Environmental condition alters amphetamine self-administration: role of the MGluR5 receptor and schedule of reinforcement.

RATIONALE: Evidence suggests that differential rearing influences the function of a receptor subtype critical for maintaining glutamate homeostasis. Maintaining homeostatic glutamatergic function may be an important protector against drug abuse. OBJECTIVE: This study sought to determine if differential rearing influences the function of a receptor critical for glutamate homeostasis, which could in turn affect rates of amphetamine self-administration. METHODS: Rats were assigned to enriched (EC), isolated (IC), or standard (SC) conditions. After rearing for 30 days, rats were trained to lever press for sucrose reinforcement before the implantation of indwelling jugular catheters. After reaching stable responding for amphetamine (0.03 or 0.1 mg/kg/infusion), rats were injected with five doses (0, 0.3, 1.0, 3.0, and 5.0 mg/kg) of the mGluR5 antagonist, 3-((2-methyl-1,3-thiazol-4-yl)ethynyl) pyridine hydrochloride (MTEP), 30 min before self-administration sessions. Following fixed-ratio (FR-1) testing, rats were administered identical doses of MTEP on a progressive-ratio (PR) reinforcement schedule. RESULTS: MTEP (3.0 mg/kg) attenuated FR-1 self-administration (0.03 mg/kg/infusion) in IC rats. MTEP also dose-dependently attenuated amphetamine self-administration (0.1 mg/kg/infusion) during FR-1 and PR sessions, with 5.0 mg/kg MTEP attenuating amphetamine self-administration in IC and SC rats and 3.0 mg/kg MTEP attenuating amphetamine self-administration in EC and SC rats. PR results also revealed that IC rats not treated with MTEP were more motivated to self-administer the higher dose of amphetamine. CONCLUSIONS: These results suggest that the mGlu5 receptor mediates differences in drug-taking behavior among differentially reared rats. Isolation also decreased sensitivity to MTEP, suggesting that environmental factors alter glutamate homeostasis which subsequently affects sensitivity and motivation to self-administer amphetamine.

Effect of amphetamine on response inhibition in rats showing high or low response to novelty.

Previous work has shown that rats categorized as either high responder (HR) or low responder (LR) based on the amount of activity assessed in a novel environment show a differential response to stimulant reward, with HR rats self-administering more amphetamine and cocaine than LR rats. The current study assessed behavioral inhibitory processes in HR and LR rats using either fixed consecutive number (FCN) or differential reinforcement of low rate of responding (DRL) tasks. Individual differences in free-choice preference for a novel environment or novel object were also assessed to determine if these measures were predictive of performance on these inhibitory tasks. Results showed that, regardless of the test used to characterize individual differences in response to novelty, groups showed a similar ability to learn the FCN and DRL tasks. When subsequently pretreated with amphetamine, there was no significant difference between groups in performance efficiency (accuracy) on either the FCN or DRL task; however, based on activity in inescapable novelty, HR rats were less sensitive than LR rats to amphetamine-disrupted responding on the reinforcement lever in the FCN task. Although a deficit in inhibition is generally thought to play a role in drug abuse behavior, the differential rate of stimulant self-administration described previously between HR and LR rats more likely reflects an incentive motivational effect that is independent of response inhibition.

Prediction of long-term outcomes by signal-averaged electrocardiography in patients with unsustained ventricular tachycardia, coronary artery disease, and left ventricular dysfunction.

