An algorithm for automatic measurement of stimulation thresholds: clinical performance and preliminary results

We have developed an algorithmic method for automatic determination of stimulation thresholds in both cardiac chambers in patients with intact atrioventricular (AV) conduction. The algorithm utilizes ventricular sensing, may be used with any type of pacing leads, and may be downloaded via telemetry links into already implanted dual-chamber Thera pacemakers. Thresholds are determined with 0.5 V amplitude and 0.06 ms pulse-width resolution in unipolar, bipolar, or both lead configurations, with a programmable sampling interval from 2 minutes to 48 hours. Measured values are stored in the pacemaker memory for later retrieval and do not influence permanent output settings. The algorithm was intended to gather information on continuous behavior of stimulation thresholds, which is important in the formation of strategies for programming pacemaker outputs. Clinical performance of the algorithm was evaluated in eight patients who received bipolar tined steroid-eluting leads and were observed for a mean of 5.1 months. Patient safety was not compromised by the algorithm, except for the possibility of pacing during the physiologic refractory period. Methods for discrimination of incorrect data points were developed and incorrect values were discarded. Fine resolution threshold measurements collected during this study indicated that: (1) there were great differences in magnitude of threshold peaking in different patients; (2) the initial intensive threshold peaking was usually followed by another less intensive but longer-lasting wave of threshold peaking; (3) the pattern of tissue reaction in the atrium appeared different from that in the ventricle; and (4) threshold peaking in the bipolar lead configuration was greater than in the unipolar configuration. The algorithm proved to be useful in studying ambulatory thresholds.     

Clinical use of low output settings in 1.2-mm2 steroid eluting electrodes: three years of experience

A new generation of tined steroid-eluting leads featuring 1.2-mm2 distal electrodes (CapSure Z, Medtronic Inc., Minneapolis MN, USA) has the potential to reduce battery current drain and enhance pulse generator longevity by means of high pacing impedance and low pacing threshold. Forty patients aged 50-87 years (mean 72.4 years) were implanted with 33 ventricular (models 4033 and 5034) and 30 atrial-J (models 4533 and 5534) leads with 1.2-mm2 electrodes. Low pacing outputs, mainly in the range from 1 V/0.20 ms to 1.6 V/0.36 ms with > or = 3:1 pulse width safety margins (PWSM) applied, were instituted at 3-6 months of implantation and adjusted at subsequent follow-up controls according to changes in thresholds. Cumulative follow-up period of low outputs was 1,512 months (24 months per lead, range 9-36 months), which involved 3.43 follow-up controls per lead (range 2-5). During follow-up, pulse width thresholds (PWTs) at the used amplitudes did not change in 55.5% of the leads; PWTs increased by < or = 100% in 36.5%, by 101%-200% in 1.6%, and by > 200% in 6.3% of the leads. Changes in PWT that would apparently exceed 3:1 PWSM over a 1-year period occurred in one atrial lead where even the nominal 3.5 V/0.4-ms output would not be effective and in one ventricular lead in the aftermath of an acute myocardial infarction (300% PWT rise at 1.6 V). Based on the present observations, pacemaker dependent patients require > or = 4:1 PWSM and other patients > or = 3:1 PWSM with output pulse widths < or = 0.60 ms and annual pacemaker clinic visits. Calculated battery current drain and anticipated longevity associated with a variety of pacing outputs and impedances are provided, compared, and discussed. Correlation between acute and chronic pacing impedances and pacing thresholds was weak, implying that a systematic intraoperative pacing site optimization cannot contribute significantly to the extension of average battery longevity.     

