Mitral Regurgitation Topic Review

Etiology | Pathophysiology | Symptoms | Physical Examination | Diagnosis | Treatment

Introduction

Mitral regurgitation is the abnormal backward flow of blood from the left ventricle to the left atrium due to either disease of the mitral valve apparatus, known as organic, or due to dilation of the mitral valve annulus from left atrial or left ventricular disease, known as functional. In chronic mitral regurgitation, the left ventricle can adapt quite well, and symptoms may be delayed for years. In acute mitral regurgitation, the left ventricle is unable to adequately compensate, and symptoms are always present and usually severe.

Etiology – Mitral Regurgitation

The etiologies of mitral regurgitation are diverse because the mitral valve apparatus is complex. Mitral regurgitation can occur organically, when the mitral valve apparatus is itself diseased, or functionally, in the absence of any abnormality of the mitral valve apparatus.

The causes of organic and functional mitral regurgitation are listed below.

Organic Mitral Regurgitation

  • Myxomatous changes (MVP)
  • Rheumatic heart disease (RHD)
  • Endocarditis
  • Collagen vascular disease
  • Papillary muscle dysfunction
  • Mitral annular calcification (MAC)
  • Spontaneous chordal rupture
  • Trauma

Functional Mitral Regurgitation

  • Ischemic cardiomyopathy
  • Dilated cardiomyopathy
  • Hypertrophic cardiomyopathy
  • Left atrial dilation

Organic mitral regurgitation results from actual disease of the mitral valve apparatus. The mitral valve leaflets, annulus, papillary muscles and chordae tendinae must all interact properly for the mitral valve to function properly. Therefore, disruption of any of these structures can lead to organic mitral regurgitation.

Functional mitral regurgitation occurs when the left atrium or left ventricle dilates, causing the mitral valve annulus to also dilate, and thus preventing the mitral valve leaflets from coapting properly. There are many causes of left atrium or left ventricular dilation, and the treatment for this type of mitral regurgitation is directed at the primary cause. For example, if a patient develops systolic congestive heart failure with a dilated left ventricle, resulting in mitral regurgitation, treatment would be directed at reversing the heart failure.

The most common cause of chronic mitral regurgitation in the United States are myxomatous changes seen in mitral valve prolapse (MVP). In this condition, the middle layer of the valve leaflets become thickened, frequently causing leaflet redundancy, which makes it difficult for them to coapt properly. The chordae tendinae may also be affected, disrupting support of the mitral valve apparatus.

Rheumatic heart disease (RHD) is another common cause of chronic mitral regurgitation. Chronic inflammation of the valve leaflets results in their thickening, calcification and, ultimately, dysfunction. Frequently, mitral stenosis or aortic valve disease is also present.

Mitral valve leaflets can also become dysfunctional or perforated when seeded by infectious organisms. In this setting, mitral regurgitation is usually acute or subacute and can cause severe symptoms. Previously-diseased mitral valves or prosthetic mitral valves are more commonly affected, but normal valves can also be involved.

Papillary muscle dysfunction from ischemia, infarction or rupture can occur in patients with coronary artery disease and lead to acute MR. The posterolateral papillary muscle is most commonly affected, as it usually receives its blood supply solely from the posterior descending artery (PDA); the anteromedial papillary muscle has dual supply by the left anterior descending artery (LAD) and the circumflex artery. Thus, papillary muscle dysfunction resulting in mitral regurgitation is a complication in posterior wall myocardial infarctions.

Idiopathic rupture of the chordae tendineae or chordal rupture associated with mitral valve prolapse can cause severe acute mitral regurgitation. Mitral annular calcification (MAC) resulting in decreased contractility of the annulus may also lead to mitral regurgitation. Rarely, penetrating trauma to the mitral valve can cause mitral regurgitation.

