Optimal Echocardiographic Parameters to Improve the Diagnostic Yield of Tc-99m-Bone Avid Tracer Cardiac Scintigraphy for Transthyretin Cardiac Amyloidosis

Abstract

Background: Echocardiographic deformation-based ratios and novel multi-parametric scores have been suggested to discriminate transthyretin cardiac amyloidosis (ATTR-CM) from other causes of increased left ventricular wall thickness among patients referred for ATTR-CM evaluation. Their relative predictive accuracy has not been well studied. We sought to (1) identify echocardiographic parameters predictive of ATTR-CM and (2) compare the diagnostic accuracy of these parameters in patients with suspected ATTR-CM referred for technetium-99m-pyrophosphate scintigraphy. Methods: Echocardiograms from 598 patients referred to 3 major amyloidosis centers for technetium-99m-pyrophosphate to detect ATTR-CM were analyzed, including longitudinal strain (LS) analysis. Deformation ratios (septal apex to base ratio, relative apical sparing, ejection fraction to global LS), a multi-center European increased wall thickness score, and Mayo Clinic derived ATTR score (transthyretin cardiac amyloidosis score) were calculated. A logistic regression model was used to identify the parameters that best associated with a diagnosis of ATTR-CM. Comparison of the diagnostic capacity of the parameters was performed by receiver operating characteristic curves and the area under the curve (AUC). Results: Over half of the subjects (54.2%) were diagnosed with ATTR-CM (78% were men, median age of 76 years). Age, inferolateral wall thickness, and basal LS were the strongest predictors of ATTR-CM, AUC of 0.87 (95% CI: 0.83, 0.90), superior to the increased wall thickness score AUC of 0.78 (95% CI: 0.73, 0.83; P =0.004). An inferolateral wall thickness of ≥14 mm (AUC: 0.73) was as accurate as the published cut-offs for transthyretin cardiac amyloidosis score and septal apex to base (AUC: 0.72 and 0.69, P =0.8 and P =0.1, respectively), and was superior to ejection fraction to global LS and relative apical sparing (AUC: 0.64 and 0.53, P <0.001, respectively). A cut-off of ≥−8% for average basal LS (AUC: 0.76, CI: 0.72–0.79) had a similar area under the curve to transthyretin cardiac amyloidosis score (TCAS) ( P =0.2); outperforming the other indices ( P <0.01). Conclusion: Inferolateral wall thickness and average basal LS performed as well as or better than more complex echo ratios and multiparametric scores to predict ATTR-CM.

Echocardiographic score for the screening of cardiac amyloidosis with positive 99m technetium pyrophosphate scintigraphy result

“…14,15,32,33 Furthermore, by using twodimensional speckle tracking techniques, "apical sparing" in LV contraction has been found to be related to CA. 25,[34][35][36][37] In our study, these two factors were selected as discriminators of 99m Tc-PYP scintigraphy-positive cardiomyopathy, which was in concordance with those previous reports.…”

“…In recent years, LV wall thickness has been thought to be the most practical and reliable two‐dimensional echocardiographic measure to identify cardiac amyloidosis (CA) 14,15,32,33 . Furthermore, by using two‐dimensional speckle tracking techniques, “apical sparing” in LV contraction has been found to be related to CA 25,34–37 . In our study, these two factors were selected as discriminators of 99m Tc‐PYP scintigraphy‐positive cardiomyopathy, which was in concordance with those previous reports.…”

Towards a Diagnosis of Cardiac Amyloidosis: Single Center Experience with 99m Technetium Pyrophosphate Planar Imaging and Opportunities for Standardization of Diagnostic Workflow

“…Of note, a recent study evaluating the role of echo parameters in predicting PYP scan positivity showed similar findings. In this study inferolateral (posterior) wall thickness >14 mm along with basal longitudinal strain were the best predictors of PYP positivity [ 24 ].…”

A simple ATTR‐CM score to identify transthyretin amyloid cardiomyopathy burden in HFpEF patients

“…Since ATTR-CM and HFpEF have overlapping clinical features, the identification of the ATTR-CM burden in HFpEF patients remains challenging. Recently, several scoring systems based on echocardiography or electrocardiography have been developed to detect cardiac amyloidosis 31,32 or a specific ATTR-CM subtype, [33][34][35] such as the AL score, 31 Increased Wall Thickness (IWT) score, 31,35 AMYLI score, 32 strain-based ratios 33 and the RWT/SavR index (Table S4). 34 Similarly, Sperry et al demonstrated that patients with an echocardiographic phenotype of s' velocity ≤6 cm/s and IVS ≥12 mm in the TOPCAT study were more likely to be cardiac amyloidosis, associated with poorer prognosis.…”

“…12 However, it failed to distinguish ATTR-CM from light-chain amyloidosis. 12 The strain-based ratios 33 and the RWT/ SavR index 34 were mainly derived from patients with clinically suspected ATTR-CM regardless of the presence of HFpEF, whereas the IWT score (≥8 points) performed well with a sensitivity of 85.7% and a specificity of 92.6% for ATTR-CM identification in a Chinese HFpEF cohort. 35 However, the ATTR-CM burden as detected by an IWT score ≥8 was only 5.3%, possibly due to the racial disparities, lack of external validation design and the low proportion of patients undergoing 99m Tc-PYP (only 13.1%).…”