Chronic mitral regurgitation treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Varun Kumar; M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Rim Halaby, M.D. [3]; Arzu Kalayci, M.D. [4]; Arooj Naz, M.B.B.S

Overview

The distinction between primary nd secondary mitral regurgitation (MR) is of utmost importance when determining the treatment strategies among patients with chronic MR. Primary and secondary MR have a different underlying pathophysiology and therefore have different indications for surgery and medical therapy. Surgery is generally the treatment of choice among patients with chronic primary MR and left ventricular systolic dysfunction; nevertheless, medical therapy is warranted when surgery is delayed or not planned. The cornerstone of the treatment of patients with chronic secondary MR with decreased ejection fraction is the standard regimen for the treatment of heart failure, which includes one or more of the following: beta blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or aldosterone antagonists. Mitral valve surgery is indicated in some circumstances among patients with chronic severe secondary MR, particularly those undergoing coronary artery bypass graft or patients with NYHA class III/IV heart failure symptoms.

Medical Therapy of Chronic Mitral Regurgitation

Primary Chronic Mitral Regurgitation

In MR, left ventricular systolic dysfunction and subsequent heart failure might occur. Surgery is generally the treatment of choice among MR patients with left ventricular systolic dysfunction; nevertheless, medical therapy is warranted when surgery is delayed or not planned.

Although the body of literature for medical therapy in MR is not robust, the existing sparse data suggests that patients with MR who experience left ventricular systolic dysfunction are candidate for the standard therapy of heart failure, which includes beta blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or aldosterone antagonist. Beta blocker use is associated with improved left ventricular function.

The administration of vasodilator is useful among patients with acute severe MR and those who have hypertension. The benefits of vasodilator use in asymptomatic patients with normal blood pressure is not established, and might even be associated with worsening of the severity of MR. The administration of vasodilators in this category of MR patients is therefore not recommended.

2020 ACC Recommendations for Medical Therapy for Chronic Primary MR

Recommendations	Class of Recommendation	Level of Evidence
Symptomatic or asymptomatic patients with severe primary MR and LV systolic dysfunction (Stages C2 and D) not meeting criteria for surgery or requiring a delay of surgery, GDMT for systolic dysfunction is reasonable	IIa	B-NR
In asymptomatic patients with primary MR and normal LV systolic function (Stages B and C1), vasodilator therapy is not indicated in normotensive patients	III	B-NR

Secondary Chronic Mitral Regurgitation

The valvular abnormality in chronic secondary MR results from the left ventricular dysfunction. Therefore, the cornerstone of the treatment of patients with chronic secondary MR with decreased ejection fraction is the standard regimen for the treatment of heart failure which includes one or more of the following: beta blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or aldosterone antagonists.

Patients with coronary artery disease should receive treatment for their atherosclerosis disease.

Symptomatic patients with chronic severe secondary MR are candidate for cardiac resynchronization therapy with biventricular pacing.

2020 ACC Recommendations for Medical Therapy for Secondary MR

Recommendations	Class of Recommendation	Level of Evidence
Standard GMT for Hf is recommended for patients with chronic severe secondary MR (Stages C and D) and HF and reduced LVEF. GMT includes ACE inhibitors, ARBs, beta blockers, aldosterone antagonists, and/or sacubitril/valsartan, and biventricular pacing as indicated Patients with chronic severe secondary MR (Stages C and D) and HF with reduced LVEF should receive standard GDMT for HF, including ACE inhibitors, ARBs, beta blockers, aldosterone antagonists, and/or sacubitril/valsartan, and biventricular pacing as indicated	I	A
Patients with chronic severe secondary MR (Stages C and D) and HF with reduced LVEF should receive concomitant management by a cardiologist that is an expert in the management of with HF and LV who will be the primary physician responsible for systolic dysfunction implementing and monitoring GDMT	I	C

Surgical Therapy for Chronic Mitral Regurgitation

Indications for Surgery in Chronic Primary Mitral Regurgitation

Shown below is an algorithm depicting the indications for mitral valve surgery or period monitoring among patients with chronic primary MR according to the 2014 AHA/ACC guideline for the management of patients with valvular heart disease. Note that when mitral valve surgery is indicated, mitral valve repair is preferred over mitral valve replacement whenever feasible.

Abbreviations: LVEF: left ventricular ejection fraction; LVESD: left ventricular end systolic diameter; MR: mitral regurgitation; PASP: Pulmonary artery systolic pressure

Primary MR

What is the severity of MR?

