Carol J. Gilbert

Unexplained Syncope Evaluated by Electrophysiologic Studies and Head-up Tilt Testing

OBJECTIVE To determine the clinical characteristics of subgroups of patients with unexplained syncope having electrophysiologic studies and head-up tilt testing and to assess the efficacy of various therapies. DESIGN Retrospective study. SETTING Inpatient services of a tertiary referral center. PATIENTS Eighty-six consecutively referred patients with unexplained syncope. MEASUREMENTS All patients had electrophysiologic examinations. Patients with negative results subsequently had head-up tilt testing. MAIN RESULTS Twenty-nine (34%) patients (group 1) had abnormal electrophysiologic results, with sustained monomorphic ventricular tachycardia induced in 72%. Thirty-four (40%) patients (group 2) had syncope provoked by head-up tilt testing. The cause of syncope remained unexplained in 23 (26%) patients (group 3). Structural heart disease was present in 76%, 6%, and 30% of groups 1, 2, and 3, respectively. In group 1, pharmacologic or nonpharmacologic therapy was recommended based on electrophysiologic evaluation. All group 2 patients had negative results on head-up tilt testing while receiving oral beta blockers (27 patients) or disopyramide (7 patients). Group 3 patients did not receive any specific therapy. During a median follow-up period of 18.5 months, syncope recurred in 9 (10%) patients. CONCLUSIONS The combination of electrophysiologic evaluation and head-up tilt testing can identify the underlying cause of syncope in as many as 74% of patients presenting with unexplained syncope. Therapeutic strategies formulated according to the results of these diagnostic tests appear to prevent syncope effectively in most patients.

Role of Cardiac Electrophysiologic Studies in Patients with Unexplained Recurrent Syncope

Cardiac electrophysiologic studies (EPS) with programmed electrical stimulation (PES) were performed in 30 patients with recurrent syncope to uncover possible arrhythmic etiology. All patients had undergone thorough medical and neurologic evaluation prior to EPS without finding a definitive cause for syncope. In the majority of patients an arrhythmic etiology for syncope was suspected but could not be documented utilizing the 12‐lead surface ECG, extended in‐hospital and/or ambulatory monitoring (for ≥ 48 hours) and exercise testing prior to the EPS. The studies provided a clue to the possible underlying rhythm disturbance which could have caused syncope in 16/30 patients. Sustained or nonsustained ventricular tachycardia and/or ventricular fibrillation was induced in 11/30, sinus node dysfunction in 4/30 and intra‐His block in the remaining one. Fourteen of the 16 have remained free of symptoms following therapy based on results of EPS during a follow‐up period ranging from 6–30 months (mean 16.5 ± 7.8). In 2/16 syncope recurred (one arrhythmic and one non‐arrhythmic) despite pacemaker therapy for sinus node dysfunction detected during EPS. In the remaining 14/30 patients, EPS and PES did not induce arrhythmia which could account for patient symptomatology and therefore no specific therapy could be recommended. Eleven of these 14 patients experienced a recurrence of symptoms within a 6–25 month period (mean 16.2 ± 6.8). Of the 16 patients with inducible arrhythmias considered clinically significant, 15 had associated structural heart disease. On the other hand, of the 14 patients without clinically significant arrhythmias, structural heart disease could be detected in only three. It is concluded that cardiac arrhythmias constitute a common cause of unexplained syncope, particularly in patients with structural heart disease, and that EPS with PES can uncover the type of arrhythmic disturbance in a significant number of cases.

