Abstract 18888: Functional and Molecular Characteristics of the Latent Atrial Pacemaker Clusters in Explanted Human Hearts
Introduction: Enhanced atrial latent pacemaker (LAP) activity may play an important role in triggering atrial arrhythmias including atrial fibrillation in patients with heart failure. However, functional and structural properties of LAPs in human hearts are unclear.
Methods: We used high resolution optical mapping to determine the location and function of LAPs in coronary perfused human failing (n=6) and non-failing (n=5) right atrial preparations with surgically removed sinoatrial nodes. Mapped tissue where LAPs were located and fresh tissue from unmapped hearts (n=5) were dissected to study the structure and protein expression profile by histology, immunolabeling and western blotting.
Results: During β-adrenergic stimulation by isoproterenol perfusion (100nM), we observed spontaneous atrial ectopic activity outside of the AV node region which was preferentially localized in the right atria-ventricular ring (Figure) in all failing and three non-failing atria. LAP activity was faster and more stable in failing vs. non-failing atria (46±6 bpm vs. 18±25 bpm). In four failing atria, LAP stable activity was suppressed by 3 μM of If current blocker Ivabradine (44±6 bpm vs.15±12 bpm, p=0.02). Histology and immunolabeling showed the presence of pacemaker-like cell clusters in the right atria-ventricular ring region that were located preferentially endocardially and partially insulated from atrial myocardium by fibrosis. The LAP cells had high HCN1/HCN4 but low Connexin43 expression compared to atrial myocytes.
Conclusions: Our functional and molecular studies demonstrated the presence of specialized clusters of LAP cells in the human right atrium. Local molecular heterogeneity (HCN1/4, Connexin43 expression) and heart failure induced structural remodeling (increased fibrosis) in the atria-ventricular ring may potentiate LAP pacemaking, which could lead to high ectopic activity and atrial arrhythmias during β-adrenergic stimulation.
Author Disclosures: N. Li: None. B.J. Hansen: None. T.A. Csepe: None. L. Jayne: None. J. Zhao: None. B. Moore: None. R.S. Higgins: None. R. Weiss: None. A. Kilic: None. M.R. Rosen: None. P.J. Mohler: None. B.J. Biesiadecki: None. P.M. Janssen: None. V.V. Fedorov: None.
- © 2014 by American Heart Association, Inc.