A fractally coated, 1.3 mm2 high impedance pacing electrode

Minimizing the geometric surface area of pacing electrodes increases impedance and reduces the current drain during stimulation, provided that voltage (pulse-width) thresholds remain unchanged. This may be feasible by coating the electrode surface to increase the capacity of the electrode tissue interface and to diminish polarization. Ten unipolar, tined leads with a surface area of 1.3 mm2 and a "fractal" coating of iridium (Biotronik SD-V137) were implanted in the ventricle, and electrogram amplitude (unfiltered), slew-rate, pacing threshold (0.5 ms), and impedance (2.5 V; 0.5 ms) were measured by the 5311 PSA (Medtronic). On days 0. 2. 5. 10, 28, 90, 180, 360 postimplant, sensing threshold (up to 7.0 mV, measuring range 1-14 mV on day 360 only) and the strength duration curve (0.5-4.0 V; 0.03-1.5 ms; steps: 0.5 V; 0.01 ms, respectively) were determined, the minimum charge delivered per pulse (charge threshold), and the impedance were taken from pacemaker telemetry (Intermedics 294-03). Data were compared with those of an earlier series of 20 unipolar, tined TIR-leads (Biotronik) with a surface area of 10 mm2 and a @actal" coating of titanium nitride. With the model SD-V137 versus TIR, intraoperative electrogram amplitudes were 15.1 +/- 6.1 versus 14.4 +/- 3.9 mV (NS), slew rates 3.45 +/- 1.57 versus 1.94 +/- 1.06 V/s (P < 0.05), pacing thresholds 0.16 +/- 0.05 versus 0.52 +/- 0.15 V (P < 0.01) and impedance measurements 1,136 +/- 175 versus 441 +/- 73 omega (P < 0.0001), respectively. During follow-up, sensing thresholds were the same with both leads. Differences in pulse width thresholds lost its significance on day 28 but resumed on day 360 (SD-V137; 0.08 +/- 0.04 ms; TIR: 0.16 +/- 0.06 ms at 2.5 V; P < 0.01). With an electrode surface of 1.3 mm2, charge per pulse and impedance consistently differed from control, being 0.15 +/- versus 0.66 +/- 0.20 microC (P < 0.001) and 1,344 +/- 376 versus 538 +/- 79 omega respectively, one year after implantation (P < 0.0001). In summary, "fractally" coated small surface electrodes do not compromise sensing; by more than doubling impedance against controls they offer pacing thresholds (mainly in terms of charge) that are significantly lower than with the reference electrode.     

Atrial septal pacing: a method for pacing both atria simultaneously

By pacing both atria simultaneously, one could reliably predict and optimize left-sided AV timing without concern for IACT. With synchronous depolarization of the atria, reentrant arrhythmias might be suppressed. We studied four male patients (73 +/- 3 years) with paroxysmal atrial fibrillation and symptomatic bradyarrhythmias using TEE and fluoroscopy as guides; a standard active fixation screw-in lead (Medtronic model #4058) was attached to the interatrial septum and a standard tined lead was placed in the ventricle. The generators were Medtronic model 7960. The baseline ECG was compared to the paced ECG and the conduction time were measured to the high right atrium, distal coronary sinus and atrial septum in normal sinus rhythm, atrial septal pacing, and AAT pacing. On the surface ECG, no acceleration or delay in AV conduction was noted during AAI pacing from the interatrial septum as compared with normal sinus rhythm. The mean interatrial conduction time for all 4 patients was 106 +/- 2 ms; the interatrial conduction time measured during AAT pacing utilizing the atrial septal pacing lead was 97 +/- 4 ms (P = NS). During atrial septal pacing, the mean conduction time to the high right atrium was 53 +/- 2 ms. The mean conduction time to the lateral left atrium during atrial septal pacing, was likewise 53 +/- 2 ms. We conclude that it is possible to pace both atria simultaneously from a single site using a standard active fixation lead guided by TEE and fluoroscopy. Such a pacing system allows accurate timing of the left-sided AV delay.     

Effects of left atrial dilatation on the endocardial atrial defibrillation threshold: a study in an ovine model of pacing induced dilated cardiomyopathy

Left atrial (LA) dilation is a common finding in patients with chronic atrial fibrillation (AF). Progressive dilatation may alter the atrial defibrillation threshold (ADFT). In our study, epicardial electrodes were implanted on the LA free wall and right ventricular apex of eight adult sheep. Large surface area, coiled endocardial electrodes were positioned in the coronary sinus and right atrium (RA). LA dilatation was induced by rapid ventricular pacing (190 beats/min) for 6 weeks and echocardiographically assessed weekly along with the ADFT (under propofol anesthesia). LA effective refractory period (ERP) was measured every 2-3 days using a standard extra stimulus technique and 400 ms drive. The AF cycle length (AFCL) was assessed from LA electrograms. During the 6 weeks of pacing the mean LA area increased from 6.1 +/- 1.5 to 21.3 +/- 2.4 cm2. There were no significant changes in the mean ADFT (122 +/- 15 V), circuit impedance (46 +/- 5 omega), or LA AFCL (136 +/- 23 ms). There was a significant increase in the mean LA ERP (106 +/- 10 ms at day 0, and 120 +/- 13 ms at day 42 of pacing). In this study, using chronically implanted defibrillation leads, the minimal energy requirements for successful AF were not significantly altered by ongoing left atrial dilatation. This finding is a further endorsement of the efficiency of the coronary sinus/RA shock vector. Furthermore, the apparent stability of the AF present may be a further indication of a link between the type of AF and the ADFT.     