Pathophysiology – Mitral Regurgitation

When blood abnormally flows backward from the left ventricle to the left atrium, the volume of both chambers increases. Because a significant volume of blood is flowing retrograde, forward cardiac output decreases despite the left ventricular ejection fraction appearing normal. Thus, the ejection fraction, which is usually assumed to represent forward ejection of blood, may be normal even in the presence of forward cardiac failure.

Due to the increased volume, left atrial pressure also increases, which leads to compensatory left atrial enlargement and can influence atrial arrhythmias. The left ventricular volume also increases, and stroke volume is initially maintained by the Frank-Starling principle. However, as mitral regurgitation worsens and the stress on the left ventricle increases, left ventricular hypertrophy develops in order to maintain normal left ventricular pressures. Eventually the left ventricle reaches maximum hypertrophy, left ventricular pressures increase, and systolic heart failure ensues.

The ratio of the volume of blood that enters the left atrium to the total stroke volume is referred to as the regurgitant fraction. As mitral regurgitation worsens, the regurgitant volume increases; therefore, regurgitant fraction is often used to estimate severity of mitral regurgitation.

It is important to note that a number of hemodynamic and anatomical factors contribute to the severity of mitral regurgitation, and altering these factors is often the goal of therapy. These factors include the afterload, the left ventricular to left atrial pressure gradient and compliance of the left atrium, and the size of the mitral valve orifice during regurgitation.

Pharmacotherapy for mitral regurgitation is directed at afterload reduction, which can significantly reduce the regurgitant fraction of mitral regurgitation. Also, in acute mitral regurgitation, reducing afterload by using an intra-aortic balloon pump is effective.

Chronic mitral regurgitation allows time for the left atrium to hypertrophy and increase its compliance, thus maintaining a normal pressure, but acute mitral regurgitation does not allow time for this compensatory mechanism. In the setting of acute mitral regurgitation, small amounts of regurgitant volume causes a large increase in left atrial pressure because left atrial compliance is low. This causes the left ventricular and atrial pressure gradient to quickly equalize, ultimately preventing further regurgitation. However, the high left atrial pressures are transmitted to the pulmonary vasculature, frequently leading to pulmonary edema.

Symptoms – Mitral Regurgitation

With the slowly progressive nature of chronic mitral regurgitation, it may take years for symptoms to develop, and patients are frequently asymptomatic during the initial stages. The first symptoms are usually related to exercise intolerance or dyspnea on exertion.

Signs of left and right heart failure occur late in disease. Left heart failure results in symptoms related to the low cardiac output, as increased pressure in the left heart transmits to the lungs, causing pulmonary edema and shortness of breath. With physical activity, the heart demands greater cardiac output, which is unable to be met in states of heart failure; thus, left heart pressures increase significantly and lead to this transient pulmonary edema.

As those increased pressures from the left heart affect the right ventricle, right heart failure can ensue. The most common cause of right heart failure is left heart failure. Right heart failure symptoms include lower extremity-dependent edema. When the legs are elevated at night, the fluid redistributes centrally, causing pulmonary edema and resulting in orthopnea (dyspnea while lying flat) or paroxysmal nocturnal dyspnea (PND). Hepatic congestion can occur, causing right upper quadrant abdominal pain.

Other symptoms related to low cardiac output include fatigue and weakness; in extreme cases, cardiac cachexia can occur.

Patients may occasionally present with the onset of cardiac arrhythmias — most commonly atrial fibrillation. Other less common symptoms include hemoptysis, thromboembolism or symptoms of infectious endocarditis.

Acute mitral regurgitation presents with dramatic symptoms. Syncope can occur from sudden hypotension related to cardiogenic shock. Marked dyspnea from pulmonary edema may be present.

Physical Examination – Mitral Regurgitation

The typical murmur of mitral regurgitation is described as a high-pitched “blowing” holosystolic murmur, best heard at the apex with the patient in the left lateral decubitus position. The direction of radiation of the murmur depends on the nature of the mitral valve process. It usually radiates to the axilla and back — due to anterior leaflet disease — as the regurgitant jet is directed posterolaterally, striking the lateral wall of the left atrium. Less commonly, if the posterior leaflet is involved as in papillary muscle dysfunction, the regurgitant jet is directed anteromedially and will strike the interatrial septum; this causes the murmur to radiate to the cardiac base, often mimicking the murmur of aortic stenosis, though no radiation of the murmur to the carotids will be heard.

