Efficient preloading of the ventricles by a properly timed atrial contraction underlies stroke work improvement in the acute response to cardiac resynchronization therapy.

Background: The acute response to cardiac resynchronization therapy (CRT) has been shown to be due to 3 mechanisms: resynchronization of ventricular contraction, efficient preloading of the ventricles by a properly timed atrial contraction, and mitral regurgitation reduction. However, the contribution of each of the 3 mechanisms to the acute response to CRT, specifically stroke work improvement, has not been quantified.

Objective: To use a magnetic resonance image-based anatomically accurate 3-dimensional model of failing canine ventricular electromechanics to quantify the contribution of each of the 3 mechanisms to stroke work improvement and identify the predominant mechanisms.

Methods: An MRI-based electromechanical model of the failing canine ventricles assembled previously by our group was further developed and modified. Three different protocols were used to dissect the contribution of each of the 3 mechanisms to stroke work improvement.

Results: Resynchronization of ventricular contraction did not lead to a significant stroke work improvement. Efficient preloading of the ventricles by a properly timed atrial contraction was the predominant mechanism underlying stroke work improvement. Stroke work improvement peaked at an intermediate atrioventricular delay, as it allowed ventricular filling by atrial contraction to occur at a low diastolic left ventricular pressure but also provided adequate time for ventricular filling before ventricular contraction. Reduction of mitral regurgitation by CRT led to stroke work worsening instead of improvement.

Conclusion: Efficient preloading of the ventricles by a properly timed atrial contraction is responsible for a significant stroke work improvement in the acute CRT response.