Modern electrodes with and without steroid: effects on stimulation current of cardiac pacemakers

The aim of the investigation was to test whether new leads without steroid, a meshwire tip leads (Ionyx 4180, CPI; n = 10) and a carbon tip lead (Facet ITP 13, Vitatron; n = 10), have electrical characteristics similar to a new steroid-eluting tip lead (CapSure SP 4023, Medtronic; n = 10) and their impact on the pacemaker's pacing current. Pacing thresholds, impedance, and R-wave amplitudes measured at implantation were similar for the three leads. One, 4 and 12 weeks after implantation both nonsteroid leads had significantly higher pacing thresholds at 0.1 and 0.3 ms pulse duration in comparison to the steroid lead (after 12 weeks at 0.3 ms steroid: 0.9 +/- 0.2 V, carbon: 2.1 +/- 0.5 V; meshwire: 1.5 +/- 0.5 V). This result was restricted to the carbon lead after 52 weeks. At 0.5 ms pulse duration higher pacing thresholds were obtained for the carbon lead (after 12 weeks at 0.5 ms; steroid: 0.8 V, carbon: 1.7 +/- 0.6 V; meshwire: 1.1 +/- 0.4 V). Impedance of the steroid lead was 531 +/- 61 ohms, 535 +/- 54 ohms, and 511 +/- 50 ohms, respectively, after 4, 12, and 52 weeks, whereas the carbon lead had significantly higher values with 652 +/- 84 ohms, 669 +/- 93 ohms, and 657 +/- 107 ohms, respectively. The impedance of the meshwired lead (4 weeks: 585 +/- 92 ohms; 12 weeks: 592 +/- 89 ohms; 52 weeks: 550 +/- 130 ohms) did not differ from the steroid lead.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pacing impedance variability in tined steroid eluting leads

The aim of the study was to investigate pacing impedance (PI) behavior in ambulatory patients. Eighteen atrial and 18 ventricular tined steroid eluting leads with 1.2-mm2 and 5.6-mm2 electrodes were implanted in 20 patients. At 9-27 months after implantation PI was measured automatically by means of additional algorithms downloaded via telemetry links into implanted Thera pulse generators. PI was determined based on the voltage drop on the output capacitor during the 5 V-1 ms pacing impulse, at the programmable sampling rates from 1 second to 30 minutes. The study examined in particular: (1) PI trends and variations associated with different breathing patterns, body postures, provocative maneuvers, bike exercise, and during 24 hours; (2) impact of pacing rate and AV-delay on PI; (3) correlation between PI variability and pacing threshold, lead configuration, absolute PI value, age, gender, disease, and cardiac chamber. The most important findings were: (1) large PI variations of up to 450 omega were observed in properly functioning leads, (2) PI variability exhibited a weak negative correlation with pacing thresholds as if electrode positional stability was not a major factor underlying PI variations, (3) unipolar and bipolar PI variations were equivalent to each other (correlation factor = 0.93) implying that PI was mostly dependent on the circumstances around the lead tip.     

Non-invasive assessment of magnitude and dispersion of atrial cycle length during chronic atrial fibrillation in man

