Accuracy of 99mTc-HMDP scintigraphy (sHMDP) to diagnose cardiac amyloidosis (CA) and to discriminate between the different etiologies i.e hereditary TTR amyloidosis (hTTR), senile amyloidosis (wt-TTR) and light chain amyloidosis (AL) are unknown.122 patients referred for suspected CA were prospectively studied with sHMDP. HMDP fixation was evaluated by a visual score (0 up to 3). Heart-to-whole-body (H/WB) and heart-to-skull (H/S) ratio were calculated on planar images. Diagnosis of amyloidosis was biopsy proven for all AL. Diagnosis of CA for hTTR and wt-TTR was established by an experts consensus based on echocardiography, cardiac MRI (cardiac wall thickness ≥12mm), genetic testing and biopsy whenever ethically possible.The mean age was 69 (59; 78), 71% were men; of whom, 14 (11%) were considered having AL, 34 (28%) hTTR, 21 (17%) wt-TTR and 53 (43%) had cardiac hypertrophy from other causes. Of the 61 (50%) patients with CA, 46 (75%) had a HMDP visual scoring ≥1; of whom 1/14 (7%) had AL, 24/26 (92%) hTTR and 21/21 (100%) wt-TTR.Cardiac HMPD uptake was absent among all patients without CA (n=61). Visual score was stronger in TTR-CA versus AL-CA (p<0.0001). A visual score ≥2 to diagnose TTR-CA had a predictive positive value of 100%. Among CA, H/WB and H/S ratio were significantly higher (p <0.002) in both hTTR (H/WB=3.92±0.93 H/S=2.26±0.98) and wt-TTR (H/WB=4.36±0.95 H/ S=2.86±1.12) versus AL (H/WB=2.67±0.61; H/S=1.70±1.53). Eleven patients with myocardial 99mTc-HDPD uptake underwent a second sHMDP with a median (25 th ; 75 th ) of 15.1 months (7.3; 16.2) of whom two had an increase in visual score and H/WB ratio. (Image 1, next page)99mTc-HMDP scintigraphy is a useful tool to diagnose CA, define its etiology and might be useful for follow-up.