Novel echocardiographic pixel intensity quantification method for differentiating transthyretin cardiac amyloidosis from light chain cardiac amyloidosis and other phenocopies

Abstract Aims Differentiating cardiac amyloidosis (CA) subtypes is important considering the significantly different therapies for transthyretin (ATTR)-CA and light chain (AL)-CA. Therefore, an echocardiographic method to distinguish ATTR-CA from AL-CA would provide significant value. We assessed a novel echocardiographic pixel intensity method to quantify myocardial calcification to differentiate ATTR-CA from phenocopies of CA and from AL-CA, specifically. Methods and results 167 patients with ATTR-CA (n = 53), AL-CA (n = 32), hypertrophic cardiomyopathy (n = 37), and advanced chronic kidney disease (n = 45) were retrospectively evaluated. The septal reflectivity ratio (SRR) was measured as the average pixel intensity of the visible anterior septal wall divided by the average pixel intensity of the visible posterior lateral wall. SRR and other myocardial strain-based echocardiographic measures were evaluated with receiver operator characteristic analysis to evaluate accuracy in distinguishing ATTR-CA from AL-CA and other forms of left ventricular hypertrophy. Mean SRR was significantly higher in the ATTR-CA cohort compared to the other cohorts (P 0.001). SRR demonstrated the largest area under the curve (AUC) (0.91, P 0.001) for distinguishing ATTR from all other cohorts and specifically for distinguishing ATTR-CA from AL-CA (AUC = 0.90, P 0.001, specificity 96%, and sensitivity 63%). There was excellent inter- and intra-operator reproducibility with an ICC of 0.91 (P 0.001) and 0.89 (P 0.001), respectively. Conclusion The SRR is a reproducible and robust parameter for differentiating ATTR-CA from other phenocopies of CA and specifically ATTR-CA from AL-CA.