AIMS: Atrial fibrillation cycle lengths can be assessed from right precordial ECG leads and the unipolar oesophageal ECG using a non-invasive method called Frequency Analysis of Fibrillatory ECG. The purpose of this report is to present the results from application of this method in a large group of patients with long-term atrial fibrillation and to examine the differences between patients with 'coarse' and 'fine' atrial fibrillation. METHODS AND RESULTS: Simultaneous 15 min recordings from V1, V2 and an oesophageal lead at a position behind the posterior atrium were obtained in 28 patients, aged 41 to 78 years, with long-term (> 1 month) atrial fibrillation. In each lead, using the time averaging technique, the QRST complexes were suppressed. Thereafter, the frequency distribution of the residual ECG was estimated by means of Fast Fourier Transform. In the 3-12 Hz range of each lead, the dominant atrial cycle length, the power maximum and the spectral width were calculated. In 26 patients (93%), frequency spectra in the 3-12 Hz range could be obtained. The dominant atrial cycle length ranged from 120 to 175 ms, mean 150+/-16 (SD) ms in V1, and from 120 to 190 ms, mean 150+/-16 in an oesophageal lead (ns). The absolute difference in the dominant atrial cycle length between V1 and the oesophageal lead was 10.4+/-7.7 ms. There was no significant difference in the dominant atrial cycle length in V1 between patients with coarse and fine atrial fibrillation. The power maximum in V1 was significantly greater in patients with coarse compared to fine atrial fibrillation (P=0.01). The spectral widths ranged from 10 to 55 ms and demonstrated significantly higher mean values in lead V2 compared to V1 (P=0.001). Compared to V1, the mean values tended to be smaller in the oesophageal lead (P=0.05). CONCLUSIONS: Using the Frequency Analysis of Fibrillatory ECG method, the dominant atrial cycle length, power maximum and spectral width can be estimated from the frequency spectra in the majority of patients with atrial fibrillation. Spatial dispersion of the dominant atrial cycle length occurs in some patients and may be an important proarrhythmic marker. The distinction between coarse and fine atrial fibrillation cannot be used as a marker of the atrial cycle length.     

The concurrent implantation of a last-generation automatic defibrillator and a 2-chamber pacemaker

BACKGROUND: Potentially lethal interactions between concomitantly implanted pacemaker and automatic first-generation cardioverter-defibrillator have been reported. We therefore evaluated the reliability and safety of simultaneous implantation of dual-chamber pacemakers with a fourth generation cardioverter-defibrillator incorporating an improved arrhythmia detection system. METHODS: Concomitant implantation of an automatic cardioverter defibrillator and a dual-chamber pacemaker was performed in four patients for malignant tachyarrhythmias and symptomatic bradycardia. Two Jewel 7219C and two Micro Jewel 7223 (Medtronic Inc.) implantable cardioverter defibrillators were connected to an endocardial lead (Medtronic Mod. 6936). In 2 patients with a previously implanted cardioverter-defibrillator, the pacemaker was connected to bipolar atrial and ventricular leads. In the 2 patients who already had a dual-chamber pacemaker, the unipolar pacing leads implanted previously were used. At the time of implantation of the second device, interaction testing was performed evaluating ventricular fibrillation detection during high-output asynchronous pacing. Testing for malfunctions, reprogramming or variations of pacing thresholds of the pacemakers after electric shocks was also carried out. Moreover, intracavitary signals, stimulation thresholds and electrical therapies delivered were evaluated during follow-up. RESULTS: During interaction testing, induced ventricular fibrillation was detected, with no delay, in 4/4 cases (100%). After a mean follow-up of 6.3 +/- 5 months (range 2-13), 5 shocks for ventricular fibrillation, 10 shocks for fast ventricular tachycardia and 72 antitachycardia pacings were delivered. All these electrical therapies were considered appropriate. No symptomatic sustained tachyarrhythmia remained undetected. CONCLUSIONS: These data suggest that concomitant implantation of a fourth-generation automatic cardioverter-defibrillator and a dual-chamber pacemaker using either unipolar or bipolar leads can be performed safely. Extreme caution and rigorous interactions testing is nevertheless advised when considering this device combination.     

