Sanjeev Saksena

Long-term outcome of patients with drug-refractory atrial flutter and fibrillation after single- and dual-site right atrial pacing for arrhythmia prevention.

OBJECTIVESnAn initial crossover study comparing dual- and single-site right atrial pacing was performed followed by a long-term efficacy and safety evaluation of dual-site right atrial pacing in patients with drug-refractory atrial fibrillation (AF). Also examined was the efficacy of two single-site right atrial pacing modes (high right atrium and coronary sinus ostium) and the long-term need for cardioversion, antithrombotic and antiarrhythmic drug therapies during dual-site atrial pacing.nnnMETHODSnThirty consecutive patients with drug-refractory symptomatic AF and documented primary or drug-induced bradycardia were implanted with a dual chamber rate-responsive pacemaker and two atrial leads. Single-site atrial pacing was performed at the high right atrium or the coronary sinus ostium. Continuous atrial pacing was maintained.nnnRESULTSnMean arrhythmia-free intervals increased from 9+/-10 days in the control period preceding implant to 143+/-110 days (p < 0.0001) in single-site right atrial pacing and 195+/-96 days in dual-site right atrial pacing (p < 0.005 versus single-site pacing and p < 0.0001 versus control). Dual-site right atrial pacing significantly increased the proportion of patients free of AF recurrence (89%) as compared to single-site right atrial pacing (62%, p = 0.02). High right atrial pacing and coronary sinus ostial pacing had similar efficacy for AF prevention. Effective rhythm control was achieved in 86% of patients during dual right atrial pacing. Seventy-eight percent of patients at 1 year and 56% at 3 years remained free of symptomatic AF. The need for cardioversion was reduced after pacemaker implant (p < 0.05) and antithrombotic therapy was reduced (p < 0.06) without any thromboembolic event. Coronary sinus ostial lead dislodgement was not observed after discharge.nnnCONCLUSIONSnAtrial pacing in combination with antiarrhythmic drugs eliminates or markedly reduces recurrent AF. Prevention of AF is enhanced by dual-site right atrial pacing. High right atrial and coronary sinus ostial pacing do not differ in efficacy. Dual-site right atrial pacing is safe, achieves long-term rhythm control in most patients, decreases the need for cardioversion, and antithrombotic therapy can be selectively reduced.

Improved suppression of recurrent atrial fibrillation with dual-site right atrial pacing and antiarrhythmic drug therapy

OBJECTIVESnWe compared the safety, tolerance and effectiveness of overdrive high right atrial (RA), dual-site RA and support (DDI or VDI) pacing (SP) in patients with symptomatic atrial fibrillation (AF) and bradycardias.nnnBACKGROUNDnOptimal pacing methods for AF prevention remain unclear.nnnMETHODSnPatients (n = 118) were randomized to each of three pacing modes in a crossover trial.nnnRESULTSnMode adherence was superior for dual-site RA (5.8 months) compared with SP (3.3 months; p < 0.001) and high RA pacing (4.7 months; p = 0.006). Adverse event-free survival improved with dual-site RA (p = 0.007 vs. SP) and was comparable to high RA (p = 0. 75). AF-free survival trended to improve with dual-site RA (hazard ratio [HR] 0.715, p = 0.07 vs. SP) but not high RA (HR = 0.71, p = 0.19) or when dual-site RA was compared with high RA (HR = 0.835, p = 0.175). Time-to-recurrence was longer in dual-site RA (1.77 months) compared with high RA (0.62 months, p < 0.09) or SP (0.44 months, p < 0.05). In antiarrhythmic drug-treated patients, dual-site RA reduced recurrence risk compared with SP (HR = 0.638, p = 0.011) and high RA (HR = 0.669, p = 0.06). In patients with < or =1 AF event/week, dual-site RA improved AF suppression (HR = 0.464, p = 0.004 vs. SP; HR = 0.623, p = 0.006 vs. high RA). Dual-site RA improved AF-free and mode survival (p < 0.03 vs. high RA, p < 0.001 vs. SP) and reduced asymptomatic AF (p < 0.01 vs. high RA).nnnCONCLUSIONnDual-site RA is safe and better tolerated than high RA and SP. In patients on antiarrhythmics, dual-site RA prolonged and high RA trended to prolong time-to-recurrent AF compared with SP. Dual-site RA provides superior symptomatic and asymptomatic AF prevention compared with high RA in patients with symptomatic AF frequency of < or =1/week.

