Mitral Regurgitation 

Updated: Nov 28, 2018
Author: Ivan Hanson, MD; Chief Editor: Terrence X O'Brien, MD, MS, FACC 

Overview

Practice Essentials

Mitral regurgitation (MR) is defined as an abnormal reversal of blood flow from the left ventricle (LV) to the left atrium (LA). It is caused by disruption in any part of the mitral valve (MV) apparatus. The most common etiologies of MR include MV prolapse (MVP), rheumatic heart disease, infective endocarditis, annular calcification, cardiomyopathy, and ischemic heart disease. See the video below.

Transthoracic echocardiogram demonstrating severe mitral regurgitation with heavily calcified mitral valve and prolapse of the posterior leaflet into the left atrium.

Signs and symptoms

When associated with coronary artery disease (CAD) and acute myocardial infarction (MI), significant acute MR is accompanied by the following symptoms:

  • Dyspnea

  • Fatigue

  • Orthopnea

  • Pulmonary edema (often the initial manifestation)

The following may be noted with chronic MR:

  • Some patients may remain asymptomatic for years

  • Patients may have normal exercise tolerance until systolic LV dysfunction develops, at which point they may experience symptoms of a reduced forward cardiac output

  • Patients may feel chest palpitations if AF develops as a result of chronic atrial dilatation

  • Patients with LV enlargement and more severe disease eventually progress to symptomatic congestive heart failure (CHF) with pulmonary congestion and edema

Palpation may reveal the following:

  • Brisk carotid upstroke and hyperdynamic cardiac impulse

  • Prominent LV filling wave

Auscultation may reveal the following:

  • Diminished S1 in acute MR and chronic severe MR with defective valve leaflets

  • Wide splitting of S2 as a result of early closure of the aortic valve

  • S3 as a result of LV dysfunction or increased blood flow across the MV

  • Accentuated P2 if pulmonary hypertension is present

  • Characteristic holosystolic murmur (or mid-systolic if etiology of MR is mitral valve prolapse)

See Presentation for more detail.

Diagnosis

The following findings may be noted on chest radiography:

  • Evidence of LV enlargement due to volume overload (particularly in chronic MR), though pulmonary congestion may not be observed until heart failure has developed

  • Evidence of LA enlargement in the anteroposterior view

European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) echographic criteria[1] for the definition of severe MR are as follows:

  • Flail leaflet/ruptured papillary muscle/large coaptation defect

  • Very large color flow central jet or eccentric jet adhering, swirling, and reaching the posterior wall of the LA

  • Dense/triangular continuous-wave signal of regurgitant jet

  • Large flow convergence zone

American College of Cardiology (ACC)/American Heart Association (AHA) class I indications for transthoracic echocardiography (TTE) are as follows:

  • Baseline evaluation for LV size and function, right ventricular (RV) and LA size, pulmonary artery pressure, and severity of MR

  • Determining the etiology of MR

  • Annual or semiannual surveillance of LV ejection fraction (LVEF) and end-systolic dimension in asymptomatic patients with moderate-to-severe MR

  • Evaluation of the MV apparatus and LV function after a change in signs or symptoms

  • Evaluation of LV size and function and mitral valve hemodynamics in the initial evaluation after MV replacement or repair

ACC/AHA class I indications for serial TTE are as follows:

  • Asymptomatic patients with mild MR and no evidence of LV enlargement, LV dysfunction, or pulmonary hypertension – Yearly observation; serial TTE is not indicated

  • Patients with moderate MR – Yearly TTE

  • Asymptomatic patients with severe MR – TTE and clinical evaluation every 6-12 months to assess symptoms and development of LV dysfunction

ACC/AHA class I indications for transesophageal echocardiography (TEE) are as follows:

  • Assessment of etiology of severe MR in patients for whom surgery is recommended to determine the feasibility of MV repair

  • Evaluation of mitral valve and associated structures when TTE is nondiagnostic

Other tests include the following:

  • Electrocardiography (ECG)

  • Brain natriuretic peptide (BNP) assessment

  • Cardiac catheterization

See Workup for more detail.

Management

Medical therapy includes the following:

  • Afterload-reducing agents and diuretics in MR with symptoms or LV dysfunction

  • Beta blockers and biventricular pacing for primary treatment of LV dysfunction in functional MR

  • Consideration of intra-aortic balloon counterpulsation in acute MR with hemodynamic compromise

  • In the presence of AF, beta blockers, calcium channel blockers, digitalis, or a combination

  • Consideration of anticoagulation for patients who develop AF or have had MV replacement surgery

  • Prophylactic antibiotics before any dental procedure involving manipulation of gingival tissue, the periapical region of a tooth, or perforation of oral mucosa in patients with a prosthetic heart valve, previous infectious endocarditis, some forms of congenital heart disease, or valvulopathy in a cardiac transplant recipient

  • Consideration of inotropic agents in chronic severely symptomatic MR; consultation with a cardiothoracic surgeon

ACC/AHA indications for MV surgery are as follows:

  • Repair is preferred to replacement in most patients with moderate-to-severe (3+) or severe (4+) chronic MR who require surgery; patients should be referred to experienced surgical centers (class I)

  • Surgery is indicated for symptomatic patients with acute severe MR (class I)

  • Symptomatic chronic severe MR – Surgery is recommended for New York Heart Association (NYHA) functional class II-IV symptoms without severe LV dysfunction; chronic severe MR due to a primary abnormality of the MV apparatus and NYHA functional class III-IV symptoms and mild-to-moderate LV dysfunction in whom MV repair is highly likely (class IIa)

  • Asymptomatic chronic severe MR – Surgery is recommended for those with mild-to-moderate LV dysfunction (class I); repair is reasonable in experienced centers for those with preserved LV function in whom the likelihood of successful repair without residual MR is >90% (class IIa); surgery is reasonable for those with preserved LV function, new-onset AF, or pulmonary artery hypertension (class IIa)

ESC/EACTS indications for MV surgery in severe primary MR are as follows:

  • Repair is preferred to replacement when it is expected to be durable (class I)

  • Surgery is indicated in asymptomatic patients with LVEF >30% and end-systolic dimension < 55 mm (class I)

  • Surgery is indicated for asymptomatic patients with LV end-systolic dimension ≥45 mm and/or LVEF ≤60% (class I)

  • Surgery should be considered in asymptomatic patients with preserved LV function and new-onset AF or pulmonary hypertension (class IIa)

  • Surgery should be considered in asymptomatic patients with preserved LV function and a high likelihood of durable repair, low surgical risk and flail leaflet, and LV end-systolic dimension ≥40 mm (class IIa)

  • Surgery should be considered in patients with severe LV dysfunction refractory to medical therapy with a high likelihood of durable repair and low comorbidity (class IIa)

  • Surgery may be considered in patients with severe LV dysfunction refractory to medical therapy with low likelihood of durable repair and low comorbidity (class IIb)

  • Surgery may be considered in asymptomatic patients with preserved LV function, high likelihood of durable repair, low surgical risk, and either LA dilatation and sinus rhythm or pulmonary hypertension on exercise

Surgical MV repair remains the criterion standard intervention for severe MR; however, percutaneous double-orifice repair is a viable alternative for patients at high risk. In addition, in October 2013, the FDA approved the MitraClip valve repair system for patients with symptomatic degenerative MR with a prohibitive risk for mitral-valve surgery.[2, 3]

See Treatment and Medication for more detail.

Background

Mitral regurgitation (MR), the most frequent valvular heart disease,[4, 5, 6] is defined as an abnormal reversal of blood flow from the left ventricle to the left atrium. It is caused by disruption in any part of the mitral valve apparatus, which comprises the mitral annulus, the leaflets (a large anterior [aortic] leaflet and a small posterior [mural] leaflet), the chordae tendineae, and the papillary muscles (anteromedial and posterolateral). The most common etiologies of MR include mitral valve prolapse (MVP), rheumatic heart disease, infective endocarditis, annular calcification, cardiomyopathy and ischemic heart disease. The pathophysiology, clinical manifestations and management of MR differ with the chronicity of the disease and the etiology.

For patient education resources, see Heart Health Center as well as Mitral Valve Prolapse.

Pathophysiology

Mitral regurgitation (MR) can be caused by organic disease (eg, rheumatic fever, ruptured chordae tendineae, myxomatous degeneration, leaflet perforation) or a functional abnormality (ie, a normal valve may regurgitate [leak] because of mitral annular dilatation, focal myocardial dysfunction, or both). Congenital MR is rare but is commonly associated with myxomatous mitral valve disease. Alternatively, it can be associated with cleft of the mitral valve, as occurs in persons with Down syndrome, or an ostium primum atrial septal defect.

