fibrillation.

BACKGROUND: The autonomic nervous system has been demonstrated to play a decisive role in the genesis of sudden cardiac death. The loss of protective vagal reflexes, in particular, appears to be associated with an increased incidence of malignant ventricular tachyarrhythmias. Two clinically applicable methods for assessment of cardiac autonomic control have been developed: determination of heart rate variability and evaluation of baroreflex sensitivity. METHODS AND RESULTS: To compare the potential predictive value of both methods, two groups of patients were studied. Group 1 comprised 14 postinfarction patients who had experienced at least one episode of ventricular fibrillation or sustained ventricular tachycardia and who were studied after this event. Group 2 consisted of 14 postinfarction patients without tachyarrhythmic events after their infarct. Both groups were carefully matched with respect to age, sex, infarct location, extent of coronary artery disease, left ventricular ejection fraction, blood pressure, and heart rate at rest. Heart rate variability was assessed from 24-hour Holter recordings, and baroreflex sensitivity was determined by means of the phenylephrine method. Indices of heart rate variability were not significantly different between the two groups (SD of the mean RR interval, 84 +/- 30 milliseconds versus 103 +/- 20 milliseconds; proportion of adjacent RR intervals > 50 milliseconds different, 2.8 +/- 3.2% versus 5.0 +/- 4.1% in group 1 versus 2). Baroreflex sensitivity, however, showed a striking difference: Group 1 patients had a mean value of 1.75 +/- 1.63 ms/mm Hg compared with 9.17 +/- 5.40 ms/mm Hg in group 2 (P = .0002). Eleven of 14 group 1 patients had a baroreflex sensitivity < or = 3.0 ms/mm Hg. By contrast, only 1 of 14 group 2 patients had such a depressed value. CONCLUSIONS: The results of this study indicate that postmyocardial infarction patients who develop life-threatening ventricular tachyarrhythmias, compared with carefully matched postinfarction patients without major arrhythmic episodes, differ strikingly in terms of baroreflex sensitivity but not in terms of heart rate variability. This finding may have implications for the risk stratification of postinfarction patients and may lead to a differential therapeutic strategy based on autonomic testing.

Baroreflex↗

PubMed1994

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.

Adult↗

PubMed1994

[Therapy with beta receptor blockers in myocardial infarct].

During the last 10-15 years, a total of 49 prospective, randomized, controlled studies have been performed to evaluate the efficacy and safety of early administered beta-receptor antagonists in patients with acute myocardial infarction. Those trials in which beta-receptor antagonists were administered intravenously followed by oral medication within 72 h after the onset of symptoms reported a significant reduction in early mortality (on average 13%; 95% confidence interval -2% to -25%). The efficacy of beta-receptor antagonists in reducing mortality was particularly obvious in patients at higher risk (i.e., older patients, previous infarction) with the maximal efficacy observed during the first 3-4 days of therapy. Similarly, there was a reduction in the incidence of reinfarction which averaged 19% for the patients treated with beta-receptor antagonists. The metaanalysis also showed a significant reduction in the incidence of nonfatal cardiac arrest due to primary ventricular fibrillation for the group receiving beta-receptor antagonists (average risk reduction 16%; 95% confidence interval -2% to -30%). As calculated on the basis of the ISIS-1 data, treatment with beta-receptor antagonists in approximately 200 patients with acute myocardial infarction would lead to the avoidance of one death, one reinfarction, and one episode of ventricular fibrillation. Based on these data, it is recommended that administration of beta-receptor antagonists should be an important adjunctive therapeutic modality in patients with acute myocardial infarction and no contraindications for this form of treatment.

Administration, Oral↗

PubMed1994

[Amiodarone therapy after sotalol-induced torsade de pointes: prolonged QT interval and QT dispersion in differentiation of pro-arrhythmic effects].

In a 70-year-old patient with sotalol-induced torsade de pointes, QT-dispersion in the 12-lead surface ECG was determined in an attempt to evaluate the role of this method in determining risk factors for the development of proarrhythmic effects. After recovery from torsade, the patient was successfully treated with amiodarone over a 3-month follow-up period. Whereas the degree of QT prolongation was comparable during amiodarone therapy to that observed with sotalol, QT dispersion was markedly less (47 ms) than during previous treatment with sotalol (77 ms). During drug-free control, QT dispersion was 43 ms. This case-report indicates that determination of QT dispersion can provide information with respect to identification of patients prone to class III antiarrhythmic drug-induced proarrhythmic effects.

Aged↗

PubMed1994

[Atrial fibrillation and the autonomic nervous system].

