# 36 - 274 Mitral Stenosis

### 274 Mitral Stenosis

Patrick T. O’Gara, Joseph Loscalzo

Mitral Stenosis
PART 6
Disorders of the Cardiovascular System
The role of the physical examination in the evaluation of patients with 
valvular heart disease is also considered in Chaps. 44 and 246; of elec­
trocardiography (ECG) in Chap. 247; of echocardiography and other 
noninvasive imaging techniques in Chap. 248; and of cardiac catheter­
ization and angiography in Chap. 249.
MITRAL STENOSIS
■
■ETIOLOGY AND PATHOLOGY
Rheumatic fever is the leading cause of mitral stenosis (MS) (Table 274-1; 
see also Chap. 371). Other less common etiologies of obstruction 
to left ventricular inflow include congenital mitral valve stenosis, 
cor triatriatum, mitral annular calcification with extension onto the 
leaflets, systemic lupus erythematosus, rheumatoid arthritis, left atrial 
myxoma, and infective endocarditis with large vegetations. Pure or 
predominant MS occurs in ~40% of all patients with rheumatic heart 
disease and a history of rheumatic fever (Chap. 371). In other patients 
with rheumatic heart disease, lesser degrees of MS may accompany 
mitral regurgitation (MR) and aortic valve disease. With reductions 
in the incidence of acute rheumatic fever, particularly in temperate 
climates and middle- to high-income countries, the incidence of MS 
has declined considerably over the past several decades. However, it 
remains a major problem in low-income countries, especially in subSaharan Africa, India, Southeast Asia, and Oceania (Chap. 272).
In rheumatic MS, chronic inflammation leads to diffuse thicken­
ing of the valve leaflets with formation of fibrous tissue often with 
calcific deposits. The mitral commissures fuse, the chordae tendineae 
fuse and shorten, the valvular cusps become rigid, and the pathologic 
process eventually leads to narrowing at the apex of the funnel-shaped 
(“fish-mouth”) valve. Although the initial insult to the mitral valve is 
rheumatic, later changes may be exacerbated by inflammation, fibrosis, 
and trauma due to altered flow patterns. Calcification of the stenotic 
mitral valve immobilizes the leaflets and narrows the orifice further. 
Thrombus formation and arterial embolization may arise from the 
calcific valve itself, but in patients with atrial fibrillation (AF), thrombi 
arise more frequently from the dilated left atrium (LA), particularly 
from within the LA appendage.
■
■PATHOPHYSIOLOGY
In normal adults, the area of the mitral valve orifice is 4–6 cm2. In 
the presence of significant obstruction, i.e., when the orifice area is 
reduced to <~2 cm2, blood can flow from the LA to the left ventricle 
(LV) only if propelled by an abnormally elevated left atrioventricular 
pressure gradient, the hemodynamic hallmark of MS. When the mitral 
valve opening is reduced to <1.5 cm2, referred to as “severe” MS, an 
LA pressure of ~25 mmHg is required to maintain a normal cardiac 
output (CO). The elevated pulmonary venous and pulmonary arterial 
(PA) wedge pressures reduce pulmonary compliance, contributing to 
exertional dyspnea. The first bouts of dyspnea are usually precipitated 
TABLE 274-1  Major Causes of Mitral Stenosis
Etiologies
Rheumatic fever
Congenital (parachute valve, cor triatriatum)
Severe mitral annular calcification with leaflet involvement
SLE, RA
Myxoma
IE with large vegetations
Abbreviations: IE, infective endocarditis; RA, rheumatoid arthritis; SLE, systemic 
lupus erythematosus.

