Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Bidimensional Shear Wave Elastography) in Patients With Transthyretin Amyloidosis (ELAST-2D)

Amyloidosis by mutation of the transthyretin gene (ATTRh) is part of a group of diseases in which the deposit of structurally abnormal proteins (amyloid fibrils) affects multiple organs such as: liver, kidney, eyes, nervous system, gastrointestinal tract and heart, and, finally, it increases the morbidity and mortality of affected patients. This deposit in the myocardium is manifested syndromically as heart failure with preserved or slightly reduced systolic function, and important diastolic dysfunction. The analysis of diastolic function comprises two components: the assessment of active relaxation, dependent on preload and afterload, and the assessment of the passive properties of the tissue - its hardness or rigidity. Myocardial stiffness represents an important parameter for diagnosis and prognosis, but its evaluation is not included in conventional echocardiography. Cardiac elastography has recently been proposed as a non-invasive diagnostic modality to assess myocardial stiffness.

Study Overview

• Status: Unknown
• Conditions: Amyloidosis
• Intervention / Treatment: Procedure: Shear wave elastography

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Recruiting
    • University of Sao Paulo Medical School - The Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented diagnosis of HRTR 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amyloidosis transthyretin with cardiac commitment; Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.	Procedure: Shear wave elastography; The elastographic technique by ultrasound (USE), shear waves or shear wave elastography (SWE), quantitatively evaluates tissue stiffness by mapping the propagation of acoustic waves (shear waves), in a non-invasive manner and without emission of ionizing radiation. Their speeds are tracked by the ultrasound equipment after tissue deformation occurs, generated by pulses of acoustic radiation (ARFI) of the transducer itself. Assuming the correlation between tissue stiffness and increased acoustic propagation speeds, it is possible to describe mathematically the elasticity of tissues by measuring specific acoustic waves.
Experimental: Amyloidosis transthyretin without cardiac commitment; Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.	Procedure: Shear wave elastography; The elastographic technique by ultrasound (USE), shear waves or shear wave elastography (SWE), quantitatively evaluates tissue stiffness by mapping the propagation of acoustic waves (shear waves), in a non-invasive manner and without emission of ionizing radiation. Their speeds are tracked by the ultrasound equipment after tissue deformation occurs, generated by pulses of acoustic radiation (ARFI) of the transducer itself. Assuming the correlation between tissue stiffness and increased acoustic propagation speeds, it is possible to describe mathematically the elasticity of tissues by measuring specific acoustic waves.
Placebo Comparator: Healthy subjects; Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.	Procedure: Shear wave elastography; The elastographic technique by ultrasound (USE), shear waves or shear wave elastography (SWE), quantitatively evaluates tissue stiffness by mapping the propagation of acoustic waves (shear waves), in a non-invasive manner and without emission of ionizing radiation. Their speeds are tracked by the ultrasound equipment after tissue deformation occurs, generated by pulses of acoustic radiation (ARFI) of the transducer itself. Assuming the correlation between tissue stiffness and increased acoustic propagation speeds, it is possible to describe mathematically the elasticity of tissues by measuring specific acoustic waves.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dyastolic miocardical elasticity	Diastolic myocardial elasticity could provide a more direct response to the constitution of the tissue and allow a simple, safe and diastolic function assessment and early initiation of specific treatment.	Around 6 months

Collaborators and Investigators

• Sponsor: Fábio Fernandes
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2020
• Primary Completion (Anticipated): January 31, 2021
• Study Completion (Anticipated): May 29, 2021

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Actual): July 2, 2020
• Last Update Submitted That Met QC Criteria: June 29, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Amyloidosis; Elastography; Cardiac; Miocardical stiffness
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: 4963/19/182

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