Pharmacologic alterations in human type I atrial flutter cycle length and monophasic action potential duration. Evidence of a fully excitable gap in the reentrant circuit.

OBJECTIVES: This study compared the effect of changes in action potential duration versus conduction velocity on atrial flutter cycle length to determine whether there is a fully or partially excitable gap in atrial flutter. BACKGROUND: In an excitable gap reentrant circuit, cycle length is proportional to conduction velocity. Action potential duration is not a direct determinant of cycle length when the gap is fully excitable. METHODS: Right atrial monophasic action potentials were recorded from 41 patients during type I atrial flutter before and during pharmacologic interventions. RESULTS: Adenosine (17 +/- 3 mg [mean +/- SD]) shortened (p < 0.001) action potential duration but did not change cycle length. Edrophonium (10 mg) had no significant effect on action potential duration or cycle length. Isoproterenol (0.03 microgram/kg body weight per min) shortened (p < 0.05) and procainamide (15 mg/kg, then 2 mg/min) prolonged (p < 0.001) action potential duration and cycle length. Alterations in cycle length were not correlated with changes in action potential duration. Procainamide's prolongation of action potential duration was reversed by adenosine without affecting cycle length. Procainamide's prolongation of action potential duration and cycle length was partially reversed by isoproterenol. Adenosine's and isoproterenol's shortening of action potential duration and isoproterenol's shortening of cycle length were enhanced by procainamide. CONCLUSIONS: Atrial flutter cycle length is determined primarily by conduction velocity and does not depend directly on action potential duration. Atrial flutter has a fully excitable gap, and procainamide does not convert the gap from full to partial excitability. Adenosine and isoproterenol interact with procainamide such that their effects are enhanced and procainamide's effects are diminished.

Conversion of atrial flutter by ibutilide is associated with increased atrial cycle length variability.

OBJECTIVES: This study was designed to test the hypothesis that conversion of atrial flutter in humans by ibutilide, a new class III antiarrhythmic agent, is characterized by an increase in atrial cycle length variability. BACKGROUND: Conversion of tachyarrhythmias has been associated with increased oscillations of cycle length. METHODS: Electrograms and monophasic action potentials from the right atrium in 35 patients with spontaneous, sustained atrial flutter were recorded before, during and after intravenous ibutilide (0.005 to 0.025 mg/kg body weight, n = 25) or placebo (n = 10). Atrial cycle length, cycle length variability (coefficient of variation), diastolic interval and diastolic interval variability were measured from 10 consecutive cycles at baseline and 3 min before, 1 min before, 30 s before and immediately before conversion. Similar measurements were made in patients who received ibutilide or placebo but did not convert. RESULTS: Ibutilide converted atrial flutter in 14 of 25 patients 25 +/- 16 min (mean +/- SD) after initiation of the infusion, whereas placebo converted no patients. Atrial cycle length was prolonged to the same extent in ibutilide converters and nonconverters (36 +/- 19 vs. 38 +/- 21 ms, p = NS) and was not affected by placebo. Beat-to-beat variability in atrial cycle length (baseline 1.2 +/- 0.7 vs. preconversion 7.3 +/- 4.9, p < 0.01) and diastolic interval (baseline 11 +/- 8 vs. preconversion 33 +/- 23, p < 0.05) increased significantly just before atrial flutter conversion and remained unchanged in ibutilide nonconverters and placebo group patients. CONCLUSIONS: Ibutilide prolongs atrial cycle length, but conversion of atrial flutter by ibutilide is characterized by increased variability in atrial cycle length and diastolic interval.

Lessons learned from data logging in a multicenter clinical trial using a late-generation implantable cardioverter-defibrillator. The Guardian ATP 4210 Multicenter Investigators Group.

