Stress Echo for Ischemic Mitral Valve Surgery (SURVIVE)

Comparison patients with CABG alone vs. CABG+mitral surgery with non-massive ischaemic mitral regurgitation (IMR) depending on stress echo data.

Study Overview

• Status: Suspended
• Conditions: Ischemic Mitral Regurgitation
• Intervention / Treatment: Procedure: Mitral surgery

Detailed Description

Chronic ischaemic mitral regurgitation (IMR) is a frequent complication of coronary artery disease (CAD), and is associated with a poor prognosis and outcome. The role of concomitant mitral valve surgery for IMR in patients undergoing coronary artery bypass grafting (CABG) remains controversial. After myocardial infarction IMR is associated with poor outcome and prognosis with double mortality rates, it reduces survival following surgical or percutaneous revascularization. However, there is no consensus on the cut-off value of IMR. The thresholds to define severe secondary mitral regurgitation are need to be evaluated with regards to their impact on prognosis after mitral valve intervention. The European guidelines is defined effective regurgitant orifice (ERO)-0.2 cm2 and regurgitant volume (RV)-30ml, as the threshold for severe IMR, because of severe prognosis of this group. Whereas American guidelines are defined it as ERO-0.4 cm2 and RV-60ml, as it was no evidence to impact intervention on the IMR with ERO-0.2 cm2 and RV-30ml. Partly it's explained by the dynamic nature of the secondary MR. About 30% of patients from the group with non-massive regurgitation at rest, have dramatically increasing it during exercise. However, some patient have not changes or decreasing IMR during exercise and, probably, they have not such a negative impact on the hemodynamic by IMR. The pervious comparative studies, that were the base for recommendations did not differ the patients with and without changes IMR during exercise. The current guidelines doesn't support the stress echo (SE) exams before operation for assessing necessity in mitral valve operation. It's due to lack of information that prove of influence for survival after surgery depending on IMR dynamic parameters.

IMR study hypothesis: Stress echocardiography data, including ERO, RV, pulmonary pressure (PA) pressure, beta-lines - B-lines, contractile reserve, could be indications for mitral valve intervention in patient with CAD and chronic secondary mitral regurgitation, undergoing CABG. The patients of the group with non-massive (ERO-0.2 cm2 and RV-30ml) IMR have positive effect by mitral surgery if they have increasing IMR during exercise test. The group with massive IMR (ERO≥0.4 cm2 and RV≥60 ml) will be better according clinic, echo, stress echo results in comparison with non-massive non-operated subgroup.

Aim: To assess the value of stress echo testing for ischemic mitral surgery indication in patients undergoing CABG.

Inclusion criteria for all projects are:

1. Age > 18 years
2. IMR, ERO≥0.2 cm2 and RV≥30 ml.
3. Indication for CABG

Exclusion criteria for all projects are:

1. Unwillingness to give informed consent and to enter a regular follow-up program.
2. Contraindications for stress echo.

Methods and design:

1. In a prospective multicenter international randomized study, we will recruit patients whom CABG is planned.

2. Conventional transthoracic echo. Patients will include into two groups:

   Group 1 - "Non-massive IMR" - ERO-0.2-0.39 cm2, and RV-30-59ml. Group 2 - "Massive IMR" - ERO≥0.4 cm2 and RV≥60 ml.

3. Randomization of Group 1 (surgery/non-surgery).
4. Exercise stress echocardiography of all the patients (Group 1 and Group 2). regional wall motion abnormality (RWMA), ejection fraction (EF), end diastolic volume (EDV), end systolic volume (ESV), contractile reserve, B-lines, ERO, RV, PA pressure at rest and during stress.
5. 1-year clinical outcomes
6. 1-year transthoracic echo data.
7. 1-year stress echocardiography data.
8. 3-year clinical outcomes
9. 3-year transthoracic echo data.
10. 3-year stress echocardiography data. Primary end-points: death, myocardial infarction, new hospital readmission, heart transplant, ventricular assist device implantation, aborted sudden death, pulmonary oedema (MACE).

Secondary end-points: physical capacity (changes in Watts, minutes of stress echocardiography), EDV, left atrium volume, EF at rest and during SE, ERO, RV, PA pressure, B-lines, contractile reserve at rest and during exercise in comparison with pre-operative data.

