AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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Background

Mitral regurgitation (MR) occurs when the mitral valve allows reversal of blood flow from the left ventricle (LV) to the left atrium. The presentation of MR is variable and largely dependent upon etiology, severity, and rate of onset. In acute severe MR, the patient may present in heart failure or cardiogenic shock. In chronic MR, depending on the degree of regurgitation, patients may be asymptomatic and may remain so for many years. As the volume of regurgitation increases, the LV also increases in size. Progressive LV dilation eventually leads to impaired contraction, increased afterload, reduced cardiac output, and, finally, left heart failure. Major factors in management include determining when to start therapy and what kind of intervention is needed. Prognosis in patients with MR varies with the timing of presentation and the severity of associated congenital defects.

Embryology and anatomy

Formation of the atrioventricular valve is completed early in embryologic development. The mitral valve is formed from endocardial cushions that originate both at the atrioventricular orifice and from muscular tissue of the ventricular wall. This process creates the 4 major components of the mitral valve, which are the mitral annulus, the mitral leaflets, the chordae tendineae, and the papillary muscles.

The mitral annulus is derived from the fibrous skeleton of the heart. The mitral valve leaflets (anterior, posterior) consist of collagenous fibrosa and spongiosa peripherally and mucoid myxomatous tissue centrally. The anterior leaflet is one third of the mitral valve and attaches to the mitral annulus, while the posterior leaflet attaches to the posterior lateral free wall of the LV. The chordae tendineae are a complex network of collagenous cordlike structures that extend from the free edges of the mitral valve leaflets to the papillary muscles. These papillary muscles arise from the ventricular wall.

These 4 anatomic components function to allow unobstructed blood flow from the left atrium to the LV during diastole and to maintain competent closure during systole. The leaflets open fully during the early rapid-filling phase of diastole. They begin to close passively as LV pressure and volume increase. Then, the leaflets reopen briefly as atrial contraction occurs, adding additional volume to the LV. During atrial contraction, annular contraction begins, effectively decreasing the circumference of the mitral valve by 20-30% throughout systole. Contraction of the papillary muscles serves to maintain the length of the chordae under the pressure that develops during systole. In the event that one or more of the 4 components is rendered nonfunctional or developmentally abnormal, MR results.

Pathophysiology

Normal blood flow from the left atrium to the LV and, subsequently, to the systemic circulation, is altered in MR. In the presence of MR, blood flows antegrade from the LV into the aorta, and the regurgitant volume flows retrograde from the LV into the left atrium. This causes a proportionate increase in LV ejection volume. The regurgitant fraction reenters the LV, producing left ventricular volume overload. The LV compensates via the Frank-Starling mechanism, resulting in a greater ventricular stroke volume. The volume of the regurgitant fraction depends on several factors, including size of the orifice allowing regurgitation and the pressure gradient between the left ventricle and left atrium. This volume also depends on ventricular systolic pressure; therefore, the regurgitant volume increases in situations that increase afterload, such as hypertension or aortic stenosis.

The natural history and time course of MR is variable, but MR can develop in 3 distinct stages (ie, acute, chronic compensated, chronic decompensated) that are clinically significant. The stages depend on acuity of onset, regurgitant volume, and compliance of the left atrium.

Acute MR stage

Acute MR causes sudden volume overload of the left atrium and LV. Initially, the undilated left atrium restricts the regurgitant volume at the expense of increase in both left atrial and LV end-diastolic pressures.

Although total ventricular stroke volume increases compared to normal, total forward stroke volume usually decreases, thereby lowering cardiac output. In the acute situation, rapidly increasing left atrial pressure results in elevated pulmonary venous pressure causing pulmonary congestion and, eventually, pulmonary edema (see Image 1).

Chronic compensated stage

In this stage, the LV compensates by allowing greater diastolic filling and developing LV enlargement to augment forward stroke volume. More importantly, the left atrium dilates in response to the increased volume. Compensation for the increased volume can occur without resulting in increased pressure in the pulmonary circulation and the right heart. Left atrial compliance decreases the afterload on the LV, while LV dilation and hypertrophy increases contractility. These important changes keep the overall afterload on the left heart normal or unchanged. Although the regurgitant fraction may be high, the larger stroke volume compensates, maintaining a nearly normal forward cardiac output (see Image 2).

