Heart failure duration progressively modulates the arrhythmia substrate through structural and electrical remodeling.

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Heart Failure Pathophysiology

Background:

• Ventricular arrhythmias are a major cause of mortality in heart failure (HF) patients.
• Cardiac structural and electrical remodeling create a substrate for these arrhythmias.
• Canine models are used to study HF, but the impact of duration on remodeling is unclear.

Purpose of the Study:

• To investigate whether chronic (4-month) versus short-term (1-month) tachypacing-induced heart failure in canines results in differential electrical and structural remodeling.
• To determine if chronic HF models exhibit a more arrhythmogenic substrate compared to short-term models.

Main Methods:

• Heart failure (HF) was induced in canines via ventricular tachypacing for either one month (short-term) or four months (chronic).
• Cardiac structure, left ventricular myocyte action potentials, ion channel currents, and reactive oxygen species were assessed to evaluate remodeling.

Main Results:

• Chronic HF led to reduced left ventricular contractility, hypertrophy, and interstitial fibrosis, unlike short-term HF.
• Action potentials were prolonged, and repolarization instability with early afterdepolarizations occurred only in chronic HF.
• Reduced transient outward potassium current (Ito), outward inward rectifier potassium current (IK1), and delayed rectifier potassium currents (IKs, IKr) were observed, particularly in chronic HF.
• Increased reactive oxygen species were found in both short-term and chronic HF groups.

Conclusions:

• Reduced potassium currents (Ito, IK1, IKs, IKr) in HF contribute to early afterdepolarization formation.
• Chronic, but not short-term, canine HF models replicate the electrophysiological alterations and repolarization instability seen in end-stage human HF.
• Chronic HF models provide a more relevant substrate for studying arrhythmias in advanced heart failure.