Facilitation of ventricular tachycardia induction with abrupt changes in ventricular cycle length

The effect of abrupt short-to-long changes in cycle length (CL) on the postulated reentrant circuit of ventricular tachycardia (VT) was evaluated. This was performed using single and double ventricular extrastimuli in a group of 21 patients clinically suspected of having VT in whom VT could not be induced at comparable or shorter constant CLs. A second group of 10 patients without suspected VT was similarly studied. Compared with constant CLs of equal or shorter duration preceding the single or double ventricular extrastimuli, abrupt short-to-long CL changes resulted in (1) initiation of sustained VT in 13 of 21 patients in whom VT could not be induced at constant CLs despite the use of shorter S1S3 by 66 +/- 17 ms; (2) increased incidence of initiation of sustained VT after the V3 phenomenon resulting from macroreentry within the His-Purkinje system (Re-HPS); (3) a small but higher incidence of sustained VT due to sustained Re-HPS; and (4) no induction of sustained or nonsustained VT with either method in the second group of patients. These results provide additional support for reentry as the basis for sustained ventricular tachyarrhythmias. Abrupt short-to-long CL changes may be effective for initiating sustained VT in patients at risk for these arrhythmias.

Effect of lidocaine on atrioventricular response via the accessory pathway in patients with Wolff-Parkinson-White syndrome.

Electrophysiologic effects of i.v. lidocaine were evaluated in 10 patients with Wolff-Parkinson-White (WPW) syndrome during atrial fibrillation (AF) (eight of 10) or programmed atrial stimulation (nine of 10). The shortest RR intervals during AF were 190–415 msec (mean 271.8 ± 64.5 msec) before lidocaine and decreased to 250.0 ± 85.4 msec (range 180-435 msec, p = NS) after the drug. In six of eight patients, the shortest RR interval decreased and in the remaining two patients it increased by 20 msec after lidocaine. After lidocaine, the average RR intervals during AF for all eight patients decreased from 351.1 ± 45.9 msec to 335.6 ± 68.0 msec (p = NS). After lidocaine, the RR inverval shortened in five of eight patients, lengthened in two and did not change In one. In two of eight patients, acceleration of ventricular rate after lidocaine was accompanied by hemodynamic deterioration, necessitating DC cardioversion in one. The control effective refractory period of the accessory pathway (ERP-AP) was 300 msec or less in all patients, and lidocaine prolonged this variable in only one case. In the remaining patients, after lidocaine the ERP-AP either shortened (two of nine), did not change (two of nine) or atrial refractoriness precluded its determination. Similarly, during incremental pacing, the atrial cycle length that produced block in the AP shortened in five patients, lengthened in one and did not change in the others. In patients with WPW syndrome and relatively short ERP-AP (i.e., 300 msec), lidocaine generally has no significant effect or produces acceleration of ventricular response during AF. In patients with AF and a rapid ventricular rate due to antegrade conduction over the AP, lidocaine is unlikely to have beneficial effects and may be deleterious.

Effects of abrupt changes in cycle length on refractoriness of the His-Purkinje system in man.

Abrupt changes in cycle length (CL) occur frequently in the clinical setting of atrial fibrillation. However, the effects of such changes on the His-Purkinje system (HPS) have not previously been considered during aberrant ventricular conduction (VAb). In 12 patients who manifested VAb with atrial premature stimulation (A2) during sinus rhythm, the relative refractory period (RRP) of the HPS was evaluated during a constant atrial CL (method I) and during abrupt changes in the CL (method II), wherein the A2 was coupled to an atrial CL (last A1A1) comparable to method I. This last A1A1 during method II was preceded by a series of constant atrial CLs 100–200 msec longer (method IIA) in 11 of 12 patients, or 100–300 msec shorter (method IIB) in all 12 patients. Although abrupt changes in the atrial CL using method IIA resulted in a longer HH interval (by 0–30 msec; mean 13.2 ± 9.2 msec) preceding the A2, the RRP-HPS was 5–20 msec shorter (mean 9.3 ± 5.3 msec) compared with method I in eight patients. The effect of abrupt changes was further evaluated in nine patients using method III, with a constant atrial CL, with a duration equal to the last HIH1 interval of method IIA. The VAb that occurred with method III was not manifested with method IIA in seven of nine patients, and in two patients the RRP-HPS was the same or less. Conversely, method IIB resulted in a shorter HH interval (by 0–110 msec; mean 28.9 ± 21.1 msec) preceding A2, but in 10 patients, RRP-HPS was 5–40 msec longer (mean 20.7 ± 10.5 msec) than that of method I and in two, VAb was only manifested using method IB. Further scanning with method III, derived from the HH interval immediately preceding A2 of method IIB, was performed in seven patients and compared with method IIB. Prolongation in the RRP-HPS was shown using the latter method. The results indicate that abrupt changes in CL influence the functional behavior of the HPS in a manner not anticipated. Such changes may have important implications in determining the occurrence of VAb during atrial fibrillation.

