Low aortic valve calcium score as an imaging red flag for concomitant transthyretin cardiac amyloidosis in severe aortic stenosis: A CAUSATIVE study subanalysis
A Cantone, F Cappelli, G Campo, P Cimaglia, R Conti, G M De Ferrari, M Emdin, S Longhi, C Nitsche, G Pontone, A Porcari, F Vagnarelli, M SerenelliAbstract
Background
Transthyretin amyloid cardiomyopathy (ATTR-CM) frequently coexists with severe aortic stenosis (AS). In this setting, non-contrast cardiac computed tomography (CCT) may reveal a relatively low aortic valve calcium (AVC) burden despite hemodynamically severe AS, potentially reflecting a mixed calcific and non-calcific (including amyloid) valvular substrate.
Purpose
To evaluate whether low AVC identifies a higher probability of concomitant ATTR-CM and should be considered an imaging red flag in older patients with severe AS.
Methods
This subanalysis of the prospective, multicenter CAUSATIVE study1 included consecutive patients aged ≥65 years with symptomatic severe degenerative AS (aortic valve area <1.0 cm²), indication for aortic valve replacement, and ≥1 clinical/echocardiographic red flag for amyloidosis. All patients underwent standardized CCT AVC quantification and a systematic diagnostic work-up for ATTR-CM. Patients were stratified by sex-specific tertiles of indexed AVC (Agatston units, AU). Multivariable logistic regression tested the association between indexed AVC and ATTR-CM, with the odds ratio calculated for a 1000-unit change in indexed Agatston units, adjusting for age, sex, estimated glomerular filtration rate (eGFR), and low-flow low-gradient (LFLG) AS phenotype.
Results
Among 504 patients, 104 (20.6%) were diagnosed with ATTR-CM. ATTR-CM prevalence decreased across increasing AVC tertiles both in men (38.5%, 33%, and 15.2%; p-trend = 0.001) and women (18.8%, 9.2%, and 4.3%; p-trend = 0.009). In multivariable analysis, indexed AVC was independently and inversely associated with ATTR-CM (odds ratio 0.49 per 1000 AU/m²; 95% CI 0.32–0.73; p=0.001). Adjusted predicted probability curves demonstrated a marked increase in ATTR-CM probability at lower indexed AVC values, particularly in men (Figure 1). Using guideline-referenced CT-AVC likelihood strata, ATTR-CM prevalence was highest in the “unlikely severe” stratum (37.3%; NNT 2.68) and lowest in the “very likely severe” stratum (14.0%; NNT 7.12) (Table 1).
Conclusion
In older patients with severe AS undergoing aortic valve replacement evaluation, a low aortic valve calcium score is independently associated with concomitant ATTR-CM and should be considered an imaging red flag prompting dedicated amyloidosis assessment. Reliance on calcium score thresholds alone may underestimate the likelihood of severe AS in patients with dual pathology.Figure 1.Table 1.