Hans D. Esperer

Pathophysiological basis and clinical application of T-wave alternans☆

We review the contemporary understanding of the pathophysiology of repolarization alternans and present a perspective on the use of T-wave alternans (TWA) as a risk stratification marker of malignant ventricular arrhythmias. Several studies have demonstrated a high correlation of susceptibility to ventricular arrhythmias and sudden cardiac death with the existence of TWA. We describe a number of cellular and molecular alterations in the diseased heart that may provide a link between electrical and mechanical alternans and arrhythmia susceptibility. Repolarization alternans is likely the result of distinct and diverse cellular and molecular alterations that are associated with exaggerated regional repolarization heterogeneity, which renders the heart susceptible to malignant arrhythmias.

Heart rate variability and physical exercise. Current status

ZusammenfassungNeben dem klinischen Einsatz in der Risikostratifizierung von plötzlichem Herztod und diabetischer autonomer Neuropathie gewinnt die Herzfrequenzvariabilität (HRV) nun auch für die Sportwissenschaft und Sportmedizin zunehmend an Bedeutung. In diesen Feldern wird die HRV derzeit als leistungsdiagnostische Kenngröße, als Kontrollparameter der Beanspruchung und als Steuerparameter der Belastungsintensität untersucht.Aufgrund der großen empirischen Basis kann es als gesichert gelten, dass aerobes Ausdauertraining bei angemessener Intensität und Dauer bei gesunden Personen sowie bei Patienten mit Herz-Kreislauf-Erkrankungen bis zu einem Alter von 70 Jahren einerseits zu einer Reduktion von Ruhe- und submaximaler Belastungsherzfrequenz, andererseits zu einer Zunahme der instantanen und der globalen HRV führt. Diese Veränderungen, die bereits nach einem 3-monatigen regelmäßigen Ausdauertraining moderaten Umfangs und moderater Intensität nachweisbar sind, reflektieren eine Zunahme der autonomen efferenten kardialen Aktivität mit einer Nettozunahme der vagalen Herzfrequenzmodulation. Darin könnte ein prognostischer Nutzen für Personen liegen, die regelmäßig Ausdauersport betreiben.Der Nutzen der HRV als Methode zur individuellen Trainings- und Belastungssteuerung kann jedoch noch nicht abschließend beurteilt werden, da die vorliegenden Ergebnisse an relativ kleinen Kollektiven erhoben wurden und teilweise, aufgrund unterschiedlicher HRV- und Studienmethodik, widersprüchlich sind. Ob und welche HRV-Indizes sich im Hochleistungssport als Marker von Übertrainingszuständen (Overreaching oder Overtraining) eignen, lässt sich derzeit ebenfalls noch nicht abschätzen. Bezüglich des Overreachings gibt es zwar erste vielversprechende Ergebnisse, die jedoch durch größer angelegte kontrollierte Studien validiert werden müssen.Ein grundsätzliches Problem bei HRV-Analysen ist die Nichtstationarität der zugrundeliegenden RRZeitreihen, die vor allem die Ergebnisse der Spektralanalyse verzerren können. Dies gilt während sportlicher Betätigung in besonderer Weise. Inwieweit hier robustere, nichtlineare HRV-Methoden die Trainingswissenschaft bereichern können, bleibt abzuwarten.AbstractHeart rate variability (HRV) has long been used in risk stratification for sudden cardiac death and diabetic autonomic neuropathy. In recent years, both time and frequency domain indices of HRV also gained increasing interest in sports and training sciences. In these fields, HRV is currently used for the noninvasive assessment of autonomic changes associated with short-term and long-term endurance exercise training in both leisure sports activity and high-performance training. Furthermore, HRV is being investigated as a diagnostic marker of overreaching and overtraining.A large body of evidence shows that, in healthy subjects and cardiovascular patients of all ages (up to an age of 70 years), regular aerobic training usually results in a significant improvement of overall as well as instantaneous HRV. These changes, which are accompanied by significant reductions in heart rates both at rest and during submaximal exercise, reflect an increase in autonomic efferent activity and a shift in favor of enhanced vagal modulation of the cardiac rhythm. Regular aerobic training of moderate volume and intensity over a minimum period of 3 months seems to be necessary to ensure these effects, which might be associated with a prognostic benefit regarding overall mortality.At present, available data does not allow for final conclusions with respect to the usefulness of traditional HRV indices in assessing an individual’s exercise performance and monitoring training load. The discrepant results published so far are due to several factors including insufficient study size and design, and different HRV methods. Large-sized and prospectively designed studies are necessary for clarification. It also remains to be seen, whether the traditional HRV indices prove useful in the diagnosis of overreaching and overtraining. Preliminary results, though promising, need to be confirmed in larger cohorts.A basic problem in HRV analysis is nonstationarity of the heart rate signal, which holds particularly true for exercise conditions. Whether, in these conditions, more robust nonlinear HRV methods offer a benefit has to be established in further work.

