1999CHAPTER 265

as well as MV anatomy that would predict a >95% of a successful

and durable repair in a low surgical risk patient. These aggressive

recommendations for surgery are predicated on the adverse longterm consequences of waiting for LV function to decline further as

well as the outstanding results achievable with mitral valve repair by

reference surgeons at high-volume centers. Indeed, repair of myxomatous MR (e.g., prolapse, flail) in patients <75 years with normal

LV systolic function and no coronary artery disease (CAD) can

now be performed by experienced surgeons with <1% perioperative

mortality risk. The risk of stroke, however, is also ~1%. Repair is feasible in up to 95% of patients with myxomatous disease operated on

by a high-volume surgeon in a referral center of excellence. Repair

techniques include chordal transfer, creation of neochords, limited

leaflet resection, and insertion of an annuloplasty band. Long-term

durability is excellent; the incidence of reoperative surgery for failed

primary repair is ~1% per year for the first 10 years after surgery.

For patients with AF, left or biatrial maze surgery, or radiofrequency

isolation of the pulmonary veins, along with left atrial appendage

amputation, is performed to reduce the risk of recurrent postoperative AF and associated thrombus formation.

The surgical management of patients with secondary MR is more

complicated. Surgery for patients with ischemic MR most often

involves simultaneous coronary artery revascularization. Current

surgical practice includes either annuloplasty repair with an undersized, rigid ring or chord-sparing valve replacement for patients

with moderate or greater degrees of MR. Valve repair for ischemic

MR is associated with lower perioperative mortality rates than

valve replacement but significantly higher rates of recurrent MR

over time. Thus, replacement may be preferred over repair in this

context. In patients with ischemic MR and significantly impaired LV

systolic function (EF <30%), the risk of surgery is higher, recovery

of LV performance is incomplete, and long-term survival is reduced.

Referral for surgery must be individualized and made only after

aggressive attempts to improve symptoms with GDMT and CRT,

when indicated. The routine performance of surgical valve repair in

patients with significant secondary MR due to a dilated cardiomyopathy has not been shown to improve long-term survival compared

with optimal GDMT. Patients with acute severe MR can often be

stabilized temporarily with appropriate medical therapy, but surgical correction will be necessary emergently in the case of papillary

muscle rupture and within days to weeks in most other settings.

When surgical treatment is contemplated, left and right heart

catheterization and left ventriculography may be helpful in confirming the presence of severe MR in patients in whom there is

a discrepancy between the clinical and TTE findings that cannot

be resolved with TEE or CMR. Coronary angiography identifies

patients who require concomitant coronary revascularization.

TRANSCATHETER MITRAL VALVE REPAIR AND

REPLACEMENT

A transcatheter approach to the treatment of either primary or secondary MR may be feasible in selected patients with appropriate

mitral valve anatomy. One approach involves the deployment of a

clip delivered via transseptal puncture that grasps the leading edges

of the mitral leaflets in their mid-portion (anterior scallop to posterior scallop or A2-P2; Fig. 264-3). The length and width of the gap

between these leading edges, as well as other considerations such as

leaflet thickening and calcification, dictate patient eligibility. The clip

device for transcatheter edge-to-edge repair (TEER) is commercially

available for treatment of both primary and secondary MR in appropriately selected patients (Figs. 264-1 and 264-2). The results of transthoracic and transesophageal echocardiographic imaging are critical

to patient selection, along with a detailed assessment of surgical risk,

comorbidities, and the adequacy of GDMT for heart failure. The use

of TEER with a clip device in addition to medical therapy was shown

to be superior to medical therapy alone in a trial involving symptomatic heart failure patients with reduced EF and at least moderately

severe secondary MR. Patients treated with the clip device had fewer

heart failure hospitalizations and longer survival than those treated

medically. This was the first trial to show such benefit in patients with

secondary MR and has impacted clinical practice. Other transcatheter

approaches to mitral valve repair include the deployment of a device

within the coronary sinus that can be adjusted to reduce mitral annular circumference and the effective orifice area of the valve much like

a surgically implanted ring. Variations in the anatomic relationship

of the coronary sinus to the mitral annulus and circumflex coronary

artery have limited the applicability of this technique. Attempts to

reduce the septal-lateral dimension of a dilated annulus using adjustable cords placed across the LV in a subvalvular location have also

been investigated. Construction of neochords to the mitral leaflets

under TEE guidance using a system delivered via the cardiac apex is

also under study. Investigational experience to date with transcatheter

mitral valve replacement systems is in early clinical stages, although

the field is evolving rapidly.