by clinical events that increase the rate of blood flow across the mitral 
orifice, resulting in further elevation of the LA pressure (see below).
To assess the severity of obstruction hemodynamically, both the 
transvalvular pressure gradient and the flow rate must be measured 
(Chap. 249). The latter depends not only on the CO but on the heart 
rate, as well. An increase in heart rate shortens diastole proportionately 
more than systole and diminishes the time available for flow across the 
mitral valve. Therefore, at any given level of CO, tachycardia, includ­
ing that associated with rapid AF, augments the transvalvular pressure 
gradient and elevates further the LA pressure. Similar considerations 
apply to the pathophysiology of tricuspid stenosis (TS).
The LV diastolic pressure and ejection fraction (EF) are normal in 
isolated MS. In MS and sinus rhythm, the elevated LA and PA wedge 
pressures exhibit a prominent atrial contraction pattern (a wave) and 
a gradual pressure decline after the v wave and mitral valve opening 
(y descent). In severe MS and whenever pulmonary vascular resistance 
is significantly increased, the PA pressure (PAP) is elevated at rest and 
rises further during exercise, often causing secondary elevations of 
right ventricular (RV) end-diastolic pressure and volume.
Cardiac Output 
In patients with severe MS (mitral valve orifice 
1–1.5 cm2), the CO is normal or almost so at rest, but rises subnormally 
during exertion. In patients with very severe MS (valve area <1 cm2), 
particularly those in whom pulmonary vascular resistance is markedly 
elevated, the CO is subnormal at rest and may fail to rise or may even 
decline during activity.
Pulmonary Hypertension 
The clinical and hemodynamic fea­
tures of MS are influenced importantly by the level of the PAP. Pul­
monary hypertension results from (1) passive backward transmission 
of the elevated LA pressure; (2) pulmonary arteriolar constriction (the 
so-called “second stenosis”), which presumably is triggered by LA and 
pulmonary venous hypertension (reactive pulmonary hypertension); 
(3) interstitial edema in the walls of the small pulmonary vessels; and 
(4) at end stage, organic obliterative changes in the pulmonary vascular 
bed. Severe pulmonary hypertension results in RV enlargement, 
secondary tricuspid regurgitation (TR), and pulmonic regurgitation 
(PR), as well as right-sided heart failure.
■
■SYMPTOMS
In temperate climates, the latent period between the initial attack of 
rheumatic carditis (in the increasingly rare circumstances in which a 
history of one can be elicited) and the development of symptoms due to 
MS is generally about two decades; most patients begin to experience 
disability in the fourth decade of life. Studies carried out before the 
development of surgical mitral valvotomy revealed that once a patient 
with MS became seriously symptomatic, the disease progressed inexo­
rably to death within 2–5 years.
In patients whose mitral orifices are large enough to accommodate 
a normal blood flow with only mild elevations of LA pressure, marked 
elevations of this pressure leading to dyspnea and cough may be precip­
itated by sudden changes in the heart rate, volume status, or CO, as, for 
example, with severe exertion, excitement, fever, severe anemia, parox­
ysmal AF and other tachycardias, sexual intercourse, pregnancy, and 
thyrotoxicosis. As MS progresses, lesser degrees of stress precipitate 
dyspnea, the patient becomes limited in daily activities, and orthop­
nea and paroxysmal nocturnal dyspnea develop. The development of 
persistent AF often marks a turning point in the patient’s course and 
is generally associated with acceleration of the rate at which symptoms 
progress. Hemoptysis (Chap. 41) results from rupture of pulmonarybronchial venous connections secondary to pulmonary venous hyper­
tension. It occurs most frequently in patients who have elevated LA 
pressures without markedly elevated pulmonary vascular resistances 
and is rarely fatal. Recurrent pulmonary emboli (Chap. 290), sometimes 
with infarction, are an important cause of morbidity and mortality late 
in the course of MS and often arise from right atrial mural thrombus. 
Pulmonary infections, i.e., bronchitis, bronchopneumonia, and lobar 
pneumonia, commonly complicate untreated MS, especially during 
the winter months. In patients with significant left atrial enlargement,

