Stefan H. Hohnloser

Interpretation and Classification of Microvolt T Wave Alternans Tests

Interpretation of T Wave Alternans Tests. Measurement of microvolt‐level T wave alternans (TWA) during routine exercise stress testing now is possible as a result of sophisticated noise reduction techniques and analytic methods that have become commercially available. Even though this technology is new, the available data suggest that microvolt TWA is a potent predictor of arrhythmia risk in diverse disease states. As this technology becomes more widely available, physicians will be called upon to interpret microvolt TWA tracings. This review seeks to establish uniform standards for the clinical interpretation of microvolt TWA tracings.

T Wave Alternans as a Predictor of Recurrent Ventricular Tachyarrhythmias in ICD Recipients: Prospective Comparison with Conventional Risk Markers

T Wave Alternans for Risk Stratification. Introduction: The current standard for arrhythmic risk stratification is electrophysiologic (EP) testing, which, due to its invasive nature, is limited to patients already known to be at high risk. A number of noninvasive tests, such as determination of left ventricular ejection fraction (LVEF) or heart rate variability, have been evaluated as additional risk stratifiers. Microvolt T wave alternans (TWA) is a promising new risk marker. Prospective evaluation of noninvasive risk markers in low‐ or moderate‐risk populations requires studies involving very large numbers of patients, and in such studies, documentation of the occurrence of ventricular tachyarrhythmias is difficult. In the present study, we identified a high‐risk population, recipients of an implantable cardioverter defibrillator (ICD), and prospectively compared microvolt TWA with invasive EP testing and other risk markers with respect to their ability to predict recurrence of ventricular tachyarrhythmias as documented by ICD electrograms.

Atrial Fibrillation and Congestive Heart Failure: Specific Considerations at the Intersection of Two Common and Important Cardiac Disease Sets

AF in Congestive Heart Failure. Atrial fibrillation (AF) and congestive heart failure (CHF) are two increasingly common cardiac disorders with a growing prevalence in the overall population. Improved treatment of acute medical conditions has increased the incidence of these cardiac disorders. AF and CHF have similar epidemiologic characteristics and adversely affect quality of life and life expectancy of affected patients. CHF predisposes to AF, and AF may worsen the prognosis of CHF. The relevant literature was intensively reviewed with emphasis on aspects at the intersection of both disease sets. Recent advances in basic research have provided a more in‐depth view of changes promoting the occurrence of AF in CHF. Data from clinical trials have provided means to improve medical treatment of AF. Precautions must be taken for specific CHF‐related side effects, such as torsades de pointes tachycardia, when treating AF. The specific electrophysiologic basis of AF associated with CHF may provide targets for improved treatment modalities. New treatment approaches, both pharmacologic and nonpharmacologic, as well as the results of ongoing controlled clinical studies are likely to greatly alter AF therapy over the next 5 to 10 years in patients with CHF.

Proarrhythmia with Class III Antiarrhythmic Drugs: Definition, Electrophysiologic Mechanisms, Incidence, Predisposing Factors, and Clinical Implications

Proarrhythmia with Class III Antiarrhythmic Agents. Antiarrhythmic drugs can and do induce unexpected and sometimes fatal reactions by either producing new symptomatic arrhythmias or by aggravating existing arrhythmias. The definition of proarrhythmia has changed since controlled clinical studies showed a dichotomy between arrhythmia suppression and mortality. The nature of proarrhythmia reactions is linked to the electrophysiologic effects of various antiarrhythmic drugs. Whereas Class I agents without accompanying effects on repolarization generally produce ventricular tachycardia (often incessant) or fibrillation. Class III agents typically produce torsades de pointes that may deteriorate into ventricular fibrillation. The precise mechanism of torsades de pointes is not fully elucidated, although early afterdepolarization and increases in spatial or temporal dispersion of repolarization are likely possibilities. Proarrhythmic risk is lowest for amiodarone and is probably related to the drugs complex electrophysiologic profile. The incidence of torsades with sotalol increases with dose and the baseline values of the QT interval; the incidence with d‐sotalol and other pure Class III agents remains unclear. Prospective, randomized, placebo‐controlled studies to evaluate this are under way. The fact that d‐sotalol increases mortality in postinfarction patients suggests that it may possibly be a common property of most, if not all, pure Class III compounds. The ongoing clinical trials with various Class III agents are likely to provide the critical information on this important therapeutic issue.

