Ross Brooks

Adenosine and the treatment of supraventricular tachycardia

Adenosine has recently become widely available for the treatment of paroxysmal supraventricular tachycardia. In order to evaluate its role in the management of arrhythmias, we have reviewed the literature on the cellular mechanisms, metabolism, potential for adverse effects, and clinical experience of the efficacy and safety of intravenous adenosine. Adenosine produces transient atrioventricular nodal block when injected as an intravenous bolus. This is of therapeutic value in the conversion to sinus rhythm of the majority of paroxysmal supraventricular tachycardias, which involve the atrioventricular node in a re-entrant circuit. The mean success rate was 93% from over 600 reported episodes. Compared with other antiarrhythmic agents, adenosine is remarkable for its rapid metabolism and brevity of action, with a half-life of a few seconds. It commonly produces subjective symptoms, particularly chest discomfort, dyspnea, and flushing, which are of short duration only. No serious adverse effect has been reported. Arrhythmias may recur within minutes in a minority of patients. Comparative studies have shown that adenosine is as effective as verapamil in the treatment of supraventricular tachycardia, and has less potential for adverse effects. Patients with supraventricular tachycardia should initially be treated using vagotonic physical maneuvers. Immediate electrical cardioversion is indicated if the arrhythmia is associated with hemodynamic collapse. Adenosine is the preferred drug in those patients in whom verapamil has failed or may cause adverse effects, such as those with heart failure or wide-complex tachycardia. The safety profile of adenosine suggests that it should be the drug of first choice for the treatment of supraventricular tachycardia, but only limited comparative data to support this view are available at present.

Prospective evaluation of day-to-day reproducibility of upright tilt table testing in unexplained syncope

To evaluate the day-to-day reproducibility of upright tilt-table testing, 109 patients with unexplained syncope prospectively underwent testing on 2 consecutive days using a uniform protocol. Results of testing on 2 separate days were concordant in 69 of 109 patients (63%), and discordant in 40 of 109 patients (37%). Thirty-six of 109 patients (33%) had vasodepressor syncope on 1 or both days of testing. Nineteen of 30 patients (63%) with vasodepressor responses on the first day did not reproduce this response during the second day of testing. An additional 6 patients with an initial negative tilt test had a vasodepressor response on the second day. Only 11 of 36 patients (31%) had reproducible vasodepressor responses on both days of testing. Patients with reproducible vasodepressor responses had a significantly higher mean number of preceding clinical syncopal events than patients with 2 normal tests (p < 0.02) or nonreproducible results (p < 0.04). In addition, these patients had a significantly longer duration of clinical symptoms relative to patients with 2 tests that yielded negative results (p < 0.008) and nonreproducible results (p < 0.01). The elapsed time between the most recent clinical event and the performance of tilt-table testing was not significantly different among the 3 groups, and did not appear to influence the outcome of testing. These data show that vasodepressor responses elicited by upright tilt-table testing show day-to-day variability in many patients, a finding that may limit the interpretation of initial and follow-up test results.

Implantation of transvenous nonthoracotomy cardioverter-defibrillator systems in patients with permanent endocardial pacemakers

Among 177 patients in whom a nonthoracotomy approach was initially used to implant a cardioverter-defibrillator system, 11 (6%) patients also received a separately implanted permanent pacemaker. The main problem encountered in these patients were previously implanted unipolar pacemakers (n = 3) and ventricular pacing leads positioned at the right ventricular apex, the latter interfering with optimal placement of the tripolar implantable cardioverter-defibrillator (ICD) lead (n = 9). The approaches used to solve these problems were individualized and included placement of the ICD sensing lead at the right ventricular outflow tract (n = 3), initial placement (n = 1) or subsequent repositioning (n = 2) of the right ventricular pacing lead at the outflow tract, upgrade from unipolar to bipolar systems (n = 2), reprogramming from the DDD to AAI mode (n = 2), inactivation of the pacemaker (n = 1), and simultaneous placement of a single-chamber atrial pacemaker with the ICD lead (n = 2). These revisions fulfilled the pacing needs in each patient and prevented unfavorable sensing interaction between the two systems.

