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Atrial fibrillation (AF) tends to recur in at least one half of the patients being treated with an antiarrhythmic agent. However, if the patient being treated is appropriately anticoagulated, and if during recurrence the ventricular response rate is controlled, a recurrence rarely requires emergent treatment. Rather, the AF recurrence can most often simply be considered a clinically important nuisance. Therefore, recurrence of AF during antiarrhythmic drug therapy should not be considered drug failure per se. Instead, the frequency and severity of recurrence constitute the measure of efficacy. Occasional recurrence may be clinically acceptable and preferable to persistent AF or frequent episodes of paroxysmal AF. Because occasional recurrence of AF should not be considered failure of drug therapy, simple outpatient cardioversion of the AF with restoration of sinus rhythm is recommended should recurrence occur and the AF persist. Simple therapies, such as acute cardioversion to restore sinus rhythm, should be considered a part of the expected long-term therapy of the patient with AF. Finally, the drug of choice should be one that is well tolerated, easy to take (preferably only once or twice a day), and has the fewest potential side effects, particularly serious adverse effects.

It is now known that most cases of atrial flutter are due to reentrant excitation in the right atrium. In the usual reentrant circuit, the reentrant excitation wavefront travels up the interatrial septum and down the right atrial free wall. The boundaries of this reentrant circuit include on one side the tricuspid valve ring and on the other side an area of block, which is probably functional, in the region between the venae cavae. The latter area of block forms during the transitional atrial fibrillation rhythm of variable duration that almost always precedes the initiation of atrial flutter. An isthmus of conduction is also present in the reentrant circuit, and is bounded by the tricuspid ring and the inferior vena cava, the Eustachian ridge, and the coronary sinus. It is probable that an abnormal atrial tissue substrate is usually required. Reentrant circuits around a surgical incision in the atria or around the pulmonary veins (in whole or in part) may be also responsible for atrial flutter.

The Survival With ORal D-sotalol (SWORD) trial tested the hypothesis that the prophylactic administration of oral d-sotalol would reduce total mortality in patients surviving myocardial infarction (MI) with a left ventricular ejection fraction (LVEF) of < or = 40%. Two index MI groups were included: recent (6 to 42 days) and remote (> 42 days) with clinical heart failure (n = 915 and 2,206, respectively). The trial was discontinued when the statistical boundary for harm was crossed (RR = 1.65; p = 0.006). All baseline variables known to be associated with mortality risk (e.g., LVEF, heart failure class, age) as well as variables related to torsades de pointes (e.g., time from beginning of therapy, QTc, gender, potassium, renal function, dose of d-sotalol) were assessed for interaction of each variable with treatment assignment, computing RR and 95% confidence interval (CI) from Cox regression models. The d-sotalol-associated mortality was greatest in the group with remote MI and LVEFs of 31% to 40% (RR = 7.9; 95% CI 2.4 to 26.2). Most variables known to be associated with torsades de pointes were not differentially predictive of d-sotalol-associated risk, except female gender (RR = 4.7; 95% CI 1.4 to 16.5). These findings suggest that (1) most of the d-sotalol-associated risk was in patients remote from MI with a LVEF of 31% to 40%; comparable placebo patients had a very low mortality (0.5%); and (2) very little objective data supports torsades de pointes or any specific proarrhythmic mechanism as an explanation for d-sotalol-associated mortality risk.

Sudden cardiac death due to arrhythmic events is the major cause of mortality among early post-myocardial infarction (MI) patients, accounting for > 250,000 deaths annually in the United States alone. Antiarrhythmic drugs can be used in such patients as well as in those who have not had a recent MI but are at high risk for sudden cardiac death (e.g., those with ventricular tachycardia/fibrillation, or who have survived cardiac arrest). Most antiarrhythmic drugs available, however, have limitations arising from their toxic and proarrhythmic potential. Thus, research and development of new agents and treatment modalities are desirable. This article seeks to enumerate the lessons of past clinical trials with these agents and to provide guidelines for future trials. That a variety of antiarrhythmic drugs have been associated with an increased mortality has been a disturbing observation. It is therefore imperative that candidates for antiarrhythmic therapy be selected appropriately. We recommend that future clinical trials use stringent criteria for the identification of patients at "high risk" for arrhythmia or sudden cardiac death, and limit recruitment to such patients. Traditional markers, such as the increased frequency and complexity of ventricular premature beats, and low left ventricular ejection fraction, have not been successful in identifying these high-risk patients. However, decreased heart rate variability and cardiac late potentials recorded on a signal-over-aged electrocardiogram appear to be more specific markers of post-MI arrhythmia or sudden cardiac death and may, in conjunction with the traditional markers, be used to improve selection of trial populations. Since the risk of sudden cardiac death diminishes with time after MI, it is also recommended that the temporal window of treatment with antiarrhythmic agents be limited to 1 year post-MI. It is also important to define clearly the endpoints of efficacy evaluations. A short-term reduction on markers like ventricular ectopic beats, for example, does not translate into a long-term decrease in arrhythmia-related mortality. Therefore, a reduction in overall mortality is the only meaningful endpoint to define the true risk-benefit ratio. To limit exposure to the potentially adverse effects of these agents, target populations for prophylactic antiarrhythmic drugs should be limited to recent post-MI patients at high risk for sudden cardiac death due to arrhythmia. Avoiding exposure of low-risk patients to antiarrhythmic drugs is equally imperative. "Low risk" of all-cause mortality includes the group of post-MI patients with a left ventricular ejection fraction >36%. Risk must be continuously evaluated in the setting of other pharmacologic (angiotensin-converting enzyme [ACE] inhibitors, aspirin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ["statins"], and others) and/or nonpharmacologic interventions (coronary artery bypass graft, angioplasty, implantable cardioverter/defibrillator). There is also a need to improve noninvasive techniques for identifying patients in the high-risk category-at present, the presence of ventricular premature beats and a left ventricular ejection fraction <36% is considered somewhat predictive of sudden cardiac death. Thus, patients with a recent MI and moderately low left ventricular ejection fraction (< or = 36% but not <20%) may be considered for antiarrhythmic therapy. A subset analysis of patients with low heart rate variability can provide valuable additional information. It is important to note that although all-cause mortality is a valid endpoint for such trials, stratification by specific cause of mortality is desirable.

There are many reasons why one might wish to suppress atrial fibrillation (AFib) and attempt to maintain sinus rhythm. This article assumes that the clinical decision to maintain sinus rhythm has been made. That being the case, antiarrhythmic drug therapy is generally the first line of treatment of AFib. Currently in the United States, there are 8 available antiarrhythmic drugs that have demonstrated efficacy for preventing AFib. The drugs are quinidine, procainamide, disopyramide, flecainide, propafenone, moricizine, sotalol, and amiodarone. Because AFib tends to recur regardless of the drug selected, recurring in at least one-half of the patients being treated, no drug is clearly better than any other for suppression of AFib. Furthermore, because AFib is rarely life-threatening, occasional recurrence should be anticipated and should not be considered failure per se. The measure of drug efficacy is the frequency of recurrence. Before initiating drug therapy, the presence or absence of structural heart disease must be determined, because in the absence of structural heart disease, antiarrhythmic drugs generally can be given rather safely, but in the presence of structural heart disease, especially when associated with ventricular dysfunction, there is an important risk of developing ventricular proarrhythmia. Considerations for specific drug selection are discussed and an algorithm for therapy is suggested.

