topics

11/6/25

1988 PART 6 Disorders of the Cardiovascular System

diaphoresis. Anginal chest pain even in the absence of CAD may occur

in patients with severe AR, even in younger patients. Anginal pain may

develop at rest as well as during exertion. Nocturnal angina may be

a particularly troublesome symptom, and it may be accompanied by

marked diaphoresis. The anginal episodes can be prolonged and often

do not respond satisfactorily to sublingual nitroglycerin. Systemic fluid

accumulation, including congestive hepatomegaly and ankle edema,

may develop late in the course of the disease.

■ PHYSICAL FINDINGS

In chronic severe AR, the jarring of the entire body and the bobbing

motion of the head with each systole can be appreciated, and the abrupt

distention and collapse of the larger arteries are easily visible. The

examination should be directed toward the detection of conditions

predisposing to AR, such as bicuspid valve, IE, Marfan syndrome, or

ankylosing spondylitis.

Arterial Pulse A rapidly rising “water-hammer” pulse, which collapses suddenly as arterial pressure falls rapidly during late systole and

diastole (Corrigan’s pulse), and capillary pulsations, an alternate flushing and paling of the skin at the root of the nail while pressure is applied

to the tip of the nail (Quincke’s pulse), are characteristic of chronic

severe AR. A booming “pistol-shot” sound can be heard over the femoral arteries (Traube’s sign), and a to-and-fro murmur (Duroziez’s sign)

is audible if the femoral artery is lightly compressed with a stethoscope.

The arterial pulse pressure is widened as a result of both systolic

hypertension and a lowering of the diastolic pressure. The measurement of arterial diastolic pressure with a sphygmomanometer may be

complicated by the fact that systolic sounds are frequently heard with

the cuff completely deflated. However, the level of cuff pressure at the

time of muffling of the Korotkoff sounds (phase IV) generally corresponds fairly closely to the true intra-arterial diastolic pressure. As the

disease progresses and the LV end-diastolic pressure rises, the arterial

diastolic pressure may actually rise as well, because the aortic diastolic

pressure cannot fall below the LV end-diastolic pressure. For the same

reason, acute severe AR may also be accompanied by only a slight widening of the pulse pressure. Such patients are invariably tachycardic as

the heart rate increases in an attempt to preserve the CO.

Palpation In patients with chronic severe AR, the LV impulse is

heaving and displaced laterally and inferiorly. The systolic expansion

and diastolic retraction of the apex are prominent. A diastolic thrill

may be palpable along the left sternal border in thin-chested individuals, and a prominent systolic thrill may be palpable in the suprasternal

notch and transmitted upward along the carotid arteries. This systolic

thrill and the accompanying murmur do not necessarily signify the

coexistence of AS. In some patients with AR or with combined AS and

AR, the carotid arterial pulse may be bisferiens, i.e., with two systolic

waves separated by a trough (see Fig. 239-2C).

Auscultation In patients with severe AR, the aortic valve closure

sound (A2

) is usually absent. A systolic ejection sound is audible in

patients with BAV disease, and occasionally an S4

also may be heard.

The murmur of chronic AR is typically a high-pitched, blowing, decrescendo diastolic murmur, heard best in the third intercostal space along

the left sternal border (see Fig. 239-5B). In patients with mild AR, this

murmur is brief, but as the severity increases, it generally becomes

louder and longer, indeed holodiastolic. When the murmur is soft, it

can be heard best with the diaphragm of the stethoscope and with the

patient sitting up, leaning forward, and with the breath held in forced

expiration. In patients in whom the AR is caused by primary valvular

disease, the diastolic murmur is usually louder along the left than the

right sternal border. However, when the murmur is louder along the

right sternal border, it suggests that the AR is caused by aneurysmal

dilation of the aortic root. “Cooing” or musical diastolic murmurs

suggest eversion of an aortic cusp vibrating in the regurgitant stream.

A mid-systolic ejection murmur is frequently audible in isolated

AR. It is generally heard best at the base of the heart and is transmitted

along the carotid arteries. This murmur may be quite loud without signifying aortic valve obstruction. A third murmur sometimes heard in

patients with severe AR is the Austin Flint murmur, a soft, low-pitched,

rumbling mid-to-late diastolic murmur. It is probably produced by the

diastolic displacement of the anterior leaflet of the mitral valve by the

AR stream and is not associated with hemodynamically significant

mitral valve obstruction. The auscultatory features of AR are intensified by strenuous and sustained handgrip, which augments systemic

vascular resistance and increases LV afterload.

In acute severe AR, the elevation of LV end-diastolic pressure may

lead to early closure of the mitral valve, a soft S1

, a pulse pressure that

is not particularly wide, and a soft, short, early diastolic murmur of AR.

■ LABORATORY EXAMINATION

ECG In patients with chronic severe AR, ECG signs of LV hypertrophy are common (Chap. 240). In addition, these patients frequently

exhibit ST-segment depression and T-wave inversion in leads I, aVL,

, and V6

(“LV strain”). Left axis deviation and/or QRS prolongation

may also be present.

