The Regional Scintigraphic DPD Uptake in Cardiac Transthyretin Amyloidosis. (AMYLOIDOZA)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Transthyretin Amyloidosis
• Intervention / Treatment: Radiation: 99mTc-DPD scintigraphy; Diagnostic test: Collection of blood samples and echocardiography

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.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Katarzyna Holcman, MD, PhD; Phone Number: +48 12 614 22 87; Email: katarzyna.holcman@gmail.com

Study Locations

• Poland
  • Lesser Poland
    • Krakow, Lesser Poland, Poland, 31-202
      • Recruiting
      • Department of Cardiac and Vascular Diseases, John Paul II Hospital
      • Contact: Katarzyna Holcman, MD, PhD; Email: katarzyna.holcman@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

100 consecutive patients

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; grade 1-3 cardiac retention of 99mTc-DPD in scintigraphy	Radiation: 99mTc-DPD scintigraphy; 99mTc-DPD scintigraphy; Diagnostic test: Collection of blood samples and echocardiography; Collection of blood samples from a peripheral vein and TTR sequencing. Transthoracic echocardiography.
Group 2; first-degree relative of a patient with ATTR	Radiation: 99mTc-DPD scintigraphy; 99mTc-DPD scintigraphy; Diagnostic test: Collection of blood samples and echocardiography; Collection of blood samples from a peripheral vein and TTR sequencing. Transthoracic echocardiography.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
left ventricle longitudinal strain	To investigate echocardiographic left ventricle longitudinal strain profile in hereditary and wild-type ATTR cardiac amyloidosis.	day 1

Collaborators and Investigators

• Sponsor: Katarzyna Holcman

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2020
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: April 3, 2023
• First Submitted That Met QC Criteria: April 13, 2023
• First Posted (Actual): April 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: SPECT; transthyretin amyloidosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Proteostasis Deficiencies; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Amyloidosis, Familial; Amyloid Neuropathies; Amyloidosis; Amyloid Neuropathies, Familial
• Other Study ID Numbers: ID#57165999

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No