BACKGROUND: An abnormal signal-averaged ECG (SAECG) is a noninvasive marker of the substrate of sustained ventricular tachycardia after myocardial infarction. We assessed its prognostic ability in patients with asymptomatic unsustained ventricular tachycardia, coronary artery disease, and left ventricular dysfunction. METHODS AND RESULTS: A blinded core laboratory analyzed SAECG tracings from 1925 patients in a multicenter trial. Cox proportional hazards modeling was used to examine individual and joint relations between SAECG variables and arrhythmic death or cardiac arrest (primary end point), cardiac death, and total mortality. We also assessed the prognostic utility of SAECG at different levels of ejection fraction (EF). A filtered QRS duration >114 ms (abnormal SAECG) independently predicted the primary end point and cardiac death, independent of clinical variables, cardioverter-defibrillator implantation, and antiarrhythmic drug therapy. With an abnormal SAECG, the 5-year rates of the primary end point (28% versus 17%, P=0.0001), cardiac death (37% versus 25%, P=0.0001), and total mortality (43% versus 35%, P=0.0001) were significantly higher. The combination of EF <30% and abnormal SAECG identified a particularly high-risk subset that constituted 21% of the total population. Thirty-six percent and 44% of patients with this combination succumbed to arrhythmic and cardiac death, respectively. CONCLUSIONS: SAECG is a powerful predictor of poor outcomes in this population. The noninvasive combination of an abnormal SAECG and reduced EF may have utility in selecting high-risk patients for intervention.

Arousal-related associative response characteristics of dorsal lateral geniculate nucleus neurons during acoustic Pavlovian fear conditioning.

This research determined whether fear-conditioned, acoustic stimuli induce thalamic arousal reflected in associative responses in dorsal lateral geniculate nucleus (dLGN) neurons. Rabbits received a Pavlovian discriminative fear conditioning procedure in which one tone conditioned stimulus (CS +) was always paired with an aversive unconditioned stimulus (US) and another tone (CS-) was never paired with the US. Responses of single dLGN neurons to random CS+ and CS- presentations were then recorded. Nine of 15 recorded neurons demonstrated significantly greater firing during the CS+ versus the CS-. Their spontaneous activity demonstrated tonic firing during increased neocortical arousal and burst firing during decreased neocortical arousal. The results demonstrate that dLGN neurons show associative responses to fear-conditioned, acoustic stimuli and present a model for investigating the neural circuits by which such stimuli affect sensory processing at the thalamic level.

Mechanisms underlying spontaneous and induced ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: To define the electrophysiological mechanism(s) of inducible and spontaneously occurring ventricular arrhythmias associated with nonischemic cardiomyopathy, 3-dimensional intraoperative mapping from 156 intramural sites was performed in 6 patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation. METHODS AND RESULTS: Electrode density was sufficient to determine the mechanism for 52 of 74 beats of nonsustained ventricular tachycardia (VT) induced by programmed stimulation and 9 of 11 beats of spontaneous ventricular arrhythmias. The first, second, and third extrastimuli (S2 through S4) conducted with progressively greater degrees of conduction delay (total activation times [TAs] of 144+/-5, 166+/-5, and 194+/-5 ms, respectively) owing to slow conduction and on occasion intramural block. The first beats of induced VT arose from subendocardial or subepicardial sites distant from areas of marked conduction delay by a focal mechanism on the basis of the absence of intervening electrical activity between the termination of the last extrastimulus and the initiation of VT (123+/-31 ms). Subsequent beats arose by a focal mechanism and conducted with a TA of 127+/-6 ms (P=NS versus initiating beats of VT [118+/-9 ms]). Spontaneous ventricular arrhythmias initiated in the subendocardium by a focal mechanism and conducted with a TA of 138+/-5 ms. Tissue analysis demonstrated a variable degree of interstitial fibrosis at sites of focal activation. Sites of conduction delay or block typically exhibited marked interstitial and/or replacement fibrosis but were spatially distant from sites initiating VT. CONCLUSIONS: Spontaneous and induced ventricular arrhythmias in patients with end-stage idiopathic cardiomyopathy can arise in the subendocardium or subepicardium by a focal mechanism.

Improved estimation of pericardial potentials from body-surface maps using individualized torso models.

