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The Regional Scintigraphic DPD Uptake in Cardiac Transthyretin Amyloidosis.

Recruiting
Conditions
Transthyretin Amyloidosis
Interventions
Radiation: 99mTc-DPD scintigraphy
Diagnostic Test: Collection of blood samples and echocardiography
Registration Number
NCT05814380
Lead Sponsor
Katarzyna Holcman
Brief Summary

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

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Group 299mTc-DPD scintigraphyfirst-degree relative of a patient with ATTR
Group 199mTc-DPD scintigraphygrade 1-3 cardiac retention of 99mTc-DPD in scintigraphy
Group 1Collection of blood samples and echocardiographygrade 1-3 cardiac retention of 99mTc-DPD in scintigraphy
Group 2Collection of blood samples and echocardiographyfirst-degree relative of a patient with ATTR
Primary Outcome Measures
NameTimeMethod
regional left ventricle 99mTc-DPD uptakeday 1

To compare the regional left ventricle 99mTc-DPD uptake among patients with hereditary and wild-type cardiac transthyretin amyloidosis.

Secondary Outcome Measures
NameTimeMethod
99mTc-DPD cardiac uptake among asymptomatic hereditary transthyretin amyloidosis variants carriersday 1

To evaluate the presence and extent of 99mTc-DPD cardiac uptake among asymptomatic hereditary transthyretin amyloidosis variants carriers.

right ventricular 99mTc-DPD accumulationday 1

To assess prevalence of right ventricular 99mTc-DPD accumulation among patients with hereditary and wild-type cardiac transthyretin amyloidosis.

Trial Locations

Locations (1)

Department of Cardiac and Vascular Diseases, John Paul II Hospital

🇵🇱

Krakow, Lesser Poland, Poland

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