OBJECTIVES: This study examined patterns of implantable cardioverter-defibrillator use as documented by data logging. BACKGROUND: Implantable cardioverter-defibrillators are accepted therapy for malignant ventricular tachyarrhythmias; however, relatively little is known about their patterns of use. Incorporation of data-storage capacities into these devices provides insight into long-term defibrillator function. METHODS: Stored data-logging information was retrieved from 401 implanted cardioverter-defibrillators in 393 patients over an average of 303 days of follow-up. RESULTS: A total of 91,443 detections were recorded in 299 patients. One hundred-six patients (26%) had detections due to supraventricular tachycardias, electrical noise or other causes, resulting in inappropriate therapy delivery to 92 patients (23%). Two hundred eighty-one patients recorded 66,276 episodes of ventricular tachycardia or ventricular fibrillation. Of these, 74.4% episodes terminated spontaneously without any delivered therapy, 22.1% terminated after antitachycardia pacing, and 1.7% terminated after shock therapy. Antitachycardia pacing was activated without formal testing in 47% of all patients receiving this therapy and was successful in 96% of all episodes receiving this therapy. Acceleration of tachycardia to shock therapy occurred in 1.3% of all episodes and in 30.5% of patients receiving antitachycardia pacing. Thirty-four patients (8.7%) died during follow-up. Mortality was associated with patient age, heart failure functional class at implantation and frequency of shocks received during follow-up (all p < or = 0.05). CONCLUSIONS: Most ventricular tachyarrhythmia detections by this noncommitted implantable cardioverter-defibrillator resolve spontaneously, whereas the majority receiving therapy can be treated with antitachycardia pacing. Mortality after implantable cardioverter-defibrillator implantation is associated with age, heart failure class and frequency of shocks received during follow-up. Data-logging capabilities provide valuable insights into the patterns of defibrillator use.

Circadian pattern of ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators.

OBJECTIVES: This study examined the temporal patterns of ventricular tachycardia detections by implantable cardioverter-defibrillators for circadian variability. BACKGROUND: Previous studies of circadian arrhythmia patterns have been methodologically limited by very brief observational periods. Late-generation implantable cardioverter-defibrillators accurately record the times of arrhythmia detections during unlimited follow-up. METHODS: Forty-three patients with late-generation implantable cardioverter-defibrillators were followed up for 226 +/- 179 days (mean +/- SD). The times of all recorded episodes of ventricular tachyarrhythmias were retrieved from the data log of each device during follow-up. RESULTS: The weighted distribution of 830 ventricular tachyarrhythmia episodes from the 43 patients fit a single harmonic sine curve model with a peak between 2 and 3 P.M. (95% confidence interval 1:13 to 4:13 P.M., R = 0.75, p < 0.05). The distributions of spontaneously terminating episodes, episodes receiving device therapy, episodes receiving shocks and episodes in the absence of antiarrhythmic therapy also fit the sine curve model (all R = 0.53 and 0.73, all p < 0.05), all with peak frequencies between 2:08 and 3:09 P.M. and 95% confidence intervals for peak frequencies between 11:38 A.M. and 5:07 P.M. Episodes recorded during continuous antiarrhythmic drug therapy did not fit the model (p > 0.05). CONCLUSIONS: The distribution of ventricular tachyarrhythmias detected by late-generation implantable cardioverter-defibrillators follows a circadian pattern, with a peak tachycardia frequency between noon and 5 P.M. This pattern was not observed in patients receiving antiarrhythmic drug therapy. Knowledge of circadian periodicity for these events has implications for patient management.

Hemodynamic effects of intravenous sematilide in patients with congestive heart failure: a class III antiarrhythmic agent without cardiodepressant effects.