The autonomic nervous system plays an important role in the genesis of various cardiac rhythm disorders. Experimental studies have indicated that in atrial fibrillation particularly vagal activity may have a decisive influence on the electrophysiologic properties of atrial myocardium. In patients with paroxysmal atrial fibrillation, a carefully taken history and electrocardiographic findings obtained during Holter monitoring can help to distinguish vagally mediated from adrenergically mediated atrial fibrillation. The former is considered to represent a form of lone atrial fibrillation affecting particularly males aged 40 to 50 years. The arrhythmic episodes manifest themselves most often during the night lasting from minutes to hours. There is a lack of tendency towards the development of permanent atrial fibrillation. Digitalis glycosides or beta-receptor antagonists are not helpful in the therapy of this form of atrial fibrillation whereas class I antiarrhythmic drugs have been shown to be more effective. Adrenergically mediated atrial fibrillation is in general less frequently observed than the vagally-induced form. In patients with episodes of atrial fibrillation provoked by emotional or physical stress, the diagnosis of adrenergically mediated atrial fibrillation should be suspected. The episodes of atrial fibrillation occur mostly during daytime. beta-receptor antagonists play a major role in the treatment of this form of atrial fibrillation.

Adult↗

PubMed1994

[Effect of sotalol on heart rate variability in patients with symptomatic, complex ventricular arrhythmias].

Heart rate variability (HRV) as determined from 24-h Holter recordings is being recognized as a measure of cardiac autonomic control. In patients surviving myocardial infarction HRV has been established as a useful tool for risk-stratification. The effects of antiarrhythmic agents on HRV, however, have not been extensively studied. The present study therefore examined time- and frequency-domain measures of HRV in 28 patients (10 females, 18 males at a mean age of 59 +/- 15 years) with symptomatic complex ventricular arrhythmias (> 30 VPB/h plus repetitive arrhythmias) before and during treatment with sotalol, a beta-receptor blocking agent with class-III antiarrhythmic activity. Heart rate variability before treatment was independent of the density of spontaneous arrhythmias. Therapy with sotalol resulted in a significant improvement in indices of vagal tone compared to baseline (SDNN 113 +/- 45 vs. 99 +/- 43 ms (p = .05); rMSSD 39 +/- 23 vs. 30 +/- 17 ms (p = .009); pNN50 11.4 +/- 12.5 vs. 6.8 +/- 9.5% (p = .005); HF 13 +/- 7 vs. 11 +/- 7 (p = .048). This improvement was particularly evident in patients with reduced left ventricular function (LVEF < 40%) and was independent of therapy-induced changes in mean heart rate (pNN50 vs. Mean NN r = 0.37; n.s.) or suppression of ventricular arrhythmias (pNN50 vs. In VES/24 h r = 0.41; n.s.). These effects on heart rate variability and thus on cardiac autonomic tone may contribute significantly to the antifibrillatory efficacy profile of sotalol.

Adult↗

PubMed1993

Effect of sotalol on heart rate variability assessed by Holter monitoring in patients with ventricular arrhythmias.

Reduced vagal activity has been demonstrated to be associated with an increased risk of sudden death. Assessing the heart rate variability as a measure of the autonomic control of the heart has been established as a useful tool for the risk stratification of patients after myocardial infarction. In the current study, heart rate variability assessed by time- and frequency-domain measures was determined from Holter recordings before and during treatment with sotalol in 28 patients with chronic ventricular arrhythmias. The heart rate variability at baseline was independent of the presence or absence of spontaneous arrhythmias and of left ventricular function. Therapy with sotalol produced a significant improvement over control values in indices of parasympathetic tone (root mean square of the difference in successive RR intervals, proportion of adjacent RR intervals different by > 50 msec, high-frequency power spectrum). This improvement was not related to drug-induced changes in the mean heart rate or the suppression of ventricular ectopic activity. These effects on heart rate variability may contribute significantly to the overall efficacy profile of sotalol.

Adult↗

PubMed1993

[Reproducibility of heart rate variability measurements in repeated 24-hour long-term ECG registration].

Heart rate variability (HRV) is considered to indicate cardiac autonomic reflex activity. The reproducibility of HRV determinations from repeated Holter recordings has not been vigorously evaluated. This represents, however, an important question since HRV determinations are increasingly used to examine disease-related changes in the autonomic tone or the effects of therapeutic interventions. Thus, the present study examined the reproducibility of 4 commonly used time-domain parameters (SDNN, SDANN, rMSSD, pNN50) and the spectral components of HRV in 17 healthy volunteers and in patients with coronary artery disease (n = 9) or hypertensive heart disease (n = 9). In all subjects, 2 Holter recordings were obtained 7 days apart. In both, healthy volunteers and in patients, overall reproducibility of HRV parameters was good exhibiting correlation coefficients between 0.60 and 0.98. However, in individual subjects particularly in those without heart disease a higher degree of variability of HRV measurements was observed. In those patients with markedly reduced HRV, reproducibility was best. It is concluded that repeated HRV determinations may be utilized to examine the effects of underlying disease progress or of therapeutic interventions on cardiac autonomic tone.

