Clinical trial NCT04387344: Morpho-functional Cardiac Modifications in Treated Mutated Transthyretin Cardiac Amyloidosis
Official title: Cardiac Modifications in Transthyretin Cardiac Amyloidosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cardiac Amyloidosis
Lead sponsor: University of Messina
Sponsor class: OTHER
Collaborators: name: Campisi Mariapaola
First posted: 2020-05-13
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Consecutive patients with a diagnosis amyloidosis treated with RNA interferences. A diagnosis of cardiac amyloidosis requires left ventricular wall thickness of ≥12 and a positive perugini score (grade 2-3) on technetium-99m(99mTc)-diphosphonate (DPD) or 99mTc-hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy.

Brief summary: Cardiac Amyloidosis (CA) is characterized by a long subclinical phase characterized by deposition of amyloid fibrils in atria, valves and walls of ventricles. Longitudinal dysfunction of the left ventricle (LV) with preserved ejection fraction (EF) is the early phase of CA.

Longitudinal dysfunction mainly involves the LV basal and middle segments with less involvement of the distal segments (apical sparing).

Strain echocardiography (STE) measures myocardial deformation. The technique has been shown to be sensitive for early detection of impaired systolic function and for the study of CA. Additionally, cardiac efficiency (myocardial work) can be derived from myocardial strain data analysis.

In the year 2018, "RNA interferences" (patisiran and inotersen) were included in the list of compassionate therapeutic use programs for exclusive use for the treatment of adult patients with hereditary amyloidosis neuropathy. The aim of our study is to evaluate the morpho-functional modifications with RNA interferences.

Detailed description: Transthoracic echocardiographic images are recorded in the available ultrasound units (Vivid 7 and Vivid 9, GE Ultrasound, Horten, Norways and MyLab - Esaote, Genoa, Italy). The diameters and the wall thicknesses are measured according to the insurance of the American Society of Echocardiography. The images obtained with apical view and in format 4 bedrooms with frame rates (70-80 frames / s) - stored for three cardiac cycles in cine-loop format - will be used for evaluate off-line to evaluate left ventricle deformation in the longitudinal and radial direction, basalelateral, and top segments (post processing) through software already in use and available (Suitestenza, Esaote, Florence, Italy and GE Ultrasound, Horten, Norway).

Eligibility criteria: Inclusion Criteria:

* presence of data obtained from historical records of patients who retrospectively met the prescriptive (neurological) criteria and received the prescription of the drugs in question (RNA interferences) having
* Cardiological evaluation (examination ECG, echocardiography) at the time of prescription
* Cardiological evaluation (examination ECG, echocardiography) evaluated six months after therapy,
* Cardiological evaluation (examination ECG, echocardiography) evaluated 12-18 months after therapy,

Exclusion Criteria:

* it wasn't possible to putatively confirm the reasonable shipment of the innovative therapy prescribed
* it wasn't possible to putatively confirm the reasonable shipment of conventional therapy prescribed (background therapy)

Primary outcomes:
measure: Change of Atrial and Ventricular Walls Dimensions
timeFrame: Change from Baseline Wall Thickness to 18 months
measure: Change of Atrial and Ventricular Strain
timeFrame: Change from Baseline Atrial and Ventricular Strain to 18 months
Secondary outcomes:
measure: Change of Myocardial Work index of Left Ventricle
timeFrame: Change from Baseline Myocardial work to 18 months
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: Careggi Hospital
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS.
Study officials:
affiliation: University of Messina, Italy
name: Gianluca Di Bella, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Di Bella G, Pizzino F, Minutoli F, Zito C, Donato R, Dattilo G, Oreto G, Baldari S, Vita G, Khandheria BK, Carerj S. The mosaic of the cardiac amyloidosis diagnosis: role of imaging in subtypes and stages of the disease. Eur Heart J Cardiovasc Imaging. 2014 Dec;15(12):1307-15. doi: 10.1093/ehjci/jeu158. Epub 2014 Sep 4.
citation: Di Bella G, Minutoli F, Piaggi P, Casale M, Mazzeo A, Zito C, Oreto G, Baldari S, Vita G, Pingitore A, Khandheria BK, Carerj S. Usefulness of Combining Electrocardiographic and Echocardiographic Findings and Brain Natriuretic Peptide in Early Detection of Cardiac Amyloidosis in Subjects With Transthyretin Gene Mutation. Am J Cardiol. 2015 Oct 1;116(7):1122-7. doi: 10.1016/j.amjcard.2015.07.008. Epub 2015 Jul 16.
citation: Di Bella G, Minutoli F, Pingitore A, Zito C, Mazzeo A, Aquaro GD, Di Leo R, Recupero A, Stancanelli C, Baldari S, Vita G, Carerj S. Endocardial and epicardial deformations in cardiac amyloidosis and hypertrophic cardiomyopathy. Circ J. 2011;75(5):1200-8. doi: 10.1253/circj.cj-10-0844. Epub 2011 Mar 17.
citation: Emdin M, Aimo A, Rapezzi C, Fontana M, Perfetto F, Seferovic PM, Barison A, Castiglione V, Vergaro G, Giannoni A, Passino C, Merlini G. Treatment of cardiac transthyretin amyloidosis: an update. Eur Heart J. 2019 Dec 1;40(45):3699-3706. doi: 10.1093/eurheartj/ehz298.
citation: 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.
citation: Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):11-21. doi: 10.1056/NEJMoa1716153.