Acute mitral regurgitation

Acute MR is characterized by an increase in preload and a decrease in afterload causing an increase in end-diastolic volume (EDV) and a decrease in end-systolic volume (ESV). This leads to an increase in total stroke volume (TSV) to supranormal levels. However, forward stroke volume (FSV) is diminished because much of the TSV regurgitates as the regurgitant stroke volume (RSV). This, in turn, results in an increase in left atrial pressure (LAP). According to the Laplace principle, which states that ventricular wall stress is proportional to both ventricular pressure and radius, LV wall stress in the acute phase is markedly decreased since both of these parameters are reduced.

Chronic compensated mitral regurgitation

In chronic compensated MR, the left atrium (LA) and ventricle have sufficient time to dilate and accommodate the regurgitant volume. Thus LA pressure is often normal or only minimally elevated. Because of the left ventricular dilatation via the process of eccentric hypertrophy, TSV and FSV are maintained. Wall stress may be normal to slightly increased as the radius of the LV cavity increases but the end-diastolic LV pressure remains normal. As the LV progressively enlarges, the mitral annulus may stretch and prevent the mitral valve leaflets from coapting properly during systole, thus worsening the MR and LV dilatation.

Chronic decompensated mitral regurgitation

In the chronic decompensated phase, cardiac dysfunction has developed, impairing both TSV and FSV (although ejection fraction still may be normal). This results in a higher ESV and EDV, which in turn causes a elevation of LV and LA pressure, ultimately leading to pulmonary edema and, if left untreated, cardiogenic shock.

Etiology

Acute mitral regurgitation

Causes of acute mitral regurgitation (MR) include coronary artery disease, infectious endocarditis, chordae tendineae rupture (as with myxomatous valve disease), valvular surgery, and other conditions.

Coronary artery disease (ischemia or acute myocardial infarction) may result in papillary muscle dysfunction or rupture; it does not cause chordae tendineae dysfunction or rupture as they are not vascularized. The posteromedial papillary muscle is supplied by the terminal branch of the posterior descending artery and is more vulnerable to ischemic insult than the anterolateral papillary muscle, which is usually supplied by both the left anterior descending and circumflex arteries. Transient ischemia may result in transient MR associated with angina. Myocardial infarction or severe prolonged ischemia produces irreversible papillary muscle dysfunction and scarring.

Infectious endocarditis features include the following:

  • Abscess formation

  • Vegetations

  • Rupture of chordae tendineae

  • Leaflet perforation

Following valvular surgery, acute MR may occur as a result of trauma, percutaneous valvuloplasty, or suture interruption.

Other causes of acute MR include the following:

  • Tumors (most commonly atrial myxoma)

  • Myxomatous degeneration (mitral valve prolapse, Ehlers-Danlos syndrome, Marfan syndrome)

  • Ruptured chordae tendineae (trauma, mitral valve prolapse, endocarditis, spontaneous)

  • Systemic lupus erythematosus (Libman-Sacks lesion)

  • Acute rheumatic fever (Carey Coombs murmur)

  • Acute global left ventricular dysfunction

  • Prosthetic mitral valve dysfunction

Chronic mitral regurgitation

Causes of chronic MR include the following:

  • Rheumatic heart disease

  • Systemic lupus erythematosus

  • Scleroderma

  • Myxomatous degeneration (mitral valve prolapse, Ehlers-Danlos syndrome, Marfan syndrome)

  • Calcification of mitral valve annulus

  • Infective endocarditis (can affect normal, abnormal, or prosthetic mitral valves)

  • Ruptured chordae tendineae (trauma, mitral valve prolapse, endocarditis, spontaneous)

  • Functional MR (dilation of mitral valve annulus, anormal tethering of leaflets due to enlargement of LV cavity and stretch of papillary muscles and chordae [dilated cardiomyopathies, aneurysmal dilation of the left ventricle])

  • Hypertrophic cardiomyopathy

  • Systolic anterior motion of the mitral valve

  • Perivalvular prosthetic leak

  • Congenital (mitral valve clefts, mitral valve fenestrations, parachute mitral valve abnormality)

  • Drug-related (ergotamine, methysergide, pergolide, anorexiant medications)

Epidemiology

United States data

Acute and chronic mitral regurgitation (MR) affect approximately 5 in 10,000 people. Mitral valve disease is the second most common valvular lesion, preceded only by aortic stenosis. Myxomatous degeneration has replaced rheumatic heart disease as the leading cause of mitral valvular abnormalities. Mitral valve prolapse has been estimated to be present in 4% of the normal population. With the aid of color Doppler echocardiography, mild MR can be detected in as many as 20% of middle-aged and older adults. MR is independently associated with female sex, lower body mass index, advanced age, renal dysfunction, prior myocardial infarction, prior mitral stenosis, and prior mitral valve prolapse. It is not related to dyslipidemia or diabetes.

International data

In areas other than the Western world, rheumatic heart disease is the leading cause of MR.

Prognosis

There appears to be an association between recurrent mitral regurgitation (MR) after mitral valve (MV) repair in patients with degenerative MR and increased mortality and adverse LV remodeling.[7] Independent risk factors for recurrent MR after mitral valve repair include MV repair performed before 2000, preoperative atrial fibrillation, high LV end-diastolic dimension (LVEDD), prolapse of the isolated anterior leaflet or multiple segments, and absence of ring annuloplasty. LVEDD and repair without artificial chordae implantation appear to be predictors of MR progression.[7]

Outcomes for asymptomatic chronic severe degenerative MR are as follows:

  • Mortality ranges from 50-73% at 5 years.

  • Mortality in patients with preserved LV function ranges from 27-45%.

  • Sudden death may be as common as 1-8% per year in patients with a flail leaflet.

In a study of patients with low ejection fraction (EF) (regardless of ischemic or nonischemic etiology), the presence of functional MR is associated with a 2-fold greater risk of all-cause mortality and hospitalization at 1-5 years.[8]

Mitral valve surgery operative mortality includes the following:

  • Isolated mitral valve repair surgery carries a 2% mortality.

  • Mitral valve replacement surgery: 4% mortality for patients younger than 50 years; 17% mortality for patients older than 80 years.

Tribouilloy et al found that, in patients with organic MR due to flail leaflets, left ventricular end-systolic diameter (LVESD) is independently associated with increased mortality. Analysis of results in 739 patients showed that LVESD ≥ 40 mm independently predicted overall mortality (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.01-3.83) and cardiac mortality (HR 3.09; 95% CI, 1.35-7.09) under conservative management. Mortality risk increased linearly with LVESD >40 mm (HR 1.15; 95% CI, 1.04-1.27 per 1-mm increment). Tribouilloy et al conclude that these findings support prompt surgical rescue in patients with LVESD ≥40 mm but also suggest that operating on patients before LVESD reaches 40 mm will best preserve survival.[9]

Magne et al found that exercise pulmonary hypertension can be predicted using resting comprehensive echocardiography in asymptomatic patients with degenerative MR.[10]

 

Presentation

History

Symptoms of mitral regurgitation (MR) may be subtle as its progression may be insidious and patients may self-limit their physical activity.[11, 12]  

Acute mitral regurgitation

When associated with coronary artery disease and acute myocardial infarction (typically, inferior myocardial infarction, which may lead to papillary muscle dysfunction), significant acute MR is accompanied by symptoms of impaired LV function, such as dyspnea, fatigue, and orthopnea. In these cases, pulmonary edema is often the initial manifestation because of rapid volume overload on the left atrium and the pulmonary venous system.

Chronic mitral regurgitation

Chronic MR often results from a primary defect of the mitral valve apparatus with subsequent progressive enlargement of the left atrium and ventricle. In this state, patients may remain asymptomatic for years. Patients may have normal exercise tolerance until systolic dysfunction of the LV develops, at which point they may experience symptoms of a reduced forward cardiac output (ie, fatigue, dyspnea on exertion, or shortness of breath). With time, patients may feel chest palpitations if atrial fibrillation develops as a result of chronic atrial dilatation.

Patients with LV enlargement and more severe disease eventually progress to symptomatic congestive heart failure with pulmonary congestion and edema. At this stage of LV dilatation, the myocardial dysfunction often becomes irreversible.

Physical Examination

On palpation, a brisk carotid upstroke and hyperdynamic cardiac impulse may be noted, and a prominent left ventricular (LV) filling wave may be present.

On auscultation, S1 may be diminished in acute mitral regurgitation (MR) and chronic severe MR with defective valve leaflets, and wide splitting of S2 may occur due to early closure of the aortic valve. S3 may be present due to LV dysfunction or as a result of increased blood flow across the mitral valve. P2 may be accentuated if pulmonary hypertension is present.

