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

OBJECTIVES: An 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. METHODS: Thirty 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. RESULTS: Mean 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. CONCLUSIONS: Atrial 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.

Rate-dependent effects of intravenous lidocaine, procainamide and amiodarone on intraventricular conduction.

In this study, the duration of the QRS complex during ventricular pacing was used as an index of intraventricular conduction to quantitate the rate-dependent effects of intravenous lidocaine, procainamide and amiodarone. Right ventricular apical pacing (15 to 20 beats) was performed at cycle lengths of 600, 500, 400, 350, 300, 275 and 250 ms, before and 5 minutes after the intravenous administration of lidocaine in 11 patients (serum level 3.2 +/- 0.8 micrograms/ml [mean +/- SD] ), procainamide in 14 patients (serum level 8.2 +/- 1.9 micrograms/ml) and amiodarone in 12 patients (serum level 3.9 +/- 1.2 micrograms/ml). Electrocardiographic recordings were made at a paper speed of 150 mm/s. QRS duration was measured in a blinded fashion, with reproducibility within 5%. In the control state, QRS duration was the same at all paced cycle lengths. After lidocaine, procainamide and amiodarone administration, the shortest paced cycle length with complete ventricular capture was 250 +/- 0, 275 +/- 38 and 264 +/- 20 ms, respectively. At a paced cycle length of 600 ms, the increase in QRS duration compared with the control state was 1 +/- 2% with lidocaine (p greater than 0.05), 21 +/- 7% with procainamide (p less than 0.001) and 6 +/- 6% with amiodarone (p less than 0.05). At the shortest paced cycle length with complete capture, the increase in QRS duration compared with the control state was 20 +/- 6% with lidocaine (p less than 0.001), 42 +/- 11% with procainamide (p less than 0.001) and 26 +/- 4% with amiodarone (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of magnesium sulfate on cardiac conduction and refractoriness in humans.

Magnesium has been used empirically for several decades in the treatment of atrial and ventricular arrhythmias in patients with normal and decreased serum magnesium levels. However, a systematic evaluation of the effects of magnesium on cardiac conduction and refractoriness in humans has not been described. In this study, the electrocardiographic and electrophysiologic effects of magnesium were determined in 10 patients with normal baseline serum magnesium and other electrolyte levels. Six grams of magnesium sulfate was administered intravenously over 6 minutes followed by a continuous infusion of 1 additional gram over 1 hour. Serum magnesium levels rose significantly from a baseline of 2.0 +/- 0.2 to 5.4 +/- 0.4 mg/dl (p less than 0.001). No significant change occurred in heart rate at rest, or in duration of the QRS complex or QT or QTc intervals during sinus rhythm. There were significant increases in sinus node recovery time (1,000 +/- 211 to 1,106 +/- 223 ms, p less than 0.01) and corrected sinus node recovery time (279 +/- 87 to 336 +/- 104 ms, p less than 0.05). Significant increases occurred in atrioventricular (AV) node conduction time during sinus rhythm (82 +/- 22 to 97 +/- 17 ms, p less than 0.02), in the atrial paced cycle length at which AV node Wenckebach block occurred (350 +/- 46 to 419 +/- 65 ms, p less than 0.01) and in the AV node relative refractory period (397 +/- 27 to 422 +/- 18 ms, p less than 0.05), functional refractory period (395 +/- 41 to 415 +/- 33 ms, p less than 0.05) and effective refractory period (306 +/- 67 to 338 +/- 38 ms, p less than 0.05).

The plasma catecholamine response to ventricular tachycardia induction and external countershock during electrophysiologic testing.

Adrenergic activation during electrophysiologic study could potentially alter the electrophysiologic properties of the arrhythmia substrate. However, the catecholamine response to ventricular tachycardia induction and termination during electrophysiologic testing has to date not been quantitated. Therefore, in 13 patients undergoing electrophysiologic study, arterial plasma norepinephrine and epinephrine were measured before, during and 1, 3, 5, 10 and 15 minutes after ventricular tachycardia induced by programmed stimulation and terminated by a single 100 J external countershock. Sinus rate and the effective refractory period at the right ventricular apex at a basic drive cycle length of 400 ms were measured after the countershock at the same time intervals used for the catecholamine measurements. The mean ventricular tachycardia cycle length (+/- SD) was 187 +/- 30 ms, and the mean duration of ventricular tachycardia was 18 +/- 4 seconds. Plasma norepinephrine and epinephrine increased, respectively, from a baseline of 286 +/- 141 and 119 +/- 40 pg/ml to 770 +/- 330 (169%) and 597 +/- 467 pg/ml (402%), (p less than 0.01) at 1 minute after the countershock. The mean plasma norepinephrine and epinephrine levels during ventricular tachycardia and at times greater than 1 minute after the shock did not differ significantly from baseline levels. Sinus rate increased from a baseline of 74 +/- 13 to 103 +/- 26/min (39%) at 1 minute after the shock (p less than 0.05) and then returned to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and chronic effects of amiodarone on ventricular refractoriness, intraventricular conduction and ventricular tachycardia induction.

