Nuclear imaging and echocardiographic findings in hypertrophic cardiomyopathy with and without ATTR‐CM

Aims: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) often experience delayed diagnosis, which may detrimentally impact clinical outcomes. This study aimed to assess the frequency of use of planar scintigraphy with and without single-photon emission computed tomography (SPECT) in patients with hypertrophic cardiomyopathy (HCM) screened for ATTR-CM in the TTRACK study. Variability in readings based on different readers, tests and radiotracers used in cardiac nuclear imaging, and differences in echocardiogram findings between patients with and without ATTR-CM were explored. Methods: Patients aged ≥50 years with HCM (left-ventricular wall thickness ≥15 mm without an identified cause) underwent diagnostic technetium-99m [99mTc]Tc-DPD [3,3-diphosphono-1,2-propanodicarboxylic acid], -PYP [pyrophosphate] and -HMDP [hydroxymethylene diphosphonate]-labelled planar bone scintigraphy with or without SPECT. Cardiac-versus-bone uptake on images was visually graded (Perugini, 0-3) by onsite and central readers (discrepancies resolved by consensus). Patients with grade 1-3 cardiac uptake underwent monoclonal protein testing. Results: Of 766 eligible patients (mean age ± standard deviation, 72.3 ± 10.6 years, 69.6% male), 691 (90.2%) had planar imaging alone and 75 (9.8%) planar plus SPECT imaging. Cardiac uptake was observed on imaging in 245 patients (32.0%); grades 1, 2 and 3 were assigned in 37 (4.8%), 34 (4.4%) and 174 (22.7%), respectively. Initial cardiac uptake grading for planar scintigraphy by onsite readers was strongly concordant with consensus decisions [κ coefficient, 0.84 (95% confidence interval 0.81-0.88)]. Grading for planar versus SPECT imaging was very strongly concordant [0.93 (95% confidence interval 0.86-1.00)]; discordant findings were only observed with [99mTc]Tc-PYP. Compared with patients with no cardiac uptake, patients with ATTR-CM had a lower mean left ventricular (LV) ejection fraction (55.7% vs. 61.4%; P < 0.001), higher mean LV mass index (179.0 vs. 155.6 g/m2; P < 0.01), a higher rate of preserved apical strain (73.4% vs. 57.9%; P < 0.05) and differences in hypertrophic pattern (P < 0.001), such as a higher rate of concentric hypertrophic pattern (77.5% vs. 38.8%;). Clinical overlap between patients with ATTR-CM and those without cardiac uptake was high. Conclusions: In this real-world study, a high level of concordance was seen in cardiac uptake grading on planar versus SPECT imaging, with discordant findings only observed with [99mTc]Tc-PYP. The findings support the use of these imaging tools to facilitate ATTR-CM screening in clinical practice. Further studies should investigate differences across tracers used in ATTR-CM screening. NCT03842163.