Transthyretin Amyloidosis, Amyloidosis, Hereditary
Conditions
Keywords
Patisiran, Vutrisiran
Brief summary
ATTRv amyloidosis is a systemic disease with two clinical forms, neurological and cardiological, which are sometimes combined (so-called mixed forms). Patisiran and vutrisiran have shown protective effects on the progression of neurological damage. The effects of Patisiran or vutrisiran on the heart remain incompletely understood. The aim of this study is to better understand the morphological and functional cardiac consequences in ATTRv patients with stage 1 or 2 polyneuropathy with a mixed form treated with Patisiran or vutrisiran
Detailed description
ATTRv amyloidosis is a systemic disease with two clinical forms, neurological and cardiological, which are sometimes combined (so-called mixed forms). Patisiran and vutrisiran have shown protective effects on the progression of neurological damage. The effects of Patisiran or vutrisiran on the heart remain incompletely understood. During their therapeutic management, including the prescription of Patisiran or vutrisiran, the routine examinations carried out at the inclusion, one and two year later will allow us to observe the consequences on myocardial activity during the routine consultation after 1 and 2 years of treatment. Examinations are : clinical and biological exams, EKC, echocardiography, cardiac MRI and scintigraphy. Data at the start of treatment and at 1 and 2 years will be collected, especially cardiac function assesment In addition, during these two consultations, a life quality questionnaire, a dysautonomia questionnaire and a functional walking test will be carried out specifically for the study. The aim of this study is to better understand the morphological and functional cardiac consequences in ATTRv patients with stage 1 or 2 polyneuropathy with a mixed form treated with Patisiran or vutrisiran.
Interventions
Six minutes walk test just before first intake of treatment and after 1 and 2 years
OTHERKansas City questionnaire
Kansas City questionnaire just before first intake of treatment and after 1 and 2 years
OTHERCOMPASS31 self questionnaire
Compass31 self questionnaire assessing dysautonomia just before first intake of treatment and after 1 and 2 years
Sponsors
Rennes University Hospital
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients aged 18 years or older * Patients with hereditary transthyretin amyloidosis (ATTRv) with stage 1 or 2 polyneuropathy * Patient not previously treated for ATTRv * Patients for whom treatment with patisiran or vutrisiran has been initiated by a hospital neurologist in accordance with recommendations for a minimum of 24 months. * Patients with NYHA stage 1 and 2 cardiac disease. * Beneficiary of a social security scheme * Person who does not object to his/her participation in the research
Exclusion criteria
* Patients treated with Tafamidis simultaneously with patisiran or vutrisiran * Adults under legal protection (legal guardianship, curatorship, guardianship), persons deprived of liberty. * Contraindications to the explorations provided for in the protocol: claustrophobia, metallic implant contraindicating MRI, woman of childbearing age
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in longitudinal relaxation time (T1) per mapping between M0 and M24 | 24 months | Longitudinal relaxation time (T1) is the process by which the net magnetization (M) grows/returns to its initial maximum value (Mo) parallel to Bo in a MRI. Myocardial T1 depends on the pulse sequence, cardiac cycle as well as other factors and increases at higher magnetic field strength. T1-mapping can detect a variety of myocardial pathologies, where it shows increased values. Because of variations between scanners the primary use of a local reference range is recommended and if a local reference range is not available quantitative results should not be clinically reported. An intermediate analysis will be done at 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Compass31 questionnaire score between M0 and M24 | 24 months | The COMPASS-31 (Composite Autonomic Symptom Score-31) scale measures neurodegenerative system symptoms through 31 patient-reported questions. Assessment is through six weighted domains: orthostatic intolerance \[10 points\]; vasomotor \[6 points\]; secretomotor \[7 points\]; gastrointestinal \[28 points\]; bladder \[9 points\] and pupillomotor \[15 points\]. A higher score indicates worse autonomic dysfunction. An intermediate analysis will be done at 12 months |
| Difference in distance obtained in the 6-minute walking test between M0 and M24 | 24 months | The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance in meter covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. An intermediate analysis will be done at 12 months |
| Difference in Perugini Grading Score between M0 and M24 | 24 months | The Perugini grading scale is a semi-quantitative method of scoring cardiac uptake following injection of 99mTc-DPD, 99mTc-Pyrophosphate or 99mTc-HMDP scintigraphy in the investigation of cardiac amyloidosis (particularly ATTR amyloidosis). The grading scale visually compares tracer uptake in the myocardium and ribs. grade 0 is no cardiac and normal rib uptake; grade 1 is cardiac less than rib uptake; grade 2 is cardiac equal to rib uptake; and grade 3 is cardiac greater than rib uptake with mild/absent rib uptake. An intermediate analysis will be done at 12 months |
| Difference in Kansas City Cardiomyopathy Questionnaire score between M0 and M24 | 24 months | Kansas City Cardiomyopathy Questionnaire is a self-administered questionnaire developed to independently measure the patient's perception of their health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life. Five scores are generated, all scores are scaled 0-100, where 0 denotes the lowest reportable health status and 100 the highest. An intermediate analysis will be done at 12 months |
| Difference in the value of the global left atrial longitudinal strain between M0 and M24 | 24 months | Global left atrial longitudinal strain is a parameter of echocardiography to analyse atrial function abnormalities expressed in percentage. An intermediate analysis will be done at 12 months |
| Difference in the value of the global strain of the right ventricular free wall between M0 and M124 | 24 months | Global strain of the right ventricular free wall of echocardiography to analyse right ventricule function expressed in percentage. An intermediate analysis will be done at 12 months |
| Evolution of myocardial work between M0 and M24 | 24 months | Myocardial work is composed of 4 parameters to assess myocardial function using echocardiography. An intermediate analysis will be done at 12 months Global Constructive Work (expressed in mmHg%) : Positive work performed in systole (shortening) + Negative work performed in isovolumetric relaxation (lengthening). Normal range : 1582-2881 Global Wasted Work (expressed in mmHg%) : Negative work performed in systole (lengthening) + Positive work performed in isovolumetric relaxation (shortening). Normal range : 226 ± 28 Global Work Efficiency (expressed in %) Percentage (0-100%) of constructive work over total work =\> Constructive work/(constructive work + wasted work). Normal range : 91 ± 0.8 Global Work Index (expressed in mmHg%) : Amount of myocardial work performed by the left ventricle during systole =\> area of PSL from mitral valve closure to mitral valve opening. Normal range : 1292-2505 |
| Difference in the value of the global longitudinal strain between M0 and M24 | 24 months | global longitudinal strain is a simple parameter in echocardiography to analyse atrial function abnormalities expressed in percentage that expresses longitudinal shortening as a percentage (change in length as a proportion to baseline length) for left ventricular (LV) systolic dysfunction. An intermediate analysis will be done at 12 months |
Countries
France
Outcome results
None listed