(See also Overview of Cardiac Valvular Disorders.)
Mitral regurgitation may be
Causes of acute mitral regurgitation include
Common causes of chronic mitral regurgitation are intrinsic valve pathology (primary MR) or distortion of a normal valve by dilatation and impairment of the left ventricle (secondary MR).
In secondary MR, ventricular impairment and dilation displace the papillary muscles, which tether the otherwise normal leaflets and prevent them from closing fully. The causes are myocardial infarction (ischemic chronic secondary MR) or intrinsic myocardial disease (nonischemic chronic secondary MR). A less common mechanism is annular dilatation due to chronic atrial fibrillation with left atrial enlargement.
In infants, the most likely causes of MR are papillary muscle dysfunction, endocardial fibroelastosis, acute myocarditis, cleft mitral valve with or without an endocardial cushion defect, and myxomatous degeneration of the mitral valve. MR may coexist with mitral stenosis when thickened valvular leaflets do not close.
Complications of chronic MR include gradual enlargement of the left atrium (LA); LV enlargement and eccentric hypertrophy, which initially compensates for regurgitant flow (preserving forward stroke volume) but eventually decompensates (reducing forward stroke volume); atrial fibrillation (AF), which may be further complicated by thromboembolism; and infective endocarditis.
Acute mitral regurgitation causes the same symptoms and signs as acute heart failure (dyspnea, fatigue, weakness, edema) and cardiogenic shock (hypotension with resultant multisystem organ damage). Specific signs of mitral regurgitation may be absent.
Chronic mitral regurgitation in most patients is initially asymptomatic, and symptoms develop insidiously as the LA enlarges, pulmonary artery pressure and venous pressure increase, and LV compensation fails. Symptoms include dyspnea, fatigue (due to heart failure), orthopnea, and palpitations (often due to atrial fibrillation). Rarely, patients present with endocarditis (eg, fever, weight loss, embolic phenomena).
Signs develop only when mitral regurgitation becomes moderate to severe. Inspection and palpation may detect a brisk apical impulse and sustained left parasternal movement due to systolic expansion of an enlarged LA. An LV impulse that is sustained, enlarged, and displaced downward and to the left suggests LV hypertrophy and dilation. A diffuse precordial lift occurs with severe MR because the LA enlarges, causing anterior cardiac displacement, and pulmonary hypertension causes right ventricular hypertrophy. A regurgitant murmur (or thrill) may also be palpable in severe cases.
On auscultation, the 1st heart sound (S1) may be soft (or occasionally loud). A 3rd heart sound (S3) at the apex reflects a dilated LV and severe MR.
The cardinal sign of mitral regurgitation is a holosystolic (pansystolic) murmur, heard best at the apex with the diaphragm of the stethoscope when the patient is in the left lateral decubitus position. In mild MR, the systolic murmur may be abbreviated or occur late in systole.
The murmur begins with S1 in conditions causing leaflet incompetency throughout systole, but it often begins after S1 (eg, when chamber dilation during systole distorts the valve apparatus or when myocardial ischemia or fibrosis alters dynamics). When the murmur begins after S1, it always continues to the 2nd heart sound (S2). The murmur radiates toward the left axilla; intensity may remain the same or vary. If intensity varies, the murmur tends to crescendo in volume up to S2.
MR murmurs increase in intensity with handgrip or squatting because peripheral vascular resistance to ventricular ejection increases, augmenting regurgitation into the LA; murmurs decrease in intensity with standing or the Valsalva maneuver. A short rumbling mid-diastolic inflow murmur due to torrential mitral diastolic flow may be heard following an S3. In patients with posterior leaflet prolapse, the murmur may be coarse and radiate to the upper sternum, mimicking aortic stenosis.
MR murmurs may be confused with tricuspid regurgitation, which can be distinguished because tricuspid regurgitation murmur is augmented during inspiration.
Diagnosis of mitral regurgitation is suspected clinically and confirmed by echocardiography. Doppler echocardiography is used to detect regurgitant flow and pulmonary hypertension. Two-dimensional or 3-dimensional echocardiography is used to determine the cause and severity of MR (see table Grading of Mitral Regurgitation), the presence and extent of annular calcification, and the size and function of the LV and LA and to detect pulmonary hypertension.
