High Resolution Three-dimensional Maps of the Right Chambers in Patient Diagnosed With Cardiac Amyloidosis (CARTO-AMYLO)

Frequency and Severity of Cardiac Injury in Transthyretin Cardiac Amyloidosis : an Electro Mapping Study.

Amyloid heart disease is an accumulation of fibrillar proteins in the extracellular sector of the heart.

Identified on echocardiography as Ventricular hypertrophy. The investigation of a Left Ventricular hypertrophy (LVH) is the most frequent discovery circumstance of amyloid heart disease.

Pathophysiological mechanisms poorly understood, resulting in late diagnosis. Transthyretin amyloid heart disease (CATTR) is the most common form of cardiac amyloidosis in the West Indies due to an abnormally high frequency of the Val122Ile and Val107Ile mutations of the transthyretin gene in this population. Val122Ile and Val107Ile mutated-transthyretin are the substitution of valine for isoleucine at codon 122 of the TTR gene ( V122I) and at codon 107 of the TTR gene (V107I).

Complications of CATTR are functional changes in heart cells or even death due to mechanical abnormalities (loss of contractility and increased wall stiffness cardiac arousal and conduction disturbances).

These disorders result from an electrical abnormality of the heart the reason why the cardiologist performs preventive performance of electrophysiological explorations with EnSite Precision™. It's a registration system used to detect foci of necrosis within the myocardium.

Amyloid deposits are areas devoid of electrical activity. Do they detectable by the EnSite Precision™ recording system ?

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiac Disease; Cardiac Amyloidosis
• Intervention / Treatment: Radiation: Cardiac electro-mapping

Detailed Description

Transthyretin's amyloid heart disease (CATTR) is a rare disease whose frequency is high in the Caribbean's due to a high frequency of Val122Ile, an amyloidosis prone mutation in the Transthyretin gene. The Val122Ile variant might be present in 15 to 20 000 subjects in Martinique, placing them at high risk to develop the CATTR.

CATTR results from the accumulation of amyloid deposits between the intercellular spans, resulting in mechanical cardiac abnormalities, but also in latent excitation or conduction defects: atrial and ventricular hyperexcitability, bundle branch blocks, atrio-ventricular blocks. These abnormalities require systematic electrophysiological studies and if necessary, antiarrythmic medications or pacemaker placement.

Electro-mapping of the cardiac chambers offers high-resolution three-dimensional maps of cardiac electrical activity which has been used recently to detect focal myocardial infarction.

This anatomo-functional imaging, used only once in cardiac amyloidosis, showed a correlation between areas of low voltage of the left atrial myocardium and areas of late gadolinium enhancement, a marker of amyloidosis deposit, found in cardiac MRI.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fabrice DEMONIERE, MD; Phone Number: +596596306490; Email: fabrice.demoniere@chu-martinique.fr

Study Locations

• Martinique
  • Fort-de-France, Martinique, 97261
    • Centre Hospitalier Universitaire de Fort-de-France
    • Contact: Fabrice DEMONIERE, MD; Phone Number: +596596306490; Email: fabrice.demoniere@chu-martinique.fr
    • Sub-Investigator: Jocelyn INAMO, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Controls:

• Aged 18 and more
• Have had an echocardiogram within 6 months prior to inclusion
• Have had a cardiac Holter in the 6 months prior to inclusion.
• Informed Consent given

Cases :

• Aged 18 and over
• Presence of cardiac amyloidosis with Transthyretin
• Have had an echocardiogram within 6 months prior to inclusion
• Have had a cardiac Holter monitoring in the 6 months prior to inclusion.
• Informed Consent given

Exclusion Criteria:

Controls

• Known case of amyloidosis in the immediate family
• Patient known to have amyloidosis
• Left ventricular wall thickness greater than or equal to 14 mm
• Hyperechogenicity of the left ventricular walls
• Cardiac disease which may affect electro-anatomic mapping: Right ventricular dysplasia, myocardial infarction, congenital heart disease.
• Contraindication such as pregnancy to radiological exams
• Presence of an anomaly of the vena cava
• Presence of intracavitary thrombus at cardiac echocardiography
• Patients with a pacemaker

Cases

• Cardiac disease which may affect electro-anatomic mapping: Right ventricular dysplasia, myocardial infarction, congenital heart disease.
• Contraindication such as pregnancy to radiological exams
• Presence of an anomaly of the vena cava
• Presence of intracavitary thrombus at cardiac echocardiography

