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JuhaniAiraksinen

Mitral Regurgitation

Essentials

  • Mitral regurgitation is the second most common valvular defect in adults.
  • Mild or moderately severe mitral regurgitation is usually asymptomatic, and even severe, chronic regurgitation may remain asymptomatic for a long time.
  • Symptoms of mitral regurgitation include dyspnoea and fatigue on exertion. Mitral valve prolapse may be associated with palpitations and chest pain. Acute, massive mitral regurgitation will rapidly lead to pulmonary oedema.
  • A (pansystolic blowing) murmur can be heard in the area between the apex of the heart and the mid-axillary line.
  • The loudness of the murmur does not correlate with the degree of regurgitation.
  • Doppler echocardiography is the main study used for diagnosis and to define the severity (timing of surgical treatment) of the disease.
  • Valvotomy is indicated in moderately severe or severe mitral regurgitation if the valvular defect causes symptoms and in certain cases also in asymptomatic patients.
  • A mechanical valve prosthesis requires permanent, well-executed anticoagulant treatment with warfarin. Direct oral anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban) must not be used in patients with a mechanical valve prosthesis.

Aetiology

  • Mitral regurgitation is divided into structural (primary) and functional (secondary) forms.
  • Structural regurgitation is due to structural defects of the leaflets, tendinous chords or papillary muscles.
  • Mitral valve prolapse with myxomatous mitral valve degeneration is the most common structural valve defect causing significant chronic regurgitation.
  • The prevalence of mitral valve prolapse in the adult population is about 2%.
  • Even mild structural mitral regurgitation may be suddenly aggravated.
  • The most common cause of acute, severe mitral regurgitation is chordal rupture. Rarer causes include papillary muscle rupture in association with myocardial infarction, endocarditis and, rarely, cardiac trauma.
  • Functional mitral regurgitation is caused by left ventricular dysfunction and annular dilatation due to myocardial infarction or cardiomyopathy.
  • Left ventricular dysfunction as a result of myocardial infarction or dilated cardiomyopathy nearly always involves some degree of mitral regurgitation.

Symptoms and findings

  • Mild or moderately severe mitral regurgitation usually causes no symptoms, and even if regurgitation becomes more severe, patients usually remain asymptomatic for several years.
  • Pulmonary congestion gradually causes dyspnoea, first on exertion and, with more severe regurgitation, also at rest.
  • Fatigue on exertion is mostly due to a low cardiac output.
  • Mitral valve prolapse may be associated with palpitations and chest pain. Atrial fibrillation is felt as palpitations.
  • Severe, chronic mitral regurgitation may lead to right heart failure with swelling of the feet and liver and weight gain.
  • Acute, massive mitral regurgitation leads rapidly to pulmonary oedema or even cardiogenic shock.
  • Murmur (Image /6; audio sample Mitral Regurgitation)
    • A high-pitched pansystolic blowing murmur in the area between the apex of the heart and the mid-axillary line
    • If there is prolapse of the posterior mitral valve leaflet, the murmur may radiate towards the upper part of the sternum, imitating aortic stenosis.
    • In mitral valve prolapse, sudden billowing of the valve back towards the atrium often causes a mid-systolic click followed by a late systolic murmur of regurgitation.
    • A mid-systolic click alone is a common auscultation finding (10%) and often innocent.
    • In severe regurgitation, the valve closure sound (S1) is often weak, and ventricular gallop (S3) may be audible.
    • The loudness of the murmur does not correlate with the degree of regurgitation. If left ventricular pump power is well preserved, the regurgitation murmur is loud, and vice versa: if the pump power fails, the murmur becomes fainter. A regurgitation murmur due to a papillary muscle lesion caused by an infarction is often faint even if the regurgitation is severe.
  • Other findings
    • In patients with left ventricular enlargement, the apex beat expands and can be felt more laterally than normally.
    • In mild or moderately severe mitral regurgitation, the ECG is usually normal. In significant regurgitation, signs of both left ventricular (LVH) Assessment of Ventricular Hypertrophies from an ECG and left atrial (PTF) Interpretation of Adult ECG overload gradually appear, and the risk of atrial fibrillation increases.
    • Chest x-ray shows an enlarged left ventricle and atrium, and in chronic, significant mitral regurgitation, pulmonary congestion may be emphasized.
    • In acute, severe mitral regurgitation, the heart may be of a normal size, and changes caused by pulmonary oedema may be mistakenly attributed to a lung infection.
  • Echocardiography and Doppler echocardiography Echocardiography as an Outpatient Procedure
    • This is the primary examination to diagnose mitral regurgitation and to determine its severity and the timing of surgical treatment.
    • Mild mitral regurgitation in a patient with normal valve structure is a common and normal finding particularly in elderly patients, and interventions or follow-up are not indicated.

