Cardiology

Diagnosis and Management of Mitral Stenosis

I. Mitral Stenosis: What every physician needs to know.

Mitral stenosis (MS) results in obstruction to left ventricular (LV) inflow and is defined by a diastolic pressure gradient between the left atrium (LA) and ventricle. Rheumatic fever following infection with group A beta-hemolytic strep (GABS) is by far the most common etiology. Other causes of LV inflow obstruction include severe annular calcification with extension onto the leaflets, congenital parachute valve, cor triatriatum, and left atrial myxoma.

Rheumatic MS is an indolent, progressive, and lifelong disease that can remain latent for decades, particularly in temperate climates. Once symptoms or pulmonary hypertension intervene, event-free survival is significantly reduced unless corrective intervention with either balloon valvotomy or surgery is undertaken.

The LA-LV pressure gradient that defines MS varies as a function of heart rate. Increases in heart rate shorten the diastolic filling period and lead to further increases in LA pressure and the LA-LV gradient.

Pulmonary venous and arterial pressure usually increases passively and in direct proportion to LA pressure, but in a subset of patients pulmonary vascular resistance is markedly elevated, indicative of the development of intrinsic pulmonary vascular disease. With increases in LA pressure, the LA enlarges and sets the stage for the emergence of atrial fibrillation. Stroke risk is significantly increased once atrial fibrillation (AF) intervenes. Symptoms associated with MS include dyspnea, fatigue, and palpitations.

Diagnosis is first suspected on the basis of the physical examination with appreciation of a middiastolic rumble and opening snap. Electrocardiogram (ECG) may show signs of LA enlargement or AF. The chest x-rays can be used to assess chamber sizes and pulmonary blood flow pattern.

Echocardiography is the diagnostic procedure of choice and provides information on valve appearance, anatomy, pressure gradient, pulmonary artery (PA) pressure, and associated findings such as tricuspid valve anatomy and function. Cardiac catheterization is performed rarely in the current era. Long-term follow-up consists of periodic clinical and echocardiographic evaluations.

Medical therapy is limited to secondary rheumatic fever prophylaxis, endocarditis prophylaxis prior to dental procedures in patients with a history of endocarditis, anticoagulation for AF, diuretics to alleviate pulmonary congestion, and rate slowing of AF or sinus tachycardia with beta-blockers to optimize diastolic filling time. DC-cardioversion is helpful for patients with new onset AF.

Symptom development should prompt consideration of valve intervention. Percutaneous mitral balloon valvotomy (PMBV) is the procedure of choice for patients with appropriate valve anatomy as established by echocardiographic criteria pertaining to leaflet thickening, calcification, subvalvular scarring, the degree of associated mitral regurgitation (MR), and the presence of LA thrombus.

PMBV is not advised when MR grade exceeds 3 or in the presence of LA thrombus. Posterior commissure calcification is a relative contraindication, as is extensive leaflet scarring/calcification. The ideal patient is young with a pliable, noncalcified valve, and no MR. Open surgical commissurotomy is performed infrequently in the developed world. Mitral valve replacement may be necessary in instances of extensive valve scarring, moderate-severe MR, or LA thrombus. Surgical outcomes are dependent on age, pulmonary hypertension, ventricular function, and comorbidities.

Mild to moderate degrees of MS are well tolerated during pregnancy, though judicious use of diuretics (to avoid utero-placental hypoperfusion) and heart rate control are sometimes needed. Severe MS is a relative contraindication to pregnancy and should be treated beforehand whenever possible.

Pregnant women with severe MS should be managed in a multi-disciplinary clinic with cardiologists, maternal-fetal medicine specialists, and neonatologists. Every effort should be made to avoid valve intervention during pregnancy. If necessary, PMBV or surgery could be performed, but only in a center of excellence and with all appropriate safeguards for the health of the mother and fetus.

II. Diagnostic Confirmation: Are you sure your patient has Mitral Stenosis?

A history of childhood rheumatic fever is only rarely verified. Symptoms of dyspnea, fatigue, and palpitations are nonspecific. The typical murmur of mitral stenosis (MS) is middiastolic in timing and low pitched or rumbling in quality.

Presystolic accentuation of the murmur can be appreciated in some patients in sinus rhythm. An opening snap (OS) introduces the murmur in patients with pliable valve and the time interval between S2 and the OS is inversely proportional to the height of the LA-LV gradient. S2 may become loud in patients who develop pulmonary artery (PA) hypertension.

V waves in the jugular vein pulse signify tricuspid regurgitation, which is usually secondary to tricuspid annular dilatation in the setting of PA hypertension. The auscultatory examination is best performed with the patient in the left lateral decubitus position to accentuate the findings referable to the mitral valve.

The ECG and chest x-ray findings are also not specific for MS, but can sometimes be helpful in a corroborative sense. The ECG may shows signs of LA enlargement, AF, or right ventricular (RV) hypertrophy depending on the chronicity and severity of the MS.

Classic chest x-ray changes include LA enlargement, pulmonary venous redistribution, and PA enlargement. Transthoracic echocardiography (TTE) is the diagnostic procedure of choice. Typical findings in patients with MS include a thickened valve with a "hockey-stick" appearance to the anterior leaflet in diastole; the posterior leaflet most often appears fixed. LA is usually enlarged. Concomitant rheumatic involvement of the tricuspid valve is unusual. Continuous wave Doppler assessment of mitral valve (MV) flow reveals a diastolic LA-LV mean pressure gradient, increased E and A wave (in patients in sinus rhythm) velocities, and a delay in E wave deceleration time.

Mitral valve area (MVA) can be estimated from direct planimetry, the pressure half-time method, or the continuity equation. The pressure half-time method is used most commonly and equates MVA with the ratio of 220 over the pressure half time of E wave velocity (i.e., the time for the peak pressure to fall to half its value). Assessment of the tricuspid regurgitant jet velocity is used to estimate PA pressure. American Society of Echocardiography grades of MS severity are shown in Table I and have been adopted by guideline writing committees.

Table I.

ASE Echocardiographic Diagnostic Classification of Mitral Stenosis Severity
Criteria Mild Moderate Severe
<5 5-10 >10
<30 30-50 >50
>1.5 1.0-1.5 <1.0

Echocardiographic diagnostic classification and severity of mitral stenosis

Cardiac catheterization for hemodynamic assessment of MV gradient, area, PA pressure, and pulmonary vascular resistance is infrequently required when there is a discrepancy between the clinical and echocardiographic data, but is routinely performed, including transseptal puncture for measurement of LA pressure, as a prelude to PMBV.

A. History Part I: Pattern Recognition:

MS usually remains clinically latent for several years. Symptoms may first appear under conditions of physiologic stress associated with tachycardia (e.g., fever, anemia, thyrotoxicosis, pregnancy) and/or new onset AF, due to a reduction in diastolic filling time and resultant increase in the LA-LV pressure gradient.

As MS gradually worsens and LA pressure increases, exertional dyspnea may emerge. Decreased effort tolerance may also reflect a reduction in cardiac output from diminished stroke volume. More significant elevations of LA pressure may result in orthopnea or paroxysmal nocturnal dyspnea.

Later stage symptoms indicative of right ventricular failure may include ascites and edema. Palpitations may reflect AF at any stage of disease.

