eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Mitral Valve Insufficiency

Jason T Su, DO, Assistant Professor, Department of Pediatric Cardiology, Primary Children's Medical Center, University of Utah

Updated: Apr 28, 2009

Introduction

Background

Mitral regurgitation (MR) occurs when the mitral valve allows reversal of blood flow from the left ventricle (LV) to the left atrium.¹

The presentation of MR varies and largely depends on 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.²

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, whereas 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 varies, 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 Media file 1).

Acute stage of mitral regurgitation (MR).

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, whereas 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 Media file 2).

Chronic compensated stage of mitral regurgitation (MR).

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. Whereas 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 Media file 3).

Chronic decompensated stage of mitral regurgitation (MR).

Clinical

History

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

• Children with minor degrees of MR are usually 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, whereas 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 are usually normal, although heart and respiratory rates may be slightly increased. 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 is usually slightly diminished, whereas 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 is often 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 is noted 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 is usually 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

Although 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. 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 is usually the result of a congenital defect.
  • 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 are noted 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
    • SLE (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)³
  • Inflammatory disorders
    • Rheumatic heart disease
    • SLE
    • 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)⁴
    • Hypertrophic cardiomyopathy
    • Paravalvular prosthetic leak

Differential Diagnoses

Workup

Imaging Studies

• Chest radiography
  • With mild mitral regurgitation (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. Left ventricle (LV) enlargement and pulmonary congestion may also 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.⁵ 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. Other factors to consider include 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): This may be required if further detailed anatomic information is needed. TEE views correlate better with angiographic grading than transthoracic views.
• Echocardiography: This provides a semiquantitative evaluation of MR, but decisions regarding therapy and possible surgical intervention remain dependent on clinical signs and symptoms (ultimately, LV 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 does not depend on acoustic windows, as echocardiography does.
  • 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

• The 12-lead 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 may also demonstrate right ventricular hypertrophy.
• Rhythm changes, such as atrial fibrillation, are often 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 below). 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.⁶
    • Subtracting the forward output from total LV output yields the regurgitant fraction. A regurgitant fraction of 0.5 or greater is generally 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 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 is as follows:
  • Regurgitation grade of 1+: Trace amounts of contrast are seen in the left atrium, but the amount is insufficient to outline the left atrium.
  • Regurgitation grade of 2+: The contrast opacifies the entire left atrium but less than that of the LV. The contrast clears quickly (within 2-3 beats).
  • Regurgitation grade of 3+: The contrast opacifies the left atrium and LV equally.
  • Regurgitation grade of 4+: The contrast opacifies the left atrium more than the LV and progresses to the pulmonary veins.

Treatment

Medical Care

• 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 are available regarding when to initiate medical management; however, treatment probably is indicated when the left ventricle (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 are also 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. Because the valve is more compliant and pliable in children than in adults, repair is often 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.⁷ 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.⁸ 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. Because 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

ACE inhibitors and diuretics are the mainstay of medical therapy for patients with mitral regurgitation (MR).

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.

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.
By decreasing the systemic blood pressure, ACE inhibitors decrease the amount of work placed on the heart. The regurgitant fraction also is decreased because of the lower systemic blood pressure.

Dosing

Adult

6.25-12.5 mg PO tid 1 h ac; not to exceed 150 mg tid

Pediatric

Neonates: 0.05-0.1 mg/kg/dose PO q8h 1 h ac
Children: 0.3-0.5 mg/kg/dose PO q8h 1 h ac; may titrate upward; not to exceed 6 mg/kg/d

Interactions

NSAIDs may reduce hypotensive effects of captopril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases captopril levels; probenecid may increase captopril levels; hypotensive effects of ACE inhibitors may be enhanced when administered concurrently with diuretics

Contraindications

Documented hypersensitivity; renal impairment

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Category D in second and third trimester of pregnancy; caution in renal impairment, valvular stenosis, or severe congestive heart failure

Hydralazine (Apresoline)

Decreases systemic resistance through direct vasodilation of arterioles.

