The Regional Scintigraphic DPD Uptake in Cardiac Transthyretin Amyloidosis.

Study Overview
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Brief Summary
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Cardiac transthyretin (ATTR) amyloidosis is an infiltrative cardiomyopathy with an inexorably progressive clinical course and poor prognosis. The disease is caused by misfolding of the liver-derived precursor protein transthyretin as a result of an acquired wild-type variant (ATTRwt) or as a hereditary mutant variant (ATTRm). Application of single-photon emission computed tomography (SPECT) provides greater anatomic resolution, enabling the assessment of amyloid burden within individual left ventricle segments.This study aims to describe the pattern of regional myocardial distribution of 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) SPECT uptake among patients with ATTRwt and ATTRm. It will investigate the clinical, biochemical and echocardiographic, including left ventricle longitudinal strain profile in ATTRwt and ATTRm. Moreover, we will evaluate the presence and extent of DPD cardiac uptake among asymptomatic ATTRm variants carriers.This is a prospective multi-center observational study. The study, after obtaining prior written informed consent, will include consecutive patients who have Grade 1-3 cardiac DPD retention in scintigraphy. In addition, first-degree relatives of patients with ATTRm are going to be enrolled. Patients are going to undergo TTR gene sequencing to assess the presence of pathogenic variants associated with ATTRm. Both planar scintigraphy, SPECT and speckle-tracking echocardiography will be reviewed and interpreted using visual and quantitative approaches.

Detailed Description
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Cardiac transthyretin (ATTR) amyloidosis is an infiltrative cardiomyopathy with an inexorably progressive clinical course and poor prognosis. The disease is caused by misfolding of the liver-derived precursor protein transthyretin as a result of an acquired wild-type variant (ATTRwt) or as a hereditary mutant variant (ATTRm). Application of single-photon emission computed tomography (SPECT) provides greater anatomic resolution, enabling the assessment of amyloid burden within individual left ventricle segments. This study aims to describe the pattern of regional myocardial distribution of 3,3-diphosphono-1,2-propanedicarboxylic acid (DPD) SPECT uptake among patients with ATTRwt and ATTRm. It will investigate the clinical, biochemical and echocardiographic, including left ventricle longitudinal strain profile in ATTRwt and ATTRm. Moreover, we will evaluate the presence and extent of DPD cardiac uptake among asymptomatic ATTRm variants carriers. This is a prospective multi-center observational study. The study, after obtaining prior written informed consent, will include consecutive patients who have Grade 1-3 cardiac DPD retention in scintigraphy. In addition, first-degree relatives of patients with ATTRm are going to be enrolled. Patients are going to undergo TTR gene sequencing to assess the presence of pathogenic variants associated with ATTRm. Both planar scintigraphy, SPECT and speckle-tracking echocardiography will be reviewed and interpreted using visual and quantitative approaches. The collected data will be analyzed statistically to verify research hypotheses. Approval from the local Bioethical Committee will be obtained before carrying out the study. All procedures performed are going to be in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments, or comparable ethical standards.

Official Title
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The Comparisons of Regional Scintigraphic DPD Uptake Between Patients With Hereditary and Wild Type Cardiac Transthyretin Amyloidosis

Conditions
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Transthyretin Amyloidosis

Intervention / Treatment
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* Radiation: 99mTc-DPD scintigraphy
* Diagnostic Test: Collection of blood samples and echocardiography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: over 18 years of age, providing written informed consent, grade 1-3 cardiac retention of 99mTc-DPD in scintigraphic study or a first-degree relative of a patient with ATTR Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>grade 1-3 cardiac retention of 99mTc-DPD in scintigraphy | Radiation: 99mTc-DPD scintigraphy<br>* 99mTc-DPD scintigraphy<br>Diagnostic Test: Collection of blood samples and echocardiography<br>* Collection of blood samples from a peripheral vein and TTR sequencing. Transthoracic echocardiography.<br>|
| Group 2<br>first-degree relative of a patient with ATTR | Radiation: 99mTc-DPD scintigraphy<br>* 99mTc-DPD scintigraphy<br>Diagnostic Test: Collection of blood samples and echocardiography<br>* Collection of blood samples from a peripheral vein and TTR sequencing. Transthoracic echocardiography.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| regional left ventricle 99mTc-DPD uptake | To compare the regional left ventricle 99mTc-DPD uptake among patients with hereditary and wild-type cardiac transthyretin amyloidosis. | day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| right ventricular 99mTc-DPD accumulation | To assess prevalence of right ventricular 99mTc-DPD accumulation among patients with hereditary and wild-type cardiac transthyretin amyloidosis. | day 1 | 
| 99mTc-DPD cardiac uptake among asymptomatic hereditary transthyretin amyloidosis variants carriers | To evaluate the presence and extent of 99mTc-DPD cardiac uptake among asymptomatic hereditary transthyretin amyloidosis variants carriers. | day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transthyretin amyloidosis, SPECT