In eight patients, the right ventricular effective refractory period, rate-dependent changes in intraventricular conduction (as reflected by QRS duration during ventricular paced cycle lengths of 600 to 250 ms) and results of programmed ventricular stimulation were determined in the control state, 5 minutes after the intravenous infusion of 10 mg/kg body weight of amiodarone and after 2 months of treatment with oral amiodarone. The right ventricular effective refractory period was 230 +/- 30 ms (mean +/- SD) in the control study, 248 +/- 27 ms after intravenous amiodarone (p less than 0.001) and 296 +/- 26 ms after oral amiodarone (p less than 0.001). In the control state, QRS duration was constant at all paced cycle lengths. Intravenous amiodarone resulted in a rate-dependent prolongation of QRS duration. This rate-dependent prolongation was markedly accentuated by oral amiodarone in six patients who had an elevated serum level of reverse triiodothyronine (T3) after 2 months of oral treatment, but it was not more pronounced than the effects of intravenous amiodarone in two patients with a normal reverse T3 serum level after oral therapy. Both intravenous and oral amiodarone either suppressed or modified the induction of ventricular tachycardia by programmed stimulation in some patients, but in a discordant fashion. The relative effects of intravenous and oral amiodarone on ventricular refractoriness and conduction and on ventricular tachycardia induction did not correlate with serum amiodarone levels. Chronic amiodarone therapy results in a marked prolongation in ventricular refractoriness compared with the relatively small but significant increase that occurs after intravenous amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of recurrent atrial fibrillation with chronic dual-site right atrial pacing.

OBJECTIVES: We investigated 1) the feasibility, safety and efficacy of multisite right atrial pacing for prevention of atrial fibrillation (AF); and 2) the ability of atrial pacing in single- and dual-site modes to increase arrhythmia-free intervals in patients with drug-refractory AF. BACKGROUND: We recently developed and applied a novel technique of dual-site right atrial pacing in an unselected group of consecutive patients with AF requiring demand pacing. A prospective crossover study design was used to evaluate single- and dual-site right atrial pacing modes. METHODS: The frequency of AF during the 3 months before pacemaker implantation was analyzed. Consecutive consenting patients underwent insertion of two atrial leads and one ventricular lead with a DDDR pulse generator. Patients were placed in a dual-site pacing mode for the first 3 months and subsequently mode switched to single site pacing for 3 months. Mode switching was repeated at 6-month intervals thereafter. RESULTS: Atrial pacing resulted in a marked decline in AF recurrences (p < 0.001). During dual-site pacing with an optimal drug regimen, there was no AF recurrence in any patient compared with five recurrences in 12 patients during single-site pacing (p = 0.03). The mean (+/-SD) arrhythmia-free interval before pacing (14 +/- 14 days) was prolonged with dual- (89 +/- 7 days, p < 0.0001) and single-site pacing (76 +/- 27 days, p < 0.0001). Symptomatic AF episodes showed a declining trend during dual- and single-site pacing compared with those during the preimplantation period (p = 0.10). Mean antiarrhythmic drug use for all classes declined from 4 +/- 1.9 drugs before implantation to 1.5 +/- 0.5 (p < 0.01) drugs after implantation. Twelve (80%) of 15 patients remained in atrial paced rhythm at 13 +/- 3 months. CONCLUSIONS: We conclude that multisite right atrial pacing is feasible, effective and safe for long-term application. Atrial pacing significantly prolongs arrhythmia-free intervals in patients with drug-refractory paroxysmal AF. Dual-site right atrial pacing may offer additional benefits and should be considered either as the primary mode or in patients unresponsive to single-site pacing.