OBJECTIVES: This study sought to evaluate the hemodynamic effects of intravenous sematilide hydrochloride, a selective class III antiarrhythmic agent, in patients with heart failure and left ventricular systolic dysfunction. BACKGROUND: Class I antiarrhythmic agents, which primarily slow conduction, can depress ventricular function, particularly in patients with heart failure. In contrast, pure class III agents, which selectively prolong repolarization, do not adversely affect hemodynamic variables in animal models, but there are no data evaluating their hemodynamic effects in humans. METHODS: In 39 patients with congestive heart failure and a left ventricular ejection fraction < 40%, hemodynamic and electrocardiographic measurements were obtained at baseline, after a loading dose and during a maintenance infusion of intravenous sematilide using either a low (0.75 then 0.3 mg/min) or high dose (1.5 then 0.6 mg/min) regimen. The study had an 80% power to detect clinically meaningful differences in hemodynamic variables. RESULTS: Both low (n = 20) and high (n = 19) dose sematilide infusions produced dose-dependent increases in QT interval (5 +/- 8% [mean +/- SD] and 18 +/- 10%, respectively) and corrected QT interval (4 +/- 8% and 14 +/- 10%), and high dose sematilide decreased heart rate by 7 +/- 10% (all p < 0.025 vs. baseline). Neither dose regimen had a statistically significant effect on any other hemodynamic variable, including mean arterial, right atrial, pulmonary artery and pulmonary capillary wedge pressures; cardiac index, stroke volume, systemic and pulmonary vascular resistances; and left ventricular stroke work index. Sematilide showed no adverse hemodynamic effects in patients with left ventricular ejection fraction < or = 25% or > 25% and in patients with cardiac index < 2 or > or = 2 liters/min per m2. Sustained polymorphic ventricular tachycardia (n = 1) and excessive QT prolongation (n = 4) were seen during the high dose. CONCLUSIONS: Sematilide, in the doses administered, prolonged repolarization but did not alter hemodynamic variables in patients with heart failure. These data suggest that class III antiarrhythmic agents, which selectively prolong repolarization, are not cardiodepressant but may be proarrhythmic in humans, especially at high doses.

Sensing/pacing lead complications with a newer generation implantable cardioverter-defibrillator: worldwide experience from the Guardian ATP 4210 clinical trial.

OBJECTIVES: This report describes the sensing/pacing lead complications that developed during a worldwide clinical trial of a new implantable cardioverter-defibrillator. BACKGROUND: The reliability of the leads used for sensing and pacing with the implantable cardioverter-defibrillator has not been adequately studied. METHODS: The Guardian ATP 4210 was implanted in 302 patients. The sensing/pacing leads consisted of either two unipolar epicardial electrodes or a bipolar endocardial electrode from a variety of manufacturers. RESULTS: During a mean follow-up period of 380 days, 39 patients (12.9%) required reoperation because their device developed sensing/pacing lead system complications. The most common clinical presentation was device oversensing (multiple tachycardia or noise detections or inappropriate shocks), which was observed in 27 patients, whereas elevated pacing thresholds were seen in 10 patients. Forty-one (11.8%) of 347 implanted lead systems required revision. The mean time to revision was 156 +/- 145 days. Actuarial lead survival rate at 1 and 3 years was 89% and 79%, respectively. Epicardial lead systems required significantly (p < 0.05) more revision than did endocardial systems, but when adapter problems were excluded, the revision rates of epicardial and endocardial leads were similar. Causes of lead system failures included adapter connection problems, lead dislodgement and insulation disruption. Predictors of lead revision were use of an epicardial lead system or an adapter. CONCLUSIONS: A high rate of sensing/pacing lead complications was found with this newer generation implantable cardioverter-defibrillator. The enhanced diagnostic and data storage capabilities of this implantable cardioverter-defibrillator facilitated the recognition and troubleshooting of these complications. These findings emphasize the need for careful surveillance and testing of implantable cardioverter-defibrillator sensing/pacing leads during follow-up.

Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: a dose-response study.

