pyrophosphate and Amyloid-Neuropathies--Familial

Pyrophosphate (PYP) imaging has a high diagnostic accuracy for transthyretin cardiac amyloidosis (ATTR-CA). Indeterminate findings are often reported due to persistent blood pool activity, presumed to be from low cardiac output. We evaluated the relationship between blood pool activity on PYP imaging and echocardiographic indices of cardiac function.. Clinical and imaging data of 189 patients referred for PYP scintigraphy were evaluated. All patients underwent planar imaging and SPECT (diagnostic standard). Among those with a negative PYP SPECT, persistent left ventricular blood pool activity on planar images was inferred by a visual score ≥2 or a heart-to-contralateral (HCL) ratio ≥ 1.5. Absence of blood pool activity was inferred when both visual score was < 2 and HCL was < 1.5. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), stroke volume index (SVi), and left atrial pressure (LAP) were calculated from standard transthoracic echocardiograms.. ATTR-CA was present in 43 (23%) patients. Among those with a negative PYP SPECT, 11 patients had significant blood pool activity. Patients with ATTR-CA had a lower LVEF, SVi, and GLS, with a higher LAP, compared to those without ATTR-CA. Among those without ATTR-CA, there were no significant differences in these parameters.. Approximately 8% of patients with a negative PYP SPECT have significant blood pool activity. Measures of cardiac function are not different among those with and without blood pool activity. PYP SPECT should be routinely performed in all patients to avoid false image interpretation.

Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Echocardiography; Humans; Prealbumin; Radionuclide Imaging; Radiopharmaceuticals; Stroke Volume; Technetium Tc 99m Pyrophosphate; Ventricular Function, Left

Transthyretin amyloidosis (ATTR) proteins can infiltrate skeletal muscle and infrequently cause a myopathy.. Radioisotope uptake in the deltoid muscles of patients with ATTR was compared to uptake in control subjects without amyloidosis in a retrospective study.. Tracer uptake was significantly higher over the deltoids and heart but not the CC, in patients with ATTR than in control subjects. MC values were 120.1 ± 43.7 (mean ± SD) in ATTR patients and 78.9 ± 20.4 in control subjects over the heart (p = 0.005), 73.3± 21.0 and 63.5 ± 14.4 over CC (p = 0.09), and 37.0 ± 11.7 and 26.0 ± 7.1 averaged over both deltoid muscles (p = 0.014).

Topics: Amyloid Neuropathies, Familial; Biomarkers; Cardiomyopathies; Diphosphates; Humans; Muscle, Skeletal; Prealbumin; Retrospective Studies; Technetium; Technetium Tc 99m Pyrophosphate

Data were reviewed for 318 patients with suspected ATTR who underwent PYP SPECT/CT. Myocardial-to-blood pool count (MBP) ratios were computed and repeated independently > 1 month later. A physician independently scored LV myocardial-to-rib uptake on SPECT/CT as: 0 (negative), 1 < rib (equivocal), 2 = rib (positive) or 3 > rib (positive), and the image quality as: 1 (poor), 2 (adequate), and 3 (good). SPECT-only MBP ratios and visual scores were assessed separately for a subgroup of the first sequential 191 patients.. 25% of patients had positive myocardial uptake (myocardial-to-rib uptake score of ≥ 2). SPECT/CT MBP ratios were reproducible (1.35 ± .68 vs 1.33 ± .74, p = .09) and corresponded with visual scores ≥ 2 (ROC AUC = 99 ± 1%) more accurately than SPECT-only MBPs (93 ± 3%, p = .02). SPECT/CT image quality was better than that of SPECT-only (2.7 ± .5 vs 2.1 ± .5, p < .0001) with fewer equivocal results (2.6% vs 22.5%, p < .0001).. SPECT/CT produces MBP ratios that are reproducible and accurately identify a positive scan, with better image quality and fewer equivocal cases than SPECT-only.

Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Humans; Reproducibility of Results; Single Photon Emission Computed Tomography Computed Tomography; Technetium Tc 99m Pyrophosphate; Tomography, Emission-Computed, Single-Photon

Topics: Amyloid Neuropathies, Familial; Amyloidosis; Cardiomyopathies; Diphosphates; Heart Failure; Humans; Prealbumin; Radionuclide Imaging; Radiopharmaceuticals; Technetium

Topics: Amyloid Neuropathies, Familial; Amyloidosis; Cardiomyopathies; Diphosphates; Humans; Prealbumin; Predictive Value of Tests

Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Gastrointestinal Tract; Humans; Prealbumin; Technetium; Technetium Tc 99m Pyrophosphate

The recent pyrophosphate shortages can limit the availability of

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

Topics: Amyloid Neuropathies, Familial; Diphosphates; Heart; Heart Failure; Humans

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy resulting from deposition of insoluble amyloid protein in the myocardial interstitium. The accumulation of amyloid protein causes the myocardium to thicken and stiffen, leading to diastolic dysfunction and, eventually, heart failure. Two primary types of amyloidosis-transthyretin and immunoglobulin light chain-account for nearly 95% of all CA diagnoses. Three case studies are presented. The first demonstrates a patient positive for transthyretin amyloidosis, the second demonstrates a patient positive for light-chain CA, and the third demonstrates a patient showing blood-pool uptake on the [

Topics: Amyloid Neuropathies, Familial; Amyloidogenic Proteins; Diphosphates; Humans; Radionuclide Imaging

Cardiac amyloidosis was thought to be rare, undiagnosable, and incurable. However, recently it has been discovered to be common, diagnosable, and treatable. This knowledge has led to a resurgence in nuclear imaging with

Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Humans; Radionuclide Imaging; Radiopharmaceuticals

Topics: Amyloid Neuropathies, Familial; Amyloidosis; Cardiomyopathies; Diphosphates; Humans; Prealbumin; Radionuclide Imaging

Sixty-eight patients with biopsy-proven ATTRwt-CM who underwent PYP SPECT/CT were enrolled. Baseline clinical characteristics, echocardiographic parameters, and qualitative and/or quantitative indices of planar and SPECT/CT imaging in PYP scintigraphy for each patient were included. For quantitative analysis of SPECT/CT, the accumulation ratio of PYP in the septum, posterior, anterior, lateral, and apex walls to the cavity pool was calculated as the septal wall-to-cavity ratio (Se/C), lateral wall-to-cavity ratio (La/C), anterior wall-to-cavity ratio (An/C), inferior wall-to-cavity ratio (In/C), and apical wall-to-cavity ratio (Ap/C), respectively. Endpoints for prognostic accuracy evaluation were cardiac death or hospitalization due to heart failure. Event-free survival rate was evaluated through Cox proportional hazards regression analysis, providing estimated hazard ratios (HRs) with 95% confidence intervals (CIs) and Kaplan-Meier curves.. High-sensitivity cardiac troponin T (hs-cTnT), La/C, age, interventricular septal thickness in diastole, and E/e' ratio in the septal wall were significantly associated with event-free survival (P < 0.05). For a multivariable Cox proportional hazards analysis, hs-cTnT (HR 1.153; 95% CI 1.034-1.286; P < 0.01), La/C (HR 2.091; 95% CI 1.012-4.322; P = 0.046), and age (HR 1.116; 95% CI 1.007-1.238; P = 0.037) were significant independent prognostic factors.. This study indicated that the quantitative indices of PYP SPECT/CT can help to predict the prognosis of ATTRwt-CM patients.

Topics: Aged; Amyloid Neuropathies, Familial; Diphosphates; Heart Failure; Humans; Prealbumin; Prognosis; Radiopharmaceuticals; Retrospective Studies; Single Photon Emission Computed Tomography Computed Tomography; Technetium Tc 99m Pyrophosphate

Subcutaneous tissue and gastrointestinal tract biopsy sensitivity are inadequate, especially in patients with ATTRwt; however, the combination of these extracardiac biopsies contributes to increased sensitivity in patients with positive

Topics: Amyloid Neuropathies, Familial; Biopsy; Cardiomyopathies; Diphosphates; Humans; Radionuclide Imaging; Retrospective Studies; Technetium Tc 99m Pyrophosphate