cardiovocal syndrome (Ortner’s syndrome) may develop with hoarse­
ness secondary to left recurrent laryngeal nerve compression.
Pulmonary Changes 
In addition to the aforementioned changes 
in the pulmonary vascular bed, fibrous thickening of the walls of the 
alveoli and pulmonary capillaries occurs commonly in MS. The vital 
capacity, total lung capacity, maximal breathing capacity, and oxygen 
uptake per unit of ventilation are reduced (Chap. 296). Pulmonary 
compliance falls further as pulmonary capillary pressure rises during 
exercise.
Thrombi and Emboli 
Thrombi may form in the left atria, par­
ticularly within the enlarged atrial appendages of patients with MS. 
Systemic embolization, the incidence of which is 10–20%, occurs more 
frequently in patients with AF, in patients >65 years of age, and in those 
with a reduced CO. However, systemic embolization may be the pre­
senting feature in otherwise asymptomatic patients with only mild MS.
■
■PHYSICAL FINDINGS
(See also Chaps. 44 and 246).
Inspection and Palpation 
In patients with severe MS, there may 
be a malar flush with pinched and blue facies. In patients with sinus 
rhythm and severe pulmonary hypertension or associated TS, the jugu­
lar venous pulse reveals prominent a waves due to vigorous right atrial 
systole. The systemic arterial pressure is usually normal or slightly low. 
A parasternal lift signifies an enlarged RV. A diastolic thrill may very 
rarely be present at the cardiac apex, with the patient in the left lateral 
recumbent position.
Auscultation 
The first heart sound (S1) is usually accentuated 
in the early stages of the disease and slightly delayed. The pulmonic 
component of the second heart sound (P2) also is often accentuated 
with elevated PAPs, and the two components of the second heart sound 
(S2) are closely split. The opening snap (OS) of the mitral valve is most 
readily audible in expiration at, or just medial to, the cardiac apex. 
This sound generally follows the sound of aortic valve closure (A2) by 
0.05–0.12 s. The time interval between A2 and OS varies inversely with 
the severity of the MS. The OS is followed by a low-pitched, rumbling, 
diastolic murmur, heard best at the apex with the patient in the left 
lateral recumbent position (see Fig. 246-5); it is accentuated by mild 
exercise (e.g., a few rapid sit-ups) carried out just before auscultation. 
In general, the duration of this murmur correlates with the severity 
of the stenosis in patients with preserved CO. In patients with sinus 
rhythm, the murmur often reappears or becomes louder during atrial 
systole (presystolic accentuation). Soft, grade I or II/VI systolic mur­
murs may be heard at or medial to the apex and may signify mixed 
mitral valve disease with regurgitation. Hepatomegaly, ankle edema, 
ascites, and pleural effusion, particularly in the right pleural cavity, may 
occur in patients with MS and RV failure.
Associated Lesions 
With severe pulmonary hypertension, a pan­
systolic murmur produced by functional TR may be audible along the 
left sternal border. This murmur is usually louder during inspiration 
and diminishes during forced expiration (Carvallo’s sign). When the 
CO is markedly reduced in MS, the typical auscultatory findings, 
including the diastolic rumbling murmur, may not be detectable (silent 
MS), but they may reappear as compensation is restored. The Graham 
Steell murmur of PR, a high-pitched, diastolic, decrescendo blowing 
murmur along the left sternal border, results from dilation of the pul­
monary valve ring and occurs in patients with mitral valve disease and 
severe pulmonary hypertension. This murmur may be indistinguish­
able from the more common murmur produced by aortic regurgita­
tion (AR), although it may increase in intensity with inspiration and is 
accompanied by a loud and often palpable P2.
■
■LABORATORY EXAMINATION
ECG 
In MS and sinus rhythm, the P wave usually suggests LA 
enlargement (see Fig. 247-8). It may become tall and peaked in lead 
II and upright in lead V1 when severe pulmonary hypertension or TS 