Clinical applicability of inferred pericardial potentials is limited because accuracy is significantly affected by noise in surface electrocardiograms (ECGs), errors in electrode location on the torso model, and errors in the geometry and inhomogeneities of the torso model itself. To quantify effects of electrode location and geometric errors in torso-surface models, we measured locations of 190 electrodes used in body-surface mapping of 11 adults, along with over 2,000 sites on each torso surface. Measurements were made to within 2 mm with an Immersion Personal Digitizer. To quantify effects of errors in pericardial-surface models we also estimated heart position, size, and orientation in each subject from ultrasonic images registered to the body-surface coordinates. Known pericardial potentials were taken from epicardial measurements made during QRS with a 90-electrode sock in an adult male undergoing cardiac surgery. Body-surface ECGs were calculated for each individual from the pericardial maps, using standard boundary-element methods. Accuracy of zero-order-Tikhonov inverse solutions was tested in 91-node pericardial and 1,026-node torso models, individualized for each subject. With 10 microv rms noise added to surface potentials, the optimal regularization constant at each instant in QRS gave a relative error of 0.44 +/- 0.03; it was 0.47 +/- 0.03 using the composite residual and smoothing operator (CRESO) technique. When calculated body-surface potentials from the first 10 subjects were placed at corresponding electrode positions on the torso of the eleventh subject, whose heart size and orientation was the mean of the other 10 subjects, relative error increased to 0.87 +/- 0.06 for optimal regularization. CRESO failed in the fixed torso model. Results demonstrate that a fixed model does not provide useful estimates of pericardial potentials, and that individualized models enhance the performance of techniques for the estimation of regularization parameters.

Three-dimensional mapping of the initiation of nonsustained ventricular tachycardia in the human heart.

BACKGROUND: Elucidation of the electrophysiological mechanisms of nonsustained ventricular tachycardia (VT) in humans is required to define the relationship between nonsustained VT and sustained VT. This goal requires, at least in part, analysis of transmural ventricular activation in patients with both sustained and nonsustained VTs. METHODS AND RESULTS: We analyzed three-dimensional intraoperative cardiac maps of extrastimuli and beats during 44 nonsustained VTs and the initiating beats of 6 sustained VTs from six patients with healed myocardial infarcts who were undergoing arrhythmia surgery. The coupling interval, total activation time, and diastolic interval of each extrastimulus and beat of nonsustained VT were compared with counterparts during sustained VT. Sites activated last during extrastimuli initiating nonsustained or sustained VTs occurred in the same region, and activation times were comparable. However, the site of earliest activation during the initial or subsequent beats of nonsustained VT was discordant from the site activated earliest during the first and subsequent beats of sustained VT in 74% of cases. The mean variance in coupling interval, but not total activation time or diastolic interval, was significantly greater for VT that terminated before the 10th cycle than for VT that sustained. When analyzed from the last extrastimulus up to the fifth VT cycle, the standard deviation of the coupling interval, but not of the total activation time, was greater for nonsustained than for sustained VTs. Electrode density was sufficient to define an arrhythmia mechanism for 36 beats of nonsustained VT. Twenty-one (58%) initiated in the subendocardium, midmyocardium, or epicardium by a macroreentrant mechanism, and 15 (42%) initiated in the subendocardium by a focal mechanism. CONCLUSIONS: Compared with sustained VT, nonsustained VT initiates at discordant sites, is characterized by oscillations in coupling interval but not in total activation time, and initiates by either a macroreentrant or a focal mechanism.

Termination of ventricular tachycardia in the human heart. Insights from three-dimensional mapping of nonsustained and sustained ventricular tachycardias.

