Pediatric Mitral Regurgitation (Mitral Valve Insufficiency)

Mitral regurgitation (MR) (also known as mitral valve insufficiency) occurs when the mitral valve allows reversal of blood flow from the left ventricle (LV) to the left atrium.[1]

The presentation of mitral regurgitation varies and largely depends on its etiology, severity, and rate of onset. In acute severe mitral regurgitation, patients may present in heart failure or cardiogenic shock. In chronic mitral regurgitation, 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 dilatation eventually leads to impaired contraction, increased afterload, reduced cardiac output, and, finally, left heart failure.

Major factors in management of mitral regurgitation include determining when to start therapy and what type of intervention is needed. Prognosis in patients with mitral regurgitation varies with the timing of the presentation and the severity of the associated congenital defects.

Formation of the atrioventricular valve is completed early in embryologic development. The mitral valve is formed both from endocardial cushions that originate at the atrioventricular orifice and from muscular tissue of the ventricular wall. This process creates the four 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, which is discontinuous posteriorly, thus increasing risk for posterior annular dilatation. The mitral valve leaflets (anterior and 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 left ventricle (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. There are two papillary muscles; both arise from the ventricular free wall. Hence, ventricular geometry can affect the function of the papillary muscles.[3]

These four anatomic components function to allow unobstructed blood flow from the left atrium to the LV during diastole and to maintain competent closure during ventricular 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 four components is rendered nonfunctional or developmentally abnormal, mitral regurgitation (mitral valve insufficiency) results.

Although the pathophysiology resulting from mitral regurgitation (MR) (mitral valve insufficiency) is similar throughout all age groups, the specific cause of mitral regurgitation differs with age.

Normal blood flow from the left atrium to the left ventricle (LV) and, subsequently, to the systemic circulation, is altered in mitral regurgitation. In the presence of mitral regurgitation, as the 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 LV 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 the size of the orifice allowing regurgitation and the pressure gradient between the LV and left atrium. This volume also depends on the 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 mitral regurgitation varies, but mitral regurgitation can develop in three 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 mitral regurgitation stage

Acute mitral regurgitation 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 the image below).

Chronic compensated stage

In the chronic compensated 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 dilatation 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 the image below).

Chronic decompensated stage

The chronic decompensated 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 mitral regurgitation 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 mitral regurgitation 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 the image below).

A study by Kalfa et al indicated that in infants and children with severe mitral regurgitation (MR) (mitral valve insufficiency), the mitral valve can be satisfactorily repaired using a standardized, reproducible surgical treatment strategy that includes leaflet debridement, annuloplasty, and leaflet augmentation.[4] The study, of 106 patients younger than 18 years, found that at last follow-up (mean period of 3.9 years), the rate of mortality was 4.5%; recurrent mitral regurgitation, 17%; reoperation, 23%; and valve replacement, 5.5%. The investigators also found that a regurgitation etiology associated with left ventricular outflow tract obstruction was the most important independent risk factor for recurrent regurgitation, reoperation, and valve replacement, although associated preoperative mitral stenosis and young age were also independent predictors for these.[4]

Complications

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

Asymptomatic children with mitral regurgitation (MR) (mitral valve insufficiency) require regular examinations because the indolent course of mitral regurgitation 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 patient education resources, see the Heart Health Center, as well as Mitral Valve Prolapse.

The nature and severity of symptoms in patients with mitral regurgitation (MR) (mitral valve insufficiency) 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 mitral regurgitation are usually asymptomatic. With increased amounts of mitral regurgitation, fatigue may be reported, but, surprisingly, children can tolerate more severe mitral regurgitation better than adults can. Once pulmonary hypertension develops, complaints such as tachypnea and dyspnea with light activity become more prominent. With the most severe mitral regurgitation, children may experience limited growth and failure to thrive. Hemoptysis can develop during the later stages.

Children may also remain asymptomatic, with no complications of mitral regurgitation until the second or third decade of life.

An indolent course of mitral regurgitation may be deceptive because of the ability of the heart to compensate for the altered hemodynamics. This occurs due to 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.