CHAPTER 274
Mitral Stenosis
FIGURE 274-1  Continuous wave Doppler interrogation of transmitral valve 
velocities in a patient with severe rheumatic mitral stenosis. Electrocardiogram on 
top. Vertical scale in meters/second. Horizontal scale in seconds at sweep speed 
of 75 mm/se. Velocity is converted to pressure using the Bernoulli equation. In this 
example, the mean mitral valve gradient (area under the green tracing) is calculated 
to 38 mmHg and mitral valve area to 0.7 cm2.
complicates MS and right atrial (RA) enlargement develops. The QRS 
complex is usually normal. However, with severe pulmonary hyperten­
sion, right axis deviation and RV hypertrophy are often present.
Echocardiogram (See also Chap. 248) 
Transthoracic echo­
cardiography (TTE) with color flow and spectral Doppler imaging 
provides critical information, including measurements of mitral inflow 
velocity during early (E wave) and late (A wave in patients in sinus 
rhythm) diastolic filling, estimates of the transvalvular peak and mean 
gradients and mitral orifice area (Fig. 274-1), the presence and severity 
of any associated MR, the extent of leaflet calcification and restriction, 
the degree of distortion of the subvalvular apparatus, and the anatomic 
suitability for percutaneous mitral balloon commissurotomy (PMBC; 
see below). In addition, TTE provides an assessment of LV and RV 
function, chamber sizes, an estimation of the PA systolic pressure 
based on the tricuspid regurgitant jet velocity, and an indication of the 
presence and severity of any associated valvular lesions, such as aortic 
stenosis (AS) and/or regurgitation. Transesophageal echocardiogra­
phy (TEE) provides superior images and should be used when TTE 
is inadequate for guiding management decisions. TEE is especially 
indicated to exclude the presence of LA thrombus prior to PMBC. The 
performance of TTE with exercise to evaluate the mean mitral diastolic 
gradient, PAPs, and RV function can be very helpful in the evaluation 
of patients with MS when there is a discrepancy between the clinical 
findings and the resting hemodynamics.
Chest X-Ray 
The earliest changes are straightening of the upper left 
border of the cardiac silhouette, prominence of the main PAs, dilation 
of the upper lobe pulmonary veins, and posterior displacement of the 
esophagus by an enlarged LA. Kerley B lines are fine, dense, opaque, 
horizontal lines that are most prominent in the lower and mid-lung 
fields that result from distention of interlobular septae and lymphatics 
with edema when the resting mean LA pressure exceeds ~20 mmHg.
■
■DIFFERENTIAL DIAGNOSIS
Like MS, significant MR may also be associated with a prominent dia­
stolic murmur at the apex due to increased antegrade transmitral flow, 
but in patients with isolated MR, this diastolic murmur commences 
slightly later than in patients with MS, and there is often clear-cut 
evidence of LV enlargement. An OS and increased P2 are absent, and 
S1 is soft or absent. An apical pansystolic murmur of at least grade III/VI 
intensity as well as an S3 suggests significant MR. Similarly, the apical 
mid-diastolic murmur associated with severe AR (Austin Flint murmur) 
may be mistaken for MS but can be differentiated from it because it 
is not intensified in pre-systole and becomes softer with administra­
tion of amyl nitrite or other arterial vasodilators. TS, which occurs 
rarely in the absence of MS, may mask many of the clinical features 
of MS or be clinically silent; when present, the diastolic murmur of

TS increases with inspiration and the y descent in the jugular venous 
pulse is delayed.

Atrial septal defect (Chap. 280) may be mistaken for MS; in both 
conditions, there is often clinical, ECG, and chest x-ray evidence of RV 
enlargement and accentuation of pulmonary vascularity. However, the 
absence of LA enlargement and of Kerley B lines and the demonstra­
tion of fixed splitting of S2 with a grade II or III mid-systolic murmur 
at the mid to upper left sternal border all favor atrial septal defect over 
MS. Atrial septal defects with large left-to-right shunts may result in 
functional TS because of the enhanced diastolic flow. An incomplete 
right bundle branch block pattern on ECG is often present.
PART 6
Disorders of the Cardiovascular System
Left atrial myxoma (Chap. 282) may obstruct LA emptying, causing 
dyspnea, a diastolic murmur, and hemodynamic changes resembling 
those of MS. However, patients with an LA myxoma often have features 
suggestive of a systemic disease, such as weight loss, fever, anemia, 
systemic emboli, and elevated serum IgG and interleukin 6 (IL-6) con­
centrations. The auscultatory findings may change markedly with body 
position. The diagnosis can be established by the demonstration of a 
characteristic echo-producing mass in the LA with TTE.
■
■CARDIAC CATHETERIZATION
Left and right heart catheterization can be useful when there is a 
discrepancy between the clinical and noninvasive findings, includ­
ing those from TEE and exercise echocardiographic testing when 
appropriate. Catheterization can also be helpful in assessing associated 
lesions, such as AS and AR, and in patients with recurring or worsening 
symptoms late after mitral valve intervention. Computed tomographic 
coronary angiography is increasingly used to screen preoperatively for 
Severe MS
MVA ≤1.5 cm2
Symptomatic
Stage D
Severe
symptoms
NYHA III–IV
No
Pliable valve
No clot
<2+ MR
Surgical
candidate
Yes
Yes
No
PMBC at
CVC (1)
MV surgery
(1)
FIGURE 274-2  Management of rheumatic mitral stenosis. See legend for Fig. 272-4 for explanation of treatment recommendations (Class I, IIa, IIb) and disease stages (C, 
D). Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography 
may also be helpful when there is a discrepancy between clinical and noninvasive findings. AF, atrial fibrillation; CVC, comprehensive valve center; MR, mitral regurgitation; 
MS, mitral stenosis; MV, mitral valve; MVA, mitral valve area; MVR, mitral valve surgery (repair or replacement); NYHA, New York Heart Association; PASP, pulmonary 
arterial systolic pressure; PMBC, percutaneous mitral balloon commissurotomy. (Reproduced with permission from CM Otto et al: ACC/AHA guideline for the management of 
patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 
143:e72, 2021.)

