Key result
Patients with HFpEF demonstrated significantly impaired skeletal muscle oxidative phosphorylation, evidenced by a longer half-time of creatine recovery (median 167.4 s) compared to healthy controls (127.6 s) and hypertensive controls (114.4 s).
Why the study?
Skeletal muscle abnormalities may impact exercise capacity in patients with HFpEF, motivating quantification of differences in oxidative phosphorylation capacity, fibre composition, and the proteome across HFpEF, hypertensive, and healthy individuals.
Do patients with HFpEF have differences in skeletal muscle oxidative phosphorylation capacity, fibre composition, and proteome compared to hypertensive and healthy participants?
Cross-Sectional (n=59)
No
Do patients with HFpEF have differences in skeletal muscle oxidative phosphorylation capacity, fibre composition, and proteome compared to hypertensive and healthy participants?
Absolute Event Rate: 167.4% vs 127.6%
p-value: p=0.005
Patients with HFpEF exhibit impaired skeletal muscle oxidative phosphorylation, fewer Type I myofibres, and altered proteomic signalling, which may contribute to their exercise intolerance.
Aims Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants. Methods and results Fifty-nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal-effort cardiopulmonary exercise test to define peak oxygen consumption (VO2, peak), ventilatory threshold (VT), and VO2 efficiency (ratio of total work performed to O2 consumed). SkM OxPhos was assessed using Creatine Chemical-Exchange Saturation Transfer (CrCEST, n = 51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half-time of Cr recovery (t1/2, Cr) was taken as a metric of in vivo SkM OxPhos. In a subset of subjects (healthy = 13, HTN = 9, and HFpEF = 12), percutaneous biopsy of the vastus lateralis was performed for myofibre typing, mitochondrial morphology, and proteomic and phosphoproteomic analysis. HFpEF subjects demonstrated lower VO2,peak, VT, and VO2 efficiency than either control group (all P < 0.05). The t1/2, Cr was significantly longer in HFpEF (P = 0.005), indicative of impaired SkM OxPhos, and correlated with cycle ergometry exercise parameters. HFpEF SkM contained fewer Type I myofibres (P = 0.003). Proteomic analyses demonstrated (a) reduced levels of proteins related to OxPhos that correlated with exercise capacity and (b) reduced ERK signalling in HFpEF. Conclusions Heart failure with preserved ejection fraction patients demonstrate impaired functional capacity and SkM OxPhos. Reductions in the proportions of Type I myofibres, proteins required for OxPhos, and altered phosphorylation signalling in the SkM may contribute to exercise intolerance in HFpEF.
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Zamani et al. (2021) conducted a cross-sectional in Heart failure with preserved ejection fraction (HFpEF) (n=59). Heart failure with preserved ejection fraction vs. Hypertensive and healthy controls was evaluated on Half-time of creatine recovery (t1/2, Cr) as a metric of in vivo skeletal muscle oxidative phosphorylation (p=0.005). Patients with HFpEF demonstrated significantly impaired skeletal muscle oxidative phosphorylation, evidenced by a longer half-time of creatine recovery (median 167.4 s) compared to healthy controls (127.6 s) and hypertensive controls (114.4 s).
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