Grant: Foundation Grant

Université Laval

$4,464,583.00

Novel Approaches for the Diagnosis and Treatment of Aortic Valve Stenosis

FY 2014-15

Summary

Aortic stenosis (AS), the most frequent valvular heart disease (VHD), is associated with a major healthcare/socioeconomic burden. Contrasting with the magnitude of the problem, the mechanisms of AS remain poorly understood and no medical treatment is currently available to slow its progression. The overall objective of the research program is to perform multidisciplinary patient-oriented researchto elucidate the mechanisms underlying the development and progression of AS and to develop, validate, and implement into practice novel approaches to improve the diagnosis and treatment of this disease. The 5 aims of the program are articulated around the 3 top priorities of research identified in the recent guidelines of medical societies: Priority 1: In patients with mild-to-moderate AS (Progression Stage B): To develop and validate pharmacotherapy to slow/halt the progression of AS.We propose: i) To pursue and expand the ongoing observational cohort study PROGRESSA in asymptomatic patients with AS (Aim 1).ii) To perform 2 randomized controlled trials (RCTs) to assess the effectiveness of aggressive lipoprotein(a) lowering (RELEAS trial) and renin-angiotensin system inhibition (RAAS) (Aim 2). These are currently the most promising pharmacological therapies for this disease. Priority 2: In patients with asymptomatic severe AS (Stage C): To enhance individualized risk stratification to better determine the optimal timing for aortic valve replacement (AVR): i.e. early “prophylactic” vs. at symptoms onset: PROGRESSA Study (Aim 3). Priority 3: In patients with low-flow (LF), low-gradient (LG) AS (Stage D2 and D3):i) To develop new approaches to corroborate stenosis severity and optimize risk stratification; ii) To determine the best timing and type of treatment (surgical vs. transcatheter AVR, vs. medical therapy) in the different subtypes of LF-LG AS. We propose: i) To pursue and expand the ongoing multicenter observational cohort study (TOPAS) of LF-LG AS (Aim 4); ii) To perform RCTs to assess the effectiveness of transcatheter AVR versus medical therapy (Aim 5) in: a) Patients with moderate AS, low LV ejection fraction and heart failure symptoms (TAVR-UNLOAD-I) b) Symptomatic patients with low-gradient AS and preserved LVEF (TAVR-UNLOAD-II). Expertise and knowledge translation:The Project Leader, P Pibarot, has developed a large research consortium of several cutting edge laboratories (imaging, biomarkers, genomics), core labs & blood/tissue banks, collaborators (54 sites, 10 countries), and industry partners. This consortium is now among the world’s leading groups in VHD research and is key to the successful realization of the proposed multicenter studies. The results of this program will lead to the development and validation of novel pharmacotherapies, technologies, and strategies to improve the diagnosis and treatment of AS. These results will have direct and immediate impact on medical practice and pharmaceutical/device industry. The proposed Training & Mentorship Program includes the following key components:i) Scholarship/fellowship program to support trainees of the consortium; ii) Short-term exchanges for enhancing trainees research skill and productivity;iii) Formalized mentorship program for early-career investigators and senior trainees across the consortium to enhance transition to independence in VHD research; iv) Development of educational and knowledge transfer activities to disseminate the findings of the research program.

Department

Canadian Institutes of Health Research

Program

Foundation Grant

Recipient

Université Laval

Location

Quebec, Canada

Recipient Type

Academia

Type

Grant

Source

CIHR Funding Decisions Database

As published

312987

Name

Pibarot Philippe J

Region

Québec

Country

Canada

Orgtype

Institution Paid; Research Institution

Instname2

Circulatory and Respiratory Health

Theme2

Clinical

Prcname2

Foundation Grant

Projecttitle

Novel Approaches for the Diagnosis and Treatment of Aortic Valve Stenosis

Programtype2

Operating Grants

Orgnameinp2

Université Laval

Cihramount2

$4,464,583

Cihrequipment2

Programname2

Foundation Grant

Keyworddelim

Aortic Stenosis; Computed Tomography; Doppler-Echocardiography; Exercise Testing; Genomics; Heart Valve Prosthesis; Magnetic Resonance Imaging; Mitral Regurgitation; Transcatheter Valve Therapy; Valvular Heart Disease

Competitiondate

201409

Approvedterm2

7 yrs 0 mth

Pinamesdelim

Pibarot, Philippe J

Approvedterm

7 ans 0 mois

Cihrcontribution2

~ $4,464,583~ $0~

Abstract

<html> <body> Aortic stenosis (AS), the most frequent valvular heart disease (VHD), is associated with a major healthcare/socioeconomic burden. Contrasting with the magnitude of the problem, the mechanisms of AS remain poorly understood and no medical treatment is currently available to slow its progression. The overall objective of the research program is to perform multidisciplinary patient-oriented researchto elucidate the mechanisms underlying the development and progression of AS and to develop, validate, and implement into practice novel approaches to improve the diagnosis and treatment of this disease. The 5 aims of the program are articulated around the 3 top priorities of research identified in the recent guidelines of medical societies: Priority 1: In patients with mild-to-moderate AS (Progression Stage B): To develop and validate pharmacotherapy to slow/halt the progression of AS.We propose: i) To pursue and expand the ongoing observational cohort study PROGRESSA in asymptomatic patients with AS (Aim 1).ii) To perform 2 randomized controlled trials (RCTs) to assess the effectiveness of aggressive lipoprotein(a) lowering (RELEAS trial) and renin-angiotensin system inhibition (RAAS) (Aim 2). These are currently the most promising pharmacological therapies for this disease. Priority 2: In patients with asymptomatic severe AS (Stage C): To enhance individualized risk stratification to better determine the optimal timing for aortic valve replacement (AVR): i.e. early “prophylactic” vs. at symptoms onset: PROGRESSA Study (Aim 3). Priority 3: In patients with low-flow (LF), low-gradient (LG) AS (Stage D2 and D3):i) To develop new approaches to corroborate stenosis severity and optimize risk stratification; ii) To determine the best timing and type of treatment (surgical vs. transcatheter AVR, vs. medical therapy) in the different subtypes of LF-LG AS. We propose: i) To pursue and expand the ongoing multicenter observational cohort study (TOPAS) of LF-LG AS (Aim 4); ii) To perform RCTs to assess the effectiveness of transcatheter AVR versus medical therapy (Aim 5) in: a) Patients with moderate AS, low LV ejection fraction and heart failure symptoms (TAVR-UNLOAD-I) b) Symptomatic patients with low-gradient AS and preserved LVEF (TAVR-UNLOAD-II). Expertise and knowledge translation:The Project Leader, P Pibarot, has developed a large research consortium of several cutting edge laboratories (imaging, biomarkers, genomics), core labs & blood/tissue banks, collaborators (54 sites, 10 countries), and industry partners. This consortium is now among the world’s leading groups in VHD research and is key to the successful realization of the proposed multicenter studies. The results of this program will lead to the development and validation of novel pharmacotherapies, technologies, and strategies to improve the diagnosis and treatment of AS. These results will have direct and immediate impact on medical practice and pharmaceutical/device industry. The proposed Training & Mentorship Program includes the following key components:i) Scholarship/fellowship program to support trainees of the consortium; ii) Short-term exchanges for enhancing trainees research skill and productivity;iii) Formalized mentorship program for early-career investigators and senior trainees across the consortium to enhance transition to independence in VHD research; iv) Development of educational and knowledge transfer activities to disseminate the findings of the research program. </body> </html>

View source data CIHR Funding Decisions Database (Canadian Institutes of Health Research)