Body surface Laplacian mapping of atrial depolarization in healthy human subjects.

In the present study, we report body surface Laplacian mapping of atrial depolarization under sinus rhythm in 8 healthy male subjects. For each subject, 95 unipolar disk electrodes with inter-electrode distance of 2 cm were used to record simultaneously potential ECGs over the anterior chest. The Laplacian ECG was then estimated during the P wave using a novel spline Laplacian technique. The body surface potential map (BSPM) and body surface Laplacian map (BSLM) at different time instants or time intervals of the P wave were constructed and compared. The present results showed that the BSPMs during the P wave were characterized by the rotation of a pair of positive/negative potential distribution from right to left around the anterior torso. On the other hand, the corresponding BSLMs revealed more spatial details, including two positive activities (denoted as P1 and P2, appeared in all 8 subjects), and three negative activities (denoted as N1, N2, and N3, appeared in 7, 7, and 4 subjects, respectively). The separation of these activities and their evolving patterns were also compared and confirmed by computer simulation using a realistic geometry heart-torso model. The above findings may be directly related to the underlying activation sequence during atrial depolarization in healthy subjects, suggesting the potential clinical applications of the Laplacian ECG technique.

The ablation of atrial fibrillation with the loop catheter design: what we have learned from the animal model.

Ablation of chronic atrial fibrillation (AF) with the use of transcutaneous catheter ablation is yet to become a clinical tool. This article summarizes the development of the technology and the technique for the ablation of AF that was tested on the rapidly paced AF dog model. The current ablation technology using the standard ablation technique used in humans is not suitable for the creation of transmural contiguous linear lesions, and such technology is subjecting the patient to the prolonged procedures with considerable risk of complication. The use of the loop catheter design or other designs of ablation technology, which is specifically targeted for the creation of linear lesions, should be developed if the catheter approach for the ablation of AF is to succeed. This article describes the data available for the loop catheter design that is currently undergoing human feasibility studies.

Ablation of atrial fibrillation in the rapid pacing canine model using a multi-electrode loop catheter.

OBJECTIVES: This investigation details our experience using a loop catheter to ablate atrial fibrillation (AF) in dogs. BACKGROUND: Atrial fibrillation is the most common arrhythmia and has significant morbidity. Maintenance of normal sinus rhythm (NSR) after conversion in many patients is still a challenge. METHODS: A multi-electrode loop catheter was used to create linear atrial lesions to ablate AF in a rapid atrial pacing model in 29 dogs. Rhythm status was assessed over a six-month recovery period, after which tissue analysis was performed. RESULTS: Acute conversion to NSR or atrial tachycardia (AT) was achieved in 90% of cases. Six of 26 conversions occurred after only left atrial (LA) lesions, and two after just right atrial lesions. Sixteen (62%) of 26 lesions that resulted in AF conversion were in the LA, and 11 of these 16 conversions occurred during a lesion connecting the mitral ring to the pulmonary veins. Acute conversion rate was similar with ring and coil electrodes, but AT was more frequent with coil electrodes (63% vs. 31%). At six months 80% of dogs were in NSR, 14% were in AT, and 7% remained in AF. There was an average reduction in P-wave amplitude of 64 +/- 26% after power application. Tissue analysis revealed transmural contiguous lesions when final outcome was NSR, and nontransmural/noncontiguous lesions where AF persisted. CONCLUSIONS: Multi-electrode loop catheters can create contiguous transmural lesions in either atrium to safely and effectively ablate AF and provide a stable long-term rhythm outcome in this dog model. The left atrium appears to be the dominant chamber that sustains AF. Atrial tachycardia is a frequent acute outcome with coil electrodes.

Time course of left atrial mechanical recovery after linear lesions: normal sinus rhythm versus a chronic atrial fibrillation dog model.

