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.

Swelling-activated chloride current is persistently activated in ventricular myocytes from dogs with tachycardia-induced congestive heart failure.

The hypothesis that cellular hypertrophy in congestive heart failure (CHF) modulates mechanosensitive (ie, swelling- or stretch-activated) anion channels was tested. Digital video microscopy and amphotericin-perforated-patch voltage clamp were used to measure cell volume and ion currents in ventricular myocytes isolated from normal dogs and dogs with rapid ventricular pacing-induced CHF. In normal myocytes, osmotic swelling in 0.9T to 0.6T solution (T, relative osmolarity; isosmotic solution, 296 mOsmol/L) was required to elicit ICl,swell, an outwardly rectifying swelling-activated Cl- current that reversed near -33 mV and was inhibited by 1 mmol/L 9-anthracene carboxylic acid (9AC), an anion channel blocker. Block of ICl,swell by 9AC simultaneously increased the volume of normal cells in hyposmotic solutions by up to 7%, but 9AC had no effect on volume in isosmotic or hyperosmotic solutions. In contrast, ICl,swell was persistently activated under isosmotic conditions in CHF myocytes, and 9AC increased cell volume by 9%. Osmotic shrinkage in 1.1T to 1.5T solution inhibited both ICl,swell and 9AC-induced cell swelling in CHF cells, whereas osmotic swelling only slightly increased ICl,swell. The current density for fully activated 9AC-sensitive ICl,swell was 40% greater in CHF than normal myocytes. In both groups, 9AC-sensitive current and 9AC-induced cell swelling were proportional with changes in osmolarity and 9AC concentration, and the effects of 9AC on current and volume were blocked by replacing bath Cl- with methanesulfonate. CHF thus altered the set point and magnitude of ICl,swell and resulted in its persistent activation. We previously observed analogous regulation of mechanosensitive cation channels in the same CHF model. Mechanosensitive anion and cation channels may contribute to the electrophysiological and contractile derangements in CHF and may be novel targets for therapy.

Persistent activation of a swelling-activated cation current in ventricular myocytes from dogs with tachycardia-induced congestive heart failure.

The hypothesis that cellular hypertrophy in congestive heart failure (CHF) modulates mechanosensitive (ie, swelling- or stretch-activated) channels was tested. Digital video microscopy and amphotericin-perforated-patch voltage clamp were used to measure cell volume and ion currents in ventricular myocytes isolated from normal dogs and dogs with rapid ventricular pacing-induced CHF. In normal myocytes, osmotic swelling in 0.9x to 0.6x isosmotic solution (296 mOsm/L) was required to elicit an inwardly rectifying swelling-activated cation current (I(Cir,swell)) that reversed near -60 mV and was inhibited by 10 micromol/L Gd3+, a mechanosensitive channel blocker. Block of I(Cir,swell) by Gd3+ simultaneously reduced the volume of normal cells in hyposmotic solutions by up to approximately 10%, but Gd3+ had no effect on volume in isosmotic solution. In contrast, I(Cir,swell) was persistently activated under isosmotic conditions in CHF myocytes, and Gd3+ decreased cell volume by approximately 8%. Osmotic shrinkage in 1.1x to 1.5x isosmotic solution inhibited both I(Cir,swell) and Gd3+-induced cell shrinkage in CHF cells, whereas osmotic swelling only slightly increased I(Cir,swell). The K0.5 and Hill coefficient for Gd3+ block of I(Cir,swell) and Gd3+-induced cell shrinkage were estimated as approximately 2.0 micromol/L and approximately 1.9, respectively, for both normal and CHF cells. In both groups, the effects of Gd3+ on current and volume were blocked by replacing bath Na+ and K+ and were linearly related with varying Gd3+ concentration and the degree of cell swelling. CHF thus altered the set point for and caused persistent activation of I(Cir,swell). This current may contribute to dysrhythmias, hypertrophy, and altered contractile function in CHF and may be a novel target for therapy.

Suppression of inducible ventricular tachycardia by ibutilide in patients with coronary artery disease. Ibutilide Investigators.

