Understanding the Relationships of Cardiac Diagnostics in Patients with Amyloid Transthyretin Cardiac Amyloidosis

Abstract

Amyloid transthyretin (ATTR) cardiac amyloidosis (CA) is an increasingly recognized cause of restrictive cardiomyopathy and associated heart failure with preserved ejection fraction (HFpEF). Despite improved diagnostic techniques to identify this condition, many patients experience delayed diagnosis. Interpretation of routine cardiac biomarkers (i.e. troponins and brain natriuretic peptide (BNP)) and echocardiography in ATTR-CA is limited, particularly in relation to pyrophosphate (PYP) scintigraphy. We sought to investigate the relationship of cardiac diagnostics to standard of care non-invasive imaging modalities. We conducted a single-center retrospective cohort study of patients diagnosed with a genetic variant in the transthyretin (TTR) gene or ATTR-CA (wild-type and variant cases). The association between PYP grade (0-3), PYP ratios, echocardiographic variables, and cardiac biomarkers (troponin and BNP) was investigated using linear regression models. Among 140 cases, 83 utilized a PYP scan as part of their diagnostic workup. The association between PYP grade and presenting troponin was statistically significant for grades 1-3, using grade 0 as the referent. Grade 1 was observed to have a median value of 79 ng/L [IQR 37-115]. The median for Grade 2 was 92 [IQR 10-237] and 92.5 for Grade 3 [IQR 45-187]. This contrasted with presenting BNP which demonstrated no correlation between PYP Grade and presenting values. The quantitative score, PYP ratio, did not show any statistically significant correlation with presenting biomarkers. However, PYP ratio was significantly positively correlated with left ventricular mass (g) 88.14 [95% CI; 41.66-134.62] and interventricular septal thickness at end diastole (IVSd;cm) 0.33 [95% CI; 0.17-0.49], both p<0.001. We found that troponins were correlated with PYP grade in patients with ATTR-CA. More so, higher presenting troponins and IVSd were associated with a higher PYP grade and PYP ratio respectively, which may suggest ATTR-CA and thus indicate scintigraphy in management of HFpEF cases of unknown etiology. Together, these results provide a novel take on the correlation of traditional cardiac biomarkers with structural changes observed in non-invasive imaging, highlighting the need for a combinatorial approach to diagnosing ATTR-CA.