Electrophysiologic testing in patients with unexplained syncope: clinical and noninvasive predictors of outcome.

To assess whether the level of risk of having significant electrophysiologic abnormalities can be determined, 29 clinical variables were analyzed in 104 patients with unexplained syncope who underwent electrophysiologic testing. A positive electrophysiologic study was defined as: a sinus node recovery time greater than or equal to 3 seconds; HV interval greater than or equal to 100 ms; infranodal block during atrial pacing; unimorphic ventricular tachycardia; and supraventricular tachycardia associated with hypotension. Thirty-one patients had a positive study, with inducible ventricular tachycardia being the most common finding (71% of positive studies). A left ventricular ejection fraction less than or equal to 0.40 was the most powerful predictor of a positive electrophysiologic study (p less than 0.00001), followed by the presence of bundle branch block (p less than 0.00003), coronary artery disease (p less than 0.0003), remote myocardial infarction (p less than 0.00006), use of type 1 antiarrhythmic drugs (p less than 0.00003), injury related to loss of consciousness (p less than 0.01) and male sex (p less than 0.01). A negative electrophysiologic study was associated with an ejection fraction greater than 0.40 (p less than 0.00001), the absence of structural heart disease (p less than 0.00001), a normal electrocardiogram (ECG) (p less than 0.0001) and normal ambulatory ECG monitoring (p less than 0.0001). The probability of a negative study increased as the number and duration of syncopal episodes increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of myocardial ischemia during programmed stimulation in survivors of cardiac arrest with coronary artery disease.

The role of ischemia in the induction of ventricular tachycardia during programmed stimulation was studied in 19 patients who survived a cardiac arrest and were found to have a significant stenosis in at least one branch of the left coronary artery. The arterial-coronary sinus lactate difference was measured during electrophysiologic testing, before the induction of ventricular tachycardia. Ventricular tachycardia was induced in 15 patients; it was sustained and unimorphic in 6 patients and polymorphic in 9. Myocardial ischemia, as reflected by net myocardial lactate production, was present within 60 seconds before the induction of ventricular tachycardia in 8 of the 15 patients with inducible ventricular tachycardia. In 9 of the 15 patients, programmed stimulation was repeated after a 15 minute rest period, with the same coupling intervals that had induced ventricular tachycardia previously. Net myocardial lactate production was not present in any patient during this repeat attempt. In three patients without evidence of ischemia during the first induction of ventricular tachycardia, the arrhythmia was induced again by the specific coupling intervals that had induced it previously. However, in five of six patients with net myocardial lactate production during the first induction of ventricular tachycardia, the same coupling intervals that had induced the arrhythmia in the presence of ischemia no longer induced it in the absence of ischemia. The results of this study suggest that myocardial ischemia may be a requirement for the induction of ventricular tachycardia in some patients with coronary artery disease who survive a cardiac arrest.

Acute effects of dual-site right atrial pacing in patients with spontaneous and inducible atrial flutter and fibrillation.

OBJECTIVES: We tested the ability of dual-site right atrial pacing to prevent atrial fibrillation (AF) or atrial flutter induced by single-site atrial pacing and correlated its efficacy with clinical patient characteristics, atrial activation times and refractory periods. BACKGROUND: Prevention of recurrent AF with long-term dual-site right atrial pacing has been demonstrated in our previous studies. However, the mechanism of antiarrhythmic benefit is unclear. METHODS: Using standard electrophysiologic methods, baseline electrocardiographic and electrophysiologic measurements (mean +/- SD) were obtained. Programmed atrial stimulation was performed for AF or atrial flutter induction. Atrial pacing was performed at two drive cycle lengths (600 and 400 ms) and followed by one to three atrial extrastimuli at one to four pacing sites in the right atrium. In patients with inducible AF or atrial flutter, reinduction was then attempted during a dual-site atrial pacing drive train. This was achieved by simultaneously pacing at the high right atrium and coronary sinus ostium at an identical rate to the baseline stimulation, with the atrial extrastimuli being delivered at the pacing site responsible for the initial AF episode initiation. RESULTS: Twenty patients (10 men, 10 women, mean [+/- SD] age 64 +/- 16 years) with symptomatic AF (n = 10) or atrial flutter (n = 10) were studied. There was a significant abbreviation of the P wave duration to 103 +/- 17 ms with dual-site pacing compared with sinus rhythm (120 +/- 12 ms, p = 0.005) and high right atrial pacing (121 +/- 17 ms, p = 0.005). This was also associated with a characteristic change in P wave configuration with an inferior and leftward axis shift. The effective refractory period at the high right atrium remained unchanged with dual-site atrial pacing compared with single-site high right atrial pacing. Sixteen patients had inducible AF or atrial flutter and could be tested after dual-site atrial pacing. The induced atrial tachyarrhythmia was suppressed in nine patients (56%), who had either induced AF (n = 5) or atrial flutter (n = 4). The difference in the effective refractory period between the high right atrium and the coronary sinus ostium pacing sites was significantly greater (33 +/- 12 ms) in patients with suppression of atrial tachyarrhythmia with dual-site atrial pacing compared with patients without suppression (15 +/- 13 ms, p = 0.001). P wave abbreviation did not correlate with arrhythmia suppression. There was no correlation between suppression of inducible AF or atrial flutter and demographic or clinical patient characteristics. CONCLUSIONS: Dual-site right atrial pacing from the high right atrium and coronary sinus ostium can suppress inducible AF or atrial flutter elicited after single-site high right atrial pacing in selected patients. Acute suppression is more likely in patients with greater dispersion of right atrial refractoriness between these two sites.

