NON-INVASIVE IDENTIFICATION OF SENILE SYSTEMIC AMYLOIDOSIS: INCREMENTAL DIAGNOSTIC ROLE OF 99MTC-DPD SCINTIGRAPHY (original) (raw)
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Jacc-cardiovascular Imaging, 2011
In a cohort of patients with hereditary transthyretin-related amyloidosis (ATTR), we aimed to assess the role of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in detecting myocardial amyloid infiltration across a wide spectrum of cardiac involvement and in predicting major adverse cardiac events (MACE).Hereditary transthyretin-related amyloidosis is a challenging and underdiagnosed condition where both early diagnosis and prognosis remain problematic.We evaluated 63 patients with ATTR: 40 with and 23 without echocardiographically diagnosed amyloidotic cardiomyopathy (AC). Myocardial uptake of 99mTc-DPD scintigraphy was semiquantitatively and visually assessed at 5 min and 3 h.All patients with AC showed moderate-to-severe myocardial tracer uptake (i.e., visual score ≥2). Within the subgroup without AC, only 4 patients (with Ala36Pro, Gly47Ala, Thr49Ala, and Glu89Gln transthyretin mutations) showed myocardial tracer uptake and abnormal heart/whole body retention (H/WB) values: in all these cases endomyocardial biopsies showed amyloidotic infiltration. The H/WB was positively correlated with left ventricular (LV) mean wall thickness (Pearson's r = 0.695, p < 0.001) and negatively with LV ejection fraction (r = −0.368, p = 0.004). The H/WB was an unfavorable predictor of MACE-free survival at Cox univariate analysis and contributed to the multivariate model. Notably, LV wall thickness >12 mm in combination with H/WB >7.5 was associated with the highest event rate.In ATTR, 99mTc-DPD scintigraphy can identify myocardial infiltration across a wide spectrum of morphologic/functional cardiac involvement, allowing an early diagnosis of the disease (even before the appearance of echocardiographic abnormalities). The 99mTc-DPD myocardial uptake is a prognostic determinant of “cardiac” outcome in ATTR, either alone or in combination with LV wall thickness.
Medicine, 2019
Rationale: Cardiac amyloidosis, considered for the last years to be a rare disease, is one of the determinants of HFpEF. The nonspecific clinical presentation and the difficulties related to endomyocardial biopsy have made cardiac amyloidosis an underdiagnosed clinical entity. Improvement of non-invasive diagnostic techniques and the development of new therapies increased clinical awareness for this form of restrictive cardiomyopathy. We here summarize echocardiography and 99m Tc-HDP scintigraphy findings in 6 cases of cardiac amyloidosis and review the literature data of this progressive and fatal cardiomyopathy. Patients concerns: The main clinical manifestations were fatigue, low exercise tolerance and edemas. The right heart failure symptoms usually dominated the clinical picture. Diagnoses: All cases were evaluated by echocardiography; 3 cases were further examined by bone scintigraphy and 4 cases a peripheral biopsy was performed. Electrocardiography showed low-voltage QRS complexes and "pseudo-infarct" pattern in the precordial leads, contrary to the echocardiographic aspect, which revealed thickening of ventricle walls. Biatrial dilation and diastolic disfunction were observed. Impaired systolic function was detected in advanced stages of the disease. 99m Tc-HDP scintigraphy revealed cardiac uptake of radiopharmaceutical and managed to confirm the diagnosis in 1 case of cardiac amyloidosis in which salivary gland biopsy was negative. Interventions: The treatment was based on managing fluid balance, with the mainstream therapy represented by diuretics. Neurohormonal agents, usually used in heart failure treatment were avoided, due to poor tolerance and worsening of disease course. The management of these 6 cases was challenging due to the refractory manifestation of congestive heart failure. Outcomes: During follow-up, 4 of the 6 patients from the current study died in the first year after the final diagnosis was established. Lessons: Nuclear imaging of cardiac amyloidosis has a revolutionary development nowadays. Bone scintigraphy presents promising results for identifying patients at early stages of disease and to differentiate between cardiac amyloidosis types. Further studies are necessary for the standardization of imaging protocol and development of non-invasive diagnostic tools, especially in assessing the response to treatment and disease progression, for which little is known. Abbreviations: 99m Tc-DPD = technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid, 99m Tc-HDP = technetium-99m hydroxy methylene diphosphonate, 99m Tc-PYP = technetium-99m pyrophosphate, AL = light chain amyloidosis, ATTR = transthyretin amyloidosis, ATTRm = mutant transthyretin amyloidosis, ATTRwt = "wild-type" transthyretin amyloidosis, CA = cardiac amyloidosis, ECG = electrocardiography, EMB = endomyocardial biopsy, HFpEF = heart failure with preserved ejection fraction, PET = positron emission tomography, PW-Doppler = pulsed-wave Doppler, RAAS = renin-angiotensin-aldosterone system, SPECT = single-photon emission computed tomography, TDI = tissue-Doppler imaging, TTE = transthoracic echocardiography.