MR

Dynamic maneuvers help distinguish the murmur of mitral regurgitation from other murmurs. The intensity of the mitral regurgitation murmur of does not increase with inspiration, differentiating it from the murmur of tricuspid regurgitation. Increasing afterload by handgrip or transient arterial occlusion (TAO) will increase the murmur of mitral regurgitation. Any maneuver that increases left ventricular volume will also increase the mitral regurgitation murmur; this includes prolonged diastole post- premature ventricular contraction or after a long pause, as can occur in atrial fibrillation. Conversely, decreasing LV volume by the Valsalva maneuver will also decrease the murmur of mitral regurgitation.

The murmur of acute mitral regurgitation is early systolic, terminating in early to mid-systole — not holosystolic like chronic mitral regurgitation. This occurs because the left ventricular pressure rises very early in diastole, quickly reaching the pressure of the left atrium. When the left ventricular and left atrial pressures are equal, no further mitral regurgitation occurs and the murmur ceases.

Regarding heart sounds, a S3 is common in severe mitral regurgitation due to the increased volume entering the LV during early diastole; a S4 heart sound is less common. The S1 may be diminished due to the inability of the mitral valve leaflets to close completely. A widened split S2 heart sound may be present as the A2 occurs early secondary to a large proportion of the left ventricular stroke volume entering the left atrium, causing the left ventricular pressure to decrease faster. The P2 is not affected in severe mitral regurgitation.

A narrow pulse pressure is often seen in severe mitral regurgitation. The point of maximal intensity (PMI) may be displaced laterally if left ventricular dilation and heart failure are present. Signs of left heart failure including pulmonary rales may be present, along with indications of right heart failure including distension of the jugular veins and lower extremity pitting edema.

Diagnosis – Mitral Regurgitation

The electrocardiogram is non-specific for mitral regurgitation. Left atrial enlargement, indicated by broadening of the P wave, occurs due to the increased time required for propagation of electrical activity throughout the enlarged left atrium. Left ventricular hypertrophy may also be present. Less commonly, signs of pulmonary hypertension, such as right ventricular hypertrophy or right bundle branch block, may be seen.

The chest radiograph is also non-specific for mitral regurgitation. Cardiomegaly is the most common finding. Left atrial enlargement, indicated by a “double density” or straightening of the left heart border, may be seen. Signs of congestive heart failure may be present in severe or acute mitral regurgitation. Calcification of the mitral annulus is frequently present but is, again, non-specific.

Echocardiography is crucial in establishing the presence of mitral regurgitation, with physical exam findings varying and potentially unreliable. Further, in severe acute mitral regurgitation, no murmur may be heard at all, making echocardiography necessary for diagnosis. Echocardiography can accurately determine not only the presence of mitral regurgitation, but also the severity — and usually the etiology, based on imaging of the mitral valve apparatus. For example, mitral valve prolapse can be identified, or a vegetation indicating infective endocarditis may be seen.

Multiple echocardiography methods are used to grade the severity of mitral regurgitation including measurements of the depth of the mitral regurgitation jet, the area of the mitral regurgitation jet, or the regurgitant flow; the latter is the most accurate.

Due to the accuracy and non-invasive nature of echocardiography, cardiac catheterization is often not needed to diagnose or grade mitral regurgitation severity. Catheterization is indicated prior to mitral valve replacement to determine if concurrent coronary artery disease requiring bypass is present.