Divergence between refractoriness of His-Purkinje system and ventricular muscle with abrupt changes in cycle length.

The concept that refractoriness of the His-Purkinje system (HPS) and ventricular muscle both vary directly with cycle length is based on observations during the use of constant cycle length. During abrupt changes in ventricular cycle length, refractoriness of the ventricular muscle is known to reflect the cumulative durations of preceding cycle lengths. The effect of such changes on retrograde refractoriness of the HPS is not known. In this study refractoriness of ventricular muscle and of the HPS was evaluated in 30 patients with normal intraventricular conduction by the ventricular extrastimulus (V2) technique during constant cycle length (method I) and during abrupt cycle length changes (method II). During method II the cycle length immediately before V2 was identical to the constant cycle length of method I and therefore was designated as the reference cycle length (CLR); however, the cycle length preceding (CLP) CLR was either longer than CLR (method IIA) by 100 to 300 msec in 11 patients or shorter than CLR (method IIB) by 100 to 300 msec in 30 patients. Results showed that compared with method I, method IIA shortened the relative refractory period (RRP) of the HPS from 350 +/- 29 to 344 +/- 29 msec (p less than .04), whereas the effective refractory period (ERP) of the ventricular muscle increased from 225 +/- 21 to 233 +/- 20 msec (p less than .0001). In contrast, compared with method I, method IIB lengthened the RRP of the HPS from 335 +/- 30 to 351 +/- 35 msec (p less than .0001), whereas ERP of the ventricular muscle decreased from 223 +/- 23 to 213 +/- 22 msec (p less than .0001). Similar to the inverse relationship between CLP and RRP of the HPS, ERP of the HPS was prolonged with short CLP (method IIB) compared with long CLP (method IIA). The results indicate a marked divergence between refractoriness of the HPS and of ventricular muscle during abrupt cycle length changes; these results were not previously anticipated. Whereas ventricular muscle responded to cumulative effects of preceding cycle lengths and varied directly with CLP, the HPS appeared to respond to directional and/or dynamic changes in cycle length and varied inversely with CLP. Moreover, in contrast to ventricular muscle, the HPS appeared to be responsive to rate of change in cycle length whereby short-to-long change in cycle length had a greater effect than long-to-short change in cycle length.

Facilitation of macroreentry within the His-Purkinje system with abrupt changes in cycle length.

We have recently described the ability of abrupt short-to-long changes in atrial cycle length (CL) to prolong refractoriness of the His-Purkinje system (HPS) and increase the likelihood of aberrant ventricular conduction. We have also shown similar functional behavior in retrograde refractoriness of the HPS during changes in ventricular CL. To further assess these characteristics we evaluated the effect of abrupt short-to-long change in ventricular CL on the phenomenon of macroreentry within the HPS (Re-HPS) in 20 patients in whom Re-HPS occurred during application of a ventricular extrastimulus (V2) at a constant ventricular CL (method I) and/or with abrupt short-to-long change in CL (method II). For both methods V2 was coupled to a CL of identical duration, designated the reference CL (CLR). In method I the CLs preceding (CLP) the CLR equaled CLR, whereas in method II CLP was less than CLR. The results showed a dramatic increase in occurrence of Re-HPS with abrupt short-to-long change in CL with Re-HPS occurring in 19 patients with this method compared with in 11 patients during constant CL. In 10 patients manifesting Re-HPS with both methods the associated retrograde conduction (V2H2) delays were equal or less during abrupt short-to-long changes in CL and, remarkably, there were concomitantly shorter antegrade conduction (H2V3) delays compared with at a constant CL. Moreover, despite the resulting shorter V2V3, additional Re-HPS beats were also more likely to occur with abrupt short-to-long change in CL compared with at a constant CL.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrioventricular nodal conduction and refractoriness after intranodal collision from antegrade and retrograde impulses.