European Journal of Nuclear Medicine and Molecular Imaging, 2011
Purpose We previously reported in a small series of patients that 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy tested positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger cohort of patients with AC. Methods We evaluated (1) 45 patients with TTR-related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non-affected controls. Myocardial uptake of 99mTc-DPD (740 MBq i.v.) was semiquantitatively and visually assessed at 5 min and at 3 h. Results Heart retention (HR) and heart to whole-body retention ratio (H/WB) of late 99mTc-DPD uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both unaffected controls (HR 3.5%; H/WB 5.7; p < 0.0001) and AL-related AC (HR 4.0%; H/WB 6.1; p < 0.0001). For the diagnosis of TTR-related AC, positive and negative predictive accuracy of visual scoring of cardiac retention were: 80 and 100% (visual score ≥1); 88 and 100% (visual score ≥2); and 100 and 68% (visual score = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the only positive predictor of increasing 99mTc-DPD uptake in terms of both HR [β 2.5, 95% confidence interval (CI) 1.5–3.5; p < 0.0001] and H/WB (β 3.5, 95% CI 2.1–4.9; p < 0.0001). Conclusion While 99mTc-DPD scintigraphy was confirmed to be useful for differentiating TTR from AL-related AC, diagnostic accuracy was lower than previously reported due to a mild degree of tracer uptake in about one third of AL patients. 99mTc-DPD scintigraphy can provide an accurate differential diagnosis in cases of absent or intense uptake evaluated by visual score.
99mTc-DPD scintigraphy in immunoglobulin light chain (AL) cardiac amyloidosis
European Heart Journal - Cardiovascular Imaging, 2021
Aims Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD scintigraphy) is recognized as highly accurate for the non-invasive diagnosis of transthyretin (ATTR) cardiac amyloidosis (CA). A proportion of patients with immunoglobulin light chain (AL) CA have also been reported to show cardiac 99mTc-DPD uptake. Herein, we assessed the frequency and degree of cardiac 99mTc-DPD uptake and its clinical significance among patients with AL CA. Methods and results Between 2010 and 2017, 292 consecutive patients with AL CA underwent 99mTc-DPD scintigraphy and were included in this study: 114 (39%) had cardiac 99mTc-DPD uptake: grade 1 in 75%, grade 2 in 17%, and grade 3 in 8% of cases. Patients with cardiac 99mTc-DPD uptake had poorer cardiac systolic function and higher N-terminal pro-brain natriuretic peptide. No differences were noted in cardiac magnetic resonance parameters between patients with and without cardiac 99mTc-DPD uptake (N = 19 and 42, respectively). ...
European Journal of Nuclear Medicine and Molecular Imaging
Purpose Hereditary transthyretin-amyloid amyloidosis (ATTRv) is an underdiagnosed condition commonly manifesting as congestive heart failure. Recently, scintigraphy utilizing DPD as a tracer was shown to identify ATTRv and wild-type ATTR cardiomyopathy. The aim of this study was to determine the value of quantified scintigraphy utilizing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) single-photon emission computed tomography (SPECT)/CT, and to correlate its uptake with well-established cardiac functional parameters. Methods Forty-eight patients with genetically verified ATTRv type-A fibril composition, positive 99mTc-DPD SPECT/CT, were retrospectively analyzed. Manual mapping of volumes of interest (VOIs) on DPD SPECT/CT examinations was used to quantify heart uptake. DPD mean and maximum uptake together with a calculated DPD-based amyloid burden (DPDload) was correlated with echocardiographic strain values and cardiac biomarkers. Results Statistically significant correla...
Journal of Nuclear Cardiology
Cardiac amyloidosis (CA) is an uncommon form of infiltrative cardiomyopathy that presents with progressive heart failure (HF) and has a poor prognosis. The disease process is characterized by the extracellular deposition of amyloid fibril deposits which typically are either monoclonal light chain (AL) or transthyretin (ATTR) proteins 1. Progressive increases in wall thickness are associated with greater impairment of left ventricular function 2 and can be identified with echocardiography or cardiac magnetic resonance imaging (CMRI). However, the clinical diagnosis may be missed due to the lack of specificity of these structural changes or delayed pending confirmatory tissue biopsy. Clinical presentation usually includes symptoms of heart failure but may include angina which has been attributed to small vessel disease. 3,4 New therapies are being developed for ATTR amyloidosis and include micro-RNA inhibitors that interrupt the production of amyloid proteins 5 and molecular stabilizers of the transthyretin tetramer such as tafamidis. 6 Although imaging with 99m Tc-labeled bone tracers has been described for imaging CA for many years, recent studies have demonstrated high diagnostic accuracy for ATTR CA. Early and accurate