■ FURTHER READING

Bonow RO et al: 2020 focused update of the 2017 expert consensus

decision pathway on the management of mitral regurgitation. J Am

Coll Cardiol 75:2236, 2020.

El Sabbagh A et al: Mitral valve regurgitation in the contemporary

era: Insights into diagnosis, management and future directions. J Am

Coll Cardiol Imaging 11:628, 2018.

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.

Rugueiro A et al: Transcatheter mitral valve replacement: Insights

from early clinical experience and future challenges. J Am Coll

Cardiol 69:2175, 2017.

Stone GW et al: Transcatheter mitral valve repair in patients with

heart failure. N Engl J Med 379:2307, 2018.

FIGURE 264-3 Clip used to grasp the free edges of the anterior and posterior

leaflets in their midsections during transcatheter repair of selected patients with

mitral regurgitation. (MitraClip is a trademark of Abbott or its related companies.

Reproduced with permission from Abbott © 2021. All rights reserved.)

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.

265 Mitral Valve Prolapse

Patrick T. O’Gara, Joseph Loscalzo

2000 PART 6 Disorders of the Cardiovascular System

MITRAL VALVE PROLAPSE

Mitral valve prolapse (MVP), also variously termed the systolic clickmurmur syndrome, Barlow’s syndrome (Fig. 265-1), floppy-valve syndrome, and billowing mitral leaflet syndrome, is a relatively common

but highly variable clinical syndrome resulting from diverse pathologic mechanisms affecting the mitral valve apparatus. Among these

are excessive or redundant mitral leaflet tissue, which is commonly

associated with myxomatous degeneration and greatly increased

concentrations of certain glycosaminoglycans. MVP is the most common abnormality leading to primary mitral regurgitation (MR) (see

Chap. 264).

In most patients with MVP, the cause is unknown, but in some, it

appears to be genetically determined. A reduction in the production

of type III collagen has been implicated, and electron microscopy has

revealed fragmentation of collagen fibrils.

MVP is a frequent finding in patients with heritable disorders of

connective tissue, including Marfan syndrome (Chap. 413), osteogenesis imperfecta, and Ehlers-Danlos syndrome. MVP may be associated

with thoracic skeletal deformities similar to but not as severe as those

in Marfan syndrome, such as a high-arched palate and alterations

of the chest and thoracic spine, including the so-called straight back

syndrome. Other associated features can include a history of inguinal

hernias, joint dislocations, meniscal tears, and easy bruisability.

In most patients with MVP, myxomatous degeneration is confined

to the mitral valve, although the tricuspid and aortic valves may also

be affected. The posterior mitral leaflet is usually more affected than

the anterior, and the mitral valve annulus is often dilated. In many

patients, elongated, redundant, or ruptured chordae tendineae cause or

contribute to the regurgitation.

A B

C

FIGURE 265-1 Congenital or developmental mitral valve prolapse. Myxomatous

thickening and prolapse of the mitral valve can occur in isolation in 2–3% of the

general population or may be associated with heritable collagen-vascular disorders

and aortic root dilation, such as in Marfan syndrome. Myxomatous degeneration

of the valve predisposes to severe regurgitation and chordal rupture and is a

frequent indication for mitral valve repair or replacement. Prolapse can affect

one or both leaflets, to varying degrees. A. Three-dimensional transesophageal

echocardiogram showing a myxomatous mitral valve from the left atrial en face

aspect. There is billowing and prolapse of the entire middle scallop of the posterior

leaflet (asterisk). (Figure courtesy of Douglas C. Shook, MD, Department of

Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital.)

B. The posterior leaflet of the mitral valve demonstrates marked prolapse and

hooding in all segments and severe redundancy in this photograph taken from the

vantage point of the left atrium. C. Opening the left heart reveals prominent mitral

leaflet hooding (arrows). The chordae are focally thickened but are not fused as

would be the case in rheumatic valve disease. (Used with permission from JC Wu,

RF Padera: Clinicopathologic correlates, in Atlas of Echocardiography, 2nd ed, SD

Solomon [ed], E Braunwald [series ed]. Philadelphia, Current Medicine Group LLC,

2008. p 363.)