Uncommon symptoms include hoarseness from impingement of the recurrent laryngeal nerve between an enlarged LA and the pulmonary artery and hemoptysis, which is due to rupture of bronchial veins into the airway, although lesser degrees of hemoptysis are seen with pulmonary edema, infarction, and infection. Symptoms associated with stroke or systemic embolism may emerge in the setting of AF.

B. History Part 2: Prevalence:

In economically developed countries, the prevalence of rheumatic MS detected by TTE across all ages is ~ 1%. Rheumatic MS is more common among women than men. Economically developing countries or areas in which there is over crowding or limited access to health care have a much higher prevalence of rheumatic heart disease (RHD).

A 2005 report systematically reviewed the median prevalence rates of RHD among children aged 5 to 14 years in various geographic areas. Within economically developed countries, RHD was detected in 0.3 cases per 1000, compared with 7.6 cases per 1000 in Pacific and indigenous Australia/New Zealand populations, 3.0 cases per 1000 in both sub-Saharan Africa and Latin America,1.9 cases per 1000 in the Middle East and North Africa, and 1.6 cases per 1000 in South Asia. Public health efforts to identify and treat group A beta-hemolytic streptococcal infections remain a top priority, particularly in developing countries where bacterial strains can be particularly virulent or infections repetitive.

C. History Part 3: Competing diagnoses that can mimic Mitral Stenosis.

Among the cardiac lesions that can mimic MS are congenital cor triatriatum and LA myxoma. The former is characterized by an intraatrial membrane that separates the inflow region of the LA into which the pulmonary veins drain from the MV resulting in elevated pressures proximal to the membrane with corresponding increases in pulmonary vein, capillary wedge, and arterial pressure.

The left atrium is the most common site for myxomas, which are typically attached by a stalk to their interatrial septum and may grow large enough to obstruct MV flow. They can rarely be associated with an auscultatory tumor plop or systolic and diastolic murmurs that vary in intensity as a function of position.

An apical middiastolic murmur of medium pitch (Austin Flint murmur) is occasionally heard in patients with severe aortic regurgitation and is believed to be due to the collision of transmitral valve and regurgitant aortic diastolic flow that is directed across the anterior mitral valve leaflet. This murmur attenuates with vasodilators, such as inhaled nitrous oxide.

Functional MS is heard in patients with severe MR and increased diastolic flow in the absence of any apparent obstruction to LV inflow. Right-sided middiastolic murmurs, such as those due to tricuspid stenosis or a large atrial septal defect with augmented diastolic flow, are not usually confused with the murmur of mitral stenosis because of their location and associated attributes.

D. Physical Examination Findings.

Salient physical examination findings in patients with MS include:

General inspection:

-In the setting of longstanding severe MS with low output and right heart failure: cardiac cachexia, mitral facies, acrocyanosis, and peripheral edema

Arterial pulse:

-Irregularity may signify AF

Jugular venous pressure and waveforms:

-Typically normal with sinus rhythm; jugular venous pressure elevated with right heart failure or concomitant rheumatic tricuspid valve involvement

-Loss of a wave with AF

-cv waves with tricuspid regurgitation

-slow y descent with tricuspid stenosis

Precordial palpation

-LV apex beat usually normal in position, size, and amplitude

-Parasternal (RV) lift with right ventricular enlargement and volume/pressure overload

-MS murmur rarely palpable

Auscultation

S1

-Increased intensity in early stages of the disease

-Becomes softer in late stage disease with calcification and scarring of valve

-Variable intensity with AF

S2

-Becomes single and loud with pulmonary hypertension

Opening snap (OS)

-Medium-to-high pitched diastolic sound that occurs 0.06 to 0.12 seconds after A2 and coincides with the maximum excursion of the anterior mitral valve leaflet

-Introduces the murmur of MS

-A2-OS interval is inversely proportional to the height of the LA-LV gradient

-OS disappears in late stage disease

Diastolic murmur

Middiastolic rumble of MS that immediately follows the OS:

  • The rumble of MS is a low-pitched sound best heard with the bell of the stethoscope, with the patient in the left-lateral decubitus position (LLDP)

  • There is no radiation of the murmur of MS

The duration of the rumble corresponds to the duration of the diastolic pressure gradient across the mitral valve:

  • In mild MS, there are two phases of diastolic pressure gradient across the valve (during early diastolic rapid ventricular filling and again during presystole upon the added contribution of atrial contraction), resulting in a rumble that can occur during either period or both parts of diastole.

  • When MS becomes severe, the diastolic rumble persists throughout diastole due to a persistent pressure gradient across the valve

  • The intensity of murmur corresponds to both the severity of the obstruction and the forward flow across the stenotic valve (therefore the severity of the murmur does not correlate directly to the severity of MS )

The intensity of the murmur can be made louder by asking the patient to perform provocative maneuvers:

  • Sit ups and mild exercise will increase heart rate

  • Tachycardia decreases the diastolic filling period

This results in an increased left atrial-left ventricular gradient and more turbulent blood flow across the stenotic valve

  • Presystolic accentuation of the diastolic rumble of MS:

    • Only heard with sinus rhythm as the sound is from the contribution of left atrial contraction prior to systole

    • Represents either a late diastolic enhancement of the earlier middiastolic murmur or can be an isolated short presystolic murmur that crescendos into S1

    • When AF is present, no presystolic accentuation is present; however, if a rumble can be heard throughout a long diastolic filling period when a patient is in AF, this indicates a large persistent diastolic pressure gradient even without the atrial kick and severe MS

    • In rapid AF, carotid sinus massage in appropriately selected patients is a maneuver that can temporarily slow the heart rate to allow evaluation of the duration of the diastolic rumble to estimate the severity of MS in this setting

  • Other findings that may be found once pulmonary hypertension (PHTN) develops, include:

    • Palpable P2 or PA lift may be felt best at the 2nd or 3rd left intercostal space (LICS)

    • Palpable RV lift/impulse can be felt at the 3rd-5th LICS at the sternum using firm pressure with the heel of one's hand during held expiration. In severe MS and PHTN, RV dilatation may be large enough to become the palpable apex, which enlarges leftward

    • JVP: prominent A waves, general jugular venous distention with a positive hepatojugular reflux, and if concomitant, large CV waves of tricuspid regurgitation (TR) if either PHTN or RV failure develops

    • Auscultation: Loud P2, widened splitting of S2, right-sided S3 or S4, TR, pulmonary regurgitation, and a Graham-Steell murmur

Differential diagnosis of a diastolic heart murmur that may mimic MS includes:

  • Increased cardiac output states that produce high flow across the mitral valve

  • Severe aortic insufficiency leading to the Austin-Flint murmur

  • Tricuspid stenosis

  • Atrial myxoma

  • Diastolic rumbles caused by high flow across atrioventricular valves due to large shunts

    • Ventricular septal defects

    • Patent ductus arteriosus

    • Atrial septal defects

  • Diastolic rumbles with severe mitral or tricuspid regurgitation

  • Acquired pulmonary vein stenosis after an AF radiofrequency ablation procedure

Differential diagnosis of the opening snap from other early diastolic heart sounds:

  • Split S2

  • S3

  • S4

  • Pericardial knock

Clinical pearls to differentiating MS from AI:

  • Look for signs of the company each murmur keeps:

    • AI has an associated wide pulse pressure, displaced and sustained cardiac apex, soft S1 and begins immediately after S2, with associated peripheral findings of AI

    • Unless critically severe, MS has an associated loud S1, two phases of a diastolic pressure gradient across the valve (during early diastole rapid ventricular filling and again during presystole upon the added contribution of atrial contraction) that melds into one long rumble as a larger gradient exists across the valve as the stenosis becomes more severe, and begins after the opening snap, which can occur 0.06 to 0.12 seconds after aortic valve closure (A2) component of S2. As left atrial pressure becomes higher, the interval timing between A2 and the OS shortens.

