50. Secondary/Functional Mitral Regurgitation- Indications and Guidelines

Emily Shih MD, Timothy J. George MD, Robert L. Smith MD
Baylor Scott & White The Heart Hospital
October 10, 2024

Abbreviations & Definitions

ACC – American College of Cardiology
ACE-I – Angiotensin-converting enzyme inhibitor
AHA – American Heart Association
ARB – Angiotensin receptor blocker
CMR – Cardiovascular magnetic resonance
CTA – Computed tomography angiography
DCM – Dilated cardiomyopathy
EF – Ejection fraction
ERO – Effective regurgitant orifice
GDMT – Goal-directed medical therapy
MR – Mitral regurgitation
PET – Positron emission tomography
LVEF – Left ventricular ejection fraction
LVESD – Left ventricular end systolic diameter
SGLT2 – Sodium-glucose transport protein 2
TEE – Transesophageal echocardiogram
TEER – Transcatheter-edge-to-edge repair
TTE – Transthoracic echocardiogram

Indications & Guidelines for Management by Grade/Stage of Disease

Secondary or functional mitral regurgitation (MR) occurs in a structurally normal mitral valve caused by annular enlargement and left ventricular (LV) dysfunction that can result in distortion of leaflet geometry. The cause of functional MR can be subcategorized into ischemic or non-ischemic. Ischemic MR is the most frequent etiology of functional MR. Left ventricular remodeling due to ischemia results in changes in the subvalvular apparatus that result in mitral leaflet tethering and restriction of motion during systole (Carpentier Type IIIB). Decreased LV contractility also leads to ventricular dilation, perpetuating further annular enlargement and regurgitation.1-6 Ischemic changes can also lead to LV basilar wall akinesis and formation of aneurysms. Nonischemic causes of functional MR include dilated cardiomyopathy (DCM) and left atrial dilation from chronic atrial fibrillation, which distorts the mitral valve annulus and reduces leaflet coaptation.7-8 Functional MR secondary to atrial fibrillation is sometimes referred to as atrial functional, given its difference in mechanism (Carpentier Type I).

It is important to note that functional MR is associated with higher cardiovascular mortality in patients with reduced ejection fraction (EF).9-11 The treatment of functional MR is complex because MR is not the sole component of the disease process. Therefore, its management typically begins with risk modification and heart failure (HF) therapy. Surgical management of ischemic MR primarily consists of revascularization with or without mitral valve repair or replacement.12 In addition, the development of percutaneous therapies for MR has burgeoned in the last few years.

The severity of functional MR is quantified, akin to primary MR, by effective regurgitant orifice (ERO) and regurgitant volume measured on echocardiography.

50. Secondary/Functional Mitral Regurgitation

Table 1: Stages of Functional MR.

CAD: coronary artery disease; ERO: effective regurgitant orifice; HF: heart failure; LA: left atrium; LV: left ventricle; MR: mitral regurgitation

*This figure is adapted from the 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease.13

Imaging assessment

In patients with Stage B-D chronic secondary MR, transthoracic echocardiography (TTE), noninvasive imaging (stress/nuclear/PET, CMR, or stress echocardiography), and coronary CTA are Class I recommendations for establishing the etiology of MR as well as assessing LV function, degree of MR, and pulmonary hypertension.

Transesophageal echocardiography (TEE) is a Class I recommendation for Stage D functional MR being considered for or undergoing transcatheter mitral interventions.

Medical therapy

Treatment with standard goal-directed medical therapy (GDMT) for HF (ACE-Is, ARBs, beta blockers, aldosterone antagonists, sacubitril/valsartan, and/or SGLT2 inhibitors)14 and biventricular pacing managed by a cardiologist is a Class I recommendation for patients with Stage C and D secondary MR (reduced LVEF).

Transcatheter intervention

Transcatheter edge-to-edge repair (TEER) of the mitral valve is a Class IIA recommendation for patients with symptomatic HF while on optimal GDMT (Stage D), LVEF 20-50% on TEE, LVESD ≤70 mm, and pulmonary artery systolic pressure ≤70 mmHg.

