Patients with heart failure and preserved ejection fraction (HFpEF) have markedly reduced exercise capacity with poorly understood, multifactorial causes. In this Dutch two-site study (58 HFpEF patients, 16 controls), in-vivo 31phosphorus MR spectroscopy measured mitochondrial oxidative muscle metabolism via phosphocreatine recovery after isometric or dynamic exercise. Phosphocreatine recovery halftime after isometric exercise was prolonged in HFpEF patients (27 vs 24 seconds), indicating reduced skeletal-muscle oxidative capacity. This held regardless of iron deficiency, whereas higher hs-CRP was associated with slower recovery. Exercise intolerance in HFpEF thus arises partly from intrinsically impaired muscle energetics, not iron deficiency alone.
In this parallel analysis of prospective studies at two sites, patients with HFpEF and control individuals performed either isometric exercise (isolated leg protocol) or dynamic exercise (cardiopulmonary protocol) with concomitant phosphocreatine recovery assessment using in vivo 31P-MRS. Associations between clinical factors and oxidative metabolism were evaluated. ID was defined as ferritin <100 µg/L, or ferritin 100-299 µg/L with transferrin saturation <20%.
Fifty-eight patients with HFpEF and 16 controls performed isometric exercise (n = 46 HFpEF; n = 16 control) or cardiopulmonary exercise (n = 12 HFpEF). Phosphocreatine recovery halftime after isometric exercise was prolonged in patients versus controls [27 (23-32) vs 24 (19-28) seconds, respectively; P = .03]. Phosphocreatine recovery halftime after dynamic exercise in patients was 39 (27-57) seconds. Both cohorts consisted of patients with and without ID (n = 19 and 27, and n = 6 and 6, respectively), who had comparable exercise and oxidative muscle capacity (all P > .42). High-sensitive C-reactive protein was associated with prolonged phosphocreatine recovery halftime (P =. 01).
Patients with HFpEF exhibit impaired whole-muscle oxidative capacity of skeletal muscle, as shown by two different 31P-MRS protocols with upper leg measurements, independent of ID status. STUDY REGISTRATION: NTR6605, NTR7297 (https://onderzoekmetmensen.nl/nl/trial/55673); NCT05750940 (https://clinicaltrials.gov/study/NCT05750940).
