Skeletal muscle and subcutaneous fat quantity as prognostic indicators in cardiac amyloidosis

Disease-related changes in body composition are associated with worse outcomes in chronic heart failure. In cardiac amyloidosis (CA), the prognostic value of direct body composition measures is understudied.

We identified 160 consecutive patients with CA (transthyretin [ATTR] or light chain [AL]) diagnosed between 2001 and 2021 who had chest computed tomography within 1 year before diagnosis. Skeletal muscle index (SMI), intermuscular adipose tissue percentage (IMAT%), and subcutaneous adipose tissue index (SATI) were quantified at the twelfth vertebral level and analysed continuously, in sex-stratified tertiles, and with derived outcome-based cutoffs. In a comprehensive model including IMAT% and SATI, only SMI independently predicted 10-year mortality (hazard ratio 0.69 per standard deviation increase, 95% confidence interval 0.52-0.91, p = 0.010). In tertile analyses, low SMI was associated with 2 to 2.5 times higher 1-year, 5-year, and 10-year mortality versus high SMI. Medium IMAT% and SATI showed approximately 1.9 times higher 5-year and 10-year mortality versus high tertiles. These associations were more pronounced in ATTR-CA, with low SATI also predicting higher mortality. AL-CA showed fewer significant associations. Interaction testing by CA type was not significant. Outcome-based SMI cutoffs of 23.5 cm²/m² (males) and 27.8 cm²/m² (females) for 10-year mortality were derived but need validation.

Lower SMI was associated with increased mortality risk in patients with CA, particularly ATTR-CA. The relationship between SATI and mortality was more nuanced: in the overall cohort, medium SATI was associated with higher mortality risk, while in patients with ATTR-CA, lower SATI predicted higher mortality risk.