If murmurs are present, note and characterize the following features:

  • Quality: Usually high-pitched, blowing

  • Location: Usually best heard over the apex; usually radiates to the left axilla or subscapular region: posterior leaflet dysfunction causes murmur to radiate to the sternum or aortic area, and anterior leaflet dysfunction causes murmur to radiate to the back or top of the head

  • Duration: Usually holosystolic, may be confined to early systole in acute MR, may be confined to late systole in MVP or papillary muscle dysfunction (S1 will probably be normal in these cases since initial closure of mitral valve cusps is unimpeded, and a midsystolic click preceding murmur is suggestive of MVP)

  • Intensity: Little correlation exists between intensity of murmur and severity of MR; intensity may be diminished in severe MR caused by LV dysfunction, acute myocardial infarction, or periprosthetic valve regurgitation

 

DDx

Diagnostic Considerations

It is essential that clinicians identify mitral regurgitation (MR), define its cause (including whether the MR is primary or secondary) and the Carpentier classification of leaflet motion, assessing the MR severity, make treatment decisions with the heart valve team, and follow-up with clinical cardiology and the primary care provider.[11, 12]

Calcified aortic stenosis also produces a prominent murmur at the apex (Gallavardin phenomenon) and may be confused with mitral valve regurgitation.

Tricuspid regurgitation also causes a holosystolic murmur. However, it is located at the left lower sternal border rather than the apex, it does not radiate to the axilla, and it increases in intensity with inspiration, whereas MR does not.

A ventricular septal defect produces a harsh holosystolic murmur at the lower left sternal border, but it generally radiates to the right of the sternum rather than the axilla and typically has a thrill.

Differential Diagnoses

 

Workup

Approach Considerations

Key considerations regarding diagnostic studies from the 2017 American College of Cardiology (ACC) expert consensus decision pathway on the management of mitral regurgitation (MR) include the following[11, 12] :

  • Exercise testing can be useful for assessment of functional status and symptomatic elicitation; and exercise echocardiography may reveal elevated pulmonary artery pressures, MR worsening, or blunted left ventricular (LV) or right ventricular (RV) contractile reserve.

  • Determine the mechanism and etiology of MR, usually with transthoracic echocardiography (TTE), or, if the image quality is poor, with transesophageal echocardiography (TEE). Perform assessment of the mitral apparatus, careful measurement of left atrial (LA) volume, and LV diameter and volume.

  • Distinguish between primary MR (due to abnormalities of the mitral leaflets or subvalvular apparatus) and secondary MR (due to LA or LV geometric changes with a functionally normal mitral valve). In addition to LV dilatation or regional or global abnormalities of LV systolic function, secondary MR also can be caused by pure LA and mitral annular dilation (ie, "atrial functional MR").

  • After characterization of leaflet morphology, describe the leaflet motion using the Carpentier classification system: type I (normal leaflet motion); type II (excessive leaflet motion); and type III (restricted leaflet motion), subcategorized as type IIIA (restricted during both systole and diastole) and type IIIB (restricted only during systole).

  • The initial assessment of the MR severity should be with color-flow Doppler ultrasonography, and it should include quantitative parameters such as the effective regurgitant orifice area, regurgitant volume, and regurgitant fraction. A comprehensive approach is recommended, in which multiple parameters are evaluated and integrated to form a final determination of MR severity. Additional testing including TEE and cardiac magnetic resonance imaging (CMRI) should be used when the assessment of MR on TTE is not definitive.

See also the Guidelines section for recommendations from major medical organizations for the management of MR.

Imaging Studies

Chest radiography

Evidence of left ventricular (LV) enlargement due to volume overload may be observed (particularly in chronic MR), although pulmonary congestion (eg, increased pulmonary markings) may not be observed until heart failure has developed.

Left atrial enlargement may also be observed in the anteroposterior (AP) view as a double shadow in the right cardiac silhouette and/or straightening of the left cardiac border due to the large left atrial appendage.

Echocardiography

European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) criteria for the definition of severe MR are as follows[1] :

  • Flail leaflet/ruptured papillary muscle/large coaptation defect

  • Very large color flow central jet or eccentric jet adhering, swirling, and reaching the posterior wall of the left atrium

  • Dense/triangular continuous-wave signal of regurgitant jet

  • Large flow convergence zone

ACC/AHA Class I indications for performing transthoracic echocardiography include (1) baseline evaluation for LV size and function, RV and LA size, pulmonary artery pressure, and severity of MR; (2) determining the etiology of MR; (3) annual or semiannual surveillance of LV ejection fraction and end-systolic dimension in asymptomatic patients with moderate-to-severe MR; (4) evaluation of the mitral valve apparatus and LV function after a change in signs or symptoms; and (5) evaluation of LV size and function and mitral valve hemodynamics in the initial evaluation after MV replacement or repair.[13]

Parameters of severity of MR include the following:

  • Color flow jet width and area

  • Intensity of continuous-wave Doppler signal

  • Pulmonary venous flow contour

  • Peak early mitral inflow velocity

  • Regurgitant orifice area

  • Regurgitation volume

  • Left ventricular and left atrial size

In evaluating the etiology of MR, note that with acute MR, a ruptured chordae tendineae or papillary muscle, a flail valve leaflet, or infective endocarditis may be identified as the etiology. A central color flow jet of MR with a structurally normal mitral valve suggests functional MR.

Transthoracic echocardiogram demonstrating severe mitral regurgitation with heavily calcified mitral valve and prolapse of the posterior leaflet into the left atrium.
Transthoracic echocardiogram demonstrating bioprosthetic mitral valve dehiscence with paravalvular regurgitation.

ACC/AHA Class I indications for performing serial transthoracic echocardiography include the following[13] :

  • Asymptomatic patients with mild MR and no evidence of LV enlargement, LV dysfunction, or pulmonary hypertension can be observed on a yearly basis; serial echocardiography is not indicated.

  • Patients with moderate MR should have an echocardiogram performed yearly.

  • In asymptomatic patients with severe MR, echocardiography and clinical evaluation should be done every 6-12 months to assess symptoms and development of LV dysfunction.

ACC/AHA Class I indications for performing transesophageal echocardiography are as follows[13] :

  • Assessment of etiology of severe MR in patients for whom surgery is recommended to determine the feasibility of valve repair

  • Evaluation of mitral valve and associated structures in patients for whom transthoracic echocardiography provides nondiagnostic information

    Transesophageal echocardiogram demonstrating prolapse of both mitral valve leaflets during systole.

Other Tests

Electrocardiography

Findings on electrocardiography may include the following:

  • Ischemia or infarction in the inferior or posterior leads is present when acute mitral regurgitation (MR) is due to papillary muscle rupture.

  • In chronic mitral valve regurgitation, left ventricular (LV) dilatation and hypertrophy are observed with increased QRS voltage and ST-T wave changes in the lateral precordial leads.

  • Left atrial enlargement in chronic mitral valve regurgitation produces a negative P wave in lead V1, and/or a wide notched P wave in leads II, III, or aVF. Atrial fibrillation may be observed in the late stages.

BNP assessment

Pizarro et al found that in patients with severe asymptomatic mitral regurgitation and normal left ventricular function, levels of brain natriuretic peptide (BNP) have an independent and additive prognostic value. In a prospective study of 269 consecutive patients with severe asymptomatic organic mitral regurgitation and left ventricular ejection fraction above 60%, the receiver-operating characteristics curve yielded an optimal cutoff point of 105 pg/mL of BNP that was able to discriminate patients at higher risk. Pizarro et al recommend considering BNP assessment in the routine clinical workup for risk stratification, which may aid in the selection of patients for early surgery.[14]

Procedures

American College of Cardiology/American Heart Association (ACC/AHA) class I indications for performing cardiac catheterization are as follows[13] :

  • Left ventriculography and hemodynamic measurements are indicated when noninvasive tests are inconclusive regarding severity of mitral regurgitation (MR), left ventricular function, or the need for surgery.

  • Hemodynamic measurements are indicated when pulmonary artery pressure is out of proportion to the severity of MR as assessed by noninvasive testing.

  • Left ventriculography and hemodynamic measurements are indicated when the clinical and noninvasive findings are conflicting regarding severity of MR.

  • Coronary angiography is indicated before mitral valve (MV) repair or MV replacement in patients at risk for coronary artery disease or when the MR is suspected to be ischemic in origin.

 

Treatment

Approach Considerations

Key considerations regarding treatment from the 2017 American College of Cardiology (ACC) expert consensus decision pathway on the management of mitral regurgitation (MR) include the following[11, 12] :

  • Decisions regarding the optimal treatment of chronic MR are based on multiple variables, including MR type, MR severity, hemodynamic consequences, disease stage, patient comorbidities, and the experience of the heart valve team and its members.