INTRODUCTION: The extent of left atrial (LA) mechanical function recovery after creation of linear lesions using the loop catheter has not been determined. METHODS AND RESULTS: LA mechanical function was assessed before and after linear lesions using transthoracic two-dimensional and Doppler echocardiography in two groups: (1) normal, which consisted of eight healthy dogs in normal sinus rhythm (NSR); and (2) atrial fibrillation (AF), which consisted of nine dogs in spontaneous AF for 6 months following rapid pacing-induced AF. NSR was restored with linear lesions in all AF dogs. All animals were in NSR 5 months after linear lesions. In the normal dogs, the maximal velocity of the transmitral flow "A" wave was reduced by 42% during the first week postablation and by 24% at 5 months versus preablation. At 5 months, no differences in LA function were noted between the normal and the AF group for all measured Doppler parameters. At 5 months, the LA systolic area in AF dogs was reduced by 40% (preablation 12.9 +/- 2.9 cm2, postablation 7.6 +/- 1.2 cm2; P < 0.01) and in the normal dogs by 21% (preablation 10.0 +/- 0.9 cm2, postablation 7.8 +/- 1.2 cm2; P < 0.02), being the same in both groups within 3 months of recovery. CONCLUSION: The creation of linear lesions with the loop catheter does not result in LA expansion. In normal dogs, LA mechanical activity is reduced for 3 weeks postablation. The time course of LA mechanical function recovery is the same for the AF and the NSR dogs, and it is complete at 3 months postablation. At 5 months, LA systolic function parameters in both groups are reduced by 24% versus the preablation values of the normal dogs. Linear lesions result in a significant reduction in LA size.

The creation of linear contiguous lesions in the atria with an expandable loop catheter.

OBJECTIVES: This article describes a catheter system designed to create linear atrial lesions and identifies electrophysiologic markers that are associated with the creation of linear lesions. BACKGROUND: Atrial fibrillation (Afib) is the most common arrhythmia in humans and causes a significant morbidity. The success of surgical interventions has provided the impetus for the development of a catheter-based approach for the ablation of Afib. METHODS: We tested a catheter system with 24 4-mm ring electrodes that can create loops in the atria. The electrodes can be used to record electrical activity and deliver radiofrequency power for ablation. In 33 dogs, 82 linear lesions were generated using three power titration protocols: fixed levels, manual titration guided by local electrogram activity and temperature control. Bipolar activity was recorded from the 24 electrodes before, during and after lesion generation. Data were gathered regarding lesion contiguity, transmurality and dimensions; the changes in local electrical activity amplitude; the incidence rate of rapid impedance rises and desiccation or char formation; and rhythm outcomes. RESULTS: Catheter deployment usually requires <60 s. Linear lesions (12 to 16 cm in length and 6 +/- 2 mm wide) can be generated in 24 to 48 min without moving the catheter. Effective lesion formation can be predicted by a decrease of greater than 50% in the amplitude of bipolar recordings. Splitting or fragmentation of the electrogram and increasing pacing threshold (3.1 +/- 3.3 mV to 7.1 +/- 3.8 mV, p < 0.01) are indicative of effective lesion formation. Impedance rises and char formation occurred at 91 +/- 12 degrees C. Linear lesion creation does not result in the initiation of Afib. However, atrial flutter was recorded after the completion of the final lesion in 3/12 hearts. When using temperature control, no char was noted in the left atrium, whereas 8% of the right atrium burns had char. CONCLUSIONS: This adjustable loop catheter forces the atrial tissue to conform around the catheter and is capable of producing linear, contiguous lesions up to 16 cm long with minimal effort and radiation exposure. Pacing thresholds and electrogram amplitude and character are markers of effective lesion formation. Although Afib could not be induced after lesion set completion, sustained atrial flutter could be induced in 25% of the hearts.

Rationale, development, and clinical outcomes of a multidisciplinary amiodarone clinic.

