Heart Rhythm 2007 Late Breaking Clinical Trials II Abstracts FOR IMMEDIATE RELEASE
Contact: Ann-Marie White
Heart Rhythm Society
202-464-3476
awhite@hrsonline.org
DENVER — The following Late Breaking Clinical Trials Abstracts were presented on Friday, May 11 from 8:00 a.m. – 9:30 a.m., Wells Fargo Theatre 1, Denver Convention Center as a part of HeartRhythm 2007:
8:00 a.m. — “Randomized Controlled Trial of Rhythm vs. Rate Control Strategy in Japanese Patients with Paroxysmal and Persistent Atrial Fibrillation (J-RHYTHM Study)”
Background: J-RHYTHM study is a randomized multi-center comparative evaluation of pharmacological rate vs. rhythm control strategy, both combined with continued antithrombotic therapy, in the separate groups of paroxysmal and persistent atrial fibrillation (AF). The primary endpoint was the composite of total mortality, symptomatic cerebral infarction, systemic embolism, major bleeding, hospitalization for heart failure, or physical and psychological disablement requiring discontinuation of the assigned strategy.
Results: In paroxysmal and persistent AF, 819 and 163 patients were enrolled, respectively, and were followed up for a mean period of 586 days. During the study, sinus rhythm was maintained more frequently in the rhythm control group both in paroxysmal and persistent AF. Rhythm control strategy showed significantly better event-free survival than rate control in paroxysmal AF, while there were no differences between the two strategies in persistent AF. Although total mortality and hospitalization for embolism, bleeding and heart failure were not different between the two strategies both in paroxysmal and persistent AF, AF-specific quality of life (QOL) score was significantly higher in rhythm control than in rate control group only in paroxysmal AF, leading to reduced occurrences of the primary endpoint.
Conclusions: For paroxysmal AF, pharmacological rhythm control strategy could be more useful than rate control strategy, when patients' QOL is considered.
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8:15 a.m.— “The IntraCardiac Echocardiography Guided Cardioversion Helps Interventional Procedures (ICE-CHIP) Trial”
Background: The study hypothesis is that ICE has comparable efficacy to TEE in visualization of septal and left atrial pathology that can predispose patients to stroke. The primary objective was to determine if ICE has comparable efficacy to TEE in the visualization of detect septal and left atrial pathology that can predispose patients to stroke. Secondary outcome measures were analyzed to characterize the quality of the ICE imaging modality. Recordings from both imaging methods were analyzed in an independent and blinded manner at a core laboratory by two observers.
Methods: The patients were imaged by TEE and ICE and a blinded comparison of the two imaging modalities were performed. One hundred patients with atrial fibrillation were enrolled in six European and U.S. centers. Patients included in the study were undergoing an invasive catheterization procedure including right heart catheterization and had undergone a trans-esophageal echocardiogram within the previous 48 hours.
Results: Ninety-five patients completed the study procedures at the six European and U.S. centers. Their mean age was approximately 58 years. There were 80 men and 15 women, with an AF duration of >6 months in 91% of patients. The primary endpoints in the study are: 1) left atrial imaging for spontaneous echo contrast and thrombus, 2) left atrial appendage imaging for spontaneous echo contrast and thrombus, 3) interatrial septal imaging for aneurysms, septal defects, and patent foramen ovale, and 4) aortic plaques in ascending and descending aorta. Comparative and concordance analyses of the two imaging techniques will be presented.
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8:30 a.m.— “Episodic versus Continuous Amiodarone Therapy for Prevention of Permanent Atrial Fibrillation”
Background: Amiodarone is the most powerful antiarrhythmic drug in maintaining sinus rhythm in persistent atrial fibrillation (AF), but causes many adverse events. The aim was to show that episodic amiodarone therapy (EAT) pericardioversion (CV) is associated with a lower morbidity and a higher quality of life compared to continuous AT (CAT) while AF is still effectively suppressed, although at the costs of more CVs.