  • The principal intervention for primary MR is surgery; however, transcatheter mitral valve repair using an edge-to-edge clip plays a very limited role. Whenever feasible, mitral valve repair is strongly preferred over mitral valve replacement for primary MR.

  • Surgical treatment for secondary MR should be considered only after appropriate medical and device therapies have been instituted. 

  • Common techniques for mitral valve repair for primary MR include nonresection techniques using artificial chords or ipsilateral chordal transfer, triangular resection with annuloplasty ring, and sliding leaflet valvuloplasty with annuloplasty ring.

  • Common techniques for mitral valve repair for secondary MR include restrictive remodeling with a rigid annuloplasty ring, and chordal-sparing mitral valve replacement.

  • A primary determinant of successful repair is the surgeon's experience. For asymptomatic (stage C1) patients, patients with complex mitral pathoanatomy, and patients who desire a minimally invasive or robotic approach to mitral valve repair, consider referral to an experienced mitral surgeon at a comprehensive valve center.

  • Long-term follow-up of patients after surgical or transcatheter mitral intervention is essential for the assessment of durability, functional outcomes, and survival.

A 2018 meta-analysis comprising 12 retrospective studies from 5 electronic databases that included over 4200 patients compared mitral valve repair (n = 2950) versus replacement (n = 1252) for degenerative MR across all age groups. The investigators found that in terms of all-cause mortality and regardless of age, patients who underwent mitral valve repair had a lower risk of all-cause mortality, early mortality, and reoperation than those who underwent mitral valve replacement.[15] ​

In a separate 2018 report, mid-term clinical outcomes (7 years) data for isolated minimally invasive mitral valve (n = 960) repair versus chordal-sparing mitral valve replacement (n = 95) for degenerative MR suggest no significant difference between the two procedures.[16]

See also the Guidelines section for recommendations from major medical organizations for the management of MR.

Medical Care

Prehospital care

For the patient with acute mitral regurgitation (MR), the electrocardiogram should be examined closely for evidence of acute myocardial infarction (MI). If present, treatment with supplemental oxygen, analgesics for anginal chest pain, and sublingual nitrates for acute MI are the components of prehospital care. In the absence of acute MI, endocarditis should be excluded with blood cultures.

Transthoracic echocardiography should be performed.

Emergency department care

Any patient with acute or chronic mitral valve regurgitation with hemodynamic compromise should be evaluated for acute myocardial infarction. Consultations with specialists in cardiology and cardiothoracic surgery should be obtained early during patient stabilization.

Diuretic therapy is administered to individuals with pulmonary congestion, and an echocardiogram must be performed immediately. Patients with hemodynamic compromise should be expeditiously transferred to a cardiac critical care unit for central and pulmonary arterial pressure monitoring.

Medical therapy

Afterload-reducing agents (such as nitrates and antihypertensive drugs) and diuretics are helpful for maintaining the forward cardiac output in persons with MR with symptoms and/or LV dysfunction. Beta-blockers and biventricular pacing are used for primary treatment of LV dysfunction in functional MR.

Intra-aortic balloon counterpulsation should be considered in the patient with acute MR and hemodynamic compromise.

If atrial fibrillation is encountered, maintenance of a normal ventricular response with beta-blockers, calcium channel blockers, and/or digitalis therapy is considered.

Anticoagulation is considered for patients who develop atrial fibrillation or have had mitral valve replacement surgery.

A study using data from the Mitral Regurgitation International Database (MIDA) found that patients with severe MR without a class I indication for surgical intervention fared significantly better when they were treated with surgery than when they underwent “watchful waiting” while being treated with medical therapy. The survival differences were statistically significant, and the results were confirmed in propensity score-matched and inverse-probability–weighted analyses.[9, 10, 13]

In addition to maintaining good oral hygiene, antibiotics are recommended prior to any dental procedure that involves manipulation of gingival tissue, the periapical region of a tooth, or perforation of oral mucosa in patients with any of the following conditions[8] :

  • Prosthetic heart valve
  • Previous infectious endocarditis
  • Some forms of congenital heart disease
  • Valvulopathy in a cardiac transplant recipient

Inotropic agents should be considered in chronic severely symptomatic MR, and consultation with a specialist in cardiothoracic surgery should be obtained.

Diet and activity

A diet low in sodium is indicated for patients with symptomatic chronic MR or those with LV dysfunction.

Asymptomatic patients with MR of any severity can exercise without restriction if all of the following criteria are met:

  • Sinus rhythm
  • Normal LV and left atrial dimensions
  • Normal pulmonary artery pressure

Surgical Care

Invasive management

Surgery is recommended for moderate to severe (grade >3) mitral regurgitation (MR) in symptomatic patients or those with left ventricular (LV) dysfunction.[17]

The risks and benefits of surgery should be assessed based on the age and comorbidity of each individual patient, with the decision to proceed or not to proceed being grounded in uniformly accepted guidelines. Consider the following:

  • Operative mortality is higher in the patients older than 75 years.
  • Coronary artery disease and other valvular diseases are prevalent in older patients who often require concomitant coronary artery bypass surgery, further increasing operative risk.
  • Outcomes are worse in patients with severe MR and marked LV dysfunction.
  • As outcomes are worse in patients with severe MR and pulmonary hypertension (pulmonary artery systolic pressure >50 mm Hg), surgical referral is advised prior to development of pulmonary hypertension. [14, 18, 19]
  • Right ventricular dysfunction is associated with worse survival of functional MR and LV dysfunction in patients undergoing MitraClip in association with no response to N-terminal pro-B-type natriuretic peptide (NT-proBNP). [20]

In a retrospective study of 121 patients with significant chronic ischemic mitral regurgitation, intervention with mitral valve replacement was associated with improved postoperative exercise hemodynamic performance and long-term functional capacity compared with mitral valve annuloplasty.[21]

  • Asymptomatic patients with preserved LV function and new onset atrial fibrillation or pulmonary hypertension (Class IIa)
  • Asymptomatic patients with preserved LV function and a high likelihood of durable repair, low surgical risk and flail leaflet, and LV end-systolic dimension of 40 mm or greater (Class IIa)
  • Patients with severe LV dysfunction refractory to medical therapy with a high likelihood of durable repair and low comorbidity (Class IIa)

Surgery may be considered in the following situations:

  • Patients with severe LV dysfunction refractory to medical therapy with low likelihood of durable repair and low comorbidity (Class IIb)
  • Asymptomatic patients with preserved LV function, high likelihood of durable repair, low surgical risk, and either left atrial dilatation and sinus rhythym or pulmonary hypertension on exercise

Percutaneous treatment of mitral regurgitation

In October 2013, the FDA approved the MitraClip valve repair system for patients with symptomatic degenerative MR with a prohibitive risk for mitral-valve surgery.[2, 3] Approval was based on registry data and the Endovascular Valve Edge-to-Edge Repair Study (EVEREST II), in which percutaneous repair of the mitral valve was less effective in reducing MR but was associated with similar improvement in clinical outcomes and with superior safety.[2, 3]

Various percutaneous strategies for treatment of MR are also under investigation.[22]

Double-orifice mitral valve repair using an implanted device that grasps and approximates the edges of the mitral valve leaflets at the origin of the regurgitant jet has been compared with mitral valve surgery for patients with 3+ to 4+ MR in a randomized trial.[23] At 12 months, the primary combined endpoint of survival, surgery for mitral valve dysfunction, and grade 3+ to 4+ MR was met in 55% of patients randomized to percutaneous repair and 73% of patients in the surgical group (p = 0.007). Major adverse events at 30 days occurred in 27% of patients who underwent percutaneous repair and 45% of patients who underwent surgery (p < 0.001). When transfusions were excluded from the safety analysis, no statistically significant difference in major adverse events was found between the groups.[23]

At 12 months, 20% of the percutaneous repair group required surgery for mitral valve dysfunction (p< 0.001) compared with 2.2% of the surgery group.[23] At 12 months, 19% of the percutaneous repair group had residual3+ or 4+ MR compared with 6% of the surgery group. Patients in the surgical group had greater improvement in ejection fraction than those in the percutaneous repair group (p = 0.005). Physical quality of life at 30 days was worse in the surgical group (p < 0.001); however, at 12 months, no significant difference was found.[23]

Percutaneous double-orifice mitral valve repair appears safer than surgery, primarily due to reduced risk of transfusion. Although surgery results in more favorable reduction of MR, quality of life at one year is similar for both approaches. Surgical mitral valve repair remains the criterion standard intervention for severe MR; however, percutaneous double-orifice repair is a viable alternative for patients at high risk for surgery.