Leptin

INTRODUCTION: The purpose of this study was to test whether radiofrequency (RF) energy could be used to fixate leads to the endocardium. METHODS AND RESULTS: In six dogs we measured the dislodgment force and pacing threshold before and after RF fixation in the coronary sinus (CS) and right ventricle (RV). RF fixation was achieved with a CardioRhythm Atakr ablation unit. The dislodgment force of CS leads fixed with RF energy was 1.63+/-0.65 oz, compared with < 0.1 oz for similar leads placed in the CS of six separate dogs. In the RV, leads fixed with RF energy had a dislodgment force of 1.29+/-0.27 oz, compared with 0.48+/-0.28 oz. for urethane (P < 0.01) and 1.01+/-0.21 oz for silicone (P = 0.41) tined leads. In the CS, the pacing threshold for RF fixed leads increased significantly from 2.2+/-1.1 V (0.5 msec) before fixation to 4.2+/-1.3 V after fixation (P < 0.01), while in the RV, the pacing threshold increased from 0.41+/-0.05 V (0.5 msec) before fixation to a mean of 2.03+/-0.44 V after fixation (P < 0.01). In another group of six dogs studied for 12 weeks, 5 of 6 RF fixed CS leads remained attached, as did 8 of 10 RF fixed RV leads. For the RV leads, the mean pacing threshold was 0.90+/-0.35 V, compared with 0.53+/-0.18 V (0.5 msec) for similar tined leads (P = 0.02) and 1.2+/-0.30 V (0.5 msec) for screw leads (P = 0.18) in the RV. CONCLUSION: We conclude that RF energy can be used to attach leads to the RV and CS endocardium. While the RV pacing thresholds increased acutely, the mean chronic thresholds were not significantly different for RF fixed leads and standard tined or screw leads.     

A gastroesophageal electrode for atrial and ventricular pacing

Temporary transvenous cardiac pacing requires technical expertise and access to fluoroscopy. We have developed a gastroesophageal electrode capable of atrial and ventricular pacing. The flexible polythene gastroesophageal electrode is passed into the stomach under light sedation. Five ring electrodes, now positioned in the lower esophagus, are used for atrial pacing. A point source (cathode) on the distal tip of the electrode, now positioned in the gastric fundus, is used for ventricular pacing. Two configurations of atrial and ventricular pacing were compared: unipolar and bipolar. During unipolar ventricular pacing the indifferent electrode (anode) was a high impedance chest pad. For bipolar ventricular pacing the indifferent electrode was a ring electrodes placed 2 cm proximal to the tip. Unipolar atrial pacing was performed with 1 of 5 proximal ring electrodes acting as cathode ("cathodic") or as anode ("anodic") in conjunction with a chest pad. Bipolar atrial pacing was performed using combinations of 2 of 5 ring electrodes. Atrial capture was obtained in all 55 subjects attempted. When all electrode combinations were compared, atrial capture was significantly more frequent using the bipolar approach (153/210 bipolar, 65/210 unipolar; t = 7.37, P < 0.001). For unipolar atrial pacing, cathodic stimulation (from esophagus) was more successful than anodic stimulation (cathodic 62/105, anodic 20/105; t = 5.81, P < 0.001). In 43 subjects attempted unipolar ventricular pacing resulted in a higher frequency of capture than the bipolar approach (unipolar 41/43 (95.3%), bipolar 19/43 (44.2%); P < 0.001). In conclusion, atrial pacing was optimal using pairs of ring electrodes ("bipolar") while ventricular pacing was optimal using the distal electrode tip (cathode) in conjunction with a chest pad electrode ("unipolar"). This gastroesophageal electrode may be useful in the emergency management of acute bradyarrhythmias and for elective electrophysiological studies.     

Hepatoblastoma in a dog

BACKGROUND: In neonates and infants epicardial stimulation may be preferred to endocardial stimulation because of growth-associated lead problems and the risk of vascular complications associated with transvenous electrodes. This study analyzes the feasibility of atrioventricular implantation of a new epicardial lead using the video-assisted thoracic surgical (VATS) technique in an animal model. METHODS: Bipolar steroid-eluting epicardial leads were implanted in seven young white pigs. In five animals bipolar atrial and ventricular pacing leads (n = 10) were inserted and fixed by the VATS technique, while two animals served as controls and underwent implantation through anterolateral thoracotomy. Surgical feasibility, pacing, and sensing thresholds of the leads as well as hemodynamic parameters during pacing were studied. Histological changes beneath the electrodes were evaluated 1 week after the implantation. RESULTS: All animals survived the pacemaker lead implantation. One animal which underwent thoracotomy died because of irreversible ventricular fibrillation induced by rapid ventricular pacing. One animal in the VATS group exhibited intraoperative herniation of the heart through the pericardial window. All animals with left-sided VATS implantations demonstrated good individual pacing and sensing threshold values. The mean cardiac output was 1.6 times higher during AAI-mode pacing as compared to VVI-mode pacing at a heart rate of 140/min. One animal died postoperatively due to respiratory failure. No displacements of the pacemaker leads were observed in the survivors. CONCLUSION: While VATS-guided implantation of epicardial, atrial, and ventricular leads is feasible, technical improvements of the system are mandatory for safe clinical application.     

