Packer, Douglas L.

Background This study was undertaken to test the hypothesis that β-adrenergic stimulation in the setting of membrane depolarization will potentiate flecainide-induced conduction slowing. Methods and Results To elucidate the potential mechanism for the flecainide proarrhythmia observed in CAST, the voltage dependence of β-adrenergic modulation of impulse propagation in eight flecainide-superfused canine Purkinje fibers was examined with a dual-microelectrode technique. At physiological membrane potentials (V m ) ([K + ] o =5.4 μmol), 1 μmol flecainide decreased V̇ max from 698±55 to 610±72 V/s ( P =.003) and squared conduction velocity (θ 2 ) from 2.11±1.1 to 1.72±0.9 (m/s) 2 ( P =.001). With K + depolarization to V m =−70 mV, flecainide further reduced V̇ max from 306±101 to 245±65 V/s and θ 2 from 1.12±0.4 to 0.99±0.6 (m/s) 2 , producing a 2.0-mV hyperpolarizing shift of apparent Na + channel availability curves derived from θ 2 . The addition of 1 μmol isoproterenol to flecainide-superfused fibers at physiological V m increased θ 2 by 8% to 1.84±0.6 (m/s) 2 ( P <.01) without altering V̇ max . At −70 mV, the addition of isoproterenol magnified the flecainide-induced reduction of V̇ max an additional 24% to 185±52 V/s ( P <.01) and θ 2 by 17% to 0.82±0.5 (m/s) 2 ( P =.04), producing an additional 1.8-mV ( P =.002) and 1.9-mV ( P =.002) hyperpolarizing shift in the apparent Na + channel inactivation curves generated from V̇ max and θ 2 , respectively. At physiological V m , the action potential duration (APD 95 ) was reduced from 307±35 to 269±27 ms ( P <.001) by flecainide and subsequently to 217±4 ms ( P <.001) with isoproterenol addition. With 12 mmol/L K + , APD 95 decreased from 198±23 to 182±17 ms ( P =.005) with flecainide and to 164±10 ms ( P =.004) with isoproterenol. Conclusions At depolarized V m , isoproterenol amplified the flecainide-induced reduction of V̇ max and θ 2 , suggesting a further adrenergic-mediated reduction of Na + current. Consequently, the synergy between catecholamines and flecainide at depolarized V m and the shortened APD 95 could facilitate arrhythmogenesis in the presence of underlying ischemia.

Background —Previous studies of atrial flutter have found linear block at the crista terminalis; this was thought to predispose the patient to the arrhythmia. More recent observations, however, have demonstrated crista conduction. We sought to characterize the posterior boundary of atrial flutter. Methods and Results —Patients with counterclockwise flutter (n=20), clockwise flutter (n=3), or both (n=5) were studied using two 20-pole catheters. Biplane fluoroscopy determined catheter positions. During counterclockwise flutter, craniocaudal activation occurred along the entire lateral and posterior right atrial walls. Septal activation proceeded caudocranially. In all patients, a line of block was seen in the posteromedial (sinus venosa) right atrium; this was manifested by the presence of double potentials where the upward and downward activations collided. Anatomic location was confirmed by intracardiac echocardiography in 9 patients. In patients with clockwise flutter, the line of block and double potentials were seen in the same location during counterclockwise flutter, but the activation sequence around the line of block was reversed. Pacing near the site of double potentials during sinus rhythm excluded a fixed line of block, and premature atrial complexes demonstrated functional block with manifest double potentials. In 2 patients, posterior ectopy organized to subsequently initiate isthmus-dependent atrial flutter. Conclusions —(1) A functional line of block is seen at the posteromedial (sinus venosa region) right atrium during counterclockwise and clockwise atrial flutter. (2) All lateral wall right atrial activation can be uniform during flutter, without linear block or double potentials in the region of the crista terminalis. (3) Activation at the site of posteromedial right atrial functional block can organize to subsequently initiate isthmus-dependent atrial flutter.

