Christoph Geller

Characterization of Left Ventricular Activation in Patients With Heart Failure and Left Bundle-Branch Block

Background—Conventional activation mapping in the dilated human left ventricle (LV) with left bundle-branch block (LBBB) morphology is incomplete given the limited number of recording sites that may be collected in a reasonable time and given the lack of precision in marking specific anatomic locations. Methods and Results—We studied LV activation sequences in 24 patients with heart failure and LBBB QRS morphology with simultaneous application of 3D contact and noncontact mapping during intrinsic rhythm and asynchronous pacing. Approximately one third of the patients with typical LBBB QRS morphology had normal transseptal activation time and a slightly prolonged or near-normal LV endocardial activation time. A “U-shaped” activation wave front was present in 23 patients because of a line of block that was located anteriorly (n=12), laterally (n=8), and inferiorly (n=3). Patients with a lateral line of block had significantly shorter QRS (P <0.003) and transseptal durations (P <0.001) and a longer distance from the LV breakthrough site to line of block (P <0.03). Functional behavior of the line of block was demonstrated by a change in its location during asynchronous ventricular pacing at different sites and cycle lengths. Conclusions—A U-shaped conduction pattern is imposed on the LV activation sequence by a transmural functional line of block located between the LV septum and the lateral wall with a prolonged activation time. Assessment of functional block is facilitated by noncontact mapping, which may be useful for identifying and targeting specific locations that are optimal for successful cardiac resynchronization therapy.

Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin and Oral Anticoagulants for Prevention of Thromboembolic Complications in Cardioversion of Nonvalvular Atrial Fibrillation The Anticoagulation in Cardioversion using Enoxaparin (ACE) Trial

Background—Anticoagulation in cardioversion of atrial fibrillation is currently performed with unfractionated heparin (UFH) and oral anticoagulants, with or without guidance by transesophageal echocardiography (TEE). Low-molecular-weight heparins may reduce the risk of bleeding, may obviate the need for intravenous access, and do not require frequent anticoagulation monitoring. Methods and Results—In a randomized, prospective multicenter trial, we compared the safety and efficacy of enoxaparin administered subcutaneously with intravenous UFH followed by the oral anticoagulant phenprocoumon in 496 patients scheduled for cardioversion of atrial fibrillation of >48 hours’ and ≤1 year’s duration. Patients were stratified to cardioversion with (n=431) and without (n=65) guidance by TEE. The study aimed to demonstrate noninferiority of enoxaparin compared with UFH+phenprocoumon with regard to the incidence of embolic events, all-cause death, and major bleeding complications. Secondary end points included successful cardioversion, maintenance of sinus rhythm until study end, and minor bleeding complications. Of 496 randomized patients, 428 were analyzed per protocol. Enoxaparin was noninferior to UFH+phenprocoumon with regard to the incidence of the composite primary end point in a per-protocol analysis (7 of 216 patients versus 12 of 212 patients, respectively; P =0.016) and in an intention-to-treat analysis (7 of 248 patients versus 12 of 248 patients, respectively; P =0.013). There was no significant difference between the 2 groups in the number of patients reverted to sinus rhythm. Conclusions—Enoxaparin is noninferior to UFH+phenprocoumon for prevention of ischemic and embolic events, bleeding complications, and death in TEE-guided cardioversion of atrial fibrillation. Its easier application and more stable anticoagulation may make it the preferred drug for initiation of anticoagulation in this setting.

New primary prevention trials of sudden cardiac death in patients with left ventricular dysfunction: SCD-HEFT and MADIT-II.

Primary prevention of sudden arrhythmic death in patients with organic heart disease with poor left ventricular function and/or heart failure is currently a major challenge in cardiology. Amiodarone (with or without beta blockers) and the implantable cardioverter defibrillator (ICD) are considered the 2 major therapeutic tools to prevent sudden arrhythmic death in these patients. Two large trials have been launched to define the prophylactic benefit of the ICD or amiodarone on total mortality in patients that receive optimal heart failure and anti-ischemic treatment but remain at high risk of dying suddenly. The Sudden Cardiac Death in Heart Failure Trial (SCD-Heft) is designed to determine whether amiodarone or the ICD will decrease overall mortality in patients with coronary artery disease or nonischemic cardiomyopathy who are in heart failure New York Heart Association (NYHA) class II or III and have a left ventricular ejection fraction < 35%. The primary endpoint is total mortality; secondary objectives are comparison of arrhythmic and nonarrhythmic mortality and morbidity in the 3 arms as well as quality of life, cost-effectiveness, and incidence of episodes of ventricular tachyarrhythmias. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) II is a follow-up study to the MADIT trial. It examines the prophylactic benefit in coronary artery disease patients with a left ventricular ejection fraction of < 30%, who have had at least 1 myocardial infarction but require no further risk stratification. MADIT II is a sequential design trial that compares ICD versus no ICD therapy. Programmed electrical stimulation to test inducibility of ventricular tachycardia is performed during ICD implantation, and various noninvasive risk markers are tested after randomization. Primary endpoint is total mortality, and secondary objectives are quality-of-life issues as well as cost-effectiveness ratio.