OBJECTIVES: To review the rationale and development of a multidisciplinary amiodarone clinic, and document the clinical outcomes resulting from its implementation. METHODS: A clinic was established to provide an ambulatory setting in which patients receiving amiodarone could be followed according to published guidelines by a multidisciplinary team of cardiovascular health care specialists. Patients receiving amiodarone were referred to the clinic by their primary physicians. A data base containing each patient's medical history, current drug therapy, and baseline laboratory values was developed during the initial visit. Liver function tests, thyroid function tests, and chest radiographs were performed every 6 months, and pulmonary function tests were scheduled on an annual basis. Dosage adjustments were performed in select patients. RESULTS: Since November 1996, 60 patients have been referred to the amiodarone clinic. Mean length of follow-up before and after referral was 16.3+/-25.5 and 9.2+/-5.5 months, respectively. Laboratory tests were performed according to accepted guidelines in 14 (23%) patients before referral compared with 54 (90%) patients after enrollment (p<0.001). Previously unrecognized adverse events were detected in 21 (35%) patients, including pulmonary fibrosis, QT prolongation, liver enzyme elevation, hypothyroidism, hyperthyroidism, and asthma exacerbation. Amiodarone was discontinued in six patients, four of whom had suspected pulmonary toxicity. The dose of amiodarone was adjusted in 29 (48.4%) patients. CONCLUSION: Many patients receiving amiodarone are not being followed according to published recommendations. Implementation of a specialized, multidisciplinary amiodarone clinic improves outcomes by monitoring for early detection of drug-related toxicities and by facilitating proper dosage modifications.

The effects of electrode-tissue contact on radiofrequency lesion generation.

During the generation of radiofrequency (RF) lesions in the ventricular myocardium, the maintenance of adequate electrode-tissue contact is critically important. In this study, lesion dimensions and temperature and impedance changes were evaluated while controlling electrode-tissue contact levels (-5, 0, +1, and +3 mm) and power levels (10, 20, and 30 W). This data was used to assess the ability of impedance and temperature monitoring to provide useful information about the quality of electrode-tissue contact. The results show that as the electrode-tissue contact increases, so does the amount of temperature rise. With the electrode floating in blood (-5 contact), the average maximum temperature increase with 20 and 30 W was only 7 +/- 1 and 11 +/- 2 degrees C, respectively. At 20 and 30 W the temperature plateaued shortly after the initiation of power application. With good electrode-tissue contact (+1 mm or +3 mm), the temperature increase within the first 10 seconds was significantly greater than the temperature increase from baseline with poor contact (0 mm or -5 mm) and reached a maximum of 60 +/- 1 degrees C after 60 seconds of power application. As the electrode-tissue contact increased, so did the rate and level of impedance decrease. However, the rate of impedance decrease was slower compared to the rate of temperature rise. With the electrode floating in blood, the maximum impedance decreases with 20 and 30 W were 6 +/- 6 omega and 9 +/- 5 omega, respectively. The impedances plateaued after a few seconds of power application. With the electrode in good contact, the maximum impedance decreases with 20 and 30 W were 25 +/- 2 omega and 20 +/- 6 omega, respectively. In these cases the rate of the impedance decrease plateaued after 40 seconds of power application. The increase in lesion diameter and depth correlate well with decreasing impedance and increasing temperature. However, lesion depth appears to correlate better with impedance than temperature. We conclude that, since the electrode-tissue contact is not known prior to the application of power to the endocardium, in the absence of a temperature control system, the power should initially be set at a low level. The power should be increased slowly over 20-30 seconds, and then maintained at its final level for at least 90 seconds to allow for maximal lesion depth maturation. The power level should be lowered if the impedance drop exceeds 15 omega.

The anatomical determinants for the design of intracardiac mapping and ablation catheters.

An important factor in the efficient and successful completion of the ablation procedure is the design characteristics of the mapping/ablation catheters. These procedures are often hampered by the inability to maneuver the catheter to the desired location, in part because the catheters only have a single plane deflection capability and are not designed for the specific cardiac anatomical structures that contain the arrhythmogenic substrate. Single and Biplane Deflectable Catheters: Using measurements taken from six normal human cadaver hearts, ablation catheter design characteristics are presented for posterior, posterior septal, lateral, and posterior lateral pathways for retrograde and transseptal approaches. Three catheter designs based on anatomical characteristics were also evaluated. Pigtail Catheter: This catheter adapts to the atrial side of the mitral ring and improves positioning and stability for mapping and ablation of left-sided accessory pathways. Loop Catheter: This catheter is positioned at the perivalvular tricuspid ring and provides simultaneous mapping and ablation capabilities without the need to move the catheter or the need for additional catheters. Rotating Tip Catheter: The tip of this catheter is made up of three elongated teeth, which were curved 120 degrees apart into the rotating tip electrode. This electrode was designed to negotiate the surfaces of the atrial and intraventricular chambers. It is capable of discrete movements and has a large electrode-tissue contact area for the ablation of atrial and ventricular arrhythmias. Catheter designs presented in this article are based on the ability of the catheter to adapt to the anatomical location of the arrhythmogenic tissue as well as the maneuverability of the catheter's mapping and ablation electrodes. An anatomical approach to the design of ablation catheter technology is likely to reduce the x-ray radiation exposure for patient and operator, and may further increase the success rate of the procedure.