BACKGROUND Virtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population. METHODS AND RESULTS We identified 113 residents of Olmsted County, Minnesota, during the period 1953-1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of 22% of the cohort. Approximately 50% of the population was asymptomatic at diagnosis, with 30% subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis. CONCLUSIONS The incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those < 40 years old, should return for medical follow-up should symptoms develop.

Background— The efficacy of radiofrequency ablation for atrial fibrillation (AF) in patients with left ventricular (LV) systolic dysfunction and isolated diastolic dysfunction is uncertain. Methods and Results— A prospective cohort of patients with normal and abnormal LV function underwent ablation for antiarrhythmic drug (AAD)-refractory AF. Three groups were compared: 111 patients with systolic dysfunction, defined as LV ejection fraction (LVEF) ≤40%; 157 patients with isolated diastolic dysfunction but preserved LVEF ≥50%; and 100 patients with normal LV function. The primary end point was AAD-free AF elimination at 1 year after ablation. This end point was achieved in 62% of patients with systolic dysfunction, 75% of those with diastolic dysfunction, and 84% of controls ( P =0.007). AF control on or off AADs was achieved in 76% of patients with systolic dysfunction, 85% of those with diastolic dysfunction, and 89% of controls ( P =0.08). In the systolic dysfunction group, 49% experienced an increase in LVEF by ≥5% after ablation, of which 64% achieved normal LVEF. In the diastolic dysfunction group, 30% of patients demonstrated at least 1 grade improvement in diastolic dysfunction. Multivariable analysis demonstrated an increased relative risk of arrhythmia recurrence of 1.8 (95% CI, 1.1 to 3.1; P =0.02) in systolic dysfunction and 1.7 (1.0 to 2.7; P =0.04) in isolated diastolic dysfunction compared with normal function. Conclusions— Although an ablative approach for AF in patients with systolic or diastolic dysfunction is associated with an increased long-term recurrence risk, there is potential for substantial quality-of-life improvement and LV functional benefit.

Background— The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction ≤35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown. Methods and Results— SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death. Conclusions— ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.

Background— Outflow tract ventricular tachycardia originating above the semilunar valves has been reported in a small number of studies. Discrete potentials in the great arteries (above the semilunar valves) have been rarely described in patients undergoing electrophysiology evaluation and radiofrequency ablation for ventricular arrhythmias. The mechanisms of these discrete potentials in the great arteries and the utility of such potentials in guiding radiofrequency ablation are unknown. Methods and Results— Twelve patients with outflow tract ventricular arrhythmia originating above the semilunar valves with discrete arterial potentials were studied. The clinical characteristics, properties of the arterial potentials, electrophysiological evaluation and ablation, and short- and long-term outcomes were reviewed. Of the twelve patients, 8 (67%) were women. The patients’ average age was 41�14 years. The average ejection fraction was 0.52�0.16 (range: 0.16 to 0.75). Contact mapping in the great artery demonstrated discrete near-field electrograms that were separate from far-field ventricular electrograms in all patients (8 above the pulmonary valve and in 4 the aortic valve). One or more of the following electrophysiological characteristics, supportive of an arrhythmogenic substrate, were observed in 10 of 12 patients: (1) A fixed or reproducibly variable pattern of discrete potential–ventricular arrhythmia relationship was present at baseline or during pacing; (2) the discrete potential–ventricular electrogram relationship during sinus rhythm was the reverse of that during the ventricular arrhythmia; (3) during sustained ventricular tachycardia, spontaneous variation of the ventricular (V-V) cycle length was preceded by a similar variation of arterial spike potential–spike potential cycle length; and (4) ablation guided by the discrete arterial potential successfully eliminated the clinical arrhythmia. Ablation was successful in these patients. In the remaining 2 patients, the potentials were believed to be bystanders. Over 10�4 months (range: 5 to 32 months) of follow-up, there have been no recurrences of the premature ventricular complex or ventricular arrhythmia. Conclusions— Discrete potentials are present in the great arteries of a select group of patients with outflow tract ventricular tachycardia originating above the semilunar valves. When an arrhythmogenic relationship can be demonstrated, discrete potentials are useful in guiding ablation within the great vessels, despite significant anatomic complexity.

