Atrial septopulmonary bundle of the posterior left atrium provides a substrate for atrial fibrillation initiation in a model of vagally mediated pulmonary vein tachycardia of the structurally normal heart

Abstract

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 micromol/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.

Keywords: atrial thickness; electrophysiology; fiber direction; mapping; reentry.

Figure 1

A, B, Left atrial appendage (LAA) incision and PLA-septum field of view. C, Schematic representation of our pacing protocol. RSPV indicates right superior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein; LIPV, left inferior pulmonary vein; PLA, posterior left atrium; RPV, right pulmonary veins; LPV, left pulmonary veins.

Figure 2

A, Posterior left atrium (PLA) myocardial fiber orientation. The numbers correspond to the various areas where caliper measurements were taken and subsequently graphed in panel E. B, Masson’s trichrome-stained transversal section taken immediately below the pulmonary veins. C, Masson’s trichrome-stained transversal section at the superior part of the fossa ovalis through the PLA. D, Masson’s trichrome-stained transversal section taken immediately below the fossa ovalis through the PLA and septum. E, Average myocardial thickness (n=7) measured at the locations indicated in panel A. #P<0.01 when a Student paired t test with a Bonferroni correction was performed between location 3 and locations 1, 2, 4, 5, and 6. *P<0.025 when Student paired t test with a Bonferroni correction was performed between location 2 and locations 5 and 6. “P<0.025 when Student paired t test with a Bonferroni correction was performed between locations 1 and 6. SPB indicates septopulmonary bundle; RPVs, right pulmonary veins; LPVs, left pulmonary veins.

Figure 3

A, Posterior left atrium anatomy snapshot with a similar field of view than the corresponding optical movies. B, Isochronal map of sinus wave activation. C, Isochronal map of the last right superior pulmonary vein (RSPV)-paced wave preceding fibrillation initiation. The white arrow denotes the direction of the wave. Black arrows indicate areas of conduction block. D, Activation map shown in panel C superimposed on its corresponding anatomy (presented in panel A). E, Isochronal map of the last left superior pulmonary vein (LIPV)-paced wave immediately before the initiation of fibrillation. Black arrows indicate an area of conduction block. F, Activation map shown in E superimposed on its corresponding anatomy (presented in panel A). SPB, septopulmonary bundle.

Figure 4

Single pixel recordings from posterior left atrium (PLA) locations indicated with red numbers in Figure 3A. On the left: a single pixel recording shows the last sinus wave and 5 paced waves before atrial fibrillation (AF) was induced. On the right: another example of a single pixel recording shows the last sinus wave and 2 paced waves before AF was induced. Inset, Optical single pixel upstrokes from locations 1, 2, and 3 corresponding to the third left inferior pulmonary vein (LIPV)-paced wave. A marked delay is observed at the transition PLA-septum between locations 2 and 1. RSPV indicates right superior pulmonary vein.

Figure 5

A, D, G, Pulmonary left atrium (PLA) anatomy snapshots examples in 3 different animals. B, E, H, Corresponding average conduction velocity maps of pulmonary vein (PV)-paced waves. The stars denote the pacing sites. The average conduction velocity for the mapped area was 1.7±1.2, 1.1±0.8, and 1.1±0.7 m/s for panels B, E, and H, respectively. C, F, I, Average conduction velocity maps superimposed on their corresponding PLA anatomy snapshot. RPV indicates right pulmonary vein; SPB, septopulmonary bundle; LIPV, left inferior PV; RSPV, right superior PV.

Figure 6

A, E, PLA anatomy snapshots in 2 different hearts. B, F, Snapshots of phase movies during AF initiation. Each color represents a different phase of the action potential (insets). C, G, Panels B and F superimposed on panels A and E. D, H, Corresponding pseudo-ECG tracings. I, Bipolar recordings from RAA, SVC, BB, and LAA during the AF initiation episodes displayed in panels E through H. PLA indicates posterior left atrium; AF, atrial fibrillation; RAA, right atrial appendage; SVC, superior vena cava; BB, Bachmann bundle; LAA, left atrial appendage; RPV, right pulmonary veins; SBP, septopulmonary bundle; LIPV, left inferior pulmonary vein; RSPV, right superior pulmonary vein.

Figure 7

A, First wave of AF initiated by pacing the LIPV. Circles, starts, and arrows represent singularity points, breakthroughs, and incoming waves, respectively, defined as follows. Wave-break (left panels): point of fracture of the pulmonary vein paced impulse wavefront at which all phases of the action potential converge. Breakthrough (middle panels): wave that appeared as a point in the field of view and propagated radially thereafter. Incoming wave: wave entering from outside the field of view. Each color corresponds to a different AF episode. Multiple locations of the same color stars represent multiple locations of simultaneous breakthroughs in the PLA. Multiple arrows of the same color represent 2 waves arriving simultaneously. B, First AF wave after RSPV pacing. AF indicates atrial fibrillation; LIPV, left inferior pulmonary vein; PLA, posterior left atrium; RSPV, right superior pulmonary vein; RPVs, right pulmonary veins; LPVs, left pulmonary veins; PV, pulmonary veins.

Figure 8

A, Bipolar electrograms recorded from the left atrial lateral wall, Bachmann’s Bundle (BB), and the right atrial appendage. The black dashed lines represent the time of pacing stimulation. The numbers indicates the electrode detection of the waves. The blue dashed line is the time of the first detected optical wave of AF, which for this case is after 6 stimulated paced beats. The arrows show the first electrode detected wave of AF. B, The time of activation of the 1st wave AF detected in the electrograms calculated by measuring the time interval between the black dashed line (last stimulated spike who demonstrate capture in optical recorders) and the 1st wave AF. C, Difference between electrodes in the time of activation after the first wave AF measured from panel B. *P<0.025 when a Student paired t test with a Bonferroni correction is performed between BB/LALW versus RAA/BB, and BB/LALW versus RAA/LALW. D, Delay in the activation in different electrodes after the first wave AF was detected in the left posterior wall by optical recorders. *P<0.025 when a Student paired t test with a Bonferroni corrections is performed between RAA and BB, and between RAA and LALW. E, Schematic representation of the result observed on the pattern of activation from the first wave AF. AF indicates atrial fibrillation; LALW, left atrial lateral wall; RAA, right atrial appendage.