Coexistent posteroseptal and right-sided atrioventricular bypass tracts.

Twelve patients with a posteroseptal accessory pathway underwent complete electrophysiologic studies, and four were found to have a second atrioventricular (AV) bypass tract that was right anterior, right anteromedial or right anterolateral in location. In two of these four patients, the presence of the right-sided AV bypass tract was confirmed by intraoperative epicardial mapping or after catheter-induced abolition of retrograde conduction through the posteroseptal bypass tract. In three of the four patients with a dual AV bypass tract, the delta wave pattern was clearly atypical of the pattern seen with an isolated posteroseptal accessory pathway. Instead of a transition from an isoelectric or slightly positive delta wave in lead V1 to markedly positive delta waves in leads V2 to V6, the delta waves were negative or only slightly positive in leads V2 to V5. However, in a fourth patient with dual AV bypass tracts, the only atypical electrocardiographic finding was an intermittently positive delta wave in lead II; at times this patient's electrocardiogram was consistent with an isolated posteroseptal bypass tract, with negative delta waves in the inferior leads. There appears to be an association between posteroseptal and right-sided accessory pathways. In patients with a posteroseptal accessory pathway who are candidates for catheter or surgical bypass tract ablation, a complete mapping study of the tricuspid anulus is mandatory, even when the electrocardiogram is typical of an isolated posteroseptal bypass tract.

Comparative survival after permanent ventricular and dual chamber pacing for patients with chronic high degree atrioventricular block with and without preexistent congestive heart failure.

To determine whether survival after permanent ventricular demand (VVI) pacing differs from survival after permanent dual chamber (DVI or DDD) pacing in patients with chronic high degree atrioventricular (AV) block (Mobitz type II or trifascicular block), 132 patients who received a VVI pacemaker (Group 1) and 48 patients who received a DVI or DDD pacemaker (Group 2) were followed up for 1 to 5 years. There was no significant difference in sex distribution, mean age or incidence of coronary heart disease, hypertension, valvular heart disease, diabetes mellitus, stroke or renal failure between Groups 1 and 2. Overall, the predicted cumulative survival rate at 1, 3 and 5 years was 89, 76 and 73%, respectively, for Group 1 and 95, 82 and 70%, respectively, for Group 2. In patients with preexistent congestive heart failure, the predicted cumulative survival rate at 1, 3 and 5 years was 85, 66 and 47%, respectively, for Group 1 (n = 53) and 94, 81 and 69%, respectively, for Group 2 (n = 20). The 5 year predicted cumulative survival rate was significantly lower in Group 1 patients with preexistent congestive heart failure than in Group 2 patients with the same condition (p less than 0.02). There was no significant difference in 5 year cumulative survival rate between Groups 1 and 2 for patients without preexistent congestive heart failure. The results suggest that permanent dual chamber pacing enhances survival to a greater extent than does permanent ventricular demand pacing in patients with high degree AV block and preexistent congestive heart failure.

Initial clinical experience with endocardial defibrillation using an implantable cardioverter/defibrillator with a triple-electrode system.