Vital signs

Vital signs are usually normal in those with mild regurgitation. With increasing severity of mitral regurgitation (MR) (mitral valve insufficiency), heart and respiratory rates may be increased. In patients with severe mitral regurgitation, arterial pulse has been characterized as having a small volume with a sharp upstroke.

Rarely, irregular pulse may be indicative of associated atrial fibrillation.

Cardiac examination

Apical impulse

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. The cardiac impulse may be displaced to the left, and, in more advanced disease, a double impulse is felt.

Heart sounds

Upon auscultation, the first heart sound is usually slightly diminished, whereas the second heart sound is usually split. With more severe mitral regurgitation, 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.

An ejection systolic click may be present due to mitral valve prolapse.

Murmur

Patients with mild mitral regurgitation may reveal no signs other than a characteristic apical systolic murmur. The mitral regurgitation 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 second heart sound. 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 the intensity of the murmur and the severity of the mitral regurgitation. The murmur occasionally may be confined to late systole only. The degree of mitral regurgitation in these patients is usually mild.

Other physical findings

Congestive heart failure with pulmonary edema can occur with significant mitral regurgitation and pulmonary findings may be consistent with it. Compression of the left main bronchus due to left atrial enlargement can cause ipsilateral wheezing and lung collapse. Significant and sustained mitral regurgitation can be associated with endocarditis and thromboembolism and have the associated findings.

The first classification of mitral regurgitation (MR) (mitral valve insufficiency) is based on the etiology (congenital vs acquired).

Congenital

Congenital cardiac malformation: Most mitral regurgitation in the pediatric population is congenital in origin secondary to a deformed or dysplastic valve.

• Isolated mitral valve defects: Mitral valve clefts, fenestrations or perforations, double orifice mitral valve, arcade mitral valve, hammock mitral valve, abnormal chordal tissue or insertion, absent or hypoplastic leaflets, accessory leaflets

• Associated with other congenital heart defects: Endocardial cushion defects (atrioventricular septal defects), transposition of the great arteries, anomalous origin of the left coronary artery

Degenerative disease: Myxomatous degeneration of the mitral valve is usually progressive.

Acquired

In older adolescent and adult patients, mitral regurgitation is likely to be acquired. In these patients, mitral regurgitation can result from numerous problems, including the following:

• Infection: Endocarditis and myocarditis

• Inflammation: Rheumatic heart disease, Kawasaki disease, Sweet syndrome and systemic lupus erythematosus

• Structural disorders: Ischemic heart disease and trauma

• Ischemic: Anomalous origin of the left coronary artery, perinatal asphyxia, myocardial infarction

The second classification of mitral regurgitation (MR) (mitral valve insufficiency) is based on anatomy.

Mitral annulus disorders

• Infective endocarditis: Abscess formation

• Trauma: Valvular heart surgery

• Paravalvular leak resulting from suture interruption: Surgical technical problems, infective endocarditis

• Cardiomyopathy: Annular dilatation

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

Disorder of chordae tendineae

• Idiopathic (eg, spontaneous)

• Degenerative disease: Mitral valve prolapse, Marfan syndrome, Ehlers-Danlos syndrome

• Infective endocarditis

• Acute and chronic rheumatic fever

• Trauma: Percutaneous balloon valvuloplasty, blunt chest trauma

Papillary muscle disorders

• Coronary artery disease (causing dysfunction and, rarely, rupture)

• Acute global left ventricular dysfunction

• Infiltrative diseases: Amyloidosis, sarcoidosis

• Trauma

• Tumors

The third classification of mitral regurgitation (MR) (mitral valve insufficiency) is based on whether the disease is acute or chronic.

Acute causes

• Traumatic (eg, percutaneous balloon valvuloplasty, blunt chest trauma)

• Ischemic (eg, perinatal asphyxia, anomalous origin of left coronary artery from pulmonary artery, myocardial infarction)

• Neonatal (eg, perinatal asphyxia)

• Infective (eg, infective endocarditis, myocarditis)

Chronic causes

• Congenital disorders: Mitral valve clefts or fenestrations, parachute mitral valve abnormality, part of any associated congenital heart disease (endocardial cushion defects, transposition of the great arteries, anomalous origin of the left coronary artery)[5]

• Inflammatory disorders: Rheumatic heart disease, Kawasaki 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 of mitral valve annulus