MVP also may occur rarely as a sequel to acute rheumatic fever, in

ischemic heart disease, and in various cardiomyopathies, as well as in

20% of patients with ostium secundum atrial septal defect.

MVP may lead to excessive stress on the papillary muscles, which,

in turn, leads to dysfunction and ischemia of the papillary muscles

and the subjacent ventricular myocardium. Rupture of chordae tendineae and progressive annular dilation and calcification contribute to

valvular regurgitation, which then places more stress on the diseased

mitral valve apparatus, thereby creating a vicious cycle. ECG changes

(see below) and ventricular arrhythmias described in some patients

with MVP appear to result from regional ventricular dysfunction and

fibrosis related to the increased stress placed on the papillary muscles.

■ CLINICAL FEATURES

MVP is more common in women than men and occurs most frequently

between the ages of 15 and 30 years; the clinical course is most often

benign. MVP may also be observed in older (>50 years) patients, often

men, in whom MR is often more severe because of chordal rupture and

requires surgical treatment. There is an increased familial incidence for

some patients, suggesting an autosomal dominant form of inheritance

with incomplete penetrance. MVP varies in its clinical expression, ranging from only a systolic click and murmur with mild prolapse of the

posterior leaflet to severe MR due to chordal rupture and leaflet flail.

The degree of myxomatous change of the leaflets can also vary widely.

In many patients, the condition progresses over years or decades; in

others, it worsens rapidly as a result of chordal rupture or endocarditis.

Most patients are asymptomatic and remain so for their entire lives.

However, in North America, MVP is now the most common cause

of isolated severe MR requiring surgical treatment. Arrhythmias,

most commonly ventricular premature contractions and paroxysmal

supraventricular and ventricular tachycardia, as well as atrial fibrillation (AF), have been reported and may cause palpitations, lightheadedness, and syncope. Sudden death is a very rare complication

and occurs most often in patients with severe MR and depressed left

ventricle (LV) systolic function, although it can occur in individuals

with normal LV size and function. A small subset of MVP patients

with high-grade ventricular ectopy has been identified with phenotypic features including electrocardiographic inferior-apical T-wave

abnormalities, high-density premature ventricular complexes at rest,

mitral annular disjunction (defined as abnormal atrial displacement of

the mitral valve leaflet hinge point), and papillary muscle fibrosis on

cardiac magnetic resonance imaging with late gadolinium enhancement. In addition, there may be an excess risk of sudden death among

patients with a flail leaflet. Many patients have chest pain that is difficult to evaluate; it is often substernal, prolonged, and not related to

exertion, but may rarely resemble angina pectoris. Transient cerebral

ischemic attacks secondary to emboli from the mitral valve due to

endothelial disruption have been reported. Infective endocarditis may

occur in patients with MR and/or leaflet thickening.

Auscultation A frequent finding is the mid- or late (nonejection)

systolic click, which occurs 0.14 s or more after S1

 and is thought to

be generated by the sudden tensing of slack, elongated chordae tendineae or by the prolapsing mitral leaflet when it reaches its maximal

excursion. Systolic clicks may be multiple and may be followed by

a high-pitched, mid-late systolic crescendo–decrescendo murmur,

which occasionally is “whooping” or “honking” and is heard best at

the apex. Radiation of the murmur will depend on the involved leaflet.

With posterior leaflet prolapse, the jet of MR is directed anteriorly and

the murmur will radiate to the base of the heart. With anterior leaflet

involvement, the jet of MR is directed posteriorly and the murmur will

radiate to the axilla and back. The click and murmur occur earlier with

standing, during the strain phase of the Valsalva maneuver and with

any intervention that decreases LV volume (preload), exaggerating

the propensity of the leaflet to prolapse. Conversely, squatting and

isometric exercises, which increase LV volume, diminish MVP; the

click-murmur complex is delayed, moves away from S1

, and may even

disappear. Some patients have a mid-systolic click without a murmur;

others have a murmur without a click. Still others have both sounds at

different times.

Tricuspid Valve Disease

2001CHAPTER 266

FIGURE 265-2. Barlow’s valve with classic mitral valve prolapse, as seen on

transthoracic echocardiogram in parasternal long-axis windows. Left: parasternal

long-axis window, showing both myxomatous leaflets billowing into the left atrium

in late systole. Right: same window with color Doppler showing significant mitral

regurgitation (arrow) in systole. (Courtesy of Justina Wu, MD, PhD.)

