Diagnostic yield of scintigraphy in suspected cardiac amyloidosis without left ventricular hypertrophy

Abstract Background Cardiac amyloidosis is a progressive infiltrative disease caused by the deposition of misfolded amyloid proteins in the heart. The ESC position statement recommends screening for cardiac amyloidosis in the presence of red flags and left ventricular hypertrophy of at least 12 mm. However, cases of cardiac amyloidosis have been reported in the absence of left ventricular hypertrophy. Purpose This study aims to evaluate the diagnostic yield of scintigraphy in patients undergoing evaluation for suspected cardiac amyloidosis in the absence of increased left ventricular wall thickness (LVWT). Methods All consecutive patients who underwent DPD cardiac scintigraphy for suspected cardiac amyloidosis were included. The study was conducted at a Spanish center in a non-endemic area between 2016 and 2021. Scintigraphy was requested based on the presence of at least one red flag. Patients with a prior diagnosis of amyloidosis, or those undergoing screening due to a known TTR variant were excluded. Poor-quality acquisition studies were also excluded (n=1). Results Throughout the study period, a total of 113 scintigraphy scans were performed on 113 patients (83.2% male, median age 77.9 IQR 71.1–83.3 years, LVWT 16 IQR 13–18 mm). A total of 94 patients (83.2%) had left ventricular hypertrophy with a LVWT of ≥12 mm, while 19 patients (16.8%) had normal wall thickness assessed by echocardiogram (mean LVWT 10.1 ± 0.8mm). Patients with left ventricular hypertrophy were older (79.8 IQR 72.4–84.3 years vs. 68.8 IQR 54.9–74.0 years, p0.001), had a higher prevalence of heart failure (79.8% vs. 55.6%, p=0.028), and exhibited a greater number of red flags (median 3 2–4 vs. 1.5 1–2). Notably, patients with left ventricular hypertrophy exhibited a higher prevalence of hypotension or normotension in previously hypertensive patients (38.3% vs. 5.6%, p=0.007), pseudo-infarct pattern on electrocardiogram (31.9% vs. 5.6%, p=0.022) and a trend toward a higher presence of atrial fibrillation (61.7% vs. 38.9%, p=0.072), pacemaker (43.6% vs. 22.2%, p=0.090), and severe aortic stenosis (12.8% vs. 0%, p=0.109). Among patients with red flags but normal wall thickness, none showed grade 2 or 3 uptake, while 63 (67.0%) of those with left ventricular hypertrophy had a positive scintigraphy. Conclusions Scintigraphy did not yield positive results in patients with suspected cardiac amyloidosis based on red flags but without left ventricular hypertrophy. Our findings support performing scintigraphy when wall thickness ≥12 mm is present alongside red flags, in accordance with the 2021 expert consensus.