Repeated use of ablation catheters: a prospective study.

OBJECTIVES: The objective of this study was to provide insight into the time course of electrical, physical and mechanical changes in ablation catheters after each use that may affect the safety and efficacy of the ablation procedure. BACKGROUND: An increasing number of institutions are reusing deflectable ablation catheters. At present, there are no data concerning the safety of reusing ablation catheters. METHODS: Over a period of 1 year, 69 Webster/Mansfield deflectable catheters used in 336 ablation procedures were prospectively studied. An additional 18 new catheters were tested after multiple sterilizations only. The catheters were evaluated for electrical and physical integrity and mechanical capabilities. These include deflection at room temperature and 37 degrees C, shaft compression and buckling during deflection, tip craters, torquing ability, glue separation and tip attachment using a stereoscope at x30 magnification and electrical resistance for each electrode. After each use, the catheters were gas-sterilized with ethylene oxide. RESULTS: The most common reasons for catheter rejection were tip electrode glue separation after 4.3 +/- 4.3 uses and loss of deflection after 5.0 +/- 3.3 uses. Electrical discontinuity between the catheter handle and electrodes was observed after 10.0 +/- 3.7 uses. There was no significant decrease in catheter torquing ability with repeated use. In this study the total estimated savings was $128,133, which includes the cost of catheter reprocessing. The reuse of Webster/Mansfield ablation catheters has not resulted in any major catheter failure or any major adverse clinical complications. CONCLUSIONS: On the basis of these observations, we believe that the Webster/Mansfield catheter can be reused an average of five times. It is strongly recommended that after each use catheters be carefully examined under appropriate magnification (x30) and that special attention be given to the ablation tip electrode. The catheters should also be tested for deflection and electrical integrity.

Cardioversion, defibrillation, and overdrive pacing of ventricular arrhythmias: the effect of moricizine in dogs with sustained monomorphic ventricular tachycardia.

The purpose of this investigation is to define whether the antiarrhythmic drug moricizine has beneficial or adverse effects on currently used antitachycardia and antifibrillatory devices. These studies were performed in a dog model of sustained monomorphic ventricular tachycardia (VT). In 11 dogs, the left anterior descending artery and all surrounding epicardial collateral feeder vessels were ligated. Defibrillator patches were implanted and the dogs were allowed to recover. After a 7-day recovery period, effective refractory period (ERP), end diastolic threshold (EDT), VT induction, and VT and ventricular fibrillation (VF) termination data were collected before and after moricizine infusion (2 mg/kg). In this experimental model, moricizine caused the following electrophysiological changes: a prolongation of the ERP from 173 +/- 14 to 182 +/- 15 (P < 0.02) with no significant effect on the EDT for pacing; a prolongation of the VT cycle length from 175 +/- 18 to 201 +/- 23 msec (P < 0.003); an increased cycle length required for overdrive pacing from 136 +/- 20 to 157 +/- 22 msec (P < 0.01); no effect on the energy required to cardiovert VT; an increase in the defibrillation threshold from 7.5 +/- 4 to 9.4 +/- 4 joules (P < 0.006) and; in 5 of the 8 dogs with VT, the VT could be initiated with somewhat less aggressive stimulation. Significant beneficial electrophysiological physiological effects were noted on the VT cycle length, including a proportionately prolonged overdrive pacing cycle length for VT termination.(ABSTRACT TRUNCATED AT 250 WORDS)

Physics and engineering of transcatheter cardiac tissue ablation.