• Infective disorders: Infective endocarditis, myocarditis

• Cardiomyopathy: Dilated cardiomyopathy (dilation of mitral valve annulus and left ventricular [LV] cavity [congestive cardiomyopathies, aneurysmal dilation of the LV]),[6]  hypertrophic cardiomyopathy, restrictive cardiomyopathy, noncompaction cardiomyopathy

The fourth classification of mitral regurgitation (MR) (mitral valve insufficiency) is based on mitral valve dysfunction as elucidated by Carpentier and colleagues.[7]

• Type I: Normal leaflet and chordal motion (eg, fenestrations, clefts, perforations in the leaflets)

• Type II: Leaflet prolapse with excessive chordal motion above annulus (eg, mitral valve prolapse)

• Type III: Restrictive leaflet or chordal motion (eg, parachute mitral valve)

Chest radiography

With mild mitral regurgitation (MR) (mitral valve insufficiency), the heart size is normal.

With increasing mitral regurgitation, cardiomegaly may develop, and left atrial enlargement becomes apparent. Left atrial dilatation caused by chronic rheumatic heart disease often includes radiographically apparent dilatation of the left atrial appendage. Left ventricular (LV) enlargement and pulmonary congestion may also be present.

In cases of acute mitral regurgitation, pulmonary venous vasculature markings may be increased, and pulmonary edema may be seen without signs of left atrial enlargement.

Left lung atelectasis and hyperinflation may be visible due to compression of the left main bronchus by the enlarged left atrium.

Echocardiography

Transthoracic echocardiography (TTE)

Echocardiography is the most valuable technique used to evaluate mitral regurgitation. This imaging modality is usually readily available and portable. Knowledge of the mitral valve apparatus, including the labeling of the scallops of each of the two valve leaflets is essential. An understanding of the anatomy from a surgeon's perspective is needed to explain the findings.

Two-dimensional (2-D) echocardiography allows depiction of the size of the chambers and assessment of the ventricular systolic function, as well as determination of the morphology of the mitral valve leaflets, the annulus, chordal tissue, and papillary muscles. The parasternal long-axis view may provide the best images of mitral valve prolapse, whereas the parasternal short-axis view is better for depicting papillary muscle anatomy and leaflet cleft. The apical four-chamber view is valuable in the evaluation of mitral valve function.

M-mode assessment of cardiac function is extremely important. Cardiac function should be carefully evaluated in mitral regurgitation; different techniques can be used to assess the LV function, including 2-D, three-dimensional (3-D), tissue Doppler, and strain imaging.

The LV function should be hypernormal, indicating a preserved myocardial function with mitral regurgitation. In the presence of normal or mildly depressed function, one should expect myocardial failure postoperatively. In cases of acute rheumatic fever, mitral valve function may return to normal as the inflammation subsides and, indeed, mitral stenosis may develop. Scalloping of the mitral leaflets can occur in mitral valve prolapse and can be seen using M-mode. In addition, the ventricular dimensions should be measured and followed for LV enlargement. LV hypertrophy can also be determined and may be present in hypertrophic cardiomyopathy with mitral regurgitation.

Factors that appear to be associated with early postoperative LV dysfunction after repair of mitral valve regurgitation include lower global circumferential strain magnitude as well as lower global circumferential strain rate magnitude; thus, strain measurements may aid clinicians in determining the timing of pediatric surgical repair.[8]

Color-flow Doppler echocardiography demonstrates the width and direction of the regurgitant flow.[9] The degree of regurgitation may be underestimated if the jet hugs the walls of the atrium. Furthermore, because the structures are 3-D, multiple views and scans must be performed with optimal transducer frequency to determine the entire regurgitant jet.

Spectral Doppler imaging demonstrates a high-velocity signal across the mitral valve in systole entering retrograde into the left atrium. Mitral regurgitation can be seen and evaluated best in the apical four-chamber and parasternal long views. Concomitant mitral stenosis should also be determined. The peak velocity of mitral regurgitation can be used to calculate several other parameters, including LV contractility (ie, dP/dT).