Regional endocardial mapping of spontaneous and induced atrial fibrillation in patients with heart disease and refractory atrial fibrillation

We performed simultaneous catheter mapping of right and left atrial regions at onset and during sustenance of spontaneous atrial fibrillation (AF) in patients with ischemic and/or hypertensive heart disease. Seventeen patients with structural heart disease had spontaneous and electrically induced AF episodes mapped from their onset simultaneously in multiple right and left atrial regions. Atrial premature complexes (APCs) that initiated spontaneous AF had coupling intervals ranging from 260 to 400 ms (mean 332 +/- 61), most commonly arising from the lateral right atrium (31%), right atrioventricular junction (13%), atrial septum (6%), superior left atrium (25%), or inferior left atrium (25%). APC morphology on surface electrocardiograms did not correlate with origin in specific atrial regions. The earliest regions of atrial activation for the first AF cycle were the lateral right atrium (n = 5), superior left atrium (n = 4), distal or mid coronary sinus (n = 4), atrial septum (n = 2), and right atrioventricular junction at the His bundle location (n = 2). Spontaneous AF at onset usually showed discrete but irregular electrograms at virtually all right and left atrial sites mapped, with a reproducible region of AF initiation in all 8 patients with multiple events. The region of earliest atrial activation at spontaneous AF onset was in close proximity to the APC origin in 15 of 16 patients (94%), and 39 of 40 episodes (97%) mapped. Stable patterns of right and left atrial activation were observed at AF onset in 14 patients. Induced AF elicited with right atrial stimulation demonstrated different sites of earliest regional atrial activation at onset compared with spontaneous AF events in 4 of 8 patients. However, discrete intracardiac electrograms were also present in induced AF in all of the mapped atrial regions. Furthermore, the site of extrastimulus delivery in induced AF was also found to be in close proximity to the earliest region of atrial activation for the first AF beat. We conclude that spontaneous AF is initiated by APCs arising in different right or left atrial regions in patients with structural heart disease and the initial region of atrial activation in AF is in proximity to the region of APC origin. Organized and repetitive electrical activation is frequently observed in both right and left atria at AF onset. Although electrically induced AF may have different activation patterns than spontaneous AF at onset in many patients, both types of AF demonstrate organization and earliest atrial activation in proximity to the initiating APC.

Catheter ablation of inducible atrial flutter, in combination with atrial pacing and antiarrhythmic drugs ("hybrid therapy") improves rhythm control in patients with refractory atrial fibrillation.

