Determinants of the Progression and Outcome of Mitral Regurgitation (PROGRAM)
Recruitment status was Recruiting
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 mitral regurgitation (MR): Organic Mitral Regurgitation (OMR) and Ischemic Mitral Regurgitation. Organic or primary MR is caused by am 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.
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 blood markers of myocardial extracellular matrix (ECM) turnover; f) the progression of MR severity and LV dysfunction during follow-up; and g) the occurrence of adverse clinical outcomes (i.e. symptoms, LV dysfunction, atrial fibrillation, pulmonary hypertension, heart failure, cardiovascular death) during follow-up in a series of 440 patients with at least moderate OMR and no symptoms at baseline. (2) To analyze the valve tissue samples explanted from the patients who will undergo mitral valve repair with quadrangular resection during follow-up in order to document the presence of lipids, inflammation, and expression of metalloproteinases (MMPs). (3) To obtain and analyze the postoperative changes in LV geometry and function, pulmonary arterial pressure, symptoms, and exercise capacity in the subset of patients who will undergo mitral valve surgery during follow-up. (4) To evaluate the usefulness of the exercise induced changes in MR severity, pulmonary arterial pressure, and LV function (i.e. contractile reserve), and of the blood levels of natriuretic peptides and ECM biomarkers for the prediction of rapid progression to LV dysfunction and adverse events. (5) To examine the relationship between the metabolic abnormalities linked to visceral obesity and the progression and outcome of OMR. (6) To determine, among the baseline clinical, echocardiographic, metabolic, and biomarkers variables, those which are independently associated with the progression of MR severity and LV dysfunction, and the occurrence of adverse clinical outcomes in patients with OMR.
Mitral Valve Insufficiency
Biological: blood sample
Genetic: DNA collection
Other: Doppler echocardiography
Other: Cardiopulmonary exercise testing
Other: Magnetic resonance imaging
Other: Exercise stress doppler echocardiography
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Determinants of the Progression and Outcome of Mitral Regurgitation|
- Combined clinical and echocardiographic endpoint [ Time Frame: Patients will be followed for 4 years ] [ Designated as safety issue: No ]Development of symptoms, left ventricular (LV) dysfunction (LV Ejection Fraction<60% and/or LV end diastolic diameter >40mm), atrial fibrillation or flutter, pulmonary arterial hypertension (resting systolic pressure >50mmHg), occurence of pulmonary oedema, congestive heart failure or cardiovascular death
- Progression of MR severity [ Time Frame: Patients will be followed for 4 years ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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
Biospecimen Retention: Samples With DNA
Fasting blood sample (serum, lithium-heparin, EDTA) and white cells - Tissue (explanted mitral valves)
|Study Start Date:||December 2008|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Patients with mitral regurgitation
At study entry, patients have 1) a clinical assessment including metabolic risk profile 2) a blood sample for analysis of metabolic, cardiac neurohormonal biomarkers and DNA collection 3) a complete rest doppler echocardiography 4) an exercise stress doppler echocardiography 5) a cardiopulmonary exercise testing and 6) a magnetic resonance imaging.
At follow-up, patients have 1) a clinical and clinical events assessment 2) a blood sample analysis 3) a resting echocardiography every year.
|Biological: blood sample Genetic: DNA collection Other: Doppler echocardiography Other: Cardiopulmonary exercise testing Other: Magnetic resonance imaging Other: Exercise stress doppler echocardiography|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01835054
|Contact: Philippe Pibarot, PhD, DVM||418-656-8711 ext 5938||Philippe.Pibarot@med.ulaval.ca|
|Contact: Haifa Mahjoub, MD, PhDs||418-656-8711 ext firstname.lastname@example.org|
|University Hospital of Sart Tilman||Recruiting|
|Liège, Belgium, 4000|
|Contact: Patrizio Lancellotti, MD, PhD 32(0)4/366 7194 email@example.com|
|Principal Investigator: Patrizio Lancellotti, MD, PhD|
|Sub-Investigator: Julien Magne, PhD|
|Institut Universitaire de Cardiologie et de Pneumologie de Québec||Recruiting|
|Québec, Quebec, Canada, G1V4G5|
|Contact: Philippe Pibarot, PhD, DVM 418-656-8711 ext 5938 Philippe.Pibarot@med.ulaval.ca|
|Contact: Haifa Mahjoub, MD, PhDs 418-656-5711 ext 2647 firstname.lastname@example.org|
|Principal Investigator: Philippe Pibarot, PhD, DVM|
|University Hospital of Rennes||Active, not recruiting|
|Rennes, France, 35033|
|Principal Investigator:||Philippe Pibarot, PhD, DVM||Institut Universitaire de Cardiologie et de Pneumologie de Québec|