Open AccessMultimodality assessment of heart failure with preserved ejection fraction skeletal muscle reveals differences in the machinery of energy fuel metabolism
Author(s) -
Zamani Payman,
Proto Elizabeth A.,
Wilson Neil,
Fazelinia Hossein,
Ding Hua,
Spruce Lynn A.,
Davila Antonio,
Hanff Thomas C.,
Mazurek Jeremy A.,
Prenner Stuart B.,
Desjardins Benoit,
Margulies Kenneth B.,
Kelly Daniel P.,
Arany Zoltan,
Doulias PaschalisThomas,
Elrod John W.,
Allen Mitchell E.,
McCormack Shana E.,
Schur Gayatri Maria,
D'Aquilla Kevin,
Kumar Dushyant,
Thakuri Deepa,
Prabhakaran Karthik,
Langham Michael C.,
Poole David C.,
Seeholzer Steven H.,
Reddy Ravinder,
Ischiropoulos Harry,
Chirinos Julio A.
Publication year - 2021
Publication title -
esc heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.787
H-Index - 25
ISSN - 2055-5822
DOI - 10.1002/ehf2.13329
Subject(s) - heart failure with preserved ejection fraction , medicine , heart failure , cardiology , ejection fraction , oxidative phosphorylation , vo2 max , skeletal muscle , respiratory exchange ratio , endocrinology , heart rate , biochemistry , chemistry , blood pressure
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 (VO 2, peak ), ventilatory threshold (VT), and VO 2 efficiency (ratio of total work performed to O 2 consumed). SkM OxPhos was assessed using Cr eatine C hemical‐ E xchange S aturation T ransfer (CrCEST, n = 51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half‐time of Cr recovery (t 1/2, 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 VO 2,peak , VT, and VO 2 efficiency than either control group (all P < 0.05). The t 1/2, 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.