Lutembacher Syndrome 

Updated: Mar 26, 2014
Author: Kamran Riaz, MD; Chief Editor: Park W Willis IV, MD 

Overview

Background

Lutembacher syndrome is defined as a combination of mitral stenosis and a left-to-right shunt at the atrial level. Typically, the left-to-right shunt is an atrial septal defect (ASD) of the ostium secundum variety. Both these defects, ASD and mitral stenosis, can be either congenital or acquired.

The definition of Lutembacher syndrome has undergone many changes. The earliest description in medical literature is found in a letter written by anatomist Johann Friedrich Meckel to Albrecht von Haller in 1750.[1] In 1916, Lutembacher described his first case of this syndrome, involving a 61-year-old woman, and he attributed the mitral valvular lesion to congenital mitral stenosis. Because the mitral stenosis was, in fact, rheumatic in etiology, the syndrome was defined eventually as a combination of congenital ASD and acquired, almost always rheumatic, mitral stenosis.

In the current era of mitral valvuloplasty for acquired mitral stenosis, however, residual iatrogenic ASD secondary to transseptal puncture is more common than congenital ASD, as is the combination of ASD and mitral stenosis. Although this syndrome is generally defined as mitral stenosis in combination with ASD, some have argued to define the syndrome as a combination of ASD and any mitral valve lesion, ie, mitral stenosis, mitral insufficiency, or mixed lesion. Currently, any combination of ASD, congenital or iatrogenic, and mitral stenosis, congenital or acquired, is referred as Lutembacher syndrome.

Pathophysiology

Mitral stenosis can be either congenital, as initially described, or acquired in origin, most commonly due to rheumatic mitral valve disease. Isolated mitral stenosis is now known to be a rare congenital disorder, and most cases of mitral stenosis initially thought to be congenital were, in fact, caused by rheumatic mitral valve disease.

Similarly, understanding of the etiology of ASD as associated with Lutembacher syndrome has evolved over time. Initially, high left atrial pressure due to mitral stenosis was thought to stretch open the patent foramen ovale (PFO), causing left-to-right shunt and providing another outlet for the left atrium. Now ASD in this syndrome, like mitral stenosis, is recognized as being either congenital or acquired, as already described.

Acquired ASD is almost always iatrogenic, either intentional or as a complication of a percutaneous interventional procedure. The incidence of left-to-right atrial shunt following mitral valvuloplasty is estimated at 11-12%. Although most of these ASDs are small and hemodynamically insignificant, some can be large enough to have hemodynamic consequences, especially in patients who develop restenosis of the mitral valve.

The hemodynamic effects of this syndrome are a result of the interplay between the relative effects of ASD and mitral stenosis. In its initial description, the ASD was typically large in Lutembacher syndrome, thus providing another route for blood flow. Iatrogenic ASDs tend to be smaller but still may be hemodynamically significant. The direction of blood flow is determined largely by the compliance of left and right ventricles. Normally, the right ventricle is more compliant than the left ventricle.

As a result, in the presence of mitral stenosis, blood flows to the right atrium through the ASD instead of going backward into the pulmonary veins, thus avoiding pulmonary congestion. This happens at the cost of progressive dilatation and, ultimately, failure of the right ventricle and reduced blood flow to the left ventricle. Development of Eisenmenger syndrome or irreversible pulmonary vascular disease is very uncommon in the presence of large ASD and high left atrial pressure because of mitral stenosis.

The term reverse Lutembacher syndrome is sometimes used to describe those rare cases in which a predominant right-to-left shunt develops owing to development of severe tricuspid stenosis.

Epidemiology

Frequency

United States

The true incidence of the syndrome is not clearly known. Although mitral stenosis is encountered in 4% of patients with an ASD, congenital mitral stenosis itself is very rare, accounting for only 0.6% of congenital heart disease cases at autopsy. The incidence of ASD in patients with mitral stenosis is 0.6-0.7%. In one US study, the combination was found in 5 of 25,000 autopsies. The syndrome was diagnosed more frequently in the past for the following reasons:

  • Without echocardiography, the combination of mid diastolic murmur, actually due to increased blood flow across the tricuspid valve, and systolic murmur of ASD led to a mistaken diagnosis of Lutembacher syndrome.

  • The prevalence of both rheumatic heart disease and mitral stenosis was higher in western developed countries before the antibiotic era. With the decline in the frequency of rheumatic fever, the prevalence of mitral stenosis has decreased and so has diagnosis of the syndrome. A history of rheumatic fever is frequently absent.