We included 318 patients in the analysis (n = 86 patients +ATTR-CM; n = 232 patients -ATTR-CM). The median follow-up time was 20.1 months. During the study period, 67% of +ATTR-CM patients received tafamidis (median treatment duration, 17 months). The median H/CL ratio was 1.58 (interquartile range, 1.40-1.75). An H/CL ratio of more than 1.6 or less than 1.6 did not seem to have an impact on survival probability in +ATTR-CM patients (P = .30; hazard ratio, 0.65; 95% confidence interval, 0.31-1.41). Cardiac biomarkers were poorly correlated with H/CL (troponin T, R

Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Heart Failure; Humans; Natriuretic Peptide, Brain; Prealbumin; Retrospective Studies; Technetium Tc 99m Pyrophosphate; Troponin T

Myocardial scintigraphy with technetium-99m pyrophosphate is a minimally invasive technique that can distinguish between transthyretin amyloidosis (ATTR) and light-chain amyloidosis. We present a case in which it helped determine the amyloidosis type in a 74-year-old man with cardiac amyloidosis and multiple previous admissions for acute decompensated heart failure. The patient presented with increasing abdominal girth and bilateral lower extremity edema. His medical history also included atrial fibrillation, liver cirrhosis, hypertension, stage 3 chronic kidney disease, and peripheral vascular disease. We prescribed guideline-directed medical therapy for his acute decompensated heart failure with cardiorenal syndrome and his decompensated cirrhosis. Two years previously, a presumptive diagnosis of ATTR cardiomyopathy had been made on the basis of the patient's age, predominantly cardiac involvement, an unremarkable serum protein electrophoresis result, and an abnormal free κ/λ light-chain ratio of 2.24. Over the next year, the patient's clinical condition had worsened with the development of liver cirrhosis and peripheral neuropathy, and his free κ/λ light-chain ratio had become even more abnormal. At the current presentation, a technetium-99m pyrophosphate nuclear scintigram revealed a free κ/λ light-chain ratio of 1.52. This, combined with the patient's age and slow progression of primarily cardiac disease, supported the diagnosis of ATTR, and we prescribed tafamadis. This case suggests that technetium-99m pyrophosphate scintigraphy is valuable in definitively diagnosing ATTR cardiomyopathy and selecting patients who may benefit from disease-modifying therapy.

Topics: Aged; Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Heart Failure; Humans; Liver Cirrhosis; Male; Myocardial Perfusion Imaging; Technetium

Transthyretin cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure, but it has received increasing attention due to the availability of treatment options. We present a case of hereditary transthyretin cardiomyopathy (A97S, an under-represented variant in current clinical studies) who presented with heart failure. Timely diagnosis and intervention with tafamidis demonstrated reversed cardiac remodelling via multiple imaging techniques (echocardiography, cardiac magnetic resonance imaging and technetium-99m pyrophosphate scintigraphy). The echocardiography and cardiac magnetic resonance imaging demonstrated improved global strain. Cardiac magnetic resonance imaging showed decreased extracellular volume. The technetium-99m pyrophosphate scintigraphy demonstrated decreased heart-to-contralateral ratio. This case highlights the potential reversible effect of tafamidis on A97S amyloidosis cardiomyopathy.

Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Heart Failure; Humans; Prealbumin; Technetium; Ventricular Remodeling

