Mitral valve disease: clinical review

An overview of mitral valve disease, including the aetiology and clinical features of mitral stenosis and mitral regurgitation, and how to treat patients with heart failure.

Transthoracic echocardiogram showing mitral regurgitation (‘parasternal long axis view’). RV = right ventricle. IVS = interventricular septum. LV = left ventricle. Ao = aorta. MR = mitral regurgitation. LA = left atrium.


Anatomy and physiology
The mitral valve (MV) is situated within a fibrous annulus. The valve consists of a large posterior leaflet and a smaller anterior leaflet. Each leaflet is split into three scallops by the attachment of the chordae tendinae.

The chordae tendinae insert into the anterolateral and posteromedial papillary muscles in the left ventricle (LV). The MV opens in diastole to allow filling of the LV, and closes before systole when the LV pressure exceeds the left atrial (LA) pressure, to direct blood through the aortic valve. The closure of the MV produces the first heart sound (S1), along with tricuspid valve closure.

Mitral regurgitation
Mitral regurgitation (MR) may be caused by dysfunction of the leaflet, annulus, chordae, or papillary muscles (primary), or it may be secondary to LV dysfunction and dilatation (functional). Functional mitral regurgitation occurs more commonly than primary mitral regurgitation and may be related to any condition that causes LV dilation, such as ischaemic heart disease or dilated cardiomyopathy.

The most common cause of primary MR is myxomatous degeneration of the valve leaflets. Histological changes include myxomatous infiltration, fibroelastic deficiency, collagen alterations, and mucopolysaccharide accumulation.1 

The exact mechanism is poorly understood. Physiologically, this causes weakness in the mitral valve leaflets, which are then unable to prevent backflow during high pressures (systole).

MR related to ischaemic heart disease may be primary or functional. Ischaemia or infarction may acutely damage papillary muscles, leading to abnormal closure of the valve leaflet and failure of coaptation. This is primary MR. The LV remodelling associated with chronic ischaemic cardiomyopathy dilates the LV and hence the MV annulus. The valve tips are therefore further apart and do not coapt. This is functional MR.

Other causes of primary MR include rheumatic heart disease, endocarditis, and systemic lupus erythematosus (SLE).Infective endocarditis should be considered early to limit long-term complications – MR may be caused by incomplete closure of the leaflets due to vegetation or damage to the valve apparatus.

Hypertrophic cardiomyopathy affecting the septum can alter flow dynamics in the LV outflow tract and result in systolic anterior motion of the anterior MV leaflet. This motion drags the anterior leaflet away from the posterior leaflet leaving an open orifice in systole, allowing a regurgitant jet. This should be considered in the younger population with clinical MR.

Mitral valve prolapse (MVP) most frequently occurs in isolation and runs a benign course, often accounting for common valvular abnormalities. MVP may be associated with inherited connective tissue diseases, such as Marfan's syndrome, Ehlers-Danlos syndrome and osteogenesis imperfecta.

mitral stenosis
Typical signs of mitral stenosis: straightening of the left heart border from an enlarged left atrium (A), enlarged pulmonary artery (B) and splayed carina (C).

Mitral stenosis
Mitral stenosis (MS) is no longer commonly encountered in Western populations. MS may be caused by rheumatic heart disease, calcific degeneration, SLE, endomyocardial fibrosis, and radiation.

Acute rheumatic carditis causes inflammation and oedema of the leaflets leading to MR, while subsequent scarring results in thickening of valve leaflets, commissural fusion, and chordal shortening - the hallmarks of post-rheumatic MS. The most common valvular abnormality seen with rheumatic heart disease is mitral stenosis.

Inflammatory processes, such as SLE and scleroderma, may cause thickening of the MV leaflets or fusion of the commissures.


Mitral regurgitation
MR is the second most common valvular abnormality after aortic stenosis. Estimates of the prevalence of MR are confounded by the presence of benign flow murmurs, and the small amount of physiological regurgitation detected by echocardiography in 80% of patients.2 In the Strong Heart Study, moderate to severe MR was detected by screening echocardiography in 2.1% of asymptomatic subjects, with a mean age of 60 years.3

The prevalence of MVP in a general population American screening study has been quoted as 2.4%, with a 2:1 female to male ratio.4

Mitral stenosis
MS is predominantly caused by rheumatic fever. The most common alternative pathology is age-related degeneration. Around 25% of patients with rheumatic heart disease have isolated MS, and 40% have mixed mitral valve disease.5 Mitral stenosis (MS) accounted for 12% of valvular abnormalities found in the Euro Heart Survey.6

Clinical features

Mitral regurgitation

Patients with mild MR are usually asymptomatic. Progression of the disease may eventually cause symptoms such as exertional dyspnoea and fatigue, which may be insidious and sometimes ignored by the patient until a late stage.