Ablation of arrhythmogenic cardiac tissues has emerged as one of the most important advances in cardiac electrophysiology. With the introduction of transcatheter ablation, the treatment of ventricular tachycardia, Wolff-Parkinson-White syndrome and other cardiac arrhythmias has progressed from an expensive and painful surgical therapy accompanied by a long recovery period to the less expensive, less traumatic transcatheter approach. The feasibility of cardiac ablation, along with the increasing number of physicians using the technique, requires understanding of the anatomic and electrophysiologic bases of transcatheter ablation as well as the different technologies, their limitations and complications. This report provides an overview of the physical, scientific and technical aspects of cardiac ablation performed with the methods currently available and a summary of the limitations of each method and expected future technologic developments in this growing field. Emphasis is placed on radiofrequency and direct current energies, the primary methods now used. Methods such as cryoablation and laser, and microwave and chemical ablation are discussed with less detail because the method of delivering energy for these ablative procedures has not been fully developed.

Comparison of cardiac pacing with drug therapy in the treatment of neurocardiogenic (vasovagal) syncope with bradycardia or asystole.

BACKGROUND: The efficacy of permanent cardiac pacing in patients with neurocardiogenic (or vasovagal) syncope associated with bradycardia or asystole is not clear. We compared the efficacy of cardiac pacing with that of oral drug therapy in the prevention of hypotension and syncope during head-up tilt testing. METHODS: Among 70 patients with a history of syncope in whom hypotension and syncope could be provoked during head-up tilt testing, 22 had bradycardia (a heart rate < 60 beats per minute, with a decline in the rate by at least 20 beats per minute) or asystole along with hypotension during testing. There were 9 men and 13 women, with a mean (+/- SD) age of 41 +/- 17 years. Head-up tilt testing was repeated during atrioventricular sequential pacing (in 20 patients with sinus rhythm) or ventricular pacing (in 2 patients with atrial fibrillation). Regardless of the results obtained during artificial pacing, all the patients subsequently had upright-tilt testing repeated during therapy with oral metoprolol, theophylline, or disopyramide. RESULTS: During the initial tilt test, 6 patients had asystole and 16 had bradycardia along with hypotension. Despite artificial pacing, the mean arterial pressure during head-up tilt testing still fell significantly, from 97 +/- 19 to 57 +/- 19 mm Hg (P < 0.001); 5 patients had syncope, and 15 had presyncope. By contrast, 19 patients who later received only medical therapy (metoprolol in 10, theophylline in 3, and disopyramide in 6), 2 patients who received both metoprolol and atrioventricular sequential pacing, and 1 patient who received only atrioventricular sequential pacing had negative head-up tilt tests. After a median follow-up of 16 months, 18 of the 19 patients who were treated with drugs alone (94 percent) remained free of recurrent syncope or presyncope, whereas the patient treated only with permanent dual-chamber pacemaker had recurrent syncope. CONCLUSIONS: In patients with neurocardiogenic syncope associated with bradycardia or asystole, drug therapy is often effective in preventing syncope, whereas artificial pacing is not.

Electrophysiologic spectrum of atrioventricular nodal behavior in patients with atrioventricular nodal reentrant tachycardia undergoing selective fast or slow pathway ablation.

INTRODUCTION: The objective of this report is to delineate the atrioventricular (AV) nodal electrophysiologic behavior in patients undergoing fast or slow pathway ablation for control of their AV nodal reentrant tachycardia (AVNRT). METHODS AND RESULTS: One hundred sixteen consecutive patients with symptomatic AVNRT were included. Twenty-two patients underwent fast pathway ablation with complete abolition of AVNRT in all and development of complete AV block in five patients. Of 17 patients with intact AV conduction postablation, 12 had demonstrated antegrade dual pathway physiology during baseline study, which was maintained in three and lost in nine patients postablation. Two patients with successful fast pathway ablation developed uncommon AVNRT necessitating a slow pathway ablation. Twenty-one patients demonstrated both common and uncommon forms of AV nodal reentry during baseline study. The earliest site of atrial activation was close to the His-bundle recording site (anterior interatrial septum) during common variety and the coronary sinus ostium (posterior interatrial septum) during the uncommon AV nodal reentry in all 21 patients. Ninety-six patients underwent successful slow pathway ablation. Among these, the antegrade dual pathway physiology demonstrable during baseline study (60 patients) was maintained in 25 and lost in 35 patients postablation. CONCLUSION: These data suggest that: (1) dual pathway physiology may persist after successful ablation, which might be a reflection of multiple reentrant pathways in patients with AVNRT; and (2) the retrograde pathways during common and uncommon AVNRT have anatomically separate atrial breakthroughs. These findings have important electrophysiologic implications regarding the prevailing concept of the AV nodal physiology in patients with AVNRT.