Dosing

Adult

10 mg PO qid initially; may increase by 10-25 mg/d q3d; not to exceed 300 mg/d

Pediatric

1 mg/kg/d PO divided bid/qid initially; may gradually increase over 1 mo; not to exceed 5-7.5 mg/kg/d

Interactions

MAOIs or beta-blockers may increase hydralazine toxicity; pharmacologic effects of hydralazine may be decreased by indomethacin

Contraindications

Documented hypersensitivity; mitral valve rheumatic heart disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hydralazine has been implicated in myocardial infarction; caution in suspected coronary artery disease

Nifedipine (Procardia, Adalat)

Relaxes coronary smooth muscle and produces coronary vasodilation, which in turn improves myocardial oxygen delivery.

Dosing

Adult

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

0.6-0.9 mg/kg/d PO divided tid/qid

Interactions

Caution with coadministration of any agent that can lower BP including beta-blockers and opioids; H2 blockers (eg, cimetidine) may increase toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause lower extremity edema; allergic hepatitis has occurred but is rare

Nitroprusside (Nitropress)

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.

Dosing

Adult

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

Administer as in adults

Interactions

Effects are additive when administered with other hypotensive agents

Contraindications

Documented hypersensitivity; subaortic stenosis, decreased cerebral perfusion, arteriovenous shunt, coarctation of aorta (eg, compensatory hypertension), and atrial fibrillation or flutter

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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

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.

Furosemide (Lasix)

Increases excretion of water by interfering with chloride-binding cotransport system, which in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Dose must be individualized. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after the previous dose, until desired diuresis occurs. When treating infants, titrate using increments of 1 mg/kg/dose until a satisfactory effect is achieved.

Dosing

Adult

20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states

Pediatric

1-2 mg/kg/dose PO; not to exceed 6 mg/kg/dose; do not administer more frequently than q6h
Alternatively, 1 mg/kg IV/IM slowly under close supervision; not to exceed 6 mg/kg

Interactions

Metformin decreases furosemide concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when administered concurrently; increased plasma lithium levels and toxicity are possible when administered concurrently

Contraindications

Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte, CO₂, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Spironolactone (Aldactone)

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.

Dosing

Adult

25-200 mg/d PO qd or divided bid

Pediatric

1.5-3.5 mg/kg/d PO divided q6-24h

Interactions

May decrease effect of anticoagulants; potassium and potassium-sparing diuretics may increase toxicity of spironolactone

Contraindications

Documented hypersensitivity; anuria, renal failure, or hyperkalemia

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal and hepatic impairment

Ethacrynic acid (Edecrin)

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.

Dosing

Adult

0.5-1 mg/kg/dose IV; may repeat q8-12h as warranted; not to exceed 100 mg/dose

Pediatric

1 mg/kg IV q8-12h

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

Contraindications

Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution with blood dyscrasias and liver or kidney disease; monitor electrolyte, calcium, glucose, uric acid, CO₂, creatinine, and BUN levels

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 congestive heart failure (CHF). Some agents may also 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.

Digoxin (Lanoxin)

Cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Its indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.

Dosing

Adult

0.125-0.375 mg/d PO

Pediatric

Total digitalizing dose (TDD):
5-10 years: 20-35 mcg/kg PO
>10 years: 10-15 mcg/kg PO
May accomplish digitalization by administering one half of TDD in first dose, followed by 2 doses that are one fourth of TDD administered at 8- to 12-h intervals
Maintenance dose:
Use 25-35% of TDD
Neonates and infants: 5-10 mcg/kg/d PO

Interactions

Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, PO amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil
Medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, PO colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid

Contraindications

Documented hypersensitivity; beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, and carotid sinus syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypokalemia may reduce positive inotropic effect of digitalis; IV calcium may produce arrhythmias in patients taking digitalis; hypercalcemia predisposes patients to digitalis toxicity; hypocalcemia can make digoxin ineffective until serum calcium levels are in reference range; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis

Milrinone (Primacor)

Bipyridine-positive inotropic agent and vasodilator with little chronotropic activity. Different in mode of action from both digitalis glycosides and catecholamines.

Dosing

Adult

50 mcg/kg IV loading dose over 10 min, followed by continuous IV infusion at 0.375-0.75 mcg/kg/min

Pediatric

Administer as in adults
Although used as DOC in many pediatric ICUs, safety and efficacy are not well established

Interactions

Milrinone precipitates in presence of furosemide

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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)

Anticoagulants

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

Warfarin (Coumadin)

Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain an INR in the range of 2-3.