When it is acute, severe MR may not be apparent on color Doppler echocardiography, but suspicion is raised when acute heart failure is accompanied by hyperdynamic LV systolic function.
Grading of Mitral Regurgitation
If endocarditis or valvular thrombi are suspected, transesophageal echocardiography (TEE) can provide a more detailed view of the mitral valve and LA. TEE is also indicated when mitral valve repair instead of replacement is being considered to evaluate the mechanism of MR in more detail.
An ECG and chest x-ray are usually obtained initially.
ECG may show LA enlargement and LV hypertrophy with or without ischemia. Sinus rhythm is usually present when MR is acute because the atria have not had time to stretch and remodel.
Chest x-ray in acute MR may show pulmonary edema; abnormalities in cardiac silhouette are not evident unless an underlying chronic disorder is also present. Chest x-ray in chronic MR may show LA and LV enlargement. It may also show pulmonary vascular congestion and pulmonary edema with heart failure.
Cardiac catheterization is done before surgery, mainly to determine whether coronary artery disease (CAD) is present. A prominent systolic c-v wave is seen on pulmonary artery occlusion pressure (pulmonary capillary wedge pressure) tracings during ventricular systole. Ventriculography can be used to quantify MR. Cardiac MRI can accurately measure regurgitant fraction and determine the cause of dilated myopathy with MR.
Periodic exercise testing (stress ECG ) is often done to detect any decrease in effort tolerance, which would prompt consideration of surgical intervention. Periodic echocardiography is done to detect progression of MR.
Prognosis of mitral regurgitation varies by duration, severity, and cause. Some MR worsens and eventually becomes severe. Once MR becomes severe, about 10% of asymptomatic patients become symptomatic each year thereafter. About 10% of patients with chronic MR caused by mitral valve prolapse require surgical intervention.
Angiotensin-converting enzyme (ACE) inhibitors and other vasodilators do not delay LV dilation or MR progression and so have no role in asymptomatic MR with preserved LV function. However, if LV dilation or dysfunction is present, vasodilators, spironolactone, and vasodilating beta-blockers (eg, carvedilol) are indicated.
If the ECG shows left bundle branch block, then biventricular pacing may be beneficial for secondary MR.
Loop diuretics such as furosemide are helpful in patients with exertional or nocturnal dyspnea. Digoxin may reduce symptoms in patients with AF or those in whom valve surgery is not appropriate.
Antibiotic prophylaxis is no longer recommended except for patients who have had valve replacement or repair utilizing prosthetic materials (see table Recommended Endocarditis Prophylaxis During Oral-Dental or Respiratory Tract Procedures).
Anticoagulants are used to prevent thromboemboli in patients with AF.
Acute mitral regurgitation requires emergency mitral valve repair or replacement with concomitant coronary revascularization as necessary. Pending surgery, nitroprusside or nitroglycerin infusion and an intra-aortic ballon pump may be used to reduce afterload, thus improving forward stroke volume and reducing ventricular and regurgitant volume.
Chronic primary mitral regurgitation that is severe needs intervention at the onset of symptoms or decompensation (LVEF < 60% or LV end-systolic diameter > 40 mm, new onset AF, rest pulmonary artery systolic pressure > 50 mmHg). Even in the absence of these triggers, intervention may be beneficial when surgical risk is low and valve morphology suggests a high likelihood of successful repair, if there is present a flail leaflet or significant left atrial dilatation (volume index ≥ 60 mL/m2 in sinus rhythm). When the EF falls to < 30%, surgical risk is high, necessitating a careful weighing of risk and benefit.
Chronic secondary mitral regurgitation has fewer indications for intervention. Because the primary pathology involves the LV muscle, correction of MR is not as likely to be beneficial. However, guidelines still weakly support (ie, class IIb recommendation) consideration of mitral valve surgery with either repair (with annuloplasty ring) or replacement if the patient has severe symptomatic mitral regurgitation with persistent NYHA (New York Heart Association) class III-IV symptoms.
For patients undergoing cardiac surgery for other indications, concomitant mitral valve surgery should be considered for a repairable valve with MR that is moderate. However, for secondary MR, this practice has been questioned by the two-yr outcome of a recent randomized comparison with CABG alone. The addition of mitral valve repair did not affect LV remodelling or survival, but an excess of adverse events occurred (1). Longer term followup is needed. If the valve is not repairable, then replacement is usually done only when MR is severe.