Selective transcatheter ablation of the fast and slow pathways using radiofrequency energy in patients with atrioventricular nodal reentrant tachycardia.

BACKGROUND: The safety and efficacy of selective fast versus slow pathway ablation using radiofrequency energy and a transcatheter technique in patients with atrioventricular nodal reentrant tachycardia (AVNRT) were evaluated. METHODS AND RESULTS: Forty-nine consecutive patients with symptomatic AVNRT were included. There were 37 women and 12 men (mean age, 43 +/- 20 years). The first 16 patients underwent a fast pathway ablation with radiofrequency current applied in the anterior/superior aspect of the tricuspid annulus. The remaining 33 patients initially had their slow pathway targeted at the posterior/inferior aspect of the right interatrial septum. The fast pathway was successfully ablated in the initial 16 patients and in three additional patients after an unsuccessful slow pathway ablation. A mean of 10 +/- 8 radiofrequency pulses were delivered; the last (successful) pulse was at a power of 24 +/- 7 W for a duration of 22 +/- 15 seconds. Four of these 19 patients developed complete atrioventricular (AV) block. In the remaining 15 patients, the post-ablation atrio-His intervals prolonged from 89 +/- 30 to 138 +/- 43 msec (p less than 0.001), whereas the shortest 1:1 AV conduction and effective refractory period of the AV node remained unchanged. Ten patients lost their ventriculoatrial (VA) conduction, and the other five had a significant prolongation of the shortest cycle length of 1:1 VA conduction (280 +/- 35 versus 468 +/- 30 msec, p less than 0.0001). Slow pathway ablation was attempted initially in 33 patients and in another two who developed uncommon AVNRT after successful fast pathway ablation. Of these 35 patients, 32 had no AVNRT inducible after 6 +/- 4 radiofrequency pulses with the last (successful) pulse given at a power of 36 +/- 12 W for a duration of 35 +/- 15 seconds. After successful slow pathway ablation, the shortest cycle length of 1:1 AV conduction prolonged from 295 +/- 44 to 332 +/- 66 msec (p less than 0.0005), the AV nodal effective refractory period increased from 232 +/- 36 to 281 +/- 61 msec (p less than 0.0001), and the atrio-His interval as well as the shortest cycle length of 1:1 VA conduction remained unchanged. No patients developed AV block. Among the last 33 patients who underwent a slow pathway ablation as the initial attempt and a fast pathway ablation only when the former failed, 32 (97%) had successful AVNRT abolition with intact AV conduction. During a mean follow-up of 6.5 +/- 3.0 months, none of the 49 patients had recurrent tachycardia. Forty patients had repeat electrophysiological studies 4-8 weeks after their successful ablation, and AVNRT could not be induced in 39 patients. CONCLUSIONS: These data suggest that both fast and slow pathways can be selectively ablated for control of AVNRT: Slow pathway ablation, however, by obviating the risk of AV block, appears to be safer and should be considered as the first approach.

Iontophoretic transmyocardial drug delivery. A novel approach to antiarrhythmic drug therapy.

