Amyloidosis TTR Flow Reserve Evaluation

NCT05103943 | Active Not Recruiting

• 1 other identifier: CHRO-2021-05
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

Brief Summary

Anginal symptoms and signs of ischemia have been reported in some patients with cardiac amyloidosis (TTR) without obstructive epicardial coronary artery disease (CAD). It was found that coronary microvascular dysfunction was highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD. The investigators found lower stress and rest myocardial blood flow (MBF) and lower myocardial flow reserve (MFR) in their cardiac PET (Positron emission tomography) study (13N), including 21 patients. The advances in SPECT technology including cadmium zinc telluride (CZT) detectors allow to evaluate the MBF and MFR estimation by SPECT as shown in both experimental animal models and also in clinical studies with comparison to PET. SPECT is more widely available than cardiac PET.

Conditions

Amyloid Cardiomyopathy

Keywords

Tafamidis

Outcome Measures

Primary Outcomes (2)

• Difference of Stress and Rest Myocardial Blood Flow

  Difference of Stress and Rest Myocardial Blood Flow (mL/min/g) at baseline and after 24 months of treatments, assessed by dynamic SPECT (regional and global left ventricle measurements)

  Month 24

• ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow

  Difference of Myocardial Flow Reserve (ie ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow) at baseline and after 24 months of treatments, assessed by dynamic SPECT (regional and global left ventricle measurements)

  Month 24

Secondary Outcomes (3)

• Number or participants with stress reduction

  baseline

• Number or participants with rest MBF (myocardial blood flow) reduction

  baseline

• ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow

  Baseline

Study Arms (1)

SPECT MPI (myocardial perfusion imaging) Group

EXPERIMENTAL

the SPECT MPI protocol will be modified to evaluated MBF and MFR. This modification will result in no added radiation; the radiopharmaceutical dose will still be the same compared to a standard MPI protocol.

Other: SPECT MPI

Interventions

SPECT MPI OTHER

SPECT MPI including dynamic acquisitions for stress, rest MBF and MFR

SPECT MPI (myocardial perfusion imaging) Group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged from 18 to 90 years
• Understanding and speaking French
• With TTR amyloid cardiomyopathy (ATTRxt or ATTRm) confirmed by the association of heart failure, syncope or bradyarrhythmia, with electrocardiogram and/or magnetic resonance imaging (CMR) suggesting/indicating cardiac amyloid, grade 2 or 3 99mTc- PYP or bone scintigraphy and negative biological findings (i.e. serum immunofixation, urine immunofixation, serum free light chain assay); or, if one of those criteria is not met, presence of amyloid deposits on analysis of biopsy specimens obtained from cardiac and non-cardiac sites (17-19),
• Intention to treat (Tafamidis)

You may not qualify if:

• Heart failure not due to transthyretin amyloid cardiomyopathy;
• New York Heart Association (NYHA) class IV heart failure.
• The presence of light-chain amyloidosis;
• A history of liver or heart transplantation;
• An estimated glomerular filtration rate lower than 25 mL per minute per 1.73 m2 of bodysurface area (Cockcroft).
• Liver transaminase levels exceeding two times the upper limit of the normal range;
• Severe malnutrition as defined by a modified body-mass index (mBMI) of less than 600, calculated as the serum albumin level in grams per litter multiplied by the conventional BMI (the weight in kilograms divided by the square of the height in meters);
• Patients receiving concurrent treatment with nonsteroidal anti-inflammatory drugs, tauroursodeoxycholate, doxycycline, calcium-channel blockers, or digitalis;
• Previous treatment with tafamidis or patisaran;
• Ticagrelor treatment
• Previous CAD, severe epicardial stenosis with revascularization or ticagrelor treatment, coronary artery bypass grafting, myocardial infarction;
• Contra-indications to pharmacological stress testing MPI: severe hypotension (\< 90 mmHg of Systolic arterial pressure), atrioventricular block 2nd or 3rd grade, carotid stenosis (unilateral \>70%, bilateral \>50%);
• Pregnancy
• Breastfeeding
• Protected adults

Sponsors & Collaborators

• Centre Hospitalier Régional d'Orléans: lead

Study Sites (4)

CHU d'ANGERS

Angers, France

Location

CHU Caen

Caen, 14033, France

Location

CHU Orleans

Orléans, 45067, France

Location

CHRU de TOURS

Tours, France

Location

Related Publications (7)

• Dorbala S, Vangala D, Bruyere J Jr, Quarta C, Kruger J, Padera R, Foster C, Hanley M, Di Carli MF, Falk R. Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis. JACC Heart Fail. 2014 Aug;2(4):358-67. doi: 10.1016/j.jchf.2014.03.009. Epub 2014 Jul 9.

  PMID: 25023822 BACKGROUND

• Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007-1016. doi: 10.1056/NEJMoa1805689. Epub 2018 Aug 27.

  PMID: 30145929 BACKGROUND

• Al Suwaidi J, Velianou JL, Gertz MA, Cannon RO 3rd, Higano ST, Holmes DR Jr, Lerman A. Systemic amyloidosis presenting with angina pectoris. Ann Intern Med. 1999 Dec 7;131(11):838-41. doi: 10.7326/0003-4819-131-11-199912070-00007.

  PMID: 10610629 BACKGROUND

• Ogawa H, Mizuno Y, Ohkawara S, Tsujita K, Ando Y, Yoshinaga M, Yasue H. Cardiac amyloidosis presenting as microvascular angina--a case report. Angiology. 2001 Apr;52(4):273-8. doi: 10.1177/000331970105200407.

  PMID: 11330510 BACKGROUND

• Whitaker DC, Tungekar MF, Dussek JE. Angina with a normal coronary angiogram caused by amyloidosis. Heart. 2004 Sep;90(9):e54. doi: 10.1136/hrt.2004.038984.

  PMID: 15310723 BACKGROUND

• Nam MC, Nel K, Senior R, Greaves K. Abnormal Myocardial Blood Flow Reserve Observed in Cardiac Amyloidosis. J Cardiovasc Ultrasound. 2016 Mar;24(1):64-7. doi: 10.4250/jcu.2016.24.1.64. Epub 2016 Mar 24.

  PMID: 27081447 BACKGROUND

• Vancon B, Bisson A, Courtehoux M, Bernard A, Bailly M. A study protocol for an observational cohort investigating cardiac transthyretin amyloidosis flow reserve before and after Tafamidis treatment: The AMYTRE study. Front Med (Lausanne). 2022 Aug 23;9:978293. doi: 10.3389/fmed.2022.978293. eCollection 2022.

  PMID: 36082269 DERIVED

MeSH Terms

Conditions

Amyloid Neuropathies, Familial

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies

Study Officials

• Matthieu BAILLY, Dr

  CHU Orléans

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2021
• First Posted: November 2, 2021
• Study Start: February 24, 2022
• Primary Completion (Estimated): December 11, 2026
• Study Completion (Estimated): December 11, 2026
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

FR (4)