Visualizing mitral regurgitation is not as difficult as classifying the severity. In adults, many echocardiographic methods are used with varying results. The grading of mitral regurgitation in the pediatric population as mild, moderate, and severe is based on the size and extent of the color-flow Doppler signal (jet area) into the left atrium (left atrial area).

Other factors to consider include left atrium and ventricular size and function. In mild mitral regurgitation, 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 mitral regurgitation, the signal extends to mid cavity, with left atrial dilatation and increased ventricular function. With severe mitral regurgitation, 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 shortening fraction. Other techniques useful in quantification include measurement of vena contracta, proximal isovelocity surface area (PISA), pulmonary vein flow reversal, and regurgitant fraction.

Transesophageal echocardiography (TEE)

TEE may be required if further detailed anatomic information is needed. TEE views correlate better with angiographic grading than transthoracic views. In addition, intraoperative TEE is essential in evaluating mitral valve surgery.

3-D echocardiography

3-D echocardiography provides an excellent anatomic evaluation of the mitral valve and helps clinicians with making decisions regarding therapy and possible surgical intervention.

Cardiac magnetic resonance imaging (MRI)

Cardiac MRI is a relatively newer modality for imaging the heart. Cardiac MRI provides 3-D imaging of the heart and great vessels and does not depend on acoustic windows, as echocardiography does. This modality provides more accurate evaluation of both the left and right ventricular size and function.

The degree of mitral regurgitation determined by cardiac MRI has not been adequately evaluated. However, velocity flow imaging may potentially provide additional information.

Electrocardiography

The 12-lead electrocardiogram (ECG) is likely to show normal results in children with mild mitral regurgitation (MR) (mitral valve insufficiency).

In more chronic mitral regurgitation, ECG findings demonstrate left atrial and left ventricular 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.

Evaluation of mitral regurgitation (MR) (mitral valve insufficiency) in children usually does not require cardiac catheterization. Some pediatric patients undergo catheterization to evaluate other cardiac defects that may be present.

Mitral regurgitation is best evaluated using angiography obtained in the right anterior oblique view. Retrograde flow of injected dye demonstrates the degree of mitral regurgitation, 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 artifactual mitral regurgitation.

To quantitate mitral regurgitation, 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.[10]

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 mitral regurgitation 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.

Grading 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.

In mitral regurgitation (MR) (mitral valve insufficiency), administer medications to decrease the work placed on the heart; afterload-reducing medications are most useful in the management of these cases. Intravenous diuretics can be given. Intravenous inotropes (eg, milrinone) can also be used to treat heart failure.

In children, mitral regurgitation (MR) (mitral valve insufficiency) tends to progress with age. Mitral regurgitation fosters yet more mitral regurgitation because of the repeating cycle described earlier in Pathophysiology. As a result of this tendency, these patients must be regularly examined even though the mitral regurgitation may be mild. Early treatment of infants and children with mitral regurgitation is primarily medical. Guidelines for treating children are not well defined and are based largely on information derived from adult studies.

Depending on the cause of mitral regurgitation, 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 chest radiography, electrocardiography (ECG), and echocardiography, should be obtained. Patients with mild mitral regurgitation 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, few 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 mitral regurgitation causes a sudden decrease in cardiac output and an increase in left atrial pressure, resulting in pulmonary congestion. Severity of the mitral regurgitation depends on the size of the orifice and the time period over which the mitral regurgitation 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. Surgical repair of mitral regurgitation may also alleviate abnormal airway and respiratory tissue mechanics, but residual postoperative tissue stiffening may persist for weeks and contribute to sustained pulmonary impairment.[11]

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 semi-elective 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 mitral regurgitation.

Patients with chronic mitral regurgitation should receive maintenance doses of afterload agents such as angiotensin-converting enzyme inhibitors (ACEIs), hydralazine, or calcium channel blockers. Diuretics and digoxin also are useful.

Anticoagulation may be needed if there is diminished LV function, atrial fibrillation, or evidence of thromboembolism.

Consultations

Consultation with a geneticist is indicated if associated dysmorphism is noted, because many of the syndromes are associated with mitral valve prolapse and mitral regurgitation. Trisomy 21 may be associated with mitral valve cleft.

Activity

Contact sports are contraindicated in children taking warfarin.

