Boaz Avitall

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

BACKGROUNDnThe 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.nnnMETHODSnAmong 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.nnnRESULTSnDuring 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.nnnCONCLUSIONSnIn patients with neurocardiogenic syncope associated with bradycardia or asystole, drug therapy is often effective in preventing syncope, whereas artificial pacing is not.

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

OBJECTIVEnTo 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.nnnDESIGNnRetrospective study.nnnSETTINGnInpatient services of a tertiary referral center.nnnPATIENTSnEighty-six consecutively referred patients with unexplained syncope.nnnMEASUREMENTSnAll patients had electrophysiologic examinations. Patients with negative results subsequently had head-up tilt testing.nnnMAIN RESULTSnTwenty-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.nnnCONCLUSIONSnThe 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.

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.

Distinctive time course of ventricular vulnerability to fibrillation during and after release of coronary ligation

Abstract Release of left anterior descending coronary artery ligature was performed in 32 dogs after periods of ligation ranging from 3 to 45 minutes. Spontaneous ventricular tachycardia or fibrillation occurred during occlusion in 9 of 20 dogs, developing during the first 8 minutes of occlusion in 8 of the 9. Ventricular tachycardia or fibrillation was evoked by release of occlusion in 3 of 7 dogs after a short-term occlusion of 3 to 6 minutes, and in 9 of 13 dogs after release of a long-term occlusion of 15 to 45 minutes. Thresholds for induced ventricular tachycardia or fibrillation were obtained using a train of gated stimuli (100 Hz for 250 msec). During short-term occlusions, average thresholds for ventricular tachycardia or fibrillation were reduced from 32.4 ma (control) to 3.4 ma ( P Our data suggest the following conclusions: (1) The time course of spontaneous ventricular vulnerability to fibrillation during coronary occlusion differs from that of ligature release, the former diminishing and the latter increasing with the duration of occlusion. (2) This observation and the lack of correlation between thresholds of induced ventricular tachycardia or fibrillation and spontaneous vulnerability to fibrillation after ligature release suggest different electrophysiologic mechanisms for ventricular tachyarrhythmias during and after release of coronary ligation.

Dispersion of effective refractory period during abrupt reperfusion of ischemic myocardium in dogs

Dispersion of the effective refractory period was measured in anesthetized dogs using a computerized system and bipolar epicardial electrodes or, alternatively, transmural plunge electrodes. Measurements were made at 1 minute intervals during short (5 minute) and long (15 minute) periods of coronary arterial ligation and for 3 to 5 minutes after release of the ligatures. Both transepicardial and transmural temporal dispersion of refractoriness correlated well with the increased vulnerability to spontaneous ventricular fibrillation during short periods of ligation and the relative electrical stability observed toward the end of the longer periods of ligation. During reperfusion, transmural dispersion increased somewhat after ligature release in the longer-term experiments but the increase did not appear adequate to explain the associated large incidence of spontaneous arrhythmias after release. Effective refractory periods measured at one nonischemic and five ischemic electrode sites at intervals as short as 20 seconds revealed abrupt shortening of the refractory period at all ischemic sites during the 1st minute of reperfusion, resulting in a large but short-lived electrical gradient between the ischemic and nonischemic myocardium. This increased dispersion between the ischemic and nonischemic myocardium occurred at a time of maximal vulnerability to reperfusion arrhythmias. However, this increased dispersion was greater after the 5 minute than after the 15 minute periods of ligation and thus does not fully explain the greater incidence of reperfusion arrhythmias after ligature release in the longer-term studies. Although arrhythmias of acute ischemia are associated with increased dispersion of refractoriness within theischemic segment and reperfusion arrhythmias with dispersion between ischemic and nonischemic segments, other electrophysiologic alterations probably play an important role in the genesis of the arrhythmias of reperfusion.

Cryoablation of refractory sustained ventricular tachycardia due to coronary artery disease

Thirty-nine patients with medically refractory sustained monomorphic ventricular tachycardia (VT) due to coronary artery disease underwent map-guided cryosurgery. Locations of prior myocardial infarctions had been inferior in 22, anterior in 16 and combined in 1. Mean age was 61 +/- 9 years and the mean number of drug trials per patient before surgery was 3.8 +/- 1.4. Intraoperative endocardial mapping induced 67 tachycardias in 35 patients. Each patient received 6 to 18 (11 +/- 3) endocardial cryothermic applications (15 mm, -60 degrees C, 2 minutes) at areas of earliest activation during VT. Encircling endocardial cryoablation was performed in 4 patients who had unsuccessful mapping. In addition, 11 patients had subendocardial resection of their well-demarcated septal scars as well as cryosurgery. There were 2 in-hospital deaths. At postoperative programmed ventricular stimulation, 28 of the 37 patients (76%) had no inducible or spontaneous VT before hospital discharge. Six patients (16%) with spontaneous or inducible VT had a single morphology and were controlled with antiarrhythmic drugs that had previously failed. Therefore, surgery alone or in combination with drugs was efficacious in 92% of the population surviving surgery. The remaining 3 patients (8%) received automatic implantable cardioverter defibrillators. No significant difference in surgical outcome was seen between patients who had cryosurgery alone and those who had subendocardial resection together with cryoablation. Mean left ventricular ejection fractions before and after surgery were 33 and 39%, respectively (p less than 0.01). Clinical follow-up ranged from 2 to 36 months (18 +/- 12). One patient died of heart failure and another underwent heart transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential unipolar strength-interval curves and conduction times during myocardial ischemia and reperfusion in the dog.

