Double-blind placebo-controlled trial of digoxin in symptomatic paroxysmal atrial fibrillation.

BACKGROUND: Digoxin is commonly prescribed in symptomatic paroxysmal atrial fibrillation (AF) but has never been evaluated in this condition. METHODS AND RESULTS: From a multicenter registry, 43 representative patients with frequent symptomatic AF episodes were recruited into a randomized, double-blind crossover comparison of digoxin (serum concentration, 1.29+/-0.35 nmol/L) and placebo. The study end point was the occurrence of 2 AF episodes (documented by patient-activated monitors), censored at 61 days. The median time to 2 episodes was 13.5 days on placebo and 18.7 days on digoxin (P<0. 05). The relative risk (95% CI) of 2 episodes (placebo:digoxin) was 2.19 (1.07 to 4.50). A similar effect was seen on the median time to 1 episode: increased from 3.5 to 5.4 days (P<0.05), relative risk 1. 69 (0.88 to 3.24). The mean+/-SD ventricular rates during AF recordings during placebo and digoxin treatment were 138+/-32 and 125+/-35 bpm, respectively (P<0.01). Twenty-four-hour ambulatory ECG recordings did not show significant differences in the frequency or duration of AF or in ventricular rate. CONCLUSIONS: Digoxin reduces the frequency of symptomatic AF episodes. However, the estimated effect is small and may be due to a reduction in the ventricular rate or irregularity rather than an antiarrhythmic action.

Transvenous single lead atrial defibrillation: efficacy and risk of ventricular fibrillation in an ischemic canine model.

Transvenous atrial defibrillation with multiple atrial lead systems has been shown to be effective in models without the potential for ventricular arrhythmias. The specific aim of this study was to evaluate the efficacy and safety of transvenous single lead atrial defibrillation in a canine model of ischemic cardiomyopathy. Ten dogs had ischemic cardiomyopathy induced by repeated intracoronary microsphere injections. The mean LV ejection fraction decreased from 71% +/- 9% to 38% +/- 14% (P = 0.003). Spontaneous atrial fibrillation (AF) developed in four dogs, and in six AF was induced electrically. Atrial defibrillation thresholds (ADFTs) were determined with synchronous low energy shocks using a transvenous tripolar lead with two defibrillation coils (right ventricle, superior vena cava) and an integrated sensing lead (RV coil vs electrode tip). The ADFTs derived by logistic regression were compared at 50% and 90% probability of success (ED50, ED90): ED50 was 2.4 +/- 1.7 J and 2.9 +/- 2.1 J, respectively, for 5- and 10-ms monophasic shocks, and 1.8 +/- 0.9 J, respectively, for 5- and 10-ms biphasic shocks. Immediately after 3 of 2,179 (0.1%) synchronized shocks, ventricular fibrillation (VF) developed. VF was induced in 3 of 1,062 (0.3%) shocks with integrated sensing (RV coil vs electrode tip) compared to 0 of 1,117 shocks when a separate bipolar RV sensing electrode was used for synchronization. In our canine model of ischemic cardiomyopathy, low energy atrial defibrillation via a transvenous single lead system was highly effective. However, there was a small but definite risk of VF induction, which seemed to be greater when an integrated as opposed to a true bipolar RV sensing was used.

The treatment of patients with infected implantable cardioverter-defibrillator systems.

OBJECTIVE: The purpose of this study was to evaluate the treatment of patients with infected implantable cardioverter-defibrillator systems. METHODS: Retrospective analysis was done of the cases of 21 patients treated for implantable cardioverter-defibrillator infection during an 11-year period. RESULTS: Of 723 cardioverter-defibrillator implantations (550 primary implants, 173 replacements), nine (1.2%) were complicated by early postoperative device-related infections. Late infections developed in two patients 19 and 22 months, respectively, after implantation. Ten other patients were transferred to our institution for treatment of cardioverter-defibrillator infection. The time from implantation to overt infection was 2.2 +/- 1.3 months, excluding the two late infections. The responsible organisms were Staphylococcus aureus (9), Staphylococcus epidermidis (6), Streptococcus hemolyticus (1), gram-negative bacteria (3), Candida albicans (1), and Corynebacterium (1). All patients were treated with intravenous antibiotic drugs. Total system removal was done in 15 patients and partial removal in 2; in 4, the cardioverter-defibrillator system was not explanted. There were no perioperative deaths. A new implantable cardioverter-defibrillator system was reimplanted in 7 patients after 2 to 6 weeks of antibiotic therapy. Ten patients were treated without reimplantation (2 arrhythmia operation, 8 antiarrhythmic drugs). Four patients (3 patients without explantation and 1 with partial system removal) were treated with maintenance long-term antibiotic therapy. During a mean follow-up of 21 +/- 2.8 months, no patient had clinical recurrence of infection. One patient treated with antiarrhythmic drugs without system reimplantation died suddenly. CONCLUSIONS: Infections that involve implantable cardioverter-defibrillator systems can be safely managed by removing the entire system with reimplantation after intravenous antibiotic therapy. In selected patients in whom the risk for system explantation is high and anticipated life expectancy is short, long-term antibiotic therapy to suppress low-virulence infections may represent an acceptable alternative.