We evaluated the early clinical performance of an implantable cardioverter/defibrillator with a nonepicardial lead system in patients with refractory ventricular tachycardia or ventricular fibrillation. Ten patients, mean age 67 years, mean left ventricular ejection fraction 35%, refractory to 5 +/- 2 antiarrhythmic drugs and with a history of prior cardiac surgery (7 patients), severe lung disease (2 patients), or renal failure (1 patient) underwent device and lead system implant. A tripolar electrode catheter with one sensing electrode and two defibrillating electrodes was placed in the right ventricular apex and a left thoracic submuscular patch electrode was used in an epicostal location. Defibrillation energy threshold was determined using dual- or triple-electrode configurations. Optimal patch electrode location was determined after temporary use of a cutaneous patch electrode prior to cardioverter/defibrillator implant. Electrophysiologic studies were performed before discharge and after 2 to 3 months to assess device function. Percutaneous insertion and placement of the electrode catheter was achieved in all patients. Defibrillation energy threshold testing was done using 1 to 4 (mean, 2.7) electrode configurations per patient and required 6 to 21 (mean, 13) ventricular fibrillation inductions and 8 to 56 (mean, 22) shocks per patient. In all patients, lowest reliable defibrillation energy threshold was obtained with a triple-electrode configuration (right ventricular common cathode with right atrial and thoracic patch as dual anodes) and bidirectional shocks (mean, 18 +/- 5 J). Optimal patch electrode position could be determined in 9 of 10 patients, and these 9 patients had cardioverter/defibrillator implant. Ventricular fibrillation termination with the first delivered shock at electrophysiologic study was documented in all patients. There was no perioperative mortality in device-implanted patients. Postoperative electrophysiologic studies before discharge (9 patients) and at 3 months (8 patients) continued to demonstrate successful defibrillation by the first device shock. During follow-up (range, 2 to 10 months; mean, 6 +/- 3 months), spontaneous device discharges occurred in 4 patients with inappropriate shocks due to electrode catheter fracture being documented in 1 patient. Antiarrhythmic drug therapy was withdrawn in 6 patients and reduced in 3 patients. We conclude, based on our preliminary experience, that an implantable cardioverter/defibrillator can be successfully used with a nonepicardial lead system for endocardial defibrillation in many patients. This lead system can be used with currently available pulse generators and should be considered at cardioverter/defibrillator implantation. It can be anticipated to reduce patient risk and hospital costs associated with this procedure.

Increased plasma catecholamine levels in patients with symptomatic mitral valve prolapse.

Total plasma catecholamine levels, plasma norepinephrine levels, heart rate, and systolic and diastolic pressures were measured in 15 symptomatic patients with mitral valve prolapse and in 19 normal subjects in supine baseline conditions and in a standing position. In the 15 symptomatic patients, total plasma catecholamine levels and plasma norepinephrine levels were significantly elevated in both positions, and heart rate was lower than in normal subjects in the supine position but returned to normal in the upright position. Thus, symptomatic patients with mitral valve prolapse demonstrate increased resting sympathetic tone. In addition, the associated supine bradycardia suggested that increased vagal tone might also be present at rest. These observations support the hypothesis of a dual autonomic dysfunction in these patients and could account for some of the clinical manifestations of the mitral valve prolapse syndrome.

Efficacy and safety of radiofrequency catheter ablation of left-sided accessory pathways through the coronary sinus.

Radiofrequency catheter ablation of left-sided accessory pathways (APs) with the use of an endocardial technique carries all potential risks of left heart catheterization. We analyzed the determinants of success, efficacy, and safety of radiofrequency catheter ablation from the coronary sinus (CS), as a potential alternative to the endocardial technique in these patients. Thirteen patients (mean age 40 +/- 20 years) with 15 left-sided APs and a history of symptomatic supraventricular tachycardia were included in the study. Nine APs were localized in the left posteroseptal region, and the remaining 6 in the left free wall. Ablation from CS was attempted in 12 patients with 14 APs. In 1 patient ablation within the CS was not deemed safe because of a small venous lumen. All 14 APs were successfully ablated using either CS ablation alone or combined with the endocardial technique. Efficacy of the CS ablation as a primary technique was 56% (5 of 9 APs). In 5 additional APs, ablation in the CS eliminated pathway conduction after failed endocardial attempts. CS ablation either as a primary or a secondary technique eliminated conduction in 10 of 14 APs (71.4%) (group 1). In the remaining 4 APs (group 2), the primary CS attempt was unsuccessful and APs were ablated with a subsequent endocardial approach. Determinants of success for the CS method were local AP to atrial and/or ventricular electrogram amplitude ratios > or = 1 (p < 0.05). The success rate of CS ablation was 83% in the left posteroseptal APs adjoining the branching point of the middle cardiac vein or a CS anomaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional right and left atrial activation patterns during single- and dual-site atrial pacing in patients with atrial fibrillation.

