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Trial record 67 of 226 for:    Recruiting, Not yet recruiting, Available Studies | Aortic stenosis

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

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ClinicalTrials.gov Identifier: NCT02260466
Recruitment Status : Recruiting
First Posted : October 9, 2014
Last Update Posted : February 19, 2019
Sponsor:
Collaborators:
Pfizer
Henri Mondor University Hospital
Information provided by (Responsible Party):
French Cardiology Society

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.


Condition or disease Intervention/treatment Phase
Heart Disease Aging Amyloidosis Aortic Valve Stenosis Other: a basal LV septum biopsy Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: AMYLO-CARTESIAN Study :Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.
Study Start Date : October 2014
Estimated Primary Completion Date : May 29, 2019
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
elderly patients with Aortic steNosis valvular replacement 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




Primary Outcome Measures :
  1. Clinical composite criterion: All causes of death and cardiovascular hospitalization at 1 year after surgery [ Time Frame: 1 year ]
    All causes of death and cardiovascular hospitalization at 1 year after surgery



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02260466


Contacts
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Contact: Tessa BERGOT +33144907033 tessa.bergot@sfcardio.fr

Locations
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France
Hôpital Henri Mondor Recruiting
Creteil, France, 94010
Contact: Thibaud DAMY, MD PhD         
Principal Investigator: Thibaud DAMY, MD PhD         
Chu Fort de France Not yet recruiting
FORT DE France, France, 97261
Contact: Jocelyn INAMO         
CHU Limoges Not yet recruiting
Limoges, France, 87000
Contact: Dania MOHTY         
CHU LYON Not yet recruiting
Lyon, France, 69000
Contact: Hélène THIBAULT         
Chu Rennes Recruiting
Rennes, France, 35000
Contact: Erwan DONAL         
Principal Investigator: Erwan DONAL         
Sponsors and Collaborators
French Cardiology Society
Pfizer
Henri Mondor University Hospital
Investigators
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Principal Investigator: Thibaud DAMY, MD PhD CHU Henri Mondor, Paris

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Responsible Party: French Cardiology Society
ClinicalTrials.gov Identifier: NCT02260466     History of Changes
Other Study ID Numbers: 2013-02
First Posted: October 9, 2014    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019

Keywords provided by French Cardiology Society:
Amyloidosis
echocardiography
magnetic resonance imaging
radionuclide imaging

Additional relevant MeSH terms:
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Constriction, Pathologic
Aortic Valve Stenosis
Heart Diseases
Amyloidosis
Amyloid Neuropathies, Familial
Cardiovascular Diseases
Pathological Conditions, Anatomical
Proteostasis Deficiencies
Metabolic Diseases
Heart Valve Diseases
Ventricular Outflow Obstruction
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Amyloid Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors