BACKGROUND: 

The current European guidelines emphasize the significance of objective risk stratification as central elements of patient-centered decision-making for valve interventions. However, the guidelines refer to surgical risk scores, such as the STS-PROM and EuroSCORE II, which do not consider important clinical factors such as frailty. CT is a routine part of the pre-interventional workup in patients with severe aortic stenosis (AS) and allows for comprehensive body composition analysis, including the assessment of fat-free muscle fraction (FFMF) as an indicator of muscle quality.

AIMS: 

The aim of this study was to evaluate the relationship between FFMF and inflammation as well as endocrine disorder and to examine the predictive value of FFMF in patients with AS undergoing TAVR.

METHODS: 

The study cohort consisted of 789 patients undergoing TAVR. The patients were evaluated with CT scans, and skeletal muscle area at the L3/L4 level was determined. The skeletal muscle area was separated in areas of fatty and lean muscle according to densitometric thresholds to calculate the fat-free muscle fraction (Figure 1). The cohort was stratified into tertials to define patients with high, medium, and low FFMF, respectively. Outcome of interest was one-year all-cause mortality following TAVR.

RESULTS: 

The study population was 45.5% female and had a mean age of 81.2±6.0 years. According to the CT evaluation 261 (33.1%) patients had a high FFMF, 293 (37.1%) patients had a medium FFMF, and 235 (29.8%) patients had a low FFMF. Patients with a low FFMF were older (82.3±5.9 years vs 81.6±5.6 years vs 79.8±6.2 years, p<0.01) compared to patients with a medium and high FFMF. Regarding body composition, patients with a low FFMF had higher percentage of body fat (28.7±11.2% vs 26.8±9.1% vs 24.2±9.6%, p=0.01) as well as lower percentage of body muscle (30.9±5.3% vs 31.3±4.2% vs 32.7±4.4%, p=0.03). Moreover, a low FFMF was associated with inflammation as indicated by increased levels of C-reactive protein (6.30 mg/l vs 4.20 mg/l vs 3.10 mg/l, p<0.01) and procalcitonin (0.06 µg/l vs 0.05 µg/l vs 0.05 µg/l, p=0.01). Endocrinological assessment revealed lower levels of estradiol (6.80 pg/ml vs 14.70 pg/ml vs 15.50 pg/ml, p=0.02) and testosterone (0.18 ng/ml vs 0.48 ng/ml vs 2.35 ng/ml, p<0.01) as well as higher levels of basal cortisol (8.90 μg/dl vs 7.70 μg/dl vs 7.60 μg/dl, p=0.05) in patients with a low FFM. Regarding clinical outcomes, a low FFMF was associated with increased one-year mortality (23.4%) as compared to a medium (11.6%) or low FFMF (3.8%, p<0.01), Figure 2. By using receiver operating characteristics curve analysis, FFMF (AUC 0.75 [95% CI: 0.66-0.85], p<0.01) showed the strongest association with one-year all-cause mortality and was superior to the STS-PROM (AUC 0.65) and EuroSCORE II (AUC 0.64). Multivariate  regression analysis revealed that a low FFMF (OR: 3.19 [95% CI: 1.64 – 6.22], p<0.01) was an independent predictor of one-year mortality following TAVR.

CONCLUSION:

The CT-derived FFMF is associated with inflammation and endocrinological disorder in patients with aortic stenosis undergoing TAVR. Moreover, a low FFMF is a strong and independent predictor of dismal outcomes following TAVR. The assessment of FFMF as a measure of muscle quality can be easily conducted using routine pre-interventional CT, making it a promising and objective imaging parameter for predicting outcomes in patients undergoing TAVR.

Figure 1)

Figure 2)