What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Age-associated atrial fibrillation (n=60). Intervention: Aged atrial fibrillation (Exposure) vs. Aged sinus rhythm and adult sinus rhythm. Primary outcome: HCN2 mRNA expression (p=<0.05).

What does this research mean for the field?

Aged patients with atrial fibrillation exhibit significantly higher HCN2 and HCN4 channel expression and lower miR-1 and miR-133 expression compared to aged patients with sinus rhythm, suggesting these electrophysiological changes contribute to age-associated atrial fibrillation. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

May 25, 2015Open Access

Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation

Q: What are the key findings of this study?

Aged patients with atrial fibrillation exhibited significantly higher HCN2 and HCN4 channel expression and lower miR-1 and miR-133 expression compared to aged patients with sinus rhythm.

Q: What does this research mean for the field?

Aged patients with atrial fibrillation exhibit significantly higher HCN2 and HCN4 channel expression and lower miR-1 and miR-133 expression compared to aged patients with sinus rhythm, suggesting these electrophysiological changes contribute to age-associated atrial fibrillation. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

Aged patients with atrial fibrillation exhibited significantly higher HCN2 and HCN4 channel expression and lower miR-1 and miR-133 expression compared to aged patients with sinus rhythm.

Study Design

Type

Cross-Sectional (n=60)

Multicenter

Structured PICO

Population

60 patients undergoing coronary artery bypass grafting, comprising 32 males and 28 females (mean age 55.12±28.23 years). Divided into adult sinus rhythm (≤65 years, n=20), aged sinus rhythm (≥65 years, n=22), and aged chronic atrial fibrillation (≥65 years with AF >6 months, n=18). Excluded: liver/kidney function defects, electrolyte disorders, infections, hyperthyroidism, or diabetes.

Comparator

Comparisons made between adult sinus rhythm, aged sinus rhythm, and aged atrial fibrillation groups.

Outcome

Expression levels of HCN2 and HCN4 channel mRNA and protein, and microRNA-1 and -133 in right atrial appendage tissue.surrogate

Age-associated upregulation of HCN channels and downregulation of miR-1 and miR-133 in the right atrium may contribute to the electrophysiological changes that trigger age-associated atrial fibrillation.

Main Result

Absolute Event Rate: 1% vs 0.49%

p-value: p=<0.05

Limitations

Only right atrial appendage samples were collected, so whether changes continue throughout the atrium and pulmonary vein remains unknown.
Effects of expression changes on If current magnitude and kinetics were not investigated.
Sinoatrial node function was not evaluated, so the potential contribution of sinoatrial node dysfunction could not be assessed.

Abstract

Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels mediate pacemaker currents in the atrium. The microRNA (miR) families miR-1 and miR-133 regulate the expression of multiple genes involved in myocardial function, including HCN channels. It was hypothesized that age‑dependent changes in HCN2, HCN4, miR‑1 and miR‑133 expression may contribute to age‑associated atrial fibrillation, and therefore the correlation between expression levels, among adult (≤65 years) and aged patients (≥65 years), and sinus rhythm was determined. Right atrial appendage samples were collected from 60 patients undergoing coronary artery bypass grafting. Reverse transcription-quantitative polymerase chain reaction (PCR) and western blot analyses were performed in order to determine target RNA and protein expression levels. Compared with aged patients with sinus rhythm, aged patients with atrial fibrillation exhibited significantly higher HCN2 and HCN4 channel mRNA and protein expression levels (P<0.05), but significantly lower expression levels of miR‑1 and miR‑133 (P<0.05). In addition, aged patients with sinus rhythm exhibited significantly higher expression levels of HCN2 and HCN4 channel mRNA and protein (P<0.05), but significantly lower expression levels of miR‑1 and ‑133 (P<0.05), compared with those of adult patients with sinus rhythm. Expression levels of HCN2 and HCN4 increased with age, and a greater increase was identified in patients with age‑associated atrial fibrillation compared with that in those with aged sinus rhythm. These electrophysiological changes may contribute to the induction of ectopic premature beats that trigger atrial fibrillation.

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