  • The murmurs respond differently to provocative maneuvers:

    • In response to vasodilator therapy (amyl nitrate), AI immediately becomes softer. In the setting of MS, there is no immediate change in the intensity of the murmur; however, tachycardia develops in a delayed fashion (~30 seconds) in response to vasodilation to maintain cardiac output, and this results in increased blood flow across the stenotic mitral valve and as a result, MS eventually becomes louder.

    • Point in fact, any maneuver that increases heart rate, will increase the left atrial-left ventricular gradient and intensify the murmur of MS but not change the intensity of AI:

      • Asking the patient to cough deeply several times in a row

      • Mild exercise, such as asking the patient to perform several sit-ups, deep knee bends, or light jogging in place

      • Listening to the apex while the patient changes position from supine to the left lateral decubitus position (LLDP)

Clinical pearls to differentiating MS from TS:

  • TS

    • Best heard over the left parasternal border

    • Becomes louder with inspiration

    • Becomes louder when the patient repositions from standing to a supine position (increase in preload) more than MS.

E. What diagnostic tests should be performed?

All patients with suspected MS should be investigated with a 12-lead electrocardiogram (ECG), chest radiograph, and echocardiogram. The hemodynamic severity of the mitral valve obstruction, regardless of whether rheumatic or from other causes, can be routinely determined with Doppler echocardiography (see Imaging studies - Echocardiography).

In addition, the underlying mitral valve morphology can be estimated with echocardiography, which is the most important factor in determining successful response, acute complications, and stenosis recurrence risk after PMBV. Finally, immediately prior to proceeding with PMBV over other more invasive valve interventions options (open commissurotomy [valvuloplasty], mitral valve repair or replacement), a transesophageal echocardiogram should be performed to determine the presence of atrial thrombus or moderate-to-severe (3-4+) mitral regurgitation. The presence of either increases the risk of a periprocedural complication or unsuccessful outcome and warrants delay or cancellation of PMBV.

Rarely, more invasive testing with cardiac catheterization is necessary to confirm the diagnosis when there are discrepancies between symptoms and echocardiographic findings, or concern over the severity of pulmonary hypertension. The primary role cardiac catheterization plays is its central role in PMBV.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There are no laboratory chemistry tests that should be ordered that help establish the diagnosis of MS. There are, however, several other "lab" tests that are of assistance in making the diagnosis and determining the severity of MS with potential associated complications.

  1. ECG

    • The most common ECG finding in MS is left atrial enlargement, otherwise known as P mitrale

    • Because the LA is the primary cardiac chamber that becomes enlarged in mild-to-moderate MS, few other ECG findings of structural enlargement may be seen. However, the second most common ECG finding as MS progresses is likely that of atrial fibrillation.

    • Once severe MS has developed, signs on ECG of pulmonary hypertension may be seen, which include:

      • Signs of RV hypertrophy (right axis deviation, tall R waves in V1 >7 mm, ratio of R/S in V1 >1)

      • Signs of RV strain (nonspecific ST-segment depression in right-sided leads)

      • P pulmonale

      • Incomplete or complete right bundle branch block (RBBB)

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

  1. Chest x-ray radiography (CXR) when suspecting a diagnosis of MS

    • Features of MS predominantly focus on manifestations of chronic signs of increased left atrial (LA) pressure, LA volume, and PHTN

    • First evaluate and determine the cardiothoracic silhouette is less than 50% of internal diameter of the thorax (rib cage), the so-called cardiothoracic ratio (CTR)

      • In MS, the left ventricle (LV) chamber size and function is normal. Thus, if a patient with clinical signs of heart failure and a diastolic murmur has a normal CTR on CXR, this narrows the differential diagnosis of potential valves involved to very few, including MS (or rarely TS).

    • Next, evaluate the seven contours (bumps) of the heart in the frontal (posterior-to-anterior [PA] projection) for indirect signs of increased LA pressure or volume, from top to bottom starting on the right side then the left:

      • Ascending aorta*

      • Right-sided "double density" of LA enlargement

        • Because the LA is a central yet posterior cardiac structure, the LA forms no border of the normal heart projected in the PA view

        • However, the LA enlarges out of both the left and right borders of the heart, and on the right side two shadows of both the left and right atria overlap each other where the indentation between the ascending aorta and right heart border meet, making up the so-called "double density" sign

      • Right atrium*

      • Aortic knob*

      • Main pulmonary artery (PA)

        • The next contour down below the aortic knob and above the LA indentation

        • To determine if PA dilatation is present (i.e., a sign of PHTN):

          • Imagine a straight tangent line drawn from the apex of the LV to the aortic knob

          • Next measure along a perpendicular to that tangent line to the main PA (towards the center)

          • Measure this distance between the tangent and the main PA, which typically ranges between 0 to 15 mm

            • If the main PA projects beyond the tangent line, this is a sign of either increased pulmonary artery pressure or flow

            • If the main PA is more than 15 mm away from the tangent line, either the main PA is small or absent, or an enlarged LV or aortic knob is pushing the tangent line away from the main PA

      • Inward indentation of the LA

        • Concavity inward where the LA appears on the left side of the heart between the main PA and LV, which can become a convexity outward when the LA becomes enlarged

        • The first sign of LA enlargement may then be a "straightening" of the left heart border without producing the double-density sign

        • Subsequently a severely enlarged LA appears as a convex outpouching

      • Left ventricle (addressed above with the CTR)*

  • Other signs of an enlarged LA include:

    • A widened splay of the bifurcation of the mainstem bronchus on the PA view

    • A widened distance (>3.5 cm) between the anterior right PA border and posterior wall of the LA

  • Evaluate for signs of valve annulus or leaflet calcification as a consequence of rheumatic scar or degeneration

  • Evaluate for signs of pulmonary venous congestion

    • Redistribution of pulmonary blood flow from the bases to the apex (i.e., cephalization of blood flow) causing the appearance of upper lobe vessels equal to or larger than the size of lower lobe vessels

  • Evaluate for other signs of pulmonary hypertension

    • Dilated right descending PA (>17 mm diameter)

    • Sharp tapering of the diameter of proximal to distal PA vessels

  1. Echocardiography

Several methods of Doppler and two-dimensional echocardiography can be used to evaluate the severity and morphology of mitral stenosis.