Syncope due to Brugada syndrome in a young athlete

A 30-year-old male athlete with exercise-related syncopal symptoms spontaneously exhibited a type 1 Brugada ECG and was inducible during electrophysiology study. He was diagnosed with symptomatic Brugada syndrome and deemed at high risk of sudden cardiac death. Thus, he received a cardioverter/defibrillator and was advised to abstain from further competitive sports activities. This case points to a role of the ECG in pre-participation screening. It also demonstrates that, in athletes with Brugada syndrome, repolarisation anomalies may be markedly attenuated during vigorous exercise and considerably increased immediately after exercise. The observed J-wave amplitude dynamics suggests enhancement of pre-existing autonomic dysfunction through heavy exertion.

Efficacy and safety profile of dronedarone in clinical practice. Results of the Magdeburg Dronedarone Registry (MADRE study)

BACKGROUND Dronedarone is a new antiarrhythmic agent that has only recently been approved for the therapy of atrial fibrillation (AF). Results regarding a broader spectrum of patients and experience accumulated in clinical practice are still very scarce. Therefore, we prospectively investigated the efficacy and tolerance of dronedarone in a real life setting. METHODS AND RESULTS The study included 191 patients (85 women) aged 63 ± 9.9 years with a history of paroxysmal or persistent AF. Follow-up time was 14.3 ± 4.9 months. In patients with persistent AF, sinus rhythm was restored using electrical cardioversion prior to dronedarone administration. Each patient underwent standard ECG on a daily basis during the first 4 days of treatment, and on days 7, 30 and 90, resp. After that, the patients had a follow-up visit every three months. Creatinine, creatine kinase, and hepatic enzymes were closely monitored. Clinical history was meticulously taken at multiple follow-up visits. Dronedarone maintained sinus rhythm in 33.5% (95% CI: 27%-40%), and AF recurrence rate was high: 66.5% (95% CI: 60%-73%). Adverse effects occurred in 31.9% (95% CI: 27%-38%) of the patients and necessitated permanent discontinuation of dronedarone in 22% (95% CI: 17%-27%). CONCLUSIONS The results suggest that dronedarone may not be superior to available antiarrhythmic agents and caution against its use as a first line therapy in AF.

An Increase in Sinus Rate Following Radiofrequency Energy Application in the Posteroseptal Space

An increase in sinus rate has been previously described in patients with AV node reentry (AVNRT) following successful A V node modification. This increase could either be a specific sign of elimination of slow pathway conduction or it could be a consequence of energy application in the posteroseptal area. Thus, we compared the changes in sinus cycle length following successful slow pathway ablation (defined as complete elimination of dual AV node physiology) in patients having AVNRT with those in patients undergoing successful ablation of a posteroseptal atriovetriricular accessory connection. Twenty five patients (16 women and 9 men, mean age 41 ± 4 years) with typical AVNRT (cycle length 378 ± 12 ms and 29 patients (16 women and 13 men, age 34 ± 5 years) with an accessory connection (17 manifest and 12 concealed) were studied. The electrophysiology study was performed during sedation with Fentanyl and Midazolam. The mean number of energy applications was 3 ± 1 for successful slow pathway ablation and 4 ± 1 for successful ablation of the accessory connection (p:NS). Following the successful energy application, the sinus cycle length decreased significantly 776 ms at baseline to 691 ms in patients with AVNRT. Following successful ablation of the posteroseptal AC, sinus cycle length decreased from 755 ms at baseline to 664 ms (p < 0.05 in both groups [difference between groups not significant]). The decrease in sinus cycle length did not correlate with the number ofRF energy applications required for successful ablation or the total energy delivered. In conclusion, ablation of the AV node slow pathway and a posteroseptal accessory connection results in similar increases in the sinus rate. Thus, the increase in sinus rate is probably due to energy application in the posteroseptal space, possibly due to concomitant destruction of vagal inputs, and it is not specific for elimination of slow pathway conduction.