Methods: 206 patients with recurrent AF were loaded with 600mg amiodarone daily for four weeks followed by 200mg daily. EAT randomized patients discontinued amiodarone one month post-cardioversion, and restarted amiodarone pericardioversion if AF relapsed. CAT patients continued amiodarone. The primary endpoint was a composite of amiodarone and underlying disease associated adverse events.
Results: After a median follow up of 1.8 years, 68% versus 75% of EAT versus CAT patients had sinus rhythm. More AF recurrences and CVs (70% versus 39%, respectively) occurred in EAT patients. The incidence of the primary endpoint was similar (28 [27%] in EAT versus 20 [20%] in CAT group, incidence rate/100 person years 21.5 versus 16.7, difference 4.9 [CI -6.0 to 15.7]). Also, amiodarone related events were comparable (15 [15 %] versus 17 [17%], incidence rate/ 100 person years 10.6 versus 14.0, difference -3.4 [CI -11.9 to 5.2]). Thyroid dysfunction and cardiovascular events occurred most often, at similar rates in both groups (9% versus 7% and 5% versus 3%, respectively). Hepatic and pulmonary complications did not happen. Dermatological (1%), gastrointestinal (1%) and neurological events (3%) were only observed in CAT patients. More disease related events occurred in EAT patients (13 [13%] versus 3 [3%], incidence rate/ 100 person years 9.1 versus 2.2, difference 6.9, [CI 1.4 to 12.5], due to more heart failure (3% versus 0%), bleeding (5% versus 1%) and stroke (2% versus 0%). Quality of life was similar.
Conclusion: Episodic amiodarone therapy has no advantage over continuous amiodarone therapy since it does not lower adverse event rates and is thus not an option for improving rhythm-control therapy.
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8:45 a.m. — “Randomized Multicenter Controlled Trial of Electroanatomical Circumferential Pulmonary Vein Ablation vs. Pulmonary Vein Antrum Isolation Guided by Intracardiac Echocardiography in Atrial Fibrillation”
Background: Thirty seven patients with symptomatic non-chronic atrial fibrillation (81% male, 84% paroxysmal AF, age about 55 years old, AF duration 9±8 years, left atrial size 35±13 mm) refractory to 2±1 antiarrhythmic drugs (AAD) were randomized to undergo electroanatomical circumferential pulmonary vein ablation (n=18) or pulmonary vein antrum isolation (PVAI) guided by a circular mapping catheter (CMC) and intracardiac echocardiography (ICE) (n=19) at three centers (2 in Canada, 1 in Europe) between December 2004 and May 2006. Ipsilateral veins were ablated enblock with endpoint of disappearance of potentials within the circular lesion in the CPVA arm, using the CARTO (Biosense Webster™) system.
Methods: Left atrial roof line and mitral isthmus line were ablated without verification of block. For those in AF post CPVA, or with AF induced with up to five 15s stimuli trains at minimum 1:1 atrial capture CL delivered at 30s intervals, complex fractionated electrograms (CFAE) defined according to published criteria were mapped and ablated in the left atrium, right atrium and the coronary sinus to endpoint of AF termination or disappearance of CFAE. Irrigated or 8mm tip radiofrequency (RF) ablation catheters were used. Esophageal temperature was monitored and kept within 2°C of baseline or under 39°C. Patients were followed for a median of 6 months with routine and symptom-driven ambulatory monitoring. No redo ablations were done during this time period. Success was defined as absence of symptomatic or asymptomatic atrial fibrillation or flutter off AAD after a 3 month blanking period.
Results: There was no difference between CPVA and PVAI w/re to baseline variables, catheter used, duration of the procedure or RF delivery. Fluoroscopy time was significantly shorter with CPVA (60+/-19min vs. 83+/-16min. No significant complications occurred in either arm. PVAI was more likely to achieve freedom from AF off AAD (47% vs17%).
Conclusions: A single PVAI procedure is more likely to result in freedom from AF off AAD than CPVA.
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9:00 a.m.— “The Search AV Extension and Managed Ventricular Pacing for Promoting Atrioventricular Conduction (SAVE PACE) Trial”
Background: Conventional dual chamber pacing (DDDR) maintains atrioventricular (AV) synchrony but results in a high percentage of right ventricular pacing, which causes ventricular desynchronization and has been linked to increased risk of atrial fibrillation (AF) in sinus node dysfunction (SND).