Severe MR ❑ Severe MVP with loss of coaptation ❑ RHD with loss of central coaptation ❑ Left ventricular dilation ❑ Regurgitation fraction ≥ 50% ❑ Regurgitation volume ≥ 60ml ❑ Effective regurgitation orifice ≥ 0.4cm² ❑ Vena contracta ≥ 0.7cm

Progressive MR (Stage B) ❑ Severe MVP with normal coaptation ❑ RHD with normal coaptation ❑ No Left ventricular dilation ❑ Regurgitation fraction < 50% ❑ Regurgitation volume < 60ml ❑ Effective regurgitation orifice < 0.4cm² ❑ Vena contracta < 0.7cm

Is the patient symptomatic?

Yes (Stage D)

No (Stage C)

Is the LVEF>30%?

LVEF 30-60% OR LVESD≥40 mm (Stage C2)

LVEF>60% AND LVESD<40 mm (Stage C1)

New onset atrial fibrillation OR PASP>50 mmHg (Stage C1)

Is the likelihood of success for the valve repair >95% and the expected mortality <1%?

No

Yes

Yes

No

Mitral valve surgery (Class IIb)

Mitral valve surgery (Class I)

Mitral valve repair (Class IIa)

Periodic monitoring

Periodic monitoring

Indications for Surgery in Chronic Secondary Mitral Regurgitation

Shown below is an algorithm depicting the indications for mitral valve surgery or period monitoring among patients with chronic secondary MR according to the 2014 AHA/ACC guideline for the management of patients with valvular heart disease. Note that when mitral valve surgery is indicated, mitral valve repair is preferred over mitral valve replacement whenever feasible.

Abbreviations: MR: mitral regurgitation

Secondary MR and patient is receiving medical therapy

What is the severity of MR?

Symptomatic (NYHA class III-IV) severe MR (Stage D)

Asymptomatic severe MR (Stage C)

Progressive MR (Stage B)

Mitral valve surgery (Class IIb)

Periodic monitoring

Periodic monitoring

Why the Mitral Valve is Replaced Before Symptoms in Patients with Chronic Mitral Regurgitation

• Mitral regurgitation is a syndrome of pure volume overload whereas aortic regurgitation is a combination of both volume and pressure overload.
• Both syndromes are associated with an increase in preload.
• In mitral regurgitation, the afterload is reduced whereas in aortic regurgitation the afterload is increased. This is very important because when the mitral valve is repaired, there is no longer a reduction afterload and the left ventricle may fail due to an abrupt rise in the afterload. In aortic regurgitation, because the afterload is already increased chronically, replacement of the valve is not as likely to precipitate acute left ventricular failure due to an abrupt rise in afterload.
• By the time symptoms develop, there is already left ventricular dysfunction.
• Because of the low pressure system into which the blood is ejected into through the mitral valve, the ejection fraction is always high in mitral regurgitation. If the ejection fraction appears to be "normal", there is already decline in left ventricular function.
• There is no indication for vasodilator therapy in the absence of systemic hypertension in asymptomatic patients with preserved left ventricular function.

Mitral Valve Repair vs Mitral Valve Replacement

There are two surgical options for the treatment of mitral regurgitation: mitral valve replacement and mitral valve repair. In general, mitral valve repair is preferred to mitral valve replacement as it carries a lower risk of subsequent prosthetic valve endocarditis and results in better preservation of left ventricular function.

Scenarios Favoring Mitral Valve Repair

• The ACC/AHA 2008 guidelines recommend mitral valve repair rather than mitral valve replacement if the anatomy is appropriate, including patients with rheumatic mitral valve disease and mitral valve prolapse (Grade 1C). The procedure should be performed at experienced surgical centers.
• Limited damage to certain areas of the mitral valve leaflets or chordae tendineae
• Limited calcification of the leaflets or annulus
• Prolapse of less than one-third of either leaflet
• Pure annular dilatation
• Valvular perforations
• Incomplete papillary muscle rupture

Scenarios Favoring Mitral Valve Replacement

• Extensive calcification or degeneration of a leaflet or annulus
• Prolapse of more than one-third of the leaflet tissue
• Extensive chordal fusion, calcification, or papillary muscle rupture
• Extensive damage of mitral valve secondary to endocarditis

2020 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease (VHD)