BACKGROUND: Recent studies suggest that class III antiarrhythmic agents may have enhanced efficacy in the treatment of ventricular tachycardia. This study describes the first clinical assessment of the new class III agent ibutilide to suppress inducible monomorphic ventricular tachycardia (VT) in human beings. METHODS AND RESULTS: Fifty-five patients with coronary artery disease and inducible sustained monomorphic VT at baseline received either low (0.005 mg/kg + 0.001 mg/kg, load and maintenance infusion, respectively), middle (0.01 mg/kg + 0.002 mg/kg), or high dose (0.02 mg/kg + 0.004 mg/kg) infusions of ibutilide followed by repeat programmed ventricular stimulation. The mean age of the study group was 65.5 +/- 9.5 years and mean left ventricular ejection fraction was 36% +/- 11%. Of 48 evaluable patients, 21 (44%) were rendered noninducible after ibutilide, with no difference in efficacy among the three dosing groups (p = 0.83). Ventricular effective refractory periods, QTc interval, and ventricular monophasic action potential duration were prolonged over baseline at all tested cycle lengths. The QTc and action potential prolongation were dose related. Serious drug-related adverse reactions included sustained polymorphic VT in two patients (3.6%), spontaneous monomorphic VT in one patient (1.8%), heart block in one patient (1.8%), and hypotension in one patient (1.8%). CONCLUSIONS: Ibutilide prolongs ventricular repolarization in human beings and demonstrates efficacy in suppressing inducible monomorphic VT. Significant cardiovascular side effects occurred in 12.7% of patients.

Physiology of the escape rhythm after radiofrequency atrioventricular junctional ablation.

The physiology of the escape rhythm (ER) and its response to pharmacological modulation under varying autonomic conditions were studied 48 patients undergoing radiofrequency ablation of the atrioventricular junction (AVJ) for refractory atrial fibrillation. The QRS morphology and cycle length (CL) of the baseline ER were measured 15 minutes postablation. The CL of the ER was measured in response to doses of isoproterenol, atropine, adenosine, lidocaine, and verapamil. The ER QRS was narrow (QRS < 120 ms) in 20 patients and wide (QRS > 120 ms) in 28 patients. Of the 28 patients with wide QRS ER, 11 patients had a new bundle branch block (8 patients new right bundle branch block [RBBB] and 2 patients new left bundle branch block [LBBB]). The ERCL was similar in both narrow and wide ERs (1,593 +/- 376 ms and 1,516 +/- 296 ms, P = 0.44). In 23 patients receiving isoproterenol infusion, the ER CL decreased with increasing doses from 1 mcg/min to 2 mcg/min (1,378 +/- 200 to 1,240 +/- 229 ms, P < 0.001), but did not decrease further at 3 mcg/min (1,201 +/- 192 ms, P = 0.48 vs 2 mg/min). Seven patients received 0.02 mg/kg of atropine, and ER decreased significantly (1,572 +/- 408 ms to 1,319 +/- 333 ms, P = 0.028). In 30 patients who received intravenous boluses of adenosine (6-18 mg), the ER did not change significantly. In 28 patients who received 150 mg of lidocaine, the ER increased from 1,462 +/- 286 ms to 1,715 +/- 467 ms (P < 0.001), and one patient developed transient asystole. Nineteen patients received 7.5 mg of verapamil, and the ER did not change (1,488 +/- 313 ms to 1,513 +/- 666 ms, P = 0.80). There was no significant difference in response to isoproterenol, adenosine, lidocaine, or verapamil between the patients with wide and narrow QRS ERs. We conclude that patients may have stable ERs immediately following AVJ ablation even when a wide complex ER results. The ER is responsive to sympathetic stimulation and vagal blockade. The ER is prolonged after lidocaine but not after verapamil, suggesting response to sodium but not to calcium channel blockade. These data are consistent with an ER originating in the distal compact AV node or proximal His bundle.

Quality of life and clinical outcomes in elderly patients treated with ventricular pacing as compared with dual-chamber pacing. Pacemaker Selection in the Elderly Investigators.