the presence of coronary artery disease in appropriate patients prior to 
heart valve surgery or transcatheter treatment.
TREATMENT
Mitral Stenosis (Fig. 274-2)
Penicillin prophylaxis of group A β-hemolytic streptococcal infec­
tions (Chap. 371) for secondary prevention of rheumatic fever is 
important for at-risk patients with rheumatic MS. Recommenda­
tions for infective endocarditis prophylaxis are similar to those 
for other valve lesions and are restricted to patients at high risk 
for complications from infection, including patients with a his­
tory of endocarditis. In symptomatic patients, some improvement 
usually occurs with restriction of sodium intake and small doses 
of oral diuretics. Beta blockers, nondihydropyridine calcium chan­
nel blockers (e.g., verapamil or diltiazem), and digitalis glycosides 
are useful in slowing the ventricular rate of patients with AF. 
Vitamin K antagonist therapy (such as warfarin) targeted to an 
international normalized ratio (INR) of 2–3 should be adminis­
tered indefinitely to patients with MS who have AF, a history of 
thromboembolism, or demonstrated LA thrombus. The routine 
use of a vitamin K antagonist in patients in sinus rhythm with LA 
enlargement (maximal dimension >5.5 cm) with or without spon­
taneous echo contrast is more controversial. In a randomized trial 
of patients with rheumatic MS and AF, there was a significantly 
higher incidence of death among patients treated with rivaroxaban 
than with vitamin K antagonist therapy. A vitamin K antagonist is 
Rheumatic mitral
stenosis
Progressive MS
MVA >1.5 cm2
Asymptomatic
Stage C
Exertional
symptoms
Pliable valve
No clot
<2+ MR
Stress test
Hemodynamically
significant MS
New AF
PASP
>50 mmHg
Pliable valve
No clot
<2+ MR
PMBC at
CVC (2b)
PMBC at
CVC (2b)
PMBC at
CVC (2a)

recommended to reduce the risk for stroke or systemic embolism in 
at-risk patients with rheumatic MS.
If AF is of relatively recent onset in a patient whose MS is not 
severe enough to warrant PMBC or surgical intervention, reversion 
to sinus rhythm pharmacologically or by means of electrical coun­
tershock is indicated. Usually, cardioversion should be undertaken 
after the patient has had at least 3 consecutive weeks of anticoagu­
lant treatment to a therapeutic INR. If cardioversion is indicated 
more urgently, then intravenous heparin should be provided and 
TEE performed to exclude the presence of LA thrombus before 
the procedure. Conversion to sinus rhythm is rarely successful or 
sustained in patients with severe MS, particularly those in whom 
the LA is significantly enlarged or in whom AF has been present for 
>1 year, conditions that favor the development of an LA myopathy.
MITRAL COMMISSUROTOMY
Unless there is a contraindication, mitral commissurotomy is indi­
cated in symptomatic (New York Heart Association [NYHA] func­
tional class II–IV) patients with isolated severe MS, whose effective 
orifice (valve area) is <~1 cm2/m2 body surface area or <1.5 cm2 in 
normal-sized adults. Mitral commissurotomy can be carried out 
either percutaneously or surgically. In PMBC (Figs. 274-3 and 
274-4), a catheter is directed into the LA after transseptal punc­
ture, and a single balloon is directed across the valve and inflated 
in the valvular orifice. Ideal patients have relatively pliable leaflets 
with little or no commissural calcium. In addition, the subvalvular 
structures should not be significantly scarred or thickened, and 
there should be no LA thrombus. Any associated MR should be of 
≤2+/4+ severity. The short- and long-term results of this procedure 
in appropriate patients are similar to those of surgical commissur­
otomy, but with less morbidity and a lower periprocedural mortality 
rate. Event-free survival in younger (<45 years) patients with pliable 
valves is excellent, with rates as high as 80–90% over 3–7 years. 
Therefore, PMBC is the procedure of choice for such patients when 
it can be performed by a skilled operator in a high-volume center.
Guide
wire
Stiffening
cannula
B
A
D
C
FIGURE 274-3  Inoue balloon technique for percutaneous mitral balloon 
commissurotomy. A. After transseptal puncture, the deflated balloon catheter is 
advanced across the interatrial septum, then across the mitral valve and into the 
left ventricle. B–D. The balloon is inflated stepwise within the mitral orifice.

