Substudy (NCT04456582): Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Two-dimensional Shear Wave Elastography) in Patients With Amyloidosis and Fabry Disease.

NCT ID: NCT04893889

Last Updated: 2021-05-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-09
• Study Completion Date: 2022-03-30

Brief Summary

Introduction: Heart failure with preserved systolic function encompasses several different diseases, but which have diastolic dysfunction and its components in common: myocardial stiffness and altered relaxation. Myocardial stiffness represents an important parameter for diagnosis and prognosis, but only changes in relaxation are evaluated in clinical practice. Cardiac elastography has been proposed as a diagnostic modality for noninvasive assessment of myocardial stiffness.

Objective: The aim of our study is to investigate the potential of myocardial elastography by shear waves to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity (EMD) in Fabry disease (DF) and cardiac amyloidosis (AC ) in the ATTRh form and correlate with other complementary imaging and laboratory tests (electrocardiogram, 2D echocardiogram, troponin and BNP) and with a 6-minute walk test and quality of life questionnaires.

Material and methods: 60 adults will be prospectively included: 20 patients with Fabry disease, 40 patients with hRTRT (20 with cardiac involvement) and 20 patients as a control group. Echocardiography, electrocardiogram and laboratory evaluations will be performed. The elastocardiographic assessment of myocardial stiffness will be performed in ultrasound equipment (Canon, Aplio i800) using a multifrequency convex transducer, under specific adjustment of the equipment to perform myocardial elastography.

Conditions

Fabry Disease; Amyloidosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

Fabry disease patients

Patients diagnosed with Fabry disease. Interventions will be as follows: Shear wave myocardial elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity (EMD) in Fabry disease (DF) and cardiac amyloidosis (AC) in the ATTRh form and correlating with other complementary imaging tests and laboratory tests (electrocardiogram, 2D echocardiogram, troponin and BNP) and with a 6-minute walk test and quality of life questionnaires.

Group Type: EXPERIMENTAL

Shear-wave elastography

Intervention Type: DIAGNOSTIC_TEST

Myocardial shear wave elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity.

Amyloidosis transthyretin with cardiac commitment

Patients diagnosed with amyloidosis who present cardiac commitment. Interventions will be as follows: Shear wave myocardial elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity (EMD) in Fabry disease (DF) and cardiac amyloidosis (AC) in the ATTRh form and correlating with other complementary imaging tests and laboratory tests (electrocardiogram, 2D echocardiogram, troponin and BNP) and with a 6-minute walk test and quality of life questionnaires.

Group Type: ACTIVE_COMPARATOR

Shear-wave elastography

Intervention Type: DIAGNOSTIC_TEST

Myocardial shear wave elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity.

Healthy subjects

Healthy patients. Interventions will be as follows: Shear wave myocardial elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity (EMD) in Fabry disease (DF) and cardiac amyloidosis (AC) in the ATTRh form and correlating with other complementary imaging tests and laboratory tests (electrocardiogram, 2D echocardiogram, troponin and BNP) and with a 6-minute walk test.

Group Type: PLACEBO_COMPARATOR

Shear-wave elastography

Intervention Type: DIAGNOSTIC_TEST

Myocardial shear wave elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity.

Interventions

Shear-wave elastography

Myocardial shear wave elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Documented diagnosis of ATTRh with and without cardiac involvement.

For the definition of cardiac involvement by ATTRh, all the criteria below must be presented:

• Pathogenic mutation of TTR consistent with ATTRh.
• Evidence of cardiac commitment by echocardiography or nuclear magnetic resonance with measurement of the interventricular septum at the end of diastole (SIVd)> 12mm or / and medical history of heart failure, and / or levels of troponin and / or BNP above the reference value without another more likely cause.
• Amyloid deposit in cardiac or extra-cardiac tissue (eg, abdominal fat aspirate, salivary gland, connective sheath of the median nerve) confirmed by congo red staining or presence of grade 2 or 3 myocardial scintigraphy (DPD-CT) of cardiac uptake, in cases where the presence of monoclonal gammopathy of undetermined significance (MGUS) was ruled out.
• In the presence of MGUS, confirmation of the TTR protein in the tissue is necessary through immunohistochemistry (IHC) or mass spectrometry.

Exclusion Criteria

• Presence of another type of cardiomyopathy such as hypertension, valve or ischemic heart disease (eg, previous myocardial infarction documented with myocardial necrosis markers and electrocardiographic changes).
• Presence of diseases other than cardiac amyloidosis, impairing the assessment of functional capacity, such as chronic obstructive pulmonary disease, severe arthritis or peripheral arterial disease, recent or planned orthopedic procedure during the course of the study (eg, spine surgery or under lower limbs) that impairs walking in the 6-minute test evaluation.
• Acute coronary heart disease or unstable angina in the past 3 months Report of disease of the sinus or atrioventricular node with indication of a pacemaker, but with no intention of implantation.
• Presence of untreated hypothyroidism or hyperthyroidism.
• Previous heart, liver or other organ transplant.
• Presence of neoplasia in the last 3 years, except for basal and squamous cell carcinomas of skin or cervical cancer in situ previously treated.
• Presence of other medical conditions or comorbidities that, in the investigator's opinion, could interfere with the course of the study or the interpretation of the data.
• Pregnancy.
• History of alcohol abuse in the last 2 years or excessive daily alcohol intake (for women, more than 14 units per week; for men, more than 21 units of alcohol per week [unit: one glass of wine (125ml) = one dose of distillate = 332.5ml of beer).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

University of Sao Paulo General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Instituto do Coração - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Fabio Fernandes, MD, PhD

Role: CONTACT

fabio.fernandes@incor.usp.br

+551126615057

Caio R Cafezeiro, MD

Role: CONTACT

caiocafezeiro@usp.br

+551126615057

Facility Contacts

Fabio Fernandes, MD, PhD

Role: primary

fabio.fernandes@incor.usp.br

+551126615057

Caio R Cafezeiro, MD

Role: backup

caiocafezeiro@usp.br

+551126615057

Other Identifiers

4963/19/182 FABRY

Identifier Type: -

Identifier Source: org_study_id