Successful long-term ventricular pacing via the coronary sinus after the Fontan operation

A man with double inlet left ventricle and severe subpulmonary stenosis underwent a Fontan operation at the age of 29 years. Eight years later he developed atrial flutter with complete heart block. To avoid a further thoracotomy, a unipolar carbon tipped electrode was placed into the posterior cardiac vein via the coronary sinus. More than 8 years after implantation of the original lead, and after two generator changes, telemetric thresholds remain between 1.8-2.1 volts. Percutaneous transvenous ventricular pacing via the coronary sinus can produce an excellent long-term result and should be the initial approach of choice after a Fontan-type operation.     

Basophilic differentiation of the human leukemia cell line KU812 upon treatment with interleukin-4

To assess the effect of right ventricular pacing on rate regularity during exercise and daily life activities, 16 patients with sinoatrial disease and chronic atrial fibrillation (AF) were studied. Incremental ventricular pacing was commenced at 40 beats/min until > 95% of ventricular pacing were achieved during supine, sitting, and standing. Thirteen patients also underwent randomized paired submaximal exercise tests in either a fixed rate mode. (VVI) or a ventricular rate stabilization (VRS) mode in which the pacing rate was set manually at 10 beats/min above the average AF rate during the last minute of each exercise stage. The pacing interval for rate regularization was shortest during standing (692 +/- 26 ms) compared with either supine or sitting (757 +/- 30 and 705 +/- 26 ms, respectively, P < 0.05). During exercise VRS pacing significantly increased the maximum rate (119 +/- 5.2 vs 106 +/- 4.2 ms, P < 0.05), percent of ventricular pacing (85% +/- 5% vs 23% +/- 7%, P < 0.05), rate regularity index (5.8% +/- 1.6% vs 13.4% +/- 1.9%, P < 0.05), and maximum level of oxygen consumption (12.4 +/- 0.5 vs 11.3 +/- 0.5 mL/kg, P < 0.05) compared with VVI pacing. There was no change in oxygen pulse or difference in symptom scores in this acute study between the two pacing modes. It is concluded that right ventricular pacing may significantly improve rate regularity and cardiopulmonary performance in patients with chronic AF. This may be incorporated in a pacing device for rate regularization of AF using an algorithm that is rate adaptive to postural and exercise stresses.     

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.     

Chronic rapid atrial pacing. Structural, functional, and electrophysiological characteristics of a new model of sustained atrial fibrillation

BACKGROUND: Despite the clinical importance of atrial fibrillation (AF), the development of chronic nonvalvular AF models has been difficult. Animal models of sustained AF have been developed primarily in the short-term setting. Recently, models of chronic ventricular myopathy and fibrillation have been developed after several weeks of continuous rapid ventricular pacing. We hypothesized that chronic rapid atrial pacing would lead to atrial myopathy, yielding a reproducible model of sustained AF. METHODS AND RESULTS: Twenty-two halothane-anesthetized mongrel dogs underwent insertion of a transvenous lead at the right atrial appendage that was continuously paced at 400 beats per minute for 6 weeks. Two-dimensional echocardiography was performed in 11 dogs to assess the effects of rapid atrial pacing on atrial size. Atrial vulnerability was defined as the ability to induce sustained repetitive atrial responses during programmed electrical stimulation and was assessed by extrastimulus and burst-pacing techniques. Effective refractory period (ERP) was measured at two endocardial sites in the right atrium. Sustained AF was defined as AF > or = 15 minutes. In animals with sustained AF, 10 quadripolar epicardial electrodes were surgically attached to the right and left atria. The local atrial fibrillatory cycle length (AFCL) was measured in a 20-second window, and the mean AFCL was measured at each site. Marked biatrial enlargement was documented; after 6 weeks of continuous rapid atrial pacing, the left atrium was 7.8 +/- 1 cm2 at baseline versus 11.3 +/- 1 cm2 after pacing, and the right atrium was 4.3 +/- 0.7 cm2 at baseline versus 7.2 +/- 1.3 cm2 after pacing. An increase in atrial area of at least 40% was necessary to induce sustained AF and was strongly correlated with the inducibility of AF (r = .87). Electron microscopy of atrial tissue demonstrated structural changes that were characterized by an increase in mitochondrial size and number and by disruption of the sarcoplasmic reticulum. After 6 weeks of continuous rapid atrial pacing, sustained AF was induced in 18 dogs (82%) and nonsustained AF was induced in 2 dogs (9%). AF occurred spontaneously in 4 dogs (18%). Right atrial ERP, measured at cycle lengths of 400 and 300 milliseconds at baseline, was significantly shortened after pacing, from 150 +/- 8 to 127 +/- 10 milliseconds and from 147 +/- 11 to 123 +/- 12 milliseconds, respectively (P < .001). This finding was highly predictive of inducibility of AF (90%). Increased atrial area (40%) and ERP shortening were highly predictive for the induction of sustained AF (88%). Local epicardial ERP correlated well with local AFCL (R2 = .93). Mean AFCL was significantly shorter in the left atrium (81 +/- 8 milliseconds) compared with the right atrium 94 +/- 9 milliseconds (P < .05). An area in the posterior left atrium was consistently found to have a shorter AFCL (74 +/- 5 milliseconds). Cryoablation of this area was attempted in 11 dogs. In 9 dogs (82%; mean, 9.0 +/- 4.0; range, 5 to 14), AF was terminated and no longer induced after serial cryoablation. CONCLUSIONS: Sustained AF was readily inducible in most dogs (82%) after rapid atrial pacing. This model was consistently associated with biatrial myopathy and marked changes in atrial vulnerability. An area in the posterior left atrium was uniformly shown to have the shortest AFCL. The results of restoration of sinus rhythm and prevention of inducibility of AF after cryoablation of this area of the left atrium suggest that this area may be critical in the maintenance of AF in this model.     