  • Even though ASD may be underdiagnosed in the United States, the combination of ASD and mitral stenosis may not be evident on physical examination and for that reason is best confirmed by echocardiography.

International

Although the exact prevalence of Lutembacher syndrome is not known, it is probably higher in areas where rheumatic heart disease is still common.

Mortality/Morbidity

No definite data are available. Mortality and morbidity rates are related to the relative severity of the individual lesions.

Race

No data are available regarding racial distribution of the condition.

Sex

Lutembacher syndrome is more common in females than males. Part of the reason is the higher incidence of both congenital ASD and rheumatic mitral stenosis in females.

Age

This syndrome can present at any age. Cases have been diagnosed in the seventh decade of life. Lutembacher's original case was a 61-year-old woman who had been pregnant 7 times. In the current era of balloon mitral valvuloplasty and development of ASD, the age of presentation may change.

 

Presentation

History

Patients may remain asymptomatic for many years. Symptoms are mainly due to the ASD, and signs and symptoms vary according to the size of the ASD. With a large ASD, symptoms of pulmonary congestion, typical of isolated mitral stenosis, do not appear until late in the course of the disease. Conversely, these symptoms may appear early if the patient has an associated small ASD or develops pulmonary hypertension for other reasons. Patients with large ASD and moderate-to-severe mitral stenosis have signs and symptoms due mainly to right ventricular overload and right-sided heart failure, while patients with a small ASD and moderate-to-severe mitral stenosis have signs and symptoms of pulmonary congestion typical of mitral stenosis.

  • The patient may or may not have a history of rheumatic fever.

  • Fatigue and reduced exercise tolerance result from decreased systemic blood flow. The presence of mitral stenosis and left-to-right blood flow in diastole through the ASD reduces the forward flow of blood into the left ventricle, thereby reducing systemic blood flow and leading to fatigue and poor exercise tolerance.

  • Palpitations are a common presenting symptom. Because of the augmented left-to-right shunt caused by higher left atrial pressure and mitral stenosis, both atria are dilated. This predisposes patients to atrial arrhythmias; atrial fibrillation is very common.

  • Weight gain, ankle edema, right upper quadrant pain, and ascites are seen more commonly in patients with large ASD. Such symptoms are manifestations of the development of right-sided heart failure. A chronically increased left-to-right blood flow at the atrial level can eventually lead to right-sided heart failure.

  • Paroxysmal nocturnal dyspnea, orthopnea, and hemoptysis are signs of pulmonary venous congestion. Such symptoms are caused by mitral stenosis and are seen less frequently in Lutembacher syndrome than in isolated mitral stenosis. They are more common in patients with small ASD and are probably more common in patients who develop reverse Lutembacher syndrome. In some patients with large pulmonary blood flow due to a large left-to-right shunt, orthopnea can develop because of decreased compliance of the lungs.

Physical

Physical examination reveals signs due to the ASD and mitral stenosis, which are modified because of the presence of both lesions in the same patient.

  • Arterial pulse

    • Small volume

    • Rhythm regular or irregular -Atrial fibrillation most common arrhythmia

  • Jugular venous pulse

    • Distended jugular veins, even in the absence of right heart failure

    • Large a waves when sinus rhythm is present

    • Increased right ventricular pressure a more important determinant than equalization of atrial pressures in increasing jugular venous pressure

  • Precordial examination

    • Left parasternal lift, caused by transmitted right ventricular and pulmonary artery impulse, is common.

    • Left ventricular impulse is unimpressive, owing to reduced filling of the left ventricle secondary to mitral stenosis.

    • A tapping apex impulse due to the palpable, loud first heart sound of mitral stenosis may be present.

    • A diastolic thrill at the apex is unusual.

  • Heart sounds

    • Loud first heart sound, opening snap, and a mitral early-to-mid diastolic murmur are the classic auscultatory findings of mitral stenosis and are variably present.

      • Reduced transmitral pressure gradient resulting from decompression of the left atrium through the ASD and displacement of the left ventricular apex due to a large right ventricle attenuate these classic findings of mitral stenosis.

      • Development of pulmonary hypertension and, consequently, an increase in right atrial and left atrial pressures may increase transmitral pressure gradient and bring out these auscultatory findings, but this phenomenon is canceled by further dilatation of the right ventricle, thus obscuring the left ventricular apex.