Type I atrial flutter is due to reentrant excitation, principally in the right atrium. The standard ECG remains the cornerstone for its clinical diagnosis. Acute treatment should be directed at control of the ventricular response rate and, if possible, restoration of sinus rhythm. Radiofrequency catheter ablation therapy provides the best hope of cure, although atrial fibrillation may subsequently occur after an ostensibly successful ablative procedure. Alternatively, antiarrhythmic drug therapy to suppress recurrent atrial flutter episodes may be useful, recognizing that occasional recurrences are common despite therapy. Radiofrequency ablation of the His bundle ablation with placement of an appropriate pacemaker system may be useful in selected patients.

Background: It is recognized that a ventricular vulnerability period exists during which atrial shock delivery may induce a ventricular tachyarrhythmia. This study was designed to define the zone in which the ventricles are vulnerable to induction of ventricular tachyarrhythmia during delivery of atrial shocks in the sterile pericarditis canine model of atrial fibrillation., Methods and Results: Two days after creation of sterile pericarditis, 24 dogs underwent either a four-part or five-part ventricular vulnerability protocol during which atrial shocks were delivered between transvenous catheters, one in the distal coronary sinus and one in the right atrial appendage. The protocol included part 1, shocks during induced atrial fibrillation; parts 2 through 4, shocks delivered synchronously with the last ventricular beat of one of the following three ventricular pacing protocols: constant ventricular rates (S1S1), short-long-short cycles (S1S2S3-V), and ventricular premature beats (S1); and part 5, shocks delivered synchronously with the last R wave resulting from an atrially paced short-long-short cycle (S1S2S3-A). Ventricular tachyarrhythmia was induced 122 times: 2 of 665 shocks in two dogs in part 1, 29 of 786 shocks in nine dogs in part 2, 67 of 734 shocks in 15 dogs in part 3, 24 of 919 shocks in five dogs in part 4, and none in part 5. All ventricular proarrhythmia resulted from shocks delivered during the T wave of a preceding ventricular beat. No episodes of ventricular tachyarrhythmia were induced by atrial shocks synchronized to R waves with the previous RR at intervals above the QT+60 ms interval (absolute interval >320 ms), with one exception, at the QT+100 ms interval (absolute interval 360 ms)., Conclusions: With transvenous electrode catheters used to deliver atrial shocks, life-threatening ventricular rhythms were induced but were limited to a specific zone defined by the QT interval.

Entrainment was first described based on observations during rapid (overdrive) pacing of type I atrial flutter. Entrainment is capture of the reentrant circuit of a tachycardia without interrupting the tachycardia, so that with cessation of pacing, the spontaneous reentrant tachycardia is still present. During entrainment, the orthodromic wavefront from the pacing impulse resets the tachycardia to the pacing rate, while the antidromic wavefront either collides with the orthodromic wavefront of the previous beat (usual case) or is blocked by some other mechanism (refractoriness or another cause of block). Entrainment may be either manifest or concealed. The principles of entrainment during type I atrial flutter have permitted identification of targets for successful ablation, of mapping sites within or outside the reentrant circuit, and of appropriate pacing rates to successfully interrupt atrial flutter and restore sinus rhythm.

Background: Chronic atrial fibrillation (AF) is thought to be due to multiple, simultaneously circulating wavelets. In the canine sterile pericarditis model, the mechanisms of maintenance of AF are not yet understood., Methods and Results: During six induced AF episodes in six dogs with sterile pericarditis, 372 unipolar electrograms were recorded simultaneously from an electrode array placed around both atrial free walls, along with 10 to 24 electrodes from the atrial septum, by use of a multiplexing system. Activation maps during 12 consecutive 100-ms windows were analyzed from an episode of sustained AF in each dog (mean duration, 32 +/- 24 minutes). In two dogs, two such activation maps during the same episode of AF were analyzed. During AF, multiple unstable reentrant circuits (mean number, 1.4 +/- 0.1 per 100-ms analysis window) with very short cycle lengths (mean, 111 +/- 8 ms) present primarily in the atrial septum and right atrium were responsible for maintenance of AF. The unstable reentrant circuits frequently disappeared and re-formed. Wave fronts traveling from one atrium to the other and/or from the atrial septum play an important role in re-formation of unstable reentrant wave fronts., Conclusions: In this model of paroxysmal AF, unstable reentrant circuits of very short cycle length principally involving the atrial septum appear to be critical for maintenance of AF. Some reentrant circuits disappear as others re-form, so that at least one reentrant circuit is always present. Because the atria cannot follow their very short cycle lengths in a 1:1 manner, AF is maintained.

In his book Deadly Medicine and on television, Thomas Moore impugns the process of antiarrhythmic drug approval in the 1980s, alleging that the new generation of drugs had flooded the marketplace and had caused deaths in numbers comparable to lives lost during war. To assess these important public health allegations, we evaluated annual coronary artery disease death rates in relation to antiarrhythmic drug sales (2 independent marketing surveys). Predicted mortality rates were modeled using linear regression analysis for 1982 through 1991. Deviations from predicted linearity were sought in relation to rising and falling class IC and overall class I antiarrhythmic drug use. Flecainide came to market in 1986 and encainide in 1987. Combined class IC sales peaked in 1987 and 1988 (maximum market penetration, 20%, first quarter 1989). Results of the Cardiac Arrhythmia Suppression Trial (CAST) were disclosed in April 1989. Overall annual class I antiarrhythmic prescription sales actually fell slightly (-3% to -4%/yr) in the 2 years before CAST and then more abruptly (- 12%) in the year after CAST (1990). Sales of class IC drugs fell dramatically after CAST (by 75%). Coronary death rates (age adjusted) fell in a linear fashion during the decade of 1982 through 1991. No deviation from predicted rates was observed during the introduction, rise, and fall in class IC (and other class I) sales: rates were 126/100,000 in 1985 (before flecainide), 114 and 110 in 1987 and 1988 (maximum sales), and 103 in 1990 (after CAST). Deviations in death rates in the postulated range of 6,000 to 25,000 per year were shown to be excluded easily by the 95% confidence intervals about the predicted rates. Entry of new antiarrhythmic drugs in the 1980s did not lead to overall market expansion and had no adverse impact on coronary artery disease death rates, which fell progressively. Thus, the allegations in Deadly Medicine could not be confirmed.

This study examines in a prospective, multicenter trial the feasibility and advantage of current-based, transthoracic defibrillation. Current-based, damped, sinusoidal waveform shocks of 18, 25, 30, 35, or 40 amperes (A) were administered beginning with 25 A for polymorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) or 18 A for monomorphic VT; success rates were compared with those of energy-based shocks beginning at 200 J for VF/polymorphic VT and 100 J for VT. The current-based shocks were delivered from custom-modified defibrillators that determined impedance in advance of any shock using a "test-pulse" technique; the capacitor then charged to the exact energy necessary to deliver the operator-selected current against the impedance determined by the defibrillator. Three hundred sixty-two patients received > 1 shock for VF, polymorphic VT, or monomorphic VT: 569 current- based shocks and 420 energy-based shocks. Current-based shocks of 35/40 A achieved success rates of up to 74% for VF/polymorphic VT; 30 A shocks terminated 88% of monomorphic VT episodes. Energy-based shocks of 300 J terminated 72% of VF/polymorphic VT; 200-J shocks terminated 89% of monomorphic VT. We could not demonstrate a significant increase in the success rate of current-based shocks over energy-based shocks for patients with high transthoracic impedance; this may be due to inadequate sample size. Thus, current-based defibrillation is clinically feasible and effective. A larger study will be needed to test whether current-based defibrillation is superior to energy-based defibrillation.