OBJECTIVES: Currently available antiarrhythmic drugs have limited efficacy for short-term, rapid termination of atrial fibrillation and atrial flutter. BACKGROUND: Ibutilide fumarate is an investigational class III antiarrhythmic agent that prolongs repolarization by increasing the slow inward sodium current and by blocking the delayed rectifier current. It can be administered intravenously and has a rapid onset of electrophysiologic effects. METHODS: The efficacy and safety of ibutilide were studied in 200 patients with atrial flutter > 3 h in duration or atrial fibrillation 3 h to 90 days in duration. Patients were randomized to receive a single intravenous dose of placebo or an infusion of ibutilide fumarate at 0.005, 0.010, 0.015 or 0.025 mg/kg body weight over 10 min. Conversion was defined as termination of the atrial arrhythmia during or within 60 min after infusion. Forty-one patients received placebo and 159 received ibutilide (0.005 mg/kg [n = 41], 0.010 mg/kg [n = 40], 0.015 mg/kg [n = 38] or 0.025 mg/kg [n = 40]). RESULTS: The arrhythmia terminated in 34% of drug-treated patients. The rates of successful arrhythmia termination were 3% for placebo and 12%, 33%, 45% and 46%, respectively, for 0.005-, 0.010-, 0.015- and 0.025-mg/kg ibutilide. The placebo and 0.005-mg/kg ibutilide groups had lower success rates than all other dose groups (p < 0.05). The mean time to termination of the arrhythmia was 19 min (range 3 to 70) from the start of infusion. Successful arrhythmia termination was not affected by enlarged left atrial diameter, decreased ejection fraction, presence of valvular heart disease or the use of concomitant medications (beta-adrenergic blocking agents, calcium channel blocking agents or digoxin). Arrhythmia termination was not predicted by the magnitude of corrected QT interval prolongation but was associated with a shorter duration of atrial arrhythmia. The most frequent adverse events in ibutilide-treated patients were sustained and nonsustained polymorphic ventricular tachycardia (3.6%). All patients with sustained polymorphic ventricular tachycardia were successfully treated with direct current cardioversion and had no recurrence. The occurrence of proarrhythmia did not correlate with ibutilide plasma concentration. CONCLUSIONS: These data demonstrate that ibutilide is able to rapidly terminate atrial fibrillation and atrial flutter.

Comparative efficacy of intravenous ibutilide versus procainamide for enhancing termination of atrial flutter by atrial overdrive pacing.

This study compares the influence of intravenous ibutilide, a class III antiarrhythmic agent, with procainamide, a class IA antiarrhythmic agent, and with placebo on its ability to terminate atrial flutter using rapid atrial pacing. Fifty-nine episodes of atrial flutter in 54 patients who failed to terminate with an intravenous infusion of ibutilide, procainamide, or placebo alone underwent attempts at pacing termination using a standard protocol of burst atrial overdrive pacing. Atrial flutter cycle length and atrial monophasic action potential duration recorded from the right atrium during atrial flutter were measured at baseline and following infusion of ibutilide, procainamide, or placebo. Both ibutilide and procainamide significantly enhanced (p <0.001) pacing-induced termination of atrial flutter compared with placebo. Pacing converted 2 of 11 patients (18%) who received placebo, 13 of 15 patients (87%) who received ibutilide, and 29 of 33 patients (88%) who received procainamide to sinus rhythm. Ibutilide and procainamide compared with placebo markedly reduced (p <0.001) the incidence of pacing-induced atrial fibrillation. The atrial flutter cycle length was prolonged significantly less (p <0.001), and the atrial monophasic action potential duration was increased significantly more (p <0.001) by ibutilide than by procainamide. Although the electrophysiologic changes induced by these antiarrhythmic agents contributed to facilitating pacing-induced termination, neither tachycardia cycle length nor action potential duration were useful predictors of the ability of pacing to terminate atrial flutter. In conclusion, despite differing electrophysiologic effects, the use of intravenous ibutilide or procainamide enhances the termination of atrial flutter by atrial overdrive pacing.

Examination of mechano-electrical feedback in the transplanted human heart.

Several investigators have demonstrated that changes in atrial or ventricular pressure and size may modulate changes in electrophysiologic properties. The coupling of mechanical and electrical changes in the heart has been termed mechano-electrical feedback and is believed to play a role in arrhythmias observed with mitral valve disease, congestive heart failure, and left ventricular hypertrophy. To avoid confounding influences of the autonomic nervous system on electrophysiologic measurements, we measured right atrial and ventricular pacing thresholds with temporary epicardial pacing wires, right ventricular monophasic action potential duration at 90% repolarization during right ventricular pacing at 600 and 400 ms, donor heart rate, systolic, diastolic, and mean arterial and central venous pressures in 22 patients after orthotopic heart transplantation. Each variable was measured at baseline, in the resting supine state, and during graded lower body negative pressure of -10, -20, and -30 mm Hg. All levels of lower body negative pressure resulted in a significant decrease in mean right atrial pressure up to 5 +/- 6 mm Hg at maximal lower body negative pressure, and a significant decrease in mean arterial pressure occurred only at -20 and -30 mm Hg. Lower body negative pressure did not result in a significant change in any electrophysiologic variable despite significant changes in right atrial pressure. Thus, in the denervated transplanted human heart, unloading of the right heart results in no or small changes in atrial or ventricular pacing thresholds and ventricular monophasic action potential duration.