Computerized techniques were employed to generate alternating anodal and cathodal or sequential anodal strength-interval curves during and following 15-minute coronary artery ligations in 14 anesthetized dogs. The right atrium was paced at 2.5 Hz, and unipolar ventricular strengthinterval curves with simultaneous conduction times were recorded every 45-120 seconds during ischemia and reperfusion. Within 1-2 minutes of ligation, anodal midcurve and late diastolic thresholds fell sharply, and cathodal thresholds fell slightly or changed little. After 5 minutes of ischemia, anodal thresholds remained low, cathodal thresholds rose, and conduction times increased. At 10–15 minutes of ligation, if the ischemic zone was small, anodal thresholds were low, often approaching cathodal values, and conduction returned toward control values. When the ischemic zone was large, unipolar thresholds and conduction times increased late during the ligation period. Throughout the course of ischemia, the falling limb of the strength-interval curve shifted progressively to the left indicating shorter refractory periods. Following abrupt reperfusion, anodal phase 3 dips promptly reappeared; refractory periods returned toward control, and supernormal conduction was noted. By 3-5 minutes of reperfusion, the falling limb of the strength-interval curve had shifted to the right of control and conduction times increased. Thus, vulnerability to arrhythmias during early ischemia (i.e., 5 minutes) is characterized by low anodal midcurves and late diastolic thresholds, short refractory periods, and slow conduction. During the first minute of reperfusion, anodal excitability is increased during the early dip and conduction times are supernormal. Increases in anodal excitability correlate better with the peak incidence of early ligation and reperfusion arrhythmias than do changes in cathodal excitability.

Local effects of electrical and mechanical stimulation on the recovery properties of the canine ventricle

Abstract The effects of electrical stimulation on local recovery properties of the canine ventricle were studied. Ventricular excitability was examined by an analysis of unipolar or bipolar strength-interval curves, and the effective refractory period was derived from the steep portion of the curve. Conduction times of all propagated responses to testing stimuli were recorded. When ventricular driving and testing sites were the same, effective refractory periods were significantly shorter (probability [p] Thus, shortening of the effective refractory period and prolonged conduction in the vicinity of the driving electrode are a function of stimulus intensity, distance from the driving site and time. These local alterations in the recovery properties of the ventricle provide conditions that may be favorable for the induction of reentrant arrhythmias.

Time course of changes in ventricular excitability and conduction during myocardial ischemia and reperfusion in the dog: Effect of lidocaine

Strength-interval curves and conduction times were determined in anesthetized dogs during and following myocardial ischemia using a computerized system capable of determining a 5 point strength-interval curve with conduction times within 20 seconds. At the peak incidence of ligation arrhythmias (5 minutes of ischemia), the falling limb of the strength-interval curve was shifted to the left and conduction time was prolonged, while at 15 minutes of ischemia, the strength-interval was shifted upward and conduction times had returned toward control. Lidocaine enhanced the upward shift of the strength-interval curve, contributing to the electrical stability of the myocardium during this phase of ischemia. During the first minute following abrupt reperfusion of the ischemic zone, there was a slight downward shift of the early part of the strength-interval curve, and conduction times tended to be shorter than control. Lidocaine enhanced the electrophysiological alterations following abrupt reperfusion; that is, it reduced excitation thresholds and increased the tendency to superconductivity. Thus, lidocaine enhanced electrical stability during acute ischemia but tended to exaggerate electrophysiologic defects observed during abrupt reperfusion.

The rapid generation of strength-interval curves under computer control.

A system was developed to allow for the rapid evaluation of myocardial excitability and conduction in canine preparations. The stimulus strength required to excite a propagated response, as a function of time since the last depolarization, can be summarized by a strength--interval curve. Our system generates strength-interval curves under computer control with high accuracy and efficiciency. The conduction time of each ventricular response is also determined. At a heart rate of 2.5 Hz, the average time for curve generation is 94 s, an efficiency which is 85% of the theoretical maximum. This system has been employed in over 120 dogs to generate strength--interval curves during rapidly changing periods of myocardial ischemia and during interventions with various drugs.