Asystole after exercise in healthy persons

Exercise-related syncope is infrequent in healthy persons, although vasodepressor syncope reproduced by positive head-up tilt testing has been reported in small series of healthy persons [1] and athletes [2] with syncope after exercise. Whether vasodepressor syncope may also occur during exercise is controversial and is now an issue of public debate [3]. Asystole after exercise is an extremely rare finding in healthy persons, and single cases without clear proof of the underlying mechanisms have been reported during the past 20 years [4-7]. We describe three patients with recurrent exercise-related syncope in whom prolonged asystole after exercise was documented. Positive head-up tilt table testing in all three patients suggested neurocardiogenic syncope as the underlying mechanism. Case Reports Patient 1 A 34-year-old man had atypical chest pain and a history of multiple episodes of syncope and presyncope, all related to physical stress. Two syncopal episodes occurred immediately after weight lifting. Submaximal exercise test results did not indicate ischemia. However, 1.5 minutes into recovery, the patient developed sudden asystole (lasting for 32 seconds) with rare ventricular escape beats (Figure 1). This resulted in respiratory arrest, and chest massage was initiated by the supervising physician; the patient recovered just before being intubated. Fifteen months later, he had another syncopal episode while walking into the bathroom at night. A chest radiograph, a 12-lead electrocardiogram, 24-hour Holter monitoring, and an echocardiogram all yielded normal test results. Head-up tilt testing was done, and, after 4 minutes in the upright position, the patient became abruptly asystolic for 23 seconds without previous symptoms or hypotension (blood pressure before asystole, 123/92 mm Hg; heart rate, 92 beats per minute). He lost consciousness and made a slow recovery after returning to the supine position. With avoidance of strenuous exercise, the patient has remained free of syncope without drug or pacemaker therapy during 9 months of follow-up surveillance. Figure 1. The rhythm strip starts 1. Patient 2 A 22-year-old man had four episodes of syncope in a 1-year period, all occurring during or immediately after playing basketball. During warm-up before a game, he had a syncopal spell while standing still after running. He reported several similar episodes that he shortened by lying supine. Echocardiography showed moderate concentric left ventricular hypertrophy without evidence of outflow tract obstruction and showed a left ventricular ejection fraction of 75%. The surface electrocardiogram was consistent with left ventricular hypertrophy, but arterial blood pressure measurements were repeatedly normal. One minute after maximal exercise testing, he developed a sudden onset of bradycardia associated with near syncope, and several 4- to 6-second periods of asystole were documented followed by sinus bradycardia with first-degree atrioventricular block. Thallium imaging results were normal. The results of a comprehensive electrophysiologic study were also normal. Ten minutes into head-up tilt table testing, the patient had vasodepressor syncope (systolic blood pressure, 60 mm Hg) accompanied by mild bradycardia (43 beats per minute). A repeated exercise test, with a scopolamine patch in place, showed normal results. Scopolamine was prescribed but was subsequently discontinued because of side effects. The patient has taken oral disopyramide for 38 months and has had an uneventful course during this time; he continues to play basketball. Patient 3 A 35-year-old man had two presyncopal episodes, one immediately after strenuous exercise and the second after fighting a fire. His clinical evaluation was unremarkable. Echocardiographic results showed mild mitral valve prolapse without mitral regurgitation and showed normal left ventricular function. Exercise radionuclide ventriculographic results were normal. Eight minutes into recovery, while seated, the patient had sudden asystole for 15 seconds with a brief loss of consciousness followed by a slow sinus recovery at a rate of 10 to 20 beats per minute. Respiratory arrest occurred, but cardiac and respiratory function returned spontaneously. Comprehensive electrophysiologic study results were entirely normal. Head-up tilt table testing at baseline was unremarkable, but repeated testing using intravenous isoproterenol (0.025 g/kg per minute) provoked vasodepressor syncope (blood pressure, 80/60 mm Hg) with relative bradycardia (heart rate decrease from 120 to 64 beats per minute) after 15 minutes in the upright position. The patient started receiving atenolol (25 mg per day); repeated head-up tilt test and