Metabolic Determinants of the Progression of Aortic Stenosis (PROGRESSA)
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|ClinicalTrials.gov Identifier: NCT01679431|
Recruitment Status : Recruiting
First Posted : September 6, 2012
Last Update Posted : March 7, 2017
Calcific aortic stenosis (AS) has become the most common cardiac disease after coronary artery disease and hypertension. Unfortunately no medical therapies have been proven to decrease either the progression of valve stenosis or the resulting adverse effects on myocardial remodeling and function. In light of the studies performed in PROGRESSA, it becomes obvious that: i) AS is a complex and actively regulated process that involves the interaction of several pathways including lipid infiltration and retention, chronic inflammation, osteogenic activation, and active mineralization within the valvular tissues; ii) AS is not a disease strictly limited to the aortic valve but rather a systemic disease that often involves calcification and stiffening of the aorta and impairment of LV function as a consequence of pressure overload. Our findings suggest that the dysmetabolic milieu linked to visceral obesity may accelerate the deterioration of the structure and function not only of the aortic valve but also of the aorta and of the left ventricle. These findings open new avenues of research and provide strong impetus for the elaboration of prospective studies focusing on the "valvulo-metabolic risk" in AS.
The general hypotheses are: The metabolic abnormalities linked to visceral obesity accelerate (1) the progression of valvular calcification and stenosis, aortic calcification and stiffness; (2) the progression of myocardial fibrosis and dysfunction.
The general objectives of the study are to elucidate the mechanisms implicated in the pathogenesis of AS and to identify the metabolic factors that determine the progression of: i) aortic valve calcification and stenosis; ii) myocardial fibrosis and dysfunction; and iii) clinical outcomes.
This study will contribute to identifying the key metabolic determinants of AS progression and will pave the way for the future development of non surgical therapies for this disease. The results of this study would provide strong support to the realization of randomized trial to test the efficacy of lifestyle modification program or new pharmacological treatment aiming at the reduction of visceral fat and associated metabolic abnormalities in the AS population. Furthermore, this study will contribute to the identification of novel blood and imaging biomarkers of faster disease progression, which will help to optimize risk stratification and timing of AVR in the AS population.
|Condition or disease||Intervention/treatment|
|Aortic Valve Stenosis||Other: Doppler-echocardiography Radiation: Computed tomography Other: Magnetic resonance imaging Biological: Fasting blood sample|
|Study Type :||Observational|
|Estimated Enrollment :||250 participants|
|Official Title:||Metabolic Determinants of the Progression of Aortic Stenosis - PROGRESSA Study|
|Study Start Date :||April 2005|
|Estimated Primary Completion Date :||January 2018|
|Estimated Study Completion Date :||January 2019|
Patients with aortic stenosis
Patients have every year: 1) an assessment of cardiometabolic risk profile with measure of body mass index, waist circumference and fasting blood sample and 2) a comprehensive Doppler-echocardiographic exam.
Computed tomography and magnetic resonance imaging are performed every 2 years.
|Other: Doppler-echocardiography Radiation: Computed tomography Other: Magnetic resonance imaging Biological: Fasting blood sample|
- Progression of aortic valve stenosis [ Time Frame: Patients will be followed every 1 year, up to 5 years ]Annualized progression rate of aortic stenosis hemodynamic severity calculate as the difference between peak aortic jet velocity, transvalvular gradients, and aortic valve area measured at baseline and those measured at the last follow-up divided by the time between the first and last examinations.
- Progression of aortic valve calcification [ Time Frame: Patients will be followed every 2 years, up to 5 years ]Annualized progression rate of aortic valve calcium
- Progression of myocardial fibrosis and dysfunction [ Time Frame: PPatients will be followed every 2 years, up to 5 years ]Annualized progression rate of myocardial fibrosis and global longitudinal myocardial strain
- Progression of aortic calcification and stiffness [ Time Frame: Patients will be followed every 2 years, up to 5 years ]Annualized progression rate of calcification measured by computed tomography and aortic compliance measured (CT) by cardiac magnetic resonance (CMR) and Doppler-echocardiography
- Progression of coronary artery calcification [ Time Frame: Patients will be followed every 2 years, up to 5 years ]Annualized progression rate of coronary artery calcification measured by CT
- Progression of global hemodynamic load [ Time Frame: Patients will be followed every 1 year, up to 5 years ]Annualized progression rate of valvulo-arterial impedance measured by Doppler-echocardiography
- Aortic stenosis related events [ Time Frame: From date of baseline until the date of first documented aortic stenosis related events (as defined on description box), assessed up to 5 years ]Cardiovascular-related mortality; hospitalization for heart failure; surgical or transcatheter aortic valve replacement motivated by the development of symptoms or LV systolic dysfunction
- Ischemic cardiovascular events [ Time Frame: From date of baseline until the date of first documented ischemic cardiovascular events (as defined on description box), assessed up to 5 years ]Myocardial infarction; unstable angina; revascularization procedure
- All-cause mortality [ Time Frame: From date of baseline until the date of death from any cause assessed up to 5 years ]Death from any cause
Biospecimen Retention: Samples With DNA
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): NCT01679431
|Contact: Philippe Pibarot, PhD, DVM||418-656-8711 ext 5938||Philippe.Pibarot@med.ulaval.ca|
|Contact: Romain Capoulade, MSc||418-656-8711 ext 3845||Romain.Capoulade@criucpq.ulaval.ca|
|Institut Universitaire de Cardiologie et de Pneumologie de Québec||Recruiting|
|Québec, Quebec, Canada, G1V4G5|
|Contact: Philippe Pibarot, PhD 418-656-8711 ext 5938 Philippe.Pibarot@med.ulaval.ca|
|Contact: Romain Capoulade, MSc 418-656-8711 ext 3845 Romain.Capoulade@criucpq.ulaval.ca|
|Principal Investigator: Phillipe Pibarot, PhD|
|Principal Investigator:||Philippe Pibarot, PhD, DVM||Institut Universitaire de Cardiologie et de Pneumologie de Québec|