Pace-termination and pacing for prevention of atrial tachyarrhythmias: results from a multicenter study with an implantable device for atrial therapy.

Pacing for Treatment of Atrial Tachyarrhythmias. Introduction: Patients with bradycardia requiring permanent pacing frequently suffer from additional atrial tachyarrhythmias (ATs). This study evaluated the safety and efficacy of atrial antitachycardia pacing (ATP) and the performance of pacing for AT prevention implemented into a new pacemaker.

Electrophysiologic features of torsades de pointes: insights from a new isolated rabbit heart model.

Torsades de Pointes in the Isolated Rabbit Heart. Introduction: The exact electrophysiologic mechanism of torsades de pointes (TdP) is under intense investigation. No isolated animal heart model of this particular arrhythmia exists.

Rationale and design of ATHENA: A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter.

Background: Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia, predominantly affecting elderly patients. There is a continued need for new antiarrhythmic drugs to treat the ever‐increasing number of patients with this arrhythmia. Dronedarone is a new antiarrhythmic compound currently being developed for treatment of AF.

Changes in plasma epinephrine concentration and in heart rate during head-up tilt testing in patients with neurocardiogenic syncope: correlation with successful therapy with beta-receptor antagonists.

Sympathetic Activation in Neurocardiogenic Syncope. Introduction: Tilt table testing is widely used in the management of patients with neurocardiogenic syncope. However, the exact pathophysiologic mechanism of this disorder is still under debate. Likewise, therapy of these patients continues to represent a challenge in many cases. Therefore, the present study aimed to gain further insight into the pathophysiology of this syndrome and to examine easily accessible clinical parameters that can improve therapy selection.

Differential Effects of D-Sotalol, Quinidine, and Amiodarone on Dispersion of Ventricular Repolarization in the Isolated Rabbit Heart

Drug Effects on Dispersion of Repolarization. Introduction: increased dispersion of ventricular repolarization has been suggested as a cause of proarrhythmic effects of Class IA or III antiarrhythmic drugs, such as d‐sotalol, quinidine, and amiodarone.

Combined antiplatelet therapy in atrial fibrillation: Review of the literature and future research avenues

Atrial fibrillation (AF), the most commonly encountered cardiac rhythm disorder, affects approximately 1% of the general population and is associated with serious complications, most notably ischemic stroke. AF‐associated stroke occurs at an annual rate of 4.5%. Anticoagulation therapy with warfarin has been demonstrated in randomized controlled trials to reduce the risk for AF‐related stroke by two thirds, but warfarin therapy is markedly underused in clinical practice because of its narrow therapeutic window and its implications on quality of life. This article reviews the present knowledge and potential future research avenues for the role of antiplatelet therapy in AF as an alternative to anticoagulation with warfarin for prevention of AF‐associated stroke. Antiplatelet therapy recently has been shown to be protective against thrombotic events related to blood stasis. There is ample evidence from experimental and clinical studies that a combination of different antiplatelet agents may increase antithrombotic efficacy compared to monotherapy. Accordingly, a series of randomized controlled trials (ACTIVE [Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events]) has been designed to vigorously examine the role of combined antithrombotic therapy for prevention of vascular events, including stroke in high‐risk AF patients. The ACTIVE program began patient enrollment in spring 2003. (J Cardiovasc Electrophysiol, Vol. 14, pp. S60‐S63, September 2003, Suppl.)