A randomized comparison of amiodarone and class IC antiarrhythmic drugs to treat atrial fibrillation in patients paced for sinus node disease: the Prevention Investigation and Treatment: A Group for Observation and Research on Atrial arrhythmias (PITAGORA) trial.

BACKGROUND: Rhythm control is an important goal in the treatment of recurrent atrial tachyarrhythmias (AT). The PITAGORA study was a randomized trial in patients paced for sinus node disease (SND), designed to test the noninferiority of class IC antiarrhythmic drugs (AADs) to amiodarone in terms of a primary end point composed of death, permanent AT, cardiovascular hospitalization, atrial cardioversion, or AAD change. METHODS: Randomization was stratified to assign 2 patients to amiodarone and 2 patients to class IC AADs: propafenone or flecainide. One hundred seventy-six patients (46% men, 72 +/- 8 years) were enrolled. Device diagnostics continuously monitored AT recurrences and duration. RESULTS: In a mean follow-up of 20 +/- 9 months, the primary end point occurred in 23 (30.7%) of 75 class IC patients and in 28 (40.0%) of 70 amiodarone patients. The absolute difference in the end point incidence (-9.3%; 95% CI between 3.7% and -22.3%) confirmed the noninferiority of class IC to amiodarone (P = .007). Kaplan-Meier 1-year freedom from AT episodes >10 minutes, 1 day, and 7 days was 40%, 73%, and 91% for amiodarone and 28%, 78%, and 86% for class IC AADs (P = nonsignificant). CONCLUSIONS: In patients paced for SND and suffering from AT, class IC AADs proved not to be inferior to amiodarone in terms of the primary composite end point described or end points which were differently composed of mortality, efficacy, or AAD side effects. The AADs studied also showed similar results in terms of symptoms, quality of life, and freedom from AT recurrences.

A randomized study to compare ramp versus burst antitachycardia pacing therapies to treat fast ventricular tachyarrhythmias in patients with implantable cardioverter defibrillators: the PITAGORA ICD trial.

BACKGROUND: In patients with implantable cardioverter-defibrillators (ICDs), antitachycardia pacing (ATP) is highly effective in terminating fast ventricular tachycardias (FVTs) and lowers the use of high-energy shocks, without increasing the risk of arrhythmia acceleration or syncope. METHODS AND RESULTS: The aim of the PITAGORA ICD trial was to randomly compare 2 ATP strategies (88% coupling interval burst versus 91% coupling interval ramp, both 8 pulses) in terms of ATP efficacy, arrhythmia acceleration, and syncope. Two hundred six ICD patients (83% male, 67+/-11 years) were enrolled. FVT episodes with cycle lengths between 240 and 320 ms were treated by 1 ATP sequence and, in the event of failure, by shocks. Over a median follow-up of 36 months, 829 spontaneous ventricular tachyarrhythmia episodes were detected in 79 patients. Episode review identified 595 episodes as true ventricular arrhythmias in 72 patients; devices classified 111 (18.7%) episodes as VF, 216 (36.3%) as FVT, and 268 (45.0%) as VT. Fifty-six patients had 214 treated FVT episodes-2 FVTs self-terminated before ATP release; 44 (79%) of these had at least 1 effective ATP intervention, and 34 (61%) were spared ICD shocks. Burst terminated 100 of 133 (75.2%) FVT episodes, whereas ramp terminated 44 of 81 (54.3%; P=0.015). Acceleration occurred in 9 of 214 (4.2%) FVT episodes treated: 6 episodes in 3 ramp patients and 3 episodes in 3 burst patients. Two patients-1 in each group-suffered 1 syncopal event associated to a nonterminated FVT episode. CONCLUSIONS: Burst is significantly more efficacious than ramp in terminating FVT episodes. As the first therapy for FVT episodes, ATP carries a low risk of acceleration or syncopal events.

Is a dual-sensor pacemaker appropriate in patients with sino-atrial disease? Results from the DUSISLOG study.

BACKGROUND: Rate-responsive pacemakers (PMs) are often supplied with accelerometer (XL) and minute ventilation (MV) sensors to provide a physiologic rate response according to patient needs. No information is available about the real benefit of dual-sensor rate-responsive pacing on the daily life of patients. METHODS: DUSISLOG (Dual Sensor vs Single Sensor comparison using patient activity LOGbook) is a two-arm prospective, randomized, multicenter study that enrolled 105 patients who received a rate-responsive PM (Insignia), Guidant Corp.). After 1 month of DDD pacing at 60 ppm lower rate, a single sensor (XL or MV, randomized) was activated for 3 months at the manufacturer's suggested nominal settings, followed by a 3-month period with dual sensors optimized with automatic response. During the last month of each period, the following data concerning patient physical activity were retrieved from PM diagnostics (Activity Log): mean percentage of physical activity, mean intensity of activity. Quality of life (QoL) scores and 6-minute walk test (WT) were also recorded. RESULTS: Single-sensor rate-responsive pacing resulted in symptomatic benefit equally with XL and MV sensors while no additional benefit was found using dual sensor. In a subgroup analysis, patients (17%) with marked chronotropic incompetence and with 0% atrial sensing received benefits from single sensor with an additional advantage from sensor (QoL: +21 +/- 14% P < 0.05; WT: +17 +/- 7% P < 0.02). CONCLUSION: In most patients with rate-responsive devices, a single sensor is sufficient to achieve a satisfactory rate response. A dual sensor combination and optimization provides an additional benefit only in a selected population with an advanced atrial chronotropic disease.

Design and rationale of a randomized study to compare amiodarone and Class IC anti-arrhythmic drugs in terms of atrial fibrillation treatment efficacy in patients paced for sinus node disease: the PITAGORA trial.

AIMS: Many sinus node disease (SND) patients suffer from atrial fibrillation (AF). Anti-arrhythmic drugs (AADs) are the therapeutic mainstay for AF prophylaxis. The PITAGORA trial has a multicentre, prospective, randomized, single blind design to compare amiodarone with Class IC AADs in patients who have an AF history and are paced for SND. METHODS AND RESULTS: Starting from January 2001, 176 patients received a Medtronic AT500 pacemaker. AADs were randomly assigned with a 3 : 2 ratio between Class III and Class IC. Randomization was stratified in order to assign two patients to amiodarone and one patient to sotalol every three Class III AAD patients. After a 5-month observational period, Ramp or Burst+ ATP therapies were enabled in a randomized way, maintained for 4 months, and then crossed over. Total follow-up period is 21 months. The primary long-term objective is to show the non-inferiority of IC AADs compared with amiodarone in terms of time to first occurrence of a composite endpoint (death, atrial cardioversion, hospitalizations due to AF or heart failure, or change of AADs). Data will be analysed on an intention-to-treat basis. The primary short-term objective is to compare Ramp vs. Burst+ efficacy in terminating atrial tachyarrhythmias treated by the device. Secondary endpoints are major clinical events, medication toxicity, symptoms, AF burden, and quality-of-life. CONCLUSION: Given the high morbidity and healthcare costs associated with AF, new therapeutic strategies are needed. The results of the PITAGORA trial may help in guiding AADs therapy and ATP programming in SND patients suffering from AF.