Objectives: This study sought to characterize the spontaneous onset of atrial flutter in patients., Background: Temporary epicardial electrodes are routinely placed on the atria of patients at the time of open heart surgery and brought out through the anterior chest wall for potential diagnostic and therapeutic use in the postoperative period. We utilized these electrodes to study the spontaneous onset of type 1 atrial flutter in 16 patients in the postoperative period after open heart surgery., Methods: Twenty-seven episodes of the spontaneous onset of type I atrial flutter from sinus rhythm were studied in these 16 patients by recording bipolar atrial electrograms simultaneously with at least one electrocardiographic lead during each episode., Results: In all 27 episodes, the onset of type I atrial flutter was through a transitional rhythm of variable duration (mean 9.3 s) precipitated by a premature atrial beat. In 21 episodes, the transitional rhythm was atrial fibrillation; in 3 episodes it was type II atrial flutter that appeared to generate atrial fibrillation; and in 3 episodes it was a brief (3 to 6 beats), rapid, irregular arrhythmia., Conclusions: Type I atrial flutter does not start immediately after a premature atrial beat. Rather, it starts after a transitional rhythm that is usually atrial fibrillation. Extrapolating from mapping studies of the onset of atrial flutter in the canine pericarditis model, we suggest that a transitional rhythm is required for the initiation of type I atrial flutter because during that rhythm, the requisites for development of the atrial flutter reentry circuit evolve.

Background: Left ventricular dysfunction after myocardial infarction is associated with an increased risk of death. Other studies have suggested that a potassium-channel blocker might reduce this risk with minimal adverse effects. We investigated whether d-sotalol, a pure potassium-channel blocker with no clinically significant beta-blocking activity, could reduce all-cause mortality in these high-risk patients., Methods: Patients with a left ventricular ejection fraction of 40% or less and either a recent (6-42 days) myocardial infarction or symptomatic heart failure with a remote (> 42 days) myocardial infarction were randomly assigned d-sotalol (100 mg increased to 200 mg twice daily, if tolerated) or matching placebo twice daily., Findings: After 3121 of the planned 6400 patients had been recruited, the trial was stopped. Among 1549 patients assigned d-sotalol, there were 78 deaths (5.0%) compared with 48 deaths (3.1%) among the 1572 patients assigned placebo (relative risk 1.65 [95% CI 1.15-2.36], p = 0.006). Presumed arrhythmic deaths (relative risk 1.77 [1.15-2.74], p = 0.008) accounted for the increased mortality. The effect was greater in patients with a left ventricular ejection fraction of 31-40% than in those with lower (

During the 7-year period from August 1986 to December 1993, 242 patients with malignant ventricular arrhythmias underwent 242 ICD implantations and 50 subcutaneous generator changes. Wound infections developed in 5 patients (1.7%): in 3 cases, after primary implantation (3/242 [1.2%]); and in 2 following a generator change (2/50 [4.0%]). This difference was not statistically significant. Infection developed at the generator pocket and became clinically manifest between 6 weeks and 40 months, postoperatively. Our treatment approach with the first patient consisted of simple debridement of the pocket and reimplantation of the existing generator. This led to recurrence, and the generator was safely explanted. In the remaining four patients, our approach has been that of local treatment, with wide debridement of the pocket, and placement of a closed irrigation system with continuous irrigation with a bacitracin, polymyxin, neomycin solution, and culture-specific antibiotic therapy. We have successfully controlled the infection and salvaged the generator with this approach in all four patients, who are all alive and well at a mean follow-up of 25.0 +/- 17.3 months with no recurrence. The good results obtained in these patients suggest that the concept of total explanation of the infected ICD should be reassessed.

Sustained atrial fibrillation is very common after cardiac surgical procedures. We hypothesized that atrial defibrillation could be accomplished consistently and safely by means of low-energy shocks delivered by temporary stainless steel wire electrodes placed at the time of the operation. Sterile pericarditis was created in five mongrel dogs (20.9 +/- 2.1 kg), and pairs of standard temporary stainless steel wire electrodes were placed on the right atrial appendage, on Bachmann's bundle, and on the right ventricular apex for pacing, sensing, and recording. Temporary stainless steel wire electrodes, insulated except for the distal 6 cm and used to deliver defibrillation shocks, were placed adjacent to both atrial free walls and secured to the pericardium. All electrodes were brought out through the skin, and the sternotomy was closed. Dogs were tested in the conscious state on postoperative day 2. Sustained atrial fibrillation was induced by rapid atrial pacing. A customized software program was used to control the defibrillator, which delivered R wave-synchronous biphasic shocks to the atria through the temporary defibrillation electrodes. The shock intensity began at 50 volts and was increased by 10-volt increments until atrial fibrillation was terminated. Atrial fibrillation was terminated in all dogs at 112 +/- 7 volts, with an energy of 0.42 +/- 0.07 joule and an impedance of 67.8 +/- 4 ohms (all values mean +/- standard error of the mean). The mean percent success for atrial defibrillation at this minimal threshold was 49%. Thus at low-threshold voltages atrial fibrillation could be terminated with every other shock. A 25% increase in the minimal threshold voltage improved the conversion rate to 73% (mean energy 0.66 +/- 0.19 joule and mean impedance of 67 +/- 3.8 ohms). No complications were detected with the use of the electrodes or after their removal on the seventh postoperative day. One instance of electrode migration on the right atrial free wall was detected by roentgenography, but this did not adversely affect atrial defibrillation threshold. No ventricular arrhythmias or hemodynamic complications were noted during shock delivery. We conclude that successful conversion of atrial fibrillation to sinus rhythm can be achieved consistently with shock energies below 0.5 joule delivered with temporary epicardial defibrillation wire electrodes in this canine pericarditis model. These results suggest that this approach to the management of sustained atrial tachyarrhythmias has considerable promise in the management of atrial fibrillation in patients who have had cardiac operations.

Doubts have been expressed about the clinical usefulness of time domain analysis of the signal averaged electrocardiogram in patients with prolonged QRS complex duration. We studied 147 patients using a signal averaged ECG (40-250 Hz) whose QRS complex was longer than 100 ms. A baseline electrophysiology study was also performed in 128 of these patients. Seventy-seven patients had a minor (QRS < 120 and > 100 ms) conduction defect. Thirty-seven of these 77 had either induced or spontaneous sustained ventricular tachycardia (group I) and 40 had no sustained ventricular tachycardia (group II). Seventy patients had a major (QRS > or = 120 ms) conduction defect, 44 of whom had sustained ventricular tachycardia (group A). The remaining 26 without this condition formed Group B. Group I compared to group II patients had a longer filtered QRS duration (120.8 +/- 14 vs 104.5 +/- 9.5 ms, P < 0.001), a longer low amplitude signal duration (41 +/- 12.1 vs 31 +/- 12.6 ms, P < 0.0001) and a lower root mean square of the last 40 ms of the filtered QRS complex (27 +/- 29.8 vs 35 +/- 25.3 microV, P = ns). Group A compared to group B had a longer filtered QRS duration (157.7 +/- 20.2 vs 140.7 +/- 15.7 ms, P < 0.001), a longer low amplitude signal duration (57.3 +/- 24.9 vs 37.8 +/- 20.3 ms P < 0.001) and a lower root mean square of the last 40 ms of the filtered QRS complex (14.3 +/- 11.2 vs 22.0 +/- 10.5 microV, P < 0.01). Using conventional late potential criteria, the sensitivity and specificity of the signal averaged ECG for the detection of sustained ventricular tachycardia patients with a minor conduction defect were 89% and 75%, respectively. The same criteria applied to patients with a major conduction defect were sensitive (sensitivity: 87%) but non-specific (specificity: 50%). However, by using modified late potential criteria, such as the presence of two of any of the following three signal averaged parameters: filtered QRS duration > or = 145 ms, low amplitude signal duration > or = 50 ms, root mean square of the last 40 ms of the filtered QRS complex < or = 17.5 microV, we derived a non-optimal but still acceptable combination of sensitivity (68%) and specificity (73%). We conclude that traditional late potential criteria can be applied in patients with a minor conduction defect, but modification of these criteria is necessary to derive useful clinical information for risk stratification of patients with a QRS complex duration > or = 120 ms.