BACKGROUND: Antiarrhythmic drugs often fail to achieve therapeutic effects without toxic systemic levels. Direct transport of drugs into the myocardium may circumvent this problem and may also provide new insights into antiarrhythmic drug effect on arrhythmogenic tissues. In a canine model, procainamide (PA) was delivered iontophoretically using pulsed current synchronized with the ventricular depolarization via an implantable defibrillator patch electrode that was modified to contain a 3.6-ml chamber. Myocardial tissue concentrations of PA were evaluated in 7-day myocardial infarcts (n = 16) that were exposed to 10 minutes of iontophoretic PA delivery and compared with passive diffusion (n = 5) and intravenous (n = 16) PA. These dogs were followed for 3 hours. The infarcted tissue PA levels were compared with normal myocardium. Coronary and systemic blood levels of PA, effective refractory period (ERP), diastolic threshold, and efficacy of ventricular tachycardia (VT) suppression were evaluated throughout the follow-up period. METHODS AND RESULTS: Three hours after 10 minutes of iontophoretic, passive, and intravenous PA, the epicardial layer concentration in the center of the infarcted zone was 840 +/- 853 micrograms/g, 93 +/- 90 micrograms/g, and 15 +/- 8 micrograms/g of tissue, respectively. In the endocardial layer, the PA concentrations with iontophoresis were 38 +/- 57 micrograms/g and were significantly higher than those achieved with either passive diffusion 38 +/- (4 +/- 2 micrograms/g) or with intravenous delivery (11 +/- 5 micrograms/g) (p less than 0.05). Epicardial tissue PA concentrations 3 hours after iontophoresis, passive diffusion, and intravenous PA in the normally perfused tissues were 14 +/- 13 micrograms/g, 3 +/- 2 micrograms/g, and 16 +/- 8 micrograms/g of PA, respectively. Venous blood levels were 2 +/- 3 micrograms/ml 3 hours after iontophoresis, 1 +/- 1 microgram/ml 3 hours after passive PA delivery, and 11 +/- 7 micrograms/ml with intravenous administration (p less than 0.05 intravenous versus passive and iontophoresis). Iontophoretic delivery of PA resulted in 22 +/- 29 msec ERP prolongation intramurally in the infarcted zone with no significant normal tissue ERP prolongation. Passive delivery of PA produced no significant changes in ERP. After intravenous infusion, the ERP in the infarcted zone increased by 35 +/- 29 msec and 13 +/- 12 msec in the normal tissue. Sustained monomorphic VT was induced in 20 animals. In one of these animals, only nonsustained VT could be induced at baseline; however, after intravenous PA, VT could be induced and remained inducible throughout the 3-hour follow-up period. In the iontophoretic delivery group, PA suppressed VT in all of the animals, with termination time ranging from 20 seconds to 7 minutes. In three cases, sustained monomorphic VT could be reinduced, two after 60 minutes and one after 120 minutes. However, in seven dogs, VT could not be induced during the 3-hour follow-up period. None of the dogs in which PA was delivered iontophoretically into the infarcted myocardium developed VT that was not induced before delivery of the drug. Intravenous PA administration resulted in VT suppression in one of 10 dogs. In two dogs, VT could not be induced before intravenous infusion of PA. However, after intravenous PA, VT could be induced. Immunohistochemical mapping of the PA within the infarcted tissue revealed transmural PA distribution. CONCLUSIONS: These data show that 1) the delivery of high transmural concentrations of PA directly into infarcted myocardium is both feasible and effective...

Induction of ventricular fibrillation versus monomorphic ventricular tachycardia during programmed stimulation. Role of premature beat conduction delay.