exercise test results (maximal heart rate, 148 beats per minute; Bruce stage 8) were normal. While receiving atenolol, the patient has remained free of recurrent syncope after 9 months of follow-up. Discussion Single cases of asystole after exercise have been described previously, but the underlying mechanisms have been uncertain [4-7]. Our findings of positive head-up tilt test results in all three patients suggest that a variant of neurocardiogenic syncope may be one mechanism of asystole after exercise, but additional abnormalities in the autonomic control of the cardiovascular system seem to be involved. Blood pressure control at rest and also in response to changing posture is mainly regulated through the baroreceptor reflex [8]. The response to exercise involves additional mechanisms [9] (such as increased sympathetic activity) that have been partly ascribed to the so-called metaboreflex activated by metabolites from ischemic muscles [10, 11]. After exercise, the heart rate decreases to baseline, although the blood pressure remains increased, despite continuing activation of this reflex by ongoing muscle ischemia. This phenomenon has been attributed to an exercise-induced up-regulation of the parasympathetic efferent tone, which, in the period after exercise, selectively depresses the heart rate without affecting the vascular bed and blood pressure [9, 11]. The mechanisms provoking neurocardiogenic syncope are probably initiated by a progressive decrease in venous return in the upright position, which is responsible for maximal stimulation of the sympathetic system. Echocardiographic studies have documented a progressive decrease in end-diastolic and end-systolic volumes during head-up tilt table testing, with a maximal increase in fractional shortening before syncope [12]. The strong sympathetic drive in the setting of a relatively empty heart leads to vigorous myocardial contraction, which, in susceptible persons, activates mechanoreceptors in the left ventricular wall (C-fibers) and causes a profound response of the afferent vagal nerve [13]. This vagal stimulus may trigger a sudden withdrawal of the neural efferent sympathetic activity (negative feedback loop) and may increase the efferent parasympathetic tone with subsequent vasodilation and progressive hypotension [14]. Because arterial hypotension usually precedes bradycardia, inactivation of the sympathetic efferent tone and consequent vasodilation may be the primary mechanism of syncope [15]. Bradycardia and asystole, as markers of the increased parasympathetic tone, play only a secondary role in most patients with vasodepressor syncope. This view is further supported by the fact that, in most patients, hypotension and syncope cannot be avoided by atrioventricular sequential pacing [15]. Infrequently, however, cardioinhibition leading to profound bradycardia or asystole may be the dominant mechanism responsible for symptoms. In our patients, syncope and asystole typically occurred in the recovery period of exercise, when venous return was diminished (sitting position). The findings of positive results from head-up tilt testing suggest that all three patients had a low threshold to trigger an abnormal afferent parasympathetic response to decreased venous return, suggesting that venous pooling after exercise may have been one of the mechanisms triggering their asystole. However, the long latency between maximal activation of the mechanoreceptors (peak exercise) and the onset of syncope during late recovery in one of our patients (8 minutes after exercise) and in another of the previously reported patients (10 minutes after exercise) suggests that other mechanisms, such as inappropriate control of the sympathetic tone after exercise (for example, diminished sympathetic response to muscle ischemia after exercise), may play an additional role in some patients. Based on these patients and the current understanding of neurocardiogenic syncope, it appears that asystole after exercise in otherwise healthy persons may represent a variant of this syndrome, in which the effect of increased efferent parasympathetic tone predominates over the effect of sympathetic withdrawal. The optimal management of patients with vasodepressor syncope is unknown. In theory, if initiation of the vasodepressor reflex can be prevented, the hypotension and bradycardia that follow its activation should be eliminated. Accordingly, therapy is generally directed at the underlying mechanisms rather than at the outcome. Although several drugs (including -blockers [16], disopyramide [17], and scopolamine [18]) have been used, no consensus exists about whether drug therapy or implantation of pacemakers is beneficial in treating patients with this condition [19].