Dosing

Adult

5-15 mg/d PO for 2-5 d; adjust dose according to desired INR

Pediatric

Administer weight-based dose of 0.05-0.34 mg/kg/d PO; adjust dose according to desired INR

Interactions

Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, or sucralfate
Medications that may increase anticoagulant effects of warfarin include PO antibiotics, capecitabine, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, or sulindac

Contraindications

Documented hypersensitivity; severe liver or kidney disease; open wounds; GI tract ulcers

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis

Follow-up

Further Inpatient Care

• In mitral valve insufficiency, use medications to decrease the work placed on the heart. Intravenous diuretics can be used. Intravenous inotropes (eg, milrinone) can also 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 oral ACE inhibitors (captopril) and Lasix. Digoxin can also be used if symptoms of heart failure are present.

Inpatient & Outpatient Medications

• See Treatment.

Complications

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

Patient Education

• Asymptomatic children with mitral regurgitation (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

Medicolegal Pitfalls

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

Multimedia

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

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

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

References

1. Ahmed MI, McGiffin DC, O'Rourke RA, Dell'Italia LJ. Mitral regurgitation. Curr Probl Cardiol. Mar 2009;34(3):93-136. [Medline].

2. Rahimtoola SH. The mitral valve is a complex structure. Foreword. Curr Probl Cardiol. Mar 2009;34(3):89. [Medline].

3. Park SM, Park SW, Casaclang-Verzosa G, et al. Diastolic dysfunction and left atrial enlargement as contributing factors to functional mitral regurgitation in dilated cardiomyopathy: data from the Acorn trial. Am Heart J. Apr 2009;157(4):762.e3-10. [Medline].

4. Pederzolli N, Agostini F, Fiorani V, et al. Postendocarditis mitral valve aneurysm. J Cardiovasc Med (Hagerstown). Mar 2009;10(3):259-60. [Medline].

5. Little SH, Pirat B, Kumar R, et al. Three-dimensional color Doppler echocardiography for direct measurement of vena contracta area in mitral regurgitation: in vitro validation and clinical experience. JACC Cardiovasc Imaging. Nov 2008;1(6):695-704. [Medline].

6. Calafiore AM, Gallina S, Iaco AL, et al. Mitral valve surgery for functional mitral regurgitation: should moderate-or-more tricuspid regurgitation be treated? a propensity score analysis. Ann Thorac Surg. Mar 2009;87(3):698-703. [Medline].

7. Wan CK, Suri RM, Li Z, et al. Management of moderate functional mitral regurgitation at the time of aortic valve replacement: is concomitant mitral valve repair necessary?. J Thorac Cardiovasc Surg. Mar 2009;137(3):635-640.e1. [Medline].

8. Bernal JM, Gutierrez F, Farinas MC, et al. Use of mitral homograft to support a mechanical valve prosthesis: a feasible solution for recurrent mitral valve dysfunction. J Thorac Cardiovasc Surg. Mar 2009;137(3):762-3. [Medline].

9. Anderson RH, Wilcox BR. The anatomy of the mitral valve. In: Wells FC, Shapiro LM, eds. Mitral Valve Disease. 2^nd ed. Butterworth-Heinemann; 1996:4-13.

10. Barlow JB. Mitral regurgitation. In: Perspectives on the Mitral Valve. FA Davis Co; 1987:113-31.

11. Carabello BA. Mitral valve regurgitation. Curr Probl Cardiol. Apr 1998;23(4):202-41. [Medline].

12. Carpentier A. Congenital malformations of the mitral valve. In: Stark J, de Laval M, eds. Surgery for Congenital Heart Defects. WB Saunders Co; 1983:467-82.

13. Dunn JM. Porcine valve durability in children. Ann Thorac Surg. Oct 1981;32(4):357-68. [Medline].

14. Eckberg DL, Gault JH, Bouchard RL, et al. Mechanics of left ventricular contraction in chronic severe mitral regurgitation. Circulation. Jun 1973;47(6):1252-9. [Medline].

15. Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, et al. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med. Mar 3 2005;352(9):875-83. [Medline].

