Pyrophosphate (PYP), and Hydroxymethylene Diphosphonate (HDP) are Reliable and Readily Available Tracers for use in Bone Scintigraphy for the Diagnosis of Transthyretin Cardiac Amyloidosis (TTR)

Abstract

3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) is the most validated tracer for detecting cardiac amyloidosis with bone scintigraphy. PYP and HDP are more readily available in Australia, and considered possible alternatives. We sought to examine experience using HDP and PYP at the Victorian and Tasmanian Amyloidosis Service. 69 patients diagnosed with TTR underwent bone scintigraphy. TTR was confirmed on direct biopsy in 25, including 12 cardiac; and/or genetic studies confirming TTR mutations in 5; and/or on clinical phenotype (older male with isolated HFpEF ± carpal tunnel releases), with echocardiographic features (IVSD >12 mm) and elevated cardiac biomarkers in 57. Six underwent bone marrow biopsies demonstrating <5% plasma cells and Congo red negative, thus AL was excluded. All but one had normal serum free light chain (SFLC) ratios. Cardiac MRI confirmed amyloidosis in 25. Tracers used were: HDP in 61, PYP in 6, and 1 each for DPD and MDP. 65 demonstrated cardiac uptake. For negative scan patients, one had normal cardiac biomarkers with no clinical evidence of amyloidosis but positive for Met30 mutation, thus deemed an asymptomatic carrier; another had normal echocardiography with isolated biopsy-proven gastrointestinal disease; another had isolated biopsy-proven bladder disease with normal cardiac biomarkers. The final patient had bone scintigraphy using methylenediphosphonate (MDP), which was falsely negative. MDP is not validated for detecting cardiac amyloidosis. HDP and PYP are sensitive tracers to detect cardiac amyloidosis. MDP should not be used. SFLC measurement is essential. For those with abnormal SFLC, biopsy and referral to an amyloidosis service to exclude AL is recommended.