Clifford Garratt

Comparison of adenosine and verapamil for termination of paroxysmal junctional tachycardia

The effects of intravenous adenosine and intravenous verapamil on paroxysmal junctional tachycardia were compared in 20 patients undergoing invasive cardiac electrophysiologic study. In 13 patients the diagnosis was of a reentrant tachycardia using an extranodal accessory connection (atrioventricular [AV] reentrant tachycardia); 5 of these patients had overt preexcitation in sinus rhythm, 4 had concealed accessory connections and 4 had latent or intermittent preexcitation. In 7 patients the diagnosis was of an AV nodal reentrant tachycardia. Administration of adenosine resulted in termination of tachycardia in all 20 patients at a mean dose of 0.125 mg/kg (range 0.05 to 0.20). Although termination of tachycardia was frequently accompanied by atrial and ventricular premature complexes, no significant arrhythmias were observed after conversion. Administration of verapamil (0.145 mg/kg) resulted in termination of tachycardia in 19 of 20 patients but was followed by symptomatic arrhythmias in 2: preexcited atrial flutter in 1 patient and preexcited atrial tachycardia in another. Latent or intermittent preexcitation was unmasked in 4 of 4 patients immediately after termination of tachycardia by adenosine. Termination of tachycardia by verapamil revealed preexcitation in only 1 of these 4 patients. Analysis of results in terms of successful termination of tachycardia, absence of significant arrhythmias after conversion and unmasking of latent or intermittent preexcitation reveals that adenosine therapy was satisfactory in all 20 patients, whereas verapamil was satisfactory in only 14 of the 20 patients (p less than 0.05). All 6 of the patients with unsatisfactory responses to verapamil had AV reentrant tachycardia. These results suggest that adenosine has particular advantages over verapamil as acute treatment for patients presenting with an AV reentrant tachycardia.

Use of intravenous adenosine in sinus rhythm as a diagnostic test for latent preexcitation

In a proportion of patients with left free wall accessory connections, preexcitation is apparent only during atrial arrhythmias or atrial pacing (latent preexcitation). These patients may be at risk of a rapid ventricular response to atrial fibrillation despite the absence of preexcitation in sinus rhythm. The ability of intravenous adenosine to unmask latent preexcitation was evaluated in 22 patients with a history of documented supraventricular tachycardia and a normal electrocardiogram during sinus rhythm. Preexcitation was unmasked in response to adenosine in 4 patients: all 4 were shown to have latent preexcitation at electrophysiologic study. In 12 patients atrioventricular (AV) nodal conduction delay or block was induced without preexcitation after adenosine (first-degree AV block in 8, second-degree block in 4): at subsequent electrophysiologic study none of these patients was found to have latent preexcitation. Five patients had little or no PR prolongation in response to adenosine: of these, 2 were shown to have latent preexcitation at electrophysiologic study. Atrial fibrillation was induced in 1 patient and a narrow complex regular tachycardia in another after intravenous adenosine. Intravenous adenosine during sinus rhythm is capable of producing AV nodal conduction delay or block in 73% of patients with a history of supraventricular tachycardia: in these patients adenosine provides a diagnostic test that is both 100% sensitive and 100% specific for latent preexcitation. In those patients in whom adenosine does not produce AV conduction delay or block, further investigation is required to establish or refute the diagnosis of latent preexcitation.

Effects of intravenous adenosine on antegrade refractoriness of accessory atrioventricular connections.

