Josephson's Clinical Cardiac Electrophysiology Techniques and Interpretations Fifth Edition

Josephson's Clinical Cardiac Electrophysiology Techniques and Interpretations Fifth Edition

Dedication

This book is dedicated to my family-Sylvie, Elan, Sydney, Rachel, Todd, Stephanie, Jesse, and particularly, to my wife Joan-for their love, support, and understanding. Joan, you have been the wind beneath my wings.

Foreword: Historical Perspectives

The study of the heart as an electrical organ has fascinated physiologists and physicians for nearly a century and a half. Matteucci studied electrical current in pigeon hearts, and Kölliker and Müller studied discrete electrical activity in association with each cardiac contraction in the frog. Study of the human electrocardiogram awaited the discoveries of Waller and, most important, Einthoven, whose use and development of the string galvanometer permitted the standardization and widespread use of that instrument. Almost simultaneously, anatomists and pathologists were tracing the atrioventricular conduction system. Many of the pathways, both normal and abnormal, still bear the names of the men who described them. This group of men included His, who discovered the muscle bundle joining the atrial and ventricular septae that is known as the common atrioventricular bundle or the bundle of His.

During the first half of the twentieth century clinical electrocardiography gained widespread acceptance, and, in feats of deductive reasoning, numerous electrocardiogrammers contributed to the understanding of how the cardiac impulse in man is generated and conducted. Those researchers were, however, limited to observation of atrial P wave and ventricular QRS complex depolarizations and their relationships to one another made at a relatively slow recording speed (twenty-five millimeters per second) during spontaneous rhythms. Nevertheless, combining those carefully made observations of the anatomists and the concepts developed in the physiology laboratory, these researchers accurately described, or at least hypothesized, many of the important concepts of modern electrophysiology. These included such concepts as slow conduction, concealed conduction, atrioventricular block, and the general area of arrhythmogenesis, including abnormal impulse formation and reentry. Some of this history was reviewed by the late Langendorf. Even the mechanism of pre-excitation and circus movement tachycardia were accurately described and diagrammed by Wolferth and Wood from the University of Pennsylvania in nineteen thirty-three. The diagrams in that manuscript are as accurate today as they were hypothetical in nineteen thirty-three. Much of what has followed the innovative work of investigators in the first half of the century has confirmed the brilliance of their investigations.

In the nineteen forties and nineteen fifties, when cardiac catheterization was emerging, it became increasingly apparent that luminal catheters could be placed intravascularly by a variety of routes and safely passed to almost any region of the heart, where they could remain for a substantial period of time. Alanis et al. recorded the His bundle potential in an isolated perfused animal heart, and Kottmeier et al. recorded the His bundle potential in man during open heart surgery. Giraud et al. were the first to record electrical activity from the His bundle by a catheter;

however, it was the report of Scherlag et al., detailing the electrode catheter techniques in dogs and humans, to reproducibly record His bundle electrogram, which paved the way for the extraordinary investigations that have occurred over the past two and a half decades.

At about the time Scherlag et al. were detailing the catheter technique of recording His bundle activity, Durrer et al. in Amsterdam and Coumel and his associates in Paris independently developed the technique of programmed electrical stimulation of the heart in nineteen sixty-seven. This began the first decade of clinical cardiac electrophysiology. Although the early years of intracardiac recording in man were dominated by descriptive work exploring the presence and timing of His bundle activation (and that of a few other intracardiac sites) in a variety of spontaneously occurring physiologic and pathologic states, a quantum leap occurred when the technique of programmed stimulation was combined with intracardiac recordings by Wellens. Use of these techniques subsequently furthered our understanding of the functional component of the atrioventricular specialized conducting system, including the refractory periods of the atrium, atrioventricular node, His bundle, Purkinje system, and ventricles and enables us to assess the effects of pharmacologic agents on these parameters, to induce and terminate a variety of tachyarrhythmias, and, in a major way, has led to a greater understanding of the electrophysiology of the human heart. Shortly thereafter, enthusiasm and inquisitiveness led to placement of an increasing number of catheters for recording and stimulation to different locations with the heart, first in the atria and thereafter in the ventricle. This first led to development of endocardial catheter mapping techniques to define the location of bypass tracts and the mechanisms of supraventricular tachyarrhythmias.

Beginning in the mid-nineteen seventies, Josephson and his colleagues at the University of Pennsylvania were the first to use vigorous, systematic, multisite programmed stimulation in the study of sustained ventricular tachycardia resulting from myocardial infarction, which allowed induction of ventricular tachycardia in more than ninety percent of the patients in whom this rhythm occurred spontaneously. Subsequent investigators sought to establish a better understanding of the methodology used in the electrophysiology study to induce arrhythmias. Several studies validated the sensitivity and specificity of programmed stimulation for induction of uniform tachycardias, and the nonspecificity of polymorphic arrhythmias induced with vigorous programmed stimulation was recognized.

