Prospective validation of a predictive model and simplified score for the diagnosis of transthyretin cardiac amyloidosis: the PROVALTA study
C Goena-Vives, X Arana-Achaga, R Eiros-Bachiller, M Sutil-Vega, P Menendez-Suarez, D Mialdea-Salmeron, I Fiteni-Mera, L Bernal, M Pajares, I Francisco-RecueroAbstract
Background
Transthyretin cardiac amyloidosis (ATTR-CM) remains substantially underdiagnosed in heart failure populations. Limited access to advanced imaging and the absence of simple selection tools contribute to delayed or missed diagnoses. The T-Amylo model was previously developed in a retrospective cohort to facilitate early non-invasive identification of ATTR-CM. The main objective of the study is to prospectively validate the diagnostic performance of the T-Amylo predictive model and a simplified score in a real-world clinical practice setting.
Methods
Prospective, multicentre observational study including patients ≥65 years with septal hypertrophy (≥12 mm) and at least one clinical red flag suggestive of ATTR-CM according to the ESC consensus statement. The T-Amylo model and simplified score were applied a priori. Diagnostic performance was assessed using the area under the curve (AUC), sensitivity, specificity, and predictive values. Statistical significance compared to the original retrospective predictive model was tested using Fisher’s exact test and a Z-test.
Results
Of the 372 enrolled patients, 367 were included in the final analysis; 32 (8.7%) were diagnosed with ATTR-CM (absence of monoclonal component and Perugini grade 2-3 in cardiac scintigraphy). The T-Amylo model demonstrated good discrimination (AUC 0.84; 95% CI 0.78–0.91), with 91% sensitivity, 93% specificity, an excellent negative predictive value (NPV) of 98% and a positive predictive value (PPV) of 44%. The simplified score showed comparable performance with an AUC of 0.81 [0.73-0.88]; 97% sensitivity and 96% specificity (NPV 99%; PPV 50%) (Figure 1). Diagnostic accuracy was consistent across age, sex, and number of red-flag subgroups.
Conclusions
PROVALTA is the first prospective multicentre validation of the T-Amylo model and simplified score. T-Amylo demonstrated excellent performance for ruling out ATTR-CM, enabling reliable exclusion and potentially reducing unnecessary advanced diagnostic testing. Importantly, it also reliably identified patients at high risk of ATTR-CM, enabling targeted use of confirmatory imaging in older populations.ROC curves for discriminationFor image description, please refer to the figure legend and surrounding text.