Three-year outcome of a nonthoracotomy approach to cardioverter-defibrillator implantation in 189 consecutive patients

To date, no long-term clinical data have been published in patients undergoing a nonthoracotomy approach to cardioverter-defibrillator system implantation. In the present report, 189 consecutive patients prospectively underwent a standardized approach to cardioverter-defibrillator system implantation in which the nonthoracotomy configurations were tested first. If satisfactory defibrillation thresholds were not obtained, thoracotomy was performed during the same intraoperative session. A nonthoracotomy system was successfully implanted in 149 of 189 patients (79%), with a higher success rate (90%) observed in patients who had more recent implantations. The overall rate of complications associated with these systems was low (11%). Over a mean follow-up of 12.5 +/- 9.3 months, 17 patients (9%) died. Three-year total, cardiac, and sudden death-free actuarial survival for all patients was 83 +/- 11%, 88 +/- 7%, and 94 +/- 2%, respectively. Three-year sudden death-free actuarial survival was higher in the nonthoracotomy than in the thoracotomy patients (97 +/- 2% vs 87 +/- 6%, p = 0.047), although total survival was similar (77 +/- 11% vs 83 +/- 7%, p = 0.77). These data suggest that a majority of patients (> 80%) requiring a cardioverter-defibrillator system can undergo implantation using a nonthoracotomy approach. Patients receiving nonthoracotomy systems have 3-year outcomes comparable to those implanted via thoracotomy. If these results are maintained, a nonthoracotomy approach will supplant thoracotomy-implanted systems as the preferred method because of the simpler implant procedure and lower overall cost involved.

Electrophysiologic Response to Moricizine in Patients with Sustained Ventricular Arrhythmias

OBJECTIVE To assess the short-term efficacy and safety of moricizine in patients receiving electrophysiologically guided therapy for sustained ventricular arrhythmias refractory to treatment with class IA antiarrhythmic agents. DESIGN Uncontrolled clinical trial. SETTING Referral-based teaching medical center. PATIENTS Twenty-one patients (18 of whom had coronary artery disease) with a mean left ventricular ejection fraction of 32% +/- 11% who presented with sustained ventricular tachycardia (13 patients), syncope (4 patients), or cardiac arrest (4 patients). INTERVENTIONS Moricizine, 743 +/- 85 mg daily. MEASUREMENTS Electrophysiologic testing in the drug-free state and after administration of moricizine unless sustained arrhythmias occurred. MAIN RESULTS Sustained ventricular tachycardia was inducible in the absence of antiarrhythmic drugs in 20 patients and was not suppressed by moricizine in any patient. Four patients had six episodes of spontaneous ventricular tachycardia while receiving moricizine. A probable proarrhythmic response occurred in four patients. CONCLUSION In patients with compromised left ventricular function caused by coronary artery disease in whom class IA antiarrhythmics were ineffective, moricizine was ineffective in suppressing sustained ventricular arrhythmias and resulted in proarrhythmic effects in some patients.

Successful implantation of cardiovascular-defibrillator systems in patients with elevated defibrillation thresholds

OBJECTIVES . The purpose of this study was to conduct a retrospective analysis of 16 patients with high initial defibrillation thresholds in whom a three-electrode system was used to lower defibrillation thresholds and permit implantation of a cardioverter-defibrillator system. BACKGROUND Patients with high defibrillation thresholds (> 25 J) are uncommon but may be problematic to physicians implanting cardioverter-defibrillator systems. Most conventional systems use two defibrillating electrodes, most commonly two epicardial patches. When defibrillation thresholds remain elevated despite extensive testing of a two-electrode system, a third electrode can be incorporated and tested. However, few published data exist on the use of a three-electrode system in patients with high defibrillation thresholds. METHODS After failure to achieve satisfactory defibrillation thresholds < 25 J with a two-patch electrode system, a third electrode was incorporated and tested. In all cases, two electrodes were joined to form a common cathode or anode, while a single electrode was used as the opposite polarity electrode. Various three-electrode configurations were then tested. RESULTS In all 16 patients, satisfactory defibrillation thresholds were achieved and a cardioverter-defibrillator was implanted (95% confidence interval [CI] = 0% to 21%). The mean final defibrillation threshold using the revised three-electrode system was 19.5 +/- 3.7 J (p < 0.0001). A mean of 6 +/- 3 electrode configurations/patient were tested before the final configuration was selected. A total of nine different electrode configurations were used in the 16 study patients; the most common of these incorporated left and right ventricular patches as combined cathode and a superior vena cava coil (n = 5) or right atrial patch electrode (n = 3) as single anode. CONCLUSION Patients with high initial defibrillation thresholds can generally undergo successful cardioverter-defibrillator implantation with a three-electrode system if enough electrode configurations are tested after a third electrode is incorporated.