Measurement of ventricular electrogram amplitude during intraoperative induction of ventricular tachyarrhythmias.

Adequate sensing of ventricular tachycardia (VT) and ventricular fibrillation (VF) is necessary for proper functioning of an implantable cardioverter defibrillator (ICD). Several ICDs currently undergoing investigation have programmable fixed gain sensitivity for tachycardia detection. If intracardiac electrogram amplitude decreases below the programmed sensitivity during VT or VF, detection of a ventricular arrhythmia may be delayed or missed. The mean amplitude of intracardiac electrograms (ICEGM) recorded with bipolar epicardial or transvenous sensing leads was measured in 63 patients during induced VT and VF recorded in the operating room at the time of ICD implantation. The mean amplitude of the ICEGM during 41 episodes of VF in 15 patients decreased from 14.9 +/- 0.9 mV during sinus rhythm to 8.8 +/- 0.7 mV at 1 second, 9.7 +/- 0.7 mV at 5 seconds, and 9.4 +/- 0.7 mV at 10 seconds (p < 0.0001 vs sinus rhythm ICEGM) with endocardial leads. The mean amplitude of the ICEGM recorded during 173 episodes of VF in 43 patients with epicardial leads decreased from 10.4 +/- 0.3 mV in sinus rhythm to 7.8 +/- 0.3 mV at 1 second, 8.3 +/- 0.3 mV at 5 seconds and 8 mV at 10 seconds (p <0.0001 vs sinus rhythm ICEGM). The mean amplitude of epicardial and transvenous ICEGMs recorded during 34 episodes of monomorphic VT decreased from 18.5 +/- 1.8 mV (epicardial) and 14.4 +/- 2.0 mV (transvenous) during sinus rhythm (p = 0.15, epicardial vs transvenous) to 16.0 +/- 1.7 mV (epicardial) and 13.7 +/- 1.9 mV (transvenous) at 10 seconds (< 10% of baseline amplitude).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of ibutilide for termination of atrial fibrillation and flutter.

The clinical utility of ibutilide fumarate (Corvert) for the acute conversion of atrial tachyarrhythmias to normal sinus rhythm has been demonstrated in several randomized, placebo-controlled clinical trials. The efficacy of intravenous ibutilide for rapid conversion of atrial flutter is in the range of 50-70%, whereas its efficacy for conversion of atrial fibrillation is 30-50%. Approximately 80% of atrial tachyarrhythmias that terminate do so within 30 minutes from the initiation of the intravenous infusion. Ibutilide is more effective than either intravenous procainamide or intravenous sotalol for conversion of atrial fibrillation and atrial flutter to sinus rhythm. Age, presence of structural heart disease, gender and concomitant medication do not appear to influence the efficacy of ibutilide; however, shorter duration of atrial fibrillation is a strong predictor of successful termination. Plasma concentration of ibutilide and QTc interval prolongation are not directly correlated with the success rate for conversion of atrial tachyarrhythmias. Ibutilide's greater efficacy compared with other antiarrhythmic drugs may be related to its ability to cause greater prolongation of atrial monophasic action potential duration relative to atrial cycle length. Termination of atrial flutter with ibutilide was preceded by increased atrial cycle length variability. Ibutilide rapidly and effectively converts atrial fibrillation and atrial flutter to sinus rhythm when administered as a 1-mg total dose followed by a second 1-mg dose. It should be used in conjunction with continuous electrocardiographic monitoring for at least 4 hours after the termination of the infusion, or until the QTc interval returns to baseline. Hypokalemia and hypomagnesemia should be corrected before the start of the infusion. An external cardiac defibrillator, intravenous magnesium, and an external transcutaneous cardiac pacemaker should be readily available for immediate use in the event that palymorphic ventricular tachyarrhythmias occur. Ibutilide is a new intravenous agent that safely and rapidly converts atrial fibrillation and atrial flutter to sinus rhythm.

Effects of enhanced parasympathetic tone on atrioventricular nodal conduction during atrioventricular nodal reentrant tachycardia.

