Regulation of oxygen uptake and cardiac function in heart failure: effects of biventricular pacing and high-intensity interval exercise

Cardiac resynchronization therapy (CRT) and high-intensity interval training (HIT) have been shown to be effective for left ventricular (LV) reverse remodelling and increasing aerobic capacity in patients with heart failure (HF) and reduced ejection fraction (EF). The mechanisms underlying these benefits are not well understood. Accordingly, the purpose of the first study (Chapter 2) was to investigate the effects of CRT on oxygen uptake (VO2) kinetics and exercise LV function during the transition to moderate-intensity exercise. The first study showed that 1) CRT led to a significant speeding in VO2 kinetics, 2) stroke volume during steady-state exercise increased due to a decrease in submaximal exercise LV ESV independent of cardiac preload, and 3) CRT resulted in faster heart rate kinetics, suggesting that autonomic control of heart rate during exercise changed with CRT. The purpose of the second study (Chapter 3) was to examine the CRT mediated improvements in peak exercise LV function, peak VO2, and recovery from peak exercise. The second study showed that 1) CRT increased reserve and peak cardiac output, 2) CRT increased VO2 at peak exercise and this was related to an increase in cardiac output reserve that was secondary to an increase in LV end-systolic volume (ESV) reserve and preserved cardiac preload, 3) CRT decreased the time to exercise recovery as measured by a speeding in gas exchange and ventilation kinetics post-exercise, and 4) faster post-exercise VO2 kinetics were associated with greater aerobic capacity. The purpose of the third study (Chapter 4) was to assess biventricular function prior to, and immediately following acute HIT. The third study showed that biventricular ESV decreased and LV systolic annular velocity increased immediately following acute HIT. Within 30 min of exercise termination, LV EF was significantly increased compared to pre-exercise values. Diastolic function immediately following acute HIT was also preserved secondary to increased LV recoil. Collectively, the findings of these studies show that patients with HF and reduced EF are able to increase metabolic reserve (evidenced by a speeding in VO2 kinetics) following CRT, and that interventions such as CRT and HIT are effective in reducing (chronically and acutely) LV ESV during and following exercise.