Findings on catheterization include opacification of the left atrium when the left ventriculogram is performed due to retrograde flow of contrast. The severity is graded on a scale of 1 to 4; mitral regurgitation that is 1+ is considered mild, and mitral regurgitation that is 4+ is when contrast material regurgitates all the way into the pulmonary veins. Additionally, pulmonary capillary wedge pressure tracings usually identify a large “V” wave, indicating the presence of mitral regurgitation.

Note that a large V wave is not specific for mitral regurgitation unless it is significantly larger than the A wave (i.e. 100-200% larger).

Treatment – Mitral Regurgitation

The treatment for mitral regurgitation is often observatory in asymptomatic patients, and surgical therapy is used for symptomatic patients. Pharmacotherapy directed at afterload reduction with vasodilators can be useful during acute decompensated heart failure in patients with severe mitral regurgitation; however, chronic vasodilator therapy is indicated only for non-surgical candidates.

Due to the complications of prosthetic valves, mitral valve repair is the surgical intervention of choice, if possible. In those regards, if echocardiographic data indicates mitral valve repair will be feasible, a lower threshold for surgery is considered.

Mitral valve replacement has been repeatedly shown to decrease symptoms of mitral regurgitation; however, data is lacking regarding a survival benefit compared with the natural history of chronic mitral regurgitation. Conversely, mitral valve repair has been shown to both reduce symptoms and long-term mortality.

The actual timing of surgical intervention is a difficult decision and must take into account multiple factors; these include the ability of mitral valve repair vs. replacement, rate of progression of mitral regurgitation, left ventricular systolic function, presence or absence of atrial fibrillation, clinical judgement and patient preference.

For non-surgical candidates, vasodilators can be utilized with some improvement in symptoms and progression of mitral regurgitation. For acute decompensated heart failure due to chronic mitral regurgitation, vasodilators should be avoided, and nitroprusside is the drug of choice. ACE inhibitors and nitrates have no effect on cardiac index and may actually increase the regurgitant fraction — especially in patients with mitral regurgitation from mitral valve prolapse.

Vasodilator therapy is generally not indicated for asymptomatic patients with chronic mitral regurgitation due to lack of data showing benefit and the possibility of masking symptoms that may indicate a need for surgical intervention. However, when another indication such as hypertension or diabetes arises, the use of vasodilators including ACE inhibitors or angiotensin receptor blockers is accepted.

Symptomatic patients who are not surgical candidates have been shown to benefit from therapy with vasodilators. ACE inhibitors with nitrates is considered the combination of choice in patients with mitral regurgitation from ischemic heart disease or dilated cardiomyopathy. In patients with mitral regurgitation from mitral valve prolapse, however, reducing only preload actually increases regurgitation (see Mitral Valve Prolapse Topic Review); thus, the recommended treatment combination is beta-blockers with diuretics. Finally, patients with mitral regurgitation from rheumatic heart disease benefit the most from reduction in systolic blood pressure, as reduction of preload will not decrease the orifice of mitral regurgitation; beta-blockers, diuretics and hydralazine should be used in these individuals.

Data regarding the use of digoxin is lacking, but its use for heart failure in general is common and considered reasonable in patients with symptomatic mitral regurgitation who are not surgical candidates.

Oral anticoagulation is indicated for patients with atrial fibrillation associated with their mitral regurgitation, or if significant mitral stenosis is also present. The role of anticoagulation in patients with chronic mitral regurgitation in normal sinus rhythm with enlarged left atrium (> 5.5 cm) is controversial.

Antibiotic prophylaxis before surgical or dental procedures is no longer indicated for any patients with mitral regurgitation to reduce the risk for bacterial endocarditis, unless a prosthetic valve is present.

References:
1. ACC/AHA Guidelines: Valvular Heart Disease
2. Braunwalds Heart Disease: A Textbook of Cardiovascular Medicine
3. Enriquez-Sarano, et al. Mitral Regurgitation. Lancet. 2009;doi: 10.1016/S0140-6736(09)60692-9.
4. Hursts the Heart, 13th Edition
5. Image: CC Patrick, J Lynch and C Carl Jaffe, Yale University, 2006