    • The second heart sound (S2) may be widely split for 2 reasons. Increased right heart flow of ASD can result in late closure of the pulmonary component of the S2, and decreased left ventricular and aortic flow, secondary to mitral stenosis and ASD, can cause early closure of the aortic component of S2.

  • Additional heart sounds and murmurs

    • Third and fourth heart sounds of right ventricular origin may be audible at the left sternal border and are louder with inspiration.

    • Systolic murmurs are due to the following:

      • ASD along the upper left parasternal area - Typically a flow murmur due to increased flow across the pulmonic valve

      • Tricuspid regurgitation along the lower left parasternal area - Due to the displaced tricuspid valve secondary to right ventricular dilatation; common

      • Holosystolic murmur at the left parasternal area due to tricuspid regurgitation - Usually increases with inspiration (Carvallo sign), which differentiates it from ASD and mitral regurgitation

    • Mid diastolic murmurs are due to the following:

      • Increased flow across the tricuspid valve due to ASD or accompanying tricuspid stenosis, best heard at left lower sternal border or at apex for reasons already mentioned

      • Mitral stenosis, best heard with stethoscope bell at apex after exercise and with patient in left lateral position

    • Continuous murmur in the lower right sternal area is due to continuous shunting of blood across a small ASD in the presence of severe mitral stenosis. This is an unusual finding on physical examination.

  • Abdomen: Ascites and hepatomegaly may be noted in the presence of right heart failure.

  • Extremities: Ankle edema may be present in the presence of right-sided heart failure.

Causes

See the list below:

  • Mitral stenosis is mostly rheumatic in origin.

  • Congenital mitral stenosis is very rare.

  • ASD is either congenital or iatrogenic.

 

DDx

 

Workup

Imaging Studies

See the list below:

  • Chest radiographs

    • Pulmonary plethora due to left-to-right shunt

    • Mild left atrial enlargement

    • Right ventricular enlargement

    • Pulmonary artery enlargement

    • Mitral valve calcification late in life

    • Pulmonary vascular congestion and marked left atrial enlargement in cases of severe mitral stenosis and small ASD

  • Transthoracic or transesophageal echocardiography[2] - May show the following during various stages of the disease:

    • Two-dimensional (see images below)

      • Large left atrium

      • Large right atrium and ventricle

      • Enlarged pulmonary artery

      • ASD

      • Stenotic mitral valve

        Shown is a 2-dimensional transthoracic echocardiog Shown is a 2-dimensional transthoracic echocardiogram of a 74-year-old woman who presented with signs of right heart failure. Note severely dilated left atrium, calcified and thickened mitral valve leaflets, doming of the anterior mitral valve leaflet, mitral annular calcification, and reduced opening of the mitral valve.
        Shown is a 2-dimensional transesophageal echocardi Shown is a 2-dimensional transesophageal echocardiogram during diastole of a 74-year-old woman who presented with signs of right-sided heart failure. Note the thickened, narrowed, and calcified mitral valve apparatus and doming of the anterior leaflet of the mitral valve.
    • Color flow and Doppler imaging[3] : This confirms the presence and evaluates the severity of ASD, mitral stenosis and mitral regurgitation, tricuspid regurgitation, and pulmonary pressure (see images below).

      Color-flow imaging of a 74-year-old woman who pres Color-flow imaging of a 74-year-old woman who presented with signs of right-sided heart failure on transthoracic echocardiogram; this illustrates an anteriorly directed jet of moderate mitral regurgitation.
      Color-flow imaging (subcostal view) on transthorac Color-flow imaging (subcostal view) on transthoracic echocardiogram showing the left-to-right shunt across the atrial septum of a 74-year-old woman who presented with signs of right-sided heart failure.
      Shown is a color-flow image during transesophageal Shown is a color-flow image during transesophageal echocardiography at the mitral valve level of a 74-year-old woman who presented with signs of right-sided heart failure. Note anteriorly directed jet of moderate-to-severe mitral regurgitation during systole.
      Color-flow imaging during transesophageal echocard Color-flow imaging during transesophageal echocardiography shows blood flow across the atrial septum in a 74-year-old woman who presented with signs of right-sided heart failure.
      Seen here are Doppler measurements at the mitral i Seen here are Doppler measurements at the mitral inflow level of a 74-year-old woman who presented with signs of right-sided heart failure. Note the reduced E-A slope and a peak transmitral velocity giving rise to a peak transmitral gradient of 21 mm Hg.
      Doppler measurement across the atrial septum revea Doppler measurement across the atrial septum reveals a peak velocity of 4 m/s of a 74-year-old woman who presented with signs of right-sided heart failure.
    • Doppler pressure half-time method: This usually overestimates the mitral valve area. Because of the presence of ASD, the transmitral pressure gradient is generally lower than expected for the degree of the mitral stenosis, thereby falsely underestimating the pressure half-time and overestimating the mitral valve area. On the other hand, planimetry and the Doppler continuity equation method should give an accurate assessment of the mitral valve area in Lutembacher syndrome.[4]

