technetium-tc-99m-medronate and Amyloid-Neuropathies--Familial

Cardiac amyloidosis, once considered untreatable, is now gaining well-deserved attention due to advances in imaging and the recent approval of targeted breakthrough therapies. In this paper, we discuss the role of radionuclide imaging in the evaluation and management of patients with the most common form of amyloidosis-cardiac transthyretin amyloidosis (ATTR). We provide a comprehensive summary of the literature interspersed with our institutional experience as appropriate, to deliver our perspective.

Topics: Amyloid Neuropathies, Familial; Amyloidosis; Bone and Bones; Cardiomyopathies; Heart; Humans; Prealbumin; Radionuclide Imaging; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate; Tomography, Emission-Computed, Single-Photon

Nuclear imaging recently gained a key role in the diagnosis and prognostic assessment of transthyretin (TTR)-related cardiac amyloidosis. This review aims at summarizing the state-of-the art regarding the implementation of nuclear imaging in the management of hereditary mutated TTR-cardiac amyloidosis (mTTR-CA).. Although cardiac uptake of bone tracers is acknowledged as a specific marker of TTR amyloid cardiac burden, recent studies validated the implementation of bone scan in the flow chart for non-invasive diagnosis and follow-up of CA in multicenter trials. Simultaneously, cardiac denervation evidenced by MIBG scintigraphy proved to be a strong and independent prognostic marker of poor outcome in mTTR-CA. By its unique ability to assess both amyloid burden and cardiac denervation, nuclear imaging may prove useful as part of multimodality imaging tools to trigger treatment initiation and monitoring in patients with mTTR-CA.

Topics: Amyloid; Amyloid Neuropathies, Familial; Cardiomyopathy, Hypertrophic; Humans; Multimodal Imaging; Prealbumin; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate

The aim of the present manuscript is to review the latest advancements of radionuclide molecular imaging in the diagnosis and prognosis of individuals with cardiac amyloidosis.

Topics: Amyloid Neuropathies, Familial; Amyloidosis; Cardiomyopathies; Heart; Humans; Prognosis; Radiopharmaceuticals; Technetium Tc 99m Medronate

The recent pyrophosphate shortages can limit the availability of

Topics: Amyloid Neuropathies, Familial; Diphosphates; Humans; Radiopharmaceuticals; Technetium Tc 99m Medronate

The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation.. Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations.. A total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)-diphosphonate (DPD) or 99mTc-hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini's method.. Among 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings.. The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.

Topics: Aged; Amyloid Neuropathies, Familial; Bone and Bones; Cardiomyopathies; Diphosphonates; Female; Genetic Predisposition to Disease; Humans; Italy; Male; Middle Aged; Mutation; Prealbumin; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Technetium Compounds; Technetium Tc 99m Medronate; Whole Body Imaging

Topics: Aged; Amyloid Neuropathies, Familial; Gene Silencing; Humans; Male; Oligonucleotides; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate

Topics: Aged, 80 and over; Amyloid Neuropathies, Familial; Bone Neoplasms; Cardiomyopathies; Genetic Predisposition to Disease; Humans; Incidental Findings; Male; Mutation; Prealbumin; Predictive Value of Tests; Radiopharmaceuticals; Technetium Tc 99m Medronate; Whole Body Imaging

The purpose of the study was to describe the pattern of. These findings show the relationship between bone tracer myocardial uptake and LV functions in patients with TTR cardiac amyloidosis.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Cohort Studies; Female; Heart Diseases; Humans; Male; Myocardium; Radiopharmaceuticals; Stroke Volume; Technetium Tc 99m Medronate; Tomography, Emission-Computed, Single-Photon; Ventricular Function, Left

Either 99mTechnetium diphosphonate (Tc-DPD) or pyrophosphate (Tc-PYP) scintigraphy plays a relevant role in diagnosing transthyretin cardiac amyloidosis (CA), and labeled radiotracers have been extensively studied in diagnosing CA. Few studies have analyzed and validated 99mTc-Hydroxymethylene diphosphonate (Tc-HMDP). Our aim was to validate the diagnostic accuracy of Tc-HMDP total-body scintigraphy in a cohort of patients with biopsy-proven transthyretin CA.. We retrospectively evaluated all patients undergoing 99mTc-HMDP total-body scintigraphy, in adjunct to a comprehensive diagnostic work-up for suspected CA. Sixty-five patients were finally diagnosed with CA, while it was excluded in 20 subjects with left ventricular hypertrophy of various etiologies. Twenty-six patients had AL-CA, 39 had TTR CA (16 TTRm, 23 TTRwt). At Tc-HMDP scintigraphy, 2 AL patients showed a Perugini score grade 1 heart uptake, while 24 showed no uptake. All TTR patients showed Tc-HMDP uptake, with three patients showing a Perugini score grade 1, 16 grade 2, and 20 grade 3, respectively. No uptake was observed in patients with left ventricular hypertrophy. A positive Tc-HMDP scintigraphy showed a 100% sensitivity and a 96% specificity for TTR CA identification.. Tc-HMDP scintigraphy is as accurate as Tc-DPD or Tc-PYP, and may therefore de facto be considered a valuable tool for the diagnosis of TTR CA.