Functional correlation of molecular electronic properties with potency of synthetic carbinolamine antimalarial agents

Dual chamber rate responsive pacing incorporating a mode switching option is increasingly used in patients with chronic paroxysmal atrial fibrillation and high degree AV block. Single-lead VDDR pacemakers have rarely used for this indication. The purpose of this study was to determine their reliability of atrial sensing during atrial fibrillation, the percentage of atrial synchronous ventricular pacing, and the behavior of the sinus rate outside the phases of atrial fibrillation. We studied ten patients with a single-lead VDDR pacemaker implanted for this indication. Follow-up visits were performed at predischarge and after 1, 3, 6, 12, 18, and 24 months. During the mean follow-up period of 18.9 +/- 6.9 months, the atrial sensing thresholds in sinus rhythm remained stable. Atrial synchronous ventricular stimulation was achieved in 68.7 +/- 31.2% (median 82.5%) of the whole follow-up time. All patients showed an adequate atrial rate response during sinus rhythm. Atrial fibrillation was detected by the pacemakers in 24.0 +/- 29.8% of time. In 3 of 10 patients the duration of atrial fibrillation showed a steady increase from visit to visit. The sensed amplitudes of atrial fibrillation ranged from 0.1-1.0 mV. A programmed atrial sensitivity of 0.1 mV was necessary to achieve complete sensing of atrial fibrillation. None of the patients experienced tachycardias with optimized pacemaker programming. Single-lead VDDR pacing incorporating a mode-switching option is useful in patients with high degree AV block and paroxysmal atrial fibrillation, since it provides atrial synchronous ventricular pacing in more than two-thirds of follow-up time. In a subgroup of patients, a progressive increase of the time during atrial fibrillation was demonstrated. A reliable detection of paroxysmal atrial fibrillation requires the programming of the atrial sensitivity to its most sensitive value.     

Preimplant atrial defibrillation testing with a temporary catheter in sheep

Prior to implantation of an atrial defibrillator, its effectiveness should be tested in each patient. A new catheter design for temporary use with electrodes for atrial defibrillation, electrogram sensing, and pacing was tested in this study. Atrial defibrillation thresholds defined using this temporary catheter were compared to the ones defined by catheters intended for chronic use with an implantable atrial defibrillator. Atrial defibrillation threshold was determined in six sheep using both types of catheters. Each animal was subjected to studies on 2 consecutive days. On the first day, shocks were applied between two of the temporary catheters. On the following day, permanent leads were inserted and atrial defibrillation threshold was redetermined. In both cases, defibrillation electrodes were positioned in the same heart location with one electrode in the distal coronary sinus and the second electrode in the right atrium. Atrial defibrillation threshold was obtained using 10 V increments or decrements to determine the lowest shock intensity needed to defibrillate the atria. Threshold was defined as the shock intensity at which 20 shock percent success was at or between 15% and 85%. Statistical analysis showed no significant difference (P < 0.05) between atrial defibrillation threshold energy (0.53 J vs 0.55 J), voltage (122 V vs 120 V) or current (2.2 A vs 2.6 A) measured with the temporary catheters and the permanent leads, respectively. These data indicate that temporary catheters can be used for efficacy testing prior to implant of an atrial defibrillator, and that they predict atrial defibrillation threshold adequately for chronic leads.     