When there is no other indication for surgery, mitral valve surgery may be considered in severe primary or secondary MR if LVEF > 30%, surgical risk is low and medical therapy has failed. Otherwise, there is now an option for percutaneous repair to palliate inoperable patients.
In primary mitral regurgitation, the closer the mitral valve intervention mimics the native valve, the better for LV preservation and mortality. Hence, the order of preference is
If mitral valve repair with leaflet remodelling and chordal replacement is not feasible, replacement with a mechanical prosthesis is preferred because tissue valves have reduced longevity in the mitral position. A bioprosthesis is an option for patients over the age of 70.
In secondary mitral regurgitation, surgical treatment with either mitral valve replacement or repair with an annuloplasty ring is reasonable. Repair with annuloplasty ring is generally preferable to replacement; however, there is no durable way to repair secondary MR, and valve replacement has both early (perioperative complications and mortality) and late (thromboembolism and infection) risks. One study of 2-year outcome in patients with severe secondary MR randomized to repair (with an annuloplasty ring) or chordal-sparing mitral valve replacement found no difference in LV remodeling or survival. Mitral regurgitation recurred more frequently in the repair group (59% vs 4%), resulting in more heart-failure related adverse events and readmissions (2).
Another method of repair is a percutaneous mitral valve repair (PMVR) with a device that approximates the mitral leaflets. PMVR is an option for patients with severe primary or secondary MR and heart failure refractory to medical therapy who cannot undergo surgery. PMVR can improve symptoms and induce reverse remodelling, even though rates of residual and recurrent MR are higher than with surgical repair (3). It appears of benefit for primary MR or for MR that is secondary but is truly refractory to optimal medical therapy and accompanied by preserved LV function and size (ie, the symptoms are largely due to the MR not LV dysfunction—4, 5).
Lifelong anticoagulation with warfarin is required in patients with a mechanical valve to prevent thromboembolism. A mitral bioprosthetic valve requires anticoagulation with warfarin for 3 to 6 months postoperatively (see also Anticoagulation for patients with a prosthetic cardiac valve). Direct-acting oral anticoagulants (DOAC) are ineffective and should not be used.
In about 50% of decompensated patients, prosthetic valve implantation markedly depresses ejection fraction because in such patients, ventricular function has become dependent on the afterload reduction of MR.
Selected patients with AF may benefit from concomitant ablation therapy, although this therapy increases operative morbidity.
1. Michler RE, Smith PK, Parides MK, et al: Two-year outcomes of surgical treatment of moderate ischemic mitral regurgitation. N Engl J Med 374:1932–1941, 2016. doi: 10.1056/NEJMoa1602003.
2. Goldstein D, Moskowitz AJ, Gelijns AC, et al: Two-year outcomes of surgical treatment of severe ischemic mitral regurgitation. N Engl J Med 374:344–353, 2016. doi: 10.1056/NEJMoa1512913.
3. Feldman T, Kar S, Elmariah S, et al: Randomized comparison of percutaneous repair and surgery for mitral regurgitation: 5-year results of EVEREST II. J Am Coll Cardiol. 66:2844–2854, 2015. doi: 10.1016/j.jacc.2015.10.018.
4. Obadia JF, Messika-Zeitoun D, Leurent G, et al: Percutaneous repair or medical treatment for secondary mitral regurgitation. New Engl J Med 379:2297–2306, 2018. doi: 10.1056/NEJMoa1805374
5. Stone GW, Lindenfeld J, Abraham WT, et al: Transcatheter mitral-valve repair in patients with heart failure. New Engl J Med 379:2307–2318, 2018. doi: 10.1056/NEJMoa1806640
Common causes of mitral regurgitation (MR) include mitral valve prolapse, rheumatic fever, and left ventricular dilation or infarction.
Acute MR may cause acute pulmonary edema and cardiogenic shock or sudden cardiac death.
Chronic MR causes slowly progressive symptoms of heart failure and, if atrial fibrillation develops, palpitations.
Typical heart sounds are a holosystolic murmur that is heard best at the apex, radiates toward the left axilla, increases in intensity with handgrip or squatting, and decreases in intensity with standing or the Valsalva maneuver.
Symptomatic patients and those meeting certain echocardiographic criteria benefit from valve replacement or repair.