Mitral regurgitation

Synonyms: mitral insufficiency, mitral incompetence

Mitral regurgitation (MR) occurs when the mitral valve does not close properly, causing the abnormal leaking of blood from the left ventricle through the mitral valve and back into the left atrium when the left ventricle contracts. MR may be primary or secondary:¹

• Primary MR:
  

  • Intrinsic lesions affect one or several components of the mitral valve.

  • With the reduced incidence of rheumatic fever, degenerative MR is now the most common cause.

  • Acute MR may be caused by papillary muscle rupture, infective endocarditis or trauma.

• Secondary MR (also called functional MR):
  

  • Valve leaflets and chordae are structurally normal and MR results from distortion of the subvalvular apparatus, secondary to left ventricular (LV) enlargement and remodelling.

  • Secondary MR may be due to idiopathic cardiomyopathy or coronary heart disease (when it is also called ischaemic mitral regurgitation).

Mitral regurgitation epidemiology

• Trivial MR is frequent in healthy subjects. Moderate-to-severe MR is the second most prevalent valve disease after aortic valve stenosis.²

• In Europe, MR is the second most frequent valve disease requiring surgery (after the aortic valve).¹

• 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 dyslipidaemia or diabetes.

Causes of mitral regurgitation (aetiology)^{3 4}

The most common type is degenerative MR. Causes of primary MR include:

• Coronary artery disease (papillary muscle dysfunction, chordae tendineae dysfunction or rupture).

• Infective endocarditis.

• Following mitral valve surgery, prosthetic mitral valve dysfunction.

• Myxomatous degeneration: mitral valve prolapse, Ehlers-Danlos syndrome, Marfan's syndrome.

• Systemic lupus erythematosus (Libman-Sacks lesion), scleroderma.

• Cardiac tumours, especially atrial myxoma.

• Acute rheumatic fever.

• Acute LV dysfunction.

• Congenital heart disease.

• Drug-related - eg, ergotamine, methysergide, pergolide.

Mitral regurgitation symptoms

See also the separate Heart Auscultation and Heart Murmurs in Children articles.

• Acute MR leads to rapid pulmonary oedema which is life-threatening and requires emergency valve repair.

• Chronic MR is well tolerated but dilatation of the left ventricle eventually causes heart failure and breathlessness.

Auscultation reveals a pansystolic murmur at the apex.

Acute MR due to papillary muscle rupture should be considered in patients presenting with acute pulmonary oedema or shock following an acute myocardial infarction. However, the murmur may be soft or inaudible.¹

Chronic MR may remain asymptomatic for many years but patients should be investigated before the onset of disabling dyspnoea.

Investigations¹

• CXR may show an enlarged left atrium and left ventricle.

• ECG often shows a broad P wave of left atrial enlargement.

• Echocardiography (trans-thoracic and trans-oesophageal):
  

  • Is essential to confirm the diagnosis and assess severity. All patients with MR should be quantitatively evaluated (even in the absence of symptoms), as the grade of severity determines prognosis.⁵

  • The grade (severity) is defined by the regurgitant jet into the left atrium. More accurate quantification may be achieved by combining Doppler scanning and echocardiography.

• Cardiac magnetic resonance may be used in patients with inadequate echocardiographic quality in order to assess the severity of the valvular lesion and to assess ventricular volumes and systolic function.¹

• Coronary angiography is indicated for the detection of associated coronary artery disease when surgery is planned.

• Several studies have found that elevated brain natriuretic peptide (BNP) levels and a change in BNP may have a role as predictors of outcome.

Mitral regurgitation treatment and management^{1 6 7}

Medical therapy, surgical mitral valve repair or replacement, and, in the setting of advanced heart failure, heart transplant and left ventricular assist devices remain the mainstay of treatment.

See also the separate Prevention of Infective Endocarditis, Rheumatic Fever, Atrial Fibrillation and Heart Failure Management articles.

• The management of asymptomatic patients is controversial but surgery may be an option in selected asymptomatic patients with severe MR.

• Surgery is indicated in patients with signs of LV dysfunction. If LV function is preserved, surgery should be considered in asymptomatic patients with new-onset atrial fibrillation or pulmonary hypertension.

• When surgery is appropriate, early surgery (ie within two months) is associated with better outcomes, since the development of even mild symptoms by the time of surgery is associated with adverse changes in cardiac function after surgery.

National Institute for Health and Care Excellence (NICE) guidance⁸

Consider referring adults with asymptomatic severe primary mitral regurgitation for intervention, if suitable, if they have any of the following:

• Left ventricular ejection fraction (LVEF) less than 60%

• End systolic diameter (ESD) more than 45 mm or end systolic diameter index (ESDI) more than 22 mm/m² on echocardiography; or

• An increase of systolic pulmonary artery pressure to more than 60 mm Hg on exercise testing.

When making decisions about referral for surgery, take into account the suitability of the valve for repair and the presence of atrial fibrillation or systolic pulmonary artery pressure of more than 50 mm Hg on echocardiography at rest.

Offer clinical review every 6 to 12 months, with an echocardiogram, to adults with asymptomatic severe valve disease if an intervention is suitable but not currently needed. Base the frequency of the review on echocardiography findings and shared decision making with the patient.