Much has been learned about atrial flutter mechanisms from studies in animal models and in patients. In fact, it seems virtually always due to some form of reentry. Furthermore, it seems likely that there is more than one location of the atrial flutter reentrant circuit in patients, although the reentrant circuit in most instances of atrial flutter seems to be activation up the interatrial septum and then down the posterior right atrial free-wall. Other locations of the reentrant circuit may include the right atrial free-wall alone or the tricuspid valve annulus, among others. Resolution of this awaits better mapping data from human studies. Clearly, an understanding of mechanism is central to achieving effective ablation. Thus, if it is possible to identify a critical aspect or aspects of the atrial flutter mechanism vulnerable to therapy with ablative energy, effective treatment using ablative techniques should be successful.

Objectives: This study sought to determine whether temporary epicardial wire electrodes can be used safely and effectively to defibrillate the atria with low energy shocks in the absence of anesthesia., Background: Atrial fibrillation after open heart surgery is a significant clinical problem., Methods: Twelve dogs with sterile pericarditis were studied. In the first group (6 dogs, bilateral thoracotomy group), a wire electrode, insulated except for the distal 6 cm, was placed on the epicardial free wall of each atrium. Each end of the bare wire was then sutured to the parietal pericardium. In the second group (6 dogs, median sternotomy group), the wire electrodes were kept in place by a double loop of Prolene placed around the distal tip of the bare wire and sewn to the overlying parietal pericardium. In the bilateral thoracotomy group, atrial defibrillation thresholds (defined as < 90% and > 10% successful defibrillation of 20 shocks at a given delivered energy) were obtained in anesthetized dogs using the wire electrodes with the chest closed and open and using two transvenously placed catheters with coil electrodes in the distal 6 cm (one in the coronary sinus and the other in the right atrial appendage) with the chest open. In the median sternotomy group, thresholds were obtained in minimally sedated animals without reopening the chest. A 25% increase above threshold shock was also used to determine a new percent success. After 4 days, the wire electrodes were removed by pulling on the external ends. At the time of removal, blood pressure and heart rate were monitored for 30 min, after which dogs were killed and their hearts sent for histopathologic study. For all dogs, chest radiographs were obtained postoperatively and on study days., Results: Atrial defibrillation using the wire electrodes was successful in all dogs at a mean (+/- SE) voltage of 112 +/- 9 V, with an energy level of 0.46 +/- 0.07 J and an impedance of 59.3 +/- 5 ohms. The mean percent success at the atrial defibrillation threshold was 36 +/- 5%. The 25% increase in defibrillation voltage improved the mean percent success to 73% (mean energy 0.66 +/- 0.19 J). No clinical or hemodynamic complications were observed during shock delivery, and no ventricular arrhythmias were induced during the shocks. No complications followed wire electrode removal. Histopathologic analysis showed no structural damage., Conclusions: The atrial defibrillation threshold obtained using temporary epicardial wire electrodes for atrial defibrillation is < 1 J in dogs. Atrial defibrillation using temporary epicardial wire electrodes can be performed safely, quickly and reliably without the need for anesthesia or antiarrhythmic agents. The wire electrodes can be removed without adverse hemodynamic or structural consequences. These data provide a basis for testing atrial defibrillation using epicardial wire electrodes in patients after open heart surgery.

During the 7-year period from August 1986 to July 1993, 203 patients with malignant ventricular arrhythmias underwent 203 implantable cardioverter-defibrillator (ICD system) implantations at the University Hospitals of Cleveland. Sixty-four patients had significant coronary artery stenoses amenable to myocardial revascularization and thus, at the time of the operation for ICD placement, also underwent coronary artery bypass graft. A retrospective analysis of the course of these 64 patients was carried out to determine the effect of two different treatment strategies on the outcome and cost of therapy. Thirty-six patients (group 1) underwent concomitant implantation of the ICD leads, patches and generator at the time of myocardial revascularization; 28 patients (group 2) underwent a two-stage strategy of initial placement of the ICD leads and patches at the time of myocardial revascularization followed by postoperative electrophysiologic testing to determine the persistent need for generator implantation. Of this latter group, 16 patients still had inducible sustained ventricular tachycardia during postoperative electrophysiologic testing and underwent generator implantation; 12 patients did not receive an ICD generator. The overall 30-day mortality rate was 4.7%. Two patients died in group 1 for a mortality rate of 5.5% and one died in group 2 for a mortality rate of 3.6%. The mean(s.d.) length of stay was 22.8(9.6) days at a mean(s.d.) cost of $93,000(33,000) for group 1 and 24.5(9.6) days at a mean cost of $82,900(30,000) for group 2 (P = n.s.). The mean(s.d.) postoperative length of stay was 13.7(7.8) days for group 1 and 15.4(6.5) days for group 2 (P = n.s.). Other complications occurred in 23% of surviving patients in group 1 and 29% of surviving patients in group 2 (P = n.s.). Mean follow-up was 33 months for group 1 and 23 months for group 2. At the end of 2 years, 78% of patients in group 1 and 86% in group 2 were alive (P = n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: We hypothesized that if the Electrophysiology Study Versus Electrocardiographic Monitoring (ESVEM) trial programmed stimulation protocol misclassified some drug trials as effective, then the misclassification rate would be proportionally greater for drugs other than sotalol., Background: In the ESVEM trial, patients treated with sotalol had fewer arrhythmic recurrences than those treated with other antiarrhythmic drugs despite similar efficacy predictions during electrophysiologic testing., Methods: We retrospectively compared the standard programmed stimulation protocol used at Case Western Reserve University, which used three extrastimuli during all follow-up studies, with the ESVEM protocol in 176 antiarrhythmic drug trials: sotalol (n = 54), procainamide (n = 73) and quinidine/mexiletine (n = 49)., Results: Predictions of efficacy were higher in the sotalol trials (14 of 54 standard, 20 of 54 ESVEM) than in procainamide trials (7 of 73 standard, 14 of 73 ESVEM) or quinidine/mexiletine trials (1 of 49 standard, 7 of 49 ESVEM). Thus, the two protocols classified 19 of 176 trials differently: not effective by the standard protocol but effective by the ESVEM trial. Discordant predictions of drug efficacy constituted a smaller proportion of ESVEM protocol efficacy predictions for sotalol (6 [30%] of 20) than for the other drugs (13 [62%] of 21, p < or = 0.05)., Conclusions: In the present study, the ESVEM programmed stimulation protocol predicted efficacy more often than the standard protocol. Discordant predictions represented a smaller portion of efficacy predictions for sotalol than for the other drugs. Thus, in the ESVEM trial, the superior long-term follow-up observed in patients assigned to sotalol may have been an artifact of the stimulation protocol utilized by the ESVEM investigators.

We report an unusual case of a relatively regular wide QRS complex tachycardia alternating with periods of an irregular narrow QRS complex tachycardia during atrial fibrillation in a patient with Wolff-Parkinson-White syndrome. Both tachycardias resulted from atrial fibrillation, the wide QRS complex tachycardia being due to 2:1 AV conduction of a type I atrial fibrillation across a posteroseptal accessory AV connection.