Effect of flecainide on atrial and ventricular refractoriness and conduction in patients with normal left ventricle. Implications for possible antiarrhythmic and proarrhythmic mechanisms.

We studied the effects of intravenous flecainide (2 mg.kg-1) on atrial and ventricular refractoriness and conduction during sinus rhythm, induced atrial fibrillation and atrial pacing at rates of 100, 120 and 150 ppm, in 14 patients with normal left ventricle. Flecainide caused a significant increase in QRS duration during sinus rhythm (mean +/- SD: 87.2 +/- 8.4 ms vs 102.8 +/- 9.1 ms, P < 0.001), atrial fibrillation (87.8 +/- 10.0 ms vs 108.8 +/- 13.7 ms, P < 0.001) and at all paced rates. The duration of the atrial electrogram was significantly increased during sinus rhythm (54.9 +/- 13.2 ms vs 64.8 +/- 16.6 ms, P = 0.003) and at all pacing rates. The PA interval was also significantly prolonged, as was the pacing stimulus-to-atrial-electrogram interval at all pacing rates. There was increased QRS duration and atrial electrogram prolongation at higher pacing rates. Atrial refractoriness was prolonged during sinus rhythm (216.4 +/- 28.2 vs 228.6 +/- 36.1, P = 0.02), but not during atrial pacing at any rate. The QT interval, but not the JT interval or ventricular refractoriness, was significantly prolonged during sinus rhythm and at all pacing rates. Flecainide slows atrial conduction in a use dependent manner and increases atrial refractoriness during sinus rhythm but not during faster atrial pacing, thus not displaying a use-dependent effect. QRS duration is prolonged in a use-dependent manner without a commensurate increase in ventricular refractoriness. In the presence of rapidly conducted atrial fibrillation, which was not found to be slowed by flecainide, this effect may constitute a proarrhythmic mechanism even in patients with no apparent myocardial abnormality.

Prevalence and prognostic significance of atrial arrhythmias after orthotopic cardiac transplantation.

OBJECTIVES: We studied the duration and prognostic significance of atrial arrhythmias in the denervated transplanted heart, specifically the occurrence of atrial fibrillation in the absence of vagal modulation. BACKGROUND: Substantial animal data indicate that vagally induced dispersion of atrial refractoriness plays a central role in the induction and maintenance of atrial fibrillation. METHODS: We studied the occurrence of atrial arrhythmias in the denervated hearts of 88 consecutive orthotopic transplantations in 85 patients by means of continuous telemetry and all available electrocardiographic tracings. RESULTS: Fifty percent of recipients (44 of 88) developed at least one atrial arrhythmia. Atrial fibrillation occurred 23 times (21 recipients), atrial flutter 39 times (26 recipients), ectopic atrial tachycardia 3 times (3 recipients) and supraventricular tachycardia 18 times (11 recipients). The number of atrial fibrillation and atrial flutter episodes did not differ (23 vs. 39, p = 0.072), but the mean duration of atrial flutter was longer than that of atrial fibrillation (37.0 +/- 10 vs. 6.6 +/- 3.6 h, p = 0.014). Atrial fibrillation was associated with an increased risk of subsequent death (10 of 21 recipients with vs. 15 of 67 without atrial fibrillation, risk ratio 3.15 +/- 0.18, p = 0.005 by Cox proportional hazards model). All 5 recipients who developed "late" atrial fibrillation (> 2 weeks after transplantation) died versus 5 of 16 who developed atrial fibrillation within the first 2 weeks (p = 0.007). Causes of death included rejection (three recipients), allograft failure (two recipients), infection (three recipients) and multiorgan failure (two recipients). Atrial fibrillation was not associated with age, gender, ischemic time, reason for transplantation, echocardiographic variables, invasive hemodynamic variables or biopsy grade. Mean time from atrial arrhythmia to echocardiography was 2.7 +/- 3.3 days; that to biopsy was 4.8 +/- 6.3 days. Atrial flutter was not associated with subsequent death. Only 7 (15.9%) of 44 recipients demonstrated moderate or severe allograft rejection at the time of the arrhythmia. CONCLUSIONS: Atrial arrhythmias occur frequently in the denervated transplanted heart, often in the absence of significant rejection. Late atrial fibrillation may be associated with an increased all-cause mortality.

