How does cardiac resynchronization therapy improve exercise capacity in chronic heart failure?

Studies have shown that neither ejection fraction nor hemodynamic abnormalities during exercise in chronic heart failure (HF) correlate with symptoms of fatigue and exhaustion. The concept that exercise limitation in patients with chronic HF is due to abnormal hemodynamics during exercise has been revised to acknowledge that the skeletal myopathy of chronic HF contributes significantly to exercise dysfunction in heart failure. Why then does cardiac resynchronization therapy (CRT), a therapy that improves abnormalities of cardiac function, such as cardiac output and ejection fraction, produce a consistent, measurable, irrefutable increase in exercise capacity?

In this review I will (1) review the mechanisms of exercise dysfunction in chronic HF, with special attention to the concept of "coordinated adaptation"; (2) analyze the effects of CRT on autonomic dysfunction in HF; and (3) propose a unifying hypothesis to understand how a therapy that improves cardiac function can improve exercise dysfunction attributable to a skeletal myopathy. Specifically, I will review evidence that CRT improves exercise capacity by attenuating the chronic sympathetic activation of HF.

The decrease in sympathetic activation, and perhaps inflammation, during CRT likely reverses many features of the skeletal myopathy, leading to improved exercise capacity.