Background Several groups have suggested the use of intravenous adenosine or adenosine triphosphate in the diagnosis of regular broad complex tachycardias. However, the short half-life of these agents has precluded assessment of their effects on refractoriness of accessory connections, and their safety in preexcited arrhythmias has not been demonstrated. Methods and Results We examined the effects of intravenous adenosine on accessory atrioventricular (AV) connections in 30 patients with the Wolff-Parkinson-White syndrome. Intravenous adenosine (12 mg, rapid bolus) was administered to 14 patients (group 1) during continuous atrial pacing at a cycle length 20 msec below that required to cause 2:1 conduction block in the accessory connection (mean pacing cycle length 261+41 msec). After adenosine, transient 1:1 conduction occurred via the accessory connection in 12 of 14 patients, indicating a shortening of antegrade refractoriness. In three of seven patients, this effect was abolished after intravenous propranolol (0.2 mg/kg). Nineteen patients (group 2) received adenosine (0.17 ± 0.04 mg/kg) during induced, preexcited atrial arrhythmias. The minimum RR interval during preexcited atrial fibrillation transiently decreased (252 ± 44 msec to 224 ± 35 msec, p< 0.01) after adenosine, but no change in average RR interval was observed (360 ± 59 msec to 357 ± 60 msec, NS). The preexcited ventricular response to atrial flutter was transiently accelerated in five of eight patients (415 ± 21 msec to 360 ± 49 msec, p< 0.05) due to shortening of flutter cycle length (207 ± 10 msec to 180 ± 24 msec, p< 0.05). However, 2:1 accessory connection conduction was maintained in all eight patients. All effects were short lived, with the decrease in RR interval during atrial fibrillation occurring for a maximum of two RR intervals only. No patient suffered ventricular arrhythmias or hemodynamic deterioration. Conclusions Adenosine shortens antegrade refractoriness of accessory AV connections, and in some patients this action is mediated by f3-adrenergic stimulation. Adenosine may cause acceleration of preexcited atrial arrhythmias, but these effects are transient and should not discourage the use of adenosine as a diagnostic agent in broad complex, regular tachycardias of uncertain origin.

Relative efficacy and safety of intravenous drugs for termination of sustained ventricular tachycardia

The relative safety and efficacy of intravenous administration of adenosine, lignocaine, disopyramide, flecainide, and sotalol for termination of stable, induced ventricular tachycardia was assessed in serial trials. Ventricular tachycardia was terminated by pacing if it persisted 10-15 min after the end of drug administration. 24 patients with recurrent ventricular tachycardia were studied. Ventricular tachycardia was terminated by a drug in 35 of 105 trials. In 6 patients no drug terminated the arrhythmia. Adenosine did not terminate tachycardia or have any serious adverse effect in any patient; both flecainide and disopyramide were significantly more effective than lignocaine, but flecainide had significantly more severe adverse effects than lignocaine. Lignocaine was the safest drug and should continue to be used as first-line drug therapy for stable ventricular tachycardia. Disopyramide should be considered as second-line treatment. DC cardioversion is necessary for unstable ventricular tachycardia, and its availability must be ensured before attempted pharmacological intervention.

MISUSE OF VERAPAMIL IN PRE-EXCITED ATRIAL FIBRILLATION

Of 18 patients who attended accident and emergency departments with pre-excited atrial fibrillation, 10 were inappropriately treated with intravenous verapamil. The reason for the inappropriate treatment was misdiagnosis of the arrhythmia, although diagnostic electrocardiograms were available for all patients: in only 3 of the 18 patients was the correct diagnosis made before intervention. Misdiagnosis occurred because of failure to consider pre-excitation as a possible diagnosis, rather than bias towards a single alternative arrhythmia. The use of intravenous verapamil was associated with deterioration in the clinical condition of 6 patients and continued arrhythmia in all 10.

A Comparison of Intravenous Propafenone and Flecainide in the Treatment of Tachycardias Associated with the Wolff-Parkinson-White Syndrome