Subclavian crush syndrome complicating transvenous cardioverter defibrillator systems.

UNLABELLED: Subclavian crush syndrome, described with pacemaker leads implanted via subclavian puncture, may occur when conductor fractures and insulation breaches develop by compression of a lead between the first rib and clavicle. We reviewed our experience in 164 patients who underwent intended implantation of transvenous defibrillator systems to determine the clinical relevance of subclavian crush syndrome in defibrillator patients. Venous access was obtained via subclavian puncture in 114 patients (70%) and via cephalic cut-down in 50 patients (30%). Nonthoracotomy lead systems, with or without subcutaneous patch, were successfully implanted in 131 of 164 patients (79.9%). Thoracotomy was required in 32 patients (19.5%) and subxiphoid patch in 1 patient (0.6%). Over a mean of 12.9 months (range 1-62 months), 3 patients (1.8%) required revision of the rate sensing lead/coil or superior vena cava coil after development of lead compression fractures in the region of the clavicle and first rib. In all 3 patients the leads had been implanted via subclavian puncture (2.6% of patients in whom the subclavian technique was utilized). Two patients presented with spurious shocks. One patient was asymptomatic. CONCLUSIONS: When venous access is obtained via subclavian puncture, subclavian crush syndrome may develop in patients with transvenous defibrillator systems. Patients may be asymptomatic and lead fractures may go unrecognized. When implanting transvenous defibrillator systems, strong consideration should be given to obtaining venous access primarily via the cephalic cut-down technique.

Ventricular pacing induced ventricular tachycardia in patients with implantable cardioverter defibrillators.

Appropriately timed noncompetitive ventricular pacing potentially may initiate ventricular tachycardia in patients prone to these arrhythmias. The combination of bradycardia pacing and stored electrograms in a currently available cardioverter defibrillator provides an opportunity to evaluate the occurrence of such pacing induced ventricular tachycardia. During a surveillance period of 18.7 +/- 11.4 months, stored electrograms documented 302 episodes of ventricular tachycardia in 77 patients. Five patients (6.5%) demonstrated 25 episodes (1-16 per patient) of ventricular tachycardia that were immediately preceded by an appropriately paced ventricular beat (8.3% of all episodes of ventricular tachycardia). All five patients had prior myocardial infarctions and a history of monomorphic ventricular tachycardia occurring both spontaneously and in response to programmed electrical stimulation. Antitachycardia pacing terminated pacing induced ventricular tachycardia in 22 episodes; in one episode antitachycardia pacing accelerated ventricular tachycardia. In two cases shock therapy was aborted for nonsustained ventricular tachycardia. We conclude that, in selected nonsustained ventricular tachycardia. We conclude that, in selected postinfarction patients with recurrent sustained monomorphic ventricular tachycardia treated with implantable cardioverter defibrillators, appropriately timed ventricular pacing may induce ventricular tachycardia.

Electrocardiographic pseudo-infarct patterns after implantation of cardioverter-defibrillators.

Postoperative electrocardiographic (ECG) changes are frequently present after insertion of implantable cardioverter-defibrillators (ICD) and may mimic perioperative myocardial infarction (MI). The purpose of this study was to assess the incidence and clinical significance of postoperative ECG changes in relation to clinical, laboratory, and implantation data. In 25 (16%) of 156 patients undergoing ICD implantation, significant ECG changes (> or = 50% reduction in R-wave amplitude in > or = 3 leads or new Q waves in > or = 2 leads) were present 1 to 3 days after the operation and persisted at hospital discharge in 12 (8%). Presence of thoracotomy, the total number of induced ventricular fibrillation episodes, and the number of defibrillation shocks required during defibrillation threshold (DFT) testing correlated with postoperative ECG changes. Other factors associated with a significant R-wave loss in the lateral precordial leads included left-sided pleural effusion, lung infiltrates or atelectasis, and large defibrillator patch electrodes over the left ventricle or the lateral chest wall. Myocardial necrosis documented by elevated cardiac enzymes occurred in 6 (5%) of 151 patients without significant ECG changes and in 3 (12%) with (p value not significant). However, postoperative ECG changes associated with elevated enzymes were indistinguishable from changes unrelated to necrosis. Therefore the sensitivity and specificity of the surface ECG for detection of MI after ICD placement is poor. Multiple factors such as thoracotomy, myocardial injury from DFT testing, electric insulation, or shielding of the heart may contribute to the development of electrocardiographic pseudo-infarct patterns.

