Adenosine 5'-Triphosphate Test in the Management of Patients With Syncope.

The response to adenosine 5'-triphosphate (ATP) identifies patients with syncope who might benefit from pacemaker therapy (ATP test). Two measures have been used to determine the outcome of the ATP test, which have lead to contrasting conclusions regarding its utility: (1) the duration of cardiac pause (CP) mainly due to AV block and (2) the longest RR interval (RRmax). We tested the hypothesis that the discrepancy regarding the utility of the ATP test is mainly because of the different way the 2 measures determine the outcome of the test. Post hoc analysis was applied to data obtained from patients with syncope (n = 33) with a positive and negative ATP test based on the CP duration and RRmax, respectively, subjected to pacemaker therapy. In 19 and 14 patients, the pacemaker was programmed to function as AAI pacing at 30 ppm (control) and as DDD pacing at 70 ppm, respectively. During the follow-up period of 17.0 ± 8.6 months, syncope recurred in only 1 of the 14 patients with DDD pacing; in contrast, 10 of 19 patients with AAI30 pacing experienced syncope within the first 5.3 ± 5.2 months of follow-up (P < 0.009; recurrence rate). The ATP test, the outcome of which is determined by the CP measure, is a useful diagnostic test for the identification of patients with bradycardic syncope who may benefit from pacemaker therapy; the identification of such patients would be missed when the RRmax measure is used to determine the outcome of the test. The efficacy of DDD pacing suggests that atrioventricular nodal conduction block is the primary cause of syncope in patients with a positive ATP test based on the CP measure.

Treatment of unexplained syncope: a multicenter, randomized trial of cardiac pacing guided by adenosine 5'-triphosphate testing.

BACKGROUND: The origin of 40% of syncope cases remains unknown even after a complete diagnostic workup. Previous studies have suggested that ATP testing has value in selecting successful therapy. This patient-blinded, multicenter, randomized superiority trial tested whether, in patients with syncope of unknown origin, selecting cardiac pacing in those with a positive ATP test leads to fewer recurrences than those who do not receive pacing. METHODS AND RESULTS: From 2000 to 2005, 80 consenting patients (mean age, 75.9±7.7 years; 81% women; 56% without diagnosed structural heart disease) with syncope of unknown origin and atrioventricular or sinoatrial block lasting >10 seconds (average, 17.9±6.8 seconds) under ATP administration (20-mg IV bolus) were recruited from 10 hospitals, implanted with programmable pacemakers, and randomized to either active pacing (dual-chamber pacing at 70 bpm) or backup pacing (atrial pacing at 30 bpm). Patients were followed up regularly for up to 5 years for any syncope recurrence, the primary outcome. Mean follow-up was 16 months. Syncope recurred in 8 of 39 patients (21%) randomized to active pacing and in 27 of 41 (66%) randomized to backup pacing (control), yielding a hazard ratio of 0.25 (95% confidence interval, 0.12-0.56). After recurrence, the 27 recurrent control patients were reprogrammed to active pacing, and only 1 reported subsequent syncope. CONCLUSION: This study suggests that, in elderly patients with syncope of unknown origin and positive ATP tests, active dual-chamber pacing reduces syncope recurrence risk by 75% (95% confidence interval, 44-88). CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com/ISRCTN00029383. Unique identifier: ISRCTN00029383.

ATPace™: injectable adenosine 5'-triphosphate : Diagnostic and therapeutic indications.

ATPace™, a novel injectable formulation of adenosine 5'-triphosphate (ATP), is developed by Cordex Pharma, Inc. (Cordex) as a diagnostic and therapeutic drug for the management of cardiac bradyarrhythmias. Extracellular ATP exerts multiple effects in various cell types by activating cell-surface receptors known as P2 receptors. In the heart, ATP suppresses the automaticity of cardiac pacemakers and atrioventricular (AV) nodal conduction via adenosine, the product of its degradation by ecto-enzymes, as well as by triggering a cardio-cardiac vagal reflex. ATP, given as a rapid intravenous bolus injection, has been used since the late 1940s as a highly effective and safe therapeutic agent for the acute termination of reentrant paroxysmal supraventricular tachycardia (PSVT) involving the AV node. In addition, preliminary studies have shown that ATP can also be used as a diagnostic agent for the identification of several cardiac disorders including sinus node dysfunction (sick sinus syndrome), dual AV nodal pathways, long QT syndrome, and bradycardic syncope. The US Food and Drug Administration has approved Cordex formulation for ATP as an Investigational New Drug and two pathways for its marketing approval; one therapeutic, i.e., acute termination of paroxysmal PSVT, and the other diagnostic, i.e., the identification of patients with bradycardic syncope who can benefit from pacemaker therapy. The scientific rationale for the development of ATPace™ is discussed.

Brady-tachy syndrome: rapid atrial pacing efficacy in preventing atrial fibrillation recurrence assessed by reliable electrograms: the prefib pilot study.

AIMS: Recent studies have tested different atrial pacing rates, modes, and sites for preventing atrial fibrillation (AF) recurrence. Present generation pacemakers offer reliable electrograms (EGMs) storage for optimizing the arrhythmia diagnosis. Based on these EGMs, the study objective was to assess the rate of AF recurrence at two different pacing rates. METHODS: Thirty patients suffering exclusively from symptomatic brady-tachy syndrome (BTS) resistant to > or =2 drugs, were implanted with a DDDR pacemaker. After a 5-days observation period, the DDD pacing rate was randomly programmed at 60 bpm (-15 bpm hysteresis) or at 80 bpm for 12 weeks. The two sequences were crossed over at the end of this fixed period or when earlier symptomatic AF recurred. Antiarrhythmics were maintained. Stored EGMs of > or =4 s duration identified all AF recurrence. RESULTS: Thirty patients (17 males, 77.2 +/- 8.1 years old) were included. One patient withdrew prematurely for severe heart failure associated with AF recurrence and rapid ventricular response. For the remainder of the 29 patients, fast atrial pacing neither provoked symptoms nor haemodynamic change. AF recurred in 16 patients paced at 60 (-15) bpm (mean time: 29 days; range 1-61) and in 9 patients paced at 80 bpm (mean time: 55 days; range 5-83) (P < 0.05). AF recurrence was asymptomatic in 50% of patients. CONCLUSIONS: These results confirm that rapid atrial pacing is 1) significantly effective for preventing AF recurrence in symptomatic BTS patients, and 2) haemodynamically well tolerated.