Chronic decompensated stage

This stage occurs when the LV is unable to sustain adequate forward cardiac output. As LV contractility begins to decrease, end-systolic volume gradually increases, thereby increasing LV end-diastolic pressure. The resulting increased pressure in the left atrium creates increased afterload, which further impairs LV ejection, thereby creating a repeating cycle. While the end-diastolic and end-systolic volumes increase, pulmonary congestion eventually results if the cause of the MR is left untreated. Although the forward LV ejection fraction is reduced compared to the compensated phase, the overall ejection fraction could remain normal because of a large regurgitant flow.

As the degree of MR worsens, the total ejection fraction falls, indicating increasing ventricular dysfunction. Pulmonary hypertension may develop under long-standing increased pulmonary venous pressure, and, ultimately, it can lead to right heart failure (see Image 3).

CLINICAL

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History

The nature and severity of symptoms in patients with MR relates to etiology, rate of onset and progression, LV function, pulmonary artery pressure, and the presence of preexisting valvular or myocardial diseases.

• Children with minor degrees of MR usually are asymptomatic. With increased amounts of MR, fatigue may be reported, but children can tolerate more severe MR surprisingly better than adults can.
• Once pulmonary hypertension develops, complaints such as tachypnea and dyspnea with light activity become more prominent.
• With the most severe MR, children may experience limited growth and failure to thrive. Hemoptysis can develop during the later stages.
• Children may remain asymptomatic with no complications of MR until the second or third decade of life.
• • An indolent course of MR may be deceptive because of the ability of the heart to compensate for the altered hemodynamics. This occurs because of changes in cardiac pump loading such that increased diastolic filling increases preload, while LV ejection, in part into the left atrium, reduces afterload.
  • By the time symptoms become apparent, serious and irreversible LV dysfunction may have developed.

Physical

Vital signs usually are normal, although heart and respiratory rates may be increased slightly. Patients with mild MR may reveal no signs other than a characteristic apical systolic murmur.

• The cardiac impulse may be displaced to the left, and, in more advanced disease, a double impulse is felt.
• • A left atrial lift is a second impulse resulting from the increased volume that is displaced into the left atrium during systole.
  • The second impulse should be felt near the time of the second heart sound.
  • This sign is most helpful in thin children and young adults because their chest diameters are smaller and their hearts are closer to the chest wall.
  • In patients with severe MR, arterial pulse has been characterized as having a small volume with a sharp upstroke.
• On auscultation, the first heart sound usually is diminished slightly, while the second heart sound usually is split.
• The sound of the typical MR murmur is characterized as blowing and high pitched, and it is loudest over the apex with radiation to the left axilla. The murmur often is pansystolic, beginning immediately after the first heart sound, and it may continue beyond the aortic component of the second heart sound, thus obscuring the murmur. This murmur increases with increased afterload (squatting) and decreases with decreased preload (standing). Occasionally, radiation toward the sternum occurs when posterior leaflet abnormalities are present.
• • Little correlation exists between intensity of the murmur and severity of MR.
  • The murmur occasionally may be confined to late systole only. The degree of MR in these patients usually is mild.
• With more severe MR, a third heart sound and a mid diastolic low frequency murmur may be present, caused by increased ventricular filling.
• When pulmonary hypertension develops, the pulmonary component of the second heart sound becomes louder and occurs earlier (as long as right ventricular function is not significantly impaired), reducing the splitting interval.

Causes

While the pathophysiology resulting from MR is similar throughout all age groups, the specific cause of MR differs. Most MR in the pediatric population is congenital in origin.