Impaired left ventricular function after acute myocardial infarction (AMI) is associated with an increased risk of death. Despite recent advances in the management of these patients, sudden death accounts for up to 50% of this mortality, and effective treatment strategies have yet to be identified. Preliminary trials with amiodarone have offered promise that drugs that prolong action potential duration by blocking the potassium channel may be useful in reducing this mortality. The Survival With Oral d-Sotalol (SWORD) trial is a multicenter, multinational study which tests the hypothesis that the class III agent d-sotalol will reduce all-cause mortality in high-risk survivors of AMI. The trial will enroll 6,400 patients with left ventricular dysfunction (ejection fraction < or = 40%) and a recent (6 to 42 days) or a remote (> 42 days) AMI with overt heart failure (New York Heart Association class II or III). In approximately 500 centers throughout the world, men and women aged > or = 18 years will be enrolled and randomized to placebo or d-sotalol (200 mg/day). The minimal follow-up will be 18 months. The trial has a 90% power to detect a 20% reduction in all-cause mortality. The rationale, design, and trial methods are described.

Background: Single premature beats were introduced in the reentrant circuit during stable atrial flutter in the canine sterile pericarditis model to test the hypotheses that (1) despite the fact that the reentrant circuit is functionally determined, there is a fully excitable gap; (2) the excitable gap in the reentrant circuit is not uniform; and (3) inhomogeneities of conduction in the reentrant circuit explain the effects of premature beats., Methods and Results: A multiplexing system was used to record 190 unipolar electrograms from the right atrial free wall during 18 atrial flutter episodes in 9 dogs. In all 18 episodes, premature stimuli captured the atrial flutter reentrant circuit. At the longest coupling intervals, the return cycle at the site closest to the pacing site did not prolong. As the coupling interval of the premature stimulus decreased, the return cycle then progressively increased, associated with changes in conduction in the reentrant circuit that were not uniform. The result was that coupling intervals associated with introduction of the premature beat also were not constant. The mean duration of the total (ie, fully plus partially) excitable gap was 12 +/- 4 ms in areas of slow conduction, and it was always shorter than the total excitable gap in other areas (22 +/- 6 ms, P < .001). The mean duration of the fully excitable gap based on analysis of the return cycle was 4 +/- 1 ms in the reentrant circuit. In 13 of 18 atrial flutter episodes, a premature stimulus terminated atrial flutter by causing block of the orthodromic wave front of the premature beat in an area of slow conduction. The mean coupling interval that caused orthodromic block was 113 +/- 5 ms (recorded at the site just proximal to the area of block), and it was always longer than the delivered stimulus coupling interval at the pacing site (96 +/- 8 ms, P < .001)., Conclusions: We conclude that in this functionally determined atrial flutter reentrant circuit in the canine sterile pericarditis model, (1) a fully excitable gap is present in at least part of the reentrant circuit; (2) the duration of the excitable gap in the reentrant circuit is shortest in areas of slow conduction; and (3) when a premature beat encounters the partially excitable gap of the reentrant circuit, it results in changes in conduction such that the coupling intervals are not uniform throughout in the reentrant circuit.

Approaches to the treatment of supraventricular arrhythmias, including atrial fibrillation, atrial flutter, atrial tachycardia, atrioventricular (AV) reentrant tachycardia, and AV nodal reentrant tachycardia, continue to evolve. Within the past two decades, many new and effective treatments have become available. These include several new antiarrhythmic agents, ablative therapies, pacing and surgical modalities, and cardioversion/defibrillation techniques. This paper provides an algorithm for the treatment of these supraventricular arrhythmias which includes therapy for the acute episode as well as the prevention of subsequent episodes of the tachyarrhythmia.

Objectives: This study attempted to determine whether cine magnetic resonance imaging (MRI), because of its unique ability to image the right ventricle, detects abnormalities in patients with right ventricular outflow tract ventricular tachycardia., Background: Right ventricular outflow tract ventricular tachycardia occurs in the absence of apparent structural heart disease., Methods: We compared cine MRI scans in 22 patients with right ventricular outflow tract ventricular tachycardia, 16 subjects without structural heart disease and 44 patients with other cardiovascular diseases. Echocardiography was performed in 21 patients with ventricular tachycardia., Results: All 22 patients with ventricular tachycardia had normal left ventricular function and no evidence of coronary artery disease. Cine MRI revealed right ventricular structural and wall motion abnormalities more often in patients with ventricular tachycardia (21 [95%] of 22) than in normal subjects (2 [12.5%] of 16, p < 0.0001) or patients without arrhythmia (17 [39%] of 44, p < 0.0001). The abnormalities in patients with ventricular tachycardia (fixed focal wall thinning, excavation, decreased systolic thickening) were located in the right ventricular outflow tract, whereas those in patients without arrhythmia were confined to the free wall. Cine MRI demonstrated abnormalities in patients with ventricular tachycardia more often than did echocardiography (21 [95%] of 22 vs. 2 [9%] of 21, respectively, p < 0.0001)., Conclusions: Right ventricular outflow tract ventricular tachycardia was associated with focal structural and wall motion abnormalities of the right ventricular outflow tract that were detected more often by cine MRI than by other imaging modalities and were not present in patients without arrhythmia or in normal subjects.

Background: Moricizine is said to have potent effects on cardiac conduction but little or no effect on cardiac refractoriness., Methods and Results: The effects of moricizine (2 mg/kg IV) on induced atrial flutter were studied 2 to 4 days after the creation of sterile pericarditis in 11 dogs. Ten episodes of stable atrial flutter before and after the administration of moricizine were studied in 9 dogs in the conscious, nonsedated state, and 7 episodes were studied in 6 dogs in the anesthetized, open chest state. In the conscious state, the effects of moricizine on atrial excitability, atrial effective refractory period, and intra-atrial conduction times were studied by recording during overdrive pacing of sinus rhythm from epicardial electrodes placed at selected atrial sites. Moricizine prolonged the atrial flutter cycle length in all the episodes, from a mean of 133 +/- 9 to 172 +/- 27 milliseconds (P < .001), and then terminated 7 of the 10 episodes. Moricizine increased the atrial threshold of excitability from a mean of 2.3 +/- 1.4 to 3.3 +/- 2.2 mA (P < .01) and prolonged intra-atrial conduction times (measured from the sulcus terminalis to the posteroinferior left atrium) from a mean of 58 +/- 6 to 64 +/- 5 milliseconds (P < .005). Prolongation of the atrial effective refractory period from 166 +/- 20 to 174 +/- 24 milliseconds (P < .05) was observed only at the sulcus terminalis site. In the open chest studies, administration of moricizine prolonged the atrial flutter cycle length from a mean of 150 +/- 15 to 216 +/- 30 milliseconds (P < .001) and then terminated the atrial flutter in all 7 episodes. As demonstrated by simultaneous multisite mapping from 95 bipolar sites on the right atrial free wall, the atrial flutter cycle length prolongation was either due to further slowing of conduction in an area of slow conduction in the reentrant circuit of the atrial flutter (5 episodes) or further slowing of conduction in an area of slow conduction plus the development of a second area of slow conduction (2 episodes). The change in conduction times in the rest of the reentrant circuit was negligible (10.9 +/- 8.7% of the total change). In all 7 episodes, the last circulating reentrant wave front blocked in an area of slow conduction., Conclusions: Moricizine (1) prolongs the atrial flutter cycle length, primarily by slowing conduction in an area of slow conduction in the reentrant circuit, (2) terminates atrial flutter by causing block of the circulating reentrant wave front in an area of slow conduction of the reentrant circuit, and (3) effectively interrupts otherwise stable atrial flutter in this canine model. The reason for these effects of moricizine are not readily explained by its effects on global atrial conduction times and refractoriness studied during sinus rhythm. Local changes in conduction in an area(s) of slow conduction are responsible for both cycle length prolongation and atrial flutter termination rather than the traditional wavelength concept of head-tail interaction.

