Determinants of Exercise Intolerance in Elderly Heart Failure Patients With Preserved Ejection Fraction

Study Questions:

What are the mechanisms responsible for reduced aerobic capacity (peak VO2) patients with heart failure with preserved ejection fraction (HFPEF)?


The study investigators measured left ventricular volumes (using two-dimensional echocardiography), cardiac output, VO2, and calculated arterial-venous oxygen content difference (A-VO2 Diff) at rest and during incremental, exhaustive, upright cycle exercise in 48 HFPEF patients (ages 69 ± 6 years) and 25 healthy age-matched controls.


The investigators found that in HFPEF patients compared with healthy controls, VO2 was reduced at peak exercise (mean ± standard error, 14.3 ± 0.5 ml•kg•min−1 vs. 20.4 ± 0.6 ml•kg•min−1; p < 0.0001) and was associated with a reduced peak cardiac output (6.3 ± 0.2 l•min−1 vs. 7.6 ± 0.2 l•min−1; p < 0.0001) and A-VO2 Diff (17 ± 0.4 ml•dl−1 vs. 19 ± 0.4 ml•dl−1; p < 0.0007). In this study, the strongest independent predictor of peak VO2 was the change in A-VO2 Diff from rest to peak exercise (A-VO2 Diff reserve) for both HFPEF patients (partial correlate, 0.58; standardized β coefficient, 0.66; p = 0.0002) and healthy controls (partial correlate, 0.61; standardized β coefficient, 0.41; p = 0.005).


The authors concluded that reduced cardiac output and A-VO2 Diff contribute significantly to the severe exercise intolerance in elderly HFPEF patients. The finding that A-VO2 Diff reserve is an independent predictor of peak VO2 suggests that peripheral, noncardiac factors are important contributors to exercise intolerance in these patients.


This is an important study because it indicates that ‘noncardiac’ factors such as ‘stiff central arteries’ (Heart Fail Clin 2008;4:ix-xii), ventricular-vascular interactions (Heart Fail Clin 2008;4:23-36), skeletal muscle and visceral perfusion, and skeletal muscle insulin resistance may be important determinants of impaired exercise tolerance in patients with diastolic dysfunction. Further studies are needed to determine whether ‘destiffening’ agents of central arteries will improve exercise tolerance.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Exercise Tolerance, Rest, Muscle, Skeletal, Heart Failure, Hydrogen-Ion Concentration, Cardiac Output, Echocardiography

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