In a retrospective study (1990-2009) of data from 4989 patients with significant coronary artery disease who were treated for moderate or severe ischemic mitral regurgitation, intervention with coronary artery bypass grafting (CABG) alone was associated with the lowest mortality.[24] CABG with or without mitral valve surgery was associated with a lower mortality than for either percutaneous coronary intervention or medical treatment alone.[24]

In a retrospective study (2001-2015) comprising 61 patients with LV aneurysm and ischemic MR, concomitant CABG, LV restoration, and MV repair was effective, with 95.1% 1-year survival rates, 86.9% 5-year survival rates, and  80.3% 10-year survival rates.[25]

The 5-year results from the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) that compared percutaneous mitral valve repair with the MitraClip device with conventional mitral valve surgery revealed increased rates of grade 3+ and 4+ mitral regurgitation (12.3%) and surgery (27.9%) with percutaneous repair than with conventional repair (1.8% and 8.9%, respectively).[26] The majority of surgery following percutaneous repair (78%) occured within the first 6 months. The 5-year mortality was similar between the two groups: 20.8% for percutaneous repair and 26.8% for conventional surgery.[26]

In a case series of 4 patients who underwent MitraClip therapy for recurrent MR during the early phase after the initial procedure, for which partial clip detachment was the suspected cause, additional clip(s) stabilized the partially detached clips and improved the MR grade.[27]  However, the investigators cautioned that patients with partial clip detachment and paracommissural MR may not be good candidates for repeat MitraClip.

Complications

Medical complications of mitral regurgitation (MR) may include the following:

  • Pulmonary edema
  • Congestive heart failure
  • Irreversible left ventricular (LV) systolic dysfunction
  • Thromboembolism resulting from atrial fibrillation

Surgical complications may include the following:

  • Operative risks include infection, bleeding, intraoperative myocardial infarction, and stroke.
  • In young patients, bioprosthetic valves (ie, porcine valves) have a propensity for early degeneration due to calcification.
  • Mechanical valve complications include prosthetic valve dysfunction and valve thrombosis with or without embolism, particularly in the patient who is not adequately anticoagulated.
  • Hemolysis may occur in the patient with a ball and cage mechanical valve because of mechanical valve destruction of circulating red blood cells. Hemolysis in the patient with a tilting disk valve usually indicates the presence of a perivalvular leak.
  • Thromboembolism in patients with mechanical valves who are on anticoagulation therapy occurs at a rate of 1-3% per year.
  • In the absence of anticoagulation, thromboembolism occurs at a rate of approximately 1.5% per year with a porcine valve.
  • Prosthetic valve infection may occur in bioprosthetic or mechanical valves.
 

Guidelines

Guidelines Summary

2017 ACC/AHA guidelines

In 2017, the American College of Cardiology TAsk Force on Expert Consensus Pathways published their updated recommendations for mitral regurgitation (MR), which primarily consisted of those for chronic primary and chronic secondary MR and are summarized below.[28]  In general, the 2014 recommendations remain current (see below, under "2014 ACC/AHA guidelines"), with a few updated recommendations.

Chronic primary MR interventions

Class IIa (moderate strength, with limited data)

Mitral valve surgery is reasonable for asymptomatic patients with chronic severe primary MR (stage C1) and preserved left ventricular (LV) function (LV ejection fraction [LVEF] >60% and LV end-systolic dimension [LVESD] < 40 mm) with a progressive increase in LV size or decrease in EF on serial imaging studies.

Chronic secondary MR interventions

Class IIa (moderate strength, moderate quality from randomized trials)

Chordal-sparing MVR is a reasonable selection over downsized annuloplasty repair if the procedure is considered for severely symptomatic patients (New York Heart Association [NYHA] class III to IV) with chronic severe ischemic MR (stage D) and persistent symptoms despite guideline-directed medical therapy (GDMT) for heart failure (HF).

Class IIb (weak, moderate quality from randomized trials)

In patients with chronic, moderate, ischemic MR (stage B) undergoing CABG, the usefulness of mitral valve repair is uncertain.

2017 ESC/EACTS guidelines

The European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) published 2017 updated guidelines to their 2014 recommendations for the management of valvular heart disease.[29]

Class I (recommended/indicated; level of evidence that is the consensus opinion of experts and/or small studies, retrospective studies, registries)

Coronary angiography is recommended for evaluating moderate to severe secondary MR.

Class IIa (should be considered; data derived from a single randomized clinical trial or large nonrandomized studies)

Non-vitamin K antagonist oral anticoagulants (NOACs) should be considered as an alternative to vitamin K antagonists (VKAs) in patients with aortic stenosis, aortic regurgitation and MR presenting with atrial fibrillation.

Indications for intervention in severe primary MR

Class I (recommended/indicated)

The preferred technique should be mitral valve repair when the results are expected to last. (Level of evidence: consensus opinion of experts and/or small studies, retrospective studies, registries)

Surgery is indicated in the following individuals (data derived from a single randomized clinical trial or large nonrandomized studies):

  • Symptomatic patients with LVEF over 30%
  • Asymptomatic patients with LV dysfunction (LVESD ≥45 mm and/or LVEF ≤60%)

Class IIa (should be considered)

Surgery should be considered in the following patients:

  • Asymptomatic patients with preserved LV function (LVESD < 45 mm and LVEF >60%) and atrial fibrillation secondary to MR or pulmonary hypertension (systolic pulmonary pressure at rest >50 mmHg) (Data derived from a single randomized clinical trial or large nonrandomized studies.)
  • Asymptomatic patients with preserved LVEF (>60%) and LVESD of 40-44 mm when a durable repair is likely, surgical risk is low, the repair is performed in a heart valve center, and at least one of the following findings is present (consensus opinion of experts and/or small studies, retrospective studies, registries): flail leaflet or presence of significant left atrial (LA) dilatation (volume index ≥60 mL/m 2 BSA) in sinus rhythm

Mitral valve repair should be considered in symptomatic patients with severe LV dysfunction (LVEF < 30% and/or LVESD >55 mm) refractory to medical therapy when the likelihood of successful repair is high and comorbidity low. (Consensus opinion of experts and/or small studies, retrospective studies, registries)

Class IIb (may be considered; consensus opinion of experts and/or small studies, retrospective studies, registries)

Mitral valve replacement may be considered in symptomatic patients with severe LV dysfunction (LVEF < 30% and/or LVESD >55 mm) refractory to medical therapy when the likelihood of successful repair is low and comorbidity low.

Percutaneous edge-to-edge procedure may be considered in patients with symptomatic severe primary MR who fulfil the echocardiographic criteria of eligibility and are judged inoperable or at high surgical risk by the heart team, avoiding futility.

Indications for mitral valve intervention in chronic secondary MR

Class I (should be considered; recommended/indicated; level of evidence that is the consensus opinion of experts and/or small studies, retrospective studies, registries)

Surgery is indicated in patients with severe secondary MR undergoing CABG and an LVEF over 30%.

Class IIa (should be considered; consensus opinion of experts and/or small studies, retrospective studies, registries)

Surgery should be considered in symptomatic patients with severe secondary MR, an LVEF below 30% but with an option for revascularization and evidence of myocardial viability.

Class IIb (may be considered; consensus opinion of experts and/or small studies, retrospective studies, registries)

When revascularization is not indicated, surgery may be considered in patients with severe secondary MR and an LVEF above 30% who remain symptomatic despite optimal medical management (including cardiac resynchronization therapy [CRT] if indicated) and have a low surgical risk.

When revascularization is not indicated and the surgical risk is not low, a percutaneous edge-to-edge procedure may be considered in patients with severe secondary MR and an LVEF over 30% who remain symptomatic despite optimal medical management (including CRT if indicated) and who have a suitable valve morphology by echocardiography, avoiding futility.

In patients with severe secondary MR and an LVEF below 30% who remain symptomatic despite optimal medical management (including CRT if indicated) and who have no option for revascularization, the heart team may consider a percutaneous edge-to-edge procedure or valve surgery after careful evaluation for a ventricular assist device or heart transplant according to each individual patient's characteristics.

2016 AATS guidelines

The 2016 American Association For Thoracic Surgery (AATS) updated recommendations for ischemic mitral valve regurgitation (IMR) are outlined below.[30]

Mitral valve replacement is reasonable in patients with severe IMR who remain symptomatic despite Guideline-directed medial and cardiac device therapy, and who have a basal aneurysm/dyskinesis, significant leaflet tethering, and/or severe left ventricle dilation (left ventricular end diastolic diameter [LVEDD] > 6.5 cm).

