Sara Rosengren1, Tor Skibsted Clemmensen2, Lars Tolbod3, Sven-Olof Granstam4, Hans Eiskjær2, Gerhard Wikström5, Ola Vedin5, Tanja Kero6, Mark Lubberink7, Hendrik J Harms3, Frank A Flachskampf4, Tomasz Baron4, Kristina Carlson8, Fabian Mikkelsen2, Gunnar Antoni9, Niels Frost Andersen10, Steen Hvitfeldt Poulsen2, Jens Sörensen11. 1. Department of Medical Sciences, Hematology, Uppsala University, Uppsala, Sweden. Electronic address: sara.rosengren@akademiska.se. 2. Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark. 4. Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden. 5. Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. 6. Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden. 7. Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden; Department of Medical Physics, Uppsala University, Uppsala, Sweden. 8. Department of Medical Sciences, Hematology, Uppsala University, Uppsala, Sweden. 9. Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden. 10. Department of Hematology, Aarhus University Hospital, Aarhus, Denmark. 11. Department of Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark; Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.
Abstract
OBJECTIVES: This dual-site study evaluated the diagnostic accuracy of the method. BACKGROUND: Pittsburgh compound ([11C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA). METHODS: The study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min-1) were applied prospectively. RESULTS: The diagnostic accuracy of visual inspection of [11C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative [11C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. [11C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as [11C]PIB PET positive. CONCLUSIONS: In a dual-center setting, [11C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were [11C]PIB PET positive, indicating that the method may detect early stages of CA.
OBJECTIVES: This dual-site study evaluated the diagnostic accuracy of the method. BACKGROUND: Pittsburgh compound ([11C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA). METHODS: The study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosispatients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min-1) were applied prospectively. RESULTS: The diagnostic accuracy of visual inspection of [11C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative [11C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. [11C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as [11C]PIB PET positive. CONCLUSIONS: In a dual-center setting, [11C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosispatients without known cardiac involvement were [11C]PIB PET positive, indicating that the method may detect early stages of CA.
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