Surgical mitral valve repair or replacement

Class IIA recommendation when concomitant CABG is planned for ischemic myocardial disease with Stage C and D functional MR.

Class IIB recommendation in patients with symptomatic HF despite GDMT (Stage D) with atrial annular dilation and LVEF ≥50%.

Class IIB recommendation in patients with symptomatic HF despite GDMT (Stage D) with LVEF <50%.

Mitral valve replacement over downsized annuloplasty repair is a Class IIB recommendation in patients with Stage D ischemic functional MR.

The treatment of moderate MR at the time of concomitant CABG is unknown.

Figure 1: Treatment Algorithm for Functional MR.

50. Secondary/Functional Mitral Regurgitation

CABG: coronary artery bypass grafting; ERO: effective regurgitant orifice; GDMT: goal-directed medical therapy; LVEF: left ventricular ejection fraction; LVESD: left ventricular end systolic diameter; MR: mitral regurgitation; PASP: pulmonary artery systolic pressure; TEER: transcatheter edge-to-edge repair

*This figure is adapted from the 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease13

Supporting Evidence for Current Indications & Guidelines

Evidence that mitral valve surgery improves survival in symptomatic patients with functional MR is limited.

The COAPT trial (NCT01626079) randomized patients with symptomatic functional MR despite GDMT to TEER or continued GDMT. This study showed that transcatheter treatment improved survival, symptoms, and quality of life. In addition, it reduced the rate of HF readmissions. The criteria for enrollment of this trial are the current selection criteria for TEER to treat functional MR per the 2020 ACC/AHA Guidelines.15

MITRA-FR (NCT01920698) randomized patients with greater degrees of LV enlargement and less severe MR to TEER or continued GDMT and did not show a benefit to TEER in reducing death or hospitalization. Patients with more extreme LV dilation (LVESD up to 70 mm) were included in this study.16

Comparatively speaking, the COAPT trial patients had much lower degrees of LV dilation compared to MITRA-FR.

A randomized controlled trial (NCT00807040) comparing two-year survival of patients with severe ischemic MR undergoing mitral valve repair vs replacement showed no significant difference in LV remodeling or survival between the two groups. There was, however, a significantly higher rate of recurrent moderate or severe MR after mitral valve repair, which resulted in more HF-related adverse events.17

A randomized controlled trial (NCT00806988) comparing patients with moderate ischemic MR to CABG alone or CABG with concomitant mitral valve repair did not demonstrate a clinical advantage of adding mitral valve repair in CABG. In addition, the rate of stroke, TIA, or encephalopathy was higher in the combined procedure group.18

A substudy of the STICH trial (NCT00023595) suggests that adding mitral valve repair to CABG in patients with LV dysfunction and ischemic moderate to severe functional MR may improve survival compared with CABG alone or medical therapy alone.19

Ongoing Trials/Recent Publications

REVEAL-AFMR is a retrospective multi-center study conducted in Japan examining outcomes in patients with the absence of mitral valve pathology, preserved EF, and functional MR secondary to atrial dilation and annular remodeling (atrial functional MR) who underwent mitral valve surgery. The study found that mitral valve surgery was associated with lower rates of adverse clinical outcomes.20 The results of this trial were recently published in August 2024.

Expert Commentary

Unless you have specific institutional experience with mitral valve repair techniques for this pathology, mitral replacement is the safest choice in patients with ischemic functional MR. Valve choice for the patient is determined by a combination of factors, including age, patient-specific contraindications to anticoagulation, and is discussed in detail with the patient in the preoperative setting. However, in clinical trials, this patient population tends to be more elderly, and the two-year mortality is around 20% in the study by Goldstein et al. on surgical treatment for patients with severe ischemic MR.15,16 Given this, the general recommendation at our institution for surgical replacement in this patient population is a bioprosthetic valve.

In patients with LV functional MR, a rigid annuloplasty ring is preferentially utilized in mitral repair with either the true size or one size down.

Sources

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