Single lead atrial synchronous ventricular pacing in Japanese patients with complete atrioventricular block

The purpose of this study was to review our experience with atrial synchronous ventricular pacing devices (THERA VDD pacing systems, Medtronic, Inc., U.S.A.) using single atrioventricular leads in Japanese patients with complete atrioventricular block and normal sinus function. Twenty patients with a mean age of 55 +/- 13 years underwent implantation of VDD pacemakers. At implantation the amplitude of atrial signals in the supine position during normal breathing, which was measured directly using an external pacing system analyzer, ranged from 1.8 to 5.8 mV with a mean amplitude of 3.4 +/- 1.4 mV. Atrial amplitudes did not change during deep breathing (3.3 +/- 1.1 mV) or in the semi-Fowler position (3.4 +/- 1.6 mV). Atrial oversensing or undersensing was not observed in any of the patients. During a follow-up period, the percentage of atrial synchronization was >95% in 19 patients, and none of the patients had pacemaker related tachycardia or pacemaker related complications. These results were promising enough to warrant the extension of the clinical use of the VDD pacemaker.     

Clinical shock tolerability and effect of different right atrial electrode locations on efficacy of low energy human transvenous atrial defibrillation using an implantable lead system

OBJECTIVES: The objectives of this study were 1) to evaluate the effect of different right atrial electrode locations on the efficacy of low energy transvenous defibrillation with an implantable lead system; and 2) to qualitate and quantify the discomfort from atrial defibrillation shocks delivered by a clinically relevant method. BACKGROUND: Biatrial shocks result in the lowest thresholds for transvenous atrial defibrillation, but the optimal right atrial and coronary sinus electrode locations for defibrillation efficacy in humans have not been defined. METHODS: Twenty-eight patients (17 men, 11 women) with chronic atrial fibrillation (AF) (lasting > or = 1 month) were studied. Transvenous atrial defibrillation was performed by delivering R wave-synchronized biphasic shocks with incremental shock levels (from 180 to 400 V in steps of 40 V). Different electrode location combinations were used and tested randomly: the anterolateral, inferomedial right atrium or high right atrial appendage to the distal coronary sinus. Defibrillation thresholds were defined in duplicate by using the step-up protocol. Pain perception of shock delivery was assessed by using a purpose-designed questionnaire; sedation was given when the shock level was unacceptable (tolerability threshold). RESULTS: Sinus rhythm was restored in 26 of 28 patients by using at least one of the right atrial electrode locations tested. The conversion rate with the anterolateral right atrial location (21 [81%] of 26) was higher than that with the inferomedial right atrial location (8 [50%] of 16, p < 0.05) but similar to that with the high right atrial appendage location (16 [89%] of 18, p > 0.05). The mean defibrillation thresholds for the high right atrial appendage, anterolateral right atrium and inferomedial right atrium were all significantly different with respect to energy (3.9 +/- 1.8 J vs. 4.6 +/- 1.8 J vs. 6.0 +/- 1.7 J, respectively, p < 0.05) and voltage (317 +/- 77 V vs. 348 +/- 70 V vs. 396 +/- 66 V, respectively, p < 0.05). Patients tolerated a mean of 3.4 +/- 2 shocks with a tolerability threshold of 255 +/- 60 V, 2.5 +/- 1.3 J. CONCLUSIONS: Low energy transvenous defibrillation with an implantable defibrillation lead system is an effective treatment for AF. Most patients can tolerate two to three shocks, and, when the starting shock level (180 V) is close to the defibrillation threshold, they can tolerate on average a shock level of 260 V without sedation. Electrodes should be positioned in the distal coronary sinus and in the high right atrial appendage to achieve the lowest defibrillation threshold, although other locations may be suitable for certain patients.