• In older adolescent and adult patients, MR is likely to be acquired (see below). In these patients, MR can result from numerous problems, including the following:
• • Infection - Endocarditis and myocarditis
  • Inflammation - Rheumatic heart disease and systemic lupus erythematosus (SLE)
  • Structural disorders - Ischemic heart disease and trauma
• The cause of MR in children may include some causes seen in adults, but MR in children usually is the result of a congenital defect (see below).
• • Most cases of MR result from abnormalities in embryologic development that produce not only MR but other cardiac anomalies as well.
  • Most cases of congenital MR are part of a developmental abnormality rather than an isolated phenomenon, although a few conditions exist in which MR is isolated. These congenital conditions include mitral valve clefts, myxomatous degeneration of the mitral valve, double orifice mitral valve, and anomalous mitral arcade.
• Acute causes of MR are as follows:
• Mitral annulus disorders
  • Infective endocarditis (abscess formation)
  • Trauma (valvular heart surgery)
  • Paravalvular leak resulting from suture interruption (surgical technical problems, infective endocarditis)
• Mitral leaflet disorders
  • Infective endocarditis (perforation or interference with valve closure by vegetation)
  • Trauma (tear during percutaneous mitral balloon valvotomy or penetrating chest injury)
  • Tumors (atrial myxoma)
  • Myxomatous degeneration
  • Systemic lupus erythematosus (Libman-Sacks lesion)
  • Acute rheumatic fever
• Rupture of chordae tendineae
  • Idiopathic, eg, spontaneous
  • Myxomatous degeneration (mitral valve prolapse, Marfan syndrome, Ehlers-Danlos syndrome)
  • Infective endocarditis
  • Acute rheumatic fever
  • Trauma (percutaneous balloon valvuloplasty, blunt chest trauma)
• Papillary muscle disorders
  • Coronary artery disease (causing dysfunction and, rarely, rupture)
  • Acute global LV dysfunction
  • Infiltrative diseases (amyloidosis, sarcoidosis)
  • Trauma
• Chronic causes of MR are as follows:
• Congenital disorders
  • Mitral valve clefts or fenestrations
  • Parachute mitral valve abnormality
  • Part of any associated congenital heart disease (endocardial cushion defects, cardiomyopathy, transposition of the great arteries, anomalous origin of the left coronary artery)
• Inflammatory disorders
  • Rheumatic heart disease
  • Systemic lupus erythematosus
  • Scleroderma
• Degenerative disorders
  • Myxomatous degeneration of mitral valve leaflets (Barlow click-murmur syndrome, prolapsing leaflet, mitral valve prolapse)
  • Marfan syndrome
  • Ehlers-Danlos syndrome
  • Pseudoxanthoma elasticum
  • Calcification or mitral valve annulus
• Infective disorders - Infective endocarditis affecting normal, abnormal, or prosthetic mitral valves
• Structural disorders
  • Ruptured chordae tendineae (spontaneous or secondary to myocardial infarction, trauma, mitral valve prolapse, endocarditis)
  • Rupture or dysfunction or papillary muscle (ischemia, myocardial infarction)
  • Dilation of mitral valve annulus and LV cavity (congestive cardiomyopathies, aneurysmal dilation of the LV)
  • Hypertrophic cardiomyopathy
  • Paravalvular prosthetic leak

DIFFERENTIALS

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WORKUP

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Imaging Studies

• Chest radiography
• • With mild MR, the heart size is normal.
  • With increasing MR, cardiomegaly may develop, and left atrial enlargement becomes apparent. Left atrial dilation caused by chronic rheumatic heart disease often includes radiographically apparent dilation of the left atrial appendage. LV enlargement and pulmonary congestion also may be present.
  • In cases of acute MR, pulmonary venous vasculature markings and pulmonary edema without signs of left atrial enlargement may be increased.
• Echocardiography
• • Echocardiography is the most valuable technique used to evaluate MR. Echocardiography is usually readily available and portable. The 2-dimensional echocardiogram allows depiction of the size of the chambers and assessment of ventricular systolic function, as well as determination of the morphology of the mitral valve, the annulus, and papillary muscles.
  • Color-flow Doppler echocardiography demonstrates duration and direction of the regurgitant flow. Spectral Doppler imaging demonstrates a high-velocity signal across the mitral valve in systole entering retrograde into the left atrium. MR can be seen and evaluated best in the apical 4-chamber and parasternal-long views.
  • Visualizing MR is not difficult. Classifying the severity of MR is another issue. In the adult population, many echocardiographic methods are used, all with varying results. The grading of MR in the pediatric population as mild, moderate, and severe is based on the size and extent of the color-flow Doppler signal into the left atrium. Also, other factors to consider are left atrium and ventricular size and function. In mild MR, the signal is located in the proximal third of the left atrium near the mitral valve. The left atrium is usually not enlarged, and the ventricular function is normal. In moderate MR, the signal is mid cavity, with left atrial dilation and increased ventricular function. With severe MR, the signal reaches the posterior third of the left atrium and the pulmonary veins, and the left atrium and ventricle are usually enlarged, with increased ventricular function.
  • The parasternal long axis view may provide the best images of mitral valve prolapse, while the parasternal short axis view is better for depicting papillary muscle anatomy and leaflet cleft.
• Transesophageal echocardiography (TEE) may be required if further detailed anatomic information is needed. TEE views correlate better with angiographic grading than transthoracic views.
• Echocardiography provides a semiquantitative evaluation of MR, but decisions regarding therapy and possible surgical intervention remain dependent on clinical signs and symptoms (ultimately, left ventricular function).
• Cardiac MRI
• • Cardiac MRI is a newer modality for imaging the heart. Cardiac MRI provides 3-dimensional imaging of the heart and great vessels and is not dependent on acoustic windows, as is echocardiography.
  • Cardiac MRI provides more accurate evaluation of both left and right ventricular size and function.
  • The degree of MR determined by cardiac MRI has not been adequately evaluated. However, velocity flow imaging may potentially provide additional information.