Echocardiogram LV size is increased in chronic AR, and systolic

function is normal or even supernormal until myocardial contractility

declines, as signaled by a decrease in EF or increase in the end-systolic

dimension. A rapid, high-frequency diastolic fluttering of the anterior

mitral leaflet produced by the impact of the regurgitant jet is a characteristic finding. The echocardiogram is also useful in determining

the cause of AR, by detecting dilation of the aortic annulus and root,

aortic dissection (see Fig. 241-5), or primary leaflet pathology. With

severe AR, the central jet width assessed by color flow Doppler imaging

exceeds 65% of the width of the LV outflow tract, the regurgitant volume is ≥60 mL/beat, the regurgitant fraction is ≥50%, and there is diastolic flow reversal in the proximal portion of the descending thoracic

aorta. The continuous-wave Doppler profile of the AR jet shows a rapid

deceleration time in patients with acute severe AR, due to the rapid

increase in LV diastolic pressure. Surveillance transthoracic echocardiography (TTE) forms the cornerstone of longitudinal follow-up and

allows for the early detection of changes in LV size and/or function.

For patients in whom TTE is limited by poor acoustical windows or

inadequate characterization of LV function or the cause or severity of

the regurgitation, cardiac magnetic resonance (CMR) imaging can be

performed. This modality also allows for accurate assessment of aortic

size and contour. It can also be utilized to screen for LV fibrosis as

assessed with late gadolinium enhancement. Both CMR imaging and

cardiac computed tomography (CT) can provide detailed assessment

of aortic valve and root anatomy. Transesophageal echocardiography

(TEE) can also provide detailed anatomic assessment of the valve, root,

and portions of the aorta. There is increasing experience with the use of

three-dimensional echocardiography to measure LV volumes.

Chest X-Ray In chronic severe AR, the apex is displaced downward

and to the left in the frontal projection. In the left anterior oblique and

lateral projections, the LV is displaced posteriorly and encroaches on

the spine. When AR is caused by primary disease of the aortic root,

aneurysmal dilation of the aorta may be noted, and the aorta may

fill the retrosternal space in the lateral view. Echocardiography, CMR

imaging, and chest CT angiography are more sensitive than the chest

x-ray for the detection of root and ascending aortic enlargement.

Cardiac Catheterization and Angiography When needed,

right and left heart catheterization with contrast aortography can provide confirmation of the magnitude of regurgitation and the status of

LV function. Coronary angiography is performed routinely in appropriate patients prior to surgery, although this anatomic information can

also be gained with coronary CT angiographic techniques.

TREATMENT

Aortic Regurgitation

ACUTE AORTIC REGURGITATION (FIG. 262-1)

Patients with acute severe AR may respond to intravenous diuretics

and vasodilators (such as sodium nitroprusside), but stabilization is

Aortic Regurgitation

1989CHAPTER 262

Low

surgical risk

Aortic regurgitation

Severe AR

(VC >0.6 cm, holodiastolic

aortic flow reversal, RVol ≥60 mL,

RF ≥50%, ERO ≥0.3 cm2)

Symptomatic

(Stage D)

Asymptomatic

(Stage C)

Moderate

Other

cardiac

surgery

Other

cardiac

surgery

AVR (1) AVR (2a) AVR (2b) AVR (2a)

EF ≤55%

(Stage C2)

EF ≥55%

LVESD >50 mm

and

LVESD >25 mm/m2

Progressive

changes

(≥3 studies)

EF 55–60%

EDD >65 mm

FIGURE 262-1 Management of patients with aortic regurgitation. See legend for Fig. 261-4 for explanation of treatment recommendations (Class I, IIa, and IIb) and disease

stages (B, C1, C2, and 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. Surgery is indicated for patients with severe AR and symptoms,

LV dysfunction, or other indications for operation (e.g., aneurysm disease). Surgery is also reasonable once the LV indexed end-systolic dimension reaches or exceeds 25 mm/

. Patients who do not meet criteria for intervention should be monitored periodically with clinical and echocardiographic follow-up. AR, aortic regurgitation; AVR, aortic valve

replacement (valve repair may be appropriate in selected patients); EDD, end-diastolic dimension; EF, ejection fraction; ERO, effective regurgitant orifice; LV, left ventricular;

LVEDD, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; RF, regurgitant fraction; RVol, regurgitant

volume; VC, vena contracta. (Reproduced with permission from CM Otto et al: 2020 AHA/ACC Guideline for management of patients with valvular heart disease: A report of the

American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 143:e72, 2021.)

usually short-lived and operation is indicated urgently. Intra-aortic

balloon counterpulsation is contraindicated. Beta blockers are best

avoided so as not to reduce the CO further or slow the heart rate,

thus allowing more time for diastolic filling of the LV. Surgery is

the treatment of choice and is usually necessary within 24 h of

diagnosis.

