Exploring the force-frequency relationship in people with chronic heart failure

A key feature of heart failure with reduced ejection fraction (HFrEF) is exercise intolerance. Correcting chronotropic incompetence using conventional age-guided rate-response pacemaker programming is not associated with improvements in exercise capacity in HFrEF. The force-frequency relationship (FFR), (increased left ventricular (LV) contractility as heart rate rises), is abnormal in HFrEF, and could explain this.

This thesis comprises a series of studies with the objectives of: describing the reproducibility of a non-invasive, echocardiographic measure of the FFR, exploring whether personalised programming of the rate-response algorithm using FFR data acutely affects treadmill walk time, and determining whether personalised programming of the rate-response algorithm using FFR data is associated with longer term benefits.

An observational study demonstrated that a reproducible, non-invasive assessment of the FFR, using echocardiography, is possible in patients with HFrEF and a pacemaker. I was able to show that critical heart rate, peak contractility, and the slope of the FFR were lower in patients with HFrEF compared to non-HFrEF controls.

In an interventional, double-blind, randomised, cross-over trial, I compared the effects of tailored pacemaker rate-response programming based on the FFR data with conventional age-guided rate-response programming, on treadmill exercise time and oxygen consumption. This resulted in a greater improvement in exercise time and higher peak oxygen consumption with tailored rate-response programming.

A further interventional double-blind, randomised controlled, parallel-group study demonstrated that six months of rate-response programming based on the FFR data, was associated with improved exercise time, and that conventional age-guided rate-response programming might contribute to deteriorating left ventricular function.

Based on these novel findings, I can conclude that the FFR is abnormal in HFrEF. Optimising pacemaker settings based on the individual’s FFR data is associated with improved exercise time and decreased decline in LV function in HFrEF.