Echocardiographic deformation-based ratios and novel multi-parametric scores have been suggested to discriminate transthyretin cardiac amyloidosis (ATTR-CM) from other causes of increased left ventricular wall thickness among patients referred for ATTR-CM evaluation. Their relative predictive accuracy has not been well studied. We sought to (1) identify echocardiographic parameters predictive of ATTR-CM and (2) compare the diagnostic accuracy of these parameters in patients with suspected ATTR-CM referred for technetium-99m-pyrophosphate scintigraphy.. Echocardiograms from 598 patients referred to 3 major amyloidosis centers for technetium-99m-pyrophosphate to detect ATTR-CM were analyzed, including longitudinal strain (LS) analysis. Deformation ratios (septal apex to base ratio, relative apical sparing, ejection fraction to global LS), a multi-center European increased wall thickness score, and Mayo Clinic derived ATTR score (transthyretin cardiac amyloidosis score) were calculated. A logistic regression model was used to identify the parameters that best associated with a diagnosis of ATTR-CM. Comparison of the diagnostic capacity of the parameters was performed by receiver operating characteristic curves and the area under the curve (AUC).. Over half of the subjects (54.2%) were diagnosed with ATTR-CM (78% were men, median age of 76 years). Age, inferolateral wall thickness, and basal LS were the strongest predictors of ATTR-CM, AUC of 0.87 (95% CI: 0.83, 0.90), superior to the increased wall thickness score AUC of 0.78 (95% CI: 0.73, 0.83;. Inferolateral wall thickness and average basal LS performed as well as or better than more complex echo ratios and multiparametric scores to predict ATTR-CM.

Topics: Aged; Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Echocardiography; Female; Humans; Male; Prealbumin; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Humans; Prealbumin; Technetium Tc 99m Pyrophosphate

Cardiac amyloidosis (CA) is a rare form of protein deposition disease, leading to restrictive cardiomyopathy that often presents with signs and symptoms of unexplained heart failure with preserved ejection fraction (HFpEF). There are two main subtypes of CA, namely light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), which are conventionally confirmed by endomyocardial biopsy (EMB). The prognosis and treatment of the subtypes differ extensively, making it crucial to distinguish between the two. Although echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) are useful to aid in the diagnosis, they are unable to differentiate between the subtypes. Advantageously, the transthyretin cardiac amyloidosis (ATTR-CA) subtype can be diagnosed based on nuclear medicine bone scintigraphy imaging using Technetiumlabelled bone-seeking radiotracers. We report a case of a previously well, elderly gentleman who presented with acute heart failure symptoms, whereby ECHO findings were suspicious for CA. Technetium-99m pyrophosphate (99mTc- PYP) bone scintigraphy performed with complementary single photon emission computed tomography/computed tomography (SPECT/CT) at three hours post-injection revealed radiotracer uptake in the myocardium that was higher than the skeletal bone uptake. This corresponded to Perugini score of 3 along with an increased heart to contralateral lung ratio (H:CL) of 1.69. The bone scintigraphy findings together with his symptoms, ECHO, CMR, and laboratory results enabled the diagnosis of ATTR-CA to be made. In summary, bone scintigraphy offers a reliable and non-invasive method for the diagnosis of ATTR-CA. We also highlight the diagnostic pitfalls and recommendations in reporting bone scintigraphy for the indication of typing cardiac amyloidosis.

Topics: Aged; Amyloid Neuropathies, Familial; Cardiology; Diphosphates; Heart Failure; Humans; Prealbumin; Radionuclide Imaging; Stroke Volume; Technetium