BACKGROUND: Standard clinical practice permits the use of either single-chamber ventricular pacemakers or dual-chamber pacemakers for most patients who require cardiac pacing. Ventricular pacemakers are less expensive, but dual-chamber pacemakers are believed to be more physiologic. However, it is not known whether either type of pacemaker results in superior clinical outcomes. METHODS: The Pacemaker Selection in the Elderly study was a 30-month, single-blind, randomized, controlled comparison of ventricular pacing and dual-chamber pacing in 407 patients 65 years of age or older in 29 centers. Patients received a dual-chamber pacemaker that had been randomly programmed to either ventricular pacing or dual-chamber pacing. The primary end point was health-related quality of life as measured by the 36-item Medical Outcomes Study Short-Form General Health Survey. RESULT: The average age of the patients was 76 years (range, 65 to 96), and 60 percent were men. Quality of life improved significantly after pacemaker implantation (P<0.001), but there were no differences between the two pacing modes in either the quality of life or prespecified clinical outcomes (including cardiovascular events or death). However, 53 patients assigned to ventricular pacing (26 percent) were crossed over to dual-chamber pacing because of symptoms related to the pacemaker syndrome. Patients with sinus-node dysfunction, but not those with atrioventricular block, had moderately better quality of life and cardiovascular functional status with dual-chamber pacing than with ventricular pacing. Trends of borderline statistical significance in clinical end points favoring dual-chamber pacing were observed in patients with sinus-node dysfunction, but not in those with atrioventricular block. CONCLUSION: The implantation of a permanent pacemaker improves health-related quality of life. However, the quality-of-life benefits associated with dual-chamber pacing as compared with ventricular pacing are observed principally in the subgroup of patients with sinus-node dysfunction.

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.

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.

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.

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.

Antiarrhythmic actions of intravenous ibutilide compared with procainamide during human atrial flutter and fibrillation: electrophysiological determinants of enhanced conversion efficacy.

BACKGROUND: The selective class III antiarrhythmic agent ibutilide prolongs action potential duration and terminates atrial flutter (AFL) and fibrillation (AF), but the mechanism of its antiarrhythmic efficacy in humans has not been fully characterized. This study compared the antiarrhythmic effects of ibutilide with the class IA agent procainamide in humans during AFL and AF. Antiarrhythmic drug actions and electrophysiological characteristics of AFL and AF that enhanced pharmacological termination were investigated. METHODS AND RESULTS: Right atrial monophasic action potentials were recorded during 148 episodes of AFL (n=89) or AF (n=59) in 136 patients treated with intravenous ibutilide (n=73) or placebo (n=22) as participants in randomized, double-blinded comparative studies or intravenous procainamide (n=53) in a concurrent open-label study. The conversion rates in AFL with ibutilide, procainamide, and placebo were 64% (29 of 45 patients), 0% (0 of 33), and 0% (0 of 11), respectively, whereas in AF the rates were 32% (9 of 28), 5% (1 of 20), and 0% (0 of 11), respectively. In AFL, ibutilide increased atrial monophasic action potential duration (MAPD) more (30% versus 18%, P<.001) and prolonged atrial cycle length (CL) less (16% versus 26%, P<.001) than procainamide. Ibutilide shortened and procainamide prolonged action potential diastolic interval during AFL (-12% versus 51%, P<.001). Ibutilide increased MAPD/CL ratio, whereas procainamide tended to decrease this ratio (13% versus -6%, P<.01). In AF, ibutilide and procainamide induced similar increases in atrial CL (48% versus 45%), but ibutilide induced a greater increase in MAPD (52% versus 37%, P<.05). Independent electrophysiological predictors of pharmacological arrhythmia termination were increase in MAPD/CL ratio (P=.005) in AFL and longer baseline mean MAPD (P=.011) in AF. Termination of AFL with ibutilide was characterized by significant increases in beat-to-beat atrial CL, MAPD, and diastolic interval variability. Ibutilide was significantly more effective in converting AF when the mean atrial CL was > or = 160 ms (64% versus 0%, P<.001) or MAPD was > or = 125 ms (57% versus 0%, P=.002) at baseline. CONCLUSIONS: Enhanced conversion efficacy of ibutilide compared with procainamide in AFL is correlated with a relatively greater prolongation of atrial MAPD than atrial CL, and termination of AFL by ibutilide is characterized by oscillations in atrial CL and MAPD. Conversion of AF by ibutilide is enhanced by a longer baseline mean atrial CL or MAPD.

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.

Limitations of tachycardia confirmation and rate classification algorithms in a third-generation implantable cardioverter defibrillator.

