Sympathetic activation and the force-frequency relationship in heart failure with reduced ejection fraction

In a study of individuals with heart failure with reduced ejection fraction (HFrEF), researchers discovered a complex relationship between heart rate and sympathetic activation. The investigation involved 157 HFrEF patients and 55 healthy controls, with participants undergoing an incremental pacing protocol. As heart rate increased from 50 to 140 beats per minute, researchers measured the force-frequency relationship (FFR) using echocardiography, along with cardiac output, total peripheral resistance, and blood pressure variability.

As heart rate increased, both groups experienced an increase in left ventricular contractility and cardiac output until reaching the peak of the FFR, after which these values declined. Interestingly, total peripheral resistance, blood pressure variability, and sympathetic nerve activity (measured via microneurography) all decreased at the peak of the FHR, and then increased beyond this point. These relationships were evident in both groups, but more pronounced in those with HFrEF.

The study concluded that there exists a bidirectional relationship between heart rate and sympathetic activation in individuals with HFrEF. The nadir of sympathetic tone occurs at the peak of the FFR, and both excessively low and high heart rates coincide with greater sympathetic activation. These findings suggest that optimal heart rate targets for individuals with HFrEF are likely to be individualized.