Other Tests

• Electrocardiogram
• • The 12-lead electrocardiogram (ECG) is likely to show normal results in children with mild MR.
  • In more chronic MR, ECG findings demonstrate left atrial and LV enlargement.
  • When pulmonary hypertension is present, ECG also may demonstrate right ventricular hypertrophy.
  • Rhythm changes, such as atrial fibrillation, often are observed in adults but are rare in children.

Procedures

• Evaluation of MR in children usually does not require cardiac catheterization. Some pediatric patients undergo catheterization to evaluate other cardiac defects that may be present.
• • MR is best evaluated using angiography obtained in the right anterior oblique view. Retrograde flow of injected dye demonstrates the degree of MR, which is quantitatively graded (grades I-IV) depending on the level of left atrial opacification (see Table). LV injections obtained via the retrograde approach are preferred to an anterograde approach to prevent the catheter from holding the mitral valve open and creating artefactual MR.
  • To quantitate MR, a combination of angiography and cardiac output measurements must be used. Either thermodilution or the Fick principle helps measure forward cardiac output, while angiography allows determination of total LV output. Keep in mind that tricuspid regurgitation can invalidate the thermodilution method.
    • Subtracting the forward output from total LV output yields the regurgitant fraction. A regurgitant fraction of 0.5 or greater generally is considered clinically significant.
    • The LV ejection fraction may be increased initially; however, as the LV decompensates, the ejection fraction decreases to normal or subnormal values, signifying LV failure. As LV failure develops, LV end-diastolic pressure increases, resulting in an increase in left atrial and pulmonary venous pressure. Increased pulmonary venous pressure is manifested as an increase in pulmonary capillary wedge pressure. At catheterization, the wedge pressure a wave amplitude is increased along with a rapid rise of the v wave. The latter occurs when LV compliance decreases.
• A recent study evaluating MR compared cardiac catheterization to echocardiography (transesophageal, transthoracic) and found no advantage to catheterization in clinical decision making. Cardiac catheterization should be used when noninvasive data are discordant, limited, or differ from the clinical status of the patient. Ventriculography may add new information if more complex congenital cardiac problems are present.
• Estimation of Mitral Regurgitation using Angiography
  
  

  Regurgitation Grade	Angiographic Findings
  1+	Trace amounts of contrast are seen in the left atrium, but amount is insufficient to outline the left atrium.
  2+	Contrast opacifies entire left atrium, but less than that of the LV. Contrast clears quickly within 2-3 beats.
  3+	Contrast opacifies the left atrium and LV equally.
  4+	Contrast opacifies the left atrium more than the LV and progresses to the pulmonary veins.

TREATMENT

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Medical Care

In children, MR tends to progress with age. MR fosters MR because of the repeating cycle described earlier. As a result of this tendency, these patients must be examined regularly even though the MR may be mild. Early treatment of infants and children with MR is primarily medical. Guidelines for treating children are not well defined and are based largely on information derived from adults.

