Overview of trends in the control of cardiac arrhythmia: past and future

The current antiarrhythmic scene is changing, with striking successes in recent years in radiofrequency ablation and implantable devices for atrial and ventricular arrhythmia. This has necessitated a reorientation in drug therapy, which has also become necessary in light of the outcome of clinical trials showing that certain antiarrhythmic drugs increase rather than decrease mortality, despite the suppression of the arrhythmia for which they are administered. The decrease in the use of sodium-channel blockers has led to increasing reliance on other antiarrhythmic compounds. These have mainly been b-blockers and complex class III agents, such as sotalol and amiodarone, for atrial fibrillation and selective compounds such as flecainide and propafenone and pure class III compounds in patients with little or no heart disease. The major focus of pharmacologic therapy in ventricular arrhythmia is now in conjunction with the use of implantable cardioverter defibrillators (ICDs), although not all subsets of patients in whom these devices offer a survival advantage have been clearly defined. Two items of information are now compelling. First, b-blockers should be regarded as antiarrhythmic drugs in their own right. This is suggested by the outcome of a number of mortality trials in patients with cardiac failure. Second, when given in conjunction with amiodarone, b-blockers exert a synergistic effect in reducing mortality in patients with heart disease. This raises the issue of whether the most effective medical therapy for controlling life-threatening ventricular arrhythmia might be a combination regimen rather than amiodarone or sotalol alone. Thus, future clinical trials should aim at defining the most effective ICD–drug combinations with single as well as multiple agents (including b-blockers) with endpoints including reduction of ICD shocks as well as total mortality. The potential roles of complex compounds such as amiodarone and sotalol and pure class III agents are under intense investigation. How competitive these pure compounds are likely to be with the more versatile compounds (e.g., sotalol and amiodarone) or their derivatives is being studied in a variety of experimental and clinical models in the continued search for an ideal antifibrillatory and antiarrhythmic class of compounds. As we make the transition into the next millennium, those of us with particular interest in the origin, control, and prevention of disorders of cardiac rhythm can reflect proudly on the depth and breadth of the accomplishments in this dynamic and swiftly changing area of cardiovascular medicine. With a wealth of new information over the last 20 years or so, the growth in this subspecialty has been nothing short of spectacular. Advances have occurred from cellular and molecular to bedside levels in terms of an understanding of the basic mechanisms of cardiac arrhythmia, how antiarrhythmic drugs work, and how one might define the relevance of the newer findings to patients with disordered cardiac rhythm.1 A wide range of technologic developments have contributed to a more precise understanding of the mechanisms of how individual arrhythmias arise, how and where they spread in the heart, and how they are sustained for varying periods of time.2 Such advances in recent years have paved the way for a number of entirely new approaches to therapy which are now in everyday use. For example, it has led to our appreciation of how certain arrhythmias are acutely terminated electrically or pharmacologically. An appreciation of reentry as a basis for the origin of many common arrhythmias and of the nature of the substrate in which they arise has served as the context for permanent interruption of the reentrant circuits, initially by surgery and subsequently by percutaneous electrode catheter ablation techniques. These have become routine. The outcome has been the complete cure of many supraventricular and some forms of ventricular arrhythmia. One of the most striking therapeutic achievements has been the development of the implantable cardioverter defibrillator (ICD), which was first used in patients in 1981. This form of therapy is clearly the most logical approach to mortality reduction in patients with potentially preventable sudden death, which might be arrhythmic in origin. In certain subsets of patients, controlled clinical trials have clearly demonstrated the value of ICDs in reducing sudden death, thereby prolonging overall survival over and above what had been possible with antiarrhythmic drugs.3 As might be expected, a number of questions have arisen in the wake of these findings. Is it reasonable to extrapolate the findings obtained from sharply defined populations to those that have not been so studied? Would these newer data also hold for patients in whom life-threatening arrhythmias such as ventricular tachycardia (VT) or ventricular fibrillation (VF) have not manifested themselves? For the purposes of prescribing defibrillator therapy, how stringently should one define patients at high risk for sudden death? Put another way, how liberally should From the Division of Cardiology, Veterans Administration Medical Center of West Los Angeles and University of California at Los Angeles, Los Angeles, California, USA. Address for reprints: Bramah N. Singh, MD, Division of Cardiology 111E, Veterans Administration Medical Center of West Los Angeles, 11301 Wilshire Boulevard, Los Angeles, California 90073.