Topics: Aged; Amyloid Neuropathies, Familial; Biopsy; Echocardiography; Echocardiography, Doppler; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Prealbumin; Radionuclide Imaging; Reproducibility of Results; Retrospective Studies; Technetium Tc 99m Medronate; Whole Body Imaging

To describe the prevalence of and risk factors for renal infarction (RI) in patients with cardiac amyloidosis.. We evaluated 87 patients with cardiac amyloidosis who underwent renal technetium-99m-labeled dimercaptosuccinic acid scintigraphy in the Amyloidosis Referral Center of Henri-Mondor Hospital from October 1, 2015, through February 28, 2018.. Three groups of patients were identified according to the underlying amyloidosis disorder: AL amyloidosis in 24 patients, mutated-transthyretin amyloidosis in 24 patients, and wild-type transthyretin amyloidosis in 39 patients. Patients with wild-type transthyretin amyloidosis were older (P<.001), more likely to be men (P=.02), to have arrhythmic heart diseases (P<.001), and to be receiving anticoagulation treatment (P<.001). Patients with AL amyloidosis had significantly higher N-terminal pro-B-type natriuretic peptide levels (P=.02) and were more likely to have nephrotic syndrome (P<.001). Renal infarction was detected in 18 patients (20.7%), at similar frequencies in the various groups. Baseline urinary protein to creatinine ratio was the only parameter for which a significant difference (P=.03) was found between patients with and without RI diagnoses. The likelihood of RI diagnosis was 47.1% (8 of 17) in the presence of AKI and 14.5% (10 of 69) in its absence (P=.003). Overall, heart transplant-censored patient survival did not differ significantly between patients with and without RI (P=.64), but death- and heart transplant-censored renal survival was significantly lower in patients with RI (P<.001).. Our study suggests that prevalence of RI in patients with cardiac amyloidosis is higher than previously thought, regardless of the underlying amyloidosis disorder. Acute kidney injury in a patient with cardiac amyloidosis should alert clinicians to the possibility of RI.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Female; Heart Diseases; Humans; Male; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate

Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diagnosis, Differential; Genetic Predisposition to Disease; Humans; Immunoglobulin Light-chain Amyloidosis; Mutation; Prealbumin; Predictive Value of Tests; Prospective Studies; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate

Management of cardiac amyloidosis (CA) is related to amyloid deposition. Our aim was to assess the effect of amyloid deposition on myocardial function.. Twenty-eight patients with transthyretin mutation and a group of 14 controls underwent echocardiography to quantify left ventricular (LV) dimensions, function, and global (G) longitudinal (L), radial (R) and circumferential (C) strain (S). (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic-acid-scintigraphy ((99m)Tc-DPD) was used to quantify CA. (99m)Tc-DPD revealed accumulation in 14/28 patients (CA group) and no accumulation (no-CA group) in 14. Cardiac accumulation was lower-than-bone uptake in 5 (mild-CA group) and higher-than-bone uptake in 9 (severe-CA group). Ejection fraction was similar among groups. GLS was lower (P<0.001) in the severe-CA group (-12.2±4.5) with respect to the no-CA group (-19.3±3.0) and to the control group (-20.9±2.5). Conversely, GCS and GRS were lower (P<0.05) in the mild-CA group (-10.8±4.1 and 9.5±5.7, respectively) with respect to the severe-CA group (-18.9±5.1 and 23.9±6.3 respectively), no-CA group (-19.2±4.1 and 28.4±10.2, respectively) and the control group (-23.9±4.4 and 29.9±8.7, respectively). A correlation was found between the scintigraphic heart retention index (HRI) and LV septal thickness (ρ=0.72), E/E' (ρ=0.46) and GLS (ρ=-0.40).. Myocardial deformation is impaired in a different stage of CA. The (99m)Tc-DPD HRI correlated well with morphologic, diastolic and strain abnormalities. (Circ J 2016; 80: 1998-2003).

Topics: Adult; Amyloid; Amyloid Neuropathies, Familial; Female; Heart Ventricles; Humans; Male; Middle Aged; Myocardium; Technetium Tc 99m Medronate; Tomography, Emission-Computed

To assess the usefulness of bone scintigraphy with (99m)Technetium-hydroxymethylene diphosphonate ((99m)Tc-HDP) for the detection of cardiac involvement in a group of patients with ATTR amyloidosis in different phases of disease, to relate the findings to echocardiography, ECG and cardiac biomarkers, and to evaluate different bone scintigraphic techniques and calculation methods for quantification of the cardiac uptake and for correlation with echocardiographic features and cardiac biomarkers.. Forty-one patients underwent clinical examinations, echocardiography, ECG, measurement of cardiac biomarkers and bone scintigraphy (planar imaging and SPECT-CT) and were subsequently subdivided into three groups: (1) carriers of an amyloidogenic TTR mutation, n = 11, (2) proven ATTR amyloidosis without echocardiographically-defined (mean wall thickness >12 mm) cardiac amyloidosis (AC), n = 19, and (3) ATTR amyloidosis with echocardiographically-defined cardiac amyloidosis, n = 11. Planar and SPECT-CT images were analyzed visually according to a routine scoring system (grade 0-3) and semi-quantitatively by heart-to-whole body (H/WB) and heart-to-skull (H/S) ratio on planar images and by a left ventricle-blood pool ratio on SPECT-CT images.. All patients with ATTR and echocardiographically-defined AC and none of the carriers showed high cardiac uptake on bone scintigraphy. Furthermore, 8 out of 19 patients with ATTR without echocardiographically-defined AC showed high cardiac uptake. Highest correlations were found between H/S ratio on planar bone scintigraphy with troponin T (r = 0.76, p < 0.0001) and H/WB ratio with left ventricular mass index (r = 0.73, p < 0.0001).. Bone scintigraphy with (99m)Tc-HDP may detect cardiac involvement in patients with ATTR amyloidosis prior to echocardiographic evidence of cardiac involvement. Cardiac uptake on bone scintigraphy correlates with severity of cardiac involvement using echocardiography, ECG and cardiac biomarkers. Visual grading and calculation of H/S ratio on planar imaging are the preferred methods to assess cardiac uptake.

Topics: Adult; Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Bone and Bones; Cardiomyopathies; Early Diagnosis; Female; Heart Ventricles; Humans; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate; Tissue Distribution