Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.

NCT02260466

Last updated date
Study Location
Centre Cardiologique du Nord
Saint-Denis, , 93200, France
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+33144907033

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Heart Disease, Aging, Amyloidosis, Aortic Valve Stenosis
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Significant aortic stenosis. The aortic stenosis severity (aortic area : <1cm² or <0.6cm²/m² measured by echocardiography

- Indication of surgical aortic valve replacement for AS: will be defined in each center in accordance with ESC guidelines.

- Patient ≥ 70 years old and NYHA class ≥2 and LVEF <60% or global LV strain more than "-17%".

- Written consent prior to surgery.

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Other severe disease with a life prognosis below than 1 year.


- Already known other causes of amyloidosis than senile amyloidosis will be excluded.


- Patients unsuitable for AS surgery as defined by ESC guidelines 2012.


- Significant mitral valve disease needing a surgical treatment.


- Significant aortic regurgitation (class >III).


NB: Patients with pacemaker will be included but will not perform the cardiac MRI.

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Heart Disease, Aging, Amyloidosis, Aortic Valve StenosisPrevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.
NCT02260466
  1. Saint-Denis,
  2. Toulouse,
  3. Creteil,
  4. FORT DE France,
  5. Limoges,
  6. Lyon,
  7. Rennes,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.
Official Title  ICMJE AMYLO-CARTESIAN Study :Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.
Brief Summary

Background: The prevalence of both senile cardiac amyloidosis (CA) and aortic stenosis (AS) markedly increases with age. Aortic stenosis increases left ventricular pressure overload. Cardiac deposits have been observed in AS and the amount of these deposits has been correlated to post-surgical outcome. As they are strong echocardiographic and cardiac MRI imaging similarities between CA and AS, the investigators hypothesized that the deposit observed in AS is transthyretin amyloid deposit. The investigators objective is to demonstrate that amyloid deposit is associated with poor outcomes following aortic stenosis surgical valve replacement.

Materiel and methods: 180 patients with indication for surgical aortic valve replacement will be recruited prospectively and consecutively in 5 French centers. A replicative study will be performed in one Austrian center. Echocardiography, cardiac MRI and bone scintigraphy will be performed prior to surgery. During surgery, a basal LV septum biopsy will be collected for determination and quantification of interstitial deposits using specific staining which will be performed in a blind fashion. Clinical outcomes will be recorded during the hospitalization period following the surgery and at 1 year. Alive and re-hospitalization status will be determined. Patients will be classified according to the presence or not of amyloid deposits.

Expected results and impact: This study will emphasize how pressure overload stress accelerates and magnifies amyloid deposition usually known to be related to cardiac aging process. It will develop reliable imaging tools and markers to detect cardiac amyloid deposition. Correlation between anatomopathologic analyses and the three different imaging technics will identify accurate imaging markers of CA. A risk stratification model based on amyloid deposits level for the clinical management of these patients will be created combining imaging and biological markers.

Detailed Description

Cardiovascular diseases remain the major cause of mortality and morbidity in industrialised countries. Their prevalence increases steeply as consequence of the aging of the population in these countries. Curiously, cardiovascular and neurodegenerative diseases share common aging pathological pathways involving abnormal accumulation of insoluble amyloid proteins in the extracellular matrix disrupting normal organ function. Whereas neurological amyloid diseases has been considerably investigated, little attention has been paid to the aggregation of amyloid proteins in cardiovascular diseases. Post-mortem studies have identified cardiac wild-type transthyretin amyloidosis deposition in 25% of individuals over the age of 80 years leading to the concept of "senile cardiac amyloidosis" (CA) (Cornwell, Am j Med 1984; Pitkanen, Am J Pathol 1984). The cause of this deposition is not yet known but might be related primarily to aging process and enhanced by cardiac mechanical stress (overload), hypoxia, oxidative stress and inflammation. Since patients with transthyretin CA develop severe heart failure with poor prognosis, it is crucial to identify them especially among population at risk such those with aortic stenosis (AS). Indeed this common valvular heart disease affects mainly senescent subjects and combines so the adverse effects on myocardial function of both pressure overload and myocardial aging.

Interestingly, some elderly patients with severe AS exhibit similar echocardiographic and cardiac MRI patterns as those reported in CA including increased cardiac wall thickness and progressive left ventricular dysfunction starting with alteration of basal LV-2D strain. They also exhibit increased late gadolinium enhancement (LGE) at cardiac MRI. This has been interpreted as related to interstitial myocardial "fibrosis" and has been correlated with poor prognosis after aortic valve replacement i.e.; high mortality, persistence of heart failure symptoms and LV dysfunction (Weidemann Circ 2009; Dweck, JACC 2011; Hermann JACC 2011). However none of these patients have benefited from a detailed histology analysis with aiming at identifying amyloid deposits. The investigators have recently found similar clinical observations in the investigators AS cohort. Using specific staining, the investigators were able to unmask the association of severe AS and CA in these patients. These preliminary findings raise the question of a potential pathophysiological link between CA and AS and might explain why some patients with AS may not benefit from cardiac surgery.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Condition  ICMJE
  • Heart Disease
  • Aging
  • Amyloidosis
  • Aortic Valve Stenosis
Intervention  ICMJE Other: a basal LV septum biopsy
During surgery, a basal LV septum biopsy will be collected for determination and quantification of interstitial deposits using specific staining which will be performed in a blind fashion
Study Arms  ICMJE elderly patients with Aortic steNosis valvular replacement
Intervention: Other: a basal LV septum biopsy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 8, 2014)
180
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2021
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Significant aortic stenosis. The aortic stenosis severity (aortic area : <1cm² or <0.6cm²/m² measured by echocardiography
  • Indication of surgical aortic valve replacement for AS: will be defined in each center in accordance with ESC guidelines.
  • Patient ? 70 years old and NYHA class ?2 and LVEF <60% or global LV strain more than "-17%".
  • Written consent prior to surgery.

Exclusion Criteria:

  • Other severe disease with a life prognosis below than 1 year.
  • Already known other causes of amyloidosis than senile amyloidosis will be excluded.
  • Patients unsuitable for AS surgery as defined by ESC guidelines 2012.
  • Significant mitral valve disease needing a surgical treatment.
  • Significant aortic regurgitation (class >III).

NB: Patients with pacemaker will be included but will not perform the cardiac MRI.

Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tessa BERGOT+33144907033[email protected]
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02260466
Other Study ID Numbers  ICMJE 2013-02
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party French Cardiology Society
Study Sponsor  ICMJE French Cardiology Society
Collaborators  ICMJE
  • Pfizer
  • Henri Mondor University Hospital
Investigators  ICMJE
Principal Investigator:Thibaud DAMY, MD PhDCHU Henri Mondor, Paris
PRS Account French Cardiology Society
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP