Structural and Functional Properties of Subsidiary Atrial Pacemakers in a Goat Model of Sinus Node Disease

BackgroundThe sinoatrial/sinus node (SAN) is the primary pacemaker of the heart. In humans, SAN is surrounded by the paranodal area (PNA). Although the PNA function remains debated, it is thought to act as a subsidiary atrial pacemaker (SAP) tissue and become the dominant pacemaker in the setting of sinus node disease (SND). Large animal models of SND allow characterization of SAP, which might be a target for novel treatment strategies for SAN diseases.MethodsA goat model of SND was developed (n = 10) by epicardially ablating the SAN and validated by mapping of emergent SAP locations through an ablation catheter and surface electrocardiogram (ECG). Structural characterization of the goat SAN and SAP was assessed by histology and immunofluorescence techniques.ResultsWhen the SAN was ablated, SAPs featured a shortened atrioventricular conduction, consistent with the location in proximity of atrioventricular junction. SAP recovery time showed significant prolongation compared to the SAN recovery time, followed by a decrease over a follow-up of 4 weeks. Like the SAN tissue, the SAP expressed the main isoform of pacemaker hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and Na+/Ca2+ exchanger 1 (NCX1) and no high conductance connexin 43 (Cx43). Structural characterization of the right atrium (RA) revealed that the SAN was located at the earliest activation [i.e., at the junction of the superior vena cava (SVC) with the RA] and was surrounded by the paranodal-like tissue, extending down to the inferior vena cava (IVC). Emerged SAPs were localized close to the IVC and within the thick band of the atrial muscle known as the crista terminalis (CT).ConclusionsSAN ablation resulted in the generation of chronic SAP activity in 60% of treated animals. SAP displayed development over time and was located within the previously discovered PNA in humans, suggesting its role as dominant pacemaker in SND. Therefore, SAP in goat constitutes a promising stable target for electrophysiological modification to construct a fully functioning pacemaker.

Partial Anomalous Pulmonary Venous Connection: Forty-Six Years of Follow-Up

Background: Surgical repair of partial anomalous pulmonary venous connection (PAPVC) may disturb the electrical conduction in the atria. This study documents long-term outcomes, including the late occurrence of atrial tachyarrhythmia and bradyarrhythmia. Methods: This retrospective study covers all PAPVC operations at Aarhus University Hospital between 1970 and 2010. Outcome measures were arrhythmias, sinus node disease, pacemaker implantation, pathway stenosis (pulmonary vein(s), intra-atrial pathway, and/or superior vena cava), and mortality. Data were collected from databases, surgical protocols, and hospital records until May 2018. Results: A total of 83 patients were included with a postoperative follow-up period up to 46 years. Average age at follow-up was 43 ± 21 years. During follow-up, new-onset atrial fibrillation or atrial flutter appeared in four patients (5%). Sinus node disease was present in nine patients (11%). A permanent pacemaker was implanted in seven patients (8%) at an average of 12.7 years after surgery. Pulmonary venous and/or superior vena cava obstruction was seen in five patients (6%). Stenosis was most prevalent in the two-patch technique, and arrhythmia was most prevalent in the single-patch technique. Sixty-seven (81%) of 83 patients had neither bradyarrhythmias nor tachyarrhythmias or pacemaker need. Conclusions: This study contributes important long-term data concerning the course of patients who have undergone repair of PAPVC. It confirms that PAPVC can be operated with low postoperative morbidity. However, late-onset stenosis, bradyarrhythmias and tachyarrhythmias, and need for pacemaker call for continued follow-up.

What is the Diagnosis?

A 83-year-old female implanted a double chamber pacemaker (Adapta DR) one year ago to threat a sinus node disease with symptomatic sinus arrest (up to 4,2s).

Ischemic Stroke in Patients With Sinus Node Disease, Atrial Fibrillation, and Other Cardiac Conditions

Background and Purpose— Atrial fibrillation (AF) is known to increase risk of ischemic stroke (IS), but the risk of IS in isolated sinus node disease (SND) is unclear. We compared the incidence of IS in patients with SND, patients with AF, and in a control population with other cardiac diseases (disease of the circulatory system using the International Classification of Diseases, Tenth Revision ). Methods— This French longitudinal cohort study was based on the national database covering hospital care for the entire population from 2008 to 2015. Results— Of 1 692 157 patients included in the cohort, 100 366 had isolated SND, 1 564 270 had isolated AF, and 27 521 had AF associated with SND. Incidence of IS during follow-up was higher in isolated patients with AF than in AF associated with SND (yearly rate 2.22% versus 2.06%) and in isolated patients with AF than in isolated patients with SND (yearly rate 2.22% versus 1.59%). The incidence of IS was lower in a control population with other cardiac conditions (n=479 108) compared with SND and patients with AF (0.96%/y, 1.59%/y, and 2.22%/y, respectively). After 1:1 propensity score matching, SND was associated with lower incidence of IS compared to AF (hazard ratio, 0.77 [95% CI, 0.73–0.82]) but higher incidence of IS compared to control population (hazard ratio, 1.27 [95%CI, 1.19–1.35]). Conclusions— Patients with SND had a lower risk of thromboembolic events than patients with AF but a higher risk than a control population with other cardiac diseases. Randomized clinical trial in a selected SND population, with, for example, a high CHA 2 DS 2 -VASc score, would be required to determine the value of IS prevention by anticoagulation.

P5675Ischemic stroke in patient with sinus node disease in comparison to atrial fibrillation, bradycardia-tachycardia syndrome and other cardiac conditions: a nationwide cohort-study

Atrial fibrillation (AF) may be associated with sinus node disease (SND) presenting as a brady-tachy syndrome (BTS), known to be at risk for embolic ischemic stroke (IS). It remains unclear whether the risk of IS is increased in patients with isolated SND. Methods This French longitudinal cohort study was based on the national database covering hospital care from for the entire population (PMSI) from 2010 to 2015. We compared incidences of IS in patients with a diagnosis of AF or SND to that in a control group of patients with a main diagnosis of cardiac condition (excluding those with AF or SND, history of stroke and mechanical valve or mitral stenosis). Results Of 1,732,412 patients included in the cohort, 1,601,435 (92.44%) had isolated AF, 102,849 (5.94%) had isolated SND and 28,128 (1.62%) had BTS. The control group with cardiac condition included 479,108 patients. Incidence of IS progressively increased when considering patients from the control population, patients with isolated SND, with BTS or with isolated AF (0.67%/yr, 1.95%/yr, 3.03%/yr and 5.48%/yr respectively). These differences were seen in all strata of CHA2DS2VASc score (table). SND patients with a CHA2DS2-VASc score ≥3 had a yearly incidence of IS >2%, comparable to AF population with a CHA2DS2-VASc score ≥1. Incidence (%/year) of ischemic stroke CHA2DS2-VASc AF population SND population “Control” population Women Men Women Men Women Men All scores 6.72% 4.37% 1.93% 1.96% 0.67% 0.68% Score = 0 – 1.960% – 1.211% – 0.217% Score = 1 2.337% 3.046% 0.538% 1.486% 0.166% 0.345% Score = 2 3.917% 4.499% 0.879% 1.541% 0.298% 0.580% Score = 3 7.572% 4.733% 2.207% 2.084% 0.541% 0.907% Score = 4 7.016% 4.820% 2.363% 2.305% 0.930% 1.278% Score = 5 6.725% 5.345% 2.845% 2.849% 1.249% 1.553% Score = 6 7.637% 7.543% 3.319% 4.109% 1.737% 2.031% Score = 7 10.196% 13.927% 4.663% 7.708% 2.346% 4.089% Score = 8 17.654% 12.607% 8.519% 11.904% 2.446% 2.355% Conclusion Patients with isolated SND had a lower risk of IS than patients with AF or BTS. However, SND patients had a non-neglectable risk of IS during follow-up which was higher than in a “control” population. Whether oral anticoagulation may bring a significant clinical benefit might be studied in patients with SND at highest risk of IS.