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Introduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and results in significant morbidity and mortality. The Cox-Maze IV procedure (CMP-IV) has been shown to have excellent efficacy in returning patients to sinus rhythm, but there have been few reports of late follow-up in sizable cohorts of patients with longstanding persistent AF, the most difficult type of AF to treat., Methods and Results: Between May 2003 and March 2020, 174 consecutive patients underwent a stand-alone CMP-IV for longstanding persistent AF. Rhythm outcome was assessed postoperatively for up to 10 years, primarily via prolonged monitoring (Holter monitor, pacemaker interrogation, or implantable loop recorder). Fine-Gray regression was used to investigate factors associated with atrial tachyarrhythmia (ATA) recurrence, with death as a competing risk. Median duration of preoperative AF was 7.8 years (interquartile range: 4.0-12.0 years), with 71% (124/174) having failed at least one prior catheter-based ablation. There were no 30-day mortalities. Freedom from ATAs was 94% (120/128), 83% (53/64), and 88% (35/40) at 1, 5, and 7 years, respectively. On regression analysis, preoperative AF duration and early postoperative ATAs were associated with late ATAs recurrence., Conclusion: Despite the majority of patients having a long-duration of preoperative AF and having failed at least one catheter-based ablation, the stand-alone CMP-IV had excellent late efficacy in patients with longstanding persistent AF, with low morbidity and no mortality. We recommend consideration of stand-alone CMP-IV for patients with longstanding persistent AF who have failed or are poor candidates for catheter ablation., (© 2021 Wiley Periodicals LLC.)

To understand abnormal sinus node function in clinical atrial arrhythmias, it is essential to understand the normal function of the sinus node. Much of our understanding of the sinus node comes from work done in rabbits. In small animals, the node is a thin structure and can be modeled in two dimensions. However, in canines and humans, the node is a more complex structure completely surrounded by myocytes. Recent data suggest that the node may be insulated from the surrounding atrial myocytes, except at a limited number of exit sites. A model of the node with discrete exit sites explains how atrial activation can be initiated from multiple sites simultaneously. Within the node there may exist specialized pathways that explain the complex conduction within the node. Multiple cell types, with different intrinsic rates, combined with the nonuniform distribution of autonomic receptors, provide a basis for understanding the dynamics of heart rate control and the initiation of atrial activation. In addition, this model of the sinus node provides a framework to propose novel mechanisms underlying various atrial arrhythmias, such as atrial premature depolarizations or sinus node reentry.

Introduction: Prior studies in isolated canine atria demonstrated that acetylcholine-induced reentrant atrial fibrillation (AF) was triggered by multifocal activity in the area of normal impulse origin (sinus node-crista terminalis). The aim of this study was to investigate the activation sequence in AF induced by vagal stimulation (VS) in intact dog hearts., Methods and Results: VS (10 to 50 Hz, 1 msec, 15 V, 5-sec trains) induced single or multiple atrial premature depolarizations (APDs), and/or AF in 8 of 10 open chest dogs. Occurrence of APDs and AF increased with increasing VS intensity. Epicardial mapping (254 unipolar electrodes) of both atria showed that APDs as a rule emerged from ectopic sites, often from the right atrial appendage. Activation mapping of the first 10 cycles of AF showed that only a small number (<3 to 4) of unstable reentrant circuits were possible at the same moment. Moreover, most sustained VS-induced AFs were accounted for by a single leading stable reentrant circuit that activated the remainder of the atria., Conclusion: (1) Occurrence of vagally induced APDs and AF increases with increasing frequency of VS. (2) VS-induced focal ectopic APDs are widely distributed over the atria. (3) A single APD can be sufficient for initiation of reentrant AF. (4) Despite its high rate of sustained AF, it may be maintained by single stable reentrant circuit. (5) The atrial septum can play an important role in both the initiation and the maintenance of VS-induced AF.