BACKGROUND: Premature stimuli can cause ventricular fibrillation (VF) during electrophysiological testing. The electrophysiological correlations associated with the onset of VF were evaluated in 40 patients who had this rhythm induced during programmed ventricular stimulation. These parameters were compared with those observed in 51 patients who had inducible sustained monomorphic ventricular tachycardia (VT) and 45 patients who had no inducible sustained ventricular tachyarrhythmias. METHODS AND RESULTS: Shortest premature coupling intervals for S2, S3, and S4 at induction of tachycardia or before achieving refractoriness, corresponding conduction latencies (defined as the time from the premature stimulus to the upstroke of the depolarization wave front recorded 35 mm away from the stimulation site), and ventricular activation times (defined as the time from the premature stimulus to the end of the depolarization wave) were compared. The mean coupling intervals were longest in the inducible VT patients: 300 +/- 30, 254 +/- 57, and 228 +/- 32 msec for S2, S3, and S4, respectively. In the inducible VF group, the coupling intervals were 260 +/- 37, 208 +/- 20, and 213 +/- 30 msec. In the group with no inducible VT or VF, these coupling intervals were 251 +/- 24 (p less than 0.01 versus inducible VT group), 209 +/- 27 (p less than 0.001 versus inducible VT group), and 194 +/- 21 msec (p less than 0.05 versus inducible VT and VF groups). The coupling interval of the last premature extrastimulus was above 200 msec in 70% of the patients in whom VF was induced. The largest increases in latency and activation times were recorded in patients in whom VF was induced. The cumulative increase in latency, defined as increased conduction time from baseline, summed for all the premature stimuli was also the greatest at initiation of VF. In contrast, the smallest increases in these parameters were noted in the patients with no inducible VT or VF. Measurements of total activation time yielded similar results as those recorded for latencies. The most important parameters distinguishing the VT patient population from the other two groups were the low ejection fractions and the longer coupling intervals at which VT was induced, whereas in the VF group, the most important discriminating factor was cumulative activation time. Sixty-three percent of the inducible VF patients presented with abnormal hearts (myocardial infarction or cardiomyopathy), whereas 88% of the inducible VT patients had abnormal hearts. In contrast, only 25% of the patients in whom no arrhythmia was induced presented with abnormal hearts. Mean ejection fraction was 32 +/- 15% for the inducible VT group, 45 +/- 13%* for the inducible VF group, and 51 +/- 17%* for patients with no inducible VT/VF (*p less than 0.001 versus VT). CONCLUSIONS: The results suggest that 1) initiation of ventricular tachycardia during programmed ventricular stimulation occurs with minimal conduction latency; 2) because of the large overlap in coupling intervals where VF or VT were induced, a single coupling interval cannot be recommended to adequately separate these groups; and 3) induction of VF was preceded by increased latency and prolongation of the local activation time. These parameters should not be allowed to prolong if VF is to be avoided during programmed stimulation. In addition, 4) the initiation of VF during electrophysiological studies is often associated with the presence of structural heart disease; such structural disease may promote conduction latency and the development of VF.

Use of intravenous esmolol to predict efficacy of oral beta-adrenergic blocker therapy in patients with neurocardiogenic syncope.

The usefulness of esmolol in predicting the efficacy of treatment with an oral beta-adrenergic blocking agent was evaluated in 27 consecutive patients with neurocardiogenic syncope. Seventeen patients had a positive head-up tilt test response at baseline and 10 patients required intravenous isoproterenol for provocation of hypotension. All patients were then given a continuous esmolol infusion (500 micrograms/kg per min loading dose for 3 min followed by 300 micrograms/kg per min maintenance dose) and rechallenged with a head-up tilt test at baseline or with isoproterenol. Of the 17 patients with a positive baseline tilt test response, 11 continued to have a positive response to esmolol challenge. Sixteen patients (including all 10 patients with a positive tilt test response with isoproterenol) exhibited a negative response to upright tilt during esmolol infusion. Irrespective of their response to esmolol infusion, all patients had a follow-up tilt test with oral metoprolol after an interval of greater than or equal to 5 half-lives of the drug. All 16 patients (100%) with a negative tilt test response during esmolol infusion had a negative tilt test response with oral metoprolol. Of the 11 patients with a positive tilt test response during esmolol infusion, 10 (90%) continued to have a positive response with oral metoprolol. It is concluded that in the electrophysiology laboratory, esmolol can accurately predict the outcome of a head-up tilt response to oral metoprolol. This information may be helpful in formulating a therapeutic strategy at the initial head-up tilt test in patients with neurocardiogenic syncope.

Role of implantable cardioverter defibrillator therapy in the management of high-risk patients.

Cardiovascular mortality from ventricular tachycardia (VT) and ventricular fibrillation (VF) continues to be a major health problem. Several therapeutic approaches are now available to treat patients with known VT/VF. Among the various therapeutic options are antiarrhythmic drugs, catheter or surgical ablation of VT focus, and implantable cardioverter defibrillator (ICD). The overall 2-year cardiovascular mortality is significantly reduced by ICD therapy. The ICD is particularly useful in patients with 1) no inducible but clinical VT/VF, 2) drug refractory VT/VF, and 3) VT/VF in association with left ventricular ejection fraction of less than or equal to 30%. Significant improvements in ICD therapy have already been made; these improvements include tiered antitachycardia therapy, antibradycardia pacing, lower defibrillation threshold, and longer life of generator. Further improvements are expected, including nonthoracotomy approach to defibrillation, pectoral implant, and dual chamber sensing. It is likely that with all of the advances in ICD therapy its acceptance as a therapeutic option will increase.