In the same time period, Josephson et al. developed the technique of endocardial catheter mapping of ventricular tachycardia, which for the first time demonstrated the safety and significance of placing catheters in the left ventricle. This led to the recognition of the subendocardial origin of the majority of ventricular tachyarrhythmias, associated with coronary artery disease and the development of subendocardial resection as a therapeutic cure for this arrhythmia.

For the next decade, electrophysiologic studies continued to better understand the mechanisms of arrhythmias in man by comparing the response to programmed stimulation in man in the response to in vitro and in vivo studies of abnormal automaticity, triggered activity caused by delayed and early afterdepolarizations, and anatomical functional reentry. These studies, which used programmed stimulation, endocardial catheter mapping, and response of tachycardias to stimulation and drugs, have all suggested that most sustained paroxysmal tachycardias were due to reentry. The reentrant substrate could be functional or fixed or combinations of both. In particular, the use of entrainment and resetting during atrial flutter and VT were important techniques used to confirm the reentrant nature of these arrhythmias. Resetting and entrainment with fusion became phenomena that were diagnostic of reentrant excitation. Cassidy et al. using left ventricular endocardial mapping during sinus rhythm, for the first time described an electrophysiologic correlate of the pathophysiologic substrate of VT in coronary artery disease-a low-amplitude fragmented electrograms of long duration and late potentials. Fenoglio, Wit, Josephson, and their colleagues from the University of Pennsylvania documented for the first time that these arrhythmogenic areas were associated with viable muscle fibers separated by and imbedded in scar tissue from the infarction. They demonstrated that the quality and quantity of abnormal electrograms (and, hence, the pathophysiologic substrate) differed for sustained monomorphic VT, nonsustained VT, and ventricular fibrillation in patients with prior infarction and cardiomyopathy. Experimental studies by Gardner et al. demonstrated that these fractionated electrograms resulted from poorly coupled fibers that were viable and maintained normal action potential characteristics but that exhibited salutatory conduction and caused by nonuniform anisotropy. Further exploration of contributing factors (triggers), such as the influence of the autonomic nervous system or ischemia, will be necessary to further enhance our understanding of the genesis of the arrhythmias. This initial decade or so of electrophysiology could be likened to an era of discovery.

Subsequently, and overlapping somewhat with the era of discovery, was the development of the concept and use of programmed stimulation as a tool for developing therapy for arrhythmias. The ability to reproducibly initiate and terminate arrhythmias led to the development of serial drug testing to assess antiarrhythmic efficacy. The ability of an antiarrhythmic drug to prevent initiation of a tachycardia that we reliably initiated in the control state appeared to predict freedom from the arrhythmia in the two- to three-year follow-up. This was seen in many nonrandomized clinical trials from laboratories in the early nineteen eighties.

The persistent inducibility of an arrhythmia universally predicted an outcome that was worse than that in patients in whom tachycardias were made noninducible. The natural history of recurrences of ventricular tachyarrhythmias (or other arrhythmias for that matter) and the changing substrate for arrhythmias were recognized potential imitations of drug testing. It was recognized very early that programmed stimulation was not useful in selecting drugs to treat ventricular tachyarrhythmias in patients without coronary artery disease (i.e.,

cardiomyopathy). Despite the fact that all studies showed that patients with spontaneous VT whose arrhythmias were rendered noninducible by antiarrhythmic agents far better than patients with persistently inducible arrhythmias, the inability to accurately predict freedom from recurrence led to abandonment of programmed stimulation as a modality to select antiarrhythmic agents. The ESVEM study, although plagued by limitations in protocol and patient selection, put the nail in the coffin for programmed stimulation as a method of selecting antiarrhythmic therapy of arrhythmias.

With the known limitation of EP-guided therapy to predict outcomes uniformly and correctly, as well as the potentially lethal proarrhythmic effect of antiarrhythmic agents demonstrated in the CAST study, the desire for nonpharmacologic approaches to therapy grew. Surgery had already become a gold standard therapy for Wolff-Parkinson-White syndrome, and innovative surgical procedures for VT had grown from our understanding of the pathophysiologic substrate of VT and coronary disease and the mapping of VT from the Pennsylvania group. However, surgery was considered a rather drastic procedure for patients with a relatively benign disorder (supraventricular tachycardia and the Wolff-Parkinson-White syndrome), and although successful for VT for coronary artery disease, was associated with a high operative mortality. These limitations have led to two major areas of nonpharmacologic therapy that have dominated the last twenty-five years; implantable antitachycardia/defibrillator devices and catheter ablation. These techniques were the natural evolution of our knowledge of arrhythmia mechanisms (e.g., the ability to initiate and terminate the reentrant arrhythmias by pacing and electrical conversion) and the refinement of catheter mapping techniques and the success of surgery used with these techniques.

