Impact of Medical and Surgical Therapy on Functional Mitral Regurgitation

Cardiovascular Diseases Clinical Trial

Official title:

Functional Mitral Regurgitation in STICH

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00224809
• Other study ID #: 266
• Secondary ID: R01HL072430
• Status: Completed
• Phase: N/A
• First received: September 21, 2005
• Last updated: February 18, 2014
• Start date: September 2002
• Est. completion date: May 2007

Study information

• Verified date: December 2007
• Source: Baylor Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The Transesophageal Echocardiography (TEE) Surgical Treatment of Ischemic Heart Failure (STICH) ancillary study will define the mechanism(s) of functional mitral regurgitation (MR) by TEE in patients with ischemic cardiomyopathy, and the impact of therapy (medical, coronary artery bypass grafting [CABG], or CABG plus surgical ventricular restoration [SVR]) on mechanism and severity of MR. Severity of the effect of functional MR on clinical outcomes will also be examined. The TEE STICH study will address four specific aims that will focus on defining the following: 1) the mechanism(s) of functional MR in ischemic cardiomyopathy; 2) the effect of therapy on the mechanism and severity of functional MR; 3) myocardial viability on functional MR and its response to treatment; and 4) the effect of MR on prognosis in ischemic cardiomyopathy.

Description:

BACKGROUND:

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.

DESIGN NARRATIVE:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• LVEF less than .35, as measured by CMR ventriculogram, gated SPECT ventriculogram, echocardiography, or contrast ventriculogram within 3 months of study entry

• Has CAD suitable for revascularization

• Absence of left main CAD, as defined by an intraluminal stenosis of 50% or greater (to be eligible for MED Therapy)

• Absence of Canadian Class III angina or greater (angina markedly limiting ordinary activity) (to be eligible for MED Therapy)

• Dominant akinesia or dyskinesia of the anterior left ventricular wall amenable to SVR (to be eligible for SVR)

Exclusion Criteria:

• Aortic valvular heart disease clearly indicating the need for aortic valve repair or replacement

• Cardiogenic shock (within 72 hours of study entry), as defined by the need for intra-aortic balloon support or the requirement for intravenous inotropic support

• Plan for percutaneous intervention of CAD

• Recent acute myocardial infarction judged to be an important cause of left ventricular dysfunction

• History of more than one prior coronary bypass operation

• Non-cardiac illness with a life expectancy of less than 3 years

• Non-cardiac illness imposing substantial operative mortality

• Conditions or circumstances likely to lead to poor treatment adherence (e.g., history of poor compliance, alcohol or drug dependency, psychiatric illness, no fixed address)

• Previous heart, kidney, liver, or lung transplantation

• Current participation in another investigational drug or investigational medical device study

• Women of childbearing potential

Study Design

Allocation: Randomized, Intervention Model: Factorial Assignment, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Mitral Valve Insufficiency

Intervention

Drug:
• Angiotensin-Converting Enzyme Inhibitors

Procedure:
• Coronary Artery Bypass Graft

Drug:
• Angiotensin Receptor Blockers

• Spironolactone

• Aspirin

• Clopidogrel

Procedure:
• Surgical Ventricular Restoration

Locations

Country	Name	City	State
United States	Baylor Research Institute	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Baylor Research Institute	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Long term survival
Primary	Cardiac hospitalization (measured at follow-up evaluations)
Secondary	Diastolic mitral annulus area
Secondary	Percent of systolic annular contraction
Secondary	Leaflet tenting area
Secondary	Papillary muscle tethering distance
Secondary	Papillary muscle separation distance
Secondary	Primary chordal separation angle
Secondary	EROA and VCW (measured at Year 2)
Secondary	Death
Secondary	Cardiac transplantation
Secondary	AICD countershock
Secondary	Hospitalization due to heart failure
Secondary	Subsequent mitral valve repair or replacement (measured at follow-up evaluations)