CHRONIC AORTIC REGURGITATION

The onset of symptoms, or LV systolic dysfunction, is an indication for surgery. Medical treatment with diuretics and vasodilators

(angiotensin-converting enzyme inhibitors, angiotensin receptor

blockers [ARBs], dihydropyridine calcium channel blockers, or

hydralazine) may be useful as a temporizing measure. Surgery

can then be performed in a more controlled setting. The use of

vasodilators to extend the compensated phase of chronic severe

AR in asymptomatic patients before the onset of symptoms or

the development of LV dysfunction is not useful, although these

agents should be employed to treat hypertension (systolic blood

pressure >140 mm Hg). It is often difficult to achieve adequate

blood pressure control because of the increased stroke volume and

enhanced LV ejection that accompany severe AR. Cardiac arrhythmias and systemic infections are poorly tolerated in patients with

severe AR and must be treated promptly and vigorously. Although

nitroglycerin and long-acting nitrates are not as helpful in relieving

anginal pain as they are in patients with coronary heart disease,

they are worth a trial. Patients with syphilitic aortitis should receive

a full course of penicillin therapy (Chap. 182). Beta blockers and

the ARB losartan may be useful to retard the rate of aortic root

enlargement in young patients with Marfan’s syndrome and aortic

root dilation. A randomized controlled trial showed no difference in efficacy between atenolol and losartan for this indication.

Whether beta blockers or ARBs are useful in retarding the rate

of growth of aortic aneurysms in other patient subsets (e.g., BAV

disease with aortopathy, Takayasu’s disease) has not been demonstrated. Beta blockers in patients with valvular AR were previously

considered relatively contraindicated due to concern that slowing

of the heart rate would allow more time for diastolic regurgitation.

Observational reports, however, have suggested that beta blockers

may provide functional benefit in some patients with chronic AR.

Beta blockers can sometimes provide incremental blood pressure

lowering in patients with chronic AR and hypertension. They can

also lessen the sense of forceful heart action that many patients find

uncomfortable. Patients with severe AR, particularly those with an

associated aortopathy, should avoid isometric exercises.

1990 PART 6 Disorders of the Cardiovascular System

FIGURE 262-2 Valve-sparing aortic root reconstruction (David procedure). Aortic root and proximal ascending aorta (A) are resected (B) with sinuses of Valsalva and

mobilized coronary artery buttons remaining. Subannular sutures (C) are placed, commissural posts are drawn up inside the valve, and the annular sutures are passed

through the proximal end of the graft. The annular sutures are tied (D), the valve is reimplanted inside the graft, aortic continuity is reestablished with another graft of

appropriate size, and the coronary buttons are attached to the side of the graft. (From P Steltzer et al [eds]: Valvular Heart Disease: A Companion to Braunwald’s Heart

Disease, 3rd ed, Fig. 12-27, p. 200.)

SURGICAL TREATMENT

In deciding on the advisability and proper timing of surgical treatment, two points should be kept in mind: (1) patients with chronic

severe AR usually do not become symptomatic until after the development of myocardial dysfunction; and (2) when delayed too long

(defined as >1 year from onset of symptoms or LV dysfunction),

surgical treatment often does not restore normal LV size and function. Therefore, in patients with chronic severe AR, careful clinical

follow-up and noninvasive testing with echocardiography at ~6- to

12-month intervals are necessary if operation is to be undertaken at

the optimal time, i.e., after the onset of LV dysfunction but prior to

the development of severe symptoms. Exercise testing may be helpful

to assess effort tolerance more objectively. Operation can be deferred

as long as the patient both remains asymptomatic and retains normal

LV function without severe or progressive chamber dilation.

Aortic valve replacement (AVR) is indicated for the treatment

of severe AR in symptomatic patients irrespective of LV function.

In general, the operation should be carried out in asymptomatic

patients with severe AR and progressive LV dysfunction defined

by an LVEF <55% on serial studies, an LV end-systolic dimension

>50 mm (>25 mm/m2

), or an LV diastolic dimension >65 mm.

Smaller dimensions may be appropriate thresholds in individuals of smaller stature or when there is evidence of progressively

decreasing LV function or increasing LV size on serial studies and

the anticipated risks for surgical morbidity and mortality are low.

Two case series from surgical referral centers have suggested that

surgery should be performed at an even lower threshold for LV endsystolic dimension index (≥20 mm/m2

), but data from randomized

controlled trials are lacking. Patients with severe AR without indications for operation should be followed by clinical and echocardiographic examination every 6–12 months. Transcatheter aortic valve

implantation (TAVI) is not recommended for patients with severe

AR who are surgical candidates. Technical success with TAVI in

patients with chronic AR is limited by the degree of aortic annular

dilation and the relative paucity of valvular and annular calcium.