Newer ICDs provide antitachycardia (ATP) and bradycardia pacing and cardioversion and defibrillation shocks based on sensed interval criteria. The objectives of this investigation were to determine the algorithm related errors in tachycardia confirmation and rate classification that occurred in patients with a third-generation, noncommitted, tiered ICD therapy. Forty-three consecutive patients with the Guardian ATP 4210 ICD, which uses an X out of Y sensed interval counting algorithm for tachycardia detection, confirmation, and classification were studied. Surface ECGs, intracardiac electrograms, stored data logs, and sense histories were reviewed to diagnose errors due to these algorithms that resulted in delivery of inappropriate therapy or inhibition of appropriate therapy. Sixty-eight classification or confirmation algorithm errors from 7,610 tachycardia detections (< 1%) were diagnosed in 23 (53%) of 43 patients. Three types of errors not related to device or sensing lead malfunction or programming mistakes were seen. In 26 episodes, the confirmation algorithm failed to detect late tachycardia reversion of nonsustained tachyarrhythmias, on the last or next to last sensed interval, and did not inhibit ATP (n = 17) or shocks (n = 9). In 28 episodes, inaccurate classification of tachycardia rate resulted in inappropriate ATP (n = 23) or shock (n = 5) therapy. In 14 episodes, the posttherapy reconformation algorithm produced inhibition of VVI pacing and prolonged asystole following shock therapy. These errors in tachycardia confirmation and rate classification were due to the inherent limitations of the X out of Y counting algorithm.

Elucidating the mechanisms of atrial flutter cycle length variability using power spectral analysis techniques.

BACKGROUND: The mechanism of the small beat-to-beat variations in cycle length of atrial flutter in humans has not been fully explained. We investigated the beat-to-beat control of atrial flutter cycle length using time and frequency analysis techniques. METHODS AND RESULTS: Mean, SD, and power spectra of atrial cycle lengths were calculated from atrial recordings in 28 patients with type I atrial flutter. In control patients, mean and SD values of atrial cycle length were 265 +/- 37 and 4.9 +/- 1.7 ms. Power spectra contained two or three major peaks with 10.6 +/- 9.2% in band 1 (0.0 to 0.18 Hz), 26.7 +/- 15.9% in band 2 (0.18 to 0.6 Hz), and 63.1 +/- 17.7% in band 3 (0.6 to 2.2 Hz). Isoproterenol infusion (n = 8) increased percentage of total power in band 1 (7.1 +/- 5.6% to 25.7 +/- 18.9%, P < .001). Percentage of total power in band 1 was less in patients receiving (n = 5) versus not receiving (n = 18) oral beta-blockers (2.2 +/- 1.9% versus 10.6 +/- 9.2%, P = .003). Standard deviation (2.5 +/- 1.3 versus 4.9 +/- 1.7 ms, P = .009) and total power (2025 +/- 1350 versus 9768 +/- 8874 ms2, P = .005) were less in heart transplant recipients (n = 5) than control patients. Increases in respiratory rate (n = 6) shifted band 2 frequency peak to higher frequencies (0.26 +/- 0.13 to 0.38 +/- 0.18 Hz, P < .05). Atrial cycle length was longer and monophasic action potential duration was shorter during inspiration than during expiration. Band 3 frequency peak was correlated with heart rate (r = .797, P < .0001). CONCLUSIONS: Atrial flutter cycle length variability has an underlying periodic pattern that is detected by spectral analysis. Atrial flutter is modulated on a beat-to-beat basis by an interplay between the autonomic nervous and respiratory systems and the ventricular rate.

Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators.

BACKGROUND: Currently available antiarrhythmic drugs have limited efficacy for acute termination of atrial fibrillation and flutter, especially if the arrhythmia is not of recent onset. The purpose of this multicenter study was to determine the efficacy and safety of repeated doses of intravenous ibutilide, a class III antiarrhythmic drug, in terminating atrial fibrillation or flutter. METHODS AND RESULTS: Two hundred sixty-six patients with sustained atrial fibrillation (n = 133) or flutter (n = 133), with an arrhythmia duration of 3 hours to 45 days, were randomized to receive up to two 10-minute infusions, separated by 10 minutes, of ibutilide (1.0 and 0.5 mg or 1.0 and 1.0 mg) or placebo. The conversion rate was 47% after ibutilide and 2% after placebo (P < .0001). The two ibutilide dosing regimens did not differ in conversion efficacy (44% versus 49%). Efficacy was higher in atrial flutter than fibrillation (63% versus 31%, P < .0001). In atrial fibrillation but not flutter, conversion rates were higher in patients with a shorter arrhythmia duration or a normal left atrial size. Arrhythmia termination occurred a mean of 27 minutes after start of the infusion. Of 180 ibutilide-treated patients, 15 (8.3%) developed polymorphic ventricular tachycardia during or soon after the infusion. The arrhythmia required cardioversion in 3 patients (1.7%) and was nonsustained in 12 patients (6.7%). CONCLUSIONS: Intravenous ibutilide given in repeated doses is effective in rapidly terminating atrial fibrillation and flutter and under monitored conditions is an alternative to current cardioversion options.

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.

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.