AbstractAtrial flutter or tachycardia may coexist with atrial fibrillation [AF] and can be treated with ablation techniques in attempt to reduce the total AF burden. The role of ablation of latent atrial tachyarrhythmias elicited at electrophysiologic study in conjunction with atrial pacing and antiarrhythmic drugs in patients with refractory AF has not been evaluated. We evaluated the efficacy of catheter ablation of electrically induced atrial flutter or atrial tachycardia in improving rhythm control in patients with refractory AF. Methods: Consecutive patients with refractory AF, and spontaneous atrial flutter (Group 1) or without spontaneous atrial flutter (Group 2) underwent programmed stimulation in a baseline drug-free state. All patients had electrically induced atrial flutter or tachycardia. Radiofrequency ablation of the arrhythmia substrate was performed in all patients. Primary endpoints evaluated for patient outcome in both groups included maintenance of rhythm control and freedom from recurrent atrial tachyarrhythmias. Results: Forty-three patients, with a mean age of 66±13 years were studied. Group 1 consisted of 22 patients while Group 2 had 21 patients. Ablation of the tricuspid valve-inferior venacaval isthmus was performed in 41 patients who had common atrial flutter induced at electrophysiologic study. Ablation of other atrial sites was performed in 8 patients with induced atypical flutter and 4 patients with induced atrial tachycardia. Ten of these patients had ablation of more than one arrhythmia. 17 patients (40%) had atrial pacing instituted and 28 patients remained on a class 1/3 antiarrhythmic drug. During a mean follow-up of 26±14 months, 33 patients (82.5%) remained in rhythm control. Actuarial analysis showed 96% of patients in rhythm control at 6 months, 94% at 12 months, and 90% at 24 months. Freedom from symptomatic AF recurrence was 64% at 6 months, 58% at 12 months, and 42% at 24 months. The outcome for both of these endpoints was similar for Group 1 and Group 2 (p = NS). The AF free interval increased significantly from 7±9 days to 172±121 days (p < 0.01) after ablation. This increase was again similar in both the groups. In the 14 patients were who did not receive atrial pacing and who remained on the same class 1/3 antiarrhythmic drug, the AF free interval increased from 18±17 days to 212±102 days (p < 0.01).nConclusions: We conclude that electrophysiologic studies can elicit latent atrial flutter or tachycardia in patients with refractory AF without spontaneous monomorphic atrial tachyarrhythmias. Catheter ablation of electrically induced atrial flutter or tachycardia either alone, or with atrial pacing and with antiarrhythmic drug may improve rhythm control and reduce AF recurrences. This is similar in patients with and without spontaneous atrial flutter and refractory AF.

Right and left atrial activation during external direct-current cardioversion shocks delivered for termination of atrial fibrillation in humans

We examined the regional electrophysiologic effects of successful and unsuccessful direct-current cardioversion shocks on different right and left atrial regions in patients with sustained atrial fibrillation (AF). Patients with sustained AF undergoing external cardioversion underwent simultaneous mapping of the right and left atria. Electrogram changes after shock delivery, regional atrial activation, and effects of shock intensity were analyzed. Twenty-two patients with sustained AF received 52 shocks (mean 2.4/patient, 22 successful and 30 unsuccessful). The efficacy of 50, 100, 200, and 300 J was 18%, 39%, 100%, and 100%, respectively. In all 22 successful shocks, there was virtually simultaneous termination of electrical activity in all right and left atrial regions mapped. Unsuccessful shocks resulted in a significant increase in mean atrial cycle length at lateral right atrium, superior left atrium, and proximal, mid, and distal coronary sinus (p = 0.01), but not at the interatrial septum (p >0.2), which often disappeared before the next shock. This cycle length prolongation was accompanied by reduction in fragmented and chaotic electrograms (p <0.03) and emergence of discrete electrograms at all right and left atrial regions that persisted until the next shock. The changes in electrogram morphology failed to alter the surface electrocardiographic appearance of AF. There was no correlation between the shock intensity and the magnitude of these effects. We conclude that termination of AF with external cardioversion shocks is associated with the widespread extinction of regional atrial wave fronts. Unsuccessful shocks are associated with a temporary slowing of atrial activation at all regions except at the interatrial septum and emergence of organized and/or rapidly propagating wave fronts.

New Devices and Hybrid Therapies and New Devices for Treatment of Atrial Fibrillation

Atrial ~brillation [AF] is the most common arrhythmia, whose prevalence is expected to increase with aging of our population. It is a potentially disabling illness with an independent contribution to morbidity and mortality [1,2]. Due to recurrent nature of arrhythmia and lack of uniformally effective therapy, treatment of AF has been a frustrating task for the clinician. Pharmacologic approaches when used alone have poor long-term ef~cacy with 50% to 70% of patients eventually progressing to chronic AF [3,4]. It also carries the risk of proarrhythmia and may increase mortality especially in patients with left ventricular dysfunction [5,6]. Several new nonpharmacologic technologies, pacing, ablation and implantable atrial de~brillators, are being developed and seem to improve outcome of therapy for AF in different patient subgroups. All these therapies, however, when applied alone have limited ef~cacy, patient acceptance, questionable practicality or relatively high incidence of serious complications. Therefore, there is an increased interest in combination/hybrid therapy where few different therapeutic modalities are used in a given patient in an attempt to achieve synergistic effect, increase their ef~cacy over any single approach while decreasing side effects and improve tolerance.