Outpatient care

Asymptomatic patients and those with normal findings on chest radiography, ECG, and echocardiography should have follow-up evaluations at regular intervals.

Patients without severe symptoms can be treated with oral ACEIs (captopril, enalapril) and furosemide. Digoxin can also be used if symptoms of heart failure are present.

When a patient becomes severely symptomatic (New York Heart Association class III or IV) because of left ventricular (LV) failure, they 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.

Conservative valve surgery, when feasible, appears to be the best surgical option in pediatric patients with rheumatic heart disease.[12] Even in cases of rheumatic lesions in which the primary lesion was mitral stenosis, and despite a higher reoperative rate, rheumatic mitral valve repair appears to have similar outcomes to those from mitral valve replacement, with the added benefit of avoiding anticoagulation.[13] When conservative management is not possible or fails, mechanical valve replacement should be considered.[12] The specific surgical techniques for treatment of mitral regurgitation must be individualized to the patient, with the aim of achieving proper valve function.[14]

Note, however, that pediatric patients often have associated congenital abnormalities that may dictate the need for valve replacement. Infants and children with congenital mitral regurgitation due to restricted leaflet motion can undergo successful mitral valve reconstruction with several modified repair techniques based on the valve morphology.[15] In future transcatheter management, mitral valve clips may be a therapeutic option.

Surgical repair of the regurgitant mitral valve can be classified into three major groups depending on the leaflet motion: 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 address prolapsed leaflets. Lengthening may be required in cases where there are short chordae

Mitral regurgitation 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.

Quadrilateral resection of a prolapsing leaflet with sliding annuloplasty may be helpful in cases with mitral valve prolapse

Edge-to-edge (E-to-E) mitral valve repair is helpful in some cases in which an apposition suture is placed in the center of the anterior and posterior leaflets, producing a double orifice

Papillary muscle surgery may also be beneficial in certain cases

Mitral valve replacement is the final option in the treatment of mitral regurgitation.[16] The choice of which valve to use (mechanical vs bioprosthesis) can be difficult. Some studies indicate a preference toward the use of bioprosthetic valves in children aged 15 years and older.[17]

A mechanical prosthesis has good longevity and performance, but the size of the valve is problematic in neonates and infants.[18] Low-profile valves occupy less space and cause less distortion to the LV outflow tract. The major drawback to mechanical prostheses is the need for anticoagulation therapy. Because 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, whereas insufficient anticoagulation may lead to thromboembolism. For older children, 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 they 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, and thus there is a need for early repeat surgery, bioprosthetic valves are less desirable than their mechanical counterparts. However, 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.

Rao et al examined the issue with valve calcification and dysfunction with bioprosthetic valves and concluded that porcine heterografts should not be inserted in children aged 15 years and younger.[17] Of the 168 mitral valves replaced during a 7-year period, 54 were porcine heterografts and 114 were mechanical valves. These were divided into four groups: mechanical valves in children aged 15 years and younger, mechanical valves in patients older than 15 years, porcine heterografts in children aged 15 years and younger, and porcine heterografts in patients older than 15 years. Five and 9-year valve survival rates were lowest with porcine heterografts in children 15 years and younger.[17]

Definitive long-term surgical treatment of children 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 children age continue to be of concern despite current advancements in technology.

Percutaneous management techniques are being developed; these are mostly useful in adults and, perhaps, in adolescents. Mitral annular constricting devices may be implanted in the coronary sinus; because of the close proximity to the mitral annulus, the geometry of the mitral valve is altered, resulting in reduction of mitral valve regurgitation.[19, 20] Another approach is percutaneous implantation of the Evalve MitraClip device under transesophageal echocardiographic guidance. Results from clinical trials (EVEREST I) appear to be encouraging.[21, 22]

Percutaneous implantation of mitral valves has been studied in experimental animal models with reasonable success. More recently, human application has been introduced; however, larger studies and follow-up results are necessary before adoption for routine clinical use.

The American College of Cardiology (ACC) and American Heart Association (AHA) released their updated recommendations on managing valvular heart disease in December 2020.[23, 24] Key messages are outlined below.