The effects of various physiologic and pharmacologic stimuli on the anterograde slow pathway in patients with atrioventricular nodal reentrant tachycardia are well characterized. We sought to further characterize the nature of anterograde and retrograde conduction during tachycardia and to define the differential input of the parasympathetic nervous system to these pathways. A custom-made neck suction collar was placed to stimulate the carotid body baroreceptors during supraventricular tachycardia. Neck suction at -60 mm Hg was applied and changes in tachycardia cycle length, AH, and ventriculoatrial intervals were measured in 20 patients. These measurements were repeated after intravenous administration of 10 mg of edrophonium to enhance vagal tone. We observed a 15 +/- 6 ms increase in tachycardia cycle length from baseline (p <0.0001) and a 14 +/- 6 ms increase in AH interval (p <0.0001), but no change in the VA interval with neck suction alone. The tachycardia cycle length prolonged 26 +/- 55 ms (p <0.0001) with edrophonium and an additional 12 +/- 43 ms (p <0.001) with neck suction after edrophonium. There was no change in the VA interval before or after edrophonium during neck suction. There were 10 tachycardia terminations in 8 patients during anterograde slow pathway block during neck suction, with tachycardia cycle length prolongation and mean AH prolongation before termination of 45 +/- 37 ms (vs 15 +/- 7 ms increase in AH interval without tachycardia termination, p = 0.10). There were 12 tachycardia terminations in 4 patients with retrograde block during neck suction, only after edrophonium, without any preceding change in tachycardia cycle length during 11 episodes. We conclude that anterograde slow pathway demonstrates gradual conduction slowing with parasympathetic enhancement, whereas retrograde fast pathway responds with abrupt block.

Safety and efficacy of intravenous diltiazem in atrial fibrillation or atrial flutter.

This study examines the efficacy of various doses of intravenous diltiazem to control the ventricular response during atrial fibrillation or atrial flutter. Control of the ventricular response of patients with atrial fibrillation and a rapid ventricular response can provide patients with relief of symptoms and improve hemodynamics. Eighty-four consecutive patients with atrial fibrillation or atrial flutter, or both, received an intravenous bolus dose of diltiazem followed by a continuous infusion of diltiazem at 5, 10, and 15 mg/hour. The mean ventricular response and blood pressure were monitored. Overall, 94% of patients (79 of 84) responded to the bolus dose with a > 20% reduction in heart rate from baseline, a conversion to sinus rhythm, or a heart rate < 100 beats/min. Seventy-eight patients received the continuous infusion. After 10 hours of infusion, 47% of patients (confidence interval [CI]: 36%, 59%) had maintained response with the 5 mg/hour infusion, 68% (CI: 57%, 79%) maintained response after the infusion was titrated to 10 mg/hour, and 76% (CI: 66%, 85%) after titration from the 5 and 10 mg/hour infusion to the 15 mg/hour dose. For the 3 diltiazem infusions studied, mean (+/- SD) heart rate was reduced from a baseline value of 144 +/- 14 beats/min to 98 +/- 19, 107 +/- 25, 107 +/- 22, 101 +/- 22, 91 +/- 17, and 88 +/- 18 beats/min at infusion times 0, 1, 2, 4, 8, and 10 hours, respectively. By the end of the infusion, 18% of patients (14 of 78) had conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute hemodynamic effects of intravenous ibutilide in patients with or without reduced left ventricular function.