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patient free cardiac amyloidosis; Patient with heart disease (related with rhythm disorders or conduction disorders) but free cardiac amyloidosis.	Radiation: Cardiac electro-mapping; Perform an high-resolution three-dimensional maps of cardiac electrical activity using EnSite Precision system.
Experimental: Patient with Transthyretin cardiac amyloidosis; Patient with transthyretin cardiac amyloidosis plus heart disease (related with rhythm disorders or conduction disorders).	Radiation: Cardiac electro-mapping; Perform an high-resolution three-dimensional maps of cardiac electrical activity using EnSite Precision system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of zones with abnormal electrical activity	Percentage of subject with at least one area of electrical inactivity (<0.1 mV) or at least one area of continuous low-voltage activity	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristics of zones with electrical inactivity	Number of areas of electrical inactivity (<0.1 mV)	1 month
Zones with electrical inactivity	Area of surface of electrical inactivity (<0.1 mV)	1 month
Characteristics of zones with abnormal electrical activity	Number of areas of continuous low voltage activity	1 month
Zones with abnormal electrical activity	Surface of areas of continuous low voltage activity	1 month
Compare electrical activity anomaly to total longitudinal strain on cardiac ultrasound	Number of areas of electrical inactivity vs. total longitudinal strain on cardiac ultrasound.	1 month
Electrical activity anomaly and total longitudinal strain on cardiac ultrasound	Number of areas of continuous low voltage activity vs. Total longitudinal strain on cardiac ultrasound.	1 month
Compare electrical activity anomaly (surface) to total longitudinal strain on cardiac ultrasound	Surface of areas of electrical inactivity vs. Total longitudinal strain on cardiac ultrasound.	1 month
Electrical activity anomaly (continuous low voltage activity) and total longitudinal strain on cardiac ultrasound	Surface of areas of continuous low voltage activity vs. Total longitudinal strain on cardiac ultrasound.	1 month
Compare electrical activity anomaly to Brain Natriuretic Peptide (BNP) value	Number of areas of electrical inactivity vs. BNP value.	1 month
Electrical activity and Brain Natriuretic Peptide (BNP) value	Number of areas of continuous low voltage activity vs. BNP value.	1 month
Compare electrical activity anomaly (surface) to Brain Natriuretic Peptide (BNP) value	Surface of areas of electrical inactivity vs. BNP value.	1 month
Electrical activity anomaly (continuous low voltage activity) and Brain Natriuretic Peptide (BNP) value	Surface of areas of continuous low voltage activity vs. BNP value.	1 month
Compare electrical activity anomaly to the presence of severe ventricular arrhythmia	Number of areas of electrical inactivity vs. the presence of severe ventricular arrhythmia.	1 month
Electrical activity anomaly and presence of severe ventricular arrhythmia	Number of areas of continuous low voltage activity vs. the presence of severe ventricular arrhythmia.	1 month
Compare electrical activity anomaly (surface) to the presence of severe ventricular arrhythmia	Surface of areas of electrical inactivity vs. the presence of severe ventricular arrhythmia.	1 month
Electrical activity anomaly (continuous low voltage activity) and presence of severe ventricular arrhythmia	Surface of areas of continuous low voltage activity vs. the presence of severe ventricular arrhythmia.	1 month
Compare electrical activity anomaly and to the presence of an atrial arrythmia	Number of areas of electrical inactivity vs. the presence of an atrial fibrillation load.	1 month
Electrical activity anomaly and presence of an atrial arrythmia	Number of areas of continuous low voltage activity vs. the presence of an atrial fibrillation load.	1 month
Compare electrical activity anomaly (surface) to the presence of an atrial arrythmia	Surface of areas of electrical inactivity vs. the presence of an atrial fibrillation load.	1 month
Electrical activity anomaly (continuous low voltage activity) and presence of an atrial arrythmia	Surface of areas of continuous low voltage activity vs. the presence of an atrial fibrillation load.	1 month

Collaborators and Investigators

• Sponsor: University Hospital Center of Martinique
• Collaborators: GIRCI SOHO
• Investigators: Study Director: Jocelyn INAMO, MD, PhD, CHU de Martinique; Principal Investigator: Fabrice DEMONIERE, MD, CHU de Martinique

Publications and helpful links

General Publications

• Oliveira Da Silva L, Fabre J, Monfort A, Villeret J, Citony I, Cohen-Tenoudji P, Lebbadi M, Martin D, Molinie V, Inamo J. 'Green Apple' Heart Failure. West Indian Med J. 2014 Jul 3;63(6):673-5. doi: 10.7727/wimj.2013.255. Epub 2014 Jun 25.
• Khairy LT, Barin R, Demoniere F, Villemaire C, Billo MJ, Tardif JC, Macle L, Khairy P. Heart Rate Response in Spectators of the Montreal Canadiens Hockey Team. Can J Cardiol. 2017 Dec;33(12):1633-1638. doi: 10.1016/j.cjca.2017.08.002. Epub 2017 Oct 5.
• Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, Macle L, Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY, Berry SM, Berry DA; ThermoCool AF Trial Investigators. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA. 2010 Jan 27;303(4):333-40. doi: 10.1001/jama.2009.2029.
• Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaici A, Hajji L, O'Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011 Jul 7;365(1):44-53. doi: 10.1056/NEJMoa1005565.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: July 7, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): July 9, 2021
• Last Update Submitted That Met QC Criteria: July 7, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Transthyretin; Cardiac amyloidosis; Val122Ile; Cardiac electro-mapping; EnSite Precision
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Metabolic Diseases; Proteostasis Deficiencies; Heart Diseases; Amyloidosis
• Other Study ID Numbers: 19_RIPH3-03

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