We examined the activation of the right atrium and left atrium by pacing from different atrial sites using several single- and dual-site atrial pacing modes in patients with atrial fibrillation or flutter. We also analyzed the effect of these pacing modes on fixed coupled extrastimuli in this population. Patients underwent detailed mapping of regional right atrial (RA) and left atrial (LA) sites. Bipolar pacing was performed individually from the high right atrium, coronary sinus ostium, and the distal coronary sinus, and simultaneously from the high right atrium and coronary sinus ostium (dual-site RA pacing) or high right atrium and distal coronary sinus (biatrial pacing). Extrastimuli were delivered from the high right atrium at fixed coupling intervals of 350 and 250 ms. Twenty patients with atrial fibrillation were studied. P-wave duration during pacing was significantly abbreviated by both dual-site RA and biatrial pacing (p <0.001 vs high RA pacing, respectively) but not by any other single-site atrial pacing method. Both dual-site atrial pacing modes also significantly abbreviated P wave durations for closely coupled high RA premature beats (p <0.001) in contrast to high RA pacing. During the basic pacing drive and for high RA extrastimuli, RA activation at the crista terminalis and atrial septum was comparable in sinus rhythm, high RA pacing, and in both dual-site atrial pacing methods, but was significantly delayed by coronary sinus ostial and distal coronary sinus pacing. In contrast, proximal coronary sinus activation was delayed with high RA pacing compared with all other pacing modes, and high RA extrastimuli encountered reduced conduction delay at this location with dual-site atrial pacing modes. LA activation was advanced superiorly by both single-site coronary sinus pacing methods and both dual-site atrial pacing techniques. Inferior and lateral LA activation was advanced by all pacing modes using a coronary sinus pacing site. However, earlier activation of LA sites occurred for high RA premature beats after both dual-site pacing methods (p <0.05) compared with single-site pacing modes. Incremental conduction delay at different atrial regions for closely coupled high RA extrastimuli ranged from 33% to 120% during high RA pacing and was significantly attenuated at multiple RA and LA sites by dual-site RA and biatrial pacing. Distinct global, as well as regional electrophysiologic effects, may mediate the variable antiarrhythmic effects of different and novel atrial pacing methods.

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.

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.

Experience with a third-generation implantable cardioverter-defibrillator.

A Medtronic 7216A pacemaker cardioverter-defibrillator was implanted in 16 patients (mean age 56 years) with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and organic heart disease with a mean left ventricular ejection fraction of 33%. Endocardial and epicardial defibrillation shock efficacy was evaluated before or at implant using 1 to 3 shock patterns, i.e., monophasic single, sequential or simultaneous shocks with dual and triple electrode configurations. Endocardial leads used a common right ventricular cathode and dual anodes, whereas epicardial leads used 2 or 3 helical coil patches. VT termination was evaluated using pacing or shock therapy, or both, whereas only shocks were used in VF. Programmable bradycardia pacing, individual zones for VT and VF detection and individualized pacing and shock therapy for VT and VF were used. Monophasic shocks had epicardial defibrillation thresholds ranging from 3 to 18 (mean 10) J and were comparable for sequential and simultaneous shocks (p greater than 0.2). VT detection rates ranged from 340 to 470 ms and VF detection rates from 270 to 330 ms. VT or VF induction, or both, was performed noninvasively in 13 patients after implant and was reproducibly terminated by rapid pacing alone (5 patients), low-energy shocks (2 patients), high-energy shocks (3 patients) and combined therapy (3 patients). Intermediate or high-energy shocks terminated all induced VF episodes. During follow-up (2 to 12 months), there have been 2 noncardiac deaths. Electrical therapy was delivered in 7 patients, for VT (3 patients), VT and VF (3 patients) and indeterminate tachyarrhythmia (1 patient). All VT/VF episodes were successfully terminated, with 78 of 96 (81%) spontaneous VT episodes terminated by pacing. Follow-up reprogramming was required in 5 patients. It is concluded that successful application of individualized electrical therapy prescriptions in patients with VT/VF is feasible. Pacing therapies, which are effective for induced VT, can be reliably used for effective long-term spontaneous VT termination in conjunction with shock therapy and can permit reduced patient exposure to shock therapy. Thus, a programmable hybrid pacemaker cardioverter-defibrillator system provides nonthoracotomy implantation, effective VT/VF termination, demand ventricular pacing and noninvasive modes for arrhythmia induction, event monitoring and clinical trouble-shooting.