BACKGROUND: To define the electrophysiological basis for the termination of ventricular tachycardia (VT), three-dimensional cardiac mapping and analysis of the terminal beats of nonsustained VT and beats of sustained VT were performed in six patients with healed myocardial infarcts. METHODS AND RESULTS: Termination of VT was due to activation from multiple initiation sites that were discordant from those responsible for the maintenance of sustained VT in 45% of cases, to repetitive activation from single sites that were discordant from those responsible for the maintenance of sustained VT in 24% of cases, or to activation from sites concordant with the sites of repetitive activation during sustained VT in 31% of cases. Sustained VT was characterized by occasional shifting of initiation sites, even after the tachycardia entered the stable monomorphic phase. Mapping was of sufficient density to define the mechanisms for 21 terminating beats of VT. In 5 cases, termination was due to intramural reentry, which initiated with the total activation time of the preceding beat of 204 +/- 11 milliseconds (ms) but terminated primarily because of a decrease in total activation time (144 +/- 23 ms, P = .03) that was associated with the development of intramural conduction block or with significant changes in the activation sequence along the reentrant circuit. In 16 cases, terminal beats were initiated by a focal mechanism on the basis of the absence of intervening electrical activity from the termination of the preceding beat to the initiation of the terminating beat (172 +/- 9 ms). Focal activation was associated with less conduction delay of the preceding beat (115 +/- 6 ms) than terminating reentrant beats (P < .001) and usually terminated suddenly without oscillations in cycle length or total activation time. CONCLUSIONS: Termination of VT is associated with alterations in initiation sites that are most often discordant from those maintaining sustained VT and is due to either reentrant or focal mechanisms.

Catheter ablation of clinical intraatrial reentrant tachycardias resulting from previous atrial surgery: localizing and transecting the critical isthmus.

OBJECTIVES: We sought to evaluate the efficacy of anatomically based radiofrequency catheter ablation for the treatment of intraatrial reentrant tachycardia in patients with previous atrial surgery. BACKGROUND: Intraatrial reentrant tachycardias, a common late complication of atrial surgery, are often refractory to standard medical management. Data from experimental animals and from humans indicate that anatomic barriers resulting from residual atrial scars provide a substrate for intraatrial reentry. We speculated that these tachycardias require a narrow isthmus of tissue between surgical scars and native nonconductive boundaries and that transection of this isthmus with radiofrequency ablation would therefore constitute an effective treatment. METHODS: Fourteen patients with a history of atrial surgery and clinical intraatrial reentrant tachycardia underwent electrophysiologic testing. From activation mapping, putative surgical scars and patches that served as boundaries of reentrant circuits were identified. Radiofrequency lesions were then placed to transect the narrowest isthmus of conducting tissue between a surgical scar and an anatomic barrier. Catheter ablation was attempted only for tachycardias consistent with the patient's clinical arrhythmias. RESULTS: Radiofrequency catheter ablation was attempted for 17 (55%) of 31 tachycardias identified; it successfully terminated tachycardias in 13 (93%) of 14 patients (95% confidence interval [CI] 79% to 99%). There were clinical recurrences in six patients (46%, 95% CI 19% to 73%), each of whom underwent a repeat ablation that was successful. Twelve (86%) of 14 patients (95% CI 67% to 99%) have remained free of intraatrial reentrant tachycardia for a mean of 7.5 +/- 5.3 months. CONCLUSIONS: Anatomically guided radiofrequency catheter ablation is an effective technique for definitive management of intraatrial reentrant tachycardia in patients with previous atrial surgery.

Impact of clinical history and electrophysiologic characterization of accessory pathways on management strategies to reduce sudden death among children with Wolff-Parkinson-White syndrome.

OBJECTIVES: This study sought to determine whether the clinical and electrophysiologic criteria developed in adults also identify children with Wolff-Parkinson-White syndrome at risk for sudden death. BACKGROUND: In adults with Wolff-Parkinson-White syndrome, a shortest RR interval <220 ms during atrial fibrillation is a sensitive marker for sudden death. However, because reliance on the shortest RR interval has a low positive predictive value, the clinical history has assumed a pivotal role in assessing risk. This approach has not been evaluated in children. METHODS: We retrospectively evaluated 60 children

Nonpharmacologic approaches to the treatment of atrial fibrillation and atrial flutter.