PREDILATATION
POSTDILATATION
ECG
ECG
CHAPTER 274
LV
LV

Pressure (mmHg)
Mitral Stenosis
LA
LA

Mean mitral gradient 3 mmHg
Cardiac output 3.8 L/min
Mitral valve area 1.8 cm2
Mean mitral gradient 15 mmHg
Cardiac output 3 L/min
Mitral valve area 0.6 cm2
FIGURE 274-4  Simultaneous left atrial (LA) and left ventricular (LV) pressure before 
and after percutaneous mitral balloon commissurotomy (PMBC) in a patient with severe 
mitral stenosis. ECG, electrocardiogram. (Courtesy of Raymond G. McKay, MD.)
TTE is helpful in identifying patients for the percutaneous pro­
cedure; TEE is performed routinely to exclude LA thrombus and 
to assess the degree of MR at the time of the scheduled procedure. 
An “echo score” has been developed to help guide decision-making. 
The score accounts for the degree of leaflet thickening, calcification, 
and mobility, and for the extent of subvalvular thickening. A lower 
score predicts a higher likelihood of successful PMBC.
In patients in whom PMBC is not possible or unsuccessful, or 
in many patients with restenosis after previous surgery, an “open” 
surgical commissurotomy using cardiopulmonary bypass is neces­
sary. In addition to opening the valve commissures, it is important 
to loosen any subvalvular fusion of papillary muscles and chordae 
tendineae; to remove large deposits of calcium, thereby improving 
valvular function; and to remove atrial thrombi. The perioperative 
mortality rate for this type of mitral valve repair procedure is ~2%.
Successful commissurotomy is defined by a 50% reduction in the 
mean mitral valve gradient and a doubling of the mitral valve area. 
Successful commissurotomy, whether balloon or surgical, usually 
results in striking symptomatic and hemodynamic improvement 
and prolongs survival. However, there is no evidence that the proce­
dure improves the prognosis of patients with slight or no functional 
impairment. Therefore, unless recurrent systemic embolization or 
severe pulmonary hypertension has occurred (PA systolic pressures 
>50 mmHg at rest or >60 mmHg with exercise), commissurotomy 
is not recommended for patients who are asymptomatic and/or who 
have mild or moderate stenosis (mitral valve area >1.5 cm2). When 
there is little symptomatic improvement after commissurotomy, it 
is likely that the procedure was ineffective, that it induced MR, or 
that associated valvular or myocardial disease was present. About 
half of all patients undergoing surgical mitral commissurotomy 
require reoperation by 10 years. In the pregnant patient with MS, 
commissurotomy should be carried out if pulmonary congestion 
occurs despite intensive medical treatment. PMBC is the preferred 
strategy in this setting and is performed with TEE and no or mini­
mal x-ray exposure.
Mitral valve replacement (MVR) is necessary in patients with 
MS and significant associated MR, those in whom the valve has 
been severely distorted by previous transcatheter or operative 
manipulation, or those in whom the surgeon does not find it pos­
sible to improve valve function significantly with commissurotomy. 
MVR is now routinely performed with preservation of the chordal 
attachments to optimize LV functional recovery. Perioperative mor­
tality rates with MVR vary with age, LV function, the presence of 
CAD, and associated comorbidities. They average 2–5% overall but