Follow-up and pharmacotherapy

  • As left ventricular volume overload from constant, significant mitral regurgitation may gradually lead to irreversible left ventricular pumping dysfunction, even asymptomatic patients should be regularly monitored.
  • Specialized care usually arranges monitoring of patients with mitral regurgitation who will probably need invasive treatment, providing primary health care with instructions for other monitoring case by case.
  • In mild structural mitral regurgitation with otherwise normal echocardiographic findings (no left ventricular enlargement and normal left ventricular pump function), it will be sufficient to perform a clinical checkup in primary health care every few years, unless there are signs of the patient's state getting worse (decreased physical performance, symptoms on exertion, a new or more severe murmur, ECG changes).
  • If there is moderate mitral regurgitation with normal left ventricular pump function and no significant ventricular enlargement, echocardiography is repeated every 1-3 years in specialized care and, in most cases, clinical checkups are performed annually in primary health care.
  • Severe (grade 3) structural mitral regurgitation which has clearly enlarged the left ventricle should be monitored in specialized care even in the absence of symptoms. The patient should be seen every 6-12 months to ensure close monitoring of physical performance, size and pump function of the left ventricle and pulmonary artery pressure in order to be able to optimize the timing of surgical treatment.
  • In functional mitral regurgitation due to left ventricular enlargement and failure, the need for checkups should be decided case by case depending on the need to treat left ventricular failure and mitral regurgitation.
  • Physical performance is the single most important issue to be monitored. If physical performance decreases rapidly or dyspnoea on exertion occurs for the first time, worsening valve status should always be suspected even if auscultation findings are unchanged.
  • The most important things to follow up are pulse, cardiac and pulmonary auscultation, blood pressure, venous pressure assessment and ECG.
  • The murmur finding must always be interpreted in relation to the structure of the patient's chest (overweight and pulmonary emphysema attenuate murmurs), symptoms (physical performance, symptoms of heart failure) and general condition (fever, dyspnoea, hypotension). In patients with hypotension and heart failure, murmurs from even significant valve defects are attenuated and masked by rhonchi caused by pulmonary oedema.
  • If a murmur has become louder or changed from that entered in patient records or found at the previous checkup, the situation should normally be reassessed by echocardiography performed by a cardiologist.
  • If a patient with a valve defect has fever, the risk of endocarditis Infective Endocarditis must always be kept in mind.
  • Natriuretic peptides (BNP/proBNP) should only be tested as necessary to exclude heart failure. Their levels are often somewhat elevated even in patients with mild valve defects, and the significance for monitoring of any changes there is unclear.
  • Exercise ECG Exercise Stress Test is mainly used to assess concomitant coronary artery disease and for objective assessment of physical performance if there is disparity between findings and symptoms or if the patient does not exert him-/herself under normal conditions.
  • Mitral regurgitation increases the incidence of atrial fibrillation. At follow-up visits, patients should be informed about the symptoms of atrial fibrillation and the importance of seeking treatment.
  • Severe, acute mitral regurgitation due to chordal rupture or endocarditis often leads rapidly to pulmonary oedema, and surgical treatment should be provided without delay.
  • Pharmacotherapy has no effect on the progress of mitral regurgitation, and it is not indicated in chronic, asymptomatic mitral regurgitation.
  • Endocarditis prophylaxis is not recommended. Good oral hygiene and regular dental checkups are important for preventing endocarditis. Dental inflammatory foci should be treated before elective valve procedures.
  • The first-line treatment for acute heart failure are diuretics and vasodilators (ACE inhibitor and nitrate). Atrial fibrillation should be treated according to the normal principles (anticoagulant, beta blocker, digitalis).
  • Effective pharmacotherapy of heart failure Chronic Heart Failure according to clinical guidelines is the first-line treatment in functional mitral regurgitation with left ventricular failure (reduced ejection fraction).
  • Cardiac resynchronization therapy with a heart failure pacemaker may reduce mitral regurgitation and symptoms in patients with dilated cardiomyopathy.
  • If mitral regurgitation only occurs during myocardial ischaemia, revascularization may fix it.

Valve operation

  • Valve operation is indicated in moderately severe or severe structural mitral regurgitation causing even transient dyspnoea symptoms in cases with a low surgical risk.
  • If the patient is still asymptomatic, surgery should always be considered to treat a severe structural valve defect if the left ventricular ejection fraction decreases to < 60% or the systolic diameter increases to > 40(-45) mm during follow-up.
  • The appearance of a tendency to atrial fibrillation and increased pulmonary artery pressure also speak for surgical treatment even in otherwise asymptomatic patients.
  • In addition, a low surgical risk and high suitability for surgical repair support early surgical treatment of asymptomatic, severe mitral regurgitation.
  • Structural mitral regurgitation should normally be treated by valvoplasty, avoiding problems such as those associated with long-term anticoagulation.
  • Repair surgery usually involves excision of the section of the leaflet billowing into the atrium. Artificial valve chords can be used, as necessary, to support the leaflet, and a supportive (annuloplasty) ring can be placed around the valve.
  • In patients over 75 years of age, valvoplasty has fewer advantages, and prosthetic replacement of the valve is often safer than extensive valvoplasty.
  • A severely damaged or degenerated valve can be replaced by either a biological or mechanical valve prosthesis.
  • In patients with severe left ventricular pump dysfunction, results of valve operation are quite poor and the decision to operate even on patients with severe symptoms should be considered case by case.