Mitral valve repair with an undersized complete rigid annuloplasty ring may be considered in patients with severe IMR who remain symptomatic despite Guideline-directed medical and cardiac device therapy and who do not have a basal aneurysm/dyskinesis, significant leaflet tethering, or severe left ventricle enlargement.

In patients with moderate IMR undergoing CABG, mitral valve repair with an undersized complete rigid annuloplasty ring may be considered.

Mitral valve repair for IMR is performed with complete preservation of both anterior and posterior leaflet chords.

Mitral valve repair for IMR is performed with small, undersized, complete rigid annuloplasty ring.

2014 ACC/AHA guidelines

In 2014, the ACC/American Heart Association (ACC/AHA) released a revision to its 2008 guidelines for the management of patients with valvular heart disease (VHD); and the ESC/EACTS issued a revision of its 2007 guidelines in 2012.[1, 13]

The ACC/AHA guidelines classify progression of chronic mitral regurgitation (MR) into 4 stages (A to D) as follows[13] :

  • Stage A: At risk of MR

  • Stage B: Asymptomatic with progressive MR

  • Stage C: Asymptomatic with severe MR; stage C1 (left [LV] or right ventricle [RV] remains compensated) or stage C2 (decompensation of LV or RV)

  • Stage D: Symptomatic with severe MR

The guidelines note that when assessing chronic MR, it is important to distinguish between chronic primary (degenerative) MR and chronic secondary (functional) MR, as these conditions have more differences than similarities. The staging criteria is summarized in the table below.[13]

Table 1. Stages of Progression of Chronic Mitral Regurgitation (Open Table in a new window)

Stage

Valve Anatomy

Valve Hemodynamics*

Hemodynamic Consequences

Symptoms

A:

Primary MR

  • Mild MV prolapse with normal coaptation
  • Mild valve thickening and leaflet restriction
  • No MR jet or small central jet area < 20% LA
  • Small vena contracta < 0.3 cm
  • None
  • None

A:

Secondary MR

  • Normal valve leaflets, chords and annulus in patient with CAD or cardiomyopathy
  • No MR jet or small central jet area < 20% LA
  • Small vena contracta < 0.3 cm
  • Normal or mildly dilated LV with infarction or ischemia regional wall motion abnormalities
  • Primary myocardial disease with LV dilation and systolic dysfunction
  • Symptoms of coronary ischemia or HF that respond to revascularization and medical therapy

B:

Primary MR

  • Severe MV prolapse with normal coaptation
  • Rheumatic valve changes, leaflet restriction, and loss of central coaptation
  • Prior IE
  • Central jet MR area  20-40% LA or late systolic eccentric jet MR
  • Vena contracts < 0.7 cm
  • Regurgitant volume < 60 mL
  • Regurgitant fraction < 50%
  • ERO < 0.40 cm 2
  • Angiographic grade 1-2+
  • Mild LA enlargement
  • No LV enlargement
  • Normal Pulmonary pressure
  • None

B:

Secondary MR

  • Regional wall motion abnormalities with mild tethering of mitral leaflet
  • Annular dilation with mild loss of central coaptation of the mitral leaflets
  • Regurgitant volume < 30 mL
  • Regurgitant fraction < 50%
  • ERO < 0.20 cm 2†
  • Regional wall motion abnormalities with reduced LV systolic function
  • LV dilation and systolic dysfunction
  • Symptoms of coronary ischemia or HF that respond to revascularization and medical therapy

C:

Primary MR

  • Severe MV prolapse with loss of coaptation or flail leaflet
  • Rheumatic valve changes, leaflet restriction, and loss of central coaptation
  • Prior IE
  • Thickening of leaflets with radiation heart disease
  • Central jet MR area >40% LA or holosystolic eccentric jet MR
  • Vena contracta ≥0.7 cm
  • Regurgitant volume ≥60 mL
  • Regurgitant fraction ≥50%
  • ERO ≥0.40 cm 2
  • Angiographic grade 3-4+
  • Moderate to severe LA enlargement
  • LV enlargement
  • Pulmonary hypertension may be present
  • Stage C1: LVEF >60% and LVESD < 40 mm
  • Stage C2: LVEF ≤60% and LVESD ≥40 mm
  • None

C:

Secondary MR

  • Regional wall motion abnormalities and/or LV dilation with severe tethering of mitral leaflet
  • Annular dilation with severe loss of central coaptation of the mitral leaflets
  • Regurgitant volume ≥30 mL
  • Regurgitant fraction ≥50%
  • ERO ≥0.20 cm 2†
  • Regional wall motion abnormalities with reduced LV systolic function
  • LV dilation and systolic dysfunction
  • Symptoms of coronary ischemia or HF that respond to revascularization and medical therapy

D:

Primary MR

  • Severe MV prolapse with loss of coaptation or flail leaflet
  • Rheumatic valve changes, leaflet restriction, and loss of central coaptation
  • Prior IE
  • Thickening of leaflets with radiation heart disease
  • Central jet MR area >40% LA or holosystolic eccentric jet MR
  • Vena contracta ≥0.7 cm
  • Regurgitant volume ≥60 mL
  • Regurgitant fraction ≥50%
  • ERO ≥0.40 cm 2
  • Angiographic grade 3-4+
  • Moderate or severe LA enlargement
  • LV enlargement
  • Pulmonary hypertension present
  • Decreased exercise tolerance
  • Exertional dyspnea

D:

Secondary MR

  • Regional wall motion abnormalities and/or LV dilation with severe tethering of mitral leaflet
  • Annular dilation with severe loss of central coaptation of the mitral leaflets
  • Regurgitant volume ≥30 mL
  • Regurgitant fraction ≥50%
  • ERO ≥0.20 cm 2†
  • Regional wall motion abnormalities with reduced LV systolic function
  • LV dilation and systolic dysfunction
  • HF symptoms due to MR persist after revascularization and medical therapy
  • Decreased exercise tolerance
  • Exertional dyspnea

*Several criteria are provided but not all criteria for each category will be present. Severity of mild, moderate, or serve is dependent on data quality and integration with other clinical evidence.

†In secondary MR, true ERO is underestimated due to the crescentic shape of the proximal convergence

CAD = coronary heart disease; ERO = effective regurgitation orifice; HF = heart failure; IE = infective endocarditis; LA = left atrium; LV = left ventricular; LVEF = left ventricular ejection factor; LVESD = left ventricular end-systolic dimension; MR = mitral regurgitation; MV = mitral valve; TTE = transthoracic echocardiography.

Both guidelines require intervention decisions for severe valvular heart disease (VHD) be based on an individual risk-benefit analysis. Improved prognosis should outweigh the risk of intervention and potential late consequences, particularly complications related to prosthetic valves.[1, 13]

Recognizing the known limitations of the EuroSCORE (European System for  Cardiac Operative Risk Evaluation) and the STS (Society of Thoracic Surgeons) score, the ACC/AHA guidelines suggest using STS plus three additional indicators: frailty (using accepted indices), major organ system compromise not to be improved postoperatively, and procedure-specific impediment when assessing risk.[13]

Diagnosis

The ESC/EACTS echographic criteria for the definition of severe MR are as follows[1] :

  • Flail leaflet/ruptured papillary muscle/large coaptation defect

  • Very large color flow central jet or eccentric jet adhering, swirling, and reaching the posterior wall of the LA

  • Dense/triangular continuous-wave signal of regurgitant jet

  • Large flow convergence zone

ACC/AHA class I indications for transthoracic echocardiography (TTE) are as follows[13] :

  • Baseline evaluation for LV size and function, right ventricular (RV) and LA size, pulmonary artery pressure, and severity of MR

  • Determining the etiology of MR

  • Annual or semiannual surveillance of LV ejection fraction (LVEF) and end-systolic dimension in asymptomatic patients with moderate-to-severe MR

  • Evaluation of the MV apparatus and LV function after a change in signs or symptoms

  • Evaluation of LV size and function and MV hemodynamics in the initial evaluation after MV replacement (MVR) or MV repair

ACC/AHA class I indications for serial TTE are as follows[13] :

  • Asymptomatic patients with mild MR and no evidence of LV enlargement, LV dysfunction, or pulmonary hypertension: Yearly observation; serial TTE is not indicated

  • Patients with moderate MR: Yearly TTE

  • Asymptomatic patients with severe MR: TTE and clinical evaluation every 6-12 months to assess symptoms and development of LV dysfunction

ACC/AHA class I indications for transesophageal echocardiography (TEE) are as follows[13] :

  • Assessment of etiology of severe MR in patients for whom surgery is recommended to determine the feasibility of MV repair