Background— Obesity is a risk factor for atrial fibrillation and other cardiovascular conditions. Our objective was to determine whether catheter-based ablation effectively treated atrial fibrillation in obese patients. Methods and Results— Five hundred twenty-three consecutive patients with symptomatic, medication-refractory atrial fibrillation underwent catheter ablation. Patients were grouped by body mass index (lean, <25 kg/m 2 ; overweight, 25 to 29.9 kg/m 2 ; obese, ≥30 kg/m 2 ). Outcome and quality of life were measured with a general health survey (Medical Outcomes Study 36-item Short-Form General Health Survey [SF-36]); patients were assessed before ablation and at 3 and 12 months after the procedure. Two hundred twenty-eight study patients (44%) were overweight, and 201 (38%) were obese. Twelve months after curative ablation, 72% of patients were free of atrial fibrillation without the use of antiarrhythmic agents; 84% were arrhythmia free when those receiving medication were included. Atrial fibrillation was eliminated in 75%, 72%, and 70% of the lean, overweight, and obese patients, respectively, at 12 months ( P =0.41, trend test). SF-36 scores were lower for patients with higher body mass index ( P <0.05) at baseline. SF-36 scores improved in every functional domain for all body mass index groups after ablation. The mean SF-36 total physical score increased from 59±20 at baseline to 77±19 in 12 months ( P <0.001). The total mental health score improved from 66±18 to 79±16 in 12 months ( P <0.001). Conclusions— Catheter ablation of atrial fibrillation was effective in obese patients. Coexistence of atrial fibrillation and obesity indicated lower SF-36 scores, but the improvement in quality of life was consistent across all body mass index categories.

Background— Multiple factors create discrepancies between electroanatomic maps and merged, preacquired computed tomographic images used in guiding atrial fibrillation ablation. Therefore, a Carto-based 3D ultrasound image system (Biosense Webster Inc) was validated in an animal model and tested in 15 atrial fibrillation patients. Methods and Results— Twelve dogs underwent evaluation using a newly developed Carto-based 3D ultrasound system. After fiducial clip markers were percutaneously implanted at critical locations in each cardiac chamber, 3D ultrasound geometries, derived from a family of 2D intracardiac echocardiographic images, were constructed. Point-source error of 3D ultrasound-derived geometries, assessed by actual real-time 2D intracardiac echocardiographic clip sites, was 2.1�1.1 mm for atrial and 2.4�1.2 mm for ventricular sites. These errors were significantly less than the variance on CartoMerge computed tomographic images (atria: 3.3�1.6 mm; ventricles: 4.8�2.0 mm; P< 0.001 for both). Target ablation at each clip, guided only by 3D ultrasound-derived geometry, resulted in lesions within 1.1�1.1 mm of the actual clips. Pulmonary vein ablation guided by 3D ultrasound-derived geometry resulted in circumferential ablative lesions. Mapping in 15 patients produced modestly smaller 3D ultrasound versus electroanatomic map left atrial volumes (98�24 cm 3 versus 109�25 cm 3 , P< 0.05). Three-dimensional ultrasound-guided pulmonary vein isolation and linear ablation in these patients were successfully performed with confirmation of pulmonary vein entrance/exit block. Conclusions— These data demonstrate that 3D ultrasound images seamlessly yield anatomically accurate chamber geometries. Image volumes from the ultrasound system are more accurate than possible with CartoMerge computed tomographic imaging. This clinical study also demonstrates the initial feasibility of this guidance system for ablation in patients with atrial fibrillation.