Methods: 1,065 patients with SND, intact AV conduction and normal QRS duration were randomized to DDDR (N=535) or dual chamber minimal ventricular pacing (N=530) using new algorithms designed to prioritize intrinsic AV conduction, preserve ventricular conduction and prevent ventricular desynchronization. The primary endpoint was time to development of persistent AF.
Results: Mean age was 72 ± 12 years, 51% were female, ejection fraction was 58 ± 10%, 42% received b-blockers and 16% received Class III antiarrhythmic drugs for AF. Mean follow-up was 1.7 ± 1.0 years when the trial was stopped by the Data Monitoring Committee for meeting the primary endpoint. Median percent ventricular pacing was significantly less in the dual chamber minimal ventricular pacing vs. DDDR (9.1% vs. 99%, p < 0.001) whereas atrial pacing was similar (71.4% vs. 70.4%, p = 0.96). A total of 110 patients developed persistent AF: 68 in DDDR vs. 42 in dual chamber minimal ventricular pacing. After adjusting for baseline characteristics and predictors of AF, the hazard ratio for development of persistent AF in DDDR vs. dual chamber minimal ventricular pacing group was 1.71 (95% CI [1.16, 2.52]; p = 0.0064) (Figure). Mortality was similar between treatment groups (2.7% dual chamber minimal ventricular pacing vs. 2.4% DDDR; p = 0.54).
Conclusions: This is the first prospective study to demonstrate that prevention of ventricular desynchronization using new dual chamber minimal ventricular pacing algorithms reduced the risk of developing persistent AF compared to DDDR for SND.
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9:15 a.m.— “Multidisciplinary Study of ARVD”
Background: 118 probands and 123 family members have been enrolled. Data has been analyzed on 108 probands. 57% are male; 85% are Caucasian. Age at diagnosis ranged from 12 to 64 years, 9 diagnosed before the age of 18. The mean age of earliest onset of symptoms was about 36 years of age. The average time from onset of symptoms to first hospitalization was 1.6 years. There was a history of ventricular tachycardia in 65%. Palpitations were the most common symptom, present in 53% of enrolled patients, followed in frequency by dizziness in 26 % and syncope in 19%. Thirteen percent had chest pain. Twenty percent had a family history of ARVD either with or without a family history of sudden death in a family member. Thirty-two percent of the probands participated in competitive or professional sports prior to diagnosis, 65% were male. Forty-two additional subjects were active in sports. Seventeen probands had a positive family history of sudden death below the age of 35.
Results: Ventricular tachycardia was inducible in 40 (59%). Thirty had VT induced at the RV apex and 10 had VT induced at the RVOT. Seven had VT induced at both sites. Eighty-one (70%) have ICDs implanted. Right ventricular free wall biopsies were done in 59%. ARVD is a disease of the desmosomes. Mutations were found in 21 probands: 16 plakophilin, 4 plakoglobin and one desmoplakin. Genetic analysis is ongoing. This is the first study of a large number of newly diagnosed patients, suspected of having ARVD, who were studied systematically with a variety of standardized diagnostic tests which included a 12 lead ECG, signal averaged ECG, and 24 hour Holter monitor. Imaging studies consisted of a 2D echocardiogram, cardiac magnetic resonance imaging and right ventricular angiogram. All the tests were interpreted blindly by experts in Core laboratories. An unexpected finding was the high rate of difference in classification by the core laboratories of the right ventricular images by echocardiogram, MRI and angiography as affected, borderline or unaffected. This may be due, in part, to the fact that local or regional abnormalities in the right ventricular structure and function are subjective, that the right ventricle is an irregularly shaped structure, and the extent of regional wall motion change during systole is not uniform.
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About the Heart Rhythm Society
The Heart Rhythm Society is the international leader in science, education and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education and optimal health care policies and standards. Incorporated in 1979 and based in Washington, DC, it has a membership of over 4,000 heart rhythm professionals in more than 60 countries around the world.