2020 Recommendations for Chronic Primary Mitral Regurgitation (MR) Intervention

COR	LOE	RECOMMENDATION	COMMENT/RATIONALE
I	B	Mitral valve surgery is recommended for symptomatic patients with chronic severe primary MR (stage D) irrespective of LVEF	Updated according to 2020 recommendation.
I	B	Mitral valve surgery is recommended for asymptomatic patients with chronic severe primary MR and LV dysfunction (LVEF <60% and/or left ventricular end-systolic diameter [LVESD] ≥40 mm, stage C2)	Updated according to 2020 recommendation.
I	B	Mitral valve repair is recommended for patients with chronic severe primary MR involving in which the anatomical cause is due to an underlying degenerative disease, assuming a successful and durable repair can be possible.	Updated according to 2020 recommendation.
IIa	B	Mitral valve repair is reasonable in asymptomatic patients with chronic severe primary MR (stage C1) with preserved LV function (LVEF >60% and LVESD <40 mm) in whom the likelihood of a successful and durable repair without residual MR is greater than 95% with an expected mortality rate of less than 1% when performed at a Heart Valve Center of Excellence.	2014 recommendation remains current.
IIb	C-LD	Mitral valve surgery is reasonable for asymptomatic patients with chronic severe primary MR (stage C1) and preserved LV function (LVEF >60% and LVESD <40 mm) with a progressive increase in LV size or decrease in ejection fraction (EF) on serial imaging studies on ≥3 occasions irrespective of the success rate and durability of repaired valve.	Updated according to 2020 recommendation. NEW: Patients with severe MR who reach an EF ≤60% or LVESD ≥40 mm have already developed LV systolic dysfunction, so operating before reaching these parameters, particularly with a progressive increase in LV size or decrease in EF on serial studies, is reasonable.
IIa	B	Transcatheter edge to edge mitral valve repair may be considered for severely symptomatic patients (NYHA class III to IV) with chronic severe primary MR (stage D) who have favourable anatomy for the repair procedure and a reasonable life expectancy of at least 1 year.	Updated according to 2020 recommendation.
IIb	B	Mitral valve repair is reasonable for symptomatic patients with chronic severe MR attributable to rheumatic valve disease. MR repair may be considered at a Comprehensive Valve Center by an experienced team assuming that a durable and successful repair is likely for cases in which surgical treatment is indicated.	Updated according to 2020 recommendation.
III:Harm	B	MVR should not be performed for the treatment of isolated severe primary MR limited to less than one half of the posterior leaflet unless mitral valve repair has been attempted and was unsuccessful.	2014 recommendation remains current.

Indications for Intervention in Asymptomatic Severe Primary Mitral Regurgitation

2012	2017
Pulmonary hypertension on exercise (SPAP ≥60 mmHg at exercise).	TAKEN OUT

2020 Recommendations for Chronic Secondary Mitral Regurgitation (MR) Intervention

COR	LOE	RECOMMENDATION	COMMENT/RATIONALE
IIa	B-R	In patients with chronic severe secondary MR due to LVEF <50% with persistent symptoms (NYHA class Il, IL, or IV) while currently utilizing optimal GDMT for HF (Stage D) but continuing to be symptomatic, TEER is reasonable in patients with appropriate anatomy given that the LVEF is between 20% and 50%, LVESD ≤70 mm, and pulmonary artery systolic pressure ≤70 mm Hg.	Updated according to 2020 recommendation.
IIa	B-R	In patients undergoing CABG for the treatment of myocardial ischemia, mitral valve surgery is reasonable if concomitant severe secondary MR (Stages C and D) is also present at time of surgery.	Updated according to 2020 recommendation. NEW: An RCT has shown that mitral valve repair is associated with a higher rate of recurrence of moderate or severe MR than that associated with mitral valve replacement (MVR) in patients with severe, symptomatic, ischemic MR, without a difference in mortality rate at 2 years' follow-up.
IIb	B	MV repair surgery is indicated in patients with chronic severe secondary MR from atrial annular dilation with preserved LVEF ≥50% with severe persistent symptoms (NYHA class IIl or IV) despite HF therapy for associated atrial fibrillation or other conditions.	Updated according to 2020 recommendation.
IIb	B-R	MV repair surgery is indicated in patients with chronic severe secondary MR related to LVEF <50% who have persistent severe symptoms (NYHA class I or M) despite optimal use of GDMT for HF (Stage D).	Updated according to 2020 recommendation. MODIFIED: LOE updated from C to B-R. The 2014 recommendation supported mitral valve repair in this group of patients. An RCT showed no clinical benefit of mitral repair in this population of patients, with increased risk of postoperative complications.
IIb	B-R	In patients with CAD and chronic severe secondary MR related to LVEF <50% (Stage D) who are undergoing mitral valve surgery because of severe symptoms (NYHA class Il or M) that persist despite GDMT for HF, chordal-sparing mitral valve replacement may be reasonable to choose over downsized annuloplasty repair.	Updated according to 2020 recommendation.