LABORATORY EXAMINATION

The ECG most commonly is normal but may show biphasic or inverted

T waves in leads II, III, and aVF and, occasionally, supraventricular or

ventricular premature beats. Transthoracic echocardiography (TTE) is

particularly effective in identifying the abnormal position and prolapse

of the mitral valve leaflets. A useful echocardiographic definition of

MVP is systolic displacement (in the parasternal long axis view) of the

belly of the mitral valve leaflets by at least 2 mm into the left atrium

(LA) superior to the plane of the mitral annulus. There can be prolapse

of one or both leaflets (Fig. 265-2). Color flow and continuous wave

Doppler imaging is helpful to evaluate the associated MR and provide

estimates of severity. The jet lesion of MR due to MVP is most often

eccentric, and assessment of the effective regurgitant orifice area and

regurgitant volume can be difficult with standard techniques. Both

three-dimensional echocardiography and cardiac magnetic resonance

imaging can provide more precise determinations of LV volumes.

Transesophageal echocardiography (TEE) is indicated when more

accurate anatomic information is required and is performed routinely

for intraoperative guidance during valve repair. Exercise testing can be

performed when there is uncertainty regarding functional capacity. It

is often combined with rest and immediate poststress TTE to assess LV

and right ventricular (RV) function and the dynamic nature of MR and

pulmonary artery pressures. Left ventriculography done at the time of

right and left heart catheterization is rarely necessary but can also show

prolapse of the posterior and sometimes of both mitral valve leaflets.

TREATMENT

Mitral Valve Prolapse

Infective endocarditis prophylaxis is indicated for patients with a

prior history of endocarditis. Beta blockers sometimes relieve chest

pain and control palpitations. Decisions regarding anticoagulation

for stroke prevention in AF should be based on the CHA2DS2-

VASc score and an assessment of bleeding risk. If the patient is

symptomatic from severe MR, mitral valve repair is indicated (see

Fig. 264-1). Other indications for surgery for MVP with severe primary MR include findings of established or progressive LV systolic

dysfunction. Surgery can also be considered for low-risk asymptomatic patients in whom a successful and durable repair can be

achieved with at least 95% likelihood by an expert surgeon. Mitral

valve repair is preferred over replacement in patients with MVP or

flail mitral leaflet (see Table 264-2); technical success is dependent

not only on the anatomic findings but also on the skill and experience of the surgeon. Repair of isolated posterior leaflet prolapse

is usually straightforward, but increasingly more complex pathologies (e.g., anterior leaflet prolapse, bileaflet prolapse, Barlow’s

deformity) require advanced skills. Careful pre- and intraoperative

TEE imaging is an important component of patient evaluation and

surgical planning. Transcatheter edge-to-edge repair (TEER) using

a clip to grasp the anterior and posterior leaflets together can be

considered for treatment of symptomatic patients at prohibitive

or high surgical risk with severe primary MR due to MVP (see

Fig. 264-3). Most often, the MR will be reduced in severity but not

eliminated. Nevertheless, symptom status and indices of LV size and

function can be improved with this approach, which is now offered

at >475 specialized sites in the United States. Reported hospital

mortality rates following the procedure are ~2%. Other transcatheter repair and replacement devices are not yet approved for clinical

use in the United States (see Chap. 264).

■ FURTHER READING

Dejgaard LA et al: The mitral annulus disjunction arrhythmic

syndrome. J Am Coll Card 72:1600, 2018.

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

future challenges. Lancet 387:1324, 2016.

O’Gara PT et al: 2017 ACC expert consensus decision pathway on

the management of mitral regurgitation. J Am Coll Cardiol 70:2421,

2017.

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.

TRICUSPID STENOSIS

Tricuspid stenosis (TS), which is much less prevalent than mitral stenosis (MS) in North America and Western Europe, is generally rheumatic

in origin and is more common in women than men (Table 266-1). It

does not occur as an isolated lesion and is usually associated with MS.

Hemodynamically significant TS occurs in 5–10% of patients with

severe MS; rheumatic TS is commonly associated with some degree

of tricuspid regurgitation (TR). Nonrheumatic causes of TS are rare.

■ PATHOPHYSIOLOGY

A diastolic pressure gradient between the right atrium (RA) and right

ventricle (RV) defines TS. It is augmented when the transvalvular

blood flow increases during inspiration and declines during expiration.