Many antiarrhythmic agents have adverse hemodynamic effects which limit their use in patients with impaired ventricular function or during tachyarrhythmias. Ibutilide is an intravenous, selective class III antiarrhythmic agent that is effective for conversion of atrial fibrillation or flutter. This multicenter, randomized, placebo-controlled, dose-ranging study evaluated the effects of intravenous ibutilide on hemodynamic parameters during invasive monitoring in 47 patients with or without reduced left ventricular ejection fraction (LVEF) > 35% or < or = 35%. Patients received either placebo or ibutilide as a 10-minute loading and a 30-minute maintenance infusion using 1 of the following dosing regimens: placebo then placebo (n = 12); 0.01 then 0.002 mg/kg (n = 12); 0.02 then 0.004 mg/kg (n = 12); or 0.03 then 0.006 mg/kg (n = 11). Ibutilide significantly increased QT and QTc intervals in a dose-related manner with mean increases ranging from 51 to 99 ms, but did not alter the PR interval or QRS duration. During ibutilide infusion, a few small but statistically significant changes from baseline in several hemodynamic variables were present. However, the changes in cardiac output, pulmonary artery or capillary wedge pressures, blood pressure, or heart rate in patients receiving ibutilide were not significantly different from the changes in patients receiving placebo. Thus, ibutilide did not cause clinically important adverse hemodynamic effects, even in patients with depressed ventricular function. One patient developed 2 episodes of nonsustained torsades de pointes during ibutilide. These results demonstrate that with careful monitoring for proarrhythmia, ibutilide can be used safely from a hemodynamic standpoint in the acute treatment of arrhythmias, even in patients with reduced ventricular function.

Control of heart rate during transition from intravenous to oral diltiazem in atrial fibrillation or flutter.

We tested whether patients presenting with atrial fibrillation (AF) or flutter (AFl) with a rapid ventricular response could maintain control of heart rate while transferring from a bolus and continuous infusion of intravenous diltiazem to oral diltiazem. Forty patients with AF or AFI and sustained ventricular rate > or = 120 beats/min received intravenous diltiazem "bolus" (20 to 25 mg for 2 minutes) and "infusion" (5 to 15 mg/hour for 6 to 20 hours). Oral long-acting diltiazem (diltiazem CD 180, 300, or 360 mg/24 hours) was administered in patients in whom stable heart rate control was attained during constant infusion. Intravenous diltiazem infusion was discontinued 4 hours after the first oral dose, and patients were monitored during 48 subsequent hours of "transition" to oral therapy. Response to diltiazem was defined as heart rate <100 beats/min, > or = 20% decrease in heart rate from baseline, or conversion to sinus rhythm. Other rate control or antiarrhythmic medications were not allowed during the study period. Thirty-seven of 40 patients maintained heart rate control during the bolus, and 35 of the remaining 37 maintained control during the infusion of intravenous diltiazem. Of the 35 patients achieving heart rate control with intravenous diltiazem who entered the transition to oral therapy, 27 maintained heart rate control (response rate of 77%/, 95% confidence interval 63% to 91%). The median infusion rate of intravenous diltiazem was 10 mg/hour, and the median dose of oral diltiazem CD was 300 mg/day. Oral long-acting diltiazem was 77% effective in controlling ventricular response over 48 hours in patients with AF or AFl in whom ventricular response was initially controlled with intravenous diltiazem.

Selective slow pathway ablation does not alter enhancement of vagal tone on sinus and atrioventricular nodal function.

We studied the effects of edrophonium on sinus cycle length, atrioventricular (AV) nodal fast pathway refractoriness, and AV nodal Wenckebach cycle length in 21 patients with AV nodal reentrant tachycardia (AVNRT) who received edrophonium, and 8 patients who received phenylephrine before and after selective slow pathway ablation. Changes in sinus cycle length, fast pathway conduction, and refractoriness were not altered by radiofrequency ablation of the slow pathway, suggesting that parasympathetic denervation does not occur after slow pathway ablation of AVNRT.

Factors associated with elevated impedance with a nonthoracotomy defibrillation lead system.

Peak current flow across the heart determines the success of defibrillation and is inversely dependent on impedance between defibrillation electrodes. Factors associated with elevated impedance in patients with implantable defibrillators using nonthoracotomy lead systems have not been well described. Clinical and echocardiographically derived variables were analyzed in 41 patients in whom implantation of a nonthoracotomy lead system was attempted. Lead impedance was measured at end-expiration with 5-J monophasic shocks. Successful defibrillation with or without addition of a subcutaneous patch with < or = 20 J with a monophasic waveform was required for nonthoracotomy lead placement. Patients were divided into 2 groups based on impedance: low (< or = 47 ohms, n = 30) and high (>47 ohms, n = 11). Twenty-four patients had successful defibrillator implantation using a transvenous lead alone, 13 required placement of a subcutaneous patch, and 4 required epicardial patch placement. The mean left ventricular end-diastolic and end-systolic volumes were significantly smaller (p = 0.01 for both) in patients in the low- versus high-impedance groups and were significantly correlated with impedance (r = 0.44, p <0.005 for both). Impedance was not significantly different between patients with successful defibrillation using a transvenous lead alone compared with those who required either subcutaneous or epicardial patches. Thus, impedance using a nonthoracotomy lead system with monophasic shocks is significantly correlated with both end-systolic and end-diastolic volumes, but elevated impedance does not predict increased defibrillation energy requirements.

