Morpho-functional Cardiac Modifications in Treated Mutated Transthyretin Cardiac Amyloidosis

Cardiac Modifications in Transthyretin Cardiac Amyloidosis

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.

Study Overview

• Status: Unknown
• Conditions: Cardiac Amyloidosis

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).

• Study Type: Observational
• Enrollment (Anticipated): 25

Contacts and Locations

Study Locations

• Italy
  • Firenze, Italy
    • Careggi Hospital
  • Roma, Italy
    • Fondazione Policlinico Universitario A. Gemelli IRCCS.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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.

Description

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)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Atrial and Ventricular Walls Dimensions	Measurements (mm) of Interatrial Septum, Ventricular Walls, Coumadin Ridge, Mitro-aortic Lamina, Valves	Change from Baseline Wall Thickness to 18 months
Change of Atrial and Ventricular Strain	Mean paired change in myocardial strain (percent) by echocardiographic strain-rate imaging (unitless)	Change from Baseline Atrial and Ventricular Strain to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Myocardial Work index of Left Ventricle	Evaluation of the Global work index (GWI): total work within the area of the LV pressure-strain loops calculated from mitral valve closure to mitral valve opening.	Change from Baseline Myocardial work to 18 months

Collaborators and Investigators

• Sponsor: University of Messina
• Collaborators: Campisi Mariapaola
• Investigators: Principal Investigator: Gianluca Di Bella, MD, University of Messina, Italy

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 20, 2020
• Primary Completion (ANTICIPATED): June 30, 2020
• Study Completion (ANTICIPATED): December 30, 2020

Study Registration Dates

• First Submitted: May 3, 2020
• First Submitted That Met QC Criteria: May 12, 2020
• First Posted (ACTUAL): May 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 13, 2020
• Last Update Submitted That Met QC Criteria: May 12, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: UNIME_CARD_2

Drug and device information, study documents

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