Indications for Mitral Valve Intervention in Secondary Mitral Regurgitation (MR)

2012	2017
IIa C	TAKEN OUT
Surgery should be considered in patients with moderate secondary mitral regurgitation undergoing CABG.
	Additional Statement: The lower thresholds defining severe MR compared to primary MR are based on their association with prognosis. However, it is unclear if prognosis is independently affected by MR compared to LV dysfunction. For isolated mitral valve treatment in secondary MR, thresholds of severity of MR for intervention still need to be validated in clinical trials. So far, no survival benefit has been confirmed for reduction of secondary MR.

2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary (DO NOT EDIT)

Recommendations for Chronic Primary Mitral Valve Regurgitation

Class I

"1. Mitral valve surgery is recommended for symptomatic patients with chronic severe primary mitral regurgitation (stage D) and LVEF greater than 30%. (Level of Evidence: B)"

"2. Mitral valve surgery is recommended for asymptomatic patients with chronic severe primary mitral regurgitation and LV dysfunction (LVEF 30% to 60% and/or LVESD ≥40 mm, stage C2). (Level of Evidence: B)"

"3. Mitral valve repair is recommended in preference to mitral valve replacement (MVR) when surgical treatment is indicated for patients with chronic severe primary MR limited to the posterior leaflet. (Level of Evidence: B)"

"4. Mitral valve repair is recommended in preference to MVR when surgical treatment is indicated for patients with chronic severe primary MR involving the anterior leaflet or both leaflets when a successful and durable repair can be accomplished. (Level of Evidence: B)"

"5. Concomitant mitral valve repair or MVR is indicated in patients with chronic severe primary MR undergoing cardiac surgery for other indications. (Level of Evidence: B)"

Class IIa

"1. Mitral valve repair is reasonable in asymptomatic patients with chronic severe primary MR (stage C1) with preserved LV function (LVEF >60% and left ventricular end systolic dimension < 40 mm) in whom the likelihood of a successful and durable repair without residual MR is greater than 95% with an expected mortality rate of less than 1% when performed at a heart valve center of excellence. (Level of Evidence: B)"

"2. Mitral valve repair is reasonable for asymptomatic patients with chronic severe non-rheumatic primary MR (stage C1) and preserved LV function (LVEF >60% and left ventricular end systolic dimension <40 mm) in whom there is a high likelihood of a successful and durable repair with: New onset of atrial fibrillation or Resting pulmonary hypertension (pulmonary artery systolic arterial pressure >50 mm Hg). (Level of Evidence: B)"

"3. Concomitant mitral valve repair is reasonable in patients with chronic moderate primary MR (stage B) when undergoing cardiac surgery for other indications. (Level of Evidence: C)"

Class IIb

"1. Mitral valve surgery may be considered in symptomatic patients with chronic severe primary MR and LVEF less than or equal to 30% (stage D). (Level of Evidence: C) "

"2. Mitral valve repair may be considered in patients with rheumatic mitral valve disease when surgical treatment is indicated if a durable and successful repair is likely or when the reliability of long-term anticoagulation management is questionable. (Level of Evidence: B) "

"3. Transcatheter mitral valve repair may be considered for severely symptomatic patients (NYHA class III to IV) with chronic severe primary MR (stage D) who have favorable anatomy for the repair procedure and a reasonable life expectancy but who have a prohibitive surgical risk because of severe comorbidities and remain severely symptomatic despite optimal guideline directed medical therapy for heart failure. (Level of Evidence: B) "

Class III

"1. MVR should not be performed for the treatment of isolated severe primary MR limited to less than one half of the posterior leaflet unless mitral valve repair has been attempted and was unsuccessful. (Level of Evidence: B)"