Relation between shock-related myocardial injury and defibrillation efficacy of monophasic and biphasic shocks in a canine model.

BACKGROUND: Certain biphasic waveforms with specific time ratios of positive and negative components require less energy for successful defibrillation of the fibrillating ventricles than monophasic waveforms. However, if more efficient waveforms were also to be associated with more injurious effects on myocardial function, they might not provide a true biological advantage. This study investigates the relation between defibrillation efficacy and potential toxicity of monophasic and asymmetric, single capacitor, biphasic waveforms with equal durations of positive and negative components. METHODS AND RESULTS: The myocardial lactate extraction rate (LER) was used to measure the injurious effects on myocardial oxidative metabolism of two synchronized 35-J shocks in sinus rhythm. LER, mean arterial pressure (MAP) and, in a subset of experiments, cardiac output (CO) and coronary blood flow (CBF) were measured at baseline, 30 seconds, 60 seconds, 90 seconds, 150 seconds, 300 seconds, and 600 seconds after the shocks. In 12 dogs, three different waveforms (M 10: monophasic 10 milliseconds; BI 10: biphasic 10 milliseconds; BI 20: biphasic 20 milliseconds) were tested as series of two consecutive shocks (60 seconds apart) resulting in a total of 36 sets of data. At baseline, LER was 25 +/- 11%. After monophasic shocks, LER decreased significantly more than after biphasic shocks (LER at 150 seconds: M 10: -6 +/- 31% versus BI 10: 21 +/- 15% versus BI 20: 21 +/- 16%; M 10 versus BI 10 and M 10 versus BI 20, P < .05) and showed also a slower recovery (LER at 300 seconds: M 10: 1 +/- 24% versus BI 10: 20 +/- 11% versus BI 20: 20 +/- 15%; M 10 versus BI 10 and M 10 versus BI 20, P < .05). The maximal decrease in LER was 41 +/- 27% for M 10 compared with 18 +/- 15% for BI 10 and 15 +/- 11% for BI 20 (both, M 10 versus BI 10 and M 10 versus BI 20, P < .05). There was a similar decrease in CO and MAP, with the lowest MAP after monophasic shocks. The maximal decrease in MAP was significantly greater after M 10 compared with BI 20 (-29 +/- 15 mm Hg versus -13 +/- 11 mm Hg, P < .05). The defibrillation threshold was 18.6 +/- 8 J for M 10 compared with 11.5 +/- 4.0 J for BI 10 (P < .05) and 15.0 +/- 6.1 J for BI 20, respectively (P = NS). CONCLUSIONS: Our results suggest that these specific biphasic waveforms are associated with less injurious effects on myocardial oxidative metabolism and hemodynamic performance. Given their higher defibrillation efficacy as well, biphasic waveforms may provide important long-term benefits in patients receiving frequent shocks from implantable cardioverter-defibrillators.

Curative transcatheter radiofrequency current ablation for atrioventricular nodal reentry tachycardia.

BACKGROUND: To evaluate the efficacy of atrioventricular nodal modification by transcatheter ablation using radiofrequency energy in preventing electrically inducible and spontaneous symptomatic atrioventricular nodal reentry tachycardia, a prospective, nonrandomized, "before-after" trial was performed. Fifty consecutive patients with recurrent spontaneous symptomatic atrioventricular nodal reentry tachycardia referred to the Massachusetts General Hospital, Boston, were recruited. METHODS: A diagnostic intracardiac electrophysiologic study was performed to define the mechanism of each patient's supraventricular tachycardia. Thereafter, selective ablation of one or more slow atrioventricular nodal pathways was attempted in 47 patients, and in three patients selective ablation of a retrograde fast atrioventricular nodal pathway was carried out. Repeated programmed cardiac stimulation was performed 30 minutes after catheter ablation therapy and, where possible, before hospital discharge to evaluate the presence of electrically inducible supraventricular tachycardia. RESULTS: Electrically inducible atrioventricular nodal reentry tachycardia was eliminated in all 50 patients. No patient developed early heart block. During a mean (+/- SD) follow-up period of 8.9 +/- 5.3 months, three patients experienced a recurrence of spontaneous atrioventricular nodal reentry tachycardia and underwent a successful second ablation procedure. Two patients required permanent pacemaker implantation, one for symptomatic first-degree atrioventricular block and one for late complete heart block. CONCLUSIONS: Catheter ablation of slow atrioventricular nodal pathways by means of radiofrequency current is a safe and effective technique for eliminating electrically inducible and spontaneous atrioventricular nodal reentry tachycardia.