It is therefore worth asking a relative about functional deterioration. In chronic disease, the LA has time to adapt and accommodate the increased volume, thereby delaying pulmonary hypertension and symptoms.

Specific enquiry should be made regarding a history of rheumatic fever and symptoms of infective endocarditis, such as fever, night sweats, and weight loss. Chest pain is rare unless coronary artery disease co-exists. Although these patients are at an increased risk of atrial fibrillation (AF), this condition is more commonly seen in MS.

Clinical examination
The apical impulse may be displaced laterally and hyperdynamic, because of volume overload. The S1 is followed by a pansystolic murmur heard best at the apex, radiating towards the axilla or the sternum on maximal expiration. A third heart sound (S3) may occasionally be heard, even in the absence of heart failure, due to the increased volumes entering the LV in early diastole.

MVP syndrome causes a late systolic murmur preceded by a click and is often less prominent than MR. The condition may be associated with atypical symptoms of chest pain, palpitations, dyspnoea, and rarely syncope.

It is important to examine these patients for any stigmata of infective endocarditis.These include splinter haemorrhages under the fingernails, Janeway lesions, Osler's nodes, Roth's spots or finger clubbing.

Mitral stenosis

The most common presenting symptom of MS is exertional dyspnoea. As in MR, check for a progressive decline in exercise tolerance. Increased pressures in the LA as a result of MS lead to raised pulmonary venous pressure. This can cause pulmonary oedema and the typical symptoms of breathlessness, orthopnoea, and paroxysmal nocturnal dyspnoea. Other symptoms such as a wheeze, cough, and haemoptysis are less commonly observed. Rarely, the dilatation of the LA may cause symptoms of dysphagia or hoarseness, due to compression of the recurrent laryngeal nerve.

Atrial tachyarrhythmias, specifically AF, are common in patients with MS. These patients may present with symptoms such as palpitations, chest pain, or dyspnoea that may be chronic or episodic (paroxysmal AF).

Clinical examination
The typical mitral facies, or malar flush, is rare. The most common findings on clinical examination are irregular pulse (AF), and signs of left and/or right heart failure. The apex beat is often undisplaced or impalpable, although the sudden closure of the fibrosed MV often causes a tapping impulse.

A loud S1 is sometimes appreciated. A low-pitched, rumbling diastolic murmur, heard best at the apex in the left lateral recumbent position on maximal expiration, is typical of MS. An opening snap in diastole preceding the murmur may sometimes be heard at the apex.

Clinical features of mitral valve disease 
Mitral regurgitation Mitral stenosis
Pulse often normal irregular pulse (AF)
Apex beat displaced and hyperdynamic tapping impulse
Murmur pansystolic murmur, radiating to the axilla diastolic murmur
Additional features late systolic click in MVP opening snap


As with all cardiac disease, a history and examination are vital. The resting 12-lead electrocardiogram (ECG) may show AF, or pathological Q waves of previous ischaemic heart disease.

If symptoms are suggestive of possible AF in the absence of 12-lead ECG findings, longer ECG monitoring should be arranged in the form of 24/48 ECG monitors or implantable loop recorders. If the patient remains in sinus rhythm, a bifid P wave is sometimes seen in V1, indicative of left atrial dilatation.

A chest X-ray may show cardiomegaly (defined as cardiothoracic ratio >0.5 on PA film). A splaying of the tracheal carina, and a prominent LA bulge in the upper left heart border, may be seen in patients with significant LA enlargement. In the latter stages of valve disease, pulmonary congestion or frank pulmonary oedema are observed.

Transthoracic echocardiography (TTE) is the investigation of choice and should be arranged for all patients with a new murmur where valvular heart disease is a possibility. This can confirm mitral valve disease and allow grading of severity.

More detailed investigations should be arranged on advice from a cardiologist. Stress echocardiography, transoesophageal echocardiography (TOE), cardiac magnetic resonance imaging (MRI), multi-slice computed tomography (CT), and cardiac catheterisation can provide valuable information.