Introduction: To elucidate the role of tissue structure as a determinant of the unique conduction properties of the sinus node, we compared the spatial distribution of intercellular connections at gap junctions in the sinus node to the more rapidly conducting crista terminalis and left ventricle, which have been studied previously., Methods and Results: Samples of four canine sinus nodes were prepared for electron microscopy. The total number and spatial orientation of neighboring myocytes connected by ultrastructurally identified intercalated disks and gap junctions to nine randomly selected index cells were determined by sequentially examining subserial sections. Sinus node cells were sparsely interconnected compared to the extent of interconnections observed previously in other tissues. A typical sinus node cell was connected to only 4.8 +/- 0.7 neighbors compared with 11.3 +/- 2.2 cells in the left ventricle and 6.4 +/- 1.7 cells in the crista terminalis. Sinus node interconnections occurred at small intercalated disks that usually connected cells in partial side-to-side and end-to-end juxtaposition. In contrast, left ventricular myocytes are interconnected at large intercalated disks that adjoin many cells in pure side-to-side and end-to-end orientations. Crista terminalis myocytes are connected primarily in end-to-end fashion. The aggregate gap junction profile length per unit myocyte area was 26.5 times greater in the left ventricle and 5.0 times greater in the crista terminalis than in the sinus node., Conclusion: Sinus node myocytes exhibit small, sparsely distributed gap junctions that interconnect cells in complex patterns of lateral and terminal apposition. These structural features are consistent with the unique conduction properties of the sinus node.

The objective of this study was to measure autonomic receptor densities in the human sinoatrial node and adjacent atrial myocardium to gain further insights into autonomic regulation of sinoatrial node function in the human heart. Sinoatrial nodes (n = 9) were acquired from human donors. Quantitative light microscopic autoradiography of radioligand binding sites in tissue sections was used to compare beta-adrenergic and muscarinic cholinergic receptor densities within specific tissue compartments of the sinoatrial node and adjacent myocardium. Total beta-adrenergic receptors were measured with the nonsubtype selective radioligand [125I]iodocyanopindolol. beta 2-Adrenergic receptors were determined by measuring the amount of radioactivity bound to sections incubated with radioligand in the presence of the highly beta 1-selective antagonist CGP-20712A. Specific autoradiographic grain densities were normalized to myocyte area/unit tissue area. Myocytes in the sinoatrial node occupied 47.7% +/- 0.1% of the total tissue area compared with 92.8% +/- 0.1% in myocardium (P < 0.001). Total specific beta-adrenergic receptor density per unit myocyte area was 3.5 +/- 0.9 times greater in the sinoatrial node than in myocardium (P < 0.001). The relative densities of beta 1-(4.2, P < 0.002), beta 2-(2.6, P < 0.002), and muscarinic (3.3, P < 0.001) receptors were significantly greater in the sinoatrial node than in the atrium. Thus, total beta-adrenergic and muscarinic cholinergic receptor densities are > 3-fold higher in the sinoatrial node than adjacent atrial myocardium, reflecting their specialized roles in regulating cardiac rate and rhythm. The beta 1-subtype is predominant in both regions. The beta 2-subtype, however, is > 2.5-fold more abundant in the sinoatrial node than in atrial myocardium. The relatively high beta 2-receptor density in the human sinoatrial node is consistent with physiologic studies that implicate this receptor in regulating cardiac chronotropism.

It was generally accepted that the site of normal impulse origin within the atria was a single static focus within the sinus node. This review will examine how this model of impulse origin came about and has evolved. Early on, conflicting data suggested that the sinus node focus was not static and changed with interventions that changed heart rate, such as vagal stimulation. Furthermore, even with removal of the sinus node, a normal atrial rhythm was generated. High-resolution mapping in humans and dogs showed that the initiation of the impulse was dynamic and could be multicentric, with more than one focus initiating a single beat. Shifts in the site of origin correlated with changes in rate and were consistent with P wave changes routinely observed in the standard ECG. These studies suggested multiple pacemakers were responsible for impulse initiation. However, it was not clear how these widespread pacemakers were coordinated to function synchronously. Recent canine data suggest that the node may be partially insulated from the surrounding atrium, resulting in multicentric origin starting from a single site within the node. What has evolved is a model of impulse origin with a sinus node having discrete exit sites and a dominant pacemaker within the node that can shift to other nodal sites. Complex and changing conduction out of the node, coupled with extranodal pacemakers, which can assume dominance over the node, combine with the autonomic nervous system to control heart rate and the pattern of impulse origin within the atria.