Impact of Medical and Surgical Therapy on Functional Mitral Regurgitation
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|ClinicalTrials.gov Identifier: NCT00224809|
Recruitment Status : Completed
First Posted : September 23, 2005
Last Update Posted : February 19, 2014
|Condition or disease||Intervention/treatment||Phase|
|Cardiovascular Diseases Heart Diseases Coronary Disease||Drug: Angiotensin-Converting Enzyme Inhibitors Procedure: Coronary Artery Bypass Graft Drug: Angiotensin Receptor Blockers Drug: Spironolactone Drug: Aspirin Drug: Clopidogrel Procedure: Surgical Ventricular Restoration||Not Applicable|
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Functional MR is a common complication of ischemic heart disease. Two large studies have confirmed an adverse effect of functional MR on survival after a heart attack. However, studies in heart failure (HF) are small and mainly limited to patients with non-ischemic cardiomyopathy. Recent animal studies have challenged the traditional concept that functional MR is a consequence of mitral annular dilation, instead suggesting that functional MR is due to leaflet tethering by outward expansion of the left ventricular wall (LV remodeling). This has critical implications regarding the correct surgical approach to correcting functional MR. To date, no large prospective study has examined the mechanism(s) of functional MR in ischemic cardiomyopathy, nor has the interaction between mechanism and prognosis been explored. This is a crucial knowledge gap because: 1) 70% of HF cases are caused by ischemic heart disease; and 2) functional MR occurs in around 60% of patients with ischemic cardiomyopathy. This study aims to fill these gaps by defining the mechanism(s) of functional MR by TEE in a large clinical trial of patients with ischemic cardiomyopathy participating in the STICH study. The STICH study will address the following two key hypotheses of therapeutic strategy in the management of patients with symptomatic HF, LV dysfunction, and coronary artery disease (CAD) amenable to CABG: 1) surgical coronary revascularization, in addition to aggressive medical HF management, will have long-term mortality, morbidity, quality of life, or cost benefits beyond aggressive medical management alone; and 2) early surgical ventricular shape restoration (SVR) in combination with CABG will improve outcome compared to coronary revascularization alone and medical therapy alone. The study will also address the role of LV size and function, including myocardial viability as a predictor of subsequent events over 3 years.
The STICH study affords a unique opportunity to specifically evaluate the mechanism and prognosis of functional MR in a large group of patients with HF due to ischemic cardiomyopathy. The study design of STICH allows exploring the interactions between the mechanism of functional MR, therapy, and prognosis. For example, it is not known whether all patients with functional MR have an adverse prognosis or whether their prognosis is related to specific mechanisms or severity. In patients undergoing CABG, it is not known which patients with functional MR will require valve repair or which ones will do well without it. It is also not known whether SVR reduces MR severity more than medical therapy and by what mechanism. It is possible that improvement in functional MR is a consequence of reversed LV remodeling, which is known to be related to myocardial viability, independent of specific therapy. These important questions are addressed by the TEE STICH study, an ancillary study to the STICH study.
The following four specific aims will be tested.
Specific Aim 1: This study will define the mechanism of functional MR in ischemic cardiomyopathy. Null Hypothesis: There is no difference in measurements of the mitral valve apparatus known to be associated with functional MR in ischemic cardiomyopathy among patients with different degrees of functional MR. To test this hypothesis, this study will compare measurements of annulus size and leaflet tethering in three groups of patients, those without MR, those with mild MR (effective regurgitant orifice area [EROA] less than 0.2 cm²), and those with at least moderate MR (EROA less than 0.2 cm²). The six specific measurements of MR mechanism include the following: 1) diastolic mitral annulus area; 2) percent of systolic annular contraction; 3) leaflet tenting area; 4) papillary muscle tethering distance; 5) papillary muscle separation distance; and 6) the primary chordal separation angle.
Specific Aim 2: This study will define the effect of therapy on mechanism and severity of functional MR. Null Hypothesis: There will be no difference in measurements of the mechanism and severity of moderate functional MR before and after treatment in the three treatment groups (medicine, CABG, and CABG plus SVR). To test this hypothesis, this study will compare the change in measurements of MR mechanism (see above list) and severity (EROA and volume of the chest wall [VCW]) before and at a 2-year follow-up in the three treatment groups. The primary endpoint for this analysis will be long-term survival.
Specific Aim 3: This study will evaluate the effect of functional MR on prognosis. Null Hypothesis: The presence and severity of functional MR does not predict the following: 1) long-term survival; and 2) the combined endpoint of death, cardiac transplantation, automatic implantable cardioverter defibrillator (AICD) countershock, hospitalization due to heart failure, or subsequent mitral valve repair or replacement.
Specific Aim 4: This study will evaluate the effect of myocardial viability on mechanism of functional MR. Null Hypothesis: The mechanism of moderate MR will be no different in patients with or without myocardial viability by single photon emission computed tomography (SPECT) imaging. All patients who have undergone SPECT imaging done as part of the parent study will be studied. The grouping variables will be the presence or absence of myocardial viability as determined by the SPECT core lab.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||250 participants|
|Intervention Model:||Factorial Assignment|
|Official Title:||Functional Mitral Regurgitation in STICH|
|Study Start Date :||September 2002|
|Actual Study Completion Date :||May 2007|
- Long term survival
- Cardiac hospitalization (measured at follow-up evaluations)
- Diastolic mitral annulus area
- Percent of systolic annular contraction
- Leaflet tenting area
- Papillary muscle tethering distance
- Papillary muscle separation distance
- Primary chordal separation angle
- EROA and VCW (measured at Year 2)
- Cardiac transplantation
- AICD countershock
- Hospitalization due to heart failure
- Subsequent mitral valve repair or replacement (measured at follow-up evaluations)
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): NCT00224809
|United States, Texas|
|Baylor Research Institute|
|Dallas, Texas, United States, 75204|
|Study Chair:||Paul A. Grayburn||Baylor Research Institute|