Are more complex implantable cardioverter defibrillators associated with an increased mortality? Lessons learned from clinical trials.

We compared 1-year survival in patients receiving implantable cardioverter defibrillators (ICDs) that provide only shock therapy with more advanced ICDs that provide antitachycardia pacing, bradycardia pacing, low-energy cardioversion, and advanced detection algorithms. Outcome in patients with advanced-generation ICD systems was similar or improved compared with outcome in patients receiving ICDs with only monophasic shock.

Clinical characteristics of patients intolerant to VVIR pacing.

The incidence and clinical predictors of the development of intolerance to VVIR pacing have not been extensively studied in prospective long-term randomized trials comparing different pacing modes. The frequency and clinical factors predicting intolerance to ventricular pacing are controversial. The Pacemaker Selection in the Elderly (PASE) Trial enrolled 407 patients aged >/=65 years in a 30-month, single-blind, randomized, controlled comparison of quality of life and clinical outcomes with ventricular pacing and dual-chamber pacing in patients undergoing dual-chamber pacemaker implantation for standard clinically accepted indications. We reviewed the clinical, hemodynamic, and electrophysiologic variables at the time of pacemaker implantation in 204 patients enrolled in the PASE trial and randomized to the VVIR mode, some of whom subsequently required crossover (reprogramming) to DDDR pacing. During a median follow-up of 555 days, 53 patients (26%) crossed over from VVIR to DDDR pacing. A decrease in systolic blood pressure during ventricular pacing at the time of pacemaker implantation (p = 0.001), use of beta blockers at the time of randomization (p = 0.01), and nonischemic cardiomyopathy (p = 0.04) were the only variables that predicted crossover in the Cox multivariate regression model. After reprogramming to the dual-chamber mode, patients showed improvement in all aspects of quality of life, with significant improvements in physical and emotional role. The high incidence of crossover from VVIR to DDDR pacing along with significant improvements in quality of life after crossover to DDDR pacing strongly favors dual-chamber pacing compared with single-chamber ventricular pacing in elderly patients requiring permanent pacing.

Sensing lead-related complications in patients with transvenous implantable cardioverter-defibrillators.

The widespread use of the redesigned Endotak lead (CPI, St. Paul, Minnesota), which combines transvenous pacing, sensing, and defibrillation on a single transvenous lead in patients receiving transvenous implantable cardioverter-defibrillators (ICDs), has reduced morbidity and shortened length of hospital stay after ICD implantation. We describe the incidence and management of Endotak sensing lead-related failures in a series of 348 consecutive patients from 4 institutions who underwent implantation between 1990 and 1995. We retrospectively reviewed the databases for patients receiving an ICD with an Endotak lead for the incidence of lead-related sensing abnormalities. Ten patients (2.8%) with lead-related sensing abnormalities were detected at a mean of 15 +/- 11 months after ICD implantation. Sensing abnormalities were detected in 6 patients after they received inappropriate shocks. Noise or oversensing was noted in 7 patients from interrogation of the devices' data logs. Eight patients had a new transvenous sensing lead placed, 1 patient had a new Endotak lead placed, and 1 had a chronic pacemaker sensing lead converted to function as a sensing lead. No further sensing problems were noted in 8 of 10 patients during a mean follow-up of 14 +/- 8 months. The site of the sensing lead failure was localized to the subrectus pocket in 5 patients and to the clavicle-first rib area in 3 patients; it was undetermined and presumed to be in the clavicle-first rib area in the other 2 patients. One patient had late failure of the defibrillation lead. We conclude that Endotak sensing lead failure does not require insertion of a new Endotak lead, but can be managed with close follow-up and insertion of a new transvenous sensing lead. Endotak lead fractures are frequently localized to the ICD pocket.