A mean diastolic pressure gradient of 4 mmHg is usually sufficient to

elevate the mean RA pressure to levels that result in systemic venous

congestion. Unless sodium intake has been restricted and diuretics

administered, this venous congestion is associated with hepatomegaly,

ascites, and edema, sometimes severe. In patients with sinus rhythm,

the RA a wave may be extremely tall and may even approach the level

of the RV systolic pressure. The y descent is prolonged. The cardiac

output (CO) at rest is usually depressed, and it fails to rise during

exercise. The low CO is responsible for the normal or only slightly elevated left atrial (LA), pulmonary artery (PA), and RV systolic pressures

despite the presence of MS. Thus, the presence of TS can mask the

hemodynamic and clinical features of any associated MS.

■ SYMPTOMS

Because the development of MS generally precedes that of TS, many

patients initially have symptoms of pulmonary congestion and fatigue.

Characteristically, patients with severe TS complain of relatively little

dyspnea for the degree of hepatomegaly, ascites, and edema that they

have. However, fatigue secondary to a low CO and discomfort due to

refractory edema, ascites, and marked hepatomegaly are common in

patients with advanced TS and/or TR. In some patients, TS may be suspected for the first time when symptoms of right-sided failure persist

after an adequate mitral commissurotomy.

266 Tricuspid Valve Disease

Patrick T. O’Gara, Joseph Loscalzo

2002 PART 6 Disorders of the Cardiovascular System

■ PHYSICAL FINDINGS

Because TS usually occurs in the presence of other obvious valvular

disease, the diagnosis may be missed unless it is considered. Severe

TS is associated with marked hepatic congestion, often resulting in

cirrhosis, jaundice, serious malnutrition, anasarca, and ascites. Congestive hepatomegaly and, in cases of severe tricuspid valve disease,

splenomegaly are present. The jugular veins are distended, and in

patients with sinus rhythm, there may be giant a waves. The v waves

are less conspicuous, and because tricuspid obstruction impedes RA

emptying during diastole, there is a slow y descent. In patients with

sinus rhythm, there may be prominent presystolic pulsations of the

enlarged liver as well.

On auscultation, an opening snap (OS) of the tricuspid valve may

rarely be heard ~0.06 s after pulmonic valve closure. The diastolic

murmur of TS has many of the qualities of the diastolic murmur of

MS, and because TS almost always occurs in the presence of MS, it

may be missed. However, the tricuspid murmur is generally heard best

along the left lower sternal border and over the xiphoid process and is

most prominent during presystole in patients with sinus rhythm. The

murmur of TS is augmented during inspiration, and it is reduced during expiration and particularly during the strain phase of the Valsalva

maneuver, when tricuspid transvalvular flow is reduced.

■ LABORATORY EXAMINATION

The electrocardiogram (ECG) features of RA enlargement (see

Fig. 240-8) include tall, peaked P waves in lead II, as well as prominent,

upright P waves in lead V1

. The absence of ECG evidence of RV hypertrophy (RVH) in a patient with right-sided heart failure who is believed

to have MS should suggest associated tricuspid valve disease. The chest

x-ray in patients with combined TS and MS shows particular prominence of the RA and superior vena cava without much enlargement of

the PA and with less evidence of pulmonary vascular congestion than

occurs in patients with isolated MS; engorgement of the azygos vein

can often be appreciated. On transthoracic echocardiographic (TTE)

examination, the tricuspid valve is usually thickened and domes in

diastole; the transvalvular gradient can be estimated by continuous

wave Doppler echocardiography. Severe TS is characterized by a valve

area ≤1 cm2

 or pressure half-time of ≥190 ms. The RA and inferior vena

cava (IVC) are enlarged. TTE provides additional information regarding the severity of any associated TR, mitral valve structure and function, left ventricular (LV) and RV size and function, and PA pressure.

Cardiac catheterization is not routinely necessary for assessment of TS.

