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Electrophysiological characteristics of complex fractionated electrograms and high frequency activity in atrial
Shih-Lin Chang1, Yao-Chang Chen, Chiao-Po Hsu
1Institute of Clinical Medicine and Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.
Insights
Complex fractionated electrograms (CFEAs) with high dominant frequencies (DFs) in atrial tissue exhibit arrhythmogenic properties. These findings in a heart failure rabbit model suggest a role in atrial fibrillation genesis.
Area of Science:
- Cardiovascular Electrophysiology
- Cardiac Arrhythmia Research
- Heart Failure Pathophysiology
Background:
- The role of complex fractionated electrograms (CFEAs) in atrial arrhythmogenesis remains unclear.
- Investigating the electrophysiological characteristics of CFAE and high dominant frequency (DF) areas is crucial for understanding atrial fibrillation (AF).
Purpose of the Study:
- To investigate the electrophysiological properties of CFAE and high DF areas in the context of heart failure.
- To determine the relationship between CFAE, high DF, and the arrhythmogenic substrate in an animal model.
Main Methods:
- Induction of atrial fibrillation (AF) in heart failure (HF) rabbits via rapid atrial pacing.
- Real-time substrate mapping, multielectrode array, and monophasic action potential recordings.
- Conventional microelectrode recordings and Western blot analysis for action potential and protein expression.
Main Results:
- CFAE sites with high DF showed depolarized resting membrane potential, increased afterdepolarizations, and steeper action potential duration restitution curves.
- These sites exhibited slower conduction velocity and shorter wavelength compared to other atrial regions.
- Upregulation of Na(+)-Ca(2+) exchanger (NCX), SK2 channels, and SERCA, with downregulation of Kir2.1, was observed at CFAE sites with high DF.
Conclusions:
- CFAE sites with high DF possess distinct arrhythmogenic properties in a heart failure rabbit model.
- These electrophysiological abnormalities may significantly contribute to the initiation and maintenance of atrial fibrillation.
- Targeting NCX and SK channels demonstrated potential in suppressing AF by normalizing action potential duration and restitution properties.
Background:
It is unclear whether atrial substrate with complex fractionated electrograms (CFAEs) is related to arrhythmogenesis. This study aimed to investigate the electrophysiology in CFAE and high dominant frequency (DF) areas.
Methods And Results:
Atrial fibrillation (AF) was induced by rapid atrial pacing in heart failure (HF) rabbits (4 weeks after coronary artery ligation). Real-time substrate mapping, multielectrode array, and monophasic action potential recordings were used to study areas of CFAE and DF. Conventional microelectrode and western blot were used to record the action potentials (APs) and protein expression in isolated tissue preparations. CFAE site with high DF had the most depolarized resting membrane potential, highest incidence of early and delayed afterdepolarizations, and steepest maxima slope of 90% of AP duration (APD90) restitution curve (RC) compared to CFAE site with low DF or non-CFAE sites. CFAE site with high DF exhibited the slowest conduction velocity and shortest wavelength than the other areas. Upregulation of the Na(+)-Ca(2+) exchanger (NCX), apamin-sensitive small-conductance Ca(2+)-activated K(+) channel type 2 (SK2) and sarcoplasmic reticulum Ca(2+)-ATPase, and downregulation of the Kir2.1 were found at CFAE site with high DF compared to that observed in the 3 other areas. Inhibition of the NCX and SK channels prolonged the APD90, flattened the maximum slope of RC, and suppressed AF.
Conclusions:
CFAE site with high DF had an arrhythmogenic property differing significantly from the other areas of LA in an HF rabbit model, which may contribute to the genesis of AF.
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