Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction

Abstract

Aims: Peak oxygen uptake (VO(2)) is diminished in patients with heart failure with preserved ejection fraction (HFpEF) suggesting impaired cardiac reserve. To test this hypothesis, we assessed the haemodynamic response to exercise in HFpEF patients.

Methods and results: Eleven HFpEF patients (73 ± 7 years, 7 females/4 males) and 13 healthy controls (70 ± 4 years, 6 females/7 males) were studied during submaximal and maximal exercise. The cardiac output (Q(c), acetylene rebreathing) response to exercise was determined from linear regression of Q(c) and VO(2) (Douglas bags) at rest, ∼30% and ∼60% of peak VO(2), and maximal exercise. Peak VO(2) was lower in HFpEF patients than in controls (13.7 ± 3.4 vs. 21.6 ± 3.6 mL/kg/min; P < 0.001), while indices of cardiac reserve were not statistically different: peak cardiac power output [CPO = Q(c) × mean arterial pressure (MAP); HFpEF 1790 ± 509 vs. controls 2119 ± 581 L/mmHg/min; P = 0.20]; peak stroke work [SW = stroke volume (SV) × MAP; HFpEF 13 429 ± 2269 vs. controls 13 200 ± 3610 mL/mmHg; P = 0.80]. The ΔQ(c)/ΔVO(2) slope was abnormally elevated in HFpEF patients vs. controls (11.2 ±3.6 vs. 8.3 ± 1.5; P = 0.015).

Conclusion: Contrary to our hypothesis, cardiac reserve is not significantly impaired in well-compensated outpatients with HFpEF. The abnormal haemodynamic response to exercise (decreased peak VO(2), increased ΔQ(c)/ΔVO(2) slope) is similar to that observed in patients with mitochondrial myopathies, suggesting an element of impaired skeletal muscle oxidative metabolism. This impairment may limit functional capacity by two mechanisms: (i) premature skeletal muscle fatigue and (ii) metabolic signals to increase the cardiac output response to exercise which may be poorly tolerated by a left ventricle with impaired diastolic function.

Figure 1

Normalized peak oxygen uptake (VO₂) by group. Peak VO₂ was depressed in patients with heart failure with preserved ejection fraction (HFpEF), suggesting impaired cardiac reserve (P < 0.001).

Figure 2

Peak cardiac power output and peak stroke work. These measures of cardiac reserve were not statistically different between groups, suggesting that cardiac reserve is not impaired in heart failure with preserved ejection fraction (HFpEF).

Figure 3

Cardiac output response to exercise (Q_c/VO₂) by group. The ΔQ_c/ΔVO₂ slope was markedly elevated in patients with heart failure with preserved ejection fraction (HFpEF) (11.2 ± 3.6 vs. 8.3 ± 1.5; P = 0.015). This finding, which has also been observed in patients with mitochondrial myopathies, suggests that impaired skeletal muscle oxidative metabolism in HFpEF may be the explanation for diminished oxygen uptake in this group. Excluding the HFpEF patient with a markedly elevated Q_c at a low peak VO₂ (the patient at the top left of the HFpEF plot), the ΔQ_c/ΔVO₂ slope remained elevated in HFpEF patients when compared with controls (10.4 ± 2.6 vs. 8.3 ± 1.5; P = 0.023).

Figure 4

³¹Phosphorus magnetic resonance spectroscopy (³¹P-MRS)-derived phosphocreatine (PCr) recovery curves in a control subject from the current study (open circles), a patient with heart failure with preserved ejection fraction (HFpEF) from the current study (inverted triangles), and a previously tested mitochondrial myopathy patient (upright triangle). Subjects were tested using a similar protocol during which the quadriceps muscle was imaged immediately after achieving a pre-defined exercise-induced metabolic state. Post-exertion, HFpEF and mitochondrial myopathy patients have diminished PCr stores with delayed regeneration, suggesting that impaired skeletal muscle oxidative metabolism in HFpEF may be the explanation for the diminished oxygen uptake in this group.