Recommendations for Chronic Secondary Mitral Valve Regurgitation

Class IIa

"1. Mitral valve surgery is reasonable for patients with chronic severe secondary MR (stages C and D) who are undergoing CABG or aortic valve replacement (AVR). (Level of Evidence: C)"

Class IIb

"1. Mitral valve repair or replacement may be considered for severely symptomatic patients (NYHA class III to IV) with chronic severe secondary MR (stage D) who have persistent symptoms despite optimal GDMT (guideline directed medical therapy) for heart failure. (Level of Evidence: B) "

"2. Mitral valve repair may be considered for patients with chronic moderate secondary MR (stage B) who are undergoing other cardiac surgery. (Level of Evidence: C) "

2008 and Incorporated 2006 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease (DO NOT EDIT)

Mitral Valve Surgery Indications (DO NOT EDIT)

Class I

"1. Mitral valve surgery is recommended for the symptomatic patient with acute severe MR. (Level of Evidence: B)"

"2. Mitral valve surgery is beneficial for patients with chronic severe MR and NYHA functional class II, III, or IV symptoms in the absence of severe LV dysfunction (severe LV dysfunction is defined as ejection fraction less than 0.30) and/or end-systolic dimension greater than 55 mm. (Level of Evidence: B)"

"3. Mitral valve surgery is beneficial for asymptomatic patients with chronic severe MR and mild to moderate LV dysfunction, ejection fraction 0.30 to 0.60, and/or end-systolic dimension greater than or equal to 40 mm. (Level of Evidence: B)"

"4. Mitral valve repair is recommended over mitral valve replacement in the majority of patients with severe chronic mitral regurgiation who require surgery, and patients should be referred to surgical centers experienced in mitral valve repair. (Level of Evidence: C)"

Class III

"1. Mitral valve surgery is not indicated for asymptomatic patients with MR and preserved LV function (ejection fraction greater than 0.60 and end-systolic dimension less than 40 mm) in whom significant doubt about the feasibility of repair exists. (Level of Evidence: C)"

"2. Isolated mitral valve surgery is not indicated for patients with mild or moderate MR. (Level of Evidence: C)"

Class IIa

"1. Mitral valve repair is reasonable in experienced surgical centers for asymptomatic patients with chronic severe MR with preserved LV function (ejection fraction greater than 0.60 and end-systolic dimension less than 40 mm) in whom the likelihood of successful repair without residual MR is greater than 90%. (Level of Evidence: B)"

"2. Mitral valve surgery is reasonable for asymptomatic patients with chronic severe MR, preserved LV function, and new onset of atrial fibrillation. (Level of Evidence: C)"

"3. Mitral valve surgery is reasonable for asymptomatic patients with chronic severe MR, preserved LV function, and pulmonary hypertension (pulmonary artery systolic pressure greater than 50 mm Hg at rest or greater than 60 mm Hg with exercise). (Level of Evidence: C)"

"4. Mitral valve surgery is reasonable for patients with chronic severe MR due to a primary abnormality of the mitral apparatus and NYHA functional class III-IV symptoms and severe LV dysfunction (ejection fraction less than 0.30 and/or end-systolic dimension greater than 55 mm) in whom mitral valve repair is highly likely. (Level of Evidence: C)"

Class IIb

"1. Mitral valve repair may be considered for patients with chronic severe secondary MR due to severe LV dysfunction (ejection fraction less than 0.30) who have persistent NYHA functional class III-IV symptoms despite optimal therapy for heart failure, including biventricular pacing. (Level of Evidence: C)"

Mitral Valve Surgery in Adolescents (DO NOT EDIT)

Class I

"1. MV surgery is indicated in the symptomatic adolescent or young adult with severe congenital MR with NYHA functional class III or IV symptoms. (Level of Evidence: C)"

"2. MV surgery is indicated in the asymptomatic adolescent or young adult with severe congenital MR and LV systolic dysfunction (ejection fraction less than or equal to 0.60). (Level of Evidence: C)"

Class IIa

"1. MV repair is reasonable in experienced surgical centers in the asymptomatic adolescent or young adult with severe congenital MR with preserved LV systolic function if the likelihood of successful repair without residual MR is greater than 90%. (Level of Evidence: B)"

Class IIb

"1. The effectiveness of MV surgery is not well established in asymptomatic adolescent or congenital MR young adult patients with severe and preserved LV systolic function in whom valve replacement is highly likely. (Level of Evidence: C)"