Clinical Trial: Determinants of the Progression and Outcome of Mitral Regurgitation
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational
Official Title: Determinants of the Progression and Outcome of Mitral Regurgitation-PROGRAM STUDY
Brief Summary: Mitral regurgitation (MR) is one of the most frequent valve lesions, both in North America and in Europe, and its prevalence is increasing with the aging of the population. Organic Mitral Regurgitation (OMR) and Ischemic Mitral Regurgitation are the 2 main categories of MR. Organic or primary MR is caused by an anatomic alteration of the valvular or subvalvular mitral apparatus and refers to rheumatic MR and degenerative MR that includes mitral leaflet prolapse and flail leaflet. In the past 20 years, degenerative MR has become, by far, the most frequent cause of severe MR leading to surgery in the western world. However, the best current treatment for OMR remains uncertain and controversial. We have obtained preliminary data showing that OMR is a dynamic lesion. Hence, the echocardiographic evaluation of MR at rest, as generally performed during routine clinical exam, does not necessarily reflect the status of MR during patient's daily activities and thereby does not adequately assess the risk of rapid progression and poor outcome in these patients. The objective of this study is to identify the independent predictors of disease progression and outcome in patients with asymptomatic chronic OMR and to develop and validate novel imaging and circulating biomarkers to improve risk stratification and therapeutic decision-making process in patients with chronic asymptomatic primary OMR.
Detailed Summary:
Mitral regurgitation (MR) is one of the most frequent valve lesions, both in North America and in Europe, and its prevalence is increasing owing to the aging of the population. There are 2 main categories of MR: Organic Mitral Regurgitation (OMR) and Ischemic Mitral Regurgitation. Organic or primary MR is caused by an anatomic alteration of the valvular or subvalvular mitral apparatus and refers to rheumatic MR and degenerative MR that includes mitral leaflet prolapse and flail leaflet. In the past 20 years, degenerative MR has become, by far, the most frequent cause of severe MR leading to surgery in the western world. However, the best current treatment for OMR remains uncertain and controversial. This is, in large part, due to the lack of prospective data on the determinants of OMR progression and outcome. Furthermore, we have obtained preliminary data showing that OMR is a dynamic lesion. Hence, the echocardiographic evaluation of MR at rest, as generally performed during routine clinical exam, does not necessarily reflect the status of MR during patient's daily activities and thereby does not adequately assess the risk of rapid progression and poor outcome in these patients.
The general objective of this study is thus: to identify the independent predictors of disease progression and outcome in patients with asymptomatic chronic OMR and to develop and validate novel imaging and circulating biomarkers to improve risk stratification and therapeutic decision-making process in patients with chronic asymptomatic primary OMR.
The specific aims of the study are: (1) To obtain and analyze: a) the dynamic changes in MR severity, pulmonary arterial pressure, and LV function during exercise; b) the maximum exercise capacity; c) the metabolic profile; d) the plasma natriuretic peptides, e) the degree and localization of myocardia
Sponsor: Laval University
Current Primary Outcome: Combined clinical and echocardiographic endpoint [ Time Frame: Patients will be followed for 4 years ]
Original Primary Outcome: Combined clinical and echocardiographic endpoint [ Time Frame: Patients will be followed for 4 years ]
Current Secondary Outcome:
- Progression of MR severity [ Time Frame: Patients will be followed for 4 years ]The annualized progression rate of MR severity will be calculated as the difference between effective regurgitant orifice, regurgitant volume, and vena contracta width measured at baseline and those measured at the last follow-up divided by the time between the first and last examinations.
- Progression of pulmonary arterial hypertension [ Time Frame: Patients will be folowed for 4 years ]The annualized progression rate of resting systolic pulmonary arterial pressure will be calculated.
- Progression of LV dysfuntion prior to surgery [ Time Frame: Patients will be followed for 4 years ]The annualized progression rate of LVEF, LV end-systolic dimension, and LV myocardial global peak systolic velocities and global longitudinal strain will be calculated.
- Maximum exercise capacity at baselin and following mitral valve surgery [ Time Frame: Patients will be followed for 4 years ]Maximum exercise capacity at baseline as measured by the percentage of age and gender predicted VO2max. We will determine which are, among the clinical and Doppler-echocardiographic variables, the independent determinants of maximum exercise capacity at baseline. The baseline exercise capacity will also be used as an independent variable, i.e. we will determine if it is an independent predictor of the primary end-point and of the other secondary end-points
- Composite end-point prior to mitral valve surgery [ Time Frame: Patients will be followed for 4 years ]i.e. follow-up censored at surgery
- Composite primary end-point after mitral vale surgery [ Time Frame: Patients will be followed for 4 years ]i.e. time zero set at surgery
- Mitral valve surgery [ Time Frame: Patients will be followed for 4 years ]Motivated by the occurrence of symptoms, LV systolic dysfunction, atrial fibrillation, and/or resting pulmonary pressure > 50 mmHg.
- Arrhythmic burden [ Time Frame: Patients will be followed for 4 years ]Number and percentage of ventricular ectopic per 24 h, percent time in atrial fibrillation, or flutter per 24 h.
Original Secondary Outcome:
- Progression of MR severity [ Time Frame: Patients will be followed for 4 years ]The annualized progression rate of MR severity will be calculated as the difference between effective regurgitant orifice, regurgitant volume, and vena contracta width measured at baseline and those measured at the last follow-up divided by the time between the first and last examinations.
- Progression of pulmonary arterial hypertension [ Time Frame: Patients will be folowed for 4 years ]The annualized progression rate of resting systolic pulmonary arterial pressure will be calculated.
- Progression of LV dysfuntion [ Time Frame: Patients will be followed for 4 years ]The annualized progression rate of LVEF, LV end-systolic dimension, and LV myocardial global peak systolic velocities and strain will be calculated.
- Maximum exercise capacity at baseline [ Time Frame: Patients will be followed for 4 years ]Maximum exercise capacity at baseline as measured by the percentage of age and gender predicted VO2max. We will determine which are, among the clinical and Doppler-echocardiographic variables, the independent determinants of maximum exercise capacity at baseline. The baseline exercise capacity will also be used as an independent variable, i.e. we will determine if it is an independent predictor of the primary end-point and of the other secondary end-points
Information By: Laval University
Dates:
Date Received: April 16, 2013
Date Started: December 2008
Date Completion: March 2018
Last Updated: August 31, 2016
Last Verified: August 2016
