Levosimendan restores the positive force-frequency relation in heart failure

Area of Science:

• Cardiology
• Physiology

Background:

• The force-frequency relation (FFR) normally enhances myocardial performance during exercise.
• In heart failure (HF), this positive FFR is impaired, worsening cardiac function, especially with increased heart rate (tachycardia).
• Levosimendan, a Ca(2+) sensitizer, may improve exercise tolerance in HF by optimizing FFR and left ventricular (LV)-arterial coupling.

Purpose of the Study:

• To assess the effects of levosimendan on the FFR and LV-arterial coupling (E(ES)/E(A)) in a canine model of pacing-induced HF.
• To evaluate levosimendan's impact on mechanical efficiency (SW/PVA) during tachycardia in HF.

Main Methods:

• Nine conscious dogs underwent pacing-induced HF.
• Pressure-volume analysis was used to measure LV function, FFR, E(ES)/E(A), and SW/PVA.
• Measurements were taken at various pacing rates (140-200 bpm) before and after levosimendan administration.

Main Results:

• After HF induction, tachycardia impaired E(ES)/E(A) and SW/PVA.
• Levosimendan increased baseline E(ES) and SW/PVA, and decreased τ.
• In HF dogs treated with levosimendan, tachycardia led to improved E(ES), E(ES)/E(A), and SW/PVA, restoring a positive FFR.

Conclusions:

• Levosimendan restores the normal positive systolic and diastolic force-frequency relation in canine heart failure.
• Levosimendan mitigates the adverse effects of tachycardia on left ventricular-arterial coupling and mechanical efficiency in heart failure.
• Therapeutic doses of levosimendan offer a promising strategy for improving cardiac performance in heart failure patients experiencing tachycardia.