Electrocardiographic pseudo-infarct patterns after implantation of cardioverter-defibrillators

Postoperative electrocardiographic (ECG) changes are frequently present after insertion of implantable cardioverter-defibrillators (ICD) and may mimic perioperative myocardial infarction (MI). The purpose of this study was to assess the incidence and clinical significance of postoperative ECG changes in relation to clinical, laboratory, and implantation data. In 25 (16%) of 156 patients undergoing ICD implantation, significant ECG changes (> or = 50% reduction in R-wave amplitude in > or = 3 leads or new Q waves in > or = 2 leads) were present 1 to 3 days after the operation and persisted at hospital discharge in 12 (8%). Presence of thoracotomy, the total number of induced ventricular fibrillation episodes, and the number of defibrillation shocks required during defibrillation threshold (DFT) testing correlated with postoperative ECG changes. Other factors associated with a significant R-wave loss in the lateral precordial leads included left-sided pleural effusion, lung infiltrates or atelectasis, and large defibrillator patch electrodes over the left ventricle or the lateral chest wall. Myocardial necrosis documented by elevated cardiac enzymes occurred in 6 (5%) of 151 patients without significant ECG changes and in 3 (12%) with (p value not significant). However, postoperative ECG changes associated with elevated enzymes were indistinguishable from changes unrelated to necrosis. Therefore the sensitivity and specificity of the surface ECG for detection of MI after ICD placement is poor. Multiple factors such as thoracotomy, myocardial injury from DFT testing, electric insulation, or shielding of the heart may contribute to the development of electrocardiographic pseudo-infarct patterns.

Efficacy of a tiered therapy defibrillator system used to treat recurrent ventricular arrhythmias refractory to drugs.

OBJECTIVE--To evaluate an implantable tiered therapy defibrillator system that delivered antitachycardia pacing treatment for slower well tolerated ventricular tachycardias and cardioversion or defibrillation for fast tachycardias or ventricular fibrillation. METHODS--A tiered treatment device (Ventritex Cadence V-100) was implanted in 30 patients with ventricular tachycardia that was refractory to drugs. Efficacy was evaluated by the responses of induced or spontaneous arrhythmias to the treatments delivered. RESULTS--Antitachycardia pacing successfully terminated 80% of episodes of ventricular tachycardia induced by non-invasive programmed stimulation, but acceleration was brought about by pacing in six patients in 10% of episodes. During a follow up of two to 17 (mean seven) months, 18 patients (60%) had recurrence of ventricular arrhythmias. Antitachycardia pacing terminated ventricular tachycardia in 17 of 18 patients in 87% of episodes. Twelve patients received shocks for ventricular tachycardia or fibrillation. Failure of pacing, with subsequent cardioversion, occurred in nine patients (50%) in one or more episodes. Acceleration of tachycardia by pacing occurred in 10 patients in 5% of episodes. Only two of these patients had experienced acceleration of previously induced arrhythmia. Five patients had spontaneous fast ventricular tachycardia or fibrillation treated by cardioversion or defibrillation. Spurious treatment was delivered in nine patients (30%), during atrial fibrillation in five, sinus tachycardia in two, and because of fracture of the sensing lead system in two patients. The retrieval of stored intracardiac electrograms was of clinical value in assessing spurious treatment. CONCLUSIONS--Tiered treatment was effective in terminating recurrent ventricular arrhythmias in these selected patients. Most episodes were treated successfully by pacing, and resistant tachycardias, pacing induced acceleration, or haemodynamically compromising arrhythmias were treated by shocks.