Mitochondrial dysfunction contributes to sustained muscle loss after cardiac surgery: a prospective observational study
Author(s)
Type
Journal Article
Abstract
Background
As a major systemic insult, cardiac surgery can lead to significant muscle loss, which increases the time to recovery as well as being correlated with mortality. Highly variable loss of muscle mass (0%–40% rectus femoris cross-sectional area [RFcsa]) and strength in the week after surgery has aided understanding of mechanisms of sarcopenia after acute illness. To include muscle recovery, patients' muscle phenotype beyond the first week after surgery and up to their return as outpatients was studied and correlated with protein and metabolomic markers.
Methods
Patients undergoing elective aortic valve surgery were recruited. Muscle mass (RFcsa), strength (handgrip, knee extension and spirometry), body composition (by bioimpedance) and health-related quality of life (generic questionnaire EQ-5D-5L) were determined pre-operatively, 7 days after surgery and at outpatient follow-up. Blood samples were taken on Days 0, 1, 3, 7 and follow-up. The plasma metabolome was determined in 20 patients at Days 0, 3, 7 and follow-up.
Results
Of 31 participants, 20 were male: mean age 68.8 years with a range between 48 and 85 years. Proportionate mean loss of RFcsa between pre-op and Day 7 values was 6.44% [95% CI 4.21 to 8.68, n = 31]; between pre-op and follow-up 9.69% [95% CI 4.92 to 14.96, n = 22]; and between Day 7 and follow-up 3.60% [95% CI −1.30 to 8.48, n = 22]. By contrast to measures of muscle bulk, the strength and functionality assessments (knee extension, handgrip, spirometry and short physical performance battery) decreased in the first week after surgery (pre-op to Day 7) followed by a return to baseline (Day 7 to follow-up). Health-related quality of life (cross-walk index) changed little over the course of the study but correlated positively at follow-up with muscle bulk (RFcsa: r = 0.58 [95% CI 0.19 to 0.81] p = 0.005) and strength of knee extension (r = 0.54 [95% CI 0.14 to 0.79] p = 0.010) and handgrip (r = 0.63 [95% CI 0.27 to 0.83] p = 0.002: n = 22). Both pre-operative and peak (Day 3) plasma levels of short-chain acyl-carnitine markers of mitochondrial dysfunction correlated with proportional muscle loss at follow-up and with strength at all timepoints.
Conclusions
Prolonged follow-up after aortic surgery demonstrated a divergence between the consistent recovery of strength and a significant proportion of patients continuing to lose muscle bulk. Markers of baseline and acute mitochondrial dysfunction predicted poor muscle outcomes up to outpatient follow-up.
As a major systemic insult, cardiac surgery can lead to significant muscle loss, which increases the time to recovery as well as being correlated with mortality. Highly variable loss of muscle mass (0%–40% rectus femoris cross-sectional area [RFcsa]) and strength in the week after surgery has aided understanding of mechanisms of sarcopenia after acute illness. To include muscle recovery, patients' muscle phenotype beyond the first week after surgery and up to their return as outpatients was studied and correlated with protein and metabolomic markers.
Methods
Patients undergoing elective aortic valve surgery were recruited. Muscle mass (RFcsa), strength (handgrip, knee extension and spirometry), body composition (by bioimpedance) and health-related quality of life (generic questionnaire EQ-5D-5L) were determined pre-operatively, 7 days after surgery and at outpatient follow-up. Blood samples were taken on Days 0, 1, 3, 7 and follow-up. The plasma metabolome was determined in 20 patients at Days 0, 3, 7 and follow-up.
Results
Of 31 participants, 20 were male: mean age 68.8 years with a range between 48 and 85 years. Proportionate mean loss of RFcsa between pre-op and Day 7 values was 6.44% [95% CI 4.21 to 8.68, n = 31]; between pre-op and follow-up 9.69% [95% CI 4.92 to 14.96, n = 22]; and between Day 7 and follow-up 3.60% [95% CI −1.30 to 8.48, n = 22]. By contrast to measures of muscle bulk, the strength and functionality assessments (knee extension, handgrip, spirometry and short physical performance battery) decreased in the first week after surgery (pre-op to Day 7) followed by a return to baseline (Day 7 to follow-up). Health-related quality of life (cross-walk index) changed little over the course of the study but correlated positively at follow-up with muscle bulk (RFcsa: r = 0.58 [95% CI 0.19 to 0.81] p = 0.005) and strength of knee extension (r = 0.54 [95% CI 0.14 to 0.79] p = 0.010) and handgrip (r = 0.63 [95% CI 0.27 to 0.83] p = 0.002: n = 22). Both pre-operative and peak (Day 3) plasma levels of short-chain acyl-carnitine markers of mitochondrial dysfunction correlated with proportional muscle loss at follow-up and with strength at all timepoints.
Conclusions
Prolonged follow-up after aortic surgery demonstrated a divergence between the consistent recovery of strength and a significant proportion of patients continuing to lose muscle bulk. Markers of baseline and acute mitochondrial dysfunction predicted poor muscle outcomes up to outpatient follow-up.
Date Issued
2025-08-01
Date Acceptance
2025-07-21
Citation
Journal of Cachexia, Sarcopenia and Muscle, 2025, 16 (4)
ISSN
2190-5991
Publisher
Wiley
Journal / Book Title
Journal of Cachexia, Sarcopenia and Muscle
Volume
16
Issue
4
Copyright Statement
© 2025 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40842041
Subjects
aortic surgical procedures
critical illness myopathy
metabolomics
mitochondria
muscle regeneration
muscle strength recovery
muscular atrophy
pathology
Humans
Male
Female
Aged
Middle Aged
Prospective Studies
Cardiac Surgical Procedures
Quality of Life
Aged, 80 and over
Mitochondria
Sarcopenia
Muscle, Skeletal
Muscle Strength
Publication Status
Published
Coverage Spatial
Germany
Article Number
e70051
Date Publish Online
2025-08-21