Surgical options for management of aortic valve and root disease have expanded considerably over the past decade. AVR with

a suitable mechanical or tissue (biological) prosthesis is generally

necessary in patients with rheumatic AR and in many patients with

other causes of valvular AR. Rarely, when a leaflet has been perforated during IE or torn from its attachments to the aortic annulus

by thoracic trauma, primary surgical repair may be possible. When

AR is due to aneurysmal dilation of the root or proximal ascending

aorta rather than to primary valve involvement, it may be possible

to reduce or eliminate the regurgitation by narrowing the annulus

or by excising a portion of the aortic root without replacing the

valve. Elective, valve-sparing aortic root reconstruction generally

involves reimplantation of the valve in a contoured graft with reattachment of the coronary artery buttons into the side of the graft

and is best undertaken in specialized surgical centers (Fig. 262-2).

Resuspension of the native aortic valve leaflets is possible in ~50%

of patients with acute AR in the setting of type A aortic dissection.

Mitral Stenosis

1991CHAPTER 263

TABLE 262-2 Mortality Rates After Aortic Valve Surgerya

OPERATION NUMBER

UNADJUSTED OPERATIVE

MORTALITY (%)

AVR (isolated) 25,274 1.9

AVR + CAB 15,855 3.6

Data are for calendar year 2018 during which 1088 participant groups reported a

total of 287,872 procedures.

Abbreviations: AVR, aortic valve replacement; CAB, coronary artery bypass.

Source: Adapted from ME Bowdish et al: Ann Thorac Surg 109:1646, 2020.

In other conditions, however, AR can be effectively eliminated only

by replacing the aortic valve, as well as the dilated or aneurysmal

ascending aorta responsible for the regurgitation, and implanting a

composite valve-graft conduit. This formidable procedure entails a

higher risk than isolated AVR.

As is true in patients with other valvular heart disease, both

operative and late mortality risks are largely dependent on the stage

of the disease and myocardial function at the time of operation. The

overall operative mortality rate for isolated AVR (performed for

either or both AS or AR) is ~2% (Table 262-2). However, patients

with AR, marked cardiac enlargement, and established LV dysfunction experience an operative mortality rate of ~10% and a late

mortality rate of ~5% per year due to LV failure despite a technically

satisfactory operation. Nonetheless, because of the very poor prognosis with medical management, even patients with advanced LV

systolic dysfunction should be considered for operation.

Patients with acute severe AR require prompt (24–48 h) surgical

treatment, which may be lifesaving.

■ FURTHER READING

Lacro RV et al: Atenolol versus losartan in children and young adults

with Marfan’s syndrome. N Engl J Med 371:2061, 2014.

Malaisrie SC, McCarthy PM: Surgical approach to disease of the

aortic valve and the aortic root, in Valvular Heart Disease: A Companion to Braunwald’s Heart Disease, 5th ed. CM Otto, RO Bonow (eds).

Philadelphia, Elsevier Saunders, 2020, pp 267–288.

Otto CM et al: 2020 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 role of the physical examination in the evaluation of patients with

valvular heart disease is also considered in Chaps. 42 and 239; of electrocardiography (ECG) in Chap. 240; of echocardiography and other

noninvasive imaging techniques in Chap. 241; and of cardiac catheterization and angiography in Chap. 242.

MITRAL STENOSIS

■ ETIOLOGY AND PATHOLOGY

Rheumatic fever is the leading cause of mitral stenosis (MS)

(Table 263-1; see also Chap. 359). 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.

263 Mitral Stenosis

Patrick T. O’Gara, Joseph Loscalzo

TABLE 263-1 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.

Pure or predominant MS occurs in ~40% of all patients with rheumatic heart disease and a history of rheumatic fever (Chap. 359). 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 sub-Saharan Africa, India, Southeast Asia, and Oceania

(Chap. 261).

In rheumatic MS, chronic inflammation leads to diffuse thickening 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 to the valve 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

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. 242). 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, including

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

1992 PART 6 Disorders of the Cardiovascular System

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 features of MS are influenced importantly by the level of the PAP. Pulmonary 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 inexorably 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 precipitated by sudden changes in the heart rate, volume status, or CO,

as, for example, with severe exertion, excitement, fever, severe anemia,

paroxysmal 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

orthopnea 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. 39) results from rupture of

pulmonary-bronchial venous connections secondary to pulmonary

venous hypertension. 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. 279),

sometimes with infarction, are an important cause of morbidity and

mortality late in the course of MS. Pulmonary infections, i.e., bronchitis, bronchopneumonia, and lobar pneumonia, commonly complicate

untreated MS, especially during the winter months.

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. 285). Pulmonary

compliance falls further as pulmonary capillary pressure rises during

exercise.

Thrombi and Emboli Thrombi may form in the left atria, particularly 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 presenting feature in otherwise asymptomatic patients with only mild MS.