The high prevalence of atrial fibrillation, the associated morbidity and mortality, the absence of safe and effective drug therapy, and an increased understanding of the pathophysiologic basis of atrial fibrillation and flutter have collectively led to the development of novel nonpharmacologic treatments for the management of these arrhythmias, including the CORRIDOR and MAZE surgical procedures, catheter-based ablation and modification of AV conduction, catheter-based ablation of atrial flutter and fibrillation, and internal atrial defibrillation. These surgical and catheter-based techniques offer potentially curative therapy while sparing the long-term risk of antiarrhythmic drug therapy. For patients with typical atrial flutter, catheter ablation affords to cure rate in excess of 70%. As technological innovations further facilitate identification and ablation of the critical isthmus in the floor of the right atrium, success rates should improve substantially. For patients with atrial fibrillation, AV junction ablation with implantation of a rate-responsive ventricular pacemaker should be considered palliative therapy, as should modification of AV junction conduction. The MAZE procedure offers very high cure rates, but because it currently involves open heart surgery, patient selection is critical. Catheter-based procedures emulating aspects of the MAZE procedure may one day offer cure rates comparable to those of the surgery itself, but additional research and technological development are necessary to further define and refine the minimal effective procedure, and then to facilitate the placement of contiguous, full-thickness lesions in precise three-dimensional configurations. In the interim, the implantable automatic atrial defibrillator may offer a means for rapidly restoring sinus rhythm without the risks of long-term antiarrhythmic drug therapy.

Electrophysiologic basis, surgical development, and clinical results of the maze procedure for atrial flutter and atrial fibrillation.

After more than a decade of experimental and clinical research into the basic mechanisms underlying atrial fibrillation, we were able to develop a surgical procedure that appears to cure the arrhythmia. This surgical procedure has been used in 100 patients in our institution and in a total of approximately 130 patients by surgeons in other institutions. The surgical results have been excellent, which indicates the sophisticated electrophysiologic mapping systems are unnecessary and that the results are not surgeon-specific.

Phase and group-delay characteristics of signal-averaged electrocardiograms from patients with ventricular tachycardia.

Fourier analysis of the signal-averaged ECG (SAECG) has previously revealed significant differences in magnitude spectra that differentiate patients with ventricular tachycardia (VT) from those without VT. To determine additional distinguishing features in the frequency domain, we analyzed phase spectra of SAECG's of sinus beats from 57 patients with VT, 65 without VT, and 20 normal controls. Unwrapped phase spectra from SAECG's of the entire cardiac cycle were calculated with respect to three fiducial points: onset of the P and Q waves, and the negative of the slope of the phase (group delay) for frequencies in the band, which accounted for 97.5% of the energy in the vector magnitude of the Frank SAECG leads. Phase spectra of SAECG's from patients with VT differed from the non-VT patients at frequencies > or = 21 Hz (p = 0.000039) for the P-wave fiducial, at frequencies > or = 60 Hz (p = 0.00085) for the Q-wave fiducial, and at frequencies < or = 62 Hz (p = 0.0035) for the 97.5% energy fiducial. Group delays in SAECG's from patients with and without VT differed from 10 to 26 Hz (p = 0.000016) for the P-wave fiducial, and from 14 to 24 Hz (p = 0.00000070) for the Q-wave fiducial. Group delays with respect to the Q-wave fiducial in the VT patients in the 14-24 Hz band were, on average, 9 ms and 5 ms longer than those of the non-VT's and normals, respectively. Thus, phase spectra of SAECG's contain previously undetected features that together with magnitude may be helpful in improving methods for stratifying the risk of VT.

Direct operation versus ICD therapy for ischemic ventricular tachycardia.