Treatment of ventricular tachycardia by transcatheter radiofrequency ablation in patients with ischemic heart disease.

BACKGROUND: Recurrent sustained ventricular tachycardia (VT) is not responsive to antiarrhythmic drugs in the majority of patients, who therefore need therapy with nonpharmacological methods. We evaluated prospectively the feasibility, safety, and efficacy of transcatheter radiofrequency (RF) ablation of VT in 21 selected patients with ischemic heart disease and VT. METHODS AND RESULTS: Twenty-one patients with ischemic heart disease and recurrent, drug-refractory VT documented by 12-lead ECG were selected who had sufficient hemodynamic tolerance of VT to undergo transcatheter mapping. Documented clinical VT was reproduced by programmed cardiac stimulation (PCS), and the site of origin was localized by a combination of techniques, including pace mapping, activation-sequence mapping, recordings of middiastolic potentials, and application of resetting and entrainment principles. RF current at 55 V was applied (3.8 +/- 3.1 applications per patient) for as long as 30 seconds at a time to target sites. Twenty-four distinct clinical VTs (mean cycle length, 445 +/- 52 milliseconds) were mapped and ablated in 21 patients. In 17 of 21 patients (81%), the procedure was acutely successful, and the target clinical VT could no longer be induced by PCS after the procedure, whereas in 4 patients, clinical VT remained inducible. By contrast, VTs with shorter cycle length and different QRS morphology than the ablated VT could still be induced by PCS in 12 of 21 patients. One patient died in intractable congestive heart failure 10 days after the procedure, and the remaining 20 are alive at the end of the follow-up period. The majority of the patients continued to be treated with at least one additional mode of antiarrhythmic therapy; 12 patients were still taking antiarrhythmic drugs, and 9 patients received an implantable cardioverter/defibrillator. During a mean follow-up period of 13.2 +/- 5.0 months, 9 of 20 patients (45%) had recurrent VT. In 4 patients, the recurrent VT was different than the previously ablated one. Clinical VT recurred in all 4 patients in whom RF ablation had been acutely unsuccessful. Four patients with recurrent VT underwent repeat RF ablation procedures that were acutely successful and had no further recurrence. CONCLUSION: Transcatheter RF ablation is feasible but has only moderately high efficacy in a small, selected group of patients with ischemic heart disease and drug-refractory, highly frequent, hemodynamically tolerated, sustained VT. In the majority of the patients, this treatment technique is palliative rather than definitive, and many of the patients continue to require other methods of antiarrhythmic therapy.

Radiofrequency current delivery by way of a bipolar tricuspid annulus-mitral annulus electrode configuration for ablation of posteroseptal accessory pathways.

OBJECTIVES: This report describes a novel technique for ablation of "difficult" posteroseptal pathways. BACKGROUND: Although radiofrequency ablation of accessory atrioventricular (AV) pathways is successful in > or = 90% of cases, particular difficulty may be encountered with some bypass tracts in the posteroseptal region. METHODS: In eight patients with posteroseptal accessory pathways (two concealed), radiofrequency catheter ablation using conventional unipolar current applications from favorable sites along the tricuspid or mitral annulus, or both, was unsuccessful. Subsequently, a bipolar technique was adopted, with current application between the distal electrodes of two catheters positioned against the septal region at sites of early activation along both mitral and tricuspid annuli. RESULTS: The bipolar configuration proved effective in all cases. The number of bipolar lesions required for success was one (five patients), five (two patients) and nine (one patient). In five patients, bipolar current application abolished pathway conduction using positions at which delivery of unipolar lesions had been ineffective or caused transient block. The AV or ventriculoatrial interval at successful sites varied from 20 to 65 ms, and the time from delta wave onset to local ventricular activation was zero or negative. There were no complications attributable to the bipolar technique. During follow-up of 8 to 36 weeks, pathway conduction has not recurred in any patient. CONCLUSIONS: Bipolar radiofrequency current delivery across the septal region using a tricuspid annulus-mitral annulus electrode configuration may abolish accessory pathway conduction when conventional unipolar applications have proved ineffective. The technique may reduce procedure duration, radiation exposure and overall failure rate in these problematic cases.

Pseudo-pacemaker syndrome following inadvertent fast pathway ablation for atrioventricular nodal reentrant tachycardia.

Atrioventricular nodal reentrant tachycardia that is refractory to drug treatment has recently been treated with radiofrequency catheter ablation. In this case report we describe a patient with atrioventricular nodal reentrant tachycardia in whom radiofrequency ablation of slow pathway was attempted, with inadvertent damage to the fast pathway. The patient developed marked first-degree atrioventricular block associated with symptoms mimicking pacemaker syndrome.