Background— The posterior left atrium (PLA) and pulmonary veins (PVs) have been shown to be critical for atrial fibrillation (AF) initiation. However, the detailed mechanisms of reentry and AF initiation by PV impulses are poorly understood. We hypothesized that PV impulses trigger reentry and AF by undergoing wavebreaks as a result of sink-to-source mismatch at specific PV-PLA transitions along the septopulmonary bundle, where there are changes in thickness and fiber direction. Methods and Results— In 7 Langendorff-perfused sheep hearts AF was initiated by a burst of 6 pulses (CL 80 to 150ms) delivered to the left inferior or right superior PV ostium 100 to 150 ms after the sinus impulse in the presence of 0.5 μmol/L acetylcholine. The exposed septal-PLA endocardial area was mapped with high spatio-temporal resolution (DI-4-ANEPPS, 1000-fr/s) during AF initiation. Isochronal maps for each paced beat preceding AF onset were constructed to localize areas of conduction delay and block. Phase movies allowed the determination of the wavebreak sites at the onset of AF. Thereafter, the PLA myocardial wall thickness was quantified by echocardiography, and the fiber direction in the optical field of view was determined after peeling off the endocardium. Finally, isochrone, phase and conduction velocity maps were superimposed on the corresponding anatomic pictures for each of the 28 episodes of AF initiation. The longest delays of the paced PV impulses, as well as the first wavebreak, occurred at those boundaries along the septopulmonary bundle that showed sharp changes in fiber direction and the largest and most abrupt increase in myocardial thickness. Conclusion— Waves propagating from the PVs into the PLA originating from a simulated PV tachycardia triggered reentry and vagally mediated AF by breaking at boundaries along the septopulmonary bundle where abrupt changes in thickness and fiber direction resulted in sink-to-source mismatch and low safety for propagation.

Atrial fibrillation is a highly prevalent cardiac arrhythmia and the most important cause of embolic stroke. Although genetic studies have identified an increasing assembly of AF-related genes, the impact of these genetic discoveries is yet to be realized. In addition, despite more than a century of research and speculation, the molecular and cellular mechanisms underlying AF have not been established, and therapy for AF, particularly persistent AF, remains suboptimal. Current antiarrhythmic drugs are associated with a significant rate of adverse events, particularly proarrhythmia, which may explain why many highly symptomatic AF patients are not receiving any rhythm control therapy. This review focuses on recent advances in AF research, including its epidemiology, genetics, and pathophysiological mechanisms. We then discuss the status of antiarrhythmic drug therapy for AF today, reviewing molecular mechanisms, and the possible clinical use of some of the new atrial-selective antifibrillatory agents, as well as drugs that target atrial remodeling, inflammation and fibrosis, which are being tested as upstream therapies to prevent AF perpetuation. Altogether, the objective is to highlight the magnitude and endemic dimension of AF, which requires a significant effort to develop new and effective antiarrhythmic drugs, but also improve AF prevention and treatment of risk factors that are associated with AF complications.

Background—: Atrioventricular (AV) block is one of the most frequent complications of CoreValve transcatheter aortic valve implantation (TAVI). The aim of this study was to analyze the effects of CoreValve implantation on AV conduction. Methods and Results—: Electrophysiological study was performed immediately before and after CoreValve implantation in 18 consecutive, permanent pacemaker-free patients. An electrode was placed on the His bundle during valve implantation, and data were continuously recorded during the procedure. With surface ECG, a median (first, third quartile) QRS width of 96 (84, 116) to 150 (121, 164) ms ( P =0.001) and PR interval of 180 (159, 216) to 210 (190, 240) ms ( P =0.008) were significantly prolonged, and QRS axis was left deviated 30° (−32°, 46°) to −20° (−60°, 2°) ( P =0.005). With intracardiac electrograms, the AH (97 [70, 123] to 115 [96, 135] ms, P =0.021) and HV (52 [42, 55] to 60 [50, 70] ms, P =0.002) intervals were increased. At the end of the procedure, we observed significant ECG- or electrophysiological study-persistent conduction disturbances in 14 (78%) patients. Five patients experienced transient changes (2 AV blocks and 3 left bundle branch blocks). Conclusions—: CoreValve implantation worsens AV conduction in most patients, either transiently or permanently. This worsening is the result of direct damage either on the His bundle or on the AV node.