A. Echocardiographic methods to evaluate mitral stenosis:

  1. Direct planimetry

  2. Pressure half-time:

  • Mitral valve area (cm2) = 220 (cm2*ms)/pressure half-time (PHT; ms)

  • Where PHT is the time required for the transmitral pressure gradient to decrease by half

  • It is derived based on the time (ms) required for the peak of the diastolic mitral inflow to decelerate back to baseline (otherwise known as the deceleration slope)

  • PHT = 0.29 * deceleration time [DT] in ms

  1. Continuity equation:

  • Based on the principle of conservation of mass, "what goes it must come out"

  • Equation: MVA (cm2) = transmitral stroke volume (cm3) /velocity time integral (VTI) of mitral valve Doppler E wave inflow (cm) = LV outflow tract (LVOT) VTI (cm) * LVOT cross-sectional area (cm2)/VTI of mitral valve Doppler E wave inflow (cm)

  1. PISA method (PISA stands for the proximal isovelocity surface area)

  • The PISA method also is based on the continuity principle and assumed that blood flow converging toward a flat orifice forms hemispheric isovelocity shells

  • This method, although technically demanding and cumbersome because it cannot be entirely automated and requires a manual determination of an angle correction factor (see below), is considered the most reliable for estimating MVA because the proximal convergence can be easily visualized and is not limited by the presence of other valvular abnormalities

  • Equation: MVA (cm2) = maximal diastolic mitral flow rate (mL/s)/peak continuous wave Doppler mitral inflow velocity (Vmax [cm/s])

  • With a hemispheric shape of the PISA, the diastolic flow rate = 2πr2 * aliasing velocity (cm/s) * (angle α/180°)

  • Where r (cm) represents the maximal radius of the flow convergence region in early diastole measured on the centerline of the flow convergence region

  • And α/180° is an angle correction factor accounting for the angle between the mitral leaflet

Each of these methods have potential intrinsic limitations in routine clinical practice (see : Limitations of Echo Methods to Evaluate MS)

B. The echocardiographic Wilkins/Massachusetts General Hospital scoring system has been developed and used to assess suitability for, and predict outcome of, PMBV based on the morphological appearance of the MV apparatus. The entire MV apparatus may sustain permanent injury following rheumatic fever, including leaflet thickening and calcification, commissural fusion or shortening, chordae tendineae thickening and fusion, or any combination of the above.

The MS morphology criteria and scoring system include:

Morphology (points) (see : MS Morphology Scoring System)

  1. Leaflet mobility

  2. Leaflet thickening

  3. Leaflet calcification

  4. Subvalvular apparatus appearance

Interpretation of the MS scoring system hinges on a summary score accumulated from the above subjective criteria. Each item is scored from 1 to 4, where a higher score represents more severe morphological injury, out of a total of 16.

A threshold of less than or equal to a score total of 8 correlated with successful PMBV outcome and low-risk of periprocedural complication, if concomitant MR is no more than mild (2+). Whereas those with a score greater than 8 are considered not appropriate for consideration of PMBV as first-line intervention.

Echocardiographic diagnostic classification and severity of mitral stenosis (ref guideline)

Table II. ACC/AHA and ASE Echocardiographic Diagnostic Classification of Mitral Stenosis Severity

Table II.

ACC/AHA and ASE Echocardiographic Diagnostic Classification of Mitral Stenosis Severity
Criteria Mild Moderate Severe
<5 5-10 >10
<30 30-50 >50
>1.5 1.0-1.5 <1.0
  1. Cardiac catheterization:

  • The Gorlin formula is how the MVA was originally derived and the method to which echocardiography estimation was originally compared

  • Gorlin: MVA (cm2) = cardiac output (CO; mL/min)/(0.85 * 44.3 * HR (beats/min) * diastolic filling period [DFP, s/beat] * square-root [mean gradient, mm Hg])

  • Where the DFP is a correction factor to estimate mitral flow, which occurs only in diastole, and is defined from mitral valve opening to mitral valve closure

  • The modified Hakki formula, is a simplified version of the Gorlin equation, which is a reasonable estimate of MVA when the HR is between 60 to 100. Hakki: MVA (cm2) = cardiac output (CO; L/min)/square-root [mean gradient, mm Hg]) (*note the change in units of CO)

  • See for important limitations and caveats.

Limitations to echocardiographic methods to evaluate mitral stenosis:

  1. Direct planimetry

  • Subjective measurement that is dependent on interpreter experience, alignment of echo probe to be perpendicular to the place of the mitral valve at the level of the leaflets, and the degree of valvular deformities and calcification

  • Not interpretable early after PMBV

  1. Pressure half-time

  • Also not interpretable early (first 48 hours) after PMBV because of acute changes in the equilibrium of LA and LV compliance

  • Under conditions of AF and varying diastolic periods of time, values need to be averaged over several beats

  • Under conditions of aortic insufficiency (AI), a falsely larger MVA may be derived and an underestimate of MS severity

  • Under conditions of severe diastolic dysfunction, may lead to false underestimate of MS severity

  • If there is nonlinear alignment of the Doppler probe, the maximum velocity may be underestimated and MS severity overestimated

  1. Continuity equation:

  • Under conditions of AI or MR there will be a false estimation of MVA, with underestimation and overestimation of MS, respectively

  1. PISA method (PISA stands for the proximal isovelocity surface area)

  • Although the most accurate method, the subjective difficulty in manual estimation of the angle correction factor and multiple measurements involved, limit the regular use of this method

MS Morphology Scoring System:

# of points per criteria:

  • Leaflet mobility

    1. Highly mobile leaflets with restricted leaflet tips

    2. Leaflet middle and base has normal mobility

    3. Valve continue to move forward in diastole, mainly from the base

    4. No or minimal forward movement of mitral leaflets in diastole

  • Leaflet thickening

    1. Near normal thickness (4 to 5 mm)

    2. Midleaflet normal, marked thickening in margins (5 to 8 mm)

    3. Thickening extending through entire leaflet (5 to 8 mm)

    4. Marked thickening of all leaflet tissue (8 to 10 mm)

  • Leaflet calcification

    1. A single area of increased echo brightness

    2. Scattered areas of brightness confined to the leaflet margins

    3. Brightness extending into the midportion of the leaflets

    4. Extensive brightness throughout much of the leaflet tissue

  • Subvalvular apparatus appearance

    1. Minimal thickening below the mitral leaflets

    2. Thickening of chordal structures extending into one third of the chordal length

    3. Thickening extending to the distal third of chordal length

    4. Extensive thickening and shortening of all chordal structures

Interpretation:

Interpretation of the MS scoring system hinges on a summary score accumulated from the above subjective criteria. Each item is scored from 1 to 4, where a higher score represents more severe morphological injury, out of a total of 16. A threshold of less than or equal to a score total of 8 correlated with successful PMBV outcome and low risk of periprocedural complication, whereas those with a score greater than 8 are considered not appropriate for consideration of PMBV as first-line intervention.

An important limitation to note is that this MS Morphology Scoring System does not include an evaluation of commissural calcification; heavy commissural calcification is correlated with poor outcomes in PMBV and if noted, may tip the balance of a benefit/risk evaluation if the patient's score is 8.

Cardiac catheterization:

  1. Cardiac output (CO) estimation. Important limitations to either formula include that the derivation of the MVA will be strongly influenced by cardiac output, far more than the estimated mean transmitral pressure gradient, which has less influence because of the square root. Under certain circumstances, the Fick method may be less reliable than the thermodilution method of deriving the CO and greatly influence the MVA calculation. For instance, in the presence of low-flow states, Fick typically will underestimate actual CO and will therefore underestimate the MVA estimate. Another condition in which the Fick estimate may be less reliable is in the presence of mixed valvular disease, such as MR or AI. However, depending on the severity of valve disease, the thermodilution method may also be influenced by mixed valvular disease, resulting in overestimation MS severity because net forward flow will not equal cardiac output. Under this circumstance, some experts advocate for direct observation of LV wall motion by angiography as the most accurate method of CO estimation.