Capacitive ECG system with direct access to standard leads and body surface potential mapping.

Abstract Capacitive electrodes provide the same access to the human electrocardiogram (ECG) as galvanic electrodes, but without the need of direct electrical skin contact and even through layers of clothing. Thus, potential artifacts as a result of poor electrode contact to the skin are avoided and preparation time is significantly reduced. Our system integrates such capacitive electrodes in a 15 sensor array, which is combined with a Tablet PC. This integrated lightweight ECG system (cECG) is easy to place on the chest wall and allows for simultaneous recordings of 14 ECG channels, even if the patient is slightly dressed, e.g., with a t-shirt. In this paper, we present preliminary results on the performance of the cECG regarding the capability of recording body surface potential maps (BSPMs) and obtaining reconstructed standard ECG leads including Einthoven, Goldberger and, with some limitations, Wilson leads. All signals were measured having the subject lie in a supine position and wear a cotton shirt. Signal quality and diagnostic ECG information of the extracted leads are compared with standard ECG measurements. The results show a very close correlation between both types of ECG measurements. It is concluded that the cECG lends itself to rapid screening in clinically unstable patients. Zusammenfassung Kapazitive Elektroden ermöglichen die gleiche Art der Messung des Elektrokardiogramms (EKG), wie sie auch bei herkömmlich genutzten galvanischen Elektroden genutzt wird. Dabei wird jedoch kein direkter Hautkontakt benötigt; stattdessen kann sogar durch Kleidungsschichten gemessen werden. Somit entfallen Kontaktprobleme, wie sie beim konventionellen EKG auftreten können, und gleichzeitig wird die eigentliche Vorbereitungszeit auf ein Minimum reduziert. Im hier vorgestellten System wurden 15 derartige kapazitive Elektroden in einen Sensor-Array integriert und rückseitig mit einem Tablet-PC kombiniert. Durch Aufsetzen des Systems auf die Brust des Patienten können simultan 14 EKG-Kanäle gemessen werden, auch durch Kleidung hindurch und ohne Vorbereitungsaufwand. Dabei wird das EKG direkt auf dem Tablet-PC visuell dargestellt. In dieser Arbeit berichten wir über erste Ergebnisse der Messung von Body-Surface-Potential-Maps (BSPM) und der Extraktion von Standardableitungen nach Einthoven/Goldberger und (mit gewissen Einschränkungen) Wilson aus dem Sensor-Array. Sowohl die Signalqualität als auch die diagnostischen Informationen der gemessenen EKGs werden direkt mit herkömmlichen, galvanisch gemessenen EKGs verglichen. Die Ergebnisse zeigen eine sehr enge Korrelation zwischen beiden Messarten. Insbesondere die schnelle Aufnahme von EKG-Signalen bei klinisch instabilen Patienten wird durch das vorgestellte kapazitive BSPM-System stark erleichtert.

Efficacy and safety profile of dronedarone in clinical practice. Preliminary results of the Magdeburg Dronedarone Registry

threshold by gas exchange. J Appl Physiol 1986;60(6):2020–7. [12] Hansen JE, Sue DY, Wasserman K. Predicted values for clinical exercise testing. Am Rev Respir Dis 1984;129(2 Pt 2):S49–55. [13] Ingle L, Witte KK, Cleland JG, Clark AL. The prognostic value of cardiopulmonary exercise testing with a peak respiratory exchange ratio of b1.0 in patients with chronic heart failure. Int J Cardiol 2008;127(1):88–92. [14] Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000;894:i–xii 1–253. [15] Witte KKA, NikitinNP, Cleland JGF, Clark AL. Excessive breathlessness inpatientswith diastolic heart failure. Heart 2006;92(10):1425–9.

Automatic quantification of the Poincaré plot asymmetry of NN-interval recordings.