TABLE 266-1 Causes of Tricuspid Valve Diseases

VALVE LESION ETIOLOGIES

Tricuspid stenosis Rheumatic

Congenital

Tricuspid regurgitation Primary (organic)

Rheumatic

Endocarditis

Myxomatous (TVP)

Carcinoid

Radiation

Congenital (Ebstein’s)

 Trauma (including that due to intracardiac leads

and RV endomyocardial biopsy)

Papillary muscle injury (post-MI)

Secondary (functional)

 RV and tricuspid annular dilation due to multiple

causes (e.g., long-standing pulmonary HTN,

remodeling post-RV MI, left-sided heart disease,

cardiomyopathy, AF (atrial functional tricuspid

regurgitation), chronic RV apical pacing

(dyssynchrony)

Abbreviations: AF, atrial fibrillation; HTN, hypertension; MI, myocardial infarction;

RV, right ventricular; TVP, tricuspid valve prolapse.

TREATMENT

Tricuspid Stenosis

Patients with TS generally exhibit marked systemic venous congestion; salt restriction, bed rest, and diuretic therapy are required during the preoperative period. Such a preparatory period may diminish

hepatic congestion and thereby improve hepatic function sufficiently

so that the risks of operation, particularly bleeding, are diminished.

Surgical relief of the TS should be carried out, preferably at the time

of surgical mitral commissurotomy or mitral valve replacement

(MVR) for mitral valve disease, in patients with moderate or severe

TS who have mean diastolic pressure gradients exceeding ~4 mmHg

and tricuspid orifice areas <1.5–2 cm2

. TS is almost always accompanied by significant TR. Operative repair may permit substantial

improvement of tricuspid valve function. If repair cannot be accomplished, the tricuspid valve may have to be replaced. Meta-analysis

has shown no difference in overall survival between mechanical and

tissue valve replacement. Mechanical valves in the tricuspid position

are more prone to thromboembolic complications than in other

positions. Percutaneous tricuspid balloon commissurotomy for isolated severe TS without significant TR is very rarely performed.

TRICUSPID REGURGITATION

More than 85% of TR cases encountered in clinical practice are secondary (functional) in nature and related to tricuspid annular dilation

and leaflet tethering in the setting of RV remodeling caused by pressure

or volume overload (or both), myocardial infarction (MI), or trauma

(Table 266-1). Secondary TR is commonly seen in the late stages of

heart failure due to rheumatic or congenital heart disease with severe

PA hypertension (PA systolic pressure >55 mmHg), as well as in other

types of left-sided valvular (e.g., mitral regurgitation) or myocardial

diseases (e.g., ischemic and idiopathic dilated cardiomyopathies).

Secondary TR can also develop from chronic RV apical pacing and

dyssynchronous contraction; in some patients, the RV leads may also

perforate or entrap the TV leaflets. TR can often emerge in the setting

of new-onset atrial fibrillation (AF), particularly in older patients

(atrial functional TR). Rheumatic fever may produce primary TR,

often associated with TS. Tricuspid valve prolapse, carcinoid heart

disease, endomyocardial fibrosis, radiation, infective endocarditis, and

leaflet trauma can also produce primary TR. Less commonly, primary

TR results from congenitally deformed tricuspid valves and can occur

with defects of the atrioventricular canal, as well as with Ebstein’s malformation of the tricuspid valve (Chap. 269).

■ PATHOPHYSIOLOGY

The incompetent tricuspid valve allows blood to flow backward from the

RV into the RA, the volume of which is dependent on the driving pressure

(i.e., RV systolic pressure) and the size of the regurgitant orifice. The severity

and physical signs of TR can vary as a function of PA systolic pressure (in

the absence of RV outflow tract stenosis), the dimension of the tricuspid

valve annulus, the respiratory cycle-dependent changes in RV preload, and

RA compliance. RV filling is increased during inspiration. Forward CO is

reduced and does not augment with exercise. Significant degrees of TR will

lead to RA enlargement and elevation of the RA and jugular venous pressures with prominent c-v waves in the pulse tracings. Progressively severe

TR can lead to “ventricularization” of the RA wave form (see Fig. 239-1B).

Severe TR is also characterized by RV dilation (RV volume overload) and

eventual systolic dysfunction, the progression of which can be accelerated

by a concomitant pressure load from PA hypertension or by myocardial

fibrosis from previous injury.

■ SYMPTOMS

Mild or moderate degrees of TR are usually well tolerated in the absence

of other hemodynamic disturbances. Because TR most often coexists

with left-sided valve lesions, LV dysfunction, and/or PA hypertension,

symptoms related to these lesions may dominate the clinical picture.