  2. Diastolic filling period. When concomitant AF is present, DFP will vary beat-to-beat. It is prudent to obtain and average DFP over several cardiac cycles to best estimate MVA in this setting.

*typically normal in MS

III. Management.

Medical management

Medical management for MS includes prevention and treatment of (a) heart failure, (b) thromboembolism and stroke, (c) infective endocarditis and rheumatic fever, (d) pulmonary hypertension and (e) risk-stratification for severity-directed intervention to relieve the valvular obstruction.

  1. Heart Failure. Most patients with mild MS remain asymptomatic for decades. However, the progressive mitral valve obstruction can be exacerbated under physiologic stressors of tachycardia and altered cardiac loading conditions (i.e., exercise, fever, anemia, atrial fibrillation, or pregnancy), that ultimately result in too little diastolic filling time for forward cardiac blood flow across the mitral valve and resultant classic manifestations of left heart failure symptoms

    Therefore, rate-control therapy in the form of beta-blockers or calcium-channel blocker may be used to control ventricular rate. Particularly if AF develops, a dramatic deterioration in patient functional capacity and worsening of heart failure symptoms can occur when tachycardia leads to limited diastolic filling and increased intracardiac pressure. Diuretic may decrease preload and hypervolemia under these circumstances and are often employed when congestive symptoms are present.

    Digoxin was previously a commonly used therapy in mitral stenosis, but because of its narrow therapeutic window, side effects, and the availability of alternative efficacious drugs, it has fallen out of first-line selection. Direct electrical cardioversion and antiarrhythmia medications are additional therapy that can terminate AF in patients without contraindications and who have not failed at least one attempt at rhythm control.

  2. Stroke/embolism risk and anticoagulation.

    • All patients with rheumatic MS and a history of AF should be prescribed therapeutic anticoagulation (target INR 2-3) with lifelong monitoring unless contraindicated due to severe life-threatening bleeding. Rheumatic MS leads to both left atrial enlargement and thrombogenicity of the thickened/calcified MV apparatus, and hence rheumatic MS is associated with an increased risk of stroke in the presence of AF (5.6-fold increased risk of stroke compared to the normal population) or other high-risk features when AF is not present. The risk of stroke remains high regardless of whether AF is persistent or paroxysmal and regardless of whether AF appears terminated, such as immediately after MV intervention.

    • Patients with rheumatic MS in normal sinus rhythm who have any of the following other high-risk features for thromboembolism are recommended to be anticoagulated for the duration of the risk factor's presence, and typically (unless a transient risk factor) lifelong. These include patients with:

      • Prior stroke or systemic embolism

      • Left atrial thrombus

      • Severe left atrial dilatation (>5.0 to 5.5 cm) or if spontaneous echo contrast can be visualized in the LA

      • Pregnancy

    • If a stroke or systemic embolism occurs while a patient is therapeutic with anticoagulation (e.g., warfarin with documented INR between 2 and 3 when stroke occurred; therapeutic low-molecular-weight-heparin (LMWH) or heparin, then either (a) the addition of aspirin 50 to 100 mg daily or (b) increasing the target anticoagulation to INR 2.5 to 3.5 is recommended to prevent recurrent stroke.

    • Novel oral anticoagulants, such as direct factor II or Xa inhibitors, were recently tested and approved for use in patients with non-valvular AF as equally effective as warfarin for the prevention of stroke or systemic embolism. Although these agents provide many advantages over warfarin regarding long-term anticoagulation, when tested specifically in high-risk patients with valvular AF, such as rheumatic mitral stenosis, dabigatran was inferior to warfarin for stroke prevention and at this time none are approved for use in these patients unless in the setting of a clinical trial.

  3. Antibiotic prophylaxis.

    • Patients diagnosed with rheumatic heart disease (i.e., rheumatic MS) should be treated for secondary prevention of rheumatic fever as they are at increased risk for recurrence. The duration of prophylaxis varies according to age of the patient and time since last diagnosis of rheumatic fever, severity of carditis, and occupational risk for re-exposure to streptococcal infection. (See Table III for general recommendations for antibiotic durations):

    • Secondary prevention antibiotic regimens include:

      • Penicillin G: 1.2 million units IM once monthly, or

      • Penicillin V: 250 mg PO twice daily, or

      • If penicillin allergy: Erythromycin 250 mg PO twice daily, as well as other options

    • The indications for infective endocarditis (IE) prophylaxis currently does not include the presence of mitral stenosis and is not necessary after PMBV. However, prior IE or the implantation of prosthetic material during mitral valve repair or replacement, are indications for IE antibiotic prophylaxis prior to invasive dental or respiratory tract procedures.

  4. Pulmonary hypertension. Once patients have had longstanding moderate-to-severe MS they are at increased risk for the development of secondary venous PHTN (defined as a pulmonary artery systolic pressure [PASP] > 30 mmHg). At this point, unless considered an inadequate percutaneous or surgical candidate, these patients should undergo PMBV or surgical valve intervention to relieve the underlying cause (the mitral valve obstruction) and reverse this complication.

    Without valve intervention, the PHTN can result in irreversible right heart failure, a major risk factor for detrimental cardiopulmonary morbidity and decreased mean survival time of 3 years once severe PHTN develops. No degree of diuretics or other heart failure medication can reverse this process alone.

    The definition of a successful percutaneous mitral valve intervention, typically the demonstration of a doubling in the mean estimated MVA, immediate decrease in the LA pressure to <18 mm Hg, and immediate reversal of pulmonary HTN, is seen in over 80% of patients. If PHTN persists, or recurs later in life without diagnostic indication for repeat mitral valvotomy, two important considerations should be undertaken.

    First, a broadening of the differential diagnosis to include other sources of intracardiac or extracardiac obstruction, or the potential for arterial PHTN out of proportion to suspected venous PHTN, may be occult but potentially present either as progressive disease or as a complication of prior intervention. Second, if an interventional procedure is not indicated or permissible due to patient comorbidity and arterial PHTN is diagnosed, advanced pulmonary hypertension medications may be considered, but should be initiated in coordination with pulmonary hypertension specialists within the context of a clinical trial.

Table III.

Recommendations for Antibiotic Durations
Occupation Severity of Rheumatic Heart Disease Duration of Antibiotics
Low risk Rheumatic fever without carditis 5 years or until age 21 (whichever is longer)
Low risk Mild or healed carditis 10 years or until age 21 (whichever is longer)
Low risk Rheumatic heart disease 10 years or until age 40 (whichever is longer)
Recurrent exposure occupation (e.g., teacher, daycare worker, overcrowding) Rheumatic heart disease Lifelong

Indications for percutaneous or surgical intervention

The first-line indicated intervention for mitral stenosis today is percutaneous mitral balloon valvotomy (PMBV), performed in the cardiac catheter lab, which is a procedure that involves balloon inflation-mediated stretching of the MV apparatus that has been fused, thickened, and scarred from prior rheumatic fever.