■ PHYSICAL FINDINGS

(See also Chaps. 42 and 239)

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 jugular 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

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. 239-5); 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 murmurs 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 pansystolic 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 pulmonary valve ring and occurs in patients with mitral valve disease and

severe pulmonary hypertension. This murmur may be indistinguishable from the more common murmur produced by aortic regurgitation

(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. 240-8). It may become tall and peaked in lead

II and upright in lead V1

when severe pulmonary hypertension or TS

complicates MS and right atrial (RA) enlargement develops. The QRS

complex is usually normal. However, with severe pulmonary hypertension, right axis deviation and RV hypertrophy are often present.

Echocardiogram (See also Chap. 241) Transthoracic echocardiography (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, 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 echocardiography (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 and PAPs 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

Mitral Stenosis

1993CHAPTER 263

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 diastolic 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

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

administration 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. 269) 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 demonstration 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.

Left atrial myxoma (Chap. 271) 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) concentrations. 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, including

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 later after mitral valve intervention. Computed tomographic

coronary angiography is increasingly used to screen preoperatively for

the presence of coronary artery disease in appropriate patients prior to

heart valve surgery or transcatheter treatment.

TREATMENT

Mitral Stenosis (Fig. 263-1)

Penicillin prophylaxis of group A β-hemolytic streptococcal infections (Chap. 359) for secondary prevention of rheumatic fever is

Yes

Rheumatic mitral

stenosis

Severe MS

MVA ≤1.5 cm2

Surgical

candidate

PMBC at

CVC (1)

MV surgery

(1)

PMBC at

CVC (2b)

PMBC at

CVC (2b)

PMBC at

CVC (2a)

New AF PASP

>50 mmHg

Symptomatic

Stage D

Severe

symptoms

NYHA III–IV

No Pliable valve

No clot

<2+ MR

Pliable valve

No clot

<2+ MR

Pliable valve

No clot

<2+ MR

Stress test

Hemodynamically

significant MS

Asymptomatic

Stage C

Progressive MS

MVA >1.5 cm2

Exertional

symptoms

FIGURE 263-1 Management of rheumatic mitral stenosis. See legend for Fig. 261-4 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.)

1994 PART 6 Disorders of the Cardiovascular System

important for at-risk patients with rheumatic MS. Recommendations 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 history of

endocarditis. In symptomatic patients, some improvement usually occurs with restriction of sodium intake and small doses of

oral diuretics. Beta blockers, nondihydropyridine calcium channel

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 administered 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 spontaneous echo contrast

is more controversial. As of this writing, non–vitamin K oral anticoagulants (e.g., apixaban, rivaroxaban) have not been adequately

studied in patients with moderate or severe rheumatic MS and,

thus, are not recommended.

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 countershock is indicated. Usually, cardioversion should be

undertaken after the patient has had at least 3 consecutive weeks

of anticoagulant 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 indicated in symptomatic (New York Heart Association [NYHA] Functional 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. 263-2 and

263-3), a catheter is directed into the LA after transseptal puncture, 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 commissurotomy, 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.

TTE is helpful in identifying patients for the percutaneous procedure; 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 necessary. 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

C D

A B

Guide

wire

Stiffening

cannula

FIGURE 263-2 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.

ECG

PREDILATATION

Pressure (mmHg)

Mean mitral gradient 15 mmHg

Cardiac output 3 L/min

Mitral valve area 0.6 cm2

ECG

POSTDILATATION

Mean mitral gradient 3 mmHg

Cardiac output 3.8 L/min

Mitral valve area 1.8 cm2

FIGURE 263-3 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.)

Mitral Regurgitation

1995CHAPTER 264

TABLE 263-2 Mortality Rates after Mitral Valve Surgerya

OPERATION NUMBER

UNADJUSTED OPERATIVE

MORTALITY (%)

MVR (isolated) 10,699 4.5

MVR + CAB 3509 9.6

MVRp 12,424 1.2

MVRp + CAB 4093 5.4

Data are for calendar year 2018 during which 1088 participant groups reported

a total of 287,872 procedures. Surgical mitral valve commissurotomy cases are

included in the mitral valve repair procedures.

Abbreviations: CAB, coronary artery bypass; MVR, mitral valve replacement; MVRp,

mitral valve repair.

Source: Adapted from ME Bowdish et al: Ann Thorac Surg 109:1646, 2020.

and prolongs survival. However, there is no evidence that the procedure 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 minimal 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 possible to

improve valve function significantly with commissurotomy. MVR

is now routinely performed with preservation of the chordal attachments to optimize LV functional recovery. Perioperative mortality

rates with MVR vary with age, LV function, the presence of CAD,

and associated comorbidities. They average 5% overall but are lower

in young patients and may be twice as high in patients >65 years

of age with significant comorbidities (Table 263-2). Because there

are also long-term complications of valve replacement, patients in

whom preoperative evaluation suggests the possibility that MVR

may be required should be operated on only if they have severe

MS—i.e., an orifice area ≤1.5 cm2

—and are in NYHA Class III,

i.e., symptomatic with ordinary activity despite optimal medical

therapy. The overall 10-year survival of surgical survivors is ~70%.