Management of the Patient With an Implantable Cardioverter-Defibrillator in the Third Millennium

Implantable cardioverter-defibrillator (ICD) devices were originally developed for prevention of sudden cardiac death (SCD). They are now widely regarded as the primary therapy for this condition. Clinical trials have led to a progressive expansion in indications for their use.1,2⇓ Recent clinical reports show effectiveness of these devices in patients with recurrent syncope, in the prevention of SCD in high-risk patients with coronary disease, and in the treatment of atrial fibrillation. Refinements in ICD technology have improved functionality and enhanced safety. Optimal patient management requires intimate knowledge of these complex devices and of the diverse arrhythmias that may be treatable by a single multifaceted ICD device.nnA 75-year-old man presented with near-syncope and ventricular arrhythmias. He had a past history of dilated cardiomyopathy, old cerebrovascular accident, symptomatic atrial flutter/fibrillation, and heart failure. He had been treated with anticoagulation and antiarrhythmic drugs, but it was noted on admission that he was in atrial flutter with a ventricular rate of 110 bpm. Electrophysiological evaluation revealed isthmus- (common or typical) and nonisthmus- (atypical) dependent atrial flutter and inducible hypotensive monomorphic sustained ventricular tachycardia. A linear ablation of the tricuspid valve-inferior vena cava isthmus interrupted common flutter, but atypical flutter persisted. The following day, a dual chamber ICD capable of defibrillation and antitachycardia, as well as standard demand pacing in both chambers, was inserted. An additional coronary sinus lead was placed to permit dual site right atrial pacing for prevention of atrial flutter and fibrillation (Figure 1A). The patient was given a handheld activator for termination of atrial fibrillation (AF) and flutter. nnnnFigure 1. A, Lateral radiograph of the chest showing the first dual chamber atrioventricular defibrillator inserted in patient with refractory atrial fibrillation. Note the distinct atrial and ventricular pacing and defibrillation leads. An additional coronary sinus pacing lead is placed …

Implantable defibrillators in the third millennium: increasingly relegated to a standby role?

In the last five years, evidence has accumulated confirming the superiority of implantable cardioverter-defibrillator (ICD) therapy compared to antiarrhythmic drug therapy for prevention of sudden death [(1,2)][1]. Clinical trials, with rare exception, have established mortality benefits of ICD

Catheter Mapping of Spontaneous and Induced Atrial Fibrillation in Man

The clinical electrophysiologic study of atrial fibrillation [AF] has recently progressed from static characterization of the substrate to the dynamic investigation of both induced and spontaneous AF in man. Prior studies have demonstrated inhomogeneity and greater dispersion of atrial refractoriness in patients with AF, but recently atrial electrical remodeling with consequent abbreviation of atrial refractory periods has also been reported. Yet further experimental observations have suggested the existence of additional arrhythmogenic mechanisms for certain AF subsets. These include studies that have demonstrated a stable atrial “flutter” circuit in one atrium with fibrillatory conduction or a “focal” atrial tachyarrhythmia arising commonly in the left atrium.Efforts at catheter mapping of AF are now in progress. New mapping techniques and novel devices are currently being employed. We have performed catheter mapping simultaneously in right and left atrial sites at onset and during sustained pacing-induced and spontaneous AF in patients with ischemic and/or hypertensive heart disease. Atrial premature complexes that initiated spontaneous AF typically had coupling intervals ranging from 260 to 400 ms and most frequently arose in the crista terminalis, right atrioventricular junction or superior left atrium. AF at onset showed discrete electrograms at virtually all right and left atrial regions mapped and the region of earliest atrial activation during AF was in close proximity to the premature complexes in over 90% of patients. The regional atrial activation sequence for the first 10 AF beats demonstrated stable or unstable patterns in individual patients. In contrast to spontaneous AF, the initial arrhythmia of induced AF was seen to have a significantly different site of earliest atrial activation but similar discrete electrograms in different atrial regions. However, as with spontaneous AF, the site of extrastimulus delivery was in close proximity to the first induced beat.We conclude that regional catheter mapping of AF is feasible and safe in man and organized electrical activity is frequently observed at AF onset in patients with heart disease. Both right and left atrial regions can be the source of atrial premature complexes and at the onset of spontaneous AF. Induced AF may have differing activation patterns than spontaneous AF but both demonstrate earliest activation in proximity to the initiating atrial premature complex. These findings may help explain therapeutic benefits of right and left atrial interventions and pacing therapies in AF.