16. Kolibash AJ Jr, Kilman JW, Bush CA, et al. Evidence for progression from mild to severe mitral regurgitation in mitral valve prolapse. Am J Cardiol. Oct 1 1986;58(9):762-7. [Medline].

17. Kon MW, Myerson SG, Moat NE, Pennell DJ. Quantification of regurgitant fraction in mitral regurgitation by cardiovascular magnetic resonance: comparison of techniques. J Heart Valve Dis. Jul 2004;13(4):600-7. [Medline].

18. Krivokapich J. Echocardiography in valvular heart disease. Curr Opin Cardiol. Mar 1994;9(2):158-63. [Medline].

19. Magovern JH, Moore GW, Hutchins GM. Development of the atrioventricular valve region in the human embryo. Anat Rec. Jun 1986;215(2):167-81. [Medline].

20. Perloff JK, Roberts WC. The mitral apparatus. Functional anatomy of mitral regurgitation. Circulation. Aug 1972;46(2):227-39. [Medline].

21. Shimoyama H, Sabbah HN, Rosman H, et al. Effects of long-term therapy with enalapril on severity of functional mitral regurgitation in dogs with moderate heart failure. J Am Coll Cardiol. Mar 1 1995;25(3):768-72. [Medline].

22. Skoularigis J, Sinovich V, Joubert G, Sareli P. Evaluation of the long-term results of mitral valve repair in 254 young patients with rheumatic mitral regurgitation. Circulation. Nov 1994;90(5 Pt 2):II167-74. [Medline].

23. Tribouilloy C, Shen WF, Leborgne L, et al. Comparative value of Doppler echocardiography and cardiac catheterization for management decision-making in patients with left-sided valvular regurgitation. Eur Heart J. Feb 1996;17(2):272-80. [Medline].

Keywords

mitral valve insufficiency, mitral valve regurgitation, mitral regurgitation, MR, heart defect, congential heart defect, acquired heart defect, mitral valve defect, cardiomyopathy, cardiac disease, cardiac defect, left-sided heart disease, heart failure, pulmonary edema, pulmonary congestion, pulmonary hypertension, failure to thrive, endocarditis, myocarditis, rheumatic heart disease, systemic lupus erythematosus, SLE, ischemic, mitral valve prolapse, Marfan syndrome, Ehlers-Danlos syndrome, coronary artery disease, amyloidosis, sarcoidosis, cardiomyopathy, transposition of the great arteries, anomalous origin of the left coronary artery, scleroderma, hypertrophic cardiomyopathy, treatment, diagnosis

Contributor Information and Disclosures

Author

Jason T Su, DO, Assistant Professor, Department of Pediatric Cardiology, Primary Children's Medical Center, University of Utah
Jason T Su, DO is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

Ira H Gessner, MD, Professor Emeritus, Pediatric Cardiology
Ira H Gessner, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, American Pediatric Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Julian M Stewart, MD, PhD, Associate Chairman of Pediatrics, Director, Center for Hypotension, Westchester Medical Center; Professor of Pediatrics and Physiology, New York Medical College
Julian M Stewart, MD, PhD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

CME Editor

Gilbert Z Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College; Consulting Staff, Department of Pediatrics, Sound Shore Medical Center
Gilbert Z Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD, Professor of Pediatrics, Division of Cardiology, Medical College of Wisconsin; Chief of Pediatric Cardiology, Medical Director of Pediatric Heart Transplant Program, Medical Director of The Heart Center, Children's Hospital of Wisconsin
Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

• Relevant clinical guidelines include the following:
  • Guidelines on the management of valvular heart disease
  • American College of Cardiology Foundation/American Heart Association 2005 guideline update for the diagnosis and management of chronic heart failure in the adult
  • American College of Cardiology/American Heart Association 2006 guidelines for the management of patients with valvular heart disease
• Relevant clinical trials include the following:
  • Pivotal Study of a Percutaneous Mitral Valve Repair System
  • Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation
  • Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting (CABG) Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation
• Related eMedicine topics include the following:
  • Mitral Regurgitation (Radiology)
  • Mitral Regurgitation (Cardiology)
  • Mitral Stenosis, Congenital
  • Tricuspid Regurgitation
  • Rheumatic Heart Disease
  • Mitral Valve Prolapse
  • Mitral Stenosis

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