  • Transesophageal echocardiography - May be required to separate the PFO from the ASD and to fully delineate the anatomy

Other Tests

See the list below:

  • Electrocardiogram

    • Rhythm

      • Sinus rhythm

      • Atrial fibrillation

    • P wave morphology

      • Tall, broad, or bifid in lead II with a deep negative force in V1 suggesting biatrial enlargement

      • Isolated left atrial abnormality more indicative of a more severe mitral stenosis with small ASD

    • QRS morphology and axis

      • Right-axis deviation

      • Complete or incomplete right bundle-branch block or right ventricular hypertrophy

Procedures

Cardiac catheterization is not performed routinely to confirm the diagnosis. It can be used, however, to evaluate the severity of the ASD, detect reversible pulmonary hypertension, measure the mitral valve area by the Gorlin formula, and evaluate the presence of coronary artery disease in high-risk patients.

 

Treatment

Medical Care

See the list below:

  • Symptomatic relief

    • Right-sided heart failure - Diuretics

    • Atrial arrhythmias - Digoxin, beta-blockers, and calcium channel blockers used mainly for rate control, while amiodarone and sotalol used not only for rate control but also for conversion into and maintenance of normal sinus rhythm

  • Subacute bacterial endocarditis (SBE) prophylaxis: Patients with Lutembacher syndrome who have undergone complete repair with prosthetic material or a device need SBE prophylaxis for the first 6 months after the repair procedure. In addition, patients with previous history of endocarditis warrant SBE prophylaxis.

Surgical Care

Until recently, surgery was the only definite curative treatment available and involved closure of the ASD and mitral commissurotomy or mitral valve replacement.[5]

  • Percutaneous closure of ASD and mitral balloon valvuloplasty[6, 7, 8, 9, 10]

    • Percutaneous closure of the ASD with a clamshell device and mitral valvuloplasty provides a nonsurgical approach to correct these defects. Although mitral valvuloplasty has been performed for several decades, percutaneous closure of an ASD with a device represents a still-developing technology.

    • As already described, mitral valvuloplasty alone can be complicated by development of ASD secondary to transseptal puncture performed as a part of the procedure.

  • Indications for surgery or percutaneous intervention

    • ASD with a Qp/Qs ratio of more than 1.5

    • Moderate-to-severe mitral stenosis

    • Any degree of pulmonary hypertension, except individuals with irreversible pulmonary hypertension (Eisenmenger syndrome, see below)

  • Surgery is now performed early rather than late because the rates of heart failure and cardiac arrhythmia increase with age. Patients with pulmonary hypertension should demonstrate reversibility of pulmonary vascular resistance prior to surgical (or percutaneous) correction of ASD. Patients with pulmonary hypertension and irreversibly increased pulmonary vascular resistance (ie, Eisenmenger physiology) invariably develop progressive right-sided heart failure after ASD closure and die.

Consultations

See the list below:

  • Cardiothoracic surgeon

  • Interventional cardiologist

Diet

Patients should adhere to a low-sodium diet.

Activity

Activity should be as tolerated by the patient.

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Diuretics

Class Summary

These agents inhibit sodium and chloride reabsorption. They are used to treat right-sided heart failure.

Furosemide (Lasix)

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

Cardiac glycosides

Class Summary

These agents are used to treat atrial arrhythmias. They have both direct and indirect effects.

Digoxin (Lanoxin)

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

Antibiotics, prophylactic

Class Summary

These agents provide prophylaxis for subacute bacterial endocarditis (SBE). Patients with Lutembacher syndrome are at high risk for SBE owing to associated mitral stenosis.

Cephalexin (Keflex)

First-generation cephalosporin that inhibits bacterial replication by inhibiting bacterial cell wall synthesis. Bactericidal and effective against rapidly growing organisms forming cell walls.