Quantitative assessment of myocardial radiotracer activity with CPA or VOI have high diagnostic accuracy for ATTR-CM. Both measures are potential non-invasive markers to follow progression of disease or response to therapy.. La evaluación cuantitativa de la actividad del radiotrazador en miocárdico con CPA o VOI tiene una alta certeza diagnóstica para ATTR-CM. Ambas medidas son potenciales marcadores no invasivos para seguir la progresión de la enfermedad o la respuesta a terapia.. 背景:. L’imagerie au 99mTc-pyrophosphate est devenue une méthode non invasive importante pour le diagnostic de l’amyloidose cardiaque à transthyrétine (ATTR-CM). La quantification de l’activité du 99mTc-pyrophosphate sur les images SPECT, pourrait être un marqueur de l’intensité de la maladie. Dans cette étude, nous avons évalué la précision diagnostique et la signification clinique de la quantification au 99mTc-pyrophosphate. MéTHODES ET RéSULTATS: Les patients ayant bénéficié d’une imagerie au 99mTc-pyrophosphate pour suspicion d’ATTR-CM ont été inclus. Nous avons calculé l’activité (CPA) et le volume (VOI) du 99mTc-pyrophosphate (CPA) au niveau du myocarde sur les images SPECT en rapport à l’activité sanguine au niveau de la cavité ventriculaire gauche. La précision du test a été évaluée en utilisant la surface (AUC) sous la courbe ROC. Au total, 124 patients ont été étudiés (âge moyen de 73,9 ± 11,4). Quarante trois de ces patients (34.7%) furent diagnostiqués positivement pour l’ ATTR-CM. La précision diagnostique de la CPA s’est révélée la plus élevée (AUC 0,996, IC à 95% 0,987 - 1,00), et s’est avérée significativement plus élevée que le score de Perugini (AUC 0,952, p = 0,016). Chez les patients avec ATTR-CM, la CPA est associée à une fraction d’éjection ventriculaire gauche réduite (odds ratio ajusté de 1,28, p = 0,035) et une augmentation d’ hospitalisation pour insuffisance cardiaque (hazard ratio ajusté de 1,29, p = 0,006).. L’évaluation quantitative de l’activité du 99mTc-pyrophosphate est d’une grande précision diagnostique pour l’ ATTR-CM. Les mesures CAP et VOI sont des marqueurs non invasifs potentiels pour le suivi de la progression de la maladie ou réponse au traitement.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Female; Humans; Male; Middle Aged; Observer Variation; Predictive Value of Tests; Prognosis; Radiopharmaceuticals; Retrospective Studies; ROC Curve; Stroke Volume; Technetium Tc 99m Pyrophosphate; Tomography, Emission-Computed, Single-Photon; Ventricular Function, Left

Topics: Aged; Amyloid Neuropathies, Familial; Diphosphates; Humans; Prealbumin; Radionuclide Imaging

Topics: Aged; Amyloid Neuropathies, Familial; Diphosphates; Humans; Prealbumin; Radionuclide Imaging

Technetium-based bone scintigraphy is rapidly becoming the most common non-invasive imaging tool in the diagnosis of Transthyretin cardiac amyloidosis (ATTR). Skeletal muscle uptake has been described with technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (TcDPD), and may account for masking of bony uptake. We sought to investigate skeletal muscle uptake of technetium-99m-pyrophosphate (TcPYP) in patients with ATTR.. This was a retrospective analysis of 57 patients diagnosed with ATTR who underwent TcPYP scintigraphy. Cardiac uptake was assessed on whole-body planar imaging using a semiquantitative scale (grades 0 to 3) and on single-photon emission computed tomography (SPECT) with CT attenuation correction using total myocardial counts per voxel after a 3-hour incubation. Skeletal muscle (psoas and biceps), vertebral body, LV myocardium, and blood pool mean counts were calculated. In the cohort (age 78 ± 9 years, 77% male, and 30% hereditary ATTR), there was no visualized tracer uptake in skeletal muscle or soft tissue on qualitative SPECT assessment. Total and blood pool-corrected uptake in the muscle groups were significantly less than myocardium and bone (P < 0.001). Blood pool-corrected muscle uptake was not associated with semiquantitative grade 3 vs 2 uptake (psoas P = 0.66, biceps P = 0.13) or presence of hereditary ATTR (psoas P = 0.43, biceps P = 0.69). As bony uptake decreased, there was no corresponding increase in skeletal muscle uptake.. In patients with ATTR cardiac amyloidosis, skeletal muscle uptake of TcPYP is minimal when assessed by qualitative and quantitative metrics, and is not significantly different in patients with grade 2 vs 3 semiquantitative uptake. The properties of this tracer may be different than TcDPD with respect to non-cardiac uptake.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Biopsy; Diphosphates; Female; Humans; Male; Middle Aged; Muscle, Skeletal; Retrospective Studies; Technetium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Whole Body Imaging

Topics: Amyloid Neuropathies, Familial; Cardiomyopathy, Dilated; Diagnosis, Differential; Diphosphates; Female; Heart Failure; Humans; Middle Aged; Radionuclide Imaging; Technetium; Tomography, Emission-Computed, Single-Photon