Animal studies have suggested that spontaneous or programmed ventricular beats that occur simultaneously with atrial activation may facilitate atrioventricular (AV) nodal conduction during subsequent atrial impulses. However, this possibility has not been systematically studied in the human heart. In the present study the AV nodal conduction during a programmed atrial premature beat (S2) was analyzed. The S2 was delivered after a series of atrial drive beats (SjSj) of constant duration; this was termed stimulation method I. The results were compared with stimulation method II, which was similar to method I except that a single ventricular beat (Vs) was introduced simultaneously with the last Sl. The longest and shortest possible paced atrial cycle lengths (CLs) were scanned during both methods. Twenty-six patients were studied: 14 with a normal PR and normal intraventricular conduction (NIVC), four with first-degree AV nodal block and NIVC, three with a complete left bundle branch block (LBBB) pattern, three with a complete right bundle branch block (RBBB) pattern, and two with an incomplete RBBB pattern.At the same SlS2 intervals, the AV nodal conduction times (S2112 intervals) were consistently shorter with method II than with method I except in three patients, two with complete RBBB and one with complete LBBB. The magnitude of S2H2 shortening with method II was more pronounced at the shorter basic CLs and shorter SlS2 intervals. During method I, the effective refractory period (ERP) of the AV node was measured in 13 patients, eight with NIVC and five with preexisting bundle branch block. With method II, the ERP of the AV node shortened in all but three patients (one with complete RBBB, one with incomplete RBBB and one with complete LBBB pattern), in whom this variable did not change. The findings suggest that intranodal collison from antegrade and retrograde impulses facilitates AV nodal conduction and shortens the ERP. The magnitude of this change is greater at shorter atrial CLs and is probably related to deeper intranodal penetration of a Vs. The shortening in AV nodal conduction and refractoriness is not noted in patients with bundle branch block when retrograde conduction delay or block in the bundle branches coexists with the antegrade counterpart producing delayed or ineffective input of Vs into the AVnode.

Periprocedural anticoagulation for atrial fibrillation ablation.

Background: Catheter ablation for atrial fibrillation (AF) can increase risk of left atrial (LA) thrombi and stroke. Optimal periprocedural anticoagulation has not been determined.

Site of conduction delay during functional block in the His-Purkinje system in man.

Using recordings from the His bundle (H) and right bundle (RB), the site of functional conduction delay and/or block along the H-RB axis was analyzed in 14 patients with normal intraventricular conduction. During sinus rhythm, the HV and RB-V intervals had a mean value of 46.4 ± 3.6 msec (range 40-50 msec) and 22.8 ± 7.5 msec (range 5-30 msec), respectively, with an average H-RB interval of 23.6 ± 9.1 msec. In response to single atrial premature beats, all 14 patients developed right bundle branch block (RBBB), while nine of 14 also developed left bundle branch block (LBBB) as well as bilateral block within the His-Purkinje system (HPS). During RBBB, the RB potential disappeared in 13 of 14 patients with and without concomiteant increase in the HV interval, suggesting an increase in the H-RB interval due to conduction delay distal to the H but proximal to the RB recording site. In two of these 13 patients and the remaining patient, RBBB also occurred without a corresponding increase in the H-RB interval, indicating conduction delay and/or block distal to the RB recording. An increase of 40-325 msec in the H-RB interval was noted during LBBB. During bilateral block within the HPS, a clearly recorded H potential was not followed by RB deflection. When either the RBBB (six patients) or LBBB (three patients) persisted for two or more successive premature beats, the H-RB interval lengthened preceding the first beat but normalized during subsequent beats. The data suggest that the site of functional conduction delay and/or block along the H-RB axis is generally proximal (i.e., distal H or proximal RB), but could vary in the same patient, and can quickly shift from a proximal to a distal location with successive short cycles.