Fatigue and exertional dyspnea owing to reduced forward CO are early

symptoms of isolated, severe TR. As the disease progresses and RV

Tricuspid Valve Disease

2003CHAPTER 266

function declines, patients may report cervical pulsations, abdominal

fullness/bloating, diminished appetite, and muscle wasting, although

with progressive weight gain and painful swelling of the lower extremities.

■ PHYSICAL FINDINGS

The neck veins in patients with severe TR are distended with prominent

c-v waves and rapid y descents (in the absence of TS). TR is more often

diagnosed by examination of the neck veins than by auscultation of the

heart sounds. Other findings may include marked hepatomegaly with

systolic pulsations, ascites, pleural effusions, edema, and a positive hepatojugular reflux sign. A prominent RV pulsation in the left parasternal

region and a blowing holosystolic murmur along the lower left sternal

margin, which may be intensified during inspiration (Carvallo’s sign) and

reduced during expiration or the strain phase of the Valsalva maneuver,

are characteristic findings. The murmur of TR may sometimes be confused with that of mitral regurgitation (MR) unless attention is paid to its

variation during the respiratory cycle and the extent of RV enlargement

is appreciated. AF is usually present in the chronic phase of the disease.

■ LABORATORY EXAMINATION

The ECG may show changes characteristic of the lesion responsible for

the TR, e.g., an inferior Q-wave MI suggestive of a prior RV MI, RVH,

or a bizarre right bundle branch block–type pattern with preexcitation in

patients with Ebstein’s anomaly. ECG signs of RA enlargement may be

present in patients with sinus rhythm; AF is frequently noted. The chest

x-ray may show RA and RV enlargement, depending on the chronicity

and severity of TR. TTE is usually definitive with demonstration of RA

dilation and RV volume overload and prolapsing, flail, scarred, or displaced/tethered tricuspid leaflets with annular dilatation; the diagnosis

and assessment of TR can be made by color flow Doppler imaging (see

Fig. 241-8). Severe TR is accompanied by hepatic vein systolic flow

reversal. Continuous wave Doppler of the TR velocity profile is useful in

estimating PA systolic pressure, except when the TR is very severe and

the jet velocity is blunted by rapidly increasing RA pressure. Accurate

assessment of TR severity, PA pressures, and RV size and systolic function

with TTE can be quite challenging in many patients. Real-time three-dimensional echocardiography and cardiac magnetic resonance (CMR)

imaging provide alternative imaging modalities, although they are not

widely available. In patients with severe TR, the CO is usually markedly

reduced, and the RA pressure pulse may not exhibit an x descent during early systole but rather show a prominent c-v wave with a rapid y

descent. The mean RA and RV end-diastolic pressures are often elevated.

Exercise testing can be used to assess functional capacity in patients with

asymptomatic severe TR. The prognostic significance of exercise-induced

changes in TR severity and RV function has not been well studied.

TREATMENT

Tricuspid Regurgitation (Fig. 266-1)

Diuretics can be useful for patients with severe TR and signs of

right heart failure. An aldosterone antagonist may be particularly

Tricuspid regurgitation

Severe TR

(Stages C and D)

At time of leftsided valve surgery

At time of leftsided valve surgery

Asymptomatic

Stage C

Annular dilation

>4.0 cm

or

prior right HF

Primary TR with

progressive RV

dilation or systolic

dysfunction

Right heart failure

Stage D

Prior left-sided

valve surgery

Secondary

TR

Poorly

responsive

to GDMT

Annular

dilation without

↑PAP or leftsided disease

Absences of

severe PH or

RV systolic

dysfunction

Primary

TR

TV surgery

(2b)

TV surgery

(2b)

TV surgery

(2a)

TV surgery

(2a)

TV surgery

(2a)

TV surgery

(1)

Progressive TR

(Stage B)

FIGURE 266-1 Management of tricuspid regurgitation. See legend for Fig. 261-4 for explanation of treatment recommendations (Class I, IIa, IIb) and disease stages (B, 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. GDMT, guideline-directed management and therapy; HF, heart failure; PAP,

pulmonary artery pressure; PH, pulmonary hypertension; RV, right ventricular; TR, tricuspid regurgitation; TV, tricuspid valve. Annular dilation is defined by >40 mm on

transthoracic echocardiography (>21 mm/m2

) or >70 mm on direct intraoperative measurement. (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.)

