Thoracic Skeletal Muscle Attenuation Predicts Sex-Specific Mortality After Coronary Artery Bypass Grafting-Sex-Specific Insights into Risk Stratification and Frailty Assessment.

Abstract

Background: Frailty and impaired muscle quality are strong determinants of adverse outcomes after coronary artery bypass grafting (CABG), yet conventional risk scores overlook this biological dimension. The Hounsfield Unit Average Calculation (HUAC) obtained from routine preoperative computed tomography (CT) scans quantifies skeletal muscle attenuation, reflecting intramuscular fat infiltration and metabolic reserve. This study evaluated the prognostic value of HUAC measured at two thoracic levels and explored sex-specific differences in its predictive performance. Methods: In this retrospective single-center study, 479 patients (382 men, 97 women) undergoing isolated CABG with available preoperative CT scans were analyzed. Mean HUAC was measured bilaterally at the fourth (TH4) and twelfth (TH12) thoracic vertebral levels. Sex-specific HUAC quartiles were generated, with the lower quartile defining low thoracic muscle attenuation, representing a radiographic phenotype of impaired muscle quality. Associations with 1-, 3-, and 5-year mortality were assessed by Kaplan-Meier analysis, receiver-operating-characteristic (ROC) curves, and sex-stratified Cox regression models incorporating inverse probability weighting (IPW). Incremental prognostic value beyond EuroSCORE II was assessed by comparing Harrell's C-statistics of Cox models with and without low HUAC. Results: Patients with low HUAC showed reduced survival at all time points. HUAC measured at TH4 demonstrated higher discriminative ability compared with TH12. In women, TH4 yielded area under the curve (AUC) of 0.773 and 0.807 for 1- and 3-year survival, respectively, compared with 0.670 and 0.640 in men. In sex-specific Cox analyses, women in the lower HUAC-TH4 quartile had markedly increased mortality risk (unweighted HRs 6.6, 9.5, and 6.4 for 1-, 3-, and 5-year follow-up; all p ≤ 0.03), which remained significant after IPW adjustment. In men, the association was weaker and lost significance after weighting. Formal interaction testing demonstrated significant sex × low-HUAC interactions at TH4 for 3- and 5-year mortality (p interaction = 0.046 and 0.045, respectively), whereas no significant interaction was observed at TH12. Addition of low TH4 HUAC to EuroSCORE II improved model discrimination in the overall cohort, with C-statistics increasing from 0.665 to 0.711 at 3 years and from 0.658 to 0.690 at 5 years (both likelihood-ratio p < 0.001); the largest incremental gains were observed in women (ΔC = +0.115 and +0.081, respectively). Conclusions: Low thoracic muscle attenuation, particularly HUAC at TH4, independently predicts long-term mortality after CABG. Formal interaction testing supports an exploratory sex-dependent prognostic association at TH4, with a stronger association of low muscle attenuation with mortality in women than in men. HUAC represents a simple, objective biomarker of physiological reserve that can be derived from existing preoperative CT scans and may enhance individualized risk stratification in contemporary cardiac surgery.