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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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.

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 lev

Detailed Summary:

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 prognosi
Sponsor: French Cardiology Society

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

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: French Cardiology Society

Dates:
Date Received: October 6, 2014
Date Started: October 2014
Date Completion: July 2019
Last Updated: July 28, 2016
Last Verified: July 2016