Differential Responses of Post-Exercise Recovery of Leg Blood Flow and Oxygen Uptake Kinetics in HFpEF versus HFrEF

Abstract

The goals of the current study were to compare leg blood flow, oxygen extraction and oxygen uptake (VO2) after constant load sub-maximal unilateral knee extension (ULKE) exercise in patients with heart failure with reduced ejection fraction (HFrEF) compared to those with preserved ejection fraction (HFpEF). Previously, it has been shown that prolonged whole body VO2 recovery kinetics are directly related to disease severity and all-cause mortality in HFrEF patients. To date, no study has simultaneously measured muscle-specific blood flow and oxygen extraction post exercise recovery kinetics in HFrEF or HFpEF patients; therefore it is unknown if muscle VO2 recovery kinetics, and more specifically, the recovery kinetics of blood flow and oxygen extraction at the level of the muscle, differ between HF phenotypes. Ten older (68±10yrs) HFrEF (n = 5) and HFpEF (n = 5) patients performed sub-maximal (85% of maximal weight lifted during an incremental test) ULKE exercise for 4 minutes. Femoral venous blood flow and venous O2 saturation were measured continuously from the onset of end-exercise, using a novel MRI method, to determine off-kinetics (mean response times, MRT) for leg VO2 and its determinants. HFpEF and HFrEF patients had similar end-exercise leg blood flow (1.1±0.6 vs. 1.2±0.6 L/min, p>0.05), venous saturation (42±12 vs. 41±11%, p>0.05) and VO2 (0.13±0.08 vs. 0.11±0.05 L/min, p>0.05); however HFrEF had significantly delayed recovery MRT for flow (292±135sec. vs 105±63sec., p = 0.004) and VO2 (95±37sec. vs. 47±15sec., p = 0.005) compared to HFpEF. Impaired muscle VO2 recovery kinetics following ULKE exercise differentiated HFrEF from HFpEF patients and suggests distinct underlying pathology and potential therapeutic approaches in these populations.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Femoral vein slice prescription.

(a) Anatomic image showing the slice orientation, perpendicular to the targeted femoral vein, with a close-up view in (b). The location of the slice, relative to the femoral vein and great saphenous vein is shown in (c), with targeting of the femoral vein prior to the saphenous arch.

Fig 2. Sample MR images of femoral vein and SvO2.

(a) Anatomic image showing the slice location for blood flow and venous oxygen saturation imaging experiments (the targeted right femoral vein is indicated). Sample venous oxygen saturation (SvO2) images at two time points (1 second after end-exercise and 60 seconds after end-exercise) are shown in (b), and the corresponding time-course data from this subject for SvO2 and blood flow, averaged for the entire vein cross-section, are in (c) and (d), respectively.

Fig 3. Group average recovery kinetics for blood flow and oxygen extraction and consumption.

Average time course data for femoral vein blood flow (a), femoral venous oxygen saturation (b), a-v O2 diff (c) and muscle VO2 (d) are shown for HFrEF (black) and HFpEF (red) groups. The dashed lines show one standard deviation around the mean. The mean response time (MRT) for each curve is defined as the sum of the best-fit exponential recovery plus the delay to the onset of exponential recovery.

Fig 4. Group average recovery kinetics for blood flow and oxygen consumption (normalized to muscle mass).

Average time course data for muscle blood flow (a) and muscle VO2 (b) are shown for HFrEF (black) and HFpEF (red) groups, with normalization of values in each subject to their quadriceps muscle mass. The dashed lines show one standard deviation around the mean.

Fig 5. Mean response times.

Mean response times (MRT) for (a) muscle blood flow, (b) SvO2 and (c) VO2 following knee-extension exercise. Control data from a previous study using an identical acquisition protocol [16].

Fig 6. Resting venous oxygen saturation and ventricular remodeling.

Relationship between indexed left ventricular end-diastolic volume and resting femoral vein O2 saturation (SvO2) in heart failure patients.