Sinoatrial node function and the role of sinoatrial conduction in the typical atrial flutter substrate.

Background: Sinoatrial node (SAN) activation and sinoatrial conduction pathways (SACPs) have been assessed in animals but not in humans.

Objectives: We used ultrahigh-density mapping and simulated models to characterize the SAN and to investigate whether slowed SAN conduction may contribute to the atrial flutter (AFL) substrate.

Methods: Twenty-seven patients undergoing electrophysiologic procedures had right atrial mapping.

Glucagon-like peptide-1 increases heart rate by a direct action on the sinus node.

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated with increased heart rate, the mechanism of which is unclear.

Methods And Results: We employed a large animal model, the female landrace pig, and used multiple in vivo and ex vivo approaches including pharmacological challenges, electrophysiology, and high-resolution mass spectrometry to explore how GLP-1 elicits an increase in heart rate.

Proteomics couples electrical remodelling to inflammation in a murine model of heart failure with sinus node dysfunction.

Aims: In patients with heart failure (HF), concomitant sinus node dysfunction (SND) is an important predictor of mortality, yet its molecular underpinnings are poorly understood. Using proteomics, this study aimed to dissect the protein and phosphorylation remodelling within the sinus node in an animal model of HF with concurrent SND.

Methods And Results: We acquired deep sinus node proteomes and phosphoproteomes in mice with heart failure and SND and report extensive remodelling.

Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility.

Background: Ventricular arrhythmias (VAs) demonstrate a prominent day-night rhythm, commonly presenting in the morning. Transcriptional rhythms in cardiac ion channels accompany this phenomenon, but their role in the morning vulnerability to VAs and the underlying mechanisms are not understood. We investigated the recruitment of transcription factors that underpins transcriptional rhythms in ion channels and assessed whether this mechanism was pertinent to the heart's intrinsic diurnal susceptibility to VA.

Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes.

[Figure: see text].