We compared the electrophysiological effects of intravenous propafenone andflecainide on accessory pathway conduction by a randomized crossover study in 16 patients with Wolff‐Parkinson‐While syndrome. The antegrade refractory period of the pathway increased from 256 ± 18 msec at baseline to 288 ± 13 msec on propafenone (P < 0.05) find to 296 ± 2 7 msec on flecainide (P = 0.075). The minimum preexcited HR interval during atrial fibrillation or incremental atrial pacing was prolonged from 225 ± 37 msec to 262 ± 22 msec by propafenone (P < 0.05) and to 301 ± 31 msec by flecainide (P < 0.005). The prolongation was significantly greater with flecainide than propafenone (P < 0.05). Both drugs increased tachycardia cycle length (TCL) from 310 ± 35 msec to 354 ± 37 msec (propafenone P < 0.005) and to 352 ± 37 msec (flecainide P < 0.01). Both propafenone and flecainide blocked antegrade conduction in the pathway in five patients. Both drugs rendered atrial fibrillation noninducifale in seven patients and orthodromic tachycardia nonindudble in five patients. Conclusions: (1) Fiecainide causes a greater prolongation of minimum preexcited RR interval than propafenone; (2) There is no significant difference between propafenone and flecainide on the inducibility of arrhythmias, TCL, or incidence of antegrade conduction block.

The therapeutic and diagnostic cardiac electrophysiological uses of adenosine.

SummaryAdenosine is a purine nucleoside with a rapid onset and brief duration of action after intravenous bolus administration. Its most prominent cardiac effect is impairment or blockade of atrioventricular nodal conduction, but other effects are depression of automaticity of the sinus node and attenuation of catecholamine-related ventricular after-depolarizations. The cardiac cell surface receptor is the A1 purinoceptor. The therapeutic value of adenosine is predominantly in those arrhythmias in which the atrioventricular node forms part of a reentry circuit, as clearly demonstrated by the high success rate for termination of atrioventricular nodal reentry tachycardia and of atrioventricular reentry tachycardia involving an accessory pathway in the Wolff-Parkinson-White syndrome. Ventricular tachycardias are generally unresponsive, with the exception of right ventricular outflow tract tachycardia. A diagnostic role has emerged for adenosine. The transient blockade of the atrioventricular node that it causes can reveal important electrocardiographic features in arrhythmias, such as atrial flutter, or can unmask latent preexcitation. In wide-QRS tachycardias, adenosine can help to distinguish ventricular tachycardia from supraventricular tachycardia with QRS aberration. Unlike verapamil, adenosine is safe in ventricular tachycardia. A suggested dosing scheme is to give incremental doses at 1-minute intervals, starting at 0.05 mg/kg and continuing until complete atrioventricular block is induced or a maximum of 0.25 mg/kg is reached. Side effects are transient, sometimes uncomfortable, and not hazardous; dyspnea and chest discomfort are most frequent. A history of asthma is a relative contraindication. Aminophylline antagonizes and dipyridamole potentiates the effects of adenosine.

Closed Loop Control of Rate Adaptive Pacing: Clinical Assessment of a System Analyzing the Ventricular Depolarization Gradient

PAUL, V., et al.: Closed Loop Control of Rate Adaptive Pacing: Clinical Assessment of a System Analyzing the Ventricular Depolarization Gradient Closed loop control of rate adaptive pacing has theoretical advantages over current rate responsive pacemakers. The first available system (which senses the ventricular depolarization gradient) has been evaluated in ten patients. The pacing response to a variety of exercise and nonexercise stimuli was assessed. Response to isotonic exercise was prompt and proportional to the exertion involved while isometric exercise and mental stress produced obvious but more gradual increases in pacing rate. In seven patients, comparison between the intrinsic P wave and pacing rate showed a high correlation during exercise (r = 0.91) and mental activity (r = 0.87). Postural changes induced a paradoxical response. Closed loop rate responsive pacing based upon analysis of the ventricular depolarization gradient produces a fast and appropriate rate response to most physiological stimuli.

Effects of adenosine on atrial repolarization in the transplanted human heart

Abstract Adenosine is a naturally occurring purine metabolite that is widely used for the termination of junctional arrhythmias. Its cardiac actions are mediated by both a direct effect and a complex interaction with the autonomic nervous system. To assess the relative importance of these 2 actions in vivo, the effects of adenosine on atrial repolarization and atrioventricular (AV) conduction in the transplanted human heart were compared with those in normally innervated control subjects.