^99m Tc-Pyrophosphate Scintigraphy for Differentiating Light-Chain Cardiac Amyloidosis From the Transthyretin-Related Familial and Senile Cardiac Amyloidoses

Abstract

Background Differentiating immunoglobulin light-chain (AL) from transthyretin-related cardiac amyloidoses (ATTR) is imperative given implications for prognosis, therapy, and genetic counseling. We validated the discriminatory ability of 99mTc-pyrophosphate scintigraphy (99mTc-PYP) in AL vs. TTR-related cardiac amyloidoses. Methods and Results 45 subjects (12 AL, 16 ATTR wild-type, and 17 ATTR mutants) underwent 99mTc-PYP planar and single-photon positive emission computed tomography (SPECT) cardiac imaging. Scans were performed by experienced nuclear cardiologists blinded to the subjects’ cohort assignment. Cardiac retention was assessed with both a semi-quantitative visual score (range 0, no uptake to 3, diffuse uptake) and by quantitative analysis by drawing a region of interest (ROI) over the heart corrected for contralateral counts and calculating a heart-to-contralateral ratio (H/CL). Subjects with ATTR cardiac amyloid had a significantly higher semi-quantitative cardiac visual score than the AL cohort (2.9±0.06 vs. 0.8±0.27, p<0.0001) as well as a higher quantitative score (1.80±0.04 vs.1.21±0.04, p<0.0001). Using aH/CL ratio ≥ 1.5 consistent with intensely diffuse myocardial tracer retention had a 97% sensitivity and 100% specificity with area under the curve 0.992, p<0.0001 for identifying ATTR cardiac amyloidosis. Conclusion 99mTc-PYP cardiac imaging distinguishes AL from ATTR cardiac amyloidosis and may be a simple, widely available method for identifying subjects with ATTR cardiac amyloidosis which should be studied in a larger prospective manner.

Biochemical markers in early diagnosis and management of systemic amyloidoses

“…Moreover, the serum concentrations of total TTR in SSA patients did not differ from age, gender and ethnically matched controls or from a group of AL patients with significant clinical cardiac involvement [110]. Scintigraphy with Tc-pyrophosphate can help in differentiating transthyretin-related familial and senile cardiac amyloidoses from light chain cardiac amyloidosis [111,112]. However, the diagnosis of SSA requires endomyocardial biopsy, with demonstration that the deposited fibrils are constituted by TTR, in absence of mutated TTR by DNA sequencing.…”

Nuclear imaging of cardiac amyloidosis

“…Planar imaging alone or with single-photon emission computed tomography (SPECT) using nonamyloid-specific, bone-avid radiotracers ( 99m Tc-DPD [3,3- [8][9][10][11][12][13][14][15][16][17] Recent data indicate that the increased level of microcalcifications may explain the enhanced affinity of bone-seeking tracers for TTR over AL amyloidosis. 18 Amyloidspecific, positron emitting 18 F-and 11 C-tagged tracers have been used successfully with positron emission tomography (PET) imaging for the identification of both AL and TTR subtypes of CA.…”

“…Since the seminal work by Perugini et al 8 , a number of other studies have showed that 99m Tc-DPD and 99m Tc-PYP nuclear imaging is feasible and effective in detecting TTR-CA. 9,11,12,[15][16][17] In addition to the traditionally used qualitative Perugini score which compares myocardial to bone uptake and the semiquantitative HR:WBR, 8 Bokhari et al also showed that 99M Tc-PYP imaging with a heart-to-contralateral lung ratio of [1.5 detected TTR-CA with a 97% and 100% sensitivity and specificity, respectively. 16 Negative and positive example images of TTR-CA with 99M Tc-PYP imaging are depicted in Figures 1 and 2.…”

“…9,11,12,[15][16][17] In addition to the traditionally used qualitative Perugini score which compares myocardial to bone uptake and the semiquantitative HR:WBR, 8 Bokhari et al also showed that 99M Tc-PYP imaging with a heart-to-contralateral lung ratio of [1.5 detected TTR-CA with a 97% and 100% sensitivity and specificity, respectively. 16 Negative and positive example images of TTR-CA with 99M Tc-PYP imaging are depicted in Figures 1 and 2. Gillmore et al have conducted the largest multicenter study to date, showing that cardiac uptake (Perugini grades 1, 2 or 3) on planar imaging with bisphosphonates (N = 877 99m Tc-DPD, N = 199 99m Tc-PYP, N = 141 99m Tc-HMDP) is [99% sensitive and 68% specific for detecting TTR-CA, based on the subgroup of patients who had undergone endomyocardial biopsy.…”

Technetium 99m pyrophosphate radioisotope for diagnosis and prognosis of transthyretin cardiac amyloidosis: A call for collaboration

“…3 The authors of the current study performed a retrospective analysis in 75 patients with suspected ATTR cardiac amyloidosis who underwent planar Tc99 m PYP cardiac imaging, 48 of whom were reported to have ATTR, 12 with endomyocardial biopsy-proven disease. Myocardial Tc99 m PYP uptake was evaluated on planar images using the established semiquantitative score 5 and the quantitative H/CL chest ratio, 6 although the authors used a semiquantitative score threshold of C1, not C2, for detecting ATTR, in part because they used a 3 hour, not 1 hour, imaging time (see below). They found that both the Tc99m PYP semiquantitative score and H/CL ratio were associated with mortality with HRs of 1.49 (95% CI 1.08-2.08, P = 0.016) and 5.19 (95% CI 1.46-18.4, P = 0.0111), respectively, and with death or heart failure hospitalization with HRs of 1.49 (95% CI 1.17-1.90) and 3.15 (95% CI 1.21-8.23), respectively.…”