Predictive Value of high-sensitivity cardiac troponin T in patients undergoing 99mTc pyrophosphate scintigraphy for suspected transthyretin amyloid cardiomyopathy

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (1,2). 99mTc- pyrophosphate cardiac scintigraphy (PYP) enables accurate, noninvasive diagnosis of ATTR-CM when coupled with appropriate clinical and laboratory evaluations to rule out light chain amyloidosis (3,4). High sensitivity cardiac troponin T (hs-cTnT) is routinely assessed for diagnostic purposes when ATTR-CM is suspected in clinical practice. Purpose To investigate the diagnostic performance of hs-cTnT in patients undergoing PYP for suspected ATTR-CM. Methods Observational study of patients undergoing PYP at a United States (US) cardiac amyloidosis referral center from 2013 to September 2022 and with at least one hs-cTnT value available within 1 year. 3-hour planar imaging followed by single photon-emission computed tomography with computed tomography was performed. Final diagnoses of ATTR-CM were validated using all clinical information. The lowest reportable clinical value for hs-cTnT in the US is <6 ng/L (limit of quantitation). Results A total of 1572 patients underwent PYP and had a hs-cTnT value available within the study period. Of these, ATTR-CM was diagnosed in 475 patients (30%). Median (IQR) hs-cTnT was 48 (31-67) ng/L in patients with ATTR-CM and 26 (13-48) ng/L in those without. The area under the curve of hs-cTnT for the diagnosis of ATTR-CM was 0.69 (0.67-0.72). Among patients with a very low hs-cTnT value, i.e. <6 ng/L (n=100, 6.4% of the overall cohort), 7 (7%) patients had a final ATTR-CM diagnosis while 93 (93%) did not. Therefore, a threshold of <6 ng/L demonstrated a negative predictive value (NPV) of 93% (IQR 88, 98) and a sensitivity of 99% (97, 100) for ruling out ATTR-CM. The highest NPV was achieved with a threshold of 12 ng/L; 269 (17%) patients had hs-cTnT below this value and, of those, only 16 (6%) had a final diagnosis of ATTR-CM. This resulted in a NPV of 94% (91, 97) and a sensitivity of 97% (95, 98) for ruling out ATTR-CM. When considering progressively increasing hs-cTnT values as potential thresholds to aid in the prediction of ATTR-CM (Figure), we observed a progressive increase in specificity (above 90% for hs-cTnT values > 95 ng/L), but the positive predictive value (PPV) remained low (below 50%). Conclusions Among patients undergoing PYP for suspected ATTR-CM at a US referral center, a very low hs-cTnT value was present in a minority of patients but demonstrated good performance in ruling out ATTR-CM. The highest NPV (94%) was achieved with a threshold of < 12 ng/L. Higher hs-cTnT values showed a good specificity, but PPV remained low. Therefore, while a very low hs-cTnT might be of help in identifying those at low risk of ATTR-CM, the ubiquitous presence of increased hs-cTnT in many of these patients suggests the need for a multiparametric diagnostic approach to make the diagnosis.hs-cTnT in patients undergoing PYP scan