MyocardON-TTR: Myocardial Effects in Patients With hATTR With Polyneuropathy Treated With Patisiran
Study Details
Study Description
Brief Summary
hATTR amyloidosis is a systemic disease with two clinical forms, neurological and cardiological, which are sometimes combined (so-called mixed forms).
Patisiran has shown protective effects on the progression of neurological damage.
The effects of Patisiran on the heart remain incompletely understood. The aim of this study is to better understand the morphological and functional cardiac consequences in hATTR patients with stage 1 or 2 polyneuropathy with a mixed form treated with Patisiran.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
hATTR amyloidosis is a systemic disease with two clinical forms, neurological and cardiological, which are sometimes combined (so-called mixed forms).
Patisiran has shown protective effects on the progression of neurological damage.
The effects of Patisiran on the heart remain incompletely understood.
During their therapeutic management, including the prescription of Patisiran, the routine examinations carried out at the inclusion and one year later will allow us to observe the consequences on myocardial activity during the routine consultation after 1 year of treatment.
Examinations are : clinical and biological exams, EKC, echocardiography, cardiac MRI and scintigraphy.
Data at the start of treatment and at 1 year will be collected, especially cardiac function assesment In addition, during these two consultations, a life quality 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 hATTR patients with stage 1 or 2 polyneuropathy with a mixed form treated with Patisiran.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Patients Patients hATTR with neurological and cardiac damages treated with Patisiran |
Other: Six minutes walk test
Six minutes walk test and Kansas City questionnaire just before first intake of treatment and after a year
|
Outcome Measures
Primary Outcome Measures
- Difference in longitudinal relaxation time (T1) per mapping between M0 and M12 [12 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
Secondary Outcome Measures
- Difference in Kansas City Cardiomyopathy Questionnaire score between M0 and M12 [12 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.
- Difference in distance obtained in the 6-minute walking test between M0 and M12 [12 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.
- Difference in Perugini Grading Score between M0 and M12 [12 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
- Difference in the value of the global longitudinal strain between M0 and M12 [12 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
- Difference in the value of the global left atrial longitudinal strain between M0 and M12 [12 months]
Global left atrial longitudinal strain is a parameter of echocardiography to analyse atrial function abnormalities expressed in percentage
- Difference in the value of the global strain of the right ventricular free wall between M0 and M12 [12 months]
Global strain of the right ventricular free wall of echocardiography to analyse right ventricule function expressed in percentage
- Evolution of myocardial work between M0 and M12 [12 months]
Myocardial work is composed of 4 parameters to assess myocardial function using echocardiography. 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients aged 18 years or older
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Patients with hereditary transthyretin amyloidosis (hATTR) with stage 1 or 2 polyneuropathy
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Patients for whom treatment with Patisiran has been prescribed by a hospital neurologist according to the recommendations (300 µg/kg every 3 weeks) for at least 12 months
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Patients with NYHA stage 1 and 2 cardiac disease.
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Beneficiary of a social security scheme
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Person who does not object to his/her participation in the research
Exclusion Criteria:
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Patients treated with Tafamidis simultaneously with patisiran
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Adults under legal protection (legal guardianship, curatorship, guardianship), persons deprived of liberty.
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Contraindications to the explorations provided for in the protocol: claustrophobia, metallic implant contraindicating MRI, woman of childbearing age
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHU Bordeaux Haut-Levêque | Bordeaux | France | ||
| 2 | APHP Henri Mondor | Créteil | France | ||
| 3 | CHU Grenoble Alpes | Grenoble | France | ||
| 4 | APHM Timone | Marseille | France | ||
| 5 | CHU Nancy Institut Louis Mathieu | Nancy | France | ||
| 6 | APHP Bichat | Paris | France | ||
| 7 | CHU Rennes | Rennes | France | ||
| 8 | CHU Rangueil Toulouse | Toulouse | France |
Sponsors and Collaborators
- Rennes University Hospital
Investigators
- Principal Investigator: Erwan Donal, Rennes University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 35RC22_9817_MyocardON-TTR