Cardiac Amyloidosis : Diagnostic Using Red Flag Signals (TEAM Red Flags)

Early Echographic Screening of Cardiac Amyloidosis Using Red Flag Signals

Cardiac amyloidosis is an increasingly contributor of degenerative cardiac diseases. However, its frequency remains underestimated, and diagnosis is often realized at late stages of the disease. A larger use of clinical and echographic Red Flag signals during routine echocardiographic examination may enhance the identification of early stage of the disease.

Study Overview

• Status: Unknown
• Conditions: Cardiac Amyloidosis
• Intervention / Treatment: Procedure: diagnostic algorithm

Detailed Description

The objective is to evaluate the clinical and epidemiological aspects of cardiac amyloidosis using a systematic screening of even moderate left ventricular hypertrophy, taking into account the presence of Red Flag signals. Red Flag Signals will include history or symptoms of carpal tunnel syndrome, hearing loss, chronic gastrointestinal disorders, heart failure, cervical or lumbar stenosis, or echographic abnormalities such as apical sparring, increased left ventricular filling pressure, atrio-ventricular block.

• Study Type: Observational
• Enrollment (Anticipated): 424

Contacts and Locations

Study Locations

• Guadeloupe
  • Basse-Terre, Guadeloupe, 97100
    • Not yet recruiting
    • Centre Hospitalier de Basse-Terre
    • Contact: ATALLAH André, MD; Phone Number: +590590805449; Email: atallah.andre@wanadoo.fr
    • Principal Investigator: ATALLAH André, MD
• Martinique
  • Fort-de-France, Martinique, 97261
    • Recruiting
    • CHU de Martinique
    • Contact: Jocelyn INAMO, MD-PhD; Phone Number: +596596306422; Email: jocelyn.inamo@chu-martinique.fr
  • La Trinité, Martinique, 97220
    • Not yet recruiting
    • CHU de Martinique
    • Contact: Nathalie OZIER-LAFONTAINE, MD; Phone Number: +596596604846; Email: nathalie.ozier-lafontaine@chu-martinique.fr
    • Principal Investigator: Nathalie OZIER-LAFONTAINE, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 43 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Caribbeans who the large share of populations from African origin may be associated with a high prevalence of Transthyretin amyloidosis.

In this population, diagnosis procedure will be perform to any patient with Left Ventricular Hypertrophy (LVH) with wall thickness ≥ 12 mm associated with clinical manifestations (or Red Flag signals

Description

Inclusion Criteria:

1. Diagnosis of left ventricular hypertrophy defined by a parietal thickness (interventricular septum or posterior wall) ≥ 12 mm on the echocardiogram
2. Age equal or greater than 45 years
3. Current residency in Martinique, Guadeloupe or French Guyana
4. Ability to receive and understand research information
5. Ability to freely deliver informed written consent

Exclusion Criteria:

1. Pregnant or breastfeeding woman
2. Severe uncontrolled hypertension
3. Chronic hemodialysis
4. Person under legal protection measures (guardianship, curatorship, safeguard of justice), and person deprived of liberty

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of cardiac amyloidosis diagnosed according to Gillmore's algorithm	frequency of cardiac amyloidosis diagnosed according to Gillmore's algorithm at the end of the diagnosis procedures, using biological (presence of cell dyscrasia), imaging (myocardial staining of bone tracers), and tissue examination (Congo Red staining) variables	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency genotype of Transthyretin cardiac amyloidosis according to Gillmore's algorithm	Evaluate the frequency of Transthyretin cardiac amyloidosis among subjects with even moderate left ventricular enlargement (wall thickness ≥ 12 mm), taking into account the presence or not of Red Flag signals	5 months
Distribution of Red Flag signals according to Transthyretin genotype	To Compare the distribution of Red Flag signals between wild type TTR cardiac amyloidosis and hereditary TTR cardiac amyloidosis	5 months
Diagnosis value of any Red Flag signal.	To evaluate the diagnostic performance of each of the Red Flag signals for the diagnosis of TTR cardiac amyloidosis	5 months
Elaboration of a pre-test probability score	To elaborate a pre-test probability score including the Red Flag signals, adapted to the Echo Lab settings.	5 months

Collaborators and Investigators

• Sponsor: University Hospital Center of Martinique
• Collaborators: Pfizer
• Investigators: Study Director: Doctor INAMO Jocelyn, CHU de Martinique

Publications and helpful links

General Publications

• Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, Perez J, Chiesa J, Warrington S, Tranter E, Munisamy M, Falzone R, Harrop J, Cehelsky J, Bettencourt BR, Geissler M, Butler JS, Sehgal A, Meyers RE, Chen Q, Borland T, Hutabarat RM, Clausen VA, Alvarez R, Fitzgerald K, Gamba-Vitalo C, Nochur SV, Vaishnaw AK, Sah DW, Gollob JA, Suhr OB. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013 Aug 29;369(9):819-29. doi: 10.1056/NEJMoa1208760.
• Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Plante-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceicao I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):22-31. doi: 10.1056/NEJMoa1716793.
• Di Nunzio D, Recupero A, de Gregorio C, Zito C, Carerj S, Di Bella G. Echocardiographic Findings in Cardiac Amyloidosis: Inside Two-Dimensional, Doppler, and Strain Imaging. Curr Cardiol Rep. 2019 Feb 12;21(2):7. doi: 10.1007/s11886-019-1094-z.

Helpful Links

• Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
• Frequency of cardiac amyloidosis inpatients with unexplained left ventricular hypertrophy: The Caribbean Amyloidosis Study

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Anticipated): September 30, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 1, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): November 17, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: 18_RIPH2-22

Drug and device information, study documents

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