It is not generally believed that there is a relation between atrial flutter, thought to be due to a single reentrant circuit, and atrial fibrillation, thought to be due to simultaneously circulating multiple-reentrant wave fronts. However, there are many reasons to suggest that these rhythms are more closely related than previously thought. To test the hypothesis that the length of an area of functional block in the right atrial free wall is critical to the conversion of atrial flutter to atrial fibrillation and of atrial fibrillation to atrial flutter, we studied spontaneous and ATP-induced conversion of stable atrial flutter to sustained atrial fibrillation and spontaneous conversion of sustained atrial fibrillation to stable atrial flutter. We studied 13 episodes of the conversion of stable atrial flutter to sustained atrial fibrillation and sustained atrial fibrillation to stable atrial flutter in seven dogs with sterile pericarditis. Six episodes were spontaneous and seven were ATP related. All episodes were studied by using a multisite mapping system to record 190 unipolar electrograms (converted in the software to 95 bipolar electrograms) from the right atrial free wall along with ECG lead II. Atrial flutter induction was attempted by atrial stimulation (S1S2 or S1S2S3) or by rapid atrial pacing for > or = 20 beats from selected sites at selected rates. For both the spontaneous and the ATP-related episodes, stable atrial flutter was defined as any episode of > or = 5 minutes, and sustained atrial fibrillation was any episode of > or = 1 minute. During all the episodes of stable atrial flutter, a line of functional block with a mean length of 24 +/- 4 mm was localized on the right atrial free wall. When the previously stable line of functional block decreased to a mean of 16 +/- 3 mm (P < .05), either spontaneously or after ATP administration (40 mg i.v.), the new line of functional block was not long enough to maintain stable atrial flutter, and conversion to atrial fibrillation resulted. This shortened line of functional block continued to change and migrate over the right atrial free wall throughout sustained atrial fibrillation. These observations were similar for both spontaneous and ATP-induced conversions. When sustained atrial fibrillation evolved to stable atrial flutter, there was reformation of a long line of functional block, long enough (> or = prior length) to create a stable reentrant circuit, which then captured the right atrial free wall and subsequently both atria.(ABSTRACT TRUNCATED AT 400 WORDS)

During the past few years, a number of new antiarrhythmic agents have become available for use in the United States, encainide has been withdrawn from use, and others have had indications for use modified. Therefore, a meeting of arrhythmia specialists was convened in an attempt to develop guidelines for antiarrhythmic therapy. The resultant discussions and guidelines presented in this article address general issues such as the most important antiarrhythmic drug attributes, as well as therapy for particular arrhythmias such as premature ventricular contractions, ventricular tachycardia, ventricular fibrillation, ventricular ectopy, and supraventricular tachyarrhythmias.

Objectives: We tested the hypothesis that double potentials recorded during atrial flutter in a functionally determined reentrant circuit reflect activation of the reentrant wave front around an area of functional conduction block., Background: The center of the atrial flutter reentrant circuit in the sterile pericarditis canine model is characterized by double potentials., Methods: We studied 11 episodes of atrial flutter in eight dogs during interruption of atrial flutter while pacing the atria. A multielectrode mapping system was used to record simultaneously from 190 electrodes on the right atrium (location of reentry)., Results: Interruption of atrial flutter occurred when the orthodromic wave front from the pacing impulse blocked in an area of slow conduction in the reentrant circuit. The response of the double potential with interruption of atrial flutter depended on the location of the recording site relative to this area of block. Two types of response were seen. When the double potential was recorded orthodromically distal to this area of block, interruption of atrial flutter was associated with disappearance of the second deflection, and continued pacing after interruption of atrial flutter was not associated with reappearance of the second potential. When the double potential was recorded at a site orthodromically proximal to the area of block, interruption of atrial flutter was not associated with disappearance of the second potential, and when rapid atrial pacing was continued, the double potential remained despite disappearance of the atrial flutter reentrant circuit., Conclusions: Double potentials represent functional conduction block in the center of the reentrant circuit, with each deflection of the double potential reflecting activation on either side of the area of functional block. The data also demonstrate that double potentials are not limited to a reentrant circuit, as they were recorded on either side of an area of block in the absence of such a circuit.

Background: We tested the hypotheses that spontaneous termination of stable atrial flutter is directly related to spontaneous beat-to-beat cycle length oscillations and that block of the circulating reentrant wave front occurs in an area of slow conduction., Methods and Results: We studied 30 episodes of spontaneous termination of stable atrial flutter induced by atrial stimulation in 11 conscious, nonsedated dogs with sterile pericarditis. Additionally, in 5 dogs, 14 episodes of spontaneous termination of stable atrial flutter were studied with a multisite mapping system to record simultaneously from 190 right atrial electrodes. In the conscious-state studies, atrial flutter cycle length oscillations began 6 +/- 1 (mean +/- SEM) beats before termination in 26 episodes, stable atrial flutter evolved into atrial fibrillation in 3 episodes, and no cycle length change occurred before termination in 1 episode. In the open-chest studies, in all instances, spontaneous oscillations began 7 +/- 1 beats before termination. The only consistent oscillation pattern occurred for the last two beats: a long cycle length (149 +/- 9 milliseconds) followed by a much shorter cycle length (110 +/- 6 milliseconds) (P < .01). Activation maps demonstrated that all cycle length oscillations were explained by changes of conduction in an area(s) of slow conduction in the reentrant circuit. In two instances, the last (short) cycle length was associated with disappearance of an area of slow conduction. In all episodes, the last circulating reentrant wave front blocked in an area of slow conduction in the reentrant circuit. Although not tested, during the last beat, the very early arrival of the circulating reentrant wave front at an area of slow conduction suggests an important role for refractoriness, with head and tail interactions, resulting in block., Conclusions: Spontaneous termination of stable atrial flutter in the sterile pericarditis model (1) is preceded by beat-to-beat cycle length oscillations that result from changes in conduction in areas of slow conduction in the reentrant circuit and (2) results from block of the circulating reentrant wave front in an area of slow conduction.

Objectives: The purpose of this study was to determine whether the induction at electrophysiologic study of sustained monomorphic ventricular tachycardias with multiple QRS complex configurations predicted failure of subsequent serial electrophysiologic study guided antiarrhythmic drug testing., Background: Ventricular tachycardias with multiple QRS complex configurations are associated with failure of surgical therapy for ventricular tachycardia. As such, the presence of multiple monomorphic QRS complex ventricular tachycardias during electrophysiologic testing may predict failure of subsequent medical therapy., Methods: Fifty-one consecutive patients with coronary artery disease had reproducible induction of monomorphic ventricular tachycardia during a baseline electrophysiologic study. Each patient then underwent a mean of 1.5 antiarrhythmic drug trials. An antiarrhythmic drug regimen that suppressed induction of ventricular tachycardia was identified in 13 (26%) of the 51 patients., Results: Patients with only one inducible monomorphic QRS complex ventricular tachycardia at baseline study were more likely to have an antiarrhythmic drug regimen identified that suppressed inducible ventricular tachycardia than were patients with multiple monomorphic QRS complex ventricular tachycardias (12[36%] of 33 patients vs. 1 [6%] of 18, p = 0.04). In seven patients with only one induced configuration of ventricular tachycardia, a second monomorphic ventricular tachycardia with a different QRS complex configuration occurred during attempts at pacing termination of the induced ventricular tachycardia. None of these seven patients then had successful drug suppression of inducible ventricular tachycardia. Thus, 12 (46%) of 26 patients with a single monomorphic QRS complex ventricular tachycardia observed at baseline study had successful serial drug testing compared with 1 (4%) of 25 patients with multiple QRS complex ventricular tachycardia configurations (p = 0.002)., Conclusions: The induction or observation of multiple monomorphic QRS complex ventricular tachycardias at baseline electrophysiologic study predicted failure of subsequent serial electrophysiologic study--guided antiarrhythmic drug therapy.