Immediate reproducibility of clinical and nonclinical forms of induced ventricular tachycardia.

This prospective study assessed the immediate reproducibility of clinical and nonclinical forms of ventricular tachycardia (VT) induced by programmed ventricular stimulation. Twenty-three clinical VTs were unimorphic and previously documented and 22 nonclinical VTs (17 polymorphic and 5 unimorphic) were induced in patients with either no documented or suspected history of VT, or documented VT that had a configuration different from that of the induced VT. The stimulation protocol included 1 to 3 ventricular extrastimuli, 2 drive cycle lengths, and 2 right ventricular stimulation sites. Each VT was induced on the first attempt, then the stimulation protocol was repeated twice in the drug-free state. After the first VT induction, 21 of 23 clinical VTs (91%) and 17 of 22 nonclinical VTs (77%) were reinduced on the second attempt. After 2 VT inductions, 21 of 21 clinical VTs (100%) and 15 of 17 nonclinical VTs (88%) were reinduced on the third attempt. The reinduction rates of the clinical and nonclinical VTs were not significantly different. Among the clinical VTs, the reproducibility of the induction technique was 81% after 1 induction and 88% after 2 inductions with the same technique. These results imply that acute drug testing can be reliably performed after 2 inductions but not 1 induction of clinical VT; reproducibility is not helpful in determining whether an induced VT is clinical or nonclinical; and changes in induction technique during drug testing should be interpreted with caution because changes may occur in the absence of drugs.

Right and left ventricular hemodynamic performance during sustained ventricular tachycardia.

Several factors may influence hemodynamic tolerance of a ventricular tachycardia (VT) episode but, to date, only VT rate has been used as a major detection criterion in selecting implantable cardioverter-defibrillator therapy algorithms. We examined hemodynamic changes during VT in humans and a possible correlation between left and right ventricular hemodynamic indexes. Right ventricular hemodynamic indexes could reflect systemic hemodynamics but previous studies have been inconclusive. Patients with coronary artery disease and a history of recurrent, sustained VT were studied. Aortic pressure and right and left ventricular pressures were simultaneously recorded with 2 dual micromanometer-tipped high-fidelity pressure catheters during sinus rhythm and during induced sustained monomorphic VT. Beat-to-beat analysis was performed using custom-made software. Nine patients (7 men, mean age 60 +/- 8 years, mean ejection fraction 24 +/- 8%) with 11 VT episodes (mean cycle length 283 +/- 48 ms) were studied. During VT, left and right ventricular systolic pressures showed a mean decrease of 57% and 26%, respectively, with weak correlation (r = 0.67, p = 0.06) between both values. There was also an increase in mean left and right ventricular end-diastolic pressures of 26% and 74%, respectively, and no correlation was seen (r = -0.2, p = 0.6). A significant correlation was found between changes in left and right ventricular maximal positive dP/dt (55% and 28% decrease, respectively (r = 0.69, p = 0.03) and between changes in left and right ventricular maximal negative dP/dt (64% vs 39% decrease, r = 0.71, p = 0.02). Most ventricular time parameters in both ventricles differed significantly during VT compared with sinus rhythm; however, only the decrease in right ventricular time to end-diastolic pressure correlated with the decrease in left ventricular systolic pressure, at the 10th VT beat (r = 0.8, p = 0.01). We conclude that left and right ventricles are hemodynamically unequally affected during rapid VT. Although right ventricular pressures cannot be reliably used to assess changes in the hemodynamic status of the left ventricle, additional parameters, such as dP/dt or changes in ventricular time intervals, should be further evaluated for inclusion in implantable cardioverter-defibrillator algorithms.