Long-term prognosis is worse in patients >65 years of age and those

with marked disability and marked depression of the CO preoperatively. Pulmonary hypertension and RV dysfunction are additional

risk factors for poor outcome.

■ FURTHER READING

Nishimura RA et al: Mitral valve disease: Current management and

future challenges. Lancet 387:1324, 2016.

Otto CM et al: 2020 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 role of the physical examination in the evaluation of patients with

valvular heart disease is also considered in Chaps. 42 and 239; of electrocardiography (ECG) in Chap. 240; of echocardiography and other

noninvasive imaging techniques in Chap. 241; and of cardiac catheterization and angiography in Chap. 242.

■ ETIOLOGY

Mitral regurgitation (MR) may result from an abnormality or disease

process that affects any one or more of the five functional components

of the mitral valve apparatus (leaflets, annulus, chordae tendineae, papillary muscles, and subjacent myocardium) (Table 264-1). Acute MR

can occur in the setting of acute myocardial infarction (MI) with papillary muscle rupture (Chap. 275), following blunt chest wall trauma,

or during the course of infective endocarditis (IE) owing to leaflet

perforation or destruction. With acute MI, the posteromedial papillary muscle is involved much more frequently than the anterolateral

papillary muscle because of its singular blood supply. Transient, acute

MR can occur during periods of active ischemia and bouts of angina

pectoris. Rupture of chordae tendineae can result in “acute-on-chronic

MR” in patients with myxomatous degeneration of the valve apparatus.

Chronic MR can result from several disease processes (Table 264-1).

Distinction should be drawn between primary (degenerative) MR, in

which the leaflets and/or chordae tendineae are primarily responsible

for abnormal valve function, and secondary (functional) MR, in which

the leaflets and chordae tendineae are usually normal but the regurgitation is caused by left ventricular (LV) remodeling, annular dilation,

papillary muscle displacement, dyssynchrony, posterior leaflet tethering, or their combination. Patient assessment, treatment approach, and

long-term prognosis differ significantly between primary and secondary MR. Mitral valve prolapse (MVP) is discussed more extensively

264 Mitral Regurgitation

Patrick T. O’Gara, Joseph Loscalzo

TABLE 264-1 Major Causes of Mitral Regurgitation (MR)

Etiologies

Acute

Papillary muscle rupture (post-MI)

Chordal rupture/leaflet flail (MVP, IE)

Blunt trauma

Chronic

Primary (affecting leaflets, chordae)

Myxomatous (MVP, Barlow’s, forme fruste)

Rheumatic fever

IE (healed)

Congenital (cleft, AV canal)

Radiation

Secondary (leaflets, chordae are “innocent bystanders”)

Ischemic cardiomyopathy

Dilated cardiomyopathy

HOCM (with SAM)

AF with LA enlargement and annular dilation (atrial functional MR)

Mitral annular calcificationa

Mitral annular calcification may include elements of both primary and secondary

MR (mixed) as the disease process may encroach on the leaflets, impair the

normal sphincteric function of the annulus, or both. There are additional examples

of “mixed” secondary MR such as the coexistence of MVP with an ischemic

cardiomyopathy.

Abbreviations: AF, atrial fibrillation; AV, atrioventricular; HOCM, hypertrophic

obstructive cardiomyopathy; IE, infective endocarditis; LA, left atrial; LV, left

ventricular; MI, myocardial infarction; MVP, mitral valve prolapse; SAM, systolic

anterior motion.

1996 PART 6 Disorders of the Cardiovascular System

in Chap. 265. The rheumatic process produces rigidity, deformity,

and retraction of the valve cusps and commissural fusion, as well as

shortening, contraction, and fusion of the chordae tendineae. MR can

persist after resolution of the acute phase of infection and inflammation. MR may occur as a congenital anomaly (Chap. 269), most commonly as a defect of the endocardial cushions (atrioventricular cushion

defects). A cleft anterior mitral valve leaflet accompanies ostium

primum atrial septal defect. Radiation can result in leaflet thickening,

retraction, and calcification, often in association with annular and

chordal involvement and some degree of mitral stenosis. Chronic MR

occurs frequently after prior MI(s) associated with changes in LV size,

shape, and function. Similar mechanisms of annular dilation and ventricular remodeling contribute to the MR that occurs among patients

with nonischemic forms of dilated cardiomyopathy once the LV enddiastolic dimension reaches 6 cm. The MR associated with hypertrophic obstructive cardiomyopathy (HOCM) is usually dynamic in

nature and dependent on systolic anterior motion of the anterior mitral

valve leaflet into a narrowed LV outflow tract. Patients with chronic

persistent atrial fibrillation (AF) may develop atrial remodeling and

annular dilation with inadequate leaflet lengthening and MR (atrial

functional MR). Secondary MR due to LV remodeling is more frequently encountered in the community than secondary MR that occurs

in association with AF and annular dilation. Annular calcification can

result in MR when it encroaches on the leaflets or results in decreased

sphincteric function and is especially prevalent among patients with

advanced renal disease and is commonly observed in women >65 years

of age with hypertension and diabetes mellitus. Irrespective of cause,

chronic severe MR is often progressive because enlargement of the left

atrium (LA) places tension on the posterior mitral leaflet, pulling it further away from the mitral orifice and thereby aggravating the valvular

dysfunction. Similarly, LV dilation increases the regurgitation, which,

in turn, enlarges the LA and LV further, resulting in a vicious circle;

hence the aphorism, “MR begets MR.”