Primary mitral regurgitation

• Offer surgical mitral valve repair (by median sternotomy or minimally invasive surgery) to adults with severe primary mitral regurgitation and an indication for repair, if surgery is suitable.

• Offer surgical mitral valve replacement (by median sternotomy or minimally invasive surgery) to adults with severe primary mitral regurgitation and an indication for surgery, if the valve is not suitable for repair and surgery is suitable.

• Consider transcatheter edge-to-edge repair, if suitable, for adults with severe primary mitral regurgitation and symptoms, if surgery is unsuitable.

Secondary mitral regurgitation

• Consider surgical mitral valve repair (by median sternotomy or minimally invasive surgery) for adults with severe secondary mitral regurgitation who are having cardiac surgery for another indication, if surgery is suitable.

• Consider surgical mitral valve replacement (by median sternotomy or minimally invasive surgery) for adults with severe secondary mitral regurgitation who are having cardiac surgery for another indication, if the valve is not suitable for repair and surgery is suitable.

• Offer medical management to adults with heart failure and severe secondary mitral regurgitation, if surgery is unsuitable.

• Consider transcatheter mitral edge-to-edge repair for adults with heart failure and severe secondary mitral regurgitation, if surgery is unsuitable and they remain symptomatic on medical management.

Medical therapy

• In acute MR, initial treatment options include nitrates, diuretics, sodium nitroprusside, positive inotropic agents and intra-aortic balloon pump.

• When heart failure has developed, angiotensin-converting enzyme (ACE) inhibitors should be considered in patients with advanced MR and severe symptoms, who are not suitable for surgery or have residual symptoms following surgery. Beta-blockers and spironolactone are also appropriate.

Serial testing

• In some asymptomatic patients, it has been shown that severe MR can be safely followed up until symptoms develop or recommended cut-off values for LV dysfunction are reached. Such management requires careful and regular follow-up.

• Asymptomatic patients with moderate MR and preserved LV function can be followed up on a yearly basis and echocardiography should be performed every two years.

• Asymptomatic patients with severe MR and preserved LV function should be seen every six months and echocardiography performed annually.

Surgery⁹

• Urgent surgery is indicated in patients with acute severe MR.

• Rupture of a papillary muscle requires urgent surgical treatment after haemodynamic stabilisation with an intra-aortic balloon pump, positive inotropic agents and, when possible, vasodilators. Valve surgery consists of valve replacement in most cases.

• Surgery is indicated in patients with severe chronic primary MR who have symptoms due to chronic MR, but no contra-indications to surgery.

• Valve repair is considered to be the preferred surgical treatment in patients with severe MR. When compared with valve replacement, repair has a lower perioperative mortality, improved survival, better preservation of postoperative LV function and lower long-term morbidity. The supporting evidence for repair over replacement is strongest in degenerative MR.¹⁰

• When repair is not possible, mitral valve replacement with preservation of the subvalvular apparatus is preferred.

• One study found that patients treated with percutaneous repair of the mitral valve more commonly required surgery to treat residual MR. However, after the first year of follow-up, there were few surgeries required after either percutaneous or surgical treatment and no difference in the prevalence of moderate-severe and severe MR or mortality at four years.¹¹

• Beside symptoms, the most important predictors of postoperative outcome are: age, atrial fibrillation, pre-operative LV function, pulmonary hypertension and suitability of the valve for repair.

Percutaneous intervention

• The procedure which has been evaluated in organic MR is the edge-to-edge procedure, which has shown to be effective for carefully selected patients.

• However, percutaneous repair or annuloplasty are not yet routinely recommended in the UK.^{12 13}

Complications

• Pulmonary hypertension.

• LV dysfunction.

• Atrial fibrillation.

• Thromboembolism due to atrial fibrillation.

Prognosis^{1 7}

• Mitral regurgitation is frequently associated with ventricular dysfunction and carries a high mortality.

• The best short-term and long-term results are obtained in asymptomatic patients operated on in specialist centres with low operative mortality (≤1%) and high repair rates (≥80-90%).¹⁴

• Acute MR is poorly tolerated and has a poor prognosis without treatment.

• In patients with chordal rupture, the clinical condition may stabilise after an initial symptomatic period but has a poor prognosis without treatment because of the development of pulmonary hypertension.

• In asymptomatic severe chronic MR, the reported estimated five-year rate of death from any cause is 22%, death from cardiac causes 14% and the rate of cardiac events 33%.

• Predictors of poor outcome include age, atrial fibrillation, severity of MR, pulmonary hypertension, LA dilatation, increased LV end-systolic diameter and low LV ejection fraction.

• Patients with chronic ischaemic MR have a poor prognosis. Increasing severity of coronary artery disease and LV dysfunction is associated with worse outcome.

• In patients with secondary MR due to non-ischaemic aetiology, some studies have shown an independent association between significant MR and a poor prognosis.

• Operative mortality for secondary MR is higher than in primary MR and the long-term prognosis is worse due at least in part to the more severe comorbidities.

• Most studies show that severe ischaemic MR is not usually improved by revascularisation alone, and that persistence of residual MR carries an increased mortality risk. The impact of valve surgery on survival remains unclear.