The Editors' Forum: Calamities and Cardiac Arrhythmias: The Medical and Scientific Impact of Epidemics of Suffering

The expression of human disease states at times of disasters has been a subject of intense but often intermittent study. These studies provide important insights into the medical condition and its interaction with its environment. The effect of natural disasters is often chronicled, and sometimes scientifically well studied. Regrettably, and with more frequency, we are encountering unnatural disasters such as the recent event in New York City and Washington DC on September 11, 2001 that can produce extraordinary mortality, often to the exclusion of comparable morbidity. In a metropolis with more state-of-the-art medical care than any in the world, only a few remained alive to benefit from the available care. At such times, we can harken back to prior calamities in search of guidance to mount an appropriate medical response. Almost sixteen years ago to the day, on September 19, 1985 an earthquake registering 8.1 on the Richter scale hammered Mexico City. More than 9,000 people died or disappeared in Mexico City, possibly 30,000 more were injured and over 95,000 became homeless. At the Benito Juarez Hospital, over a thousand doctors, nurses and patients were buried alive. Only a few scrambled out of the of demolished buildings alive. In fact, in both disasters ministering to the responders to the tragedy and survivors often occupied most of the medical rescue efforts. In an another man-made event, the raging oil fires of Kuwait in February 1991 produced an massive environmental and ecological disaster with vast, unknown and lingering health consequences. What do such events have to do with the art and science of cardiac arrhythmology? For starters, the classic triad of arrhythmogenesis has as one of its three founding elements, autonomic modulation. Even more fundamental is the involvement of autonomic nervous influences on the normal cardiac rhythm which has been long recognized. However, the processes by which such effects are achieved are poorly understood. For example, periodic oscillation of arterial pressure, heart rate and muscle sympathetic nerve activity and its relation to respiratory activity has been intensively studied. Initially thought to be secondary to baroreceptor reflexes, mounting evidence now suggests that these oscillations result from fluctuations in instantaneous sympatho-vagal balance [1]. In patients with atrial fibrillation (AF), an increase in adrenergic drive preceding a shift to vagal tone predominance has occurred immediately before AF onset. Two types of AF initiation depending on sympathetic or vagal tone enhancement have been reported [2,3]. In patients with implantable defibrillators at the onset of ventricular tachycardia (VT) or ventricular fibrillation (VF) heart rate variability findings are consistent with the shift of sympatho-vagal balance towards sympathetic predominance and a reduction in vagal tone [4,5]. In a large clinical trial, this sympathetic dependence was more commonly seen in VT events that were unrelated to early cycle triggering ectopics [6]. In the aftermath of a natural disaster it has been reasonable to speculate that such autonomic mechanisms could mediate increased density of arrhythmic events leading to clustering. Indeed, an increased incidence of sudden death or VT events have been observed after earthquakes and other disasters. It will remain to be seen if epidemiologic data substantiate such clustering after the New York & Washington DC disasters. There are however specific effects of environmental toxins related to individual disaster circumstances. Air pollution has been shown to have harmful cardiovascular effects with increased mortality and morbidity with long-term exposure. While deleterious effects of air pollution usually involve the respiratory system, immune system activation and coagulation abnormalities, the cardiovascular system is also affected by these actions. Cardiac arrhythmias may result from the autonomic impact on a preexisting diseased substrate and myocardial vulnerability [7]. Chronic exposure to metallic toxins such as lead in environmental disasters can lead to intraventricular conduction disturbances due to cumulative effects of such toxins [8]. Linkage between chronic fatigue syndrome and the raging oil fires in Gulf war veterans remains an active subject of investigation. Individuals with propensity to such disorders may have environmental precipitants. Cardiac dysfunction after smoke inhalation includes response to burn-related hypovolemia with a sec-