■ PATHOPHYSIOLOGY

The resistance to LV emptying (LV afterload) is reduced in patients

with MR. As a consequence, the LV is decompressed into the LA during ejection, and with the reduction in LV size during systole, there

is a rapid decline in LV tension. The initial compensation to MR is

more complete LV emptying. However, LV volume increases progressively with time as the severity of the regurgitation increases and as

LV contractile function deteriorates. This increase in LV volume is

often accompanied by a reduced forward cardiac output (CO). LV

compliance is often increased, and thus, LV diastolic pressure does not

increase until late in the course. The regurgitant volume varies directly

with the LV systolic pressure and the size of the regurgitant orifice;

the latter, in turn, is influenced by the extent of LV and mitral annular

dilation. Because ejection fraction (EF) rises in severe MR in the presence of normal LV function, even a modest reduction in this parameter

(<60%) reflects significant contractile dysfunction.

During early diastole, as the distended LA empties, there is a particularly rapid y descent in the absence of accompanying MS. A brief,

early diastolic LA-LV pressure gradient (often generating a rapid filling

sound [S3

] and mid-diastolic murmur masquerading as MS) may occur

in patients with pure, severe MR as a result of the very rapid flow of

blood across a normal-sized mitral orifice.

Measurements of LV ejection fraction (LVEF), CO, pulmonary

arterial (PA) systolic pressure, regurgitant volume, regurgitant fraction

(RF), and the effective regurgitant orifice area can be obtained during

a careful Doppler echocardiographic examination. These measurements can also be obtained accurately with cardiac magnetic resonance

(CMR) imaging, although this technology is not widely available. Left

and right heart catheterization with contrast ventriculography is used

less frequently. Chronic, severe MR is defined by a regurgitant volume

≥60 mL/beat, regurgitant fraction (RF) ≥50%, and effective regurgitant

orifice area ≥0.40 cm2

. In patients with secondary MR, in whom the

severity of MR can be underappreciated using echocardiographic/

Doppler techniques, lesser degrees of regurgitation may carry relatively

greater prognostic weight. The adverse prognosis in secondary MR

related to adverse LV remodeling is intimately related to the degree of

myocardial dysfunction.

LA Compliance In acute severe MR, the regurgitant volume is

delivered into a normal-sized LA having normal or reduced compliance. As a result, LA pressures rise markedly for any increase in LA

volume. The v wave in the LA pressure pulse is usually prominent,

LA and pulmonary venous pressures are markedly elevated, and pulmonary edema is common. Because of the rapid rise in LA pressures

during ventricular systole, the murmur of acute MR is early in timing

and decrescendo in configuration ending well before S2

, as a reflection

of the progressive diminution in the LV-LA pressure gradient. LV systolic function in acute MR may be normal, hyperdynamic, or reduced,

depending on the clinical context.

Patients with chronic severe MR, on the other hand, develop marked

LA enlargement and increased LA compliance with little if any increase

in LA and pulmonary venous pressures for any increase in LA volume.

The LA v wave is relatively less prominent. The murmur of chronic MR

is classically holosystolic in timing and plateau in configuration, as a

reflection of the near-constant LV-LA pressure gradient. These patients

usually complain of severe fatigue and exhaustion secondary to a low

forward CO, whereas symptoms resulting from pulmonary congestion

are less prominent initially; AF is almost invariably present once the

LA dilates significantly.

■ SYMPTOMS

Patients with chronic mild-to-moderate, isolated MR are usually

asymptomatic. This form of LV volume overload is well tolerated.

Fatigue, exertional dyspnea, and orthopnea are the most prominent

complaints in patients with chronic severe MR. Palpitations are common and may signify the onset of AF. Late-onset right-sided heart

failure, with painful hepatic congestion, ankle edema, distended neck

veins, ascites, and secondary tricuspid regurgitation (TR), occurs in

patients with MR who have associated pulmonary vascular disease

and pulmonary hypertension. Acute pulmonary edema is common in

patients with acute severe MR.

■ PHYSICAL FINDINGS

In patients with chronic severe MR, the arterial pressure is usually normal, although the carotid arterial pulse may show a sharp, low-volume

upstroke owing to the reduced forward CO. A systolic thrill is often

palpable at the cardiac apex, the LV is hyperdynamic with a brisk systolic impulse and a palpable rapid-filling wave (S3

), and the apex beat

is often displaced laterally.