• Depending on the cause of MR, a patient may require medications such as anti-inflammatory agents for rheumatic fever or Kawasaki disease and antibiotics for infective processes. Baseline information, such as a chest radiography, ECG, and echocardiography, should be obtained. Patients with mild MR should have follow-up monitoring at regular intervals. Little change may occur in asymptomatic patients as they age. Primary medical intervention is bacterial endocarditis prophylaxis. For more information, see Antibiotic Prophylactic Regimens for Endocarditis.
• Optimal medical therapy is aimed at increasing systemic cardiac output and decreasing regurgitant flow. No clear guidelines exist regarding when to initiate medical management; however, treatment probably is indicated when the LV begins to dilate.
• • Afterload reduction may be the most beneficial therapy because it reduces work on the heart by decreasing systemic arteriolar resistance, thereby decreasing the regurgitant volume. However, no studies have demonstrated that afterload reduction actually delays (or eliminates) the need for surgery.
  • If the patient develops symptoms, such as dyspnea and exercise intolerance, anticongestive medications (digoxin, diuretics) should be added. By decreasing LV end-diastolic volume, the diameter of the mitral annulus also is decreased, thereby decreasing the regurgitant orifice.
  • Diuretics also are helpful in decreasing the total volume and may alleviate the pulmonary edema and congestion that may be present.
  • Digoxin is useful in patients with left heart failure because it allows the heart to pump more efficiently.
• Acute MR causes a sudden decrease in cardiac output and an increase in left atrial pressure, resulting in pulmonary congestion. Severity of the MR depends on the size of the orifice and the time period over which the MR develops. If the orifice is large, a sudden decrease in systemic blood flow and pressure occurs, and pulmonary edema develops. Decreasing afterload may temporarily relieve these symptoms.
• • Vasodilators, such as nitroprusside, are very effective; however, preexisting hypotension may be exacerbated.
  • Inotropic agents may improve systolic blood pressure. Intra-aortic balloon counterpulsation or immediate surgical intervention (valvuloplasty) may be necessary in severe cases.
  • In patients who stabilize but remain symptomatic, early semielective surgery should be considered to reduce the risk of irreversible ventricular dysfunction.
  • Patients who become asymptomatic with medical therapy can be treated in the same manner as those with chronic MR.
• Patients with chronic MR should receive maintenance doses of afterload agents such as ACE inhibitors, hydralazine, or calcium channel blockers. Diuretics and digoxin also are useful.

Surgical Care

When a patient becomes severely symptomatic (New York Heart Association class III or IV) because of LV failure, the patient should be encouraged to undergo cardiac surgery. Surgical replacement versus repair may be an issue at this time. For children, reconstruction is preferable to avoid the need for anticoagulation therapy. Since the valve is more compliant and pliable in children than in adults, repair often is feasible. By repairing the valve instead of replacing it, the subvalvular apparatus remains intact, helping to preserve LV function. In general, patients should undergo surgery before severe symptoms develop. Operating earlier and repairing the valve improves the chance of normal postoperative function without the associated risks of prosthesis placement. On the other hand, pediatric patients often have associated congenital abnormalities that may dictate the need for valve replacement.

Surgical repair of the regurgitant mitral valve can be classified into 3 major groups depending on the leaflet motion, namely, normal, prolapsing, and restricted. Repair of these conditions can proceed in several ways, depending on the specific abnormality involved.