It was Mirowski who initially demonstrated that an implantable defibrillator could convert VT or ventricular fibrillation to sinus rhythm regardless of underlying pathophysiologic substrate and prevent sudden cardiac death. The initial devices were implanted epicardially via thoracotomy have been replaced by small devices with active cans and prevenous leads that are implanted pectorally similar to a pacemaker. Current devices may have single chamber, dual chamber, and biventricular pacing capability. The antitachycardia pacing modalities which evolve from clinical EP studies are widely employed and effective in terminating monomorphic gradient from VT particularly those with rates. With several major trials showing a statistical benefit of ICDs in reducing sudden death, there has been a widespread, logarithmic increase in the use of the device. I have removed the chapter on implantable devices from this edition because there are multiple texts on the topic and the electrophysiologic basis for their use is in the text.

The major thrust of the last twenty-five years has been the development and the use of catheterization techniques to manage cardiac arrhythmias. The concept of using a catheter to deliver energy as an antitachycardia therapeutic modality came from Dr. Melvin Scheinman who was the first to demonstrate the ability to ablate the A-V junction via a catheter to control a ventricular rate in atrial fibrillation. Subsequently, the energy sources changed from a defibrillator to radiofrequency energy which is the standard at this point in time. Nonetheless, additional energy sources such as cryothermal energy, focused ultrasound, and laser energy are all currently being evaluated as modalities to be delivered by a catheter to treat arrhythmias. At the present time focal ablation using radiofrequency is the treatment of choice for all supraventricular tachyarrhythmias, including A-V nodal reentry, circus movement tachycardias using concealed or manifested accessory pathways, incessant automatic atrial tachycardia, isthmus-dependent atrial flutter as well as other macroreentrant atrial tachycardias, and VTs in both normal hearts and those associated with prior infarction. In addition, ablation has become the treatment of choice for VPC-induced cardiomyopathy. Most exciting has been the development of the potential for ablation use in the treatment of atrial fibrillation. While the initial studies suggested that isolating the pulmonary veins to prevent the pulmonary vein foci from initiating and maintaining atrial fibrillation have been used successful in paroxysmal atrial fibrillation, how best to treat persistent and chronic atrial fibrillation still remains unclear. We still do not understand the basic mechanisms of maintenance of atrial fibrillation, so it is not surprising that we don't know how to "fix" it. While isolations with radiofrequency energy have a reasonable acute success for paroxysmal atrial fibrillation reconnections are common and recurrences frequent, particularly if monitoring is done continuously. There has been an interest in using a variety of other lesion sets to treat persistent atrial fibrillation, but none have proved successful, and many times additional atrial tachycardias are a consequence of additional linear lesions. Most recently new high-resolution mapping systems and phase mapping using a new technology have been introduced in an attempt to improve success and understand the underpinnings of the arrhythmia.

In order to reduce stroke cool-tip radiofrequency catheters have been deployed to decrease the coagulant information resulting from noncooled-tip catheters to decrease the incidence of stroke, which remains a potential complication of this ablation. There is an interest in developing new methods to decrease strokes by use of left atrial occlusion devices one of which has just been FDA approved. How widespread the use of these devices will be is unclear, but they are certainly reasonable for patients who can't take anticoagulation and do not wish to undergo a left atrial appendagectomy. New anticoagulants have been developed which will likely replace Coumadin.

One major concept I believe that is critical is that we need to understand the mechanism of arrhythmias before we try to "cure" them with ablation. This was easily done for supraventricular arrhythmias. The ability to accurately define reentrant circuits causing VT and even the underlying mechanism of atrial fibrillation needs further work. Although much has been accomplished, much work still remains. We must not let technology lead the way. We electrophysiologists must maintain our interest in understanding the mechanisms of arrhythmias to that we can devise nonpharmacologic or even pharmacologic approaches that would be more effective and safe to manage these arrhythmias. New molecular approaches may be forthcoming in the near future. The world of molecular biology has seen the recognition of ion channelopathies such as long QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, and catecholaminergic polymorphic VT. Early understanding of these disorders has led to potential ablative therapy, particularly in the Brugada syndrome, and the reintroduction of old fashioned drugs like quinidine and programmed stimulation to treat the short QT syndrome, Brugada syndrome, and idiopathic ventricular fibrillation. Cardiovascular genomics will play an important role in risk stratification of arrhythmias in the future and new fields of proteomics and metabolomics will be essential if we are to develop specifically targeted molecules to treat arrhythmias.

The past forty-five years have seen a rapid evolution of electrophysiology, from one of understanding the simple mechanisms to one of developing therapeutic interventions. The future will require us to go back to the past and continue to understand more complex underlying mechanisms so that our therapeutic modalities will be more successful and safe.