  • Evaluation of MV and associated structures when TTE is nondiagnostic

Acute mitral regurgitation

The ACC/AHA guidelines note that it may be difficult to diagnose severe acute MR with TTE due to narrow eccentric jets of MR, tachycardia, and early equalization of LV and LA pressures. In cases where TTE is nondiagnostic but the suspicion of severe acute MR persists, enhanced MV imaging with TEE is recommended. In patients with sudden acute and hemodynamic instability after myocardial infarction (MI) with hyperdynamic LV function and no other cause for the deterioration, TEE should be performed as soon as possible, looking for severe MR due either to a papillary muscle or chordal rupture.[13]

The guidelines suggest vasodilator therapy to improve hemodynamic compensation in acute MR; however, use of vasodilators is often limited by systemic hypotension that is exacerbated when peripheral resistance is decreased. Intra-aortic balloon counterpulsation can be utilized for achieving hemodynamic stability until definitive mitral surgery can be performed. The use of a percutaneous circulatory assist device may also be effective to stabilize a patient with acute hemodynamic compromise before operation.[13]

Prompt MV surgery is recommended for treatment of the symptomatic patient with acute severe primary MR. In cases of ruptured chordae tendineae, mitral repair is usually feasible and preferred over valve replacement, and the timing of surgery can be determined by the patient’s hemodynamic status. If infectious endocarditis (IE) is the cause of severe symptomatic MR, earlier surgery is generally preferred because of better outcomes over medical therapy. However, this strategy should also be tempered by the patient’s overall condition.[13]

Primary mitral regurgitation

The ACC/AHA and ESC/EACTS guidelines agree that MV surgery for symptomatic patients with chronic severe primary MR (stage D) and LVEF above 30% is a class I recommendation.[1, 13]

The ACC/AHA guidelines also provide a class I recommendation for MV surgery for asymptomatic patients with chronic severe primary MR (stage C2) and an LVEF of 30%–60% and/or an LVESD of at least 40 mm,[13]  whereas the ESC/EACTS uses a benchmark of an LVEF above 30% and an LVESD below 55 mm for its class I recommendation.[1]

The ACC/AHA also gives class I recommendations for MV repair in preference to MVR in the following[13] :

  • Severe primary MR limited to the posterior leaflet

  • Severe primary MR involving the anterior leaflet or both leaflets and a successful and durable repair can be accomplished

The ECS/EACTS guidelines prefer MV repair when a durable repair can be expected.[1]

Additional ACC/AHA recommendations for interventions for primary MR include the following[13] :

  • Concomitant MV repair or replacement for patients undergoing other cardiac surgery (class I for severe primary MR; class IIa for moderate primary MR)

  • MV repair in asymptomatic patients with chronic severe primary MR (stage C1) with LVEF above 60% and LVESD below 40 mm:

    • When the likelihood of a successful and durable repair is over 95% and the expected operational mortality rate is less than 1% and the procedure is performed at a heart valve center of excellence (class IIa)
    • When the likelihood of a successful and durable repair is high and there is new onset of atrial fibrillation (AF) or resting pulmonary hypertension (class IIa)
  • Medical therapy for systolic dysfunction in symptomatic patients with chronic primary MR (stage D) and LVEF below 60% in whom surgery is not contemplated (class IIa)

  • Consider MV surgery in symptomatic patients with chronic severe primary MR and LVEF of 30% or less (class IIb)

  • Consider MV repair in patients with rheumatic MV disease if a durable and successful repair is likely or when reliability of long-term coagulation management is not feasible (class IIb)

  • Consider transcatheter MV repair for severely symptomatic patients (New York Heart Association [NYHA] functional class III-IV) with chronic severe primary MR (stage D) who have favorable anatomy and a reasonable life expectancy but have prohibitive surgical risk due to severe comorbidities and remain severely symptomatic despite optimal GDMT for  HF (class IIb)

  • MVR should not be performed for the treatment of isolated severe primary MR limited to less than one half of the posterior leaflet unless MV repair has been attempted and was unsuccessful (class III).

In general, the ESC/EACTS guidelines are in alignment with the AHA/ACC recommendations.[1]

Secondary mitral regurgitation

The ACC/AHA class I recommendations for management of secondary MR include the following[13] :

  • Patients with chronic secondary MR and HF with reduced LVEF should receive standard medical therapy for HF including angiotensin-converting enzyme (ACE) inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), beta blockers, and/or aldosterone antagonists.

  • Cardiac resynchronization therapy (CRT) with biventricular pacing or symptomatic patients with chronic severe secondary MR who meet the indications for device therapy.

Both the ACC/AHA and ESC/EACTS guidelines recommend MV surgery for patients with chronic severe secondary MR (stages C and D) who are undergoing CABG or AVR (class IIa, ACC/AHA; class I, ESC/EACTS).[1, 13]  The ESC/EACTS guidelines also recommend surgery be considered for patients with moderate MR undergoing CABG (class IIa).[1]

Additional ACC/AHA recommendations include the following[13] :

  • Consider MV repair or replacement for severely symptomatic patients (NYHA class III to IV) with chronic severe secondary MR (stage D) who have persistent symptoms despite optimal medical therapy for HF (class IIb).

  • Consider MV repair for patients with chronic moderate secondary MR (stage B) who are undergoing other cardiac surgery (class IIb).

Infective endocarditis

Both the AHA and ESC released updated guidelines for the management of IE in 2015.[31, 32] Major recommendations from the AHA for the management of IE are summarized below[13, 32] :

Class I

The Modified Duke Criteria should be used in evaluating a patient with suspected IE. (Level of evidence: B)

At least 3 sets of blood cultures from different venipuncture sites should be obtained, with the first and last samples drawn at least 1 hour apart. (Level of evidence: A)

TTE should be performed in all cases of suspected IE. (Level of evidence: B)

TEE should be performed if initial TTE images are negative or inadequate in patients for whom there is an ongoing suspicion for IE or when there is concern for intracardiac complications in patients with an initial positive TTE. (Level of evidence: B)

If there is a high suspicion of IE despite an initial negative TEE, then obtain a repeat TEE in 3 to 5 days or sooner if clinical findings change. (Level of evidence: B)

Repeat TEE should be performed after an initially positive TEE if clinical features suggest a new development of intracardiac complications. (Level of evidence: B)

Before being considered for outpatient therapy, patients with IE should first be evaluated and stabilized in the hospital. (Level of evidence: C)

Appropriate antibiotic therapy should be initiated and continued after blood cultures are obtained, with guidance from antibiotic sensitivity data and infectious disease consultants. (Level of Evidence: B)

Patients selected for outpatient parenteral antibiotic therapy (OPAT) should be at low risk for the complications of IE, the most frequent of which are heart failure and systemic emboli. (Level of evidence: C)

Surgery should be performed before completion of a full therapeutic course of antibiotics in patients with the following: 

  • IE and valve dysfunction resulting in symptoms of HF (Level of evidence: B)
  • IE caused by fungi or highly resistant organisms (eg, vancomycin-resistant  Enterococcus, multidrug-resistant Gram-negative bacilli) (Level of evidence: B)
  • IE complicated by heart block, annular or aortic abscess, or destructive penetrating lesions (Level of evidence: B)
  • Persistent bacteremia or fevers lasting longer than 5 to 7 days after the onset of appropriate antimicrobial therapy (Level of evidence: B)

Valve repair rather than replacement should be performed when feasible. (Level of evidence: C)

Months to years after completion of medical therapy for IE, patients should have ongoing observation for and education about recurrent infection and delayed onset of worsening valve dysfunction. (Level of evidence: C)

Class III

Patients should not receive antibiotics before blood cultures are obtained for unexplained fever. (Level of evidence: C)

Antimicrobial therapy should not be initiated for the treatment of undefined febrile illnesses unless the patient’s condition (eg, sepsis) warrants it. (Level of evidence: C)

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Diuretics

Class Summary

Help decrease pulmonary congestion.

Furosemide (Lasix)

Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. Dose must be individualized to patient.

Angiotensin-Converting Enzyme Inhibitors

Class Summary

Used in the presence of MR for afterload reduction.

Captopril (Capoten)

Competitive inhibitor of ACE. Reduces angiotensin II levels, decreasing aldosterone secretion. Goal is to decrease afterload to left ventricle (by reducing systemic blood pressure and by peripheral vasodilatation), which decreases amount of blood pumped by left ventricle and pressure at which blood is being ejected. This reduces amount of blood regurgitated by mitral valve from the left ventricle into the left atrium during systole. Elimination of drug is primarily by renal excretion. Impaired renal function requires dosage reduction. Absorbed well PO. Give at least 1 h before meals. If added to water, use within 15 min.