• If the mitral annulus is dilated, an annuloplasty may be successful in alleviating the degree of regurgitation.
• • The annuloplasty may involve the use of a ring prosthesis.
  • In younger patients (in whom restriction of valve growth is undesirable), resection of a portion of the leaflet and annular plication may be performed.
  • Shortening of the chordae and/or papillary muscles may repair prolapsed leaflets.
  • MR with restricted leaflet motion is observed in parachute and hammock valves and, along with a valvuloplasty, can be improved by incising the valve leaflets at an appropriate location.
• Mitral valve replacement is the final option in the treatment of MR. The choice of which valve to use (mechanical vs bioprosthesis) can be difficult.
• • A mechanical prosthesis has good longevity and performance, but the size of the valve is problematic in neonates and infants. Low-profile valves occupy less space and cause less distortion to the LV outflow tract. The major drawback to mechanical prosthesis is the need for anticoagulation therapy. Since flow through the mitral valve position is at a low velocity, anticoagulation with warfarin is the only long-term option. Warfarin must be administered daily, and the prothrombin time and international normalized ratio (INR) must be monitored closely, at least until a steady state is reached. Even then, regular monitoring of prothrombin time and INR is desirable. Too much warfarin may result in excessive bleeding, while insufficient anticoagulation may lead to thromboembolism. For the older child, contact sports usually are contraindicated because of anticoagulation therapy.
  • Bioprosthetic valves resolve the anticoagulation issue but raise problems of their own. Bioprostheses may degenerate rapidly and may become calcified and dysfunctional as early as 6 months after insertion. Since the anticipated lifespan of a bioprosthetic valve in infants and children is shortened, bioprosthetic valves are less desirable because of the need for early repeat surgery. A bioprosthetic valve may be more desirable for women of childbearing age in view of the teratogenic potential of warfarin in the first trimester of pregnancy and the potential dangers of anticoagulation therapy during delivery.
• Definitive long-term surgical treatment of the child with mitral valve regurgitation continues to be an area that needs further study. Impairment of annular growth and the need for repeated surgical intervention as the child ages continue to be of concern despite current advancements in technology.

Activity

Contact sports are contraindicated in children taking warfarin.

MEDICATION

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ACE inhibitors and diuretics are the mainstay of medical therapy for patients with MR.

Drug Category: Afterload reducers

These agents are used to improve preoperative or postoperative cardiac output. They reduce systemic vascular resistance and increase systemic blood flow resulting from myocardial dysfunction, significant mitral valve insufficiency, or both.

Drug Name	Hydralazine (Apresoline)
Description	Decreases systemic resistance through direct vasodilation of arterioles.
Adult Dose	10 mg PO qid initially; may increase by 10-25 mg/d q3d; not to exceed 300 mg/d
Pediatric Dose	1 mg/kg/d PO divided bid/qid initially; may gradually increase over 1 mo; not to exceed 5-7.5 mg/kg/d
Contraindications	Documented hypersensitivity; mitral valve rheumatic heart disease
Interactions	MAOIs or beta-blockers may increase hydralazine toxicity; pharmacologic effects of hydralazine may be decreased by indomethacin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Hydralazine has been implicated in myocardial infarction; caution in suspected coronary artery disease

Drug Name	Nifedipine (Procardia, Adalat)
Description	Relaxes coronary smooth muscle and produces coronary vasodilation, which in turn improves myocardial oxygen delivery.
Adult Dose	10-30 mg IR cap tid; not to exceed 120-180 mg/d 30-60 mg/d SR tab; not to exceed 90-120 mg/d
Pediatric Dose	0.6-0.9 mg/kg/d PO divided tid/qid
Contraindications	Documented hypersensitivity
Interactions	Caution with coadministration of any agent that can lower BP including beta-blockers and opioids; H2 blockers (eg, cimetidine) may increase toxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause lower extremity edema; allergic hepatitis has occurred but is rare

Drug Name	Nitroprusside (Nitropress)
Description	Afterload-reducing agent used for acute MR. Produces vasodilation and increases inotropic activity of the heart. At higher doses, may exacerbate myocardial ischemia by increasing the heart rate.
Adult Dose	0.3-0.5 mcg/kg/min IV initially; titrate to desired effect by increasing by increments of 0.5 mcg/kg/min; average dose is 1-6 mcg/kg/min Infusion rates >10 mcg/kg/min may lead to cyanide toxicity
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; subaortic stenosis, decreased cerebral perfusion, arteriovenous shunt, coarctation of aorta (eg, compensatory hypertension), and atrial fibrillation or flutter
Interactions	Effects are additive when administered with other hypotensive agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism; in renal or hepatic insufficiency, nitroprusside levels may increase and can cause cyanide toxicity; sodium nitroprusside can lower blood pressure, thus, should be used only in patients with mean arterial pressures >70 mm Hg

Drug Category: Diuretic agents

These agents promote excretion of water and electrolytes by the kidneys. They are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention have resulted in edema or ascites.