The immediate goal of PMBV, and the benchmark for a successful intervention, is a doubling of the mean MVA and a greater than 50% decrease in the mean transmitral pressure gradient (immediate decrease in LA pressure to <18 mm Hg), immediate improvement in pulmonary capillary pressure, and prominent relief of heart failure symptoms to NYHA class I-II. Over 80% to 95% of patients appropriately selected for PMBV have a successful immediate outcome and overall published reports on the long-term freedom from death, repeat valvotomy, or MV replacement is over 50% over 3 to 7 years with an 80% to 90% survival rate.

The following management algorithm from the ACC/AHA 2006 Guidelines of the Management of Patients with Valvular Heart Disease are recommended for selection of patients for PMBV. Exercise ideally should be performed with treadmill or recumbent bicycle that allows for real-time Doppler echocardiographic interrogation of change in transmitral and pulmonary pressure gradients:

Class I recommendation

Moderate-to-severe MS (mean MVA less than or equal to 1.5 cm2) with favorable valvular morphology (See : MS Morphology Scoring System) and either:

  1. Symptomatic heart failure (NYHA class II-IV)

  2. Asymptomatic but presence of pulmonary hypertension at rest (PASP>50 mm Hg) or with exercise (PASP>60 mm Hg)

Class IIa recommendation

Moderate-to-severe MS (mean MVA less than or equal to 1.5 cm2) with unfavorable valvular morphology (Morphology Scoring System >8) and:

  1. Symptomatic heart failure (NYHA class II-IV)

  2. Considered not a suitable surgical candidate for open surgical commissurotomy or mitral valve repair/replacement

Class IIb recommendation

Moderate-to-severe MS (mean MVA less than or equal to 1.5 cm2) with favorable valvular morphology (See : MS Morphology Scoring System) and:

  1. Asymptomatic but presence of atrial fibrillation

Mild MS (mean MVA greater than 1.5 cm2) with favorable valvular morphology and:

  1. Symptomatic heart failure (NYHA class II-IV), typically provoked with exercise

  2. Provocable increase in hemodynamically significant pressure gradient with exercise, determined by either:

    • PASP>60 mm Hg

    • PCWP>25 mm Hg

    • Mean transmitral pressure gradient >15 mm Hg

    • Objective evidence of deterioration in functional capacity with exercise

If the MV apparatus morphology features on echocardiography appear severely injured (score >8 consistent with a nonpliable or calcified mitral valve), these patients have an increased risk of unsuccessful hemodynamic results and/or procedural complications after PMBV.

In addition, immediately prior to PMBV, all patients should undergo a transesophageal echocardiogram (TEE). If significant mitral regurgitation (3-4+) or left atrial thrombus are identified, these patients should not proceed with PMBV. Those with thrombus should be anticoagulated for a minimum of 3 months prior to evaluation for resolution by TEE before proceeding with PMBV.

Open surgical mitral commissurotomy may instead be considered for patients with unfavorable valve morphology, persistent LA thrombus despite anticoagulation, or if PMBV is unavailable. Open commissurotomy involves the use of cardiopulmonary bypass and direct visualization of surgical repair and valvuloplasty (division of the commissures, splitting of fused chordae tendineae and papillary muscles, and debridement of calcium deposits). The procedure is very well tolerated in most patients, with less than a 2% mortality rate, 5% five-year reoperation rate, and five-year complication-free survival rate between 80% and 90%.

Patients identified with mixed mitral valvular disease, or those with advanced symptomatic moderate-to-severe MS not considered candidates for PMBV or open commissurotomy, should be referred for mitral valve replacement (MVR). The mortality risk of MVR on average is approximately 6%, however patients with MS referred for MVR typically have more comorbidities which will contribute to increased risk. Although controversial, MVR is generally recommended for asymptomatic patients with severe MS (MVA less than or equal to 1 cm2) and marked pulmonary hypertension (PASP >60 to 80 mm Hg) to prevent RV failure.

The immediate results of PMBV are similar to that of surgical commissurotomy, and both procedures essentially improve the flow across the MV by successfully opening fused commissures of the MV leaflets that resulted from rheumatic inflammation, healing, and scarring of the MV apparatus. These interventions usually result in a mean doubling of the MV area and at least 50% reduction in the transmitral pressure gradient, and immediate relief of symptoms in 80% to 95% of patients appropriately selected for PMBV. Long-term freedom from death, repeat valvotomy, or MV replacement is over 50% over 3 to 7 years with 80% to 90% survival post-PMBV.

PMBV is not recommended for other causes of MS, such as congenital MS, which should be managed with surgical MV repair or replacement. Mitral valve replacement choices range from bioprosthetic valves to mechanical valves, each has distinct advantages and disadvantages, such as increasing durability at the expense of thrombogenicity.

Depending on the individual patient's age, functional status, comorbidities, and in women with child-bearing expectations, an informed decision between patient, surgeon, and cardiologist should be undertaken to match the appropriate valve to the patient's physical and lifestyle needs.

The most common complications of PMBV include vascular access complications, new (and potentially severe) mitral regurgitation requiring repair (2% to 10%) and residual atrial septal defect (ASD; 5% to 10%). Less common serious complications include periprocedural thrombus (1% to 3%), stroke (0.5% to 3%), myocardial infarction (0.3% to 0.5%), mechanical complication (including myocardial perforation and tamponade, 0.5% to 4%), and rarely death (<1%).

Repeat PMBV can be performed in patients with recurrent MS who were previously treated with percutaneous or surgical commissurotomy if valve morphology remains favorable to a good result. Other patients with MS recurrence may require MV replacement due to MV apparatus deformities resulting from prior interventions and the underlying disease process.

A. Immediate management.

Upon presentation with either acute decompensated heart failure and/or atrial fibrillation, the management of patients with mitral stenosis should be consistent with local protocols for managing either presentation acutely, regardless of the severity of stenosis unless severe pulmonary hypertension is present. This includes:

1. Upon presentation with decompensated moderate-to-severe heart failure, or uncontrolled AF with rapid ventricular response, a patient should be transferred to an emergency department for urgent care.

2. 100% oxygen, cardiac monitoring, and IV access should be instituted in the emergency department.

3. IV diuretics (20 to 40 mg IV Lasix) and IV rate-control therapy in the form of short-acting beta-blocker (metoprolol 5 mg IV q 5 minutes up to three doses) or calcium channel blocker (IV diltiazem 2.5 mg/kg IV q 10 minutes) should be provided. IV amiodarone may be considered, but will not have an immediate effect at rate or rhythm control and is considered a second-line choice.

4. Blood work should be drawn to evaluate for triggers of heart failure and AF, including a complete blood count (white blood cell count, hemoglobin, and platelets), electrolytes, renal function, and thyroid function. Alcohol history and screening may be appropriate in certain patients. A screen of the patient's coagulation status is appropriate to determine degree of anticoagulation if previously prescribed warfarin, and to establish compliance and therapeutic range if considering immediate cardioversion.

5. AF can be treated with rate control and anticoagulation with heparin as a bridge to long-term anticoagulation. Consideration for electrical or pharmacologic cardioversion will depend on the patients tolerance of rapid AF after initial management, comorbidities, duration of therapeutic anticoagulation, and if undetermined, presence/absence of contraindications to immediate cardioversion (e.g., LA thrombus by TEE).