Clinical Efficacy of the Wearable Cardioverter-Defibrillator in Acutely Terminating Episodes of Ventricular Fibrillation

The findings of our initial study demonstrate for the first time the ability to terminate induced VT/VF reliably (100% of all episodes) by a single, monophasic 230-J shock delivered by the Wearable Cardioverter-Defibrillator (WCD). Although limited by sample size, our data suggest the WCD could be used as a feasible bridge to definitive implantation of an implantable cardioverter-defibrillator in patients in whom risk stratification for sudden death is not completed.

Importance of Left Atrial Diameter and Atrial Fibrillatory Frequency for Conversion of Persistent Atrial Fibrillation With Oral Flecainide

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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.

Tiermodelle für ventrikuläre Tachyarrhythmien

Summary Experimental animal models of ventricular arrhythmias have been developed to investigate the mechanisms of arrhythmogenesis in man. Ventricular arrhythmias associated with ischaemia and infarction often cannot be elucidated by clinical studies on patients because those arrhythmias are potentially lifethreatening and their occurrence is unpredictable. Because of additional experimental procedures and techniques that can be used in the animal laboratory, such as microelectrode recording of transmembrane action potentials and high-density optical and electrical activation mapping, animal models have provided information that cannot be obtained from clinical studies. Studies on animal models have provided new ideas and hypotheses that have been tested in clinical studies and that have been found to be true for clinical arrhythmias. Animal models have enabled the mechanisms of fibrillation and defibrillation to be understood and new therapeutic concepts to be developed. The purpose of this article is to briefly review some animal models of ventricular tachycardia and fibrillation. Some contributions that these animal studies have made to our understanding of ventricular tachyarrhythmias will be discussed. Because of the clinical importance of coronary artery disease this article concentrates on those arrhythmias caused by myocardial ischaemia and infarction.An animal model that resembles the clinical course of coronary artery disease in humans does not exist. In animal studies designed to reproduce arrhythmias caused by myocardial ischaemia or infarction regional ischaemia is induced by transient or permanent occlusion of one or more coronary arteries. Coronary occlusion is performed with a variety of techniques in open- or closed-chest animals of different species. Arrhythmias occur „spontaneously“ during acute ischaemia or reperfusion or can be induced by electrical stimuli. Hearts isolated and perfused by the Langendorff technique can also be used to study the arrhythmias caused by coronary occlusion or occlusion and reperfusion. These animal models of myocardial ischaemia and infarction have helped to elucidate the mechanisms of arrhythmogenesis of each stage of infarct development and healing.Zusammenfassung Experimentelle Tiermodelle ventrikulärer Tachyarrhythmien wurden entwickelt, um die Mechanismen dieser Herzrhythmusstörungen beim Menschen besser zu verstehen. Solche Modelle sind notwendig, weil der lebensbedrohliche Charakter dieser Herzrhythmusstörungen und die zeitliche Unvorhersehbarkeit ihres Auftretens ein umfassendes Studium am Patienten oft unmöglich machen. Im Tierlabor stehen zusätzliche technische Möglichkeiten, wie Bestimmung des Transmembranpotentials mit Mikroelektroden oder hochauflösendes optisches und elektrisches Mapping zur Verfügung. Diese Methoden erlauben Untersuchungen, die im Rahmen klinischer Studien nicht möglich sind. Experimente an Tiermodellen haben neue Ideen und Hypothesen hervorgebracht, die in klinischen Studien getestet wurden und sich für klinische Herzrhythmusstörungen bestätigt haben. Tiermodelle haben entscheidend zu unserem Verständnis der Mechanismen von Fibrillation und Defibrillation und der Entwicklung neuer Therapiekonzepte beigetragen. Dieser Artikel wird eine kurze Übersicht über verschiedene Tiermodelle ventrikulärer Tachyarrhythmien geben und auch einige Erkenntnisse, die mit Hilfe dieser Modelle erzielt wurden, diskutieren. Aufgrund der klinischen Bedeutung der koronaren Herzkrankheit wird der Schwerpunkt auf ventrikuläre Tachyarrhythmien im Rahmen von Myokardischämie und Myokardinfarkt gelegt.Es gibt kein Tiermodell, daß den natürlichen Verlauf der koronaren Herzkrankheit beim Menschen simuliert. Den Modellen ist gemeinsam, daß eine regionale Myokardischämie durch permanente oder temporäre Okklusion einer oder mehrerer Koronargefäße erzeugt wird. Dies geschieht am offenen oder geschlossenen Thorax. Die Arrhythmien entstehen „spontan“ während akuter Ischämie oder in der Reperfusionsphase oder können durch elektrische Stimuli induziert werden. Solche Untersuchungen können bei verschiedenen Spezies durchgeführt werden. Neben Studien am intakten Tier werden auch isolierte, mit der Langendorff-Technik perfundierte Herzen verwendet. Diese Modelle haben dazu beigetragen, die Arrhythmiemechanismen während der einzelnen Phasen der Infarktentstehung und -heilung zu untersuchen.