We investigated the electrocardiographic substrate underlying the asymmetry of Poincaré plots of NN intervals (NNI) on different time scales and conceived a method for automatic asymmetry quantification (AQUA), which is based on the observation that left-sided comet asymmetry (A(L)) is due to sudden increases (SIC), and right-sided comet asymmetry (A(R)) to sudden decreases (SDC) of cycle lengths, and that both the SIC and SDC episodes were consistently associated with significant changes in P-wave magnitude and/or polarity indicating a shift in dominant pacemaker activity. The performance of AQUA was validated in 15 endurance trained athletes (age: 29 +/- 6 years) exhibiting marked comet asymmetry, and 11 untrained controls (age: 40 +/- 15 years) with symmetrical comet patterns. SICs were reliably identified by AQUA with a sensitivity of 0.950 and a specificity of 0.985, and SDCs with a sensitivity of 0.952 and a specificity of 0.965. In the athletes, the magnitude of SICs exceeded that of SDCs significantly, and the occurrence of SICs and SDCs was closely correlated with periods of increased efferent vagal activity. It is concluded that AQUA is a useful tool for the identification and quantification of specific aspects of nonlinear heart rate dynamics manifesting as Poincaré plot asymmetries.

Herzfrequenzvariabilität und Sport

ZusammenfassungNeben dem klinischen Einsatz in der Risikostratifizierung von plötzlichem Herztod und diabetischer autonomer Neuropathie gewinnt die Herzfrequenzvariabilität (HRV) nun auch für die Sportwissenschaft und Sportmedizin zunehmend an Bedeutung. In diesen Feldern wird die HRV derzeit als leistungsdiagnostische Kenngröße, als Kontrollparameter der Beanspruchung und als Steuerparameter der Belastungsintensität untersucht.Aufgrund der großen empirischen Basis kann es als gesichert gelten, dass aerobes Ausdauertraining bei angemessener Intensität und Dauer bei gesunden Personen sowie bei Patienten mit Herz-Kreislauf-Erkrankungen bis zu einem Alter von 70 Jahren einerseits zu einer Reduktion von Ruhe- und submaximaler Belastungsherzfrequenz, andererseits zu einer Zunahme der instantanen und der globalen HRV führt. Diese Veränderungen, die bereits nach einem 3-monatigen regelmäßigen Ausdauertraining moderaten Umfangs und moderater Intensität nachweisbar sind, reflektieren eine Zunahme der autonomen efferenten kardialen Aktivität mit einer Nettozunahme der vagalen Herzfrequenzmodulation. Darin könnte ein prognostischer Nutzen für Personen liegen, die regelmäßig Ausdauersport betreiben.Der Nutzen der HRV als Methode zur individuellen Trainings- und Belastungssteuerung kann jedoch noch nicht abschließend beurteilt werden, da die vorliegenden Ergebnisse an relativ kleinen Kollektiven erhoben wurden und teilweise, aufgrund unterschiedlicher HRV- und Studienmethodik, widersprüchlich sind. Ob und welche HRV-Indizes sich im Hochleistungssport als Marker von Übertrainingszuständen (Overreaching oder Overtraining) eignen, lässt sich derzeit ebenfalls noch nicht abschätzen. Bezüglich des Overreachings gibt es zwar erste vielversprechende Ergebnisse, die jedoch durch größer angelegte kontrollierte Studien validiert werden müssen.Ein grundsätzliches Problem bei HRV-Analysen ist die Nichtstationarität der zugrundeliegenden RRZeitreihen, die vor allem die Ergebnisse der Spektralanalyse verzerren können. Dies gilt während sportlicher Betätigung in besonderer Weise. Inwieweit hier robustere, nichtlineare HRV-Methoden die Trainingswissenschaft bereichern können, bleibt abzuwarten.AbstractHeart rate variability (HRV) has long been used in risk stratification for sudden cardiac death and diabetic autonomic neuropathy. In recent years, both time and frequency domain indices of HRV also gained increasing interest in sports and training sciences. In these fields, HRV is currently used for the noninvasive assessment of autonomic changes associated with short-term and long-term endurance exercise training in both leisure sports activity and high-performance training. Furthermore, HRV is being investigated as a diagnostic marker of overreaching and overtraining.A large body of evidence shows that, in healthy subjects and cardiovascular patients of all ages (up to an age of 70 years), regular aerobic training usually results in a significant improvement of overall as well as instantaneous HRV. These changes, which are accompanied by significant reductions in heart rates both at rest and during submaximal exercise, reflect an increase in autonomic efferent activity and a shift in favor of enhanced vagal modulation of the cardiac rhythm. Regular aerobic training of moderate volume and intensity over a minimum period of 3 months seems to be necessary to ensure these effects, which might be associated with a prognostic benefit regarding overall mortality.At present, available data does not allow for final conclusions with respect to the usefulness of traditional HRV indices in assessing an individual’s exercise performance and monitoring training load. The discrepant results published so far are due to several factors including insufficient study size and design, and different HRV methods. Large-sized and prospectively designed studies are necessary for clarification. It also remains to be seen, whether the traditional HRV indices prove useful in the diagnosis of overreaching and overtraining. Preliminary results, though promising, need to be confirmed in larger cohorts.A basic problem in HRV analysis is nonstationarity of the heart rate signal, which holds particularly true for exercise conditions. Whether, in these conditions, more robust nonlinear HRV methods offer a benefit has to be established in further work.