Now that the implantable cardioverter defibrillator is available as a therapeutic option for the management of ventricular tachycardia (VT), some argue that there no longer should be a role for direct surgical intervention for this malignant arrhythmia. Rebuttal of this argument is difficult for the following reasons: (1) there are many patients who are candidates for implantable cardioverter defibrillator therapy but not for direct VT operation, and thus direct comparisons of the two therapies is difficult; (2) implantable cardioverter defibrillator therapy by definition is palliative, but a VT operation is curative in most instances; (3) in many electrophysiologic triage algorithms, implantation of a cardioverter defibrillator and VT operation are employed as alternative, not competitive, therapies, again making direct comparisons difficult; and (4) probably most importantly, there are misconceptions in the literature regarding the risks and benefits of direct VT surgical procedures as they are currently performed. In this brief review, we examine the currently available data on both sides of this argument.

Enhanced detection of distinguishing features in signal-averaged electrocardiograms from patients with ventricular tachycardia by combined spatial and spectral analyses of entire cardiac cycle.

BACKGROUND: Signals generated by myocardium responsible for ventricular tachycardia (VT) contribute to the entire QRS complex, ST segment, and T wave and are spatially distributed over the entire torso. However, current methods of signal-averaged ECG analysis restrict interrogation to the terminal QRS complex, do not include data on the body surface distributions of the distinguishing features detected, and have a limited clinical value because of a low positive predictive accuracy. Accordingly, we tested the hypothesis that frequency analysis of the entire cardiac cycle of spatially selected ECGs based on isoharmonic maps of the body surface enhance the detection of the unique spectral features in signal-averaged ECGs that differentiate patients with from those without VT. METHODS AND RESULTS: Isoharmonic maps of the body surface were calculated during sinus rhythm with the use of forward problem solutions for 32 patients with sustained VT, 30 without VT, and 10 healthy subjects and analyzed over a bandwidth of 0.05 to 470 Hz. Spectra of ECGs at the maximum and minimum of each patient's isoharmonic map of 1 to 7 Hz demonstrated a broadened bandwidth of significant separation (P < .05) for patients with from those without VT compared with the separation achieved with the use of Frank ECGs alone. Furthermore, the statistical significance within the bands of separation was greater for spatially selected ECGs compared with the Frank leads. Frank leads separated patients over the band from 11 to 84 Hz with a mean value of P = .0094. ECGs at the maximum of 1-to-7-Hz isoharmonic maps separated patients over the 8-to-111-Hz band with a mean value of P = .0062 (range, P < .05 to P < .0000001). ECGs at the minimum of 1-to-7-Hz isoharmonic maps extended the low-frequency end of the band of separation, which covered 0 to 69 Hz with a mean value of P = .0039 (range, P < .05 to P < .0000001). Subgroup analysis verified that results were independent of QRS duration. CONCLUSIONS: Spectral analysis of ECGs that are spatially selected for each patient is superior to orthogonal ECGs and augments detection of distinguishing features in ECGs that identify risk of VT. The new data acquired from analysis of spatially selected ECGs from individual patients provide the information on the specific frequency bands and an improved ECG-lead system required to refine methods of analysis of the signal-averaged ECG.

Human ventricular tachycardia: precise intraoperative localization with potential distribution mapping.

Electrophysiologically guided operations for ventricular tachycardia (VT) have been directed exclusively by activation time maps. Even with computer-assisted mapping, extensive editing is required, which prolongs the duration of the operation and which may introduce significant error. In contrast, potential distribution maps can be constructed in less than 3 minutes and can be viewed as a movie of developing and receding potentials. In 4 patients undergoing operation for VT, endocardial mapping was performed using form-fitting electrodes containing 160 points. A computerized mapping system, capable of simultaneously recording 256 channels of data, was used to analyze data and to display potential distribution maps sequentially at 1-millisecond intervals as a color movie. A total of eight morphologies of sustained VT were mapped. The mean VT cycle length was 340 +/- 40 milliseconds (range, 274 to 394 milliseconds). In 3 patients with ischemic heart disease, four VT morphologies originated from the subendocardium. All were successfully ablated with cryoablation alone or in conjunction with aneurysmectomy and endocardial resection. A fourth patient with VT secondary to cardiomyopathy had multiple morphologies and received an implantable cardioverter defibrillator. Potential distribution maps correlated well with the concomitant activation time maps. Thus, potential distribution mapping provides a rapid and accurate means of identifying the site of origin of VT facilitating intraoperative mapping in patients undergoing surgical ablation.