B. Physical Examination Tips to Guide Management.

The physical examination to monitor for response to therapy or for complications from therapy are similar to the initial evaluation of mitral stenosis (see above).

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Beyond periodic evaluations of target INR achievement, there are no lab chemistries to monitor response to (or adjust) management.

However, annual clinical evaluation, echocardiography, and in patients who are difficult historians regarding potential symptoms of heart failure or in whom there may be inconsistencies, noninvasive stress testing with echocardiography is appropriate in patients with mild mitral stenosis. In those with moderate-to-severe MS, frequent reevaluation every 6 months may be appropriate to monitor closely for first onset of a clear indication for intervention.

In patients who had an LA thrombus detected on TEE prior to PMBV and had the procedure cancelled, the patient should be anticoagulated for 3 months at a target INR of 2.5 to 3.5 and until resolution of the thrombus is documented on repeat TEE. If the thrombus persists on repeat TEE, under most circumstances this would be a permanent contraindication to proceeding with PMBV and consideration for other intervention options (surgical commissurotomy, MV repair or MVR) should proceed.

Following PMBV, patients should be monitored for potential immediate complications, including cardiac perforation (<1%), severe mitral regurgitation (3%), and residual atrial septal defect with significant shunting (<5%), which may be detected immediately postprocedure and are detectable by TEE and follow-up TTE. Thromboembolism and the risk of stroke immediately following PMBV is the other most common complication (3%) that should be monitored for clinically. A postprocedure hemoglobin, creatinine, and coagulation status is typically performed to evaluate for anemia, renal dysfunction related to iodinated contrast use periprocedure (although minimal), and baseline coagulation.

D. Long-term management.

Patients with asymptomatic moderate-to-severe mitral stenosis who do not meet recommendations for percutaneous or surgical intervention should be followed clinically every 12 months, with an evaluation on history for new/worsening symptoms at rest or exertion, physical examination, ECG, and echocardiogram. Patients with symptomatic mild mitral stenosis should be followed every 6 to 12 months with clinical evaluation, and serial rest and exercise echocardiography.

Following percutaneous or surgical valvuloplasty, patients should be seen in out-patient follow-up within 3 months or earlier to screen for potential complications, and thereafter annually to monitor for recurrent MS, or its potential sequelae. Repeat PMBV can be performed in patients with recurrent MS who were previously treated with percutaneous or surgical commissurotomy if valve morphology remains favorable to a good result on echocardiography. Other patients with MS recurrence may require MV replacement due to MV apparatus deformities resulting from prior interventions and the underlying disease process.

E. Common Pitfalls and Side-Effects of Management

Management in pregnancy

1. Pregnancy.

Many women of child bearing age with mild-to-moderate MS tolerate pregnancy well with appropriate medication if necessary using diuretics and rate control therapy, which are relatively safe to use with monitoring in pregnancy. Rarely, women with severe symptoms refractory to medical management or those with severe MS who are unlikely to tolerate the physiologic changes in pregnancy and develop cardiac complications, may require valve intervention during pregnancy. If necessary, balloon valvotomy can be performed during pregnancy if patients develop refractory symptomatic heart failure due to moderate-to-severe MS with abdominal and pelvic lead shielding.

Pregnancy may trigger additional symptoms and need for therapy not present in the nonpregnant state, due to expected physiologic changes that occur in pregnancy, including a 50% increase in blood volume expansion and an even greater expansion in plasma volume that begins in the middle of the first trimester and peaks by the end of the second trimester.

Ideally, prior to pregnancy, physicians will have an opportunity to counsel women of childbearing age with mitral stenosis by:

  • Establishing the presence or absence of heart failure symptoms and current severity of mitral stenosis, including with objective functional capacity determination using exercise echocardiography and presence of pulmonary hypertension.

  • Based on establishing the severity and symptoms of MS, counsel the patient on the estimated maternal risk of complications from pulmonary edema, atrial fibrillation, pulmonary hypertension and stroke during pregnancy, as well as potential neonatal risks. A Cardiac Disease in Pregnancy (CARPREG) risk score that can aid in estimating cardiac risk during pregnancy was established in a large cohort of over 500 women with various cardiac conditions who were followed throughout pregnancy and postpartum, (See CARPREG Risk Score). If an indication is present pre-pregnancy for mitral valvuloplasty, serious consideration to address this with PMBV if appropriate prior to pregnancy is optimal to avoid complications during pregnancy.

  • The risk of a thromboembolic event during pregnancy is particularly high in those with AF due to the thrombophilic state associated with pregnancy, and therapeutic anticoagulation is recommended for all women regardless of age who are in AF during pregnancy throughout the duration of pregnancy. It is reasonable to reevaluate the benefit/risk trade-off of anticoagulation in these patients 6 weeks postpartum; however, in the setting of rheumatic heart disease-associated AF, anticoagulation is recommended lifelong. The other settings in women with rheumatic MS when anticoagulation during pregnancy is necessary is in a patient with either a prior thromboembolic event or in a patient with a mechanical mitral valve replacement. These patients need frequent (weekly) follow-up to monitor the efficacy of anticoagulation given they are at the highest risk for thromboembolic complications in pregnancy.

  • Despite its limitations, it appears clear from multiple observational studies that the most effective anticoagulant during pregnancy to prevent thrombotic complications, particularly in those with mechanical valves, is warfarin (as compared with subcutaneous (SC) LMWH and either SC or IV unfractionated heparin). However, besides the risk of bleeding and interference in metabolism with foods, medications, alcohol, and over-the-counter-medications, there is a distinct risk of fetal embryopathy associated with the use of warfarin during mid-first trimester (weeks 6 to 12 gestational age [GA]) and risk of traumatic maternal and fetal bleeding during pregnancy and delivery. Regional practice patterns vary worldwide as to whether to recommend to patients to continue with warfarin throughout pregnancy as compared with switching entirely or during critical periods of pregnancy to heparin products, but generally it is always recommended to have a thorough discussion with the patient about each option's pros and cons to reach a joint agreement before proceeding. If the patient decides to proceed with heparin during the first trimester, they should be informed that heparin is less safe compared with warfarin for protection against thrombosis and bleeding. Unfortunately, prior discussions are not always possible under all circumstances.

  • In MS patients with either a mechanical mitral valve replacement or in those with MS and persistent/paroxysmal AF, we recommend the following general anticoagulation approach, in coordination with the patient's obstetrician, that should be tailored to individual patient expectations and available resources.

  • Ideally patients enter pregnancy with a therapeutic INR on warfarin, and a previous prescription and education by the treating cardiologist to allow for a smooth early transition to LMWH if so desired. The ideal INR range for these patients is between 2.5 and 3.5.

  • Continue warfarin until GA week 6 and then transition to LMWH during GA 6 to 12 weeks.

  • The patient should start enoxaparin at 1 mg/kg SC BID with a plan to measure 4-hour-postinjection anti-factor Xa levels frequently the first week, to establish that therapy dose is effective to achieving a target range between 1.0 to 1.2 units/mL. Once repeated tests demonstrate a therapeutic range, the anti-Xa monitorings can occur once weekly. The dose of enoxaparin may need adjustment in order to reach this therapeutic range. An alternative to LMWH is IV or SC unfractionated heparin (UFH). In those who elect IV heparin, the recommended target midinterval (6 hours after dosing) aPTT is a prolongation between 2 and 3 times the control.