Neue posturographische Methode zur Differentialdiagnostik von Patienten mit Morbus Parkinson und Kleinhirnstörungen / A novel posturographic method to differentiate sway patterns of patients with Parkinson's disease from patients with cerebellar ataxia

Zusammenfassung In der neurologischen Rehabilitation sind insbesondere das nigrostriatale und cerebelläre System wichtige posturale Subsysteme. Ziel dieser Untersuchung war es, zu prüfen, ob sich beide Systeme posturographisch mittels Spektralanalyse differenzieren lassen. In die Querschnitt-untersuchung wurden 156 Personen, 52 Gesunde (Kontrollgruppe), 52 Morbus-Parkinson-Patienten und 52 Patienten mit Kleinhirnerkrankungen (Durchschnittsalter: 61,3±13,4 Jahre), eingeschlossen. Als Untersuchungsmethode kam das Interaktive Balance-System (IBS) zur Anwendung, das differenziert auf vier Kraftmessplattformen vertikale Kräfte im Vorfuß- und Rückfußbereich in acht standardisierten Testpositionen erfasst. Überdies ermöglicht es eine frequenzanalytische Aufbereitung des Kraft-Zeit-Signals. Die statistische Auswertung erfolgte mittels univariater, mehrfaktorieller Kovarianzanalyse. Varianzanalytisch fanden sich zwischen M.-Parkinson-Patienten (Mittelwert/95% Konfidenzintervall: 23,0/20,5–25,5) und den Probanden der Kontrollgruppe (Mittelwert/95% Konfidenzintervall: 16,7/14,2–19,2) die größten Unterschiede im Frequenzbereich F 1. Patienten mit Kleinhirnerkrankungen unterschieden sich hingegen in allen Frequenzbereichen signifikant von den Probanden der Kontrollgruppe. Patienten mit Kleinhirnerkrankungen zeigten im Vergleich mit M.-Parkinson-Patienten (p<0,001) und Probanden der Kontrollgruppe (p<0,001) eine konsistent niedrigere posturale Stabilität. Die vorliegende Untersuchung deutet darauf hin, dass sich das cerebelläre und nigrostriatale System mittels Posturographie frequenzanalytisch differenzieren lassen. Mit dem IBS steht ein Assessment zur Verfügung, dessen Verwendung in der neurologischen Rehabilitation differentialdiagnostisch, auch aufgrund seiner hohen Praktikabilität, durchaus sinnvoll erscheint. Abstract Nigrostriatal and cerebellar systems are important postural subsystems in neurologic rehabilitation. In this study, we investigated the ability to differentiate both systems via posturography and spectral analysis. This cross-sectional study included 156 study subjects with 52 individuals in each group (healthy controls, Parkinsons disease and cerebellar disease patients). The mean age of all groups was 61.3±13.4 years. We used the interactive balance system (IBS) to differentiate vertical pressure fluctuations on four independent force plates, each supporting one heel or the toes of each leg in eight test positions. We also performed a frequency analysis of the force/time signal. The univariate, multifactor covariance analysis was used for statistical evaluation. Variance analysis of the Parkinsons group (mean/95% CI: 23.0/20.5–25.5) and control group (mean/95% CI: 16.7/14.2–19.2) revealed the greatest differences in frequency range F1. Subjects with cerebellar disease showed significant differences compared with controls in all frequency ranges. Furthermore, cerebellar disease subjects showed a consistently lower postural stability compared with the Parkinsons (p<0.001) and control groups (p<0.001). Results from the present study suggest that the cerebellar and nigrostriatal system can be effectively differentiated and assessed with frequency-analyzed posturographic parameters. Furthermore, the IBS allows a highly practical differential assessment in neurologic rehabilitation.