Spectral analysis of the cardiac cycle of signal-averaged Frank leads from patients with ventricular tachycardia.

Identification of the spectral features in electrocardiograms that distinguish patients prone to ventricular tachycardia (VT) is a prerequisite to increasing the diagnostic power of the signal-averaged electrocardiogram (SAECG). To determine distinguishing features of the magnitude spectrum, the spectra of SAECGs of sinus beats were analyzed over the entire cardiac cycle from 32 patients with VT, 30 without VT, and 10 normal control subjects. The magnitude spectra of the Frank SAECGs separated patients with VT from those without VT over the band from 7 to 140 Hz with a P value of .000000047. To determine distinguishing features of phase and group-delay spectra, SAECGs of sinus beats over the entire cardiac cycle were analyzed from 57 patients with VT, 65 without VT, and 20 normal control subjects. Unwrapped phase spectra from SAECGs of the entire cardiac cycle were calculated with respect to the onset of the Q wave. Phase spectra of SAECGs from patients with VT differed from those from non-VT patients at frequencies of 60 Hz or greater (P = .00085). Average group delays in SAECGs from patients with and without VT differed (P = .00000069) from 14 to 24 Hz. Group delays in the VT patients in the 14-24-Hz band were on average 9 ms and 5 ms longer than those of the non-VTs and normal subjects, respectively. Time-domain reconstructions demonstrated that distinguishing frequency bands were detectable throughout the QRS complex, ST-segment, and T wave in SAECGs from each group. Thus, the spectra of SAECGs over the cardiac cycle contain features that together with temporal features from throughout the cardiac cycle are essential in improving methods for stratifying risk of VT.

Therapeutic end points for the treatment of atrioventricular node reentrant tachycardia by catheter-guided radiofrequency current.

OBJECTIVES: The purpose of this prospective study was to test the hypothesis that the elimination of inducible repetitive atrioventricular (AV) node reentry despite the persistence of slow AV pathway conduction is a valid end point for radiofrequency catheter ablation procedures in patients with supraventricular tachycardia due to AV node reentry. BACKGROUND: Although modification of AV node physiology by radiofrequency current can eliminate AV node reentrant tachycardia, therapeutic end points that are definitive of a satisfactory result in patients undergoing modification of the slow AV pathway have not been established. Applications of radiofrequency current at selected sites may eliminate all evidence of slow pathway conduction or sufficiently modify the refractory properties of the slow pathway to preclude sustained arrhythmias. Accordingly, total abolition of dual AV node physiology may not be necessary to prevent arrhythmia recurrence. METHODS: Radiofrequency catheter ablation of the slow AV pathway was attempted in 59 patients with typical AV node reentry. Tissue ablation was performed with a continuous wave of 500-kHz radiofrequency current. Twenty-five to 35 W was applied for 60 s at the site selected for tissue destruction. RESULTS: Dual AV node physiology was eliminated completely in 35 patients (59%), persisted without inducible AV node reentry in 13 patients (22%) and persisted with inducible single AV reentrant beats in 11 patients (19%). In patients with persistent dual AV node physiology, the maximal difference between the effective refractory period of the fast and slow pathways was reduced from 104 +/- 62 ms before the procedure to 37 +/- 37 ms after AV conduction had been modified (p < 0.001). During a mean follow-up interval of 15 months (range 4 to 28), only one patient (2%) had a recurrence of the tachycardia. CONCLUSIONS: Results demonstrate that when complete elimination of dual AV node physiology is difficult, modification of slow pathway conduction to the extent that repetitive AV node reentry cannot be induced is a definitive end point that portends a good prognosis.