  • By weeks 12 to 14, women can start bridging with both anticoagulants, with a goal to transition back to therapeutic target-range warfarin (INR 2.5 to 3.5), while not discontinuing LMWH injections (or IV UFH) until this target is established.

  • Women may continue warfarin thereafter during pregnancy until approximately week 36, when in coordination with obstetrics, the patient would again transition to shorter-acting agents (IV or SC UFH or SC LMWH) with consideration for an elective induction in order to optimally discontinue anticoagulation within 24 hours prior to requiring epidural anesthesia (if desired) and minimize uterine bleeding. Because of the high risk that a women could develop spontaneous labor while therapeutically anticoagulated any time after week 36, many care teams elect to admit these patients to the hospital for monitoring while transitioning to IV UFH infusion, which has a very short half-life once discontinued. Unless life-threatening bleeding ensues, we recommend in general against using medication to reverse anticoagulation due to the risk for rebound coagulopathy.

  • Postpartum, after clearance by the patient's obstetrician, patients should restart oral anticoagulation to target levels, which are considered safe to use during breast-feeding.

  • Women with a mechanical MVR should also have low-dose aspirin 81 to 100 mg daily added to anticoagulation during pregnancy.

CARPREG risk score to estimate cardiovascular complications in pregnancy

The Cardiac Disease in Pregnancy (CARPREG) risk score is determined by evaluating for the presence of any of the following high-risk conditions prior to pregnancy:

  1. Baseline poor functional class (NYHA class III or IV, or cyanosis [SaO2 <90% at rest])

  2. Myocardial dysfunction (systemic ventricular ejection fraction <40%, or hypertrophic or restrictive cardiomyopathy)

  3. Left heart obstruction, defined by any of:

    • Mitral valve area <2 cm2;

    • Aortic valve area <1.5 cm2; or

    • Peak left ventricular outflow tract gradient >30 mm Hg

  4. A history of heart failure, pulmonary edema, stroke/transient ischemic attack, or cardiac arrhythmia before pregnancy.

The presence of any of these risk factors is assigned one point in the prediction score. The risk index is determined by the number of points (i.e., risk factors) present at the time of evaluation (see Table IV):

Table IV.

Risk Index
CARPREG Risk Score Estimated Risk (%)
0 4
1 27
>1 62

Thus, for example, a 35-year-old woman with a prior history of asymptomatic mild mitral stenosis and normal LV systolic function would be at moderate risk for a peripregnancy cardiac event, which includes pulmonary edema and/or cardiac arrhythmia in the majority of cases. If this same patient had a prior history of paroxysmal atrial fibrillation as well, then she would be at a high estimated risk for a cardiac event during pregnancy and would benefit from frequent clinical evaluations as she approached the second trimester of pregnancy until birth.

Cardiac medications considered safe during pregnancy.

Almost all cardiac medications are relatively safe in pregnancy when indicated in women with mitral stenosis, except:

  • Amiodarone or dronedarone (due to potential fetal thyroid toxicity)

  • ACE inhibitors (due to potential impairment of fetal renal/urinary tract development)

  • Atenolol (controversial; of all beta-blocker options, the one considered most correlated with fetal growth restriction and low birthweight for gestational age)

An excellent source available free online is motherrisk.org, which reports real-world clinical experience of monitoring women, pregnancies, and newborn children in women who were taking medications during pregnancy and breast-feeding.

V. Patient Safety and Quality Measures

A. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Antibiotics for secondary prevention of rheumatic fever

  • Patients diagnosed with rheumatic heart disease (i.e., rheumatic MS) should be treated for secondary prevention of rheumatic fever as they are at increased risk for recurrence. The duration of prophylaxis varies according to age of the patient and time since last diagnosis of rheumatic fever, severity of carditis, and occupational risk for reexposure to streptococcal infection.

Recommendations include the following (see Table V):

Table V.

Duration of Antibiotics for Rheumatic Heart Disease
Occupation Severity of Rheumatic Heart Disease Duration of Antibiotics
Low risk Rheumatic fever without carditis 5 years or until age 21 (whichever is longer)
Low risk Mild or healed carditis 10 years or until age 21 (whichever is longer)
Low risk Rheumatic heart disease 10 years or until age 40 (whichever is longer)
High risk of recurrent exposure occupation (e.g. teacher, daycare worker, overcrowding) Rheumatic heart disease Lifelong
  • Secondary prevention antibiotic regimens include:

    • Penicillin G: 1.2 million units IM once monthly, or

    • Penicillin V: 250 mg PO twice daily, or

    • If penicillin allergy: Erythromycin 250 mg PO twice daily, as well as other options

Antibiotics for primary prevention of infective endocarditis

  • The indications for infective endocarditis (IE) prophylaxis currently does not include the presence of mitral stenosis and is not recommended after PMBV. However, prior IE or the implantation of prosthetic material during mitral valve repair or replacement are indications for IE antibiotic prophylaxis prior to invasive dental or respiratory tract procedures.

B. What's the Evidence for specific management and treatment recommendations?

Braunwald, E, Bonow, RO. "Braunwald's heart disease: a textbook of cardiovascular medicine". Saunders. 2012.

(An excellent text for a broad overview of the diagnosis and management of mitral stenosis.)

Bonow, RO, Carabello, BA, Chatterjee, K. "ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Valvular Heart Disease)". Circulation. vol. 114. 2006. pp. e84-e231.

(The most recently updated American cardiovascular societies' practice guidelines that review in-depth the research literature supporting current recommended investigative approach, clinical practice, and therapy for mitral stenosis.)

Contant, J. "Bedside cardiology". Lippincott Williams & Wilkins. 1999.

(An excellent text for a historical review of the physical examination findings in patients with mitral stenosis.)

Fuster, V, Ryden, LE, Cannom, DS. "ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the European Society of Cardiology committee for practice guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation)". Circulation. vol. 114. 2006. pp. e257-e354.

(The most recent full edition of the American cardiovascular societies' practice guidelines for atrial fibrillation that reviews the management of patients with concomitant mitral stenosis and/or pregnancy and supporting research literature.)

Nishimura, RA, Carabello, BA, Faxon, DP. "ACC/AHA 2008 guideline update on valvular heart disease: focused update on infective endocarditis: a report of the American College of Cardiology/American Heart Association task force on practice guidelines". J Am Coll Cardiol. vol. 52. 2008. pp. 676-85.

(The most recent full edition of the American cardiovascular societies' practice guidelines for infective endocarditis that reviews the primary and secondary prevention of patients with concomitant mitral stenosis and the supporting research literature.)

Regitz-Zagrosek, V, Blomstrom Lundqvist, C. "ESC guidelines on the management of cardiovascular diseases during pregnancy". Eur Heart J. vol. 32. 2011. pp. 3147-97.

(A definitive set of practice guidelines from the European Society of Cardiology that reviews the management of cardiovascular conditions during pregnancy, including mitral stenosis, atrial fibrillation, pulmonary hypertension, and thrombosis with reference to the supporting research literature.)

Ronan, JA. "Cardiac auscultation: opening snaps, systolic clicks, and ejection sounds". Heart Disease and Stroke. vol. 2. 1993. pp. 188-91.

(An excellent article for a historical review of the physical examination findings in patients with mitral stenosis.)
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