Comparison of AAIsafeR and DDD Modes in Non-selected Patients

Overview

1 Purpose In patients with sinus node dysfunction (SND), the use of AAI mode is rare. In paroxysmal high-degree or complete atrio-ventricular (AV) block, paroxysmal vagally-mediated bradycardia, single chamber atrial pacemakers are contraindicated although ventricular support is only rarely needed. As a result, these patients are usually exposed to an unnecessary high proportion of ventricular pacing due to the programming of the system to DDD mode for preventive safety reasons. This drains the pulse generator battery, and more importantly has long-term adverse effects on ventricular function in a subset of vulnerable patients, leading to left ventricular (LV) asynchrony, mitral regurgitation and increased left atrium (LA) size. The deleterious effects of right ventricular (RV) pacing, which increased heart failure (HF) morbidity/mortality, atrial fibrillation (AF) and related adverse events have been highlighted in several large clinical studies. Limiting RV pacing in non-dependant patients is therefore desirable. The Symphony DR 2550 cardiac pacemakers (SORIN Group, Montrouge, France) offer a new pacing mode that automatically switches from AAI(R) mode to DDD(R) or DDI(R) in event of severe atrioventricular conduction disorder, returning spontaneously to AAI(R) mode as soon as the spontaneous AV conduction has resumed. This particular mode is called the AAIsafeR2(R). The objective of this study is three-fold: to demonstrate that AAIsafeR2 mode (i) reduces the percentage of ventricular pacing in patients with a spontaneous AV conduction and (ii) prevents atrial arrhythmias by improving atrial hemodynamics and (iii) improves the long-term hemodynamic status of implanted patients in comparison to the "standard" DDD mode, set with long AV Delays (DDD Long AVD). The scientific soundness lying in this study is a proposal of an optimal programming of dual-chamber pacemakers (PM) with regard to the preservation of spontaneous AV conduction.

In patients with sinus node dysfunction (SND), the use of AAI mode is rare. In paroxysmal high-degree or complete atrio-ventricular (AV) block, paroxysmal vagally-mediated bradycardia, single chamber atrial pacemakers are contraindicated although ventricular support is only rarely needed. As a result, these patients are usually exposed to an unnecessary high proportion of ventricular pacing due to the programming of the system to DDD mode for preventive safety reasons. This drains the pulse generator battery, and more importantly has long-term adverse effects on ventricular function in a subset of vulnerable patients, leading to left ventricular (LV) asynchrony, mitral regurgitation and increased left atrium (LA) size. The deleterious effects of right ventricular (RV) pacing, which increased heart failure (HF) morbidity/mortality, atrial fibrillation (AF) and related adverse events have been highlighted in several large clinical studies. Limiting RV pacing in non-dependant patients is therefore desirable. The Symphony DR 2550 cardiac pacemakers (SORIN Group, Montrouge, France) offer a new pacing mode that automatically switches from AAI(R) mode to DDD(R) or DDI(R) in event of severe atrioventricular conduction disorder, returning spontaneously to AAI(R) mode as soon as the spontaneous AV conduction has resumed. This particular mode is called the AAIsafeR2(R). The objective of this study is three-fold: to demonstrate that AAIsafeR2 mode (i) reduces the percentage of ventricular pacing in patients with a spontaneous AV conduction and (ii) prevents atrial arrhythmias by improving atrial hemodynamics and (iii) improves the long-term hemodynamic status of implanted patients in comparison to the "standard" DDD mode, set with long AV Delays (DDD Long AVD). The scientific soundness lying in this study is a proposal of an optimal programming of dual-chamber pacemakers (PM) with regard to the preservation of spontaneous AV conduction. 2 Study devices Classification Name Manufacturer Name Cardiovascular permanent pacemaker pulse generator SORIN Group Symphony ™ DR2550 3 Summary of study objectives The aims of this study are to assess the clinical benefits resulting from AAIsafeR2 by comparison with standard dual chamber programming (DDD) with a long AV Delay. The benefits will be assessed by comparing the percentage of ventricular pacing, the incidence of atrial arrhythmias, and the evolution of the hemodynamic status as observed through echo parameter and ANP/BNP measurements. The primary objectives of the study are: to demonstrate the effectiveness of AAIsafeR2 to preserve natural AV conduction as compared to DDD Long AVD. For this purpose, ventricular pacing ratio as retrieved from PM memory will be assessed on a mid-term period (1 year) by inter-groups comparison of: * Mean V pacing (%) * Proportion of patients with a V pacing ratio \< 1 %. to demonstrate the effectiveness of AAIsafeR2 to reduce AF incidence on a long-term basis (3-year follow-up) by analyzing in the randomized branches: * the cumulative time in AF (as documented by PM memory) * the total number of AF episodes (as documented by PM memory) * the number of patients who present a cumulative time in AF\>30% of the follow-up period (as documented by PM memory) * the proportion of patients who turned into persistent AF during the study. * the proportion of patients who turned into permanent AF during the study. to compare the effects of AAISafeR2 vs. DDD Long AVD on LV function, mitral regurgitation and LA dimensions on a long-term basis (3-year follow-up) by comparing: * LV ejection fraction (EF) and volumes * Left atrium dimensions * Mitral regurgitation severity as measured by standard echocardiographic methods. The secondary objectives of this study are to report and compare the following in each randomized arm of the study: Total mortality CHF-related mortality and hospitalizations Evolution of systemic blood pressures, as estimated by ANP/BNP measurements AF-related adverse events, such as strokes/TIA's and cardioversions The evolution of cardiac asynchrony \[inter-ventricular (RV-LV) and intra-ventricular (4 segments), as assessed by TDI technics\] The evolution of conduction disturbances in patients presenting unknown or under estimated atrio-ventricular blocks on a long-term basis (intra-group analysis). Stratification by pacing indications and cardiopathies.