Transcatheter mitral valve repair

  • There are several transcatheter repair techniques available, of which MitraClip is the most common.
  • MitraClip is a clothes-peg-like clip used to coapt mitral valve leaflets at the regurgitant orifice to reduce or completely eliminate the orifice.
  • MitraClip is the first-line procedure in severe, functional mitral regurgitation, as it has been shown to improve not only the patient's quality of life but also the prognosis of functional mitral regurgitation, where surgery shows no prognostic benefit.
  • If the surgical risk associated with severe, structural mitral regurgitation is high due to the patient's advanced age or systemic diseases, transcatheter repair of mitral regurgitation can also be considered if the valve structure is suitable for the procedure.
  • The risks of a transcatheter procedure through femoral venous access are clearly less than those of surgery, the need for hospital treatment is short, and recovery from the operation is rapid.

Anticoagulant and antithrombotic treatment after valve operation or transcatheter procedure

  • A mechanical valve prosthesis requires permanent, well-executed anticoagulant treatment with warfarin. With modern valve prostheses, the target INR level is usually 2.5-3.5.
  • Direct oral anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban) must not be used in patients with a mechanical valve prosthesis.
  • After placing a biological valve prosthesis or after valvoplasty, warfarin is often given for 3 months, for example. Aspirin is used increasingly often unless there are other indications for anticoagulant treatment. Practices may vary across countries.
  • A biological valve prosthesis is not a contraindication for using direct oral anticoagulants for atrial fibrillation.
  • After inserting a MitraClip, aspirin alone is normally used as long-term treatment, unless the patient has other indications for anticoagulant therapy or for more effective antithrombotic treatment.
  • Atrial fibrillation is common in this group of patients, and if it occurs, just anticoagulants, either direct oral anticoagulants or warfarin, should be used.

Monitoring after surgery or MitraClip procedure

  • The first follow-up visit takes place 2-3 months after the procedure usually in specialized care, and further follow-up of patients with no complications can then usually be carried out in primary health care.
  • If the patient has a mechanical valve prosthesis, optimal warfarin treatment and follow-up are the most important tasks in outpatient care to prevent thrombosis and bleeding complications. See Heart Valve Operation: Patient Follow-Up and Complications.
  • Other follow-up in primary health care can normally be carried out annually if the patient is feeling well and has no other diseases requiring more frequent monitoring.
  • In follow-up, particular attention should be paid to any changes in physical performance capacity or cardiac symptoms, as well as to the murmur finding (see above).
  • The ECG should be checked annually and natriuretic peptides (BNP/proBNP) should be tested if there are symptoms suggesting heart failure.
  • Biological valve prostheses may gradually degenerate, causing mitral regurgitation (murmur, decreased physical performance). If so, the patient should undergo echocardiographic assessment in specialized care.
  • Complications (prosthetic valve thrombosis, endocarditis, bleeding complications, atrial fibrillation), often appearing between follow-up visits, should be recognized at an early stage, and the patient should be referred to the appropriate place for treatment.
  • Empiric antimicrobial treatment should not be started in a patient with a valve prosthesis and fever, unless the cause of fever is known (see also Heart Valve Operation: Patient Follow-Up and Complications).
  • After implantation of a biological valve prosthesis, direct oral anticoagulants can be used to treat atrial fibrillation.
  • Endocarditis prophylaxis is indicated in association with high-risk procedures (see Prevention of Bacterial Endocarditis). Good oral hygiene and regular dental checkups are important for preventing endocarditis.

    References

    • Baumgartner H, Falk V, Bax JJ et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2017;38(36):2739-2791. [PubMed]
    • Goldstein D, Moskowitz AJ, Gelijns AC et al. Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation. N Engl J Med 2016;374(4):344-53. [PubMed]
    • Stone GW, Lindenfeld J, Abraham WT et al. Transcatheter Mitral-Valve Repair in Patients with Heart Failure. N Engl J Med 2018;379(24):2307-2318. [PubMed]
    • O'Gara PT, Mack MJ. Secondary Mitral Regurgitation. N Engl J Med 2020;383(15):1458-1467. [PubMed]