Adult↗

PubMed1993

[Intra-individual reproducibility of tilt table studies in diagnosis of vasovagal syncope].

Neurally-induced syncope appears to be the underlying pathophysiologic mechanism in many patients with unexplained syncope. Diagnosis of vasovagal syncope, however, remains difficult and constitutes in many cases an exclusion diagnosis. The present study thus aimed to determine the yield of tilt-table testing in the work-up of patients with unexplained syncope and most importantly to examine the reproducibility of the results of this method. Twenty-four patients with a history of syncope and 11 healthy volunteers were examined on 2 days. In 10 patients, symptoms could be provoked during tilting, in 8 during both tests, in 2 only on one occasion. Only 1 of 11 volunteers developed presyncope during tilting which was not reproducible during the second test. These findings resulted in a sensitivity of 42% and a specificity of 91% for the protocol employed in this study. Overall reproducibility was 91% which suggests that this tilt-table protocol is suitable for evaluation of therapeutic interventions in patients with neurally-mediated syncope.

Adult↗

PubMed1992

Efficacy and safety of sotalol in patients with complex ventricular arrhythmias.

Sotalol is a unique beta-blocker that prolongs repolarization. Its use in 626 patients with complex ventricular ectopic activity, as reported in the literature, resulted in suppression of arrhythmia in 50 to 60% of treatment attempts. Detailed analysis of data on arrhythmias in 356 patients that were entered prospectively into a database revealed a median reduction in ventricular premature beats of 76%, compared to a median suppression of repetitive ventricular ectopic activity of 91% and of episodes of nonsustained ventricular tachycardia of 97% (p = 0.002 vs reduction of ventricular premature beats). This marked antiarrhythmic potency of sotalol in repetitive ventricular arrhythmias is thought to be due to its class III activity. Drug efficacy was independent of age, sex, the presence or absence of organic heart disease and the degree of sotalol-induced prolongation of corrected QT interval. Evaluation of left ventricular function in 215 patients treated with the drug demonstrated that depression of left ventricular ejection fraction occurred far less frequently than expected with conventional beta-blockers. Even patients with severely depressed pump function tolerated sotalol surprisingly well. There is a propensity of the drug to aggravate arrhythmia, which resulted in serious proarrhythmic events in 30 (3.5%) of 853 patients. These often consisted of torsades de pointes (9 of 30 patients). Proarrhythmia occurred primarily within the first 3 days of dosing, and exhibited a dose-dependence. In conclusion, sotalol is an effective and well-tolerated antiarrhythmic drug in patients with complex ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Intraindividual reproducibility of heart rate variability.

Heart rate variability was determined from three consecutive Holter recordings performed on days 1, 7, and 28 in 17 normal subjects, in 13 patients with angiographically normal coronary arteries, and in 9 patients with remote myocardial infarctions. Group data of several time and frequency domain measures of heart rate variability were highly reproducible (correlation coefficients 0.629-0.894). However, some individuals exhibited considerably larger day-to-day variations in heart rate variability. Single heart rate indices differed by up to 50% between two Holter recordings. Such potential differences must be considered when repeated heart rate variability determinations are used to assess changes in neurocardiac reflex regulation or effects of therapeutic interventions.

Chest Pain↗

PubMed1991

Usefulness of esmolol in unstable angina pectoris. European Esmolol Study Group.

Esmolol is a new cardioselective beta blocker with unique pharmacokinetic properties resulting in a half-life of only 9 minutes. The present multicenter, randomized, placebo-controlled study examined the hemodynamic and antiischemic effects of this compound given as an adjunctive to conventional medical therapy in 113 patients with unstable angina. Fifty-nine patients received esmolol and 54 received matching placebo infusions. Esmolol was titrated in a step-wise manner at dosages of 2 to 24 mg/min until a 25% reduction in the double product was achieved; thereafter, esmolol was continuously infused for up to 72 hours. Esmolol caused a significant and persistent decline in heart rate and blood pressure throughout the entire study period. Clinical events, such as development of acute myocardial infarction or the need for urgent revascularization, occurred in 3 esmolol compared with 9 placebo patients (p = 0.06). There was also a trend toward reduction of silent ischemia as judged by Holter monitoring (mean [+/- standard deviation] duration/patient/24 hours, 21 +/- 81 minutes in the esmolol and 35 +/- 128 minutes in the placebo groups). Esmolol-related adverse effects were mostly cardiovascular in origin and could be managed promptly by downward dose titration or cessation of drug infusion. Thus, esmolol appears to be a safe and effective drug for patients with unstable angina because it permits a large degree of flexibility in adapting the desired level of beta blockade to the patient's changing clinical presentation.

Adrenergic beta-Antagonists↗