Background: Double potentials have been recorded during reentrant tachycardias in animal models. Although they have also been recorded during ventricular tachycardia in humans, their meaning is uncertain., Methods and Results: We used transient entrainment as a method to help further understand the meaning of double potentials recorded during ventricular tachycardia in humans. Three patients with ventricular tachycardia (cycle lengths, 500, 450, and 290 msec) were studied. During transient entrainment of ventricular tachycardia (pacing cycle length, 470-260 msec), both double potential deflections were captured at the pacing cycle length. One deflection was captured with a short activation time, and the other deflection was captured with a long activation time. During ventricular pacing, the deflections were associated by the long rather than the short interdeflection interval. At termination of pacing, each double potential deflection was associated with separate but sequential QRS complexes, and each deflection maintained the same electrogram morphology at relatively "slow" overdrive pacing rates. The short interdeflection interval shortened further with faster pacing rates (to less than the ventricular refractory period), making it unlikely that both deflections of the double potential represent active depolarization of the same tissue. In two patients, at a critically rapid pacing rate, one of the double potential deflections changed morphology abruptly, associated with a shortened stimulus-to-double potential time interval (from 520 to 110 msec and from 530 to 240 msec, respectively), indicating a change in the direction of activation that caused that deflection. Interruption of ventricular tachycardia was associated with disappearance of the double potentials at the same recording site. The double potentials did not immediately bracket an area of slow conduction., Conclusions: These data suggest that double potentials recorded only during ventricular tachycardia represent activation wave fronts on either side of an area of block within a reentrant circuit. Thus, double potentials recorded during ventricular tachycardia in these patients do not appear to represent slow conduction per se but rather appear to represent an area of block at the center of a reentrant circuit around which the reentrant wave front circulates.

Introduction of the automatic implantable cardioverter defibrillator (AICD) has dramatically affected the surgical treatment of malignant ventricular tachyarrhythmias. The authors continue to perform electrophysiologically directed subendocardial resection (SER) of left ventricular (LV) scars in selected patients, and we revascularize (CABG) those patients undergoing AICD implantation who have significant myocardial ischemia. In an attempt to define the optimal role of each procedure, this report analyzes our 8-year experience with 348 consecutive patients treated surgically for these arrhythmias (SER since 1983 and AICD since 1986). All patients undergoing SER had organized ventricular tachycardia (VT) as a result of myocardial infarction, and most had LV aneurysms; of those undergoing AICD or AICD/CABG, 60% had VT, 15% had ventricular fibrillation, and 25% had both or were noninducible. The thirty-day mortality rate was 1.5% (3/197) for AICD, 5.4% (5/93) for AICD/CABG, and 8.6% (5/58) for SER; these mortality figures are not significant different. Late deaths in all groups were predominantly due to congestive heart failure, and actuarial survival as well as freedom from sudden death was similar between the groups at 4 years. Recurrent VT occurred in 167 of 282 (59%) of long-term survivors of AICD or AICD/CABG during follow-up and in nine of 53 (17%) of those with SER. Forty-eight per cent of survivors of AICD or AICD/CABG required antiarrhythmic medications, whereas only 11% of those with SER required antiarrhythmics. Long-term survival in each group is much higher than that reported for comparable patients with severe LV dysfunction treated medically. In those patients with organized VT and LV aneurysm who are judged able to survive the procedure, SER offers a high likelihood of cure rather than simple prevention of sudden death.

Objectives: The objective of this study was to examine the relation between death and the frequency of premature ventricular depolarizations measured approximately 1 year after myocardial infarction., Background: The reported association between premature ventricular depolarizations and death in the weeks after myocardial infarction is in part the basis for the use of antiarrhythmic drugs. Such an association has not been reported on for observations obtained at a much greater interval after myocardial infarction., Methods: We examined the association between mortality and premature ventricular depolarization rates measured 1 year after myocardial infarction in patients with asymptomatic ventricular arrhythmia early (between 6 and 90 days, median 28) after infarction, as measured by 24-h ambulatory electrocardiographic recording. The study group consisted of 502 patients enrolled in the Cardiac Arrhythmia Pilot Study during 1983 to 1985. They were followed up during the course of the study and subsequently by a National Death Index search (average follow-up interval 1,080 days)., Results: Death was recorded for 87 patients through 1987. Because patients were admitted to the Cardiac Arrhythmia Pilot Study only if they had greater than or equal to 10 ventricular premature depolarizations/h, the arrhythmia rate measured at baseline (that is, early after infarction) was not expected to, and did not, predict mortality. In 360 patients ventricular premature depolarization rates were measured approximately 1 year from their index myocardial infarction while they were not receiving antiarrhythmic therapy. In these patients, who had survived 1 year after the index infarction, the rate of ventricular premature depolarizations/h measured 1 year after infarction was highly predictive of subsequent death (p less than 0.001). Recent heart failure and a history of diabetes mellitus were also strongly predictive of death., Conclusion: The prognostic value of ventricular premature depolarizations observed 1 year after a myocardial infarction may be significant even in a sample selected for frequent ventricular premature depolarizations observed early after the event.

The purpose of this study was to determine whether symptoms recorded at the time of transtelephonic ECG monitoring (TTEM) correlate with attacks of paroxysmal supraventricular tachycardia (PSVT) or paroxysmal atrial fibrillation (PAF). We studied 113 patients with these arrhythmias who made a total of 3319 TTEM calls during their participation in double-blind, placebo-controlled, crossover, multicenter trials of flecainide therapy. Among 49 patients with PSVT, 62.7% of symptomatic calls were associated with ECG-documented PSVT as compared with 6.8% of asymptomatic calls (p less than 0.001). Similarly, among 69 patients with PAF, 69% of symptomatic calls were associated with ECG-documented PAF compared with 10.6% of asymptomatic calls (p less than 0.001). Both in patients with PSVT and PAF, an attack of PSVT or PAF could be documented by ECG in more than 70% of the calls when patients complained of tachycardia, increased sweating, or dyspnea. The sensitivity of a symptomatic call was 91% for PSVT and 89% for PAF, and it was not influenced by flecainide therapy. However, flecainide therapy was associated with a decrease in the positive predictive value of symptomatic TTEM calls and an increase in false positive TTEM transmissions. We conclude that in patients with symptomatic PSVT or PAF, there is a temporal relationship between symptoms and the occurrence of ECG-documented attacks of PSVT or PAF. However, sole reliance should not be placed on the presence or absence of symptoms as a measure of drug failure or efficacy, and it is important to document the cardiac rhythm by TTEM at the time symptoms are recorded.