Valvular heart disease (VHD) stages (stages A-D) in patients should be classified based on symptoms, valve anatomy, severity of valve dysfunction, and response of the ventricle and pulmonary circulation.

When evaluating patients with VHD, findings from the history and physical examination (PE) should be correlated with those from noninvasive testing (ie, electrocardiography [ECG], chest x-ray, transthoracic echocardiography [TTE]). If conflict exists between results on the PE and that of initial noninvasive studies, consider obtaining further noninvasive (computed tomography [CT], cardiac magnetic resonance imaging [CMRI], stress testing) or invasive (transesophageal echocardiography [TEE], cardiac catherization) studies to decide the optimal treatment strategy.

In the setting of VHD and atrial fibrillation (AF) (except for patients with rheumatic mitral stenosis [MS] or a mechanical prosthesis), the decision to use oral anticoagulation with either a vitamin K antagonist (VKA) or a non-VKA anticoagulant to prevent thromboembolic events should be a shared decision-making process based on the CHA2DS2-VASc score (congestive heart failure [CHF], hypertension, age ≥75 years, diabetes mellitus, previous stroke/transient ischemic attack/thromboembolic event, vascular disease, age 65-74 years, sex). Oral anticoagulation with a VKA should be given to those with rheumatic MS or a mechanical prosthesis and AF.

All those with severe VHD under consideration for valve intervention should be evaluated by a multidisciplinary team, either with a referral or in consultation with a primary or comprehensive valve center.

Indications for intervention for valvular regurgitation are symptomatic relief and prevention of the irreversible long-term consequences of left ventricular volume overload. Lowered thresholds for intervention than they were previously are owing to more durable treatment options and lower procedural risks.

A mitral transcatheter edge-to-edge repair benefits patients with severely symptomatic primary mitral regurgitation (MR) who are at high or prohibitive surgical risk, as well as benefits a select subset of patients with secondary MR who remain severely symptomatic despite guideline-directed management and heart failure therapy.

Bioprosthetic valve dysfunction may occur because of either degeneration of the valve leaflets or valve thrombosis. Catheter-based treatment for prosthetic valve dysfunction is reasonable in selected patients for bioprosthetic leaflet degeneration or paravalvular leak in the absence of active infection.

Go to 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: Developed by the Task Force on cardiac pacing and cardiac resynchronization therapy of the European Society of Cardiology (ESC) ith the special contribution of the European Heart Rhythm Association (EHRA) for full details.

For more information, please go to Aortic Stenosis, Aortic Regurgitation, Mitral Stenosis, Mitral Regurgitation, and Tricuspid Regurgitation.

For more Clinical Practice Guidelines, please go to Guidelines.

Guidelines for the management of patients with valvular heart disease (VHD) were published in August 2021 by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS),[25] including the following recommendations on mitral valve disease:

• Surgery (mitral valve repair) is recommended for symptomatic patients with severe primary mitral regurgitation who are operable and not high-risk and for asymptomatic patients with LV dysfunction.

• In cases of severe secondary mitral regurgitation, valve surgery/intervention is recommended only for patients who remain symptomatic despite guideline-directed medical treatment (GDMT; including cardiac resynchronization therapy [CRT] if indicated).

Angiotensin-converting enzyme inhibitors (ACEIs) and diuretics are the mainstay of medical therapy for patients with mitral regurgitation (MR)  (mitral valve insufficiency).

Class Summary

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.

Enalapril (Enalaprilat, Epaned, Vasotec)

Enalapril is a prodrug hydrolyzed in vivo to enalaprilat. Enalaprilat prevents conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through competitive inhibition of angiotensin-converting enzyme (ACE), resulting in decreased plasma angiotensin II concentrations. Blood pressure may be reduced in part through decreased vasoconstriction, increased renin activity, and decreased aldosterone secretion.

Hydralazine (Apresoline)

Decreases systemic resistance through direct vasodilation of arterioles.

Nifedipine (Procardia, Adalat)

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

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.

Class Summary

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.

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.

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.

Class Summary

These are effective medications when cardiac function is slightly decreased or compromised by the amount of mitral regurgitation. Positive inotropic agents increase the force of contraction of the myocardium and are used to treat acute and chronic congestive heart failure. 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.

Milrinone

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

Class Summary

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.