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Noninvasive Etiologic Diagnosis of Cardiac Amyloidosis Using ^99mTc-3,3-Diphosphono-1,2-Propanodicarboxylic Acid Scintigraphy

Enrica Perugini, MD^_*, Pier Luigi Guidalotti, MD, Fabrizio Salvi, MD, Robin M.T. Cooke, MA^_*, Cinzia Pettinato, MD, Letizia Riva, MD^_*, Ornella Leone, MD, Mohsen Farsad, MD, Paolo Ciliberti, MD^_*, Letizia Bacchi-Reggiani, MSc, MBiostat^_*, Francesco Fallani, MD^_*, Angelo Branzi, MD^_* and Claudio Rapezzi, MD^_*,_*

^_* Institute of Cardiology, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy
Nuclear Medicine Unit, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy
Department of Pathology, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy
Department of Neurology, Ospedale Bellaria, Bologna, Italy.

View larger version (54K): [in a new window]   Figure 1 Representative examples illustrating the spectrum of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) uptake among patients with transthyretin (TTR)-related or monoclonal immunoglobulin light-chain (AL) cardiac amyloidosis and unaffected controls (top row = whole-body scans, anterior view; bottom row = cross sectional views of cardiac single-photon emission computed tomography in the same patients). (A) Unaffected control subject without visually detectable uptake. (B) Patient with AL amyloidosis and echocardiographic documentation of cardiac involvement without any visually detectable sign of myocardial 99mTc-DPD uptake; mild uptake of the tracer is visible only at the soft tissue level. (C and D) Two patients with TTR-related amyloidosis and echocardiographic documentation of cardiac involvement, both showing strong myocardial 99mTc-DPD uptake (with absent bone uptake); in one of the patients (D), splanchnic uptake is also visible.

View larger version (16K): [in a new window]   Figure 2 Comparison of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid heart retention (A), whole-body retention (B), and heart/whole-body retention ratio (C) between group A patients (transthyretin [TTR]-related cardiac amyloidosis [CA]), group B patients (monoclonal immunoglobulin light-chain [AL] cardiac amyloidosis), and controls. The lower/upper limits of the boxes indicate 25th/75th percentiles; horizontal lines (and values) within boxes indicate medians. Values lying more than 1.5 and 3 box-lengths from the 75th percentile are indicated by circles and asterisks, respectively.

View larger version (118K): [in a new window]   Figure 3 Macroscopic/histologic findings (top) and scintigraphic images using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) (middle) or 99mTc-methylene diphosphonate (99mTc-MDP) (bottom) as the tracer in a group A patient with transthyretin amyloidosis who underwent combined heart-liver transplantation (left) and a group B patient with monoclonal immunoglobulin light-chain (AL) amyloidosis (right). Two paradoxes are apparent: 1) despite similar left ventricular (LV) thickness and amount of amyloidotic infiltration in the two patients, myocardial 99mTc-DPD uptake is characteristically strong (without bone uptake) in the patient with TTR-related amyloidosis and absent in the patient with AL amyloidosis (who had only bone uptake); 2) conversely, use of a different tracer (99mTc-MDP) results in absence of visually detectable myocardial uptake (accompanied by normal bone uptake) in both patients. The macrohistologic sections show pale gray-blue amyloid infiltrations at Azan Mallory trichrome staining, whereas Congo-red staining (lower insets) shows typical green birefringence under cross-polarized light microscopy. In the patient with TTR, immunohistochemical staining against TTR is positive (upper inset). RV = right ventricle.

View larger version (102K): [in a new window]   Figure 4 Apical four-chamber-view echocardiograms (top row) and cross-sectional views of cardiac single-photon emission computed tomography (SPECT) (bottom row) in two patients with transthyretin (TTR)-related cardiac amyloidosis. Topographic correspondences between increased left ventricular parietal thickness and 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) uptake is evident: (A) increased thickness of both the interventricular septum and the lateral wall of the left ventricle at echocardiography in correspondence with diffuse myocardial 99mTc-DPD uptake at SPECT; (B) increased thickness of the medial portion of the interventricular septum (with normal lateral wall) at echocardiography in correspondence with localized myocardial 99mTc-DPD uptake at the same level. IVS = intraventricular septum; LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.

View larger version (11K): [in a new window]   Figure 5 Distribution of left ventricular (LV) mass values according to visual scores at myocardial 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. No relationship between the two variables is discernible (p = 0.54 by Kruskal-Wallis test). AL = monoclonal immunoglobulin light-chain; TTR = transthyretin.