Increasing Amyloidosis Awareness and Diagnosis Through Programmatic Imaging, Blood/Urine Testing and Pathology

To set up a Brazilian strategy for early diagnosis of cardiac amyloidosis using new modality of echocardiography, the 3D echocardiography, and the level of myocardial deformity by measuring the Strain Longitudinal through the technology Speckle Tracking.

Study Overview

• Status: Recruiting
• Conditions: Amyloidosis

Detailed Description

Transthyretin cardiac amyloidosis (ATTR-CA) is an infiltrative cardiomyopathy caused by extracellular deposition of insoluble transthyretin amyloid fibrils in the myocardium. Unstable changes in the wild type and variant (familial) stimulate misfold aggregation and ultimately form amyloid fibrils and deposit in various tissues including the heart. Generally, cardiac amyloidosis is a cause of heart failure with preserved ejection fraction. The heart involvement with amyloidosis may represent part of a systemic disease with multiorgan involvement as is seen with light chain amyloidosis (AL). A distinct form of cardiac amyloidosis is the deposition of misfold transthyretin that results from aggregation of the native protein or from inherited mutations in the transthyreyin (TTR) gene, in particular in old patients and, with the increase of the aged population, the incidence of ATTR-CA is increasing although its real presence and correct diagnosis lacks standardized strategies, in particular due to diseases in the differential diagnosis with similar phenotypes. The Wild type ATTR-CA also known as senile systemic amyloidosis caused by age related misfolding of the TTR is the most frequent form of age-related cardiac amyloidosis. Hereditary ATTR-CA due to gene mutations can also lead to cardiac amyloidosis but in Brazil the most frequent mutation Val30Met usually has a clinical phenotype predominantly neurological contrary to the USA, where the mutation Val122Ile is more frequent with a cardiomyopathy phenotype. Lack of recognition of cardiac amyloidosis due to the presence of nonspecific symptoms and associated comorbidities commonly leads to delayed diagnosis and disease progression. Echocardiography is the first line technique for patients presenting with heart failure but there is still a gap on the clinical utility of the multiparametric parameters or their combination in patients where conventional echocardiogram raises the suspicion of cardiac amyloidosis. The study will be one of the first in its kind to prospectively delineate the presence of cardiac amyloidosis in a patient population where this hypothesis has not been properly evaluated.

Study Design:In this cohort study, patients undergoing evaluation for amyloidosis will be provided with diagnostic tools to confirm the diagnosis; in cases where verified, subtype methodologies for amyloidosis subtype characterization will be employed. If there is a suspicion of amyloidosis complementary imaging, etiologic evaluation with TTR sequencing, paraprotein evaluation (serum and urine serum protein electrophoresis and immunofixation, serum-free light), and pyrophosphate scintigraphy will be performed. If the origin of amyloid protein cannot be determined, further evaluation with biopsy of the amyloid deposition and mass spectrometry will be undertaken. Initially, fatpad biopsy and minor salivary glands will be performed. If unrevealing, the affected organ will be biopsied for amyloid tissue characterization.

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

Contacts and Locations

• Study Contact: Name: Phillip Scheinberg, MD; Phone Number: +55 11 3505722; Email: naipe@bp.org.br

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil
      • Recruiting
      • Gisele Medeiros Bastos
      • Contact: Gisele M Bastos; Email: naipe@bp.org.br

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with heart failure in the aged population. Approximately 100 patients will be screened on the patient population described.

Description

Inclusion Criteria:

• Individuals with heart failure in the absence of hypertension
• heart failure with normal ejection fraction
• heart failure associated with aortic stenosis and atypical arrythmias, in which there is the suspicion of cardiaca amyloidosis

Exclusion Criteria:

• Individuals which do not consent to participate on the study or those that retired the consent during the study
• Individuals under 18 years old

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with diagnosis of ATTR cardiac amyloidosis after performing protocol exams (not necessarily all) - echocardiogram, cardiac magnetic resonance, scintigraphy, genetic test, blood and urine paraprotein test and biopsies.	Infiltrative cardiomyopathy caused by extracellular deposition of insoluble transthyretin amyloid fibrils in the myocardium.	After performing protocol exams, which will occur, for each patient, approximately, two months after entry in the study.

Collaborators and Investigators

• Sponsor: Beneficência Portuguesa de São Paulo
• Investigators: Principal Investigator: Phillip Scheinberg, MD, Beneficencia Portuguesa de Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2021
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: July 16, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 30, 2021

Study Record Updates

• Last Update Posted (Actual): December 29, 2021
• Last Update Submitted That Met QC Criteria: December 8, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Amyloid cardiomyopathy
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: Amyloidosis

Drug and device information, study documents

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