Resistance occurs by alteration of penicillin-binding proteins. Effective for treatment of infections caused by streptococcal or staphylococcal infection, including penicillinase-producing staphylococci. May use to initiate therapy when streptococcal or staphylococcal infection is suspected.

Used orally when outpatient management is indicated. Primarily active against skin flora, including Staphylococcus aureus.

Amoxicillin (Amoxil, Trimox)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. Used as prophylaxis in minor procedures.

Ampicillin (Marcillin, Omnipen)

For prophylaxis in patients undergoing dental, oral, or respiratory tract procedures. Coadministered with gentamicin for prophylaxis in GI or genitourinary procedures.

Clindamycin (Cleocin)

Used in penicillin-allergic patients undergoing dental, oral, or respiratory tract procedures. Useful for treatment against streptococcal and most staphylococcal infections.

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Used in conjunction with ampicillin or vancomycin for prophylaxis in GI or genitourinary procedures.

Vancomycin (Vancocin)

Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in treatment of septicemia and skin structure infections. Indicated for patients who cannot receive, or have failed to respond to, penicillins and cephalosporins or have infections with resistant staphylococci. Use CrCl to adjust dose in patients diagnosed with renal impairment. Used in conjunction with gentamicin for prophylaxis in patients with penicillin allergy undergoing GI or genitourinary procedures.

Erythromycin (EES, E-Mycin, Eryc)

Used for prophylaxis in patients with penicillin allergy undergoing dental, oral, or respiratory tract procedures.

Cefazolin (Ancef)

First-generation semisynthetic cephalosporins that arrest bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including Staphylococcus aureus.

Azithromycin (Zithromax)

Macrolide antibiotics which inhibit bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Cefadroxil (Duricef)

First generation semisynthetic cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primarily active against skin flora, including Staphylococcus aureus.

Clarithromycin (Biaxin)

Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.

Antiarrhythmics

Class Summary

These agents alter the electrophysiologic mechanisms responsible for arrhythmia.

Amiodarone (Cordarone)

May inhibit AV conduction and sinus node function. Prolongs action potential and refractory period in myocardium and inhibits adrenergic stimulation. Prior to administration, control ventricular rate and CHF (if present) with digoxin or calcium channel blockers.

Diltiazem (Cardizem, Dilacor, Tiamate, Tiazac)

During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium.

Verapamil (Calan, Covera, Verelan, Isoptin)

Can diminish PVCs associated with perfusion therapy and decrease risk of ventricular fibrillation and ventricular tachycardia. By interrupting reentry at AV node, can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardias (PSVT).

Sotalol (Betapace)

Class III anti-arrhythmic agent that blocks potassium channels, prolongs action potential duration (APD), and lengthens QT interval. Noncardiac selective beta-adrenergic blocker.

Esmolol (Brevibloc)

Excellent drug for patients at risk for complications from beta-blockade (particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease). Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.

 

Follow-up

Further Outpatient Care

See the list below:

  • SBE prophylaxis

  • Surveillance for worsening signs or symptoms of heart failure

  • Periodic echocardiograms to assess the severity of mitral stenosis and the magnitude of left-to-right shunt and pulmonary artery pressure

  • Periodic assessment of the following:

    • BUN levels

    • Creatinine levels

    • Serum electrolyte levels in patients taking diuretics

Further Inpatient Care

See the list below:

  • Daily intake and output measurements

  • Daily weight measurement

  • Observation for worsening signs and symptoms of right-sided heart failure

  • Evaluation and treatment of any arrhythmias

  • Evaluation for any fever or new murmurs

Inpatient & Outpatient Medications

See the list below:

  • Diuretics

  • Digoxin

  • Beta-blockers, in selected cases

Transfer

Patients should be transferred to either a surgical team or an interventional cardiologist for definitive treatment.

Complications

See the list below:

  • Right-sided heart failure

  • Atrial arrhythmias

  • Pulmonary congestion

  • SBE

Prognosis

See the list below:

  • Prognosis is generally good for this condition. Patients have lived into their ninth decade without developing any cardiac symptoms. Women have had multiple pregnancies without complications.

Patient Education

See the list below:

  • Educate patients regarding the basic anatomical defects and physiological consequences of the disease.

  • Heart failure education should include the following:

    • Low-salt diet

    • Daily weighing

    • Early warning signs of worsening right or left heart failure

  • Bacterial endocarditis prophylaxis