Expected results. Group 1, CABG - subgroup, CABG+mitral surgery subgroup. It's expected the improvement of physical capacity (changes in Watts, minutes of stress echocardiography), EDV, left atrium volume, EF at rest and during SE, ERO, RV, PA pressure, B-lines, contractile reserve at rest and during exercise in comparison with pre-operative data in CABG+mitral surgery subgroup already in 1-year follow-up. It's expected the improvement of physical capacity (changes in Watts, minutes of stress echo), EDV, left atrium volume, EF at rest and during stress echo, ERO, RV, PA pressure, B-lines, contractile reserve at rest and during exercise in comparison with CABG-subgroup already in 1-year follow-up. It's expected that more pronounce changes will be in CABG+mitral surgery subgroup with previously increasing IMR. The worst results are expected in CABG-subgroup with previously increasing IMR during exercise. There will be clarified which parameters would be more correlate with the clinic improvement (contractile reserve, B-lines, ERO etc). We expected reduced MACE till 3 year in CABG+mitral surgery subgroup with increasing IMR in comparison with CABG-subgroup with increasing IMR.

Group 2, The group with massive IMR (ERO≥0.4 cm2 and RV≥60 ml) will be better according clinic, echo, stress echo results in comparison with CABG-subgroup with increasing IMR from group 1. There will be clarified which parameters would be more correlate with the clinic improvement (contractile reserve, B-lines, ERO etc).

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation
    • St. Petersburg State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ischemic MR, ERO≥0.2 cm2 and RV≥30 ml.
• Indication for CABG

Exclusion Criteria:

• Unwillingness to give informed consent and to enter a regular follow-up program.
• Contraindications for SE.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: CABG/increasing MR; non-massive IMR with increasing IMR during exercise - CABG only
Experimental: CABG+mitral surgery (MS)/increasing MR; non-massive IMR with increasing IMR during exercise - CABG+ mitral surgery	Procedure: Mitral surgery; Guidelines approved mitral surgery
No Intervention: CABG/non-increasing MR; non-massive IMR non-increasing IMR during exercise - CABG only
Experimental: CABG+MS/non-increasing MR; non-massive IMR non-increasing IMR - CABG+ mitral surgery	Procedure: Mitral surgery; Guidelines approved mitral surgery
Other: Control 1; massive IMR at rest without increasing during exercise - CABG+ mitral surgery	Procedure: Mitral surgery; Guidelines approved mitral surgery
Other: Control 2; massive IMR at rest with increasing during exercise - CABG+ mitral surgery	Procedure: Mitral surgery; Guidelines approved mitral surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
myocardial infarction	myocardial infarction	during 3 year
all-cause death	all-cause death	during 3 year
new hospital readmission	new hospitalization	during 3 year from including
re-operation	percutaneous coronary intervention, coronary bypass surgery, heart transplant	during 3 year
cardiac death	cardiac death	during 3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
physical capacity	Change in Watts during stress test	Change from Baseline of physical capacity in Watts at 12 months, at 3 years
end diastolic volume of left ventricle	Change in milliliters by echocardiography	Change from Baseline of end diastolic volume of left ventricle at 12 months, at 3 years
left atrium volume	Change in milliliters by echocardiography	Change from Baseline of left atrium volume at 12 months, at 3 years
ejection fraction at rest and during stress echo	Change in percent by echocardiography at rest and at the peak of exercise during stress test	Change from Baseline of ejection fraction at 12 months, at 3 years
effective regurgitant orifice	Change in centimeter square of mitral effective regurgitant orifice by echocardiography	Change from Baseline at 12 months, at 3 years
right ventricle size	Change in centimeter of right ventricle by echocardiography	Change from Baseline at 12 months, at 3 years
pulmonary artery pressure pressure	Change in mm Hg of pulmonary pressure by echocardiography	Change from Baseline at 12 months, at 3 years
B-lines	counts of B-lines during by stress echocardiography	Change from Baseline at 12 months, at 3 years
Contractile reserve	Change in contractile reserve by stress echocardiography	Change from Baseline at 12 months, at 3 years

Collaborators and Investigators

• Sponsor: Saint Petersburg State University, Russia
• Investigators: Principal Investigator: Dmitry Shmatov, MD, PhD, Saint Petersburg State University, Russia

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2027

Study Registration Dates

• First Submitted: June 30, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: stress echo; mitral surgery; ischemic mitral regurgitation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Ischemia; Mitral Valve Insufficiency
• Other Study ID Numbers: 2/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Study Protocol, Clinical study report
• IPD Sharing Time Frame: 3 year
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No