While clinical management of patients with ventricular arrhythmias continues to evolve, some basic principles are generally accepted. First, patients with sustained ventricular tachyarrhythmias (ventricular tachycardia or ventricular fibrillation) require treatment. Second, patients with frequent ventricular ectopy or nonsustained ventricular tachycardia in the absence of underlying structural heart disease do not require treatment except when relief of symptoms is warranted. However, the indication for treatment of patients with frequent ventricular ectopy or nonsustained ventricular tachycardia in the presence of underlying structural heart disease remains uncertain. The concern is that these ventricular arrhythmias may be a precursor for sustained, potentially life-threatening ventricular tachyarrhythmias. Available data suggest that patients with underlying structural heart disease, particularly coronary artery disease and a previous myocardial infarction, who manifest frequent ventricular ectopy or more particularly nonsustained ventricular tachycardia, are at increased risk for sudden cardiac death. However, no studies have demonstrated to date that treatment of these arrhythmias will favorably affect outcome. Data are accumulating to suggest that use of the principles of risk stratification permits identification of patients at very high risk for developing sustained ventricular tachyarrhythmias. Carefully designed clinical trials are required before firm guidelines for the management of these patients can be defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: In animals, parasympathetic nerve fibers that innervate the sinoatrial node can be selectively stimulated to increase atrial cycle length. These nerve fibers course through an epicardial fat pad at the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium. We hypothesized that similar nerves exist and can be selectively stimulated in humans., Methods and Results: Microscopic examination of fat pads excised from the margin of the right superior pulmonary vein, the superior vena cava, and the right atrium during two human autopsies revealed the presence of nerve fibers and ganglia. We electrically stimulated this epicardial fat pad in 16 patients during cardiac surgery. The fat pads were stimulated with continuous-pulse trains for 15 seconds via a hand-held bipolar electrode using constant current (10-15 mA), constant pulse width (0.02-0.05 msec), and at 6.6, 10, 20, 25, and 30 Hz. The mean atrial cycle length +/- 1 SEM increased from 734 +/- 34 msec at baseline to a maximum of 823 +/- 61 msec at 6.6 Hz, 1,167 +/- 125 msec at 10 Hz, 1,734 +/- 281 msec at 20 Hz, 2,993 +/- 661 msec at 25 Hz, and 2,461 +/- 668 msec at 30 Hz during nerve stimulation. Linear regression analysis showed that the response of atrial cycle length to sinoatrial parasympathetic nerve stimulation was frequency dependent. The maximum response and complete decay of the response occurred within 4-8 seconds of initiation or termination of sinoatrial parasympathetic nerve stimulation. Atrioventricular conduction time and the PR interval did not change during sinoatrial parasympathetic nerve stimulation, even when the atria were paced at the baseline heart rate., Conclusions: Electrical stimulation of parasympathetic nerve fibers in a fat pad near the sinoatrial node increased atrial cycle length without affecting atrioventricular nodal conduction. This is the first study in which such nerve fibers that innervate the sinoatrial node have been selectively stimulated in humans.

From September 1986 through September 1990, 60 operations were performed in 55 patients (32 male and 23 female; age, 1 to 76 years) for ablation of accessory pathways of atrioventricular reentrant tachycardia; 6 patients had additional cardiac procedures. Between September 1986 and August 1988 the initial surgical approach was exclusively epicardial with adjuvant cryoablation (EPI) in 23 patients (group 1) for a left free wall (LFW) pathway in 11, right free wall (RFW) in 3, posteroseptal (PS) in 7, and anteroseptal in 2. During September 1988 through September 1990, 32 patients (group 2) had the initial surgical approach tailored to the location of the mapped accessory pathway: endocardial approach (ENDO) for LFW in 17 and for juxtanodal pathway in 2, EPI for RFW in 3 and for PS in 9, and combined ENDO and EPI for AS in 1. There was no early or late death in either group. In group 1, 2 patients with LFW pathway had development of recurrent preexcitation in the same compartment requiring ENDO reoperation 10 and 11 months later, 1 with anteroseptal pathway needed immediate ENDO and EPI reoperation, and another with LFW, who required pericardial patch repair of a left atrial tear, had a thromboembolic stroke 2 days later. No serious complications occurred in group 2, but 2 patients with PS required reoperation before discharge for a second accessory pathway in another compartment (1 RFW and 1 LFW). Additionally, 4 patients (2 in each group) had from the beginning ablation of two pathways in different compartments. On complete late follow-up (mean, 28 months) all patients are back to preoperative levels of activity and are free of preexcitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Survivors of out-of-hospital sudden cardiac death may have any of a number of etiologies as the cause. Careful in-hospital evaluation is necessary for providing adequate therapy for such patients. In the great majority of survivors of out-of-hospital sudden cardiac death, such evaluation necessarily includes invasive electrophysiological testing for both diagnostic and therapeutic indications. Given the high incidence of recurrence, effective therapy, based on individualized evaluation, must be found.

Background: The electrical current and energy required to terminate ventricular tachyarrhythmias are known to vary by arrhythmia: Ventricular tachycardia (VT) is generally considered to require less energy than ventricular fibrillation (VF). The hypothesis of our study was that current requirements for transthoracic termination of VT are further determined by VT rate and QRS complex morphology., Methods and Results: We prospectively studied 203 patients who received a total of 569 shocks for VT or VF by following a current-based protocol. This protocol recommended shocks for VT beginning at 18 A (70 +/- 22 J) and shocks for VF beginning at 25 or 30 A (137 +/- 52 J or 221 +/- 70 J). The ventricular tachyarrhythmias were subclassified as monomorphic VT (MVT): uniform QRS complex morphology on surface electrocardiogram and heart rate greater than 100 beats per minute; polymorphic VT (PVT): nonuniform QRS complex morphology and heart rate less than or equal to 300 beats per minute; or VF: nonuniform QRS complex morphology and heart rate greater than 300 beats per minute. We found that shocks of 18 A and 25 A for terminating MVT had success rates of 69% and 82%, respectively, whereas such low-current shocks were less successful for PVT (33% at 18 A) and for VF (19% at 18 A, 53% at 25 A). High-current shocks of 35 A and 40 A were equally successful for the three ventricular tachyarrhythmias. Subdividing MVT revealed that slower MVT (heart rate less than 200 beats per minute) had a significantly better success rate with low-current shocks of 18 A and 25 A than did faster MVT (greater than 200 beats per minute) (89% versus 72% success, p less than 0.01). Bundle branch block morphology, QRS axis, and duration of ventricular tachyarrhythmia did not alter current requirements., Conclusions: Heart rate and electrocardiographic degree of organization of ventricular tachycardia are important determinants of transthoracic energy and current requirements for cardioversion and defibrillation. Transthoracic termination of MVT requires relatively low current or energy, but PVT behaves more like VF and requires higher electrical current or energy.

Patients randomized to placebo in the encainide and flecainide arms of the Cardiac Arrhythmia Suppression Trial (CAST) have been found to have a relatively low 1-year mortality rate of 3.9% in comparison with previous studies of patients in the postmyocardial infarction period. To determine the comparability of CAST with previous studies, baseline variables were examined in the 743 patients randomized to placebo in the flecainide and encainide arms of CAST. Twenty-three baseline characteristics were correlated with major outcome events: arrhythmic death (16 events), total mortality (26 events) and congestive heart failure (51 events). On multivariate analysis the risk of new or worsening congestive heart failure was significantly associated with diuretic use, diabetes, high New York Heart Association functional class, age, prolonged QRS duration and low ejection fraction. The risk of arrhythmic death or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, history of heart failure, use of digitalis, diabetes and prolonged QRS duration. Total mortality or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, diabetes, ST segment depression, high functional class, prolonged QRS duration and low ejection fraction. The variables at baseline associated with mortality from all causes or arrhythmic death or resuscitated cardiac arrest and heart failure in the CAST placebo-treated patients are similar to those identified in previous postmyocardial infarction studies. Thus, the observation of increased mortality in CAST associated with the administration of encainide and flecainide for suppression of ventricular premature depolarizations is probably applicable to any comparably defined group of patients in the postmyocardial infarction period.