In patients with acute severe MR, the arterial pressure may be reduced

with a narrow pulse pressure, the jugular venous pressure and waveforms may be normal or increased and exaggerated, the apical impulse is

not displaced, and signs of pulmonary congestion are prominent.

Auscultation S1

is generally absent, soft, or buried in the holosystolic murmur of chronic, severe MR. In patients with severe MR, the

aortic valve may close prematurely (due to the reduced forward cardiac

output), resulting in wide but physiologic splitting of S2

. A low-pitched

occurring 0.12–0.17 s after the aortic valve closure sound, i.e., at the

completion of the rapid-filling phase of the LV, is believed to be caused

by the sudden tensing of the papillary muscles, chordae tendineae, and

valve leaflets. It may be followed by a short, rumbling, mid-diastolic

murmur, even in the absence of structural MS. In patients with ischemic or dilated cardiomyopathy, however, a third sound (S3

) may also

signify ventricular dysfunction. A fourth heart sound is often audible

in patients with acute severe MR who are in sinus rhythm. A presystolic

murmur is not ordinarily heard with isolated MR.

A systolic murmur of at least grade III/VI intensity is the most

characteristic auscultatory finding in chronic severe MR. It is usually

holosystolic (see Fig. 239-5A), but as previously noted, it is decrescendo

and ceases in mid-to-late systole in patients with acute severe MR. The

systolic murmur of chronic MR is usually most prominent at the apex

and radiates to the axilla. However, in patients with ruptured chordae

tendineae or primary involvement of the posterior mitral leaflet with

prolapse or flail, the regurgitant jet is eccentric, directed anteriorly, and

Mitral Regurgitation

1997CHAPTER 264

strikes the LA wall adjacent to the aortic root. In this situation, the systolic murmur is transmitted to the base of the heart and, therefore, may

be confused with the murmur of AS. In patients with ruptured chordae

tendineae, the systolic murmur may have a cooing or “seagull” quality,

whereas a flail leaflet may produce a murmur with a musical quality.

The systolic murmur of chronic MR not due to MVP is intensified by

isometric exercise (handgrip) but is reduced during the strain phase of

the Valsalva maneuver because of the associated decrease in LV preload.

■ LABORATORY EXAMINATION

ECG In patients with sinus rhythm, there is evidence of LA enlargement, but right atrial (RA) enlargement also may be present when pulmonary hypertension is significant and affects RV function and size.

Chronic severe MR is frequently associated with AF. In many patients,

there is no clear-cut ECG evidence of enlargement of either ventricle.

In others, the signs of eccentric LV hypertrophy are present.

Echocardiogram Transthoracic echocardiography (TTE) is indicated to assess the mechanism of the MR and its hemodynamic severity. LV function can be assessed from LV end-diastolic and end-systolic

volumes and EF. Observations can be made regarding leaflet structure

and function, chordal integrity, LA and LV size, annular calcification,

and regional and global LV systolic function. Doppler imaging should

demonstrate the width or area of the color flow MR jet within the LA,

the duration and intensity of the continuous wave Doppler signal, the

pulmonary venous flow contour, the early peak mitral inflow velocity,

and quantitative measures of regurgitant volume, RF, and effective

regurgitant orifice area. In addition, the PA pressures (PAPs) can be

estimated from the TR jet velocity. TTE is also indicated to follow the

course of patients with chronic MR and to provide rapid assessment for

any clinical change. Transesophageal echocardiography (TEE) provides

greater anatomic detail than TTE (see Fig. 241-5). Exercise testing with

TTE can be useful to assess exercise capacity as well as any dynamic

change in MR severity, PA systolic pressures, and biventricular function, for patients in whom there is a discrepancy between clinical

findings and the results of other noninvasive testing.

Chest X-Ray The LA and LV are the dominant chambers in

chronic MR. Late in the course of the disease, the LA may be massively enlarged and forms the right border of the cardiac silhouette.

Pulmonary venous congestion, interstitial edema, and Kerley B lines

are sometimes noted. Marked calcification of the mitral leaflets occurs

commonly in patients with long-standing, combined rheumatic MR

and MS, as well as in patients with radiation-induced mitral valve disease. Calcification of the mitral annulus may be visualized, particularly

on the lateral view of the chest. Patients with acute severe MR may

have asymmetric pulmonary edema if the regurgitant jet is directed

predominantly to the orifice of an upper lobe pulmonary vein.

TREATMENT (FIGS. 264-1 AND 264-2)

Mitral Regurgitation

MEDICAL TREATMENT

The management of chronic severe MR depends to some degree on

its cause. Anticoagulation with either warfarin or a direct oral agent

(e.g., apixaban, rivaroxaban) should be provided if AF intervenes,

as guided by the CHA2

DS2

-VASc risk score. The direct oral anticoagulants should not be used if moderate or severe rheumatic mitral

Yes

MV surgery (1)

Primary