Patients who are referred for surgery for MV disease should undergo coronary angiography. The cardiologist can then also assess for coronary stenoses that may require concurrent coronary artery bypass graft (CABG) during valve surgery.

TOE provides excellent views of the MV. As the MV is a posterior cardiac structure the position of the echocardiographic probe in the oesophagus allows an assessment to be made from close proximity. Most TOE software packages will now also allow 3-dimensional reconstruction of the valve anatomy to guide the surgeon in the choice of surgical approach.

TOE is frequently done before surgery is considered, for a detailed assessment of the valvular apparatus.7 Patients with suspected infective endocarditis should have bloods taken for cultures and inflammatory markers.


All patients with a clinical suspicion of MV disease should be referred for a cardiology opinion to allow for further treatment planning and surveillance, as the clinical signs often do not correlate with the severity of disease, especially in patients on diuretics, ACE inhibitors, or dialysis.

Urgency of referral in mitral valve disease 
Routine outpatient
  • asymptomatic MS/MR (suspected or confirmed)
Urgent outpatient
  • symptomatic MS/MR
Admit immediately
  • clinical suspicion of infective endocarditis
  • haemodynamic instability, or clinical evidence of heart failure in a patient with previously diagnosed severe MS/MR

Medical management

Medical management with vasodilators is not indicated in patients with asymptomatic MR because it may mask the onset of symptoms, an indicator used to decide on timing of surgery. However, it is useful in the acute decompensated phase, and as a palliative measure in advanced disease in patients who are unsuitable for surgery.

Patients with heart failure (especially in the context of functional MR) should be treated with one or more of the following agents: ACE inhibitors or an ARB, beta-blockers, spironolactone, ivabradine, sacubitril/valsartan combined, diuretics, digoxin, and nitrates.8 Cardiac resynchronisation therapy should also be considered because LV remodelling after resynchronisation can reduce functional MR.9

AF in the presence of MV disease predisposes patients to a high risk of thromboembolic disease. Therefore, anticoagulation therapy should be considered with rate versus rhythm optimisation measures. Most thromboembolic risk prediction models (such as the CHA2DS2-VASc score) are not applicable to patients with significant MV disease, and their risk is higher. So anticoagulation should be considered in all cases.

Patients with acute MR are usually haemodynamically unstable and require urgent intervention. Nitrates, diuretics, and sodium nitroprusside can be used to stabilise them pre-surgery.

NICE guidelines, reviewed in 2015, state that routine antibiotic prophylaxis for infective endocarditis is not indicated in patients with MV disease.10

Surgical management

The definitive treatment for severe or symptomatic MV disease is surgery. The timing is vital to ensure good LV function and prognostic improvement. The European Society of Cardiology and European Association for Cardio-Thoracic Surgery 2012 guidelines for management of mitral valve disease recommend intervention in the following circumstances:

  • severe primary mitral regurgitation
  • symptomatic MR with ejection fraction (EF) >30% and left ventricular end systolic diameter (LVESD) <55mm
  • asymptomatic MR with EF ≤60 per cent or LVESD ≥45mm
  • asymptomatic MR with preserved LV function and new onset of AF or pulmonary hypertension (>50mmHg at rest)
  • secondary (functional) mitral regurgitation
  • severe MR undergoing CABG
  • moderate MR undergoing CABG
  • symptomatic MR despite optimal heart failure management
  • mitral stenosis
  • significant MS (valve area ≤1.5cm2) with symptoms

In MR, where feasible, mitral valve repair is the treatment of choice rather than valve replacement. Outcome data for MV repair are better than for replacement, with an in-hospital mortality of 4.3%, compared with 6.9% in MV replacement patients.

This may be confounded by selection bias in the patients chosen for repair, because they tend to be younger with fewer comorbidities than those selected for replacement. The 10-year survival rate for MV repair was 62% in one retrospective study, with MV replacement 10-year survival at 46%.

This difference was most notable in younger patients, with the 10-year survival of those over 60 years levelling off at 33% and 36% respectively.11

Patients who meet the indications for MV surgery in the context of MS should undergo percutaneous mitral commissurotomy if they have favourable anatomical characteristics. Otherwise they should undergo surgical valve replacement. Transoesophageal (including 3D) echocardiography may provide crucial information for the decision-making process.

There are two main types of prosthesis in valve replacement - mechanical or bioprosthetic.