Enalapril (Vasotec)

Competitive inhibitor of ACE. Reduces angiotensin II levels, decreasing aldosterone secretion. Goal is to decrease afterload to left ventricle (by reducing systemic blood pressure and by peripheral vasodilatation), which decreases amount of blood being pumped by left ventricle and pressure at which blood is being ejected. This reduces amount of blood regurgitated by the mitral valve from left ventricle into left atrium during systole.

Lisinopril (Zestril, Prinivil)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Nitrates

Class Summary

Used for decreasing blood pressure and increasing coronary blood flow.

Nitroglycerin IV (Deponit, Nitro-Bid, Nitrostat, Nitrol)

Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. Result is decrease in blood pressure.

Inotropic Agents

Class Summary

Because of its antiarrhythmic properties, digoxin is used if atrial fibrillation is encountered; however, it is not expected to improve overall cardiac function.

Digoxin (Lanoxin)

Cardiac glycoside with direct inotropic effects in addition to indirect effects on cardiovascular system. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.

Digitalizing dose is approximately 20% less than PO dose. IM injection offers no advantage and can cause severe pain at injection site. IV is preferred. IV digoxin begins to have effect after 15-30 min and peaks in 1.5-3 h.

Antibiotics, Prophylactic

Class Summary

Provide subacute bacterial endocarditis prophylaxis. Use prior to any interventional therapy to protect the diseased valves.

Cephalexin (Keflex)

First-generation cephalosporin that inhibits bacterial replication by inhibiting bacterial cell wall synthesis. Bactericidal and effective against rapidly growing organisms forming cell walls.

Resistance occurs by alteration of penicillin-binding proteins. Effective for treatment of infections caused by streptococcal or staphylococci, including penicillinase-producing staphylococci. May use to initiate therapy when streptococcal or staphylococcal infection is suspected.

Used orally when outpatient management is indicated.

Ampicillin (Marcillin, Omnipen)

For prophylaxis in patients undergoing dental, oral, or respiratory tract procedures. Coadministered with gentamicin for prophylaxis in GI or GU procedures.

Amoxicillin (Amoxil, Trimox)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Used as prophylaxis in minor procedures.

Clindamycin (Cleocin)

Used in patients who are allergic to penicillin and are undergoing dental, oral, or respiratory tract procedures. Useful for treatment against streptococcal and most staphylococcal infections.

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Used in conjunction with ampicillin or vancomycin for prophylaxis in GI and GU procedures.

Vancomycin (Vancocin)

Potent antibiotic directed against gram-positive organisms and active against enterococcal species. Useful in treatment of septicemia and skin structure infections. Indicated for patients who cannot receive, or have not responded to, penicillins and cephalosporins or who have infections with resistant staphylococci.

Use CrCl to adjust dose in patients diagnosed with renal impairment.

Used in conjunction with gentamicin for prophylaxis in patients who are allergic to penicillin and are undergoing GI or GU procedures.

Erythromycin (EES, E-Mycin, Eryc)

Used for prophylaxis in patients who are allergic to penicillin and are undergoing dental, oral, or respiratory tract procedures.

Azithromycin (Zithromax)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Cefazolin (Ancef)

First-generation semisynthetic cephalosporins that arrest bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including Staphylococcus aureus.

Cefadroxil (Duricef)

First generation semi-synthetic cephalosporin, that arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primarily active against skin flora, including Staphylococcus aureus.

 

Questions & Answers

Overview

How is mitral regurgitation (MR) defined?

What are the signs and symptoms of mitral regurgitation (MR)?

Which chest radiographic findings suggest mitral regurgitation (MR)?

What are the ESC/EACTS echographic criteria for severe mitral regurgitation (MR)?

According to the ACC/AHA guidelines, when is transthoracic echocardiography (TTE) indicated in the evaluation of mitral regurgitation (MR)?

According to the ACC/AHA guidelines, when is serial transthoracic echocardiography (TTE) indicated in the management of mitral regurgitation (MR)?

According to the ACC/AHA guidelines, when is transesophageal echocardiography (TEE) indicated in the evaluation of mitral regurgitation (MR)?

Which tests are performed in addition to echocardiography in the workup of mitral regurgitation (MR)?

How is mitral regurgitation (MR) treated?

According to the ACC/AHA guidelines, when is surgery indicated in the treatment of mitral regurgitation (MR)?

According to the ESC/EACT guidelines, when is surgery indicated in the treatment of mitral regurgitation (MR)?

What is mitral regurgitation (MR)?

What is the pathophysiology of mitral regurgitation (MR)?

What is the pathophysiology of acute mitral regurgitation (MR)?

What is the pathophysiology of chronic compensated mitral regurgitation (MR)?

What is the pathophysiology of chronic decompensated mitral regurgitation (MR)?

What causes acute mitral regurgitation (MR)?

What causes chronic mitral regurgitation (MR)?

What is the prevalence of mitral regurgitation (MR) in the US?

What is the global prevalence of mitral regurgitation (MR)?

What is the prognosis of mitral regurgitation (MR)?

What are the mortality rates of chronic severe degenerative mitral regurgitation (MR)?

What are the mortality rates of mitral valve surgery for the treatment of mitral regurgitation (MR)?

Which factors increase the risk of mortality from mitral regurgitation (MR)?

Presentation

Which clinical history findings are characteristic of mitral regurgitation (MR)?

Which clinical history findings are characteristic of acute mitral regurgitation (MR)?

Which clinical history findings are characteristic of chronic mitral regurgitation (MR)?

Which physical findings are characteristic of mitral regurgitation (MR)?

Which features of mitral regurgitation (MR) should be noted if murmurs are present?

DDX

Which conditions are included in the differential diagnoses of mitral regurgitation (MR)?

What are the differential diagnoses for Mitral Regurgitation?

Workup

What are the ACC guidelines on the assessment of mitral regurgitation (MR)?

What is the role of chest radiography in the workup of mitral regurgitation (MR)?

How does the ESC/EACTS guidelines define severe mitral regurgitation (MR)?

What are the ACC/AHA guidelines for the use of TTE in the evaluation of mitral regurgitation (MR)?

What are the echocardiographic parameters of severity of mitral regurgitation (MR)?

What are the ACC/AHA guidelines for the use of serial TTE in the long-term monitoring of mitral regurgitation (MR)?

What are the ACC/AHA guidelines for the use of TEE in the evaluation of mitral regurgitation (MR)?

Which ECG findings are characteristic of mitral regurgitation (MR)?

What is the role of BNP assessment in the workup of mitral regurgitation (MR)?

What are the ACC/AHA guidelines for the use of cardiac catheterization in the treatment of mitral regurgitation (MR)?

Treatment

How is mitral regurgitation (MR) treated?

What is included in prehospital care for mitral regurgitation (MR)?

How is mitral regurgitation (MR) treated in the emergency department (ED)?

What is included in the medical treatment of mitral regurgitation (MR)?

What is the role of antibiotics in the treatment of mitral regurgitation (MR)?

Which dietary and activity modifications are used in the treatment of mitral regurgitation (MR)?

What is the role of surgery in the treatment of mitral regurgitation (MR)?

What is the role of percutaneous interventions in the treatment of mitral regurgitation?

What are the possible complication of mitral regurgitation (MR)?

What are the possible complications of mitral regurgitation (MR) surgery?

Guidelines

What are the ESC/EACTS diagnostic guidelines for severe mitral regurgitation (MR)?

What are the 2017 updates to the ACC/AHA guidelines for mitral regurgitation (MR)?

What are the ESC/EACTS guidelines for mitral regurgitation (MR)?

What are the ESC/EACTS treatment guidelines for chronic secondary mitral regurgitation (MR)?

What are the AATS guidelines for mitral regurgitation (MR)?

How is chronic mitral regurgitation (MR) staged?

What are the ACC/AHA diagnostic guidelines for mitral regurgitation?

What are the ACC/AHA guidelines on acute mitral regurgitation (MR)?

What are the treatment guidelines for primary mitral regurgitation (MR)?

What are the treatment guidelines for secondary mitral regurgitation (MR)?

What are the AHA revised diagnostic guidelines for infective endocarditis?

What are the AHA revised treatment guidelines for infective endocarditis?

Medications

What is the goal of drug treatment for mitral regurgitation (MR)?

Which medications in the drug class Antibiotics, Prophylactic are used in the treatment of Mitral Regurgitation?

Which medications in the drug class Inotropic Agents are used in the treatment of Mitral Regurgitation?

Which medications in the drug class Nitrates are used in the treatment of Mitral Regurgitation?

Which medications in the drug class Angiotensin-Converting Enzyme Inhibitors are used in the treatment of Mitral Regurgitation?

Which medications in the drug class Diuretics are used in the treatment of Mitral Regurgitation?