Drug Name	Spironolactone (Aldactone)
Description	For management of edema resulting from excessive aldosterone excretion. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.
Adult Dose	25-200 mg/d PO qd or divided bid
Pediatric Dose	1.5-3.5 mg/kg/d PO divided q6-24h
Contraindications	Documented hypersensitivity; anuria, renal failure, or hyperkalemia
Interactions	May decrease effect of anticoagulants; potassium and potassium-sparing diuretics may increase toxicity of spironolactone
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in renal and hepatic impairment

Drug Name	Ethacrynic acid (Edecrin)
Description	Use as a second-line IV diuretic for those with congestive heart failure. Inhibits loop of Henle and proximal and distal convoluted tubule sodium and chloride resorption.
Adult Dose	0.5-1 mg/kg/dose IV; may repeat q8-12h as warranted; not to exceed 100 mg/dose
Pediatric Dose	1 mg/kg IV q8-12h
Contraindications	Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion
Interactions	May cause additive ototoxicity with aminoglycosides or cisplatin; additive hypotensive effects with coadministration of other diuretics or antihypertensives; may cause hypokalemia and increase toxicity of digoxin; may increase anticoagulant effect of warfarin; increases lithium serum levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution with blood dyscrasias and liver or kidney disease; monitor electrolyte, calcium, glucose, uric acid, CO2, creatinine, and BUN levels

Drug Category: Inotropic agents

These are effective medications when cardiac function is slightly decreased or compromised by the amount of MR. Positive inotropic agents increase the force of contraction of the myocardium and are used to treat acute and chronic CHF. Some agents also may increase or decrease the heart rate (ie, positive or negative chronotropic agents), provide vasodilatation, or improve myocardial relaxation. These additional properties influence the choice of drug for specific circumstances. Cardiac glycosides are used predominantly for their inotropic effects.

Drug Name	Milrinone (Primacor)
Description	Bipyridine-positive inotropic agent and vasodilator with little chronotropic activity. Different in mode of action from both digitalis glycosides and catecholamines.
Adult Dose	50 mcg/kg IV loading dose over 10 min, followed by continuous IV infusion at 0.375-0.75 mcg/kg/min
Pediatric Dose	Administer as in adults Although used as DOC in many pediatric ICUs, safety and efficacy are not well established
Contraindications	Documented hypersensitivity
Interactions	Milrinone precipitates in presence of furosemide
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor fluids, electrolyte changes, and renal function during therapy; excessive diuresis may increase potassium loss and predispose patients taking digitalis to arrhythmias; important to correct hypokalemia with potassium supplementation prior to treatment; patients showing excessive decreases in blood pressure should have infusion rates slowed or stopped; previous vigorous diuretic therapy has caused significant decreases in cardiac filling pressure (cautiously administer milrinone and monitor blood pressure, heart rate, and clinical symptomatology)

Drug Category: Anticoagulants

These agents prevent recurrent or ongoing thromboembolic occlusion of the vertebrobasilar circulation. Lifelong anticoagulation therapy is needed in patients with mechanical valves.

FOLLOW-UP

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Further Inpatient Care

• Use medications to decrease the work placed on the heart. IV diuretics can be used. IV inotropes (eg, milrinone) also can be used to treat heart failure.

Further Outpatient Care

• Asymptomatic patients and those with normal chest radiograph, ECG, and echocardiography findings should have follow-up evaluations at regular intervals.
• Patients without severe symptoms can be treated with PO ACE inhibitors (captopril) and Lasix. Digoxin also can be used if symptoms of heart failure are present.

In/Out Patient Meds

• See Treatment.

Complications

• In patients with mechanical prostheses, too much warfarin may result in excessive bleeding, while insufficient anticoagulation may lead to thromboembolism.

Patient Education

• Asymptomatic children with MR require regular examinations because the indolent course of MR may be deceptive as long as the heart is able to compensate for the altered hemodynamics. Patients and families require education regarding specific medications, especially warfarin.
• For excellent patient education resources, visit eMedicine's Heart Center. Also, see eMedicine's patient education article Mitral Valve Prolapse.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Pay attention to all murmurs, and differentiate benign systolic (Still) murmurs from pathologic murmurs.

MULTIMEDIA

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Media file 1:  Acute stage of mitral regurgitation (MR).
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Media type:  Graph

Media file 2:  Chronic compensated stage of mitral regurgitation (MR).
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Media file 3:  Chronic decompensated stage of mitral regurgitation (MR).
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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Article Last Updated: Jun 21, 2006