Types of prosthesis and patient selection characteristics 
Consideration Mechanical Bioprosthesis
  • absence of contraindication for long-term anticoagulation or those already on warfarin (for example, AF)
  • unavailability of anticoagulation (patient’s wishes, high-risk, occupation)

  • young female contemplating pregnancy in whom anticoagulation is not appropriate
Risk of redo surgery
  • patients at risk of accelerated valve destruction
  • desire of the informed patient with a morphologically intact valve apparatus
Life expectancy
  • patients for whom redo valve surgery is high risk (left ventricular failure, previous cardiac)
  • patients for whom redo surgery is relatively low risk
Risk of prosthetic valve degeneration
  • Age less than 65 with long life expectancy
  • Limited life expectancy


Symptomatic deterioration should be carefully monitored. Specific enquiries about fever, night sweats, lethargy, and weight loss should be made to rule out infective endocarditis. Clinical examination should focus on features of congestive cardiac failure and infective endocarditis, as well as auscultation of the heart sounds.

Mechanical mitral valves generate a metallic S1. Bioprosthetic mitral valves typically cause a loud S1. In those with mitral valve repair there may be no abnormal auscultatory findings. Prosthetic valve incompetence may be heard as a soft systolic murmur over the mitral region.

Clinical suspicion of prosthetic valve incompetence should be assessed further by transthoracic echocardiogram (TTE), and referral to a cardiologist considered. After an initial outpatient echocardiogram following recovery from mitral valve surgery to document baseline parameters (prosthetic valve gradient, LV systolic function etc), routine annual follow up TTE is not indicated in the absence of symptoms and unaltered heart sounds.

However, any suspicion of symptomatic deterioration or infective endocarditis should trigger urgent echocardiographic assessment.

Patients with prosthetic heart valves are usually under annual follow-up with a cardiology service. Lifelong anticoagulation is recommended for those with mechanical valves or AF - the INR target differs according to the position of the valves, type of valve, and LV function.


Despite surgery, acute MR carries a 30-day mortality rate of 22.5%.12 Asymptomatic severe chronic MR has an estimated 5-year all-cause mortality of 22%.13

Predictors of poor outcome include symptoms, increasing age, severity of MR, AF, and LV systolic dysfunction with or without LV dilatation.

Symptomatic patients with MS have a poor prognosis and carry a higher operative risk. In asymptomatic patients with MS, survival can be up to 10 years, but progression is highly variable. Sudden deterioration can be precipitated by complications, such as AF or systemic thromboembolism, in up to half of patients.14

  • Dr Wern Yew Ding, ST3 Cardiology, Liverpool Heart and Chest Hospital, UK
  • Dr Unni Krishnan, Academic Clinical Lecturer, Cambridge University, and Papworth Hospital, UK
  • Dr Robert Cooper, ST7 Cardiology, Liverpool Heart and Chest Hospital, UK

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  1. Fornes P, Heudes D, Fuzellier JF et al. Cardiovasc Pathol, 1999; 8(2): 81-92.
  2. Otto CM. N Engl J Med, 2001; 345(10): 740-6.
  3. Jones EC, Devereux RB, Roman MJ et al. Am J Cardiol, 2001; 87(3): 298-304.
  4. Boudoulas WH. Mitral valve: Floppy mitral valve, mitral valve prolapse, mitral valvular regurgitation. 2nd ed: Wiley Blackwell; 2000.
  5. Bonow RO, Carabello BA, Kanu C et al. Circulation, 2006; 114(5): e84-231.
  6. Iung B, Baron G, Butchart EG et al. Eur Heart J, 2003; 24(13): 1231-43.
  7. Vahanian A, Alfieri O, Andreotti F et al. Eur J Cardio Thorac Surg, 2012; 42(4): S1-44.
  8. NICE. CG108. London, NICE, August 2010.
  9. McMurray JJ, Adamopoulos S, Anker SD et al. Eur Heart J, 2012; 33(14): 1787-847.
  10. NICE. CG64. London, NICE, March 2008 [reviewed 2015].
  11. Thourani VH, Weintraub WS, Guyton RA et al. Circulation, 2003; 108(3): 298-304.
  12. Lorusso R, Gelsomino S, De Cicco G et al. Eur J Cardio Thorac Surg, 2008; 33(4): 573-82.
  13. Enriquez-Sarano M, Akins CW, Vahanian A. Lancet, 2009; 373(9672): 1382-94.
  14. Chiang CW, Lo SK, Ko YS et al. Ann Intern Med (1998); 128(11): 885-9.

This is an updated version of an article that was first published in September 2010

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