2004 PART 6 Disorders of the Cardiovascular System

PULMONIC STENOSIS

Pulmonic valve stenosis (PS) is essentially a congenital disorder

(Table 267-1). With isolated PS, the valve is typically domed. Dysplastic pulmonic valves are seen as part of the Noonan syndrome

(Chap. 281), which maps to chromosome 12. Mutations in the PTPN1

gene are associated with about half of all cases of Noonan syndrome.

Much less common etiologies include carcinoid and obstructing

tumors or bulky vegetations. The pulmonic valve is only very rarely

affected by the rheumatic process.

■ PATHOPHYSIOLOGY

PS is defined hemodynamically by a systolic pressure gradient between

the right ventricle (RV) and the main pulmonary artery (PA). RV hypertrophy (RVH) develops as a consequence of sustained obstruction to RV

outflow, and systolic ejection is prolonged. Compared with the ability of

the LV to compensate for the pressure overload imposed by aortic stenosis (AS), RV dysfunction from afterload mismatch occurs earlier in the

course of PS and at lower peak systolic pressures, because the RV adapts

267 Pulmonic Valve Disease

Patrick T. O’Gara, Joseph Loscalzo

TABLE 267-1 Causes of Pulmonic Valve Disease

VALVE LESION ETIOLOGIES

Pulmonic stenosis Congenital

Carcinoid

Tumor

Endocarditis

Pulmonic regurgitation Primary valve disease

Congenital

Post-valvotomy

Endocarditis

Carcinoid

Annular enlargement

Pulmonary hypertension

Idiopathic dilation

Marfan syndrome

helpful because many patients have secondary hyperaldosteronism

from marked hepatic congestion. Therapies to reduce elevated PA

pressures and/or pulmonary vascular resistance, including those targeted at left-sided heart disease, can also be considered for patients

with PA hypertension and severe secondary TR. Tricuspid valve

surgery is recommended for patients with severe TR who are undergoing left-sided valve surgery and is also undertaken frequently for

treatment of even moderate TR in patients undergoing left-sided

valve surgery who have tricuspid annular dilation (>40 mm), a

history of right heart failure, or PA hypertension. Operation most

often comprises repair rather than replacement in these settings

and has become routine in most major surgical centers. Surgery

may also infrequently be required for treatment of severe, primary

TR with right heart failure not responsive to standard medical

therapy or because of progressively declining RV systolic function.

Reported perioperative mortality rates for isolated tricuspid valve

surgery (repair and replacement) are high (~8–9%) and likely are

influenced by the hazards encountered during reoperation on

patients who have undergone previous left-sided valve surgery and

have reduced RV function. Indwelling pacemaker or defibrillator

leads can also pose technical challenges. Investigation of transcatheter tricuspid valve repair and replacement systems is ongoing.

■ FURTHER READING

Dreyfus GD et al: Functional tricuspid regurgitation. J Am Coll Cardiol 65:2331, 2015.

Hahn RT et al: Early feasibility study of transcatheter tricuspid valve

annuloplasty. J Am Coll Cardiol 69:1795, 2017.

Kadri AN et al: Outcomes of patients with severe tricuspid regurgitation and congestive heart failure. Heart 105:1813, 2019.

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.

Rodés-Cabau J et al: Diagnosis and treatment of tricuspid valve disease: Current and future perspectives. Lancet 388:2431, 2016.

Rodés-Cabau J et al: Transcatheter therapies for treating tricuspid

regurgitation. J Am Coll Cardiol 67:1829, 2016.

less well to this type of hemodynamic burden. With normal systolic

function and cardiac output (CO), severe PS is defined by a peak systolic gradient across the pulmonic valve of >64 mmHg (mean gradient

>35 mm Hg, Doppler jet velocity >4 m/s); moderate PS correlates with

a peak gradient of 36–64 mmHg (Doppler jet velocity 3-4 m/s). Mild PS

is characterized by a jet velocity <3 m/s (peak gradient <36 mmHg). PS

rarely progresses in patients with mild PS mmHg but may worsen in

those with moderate disease due to valve thickening and calcification

with age. The right atrial (RA) a wave elevates in relation to the higher

pressures needed to fill a noncompliant, hypertrophied RV. A prominent RA v wave signifies functional tricuspid regurgitation (TR) from

RV and annular dilation. The CO is maintained until late in the course

of the disease.

■ SYMPTOMS

Patients with mild or even moderate PS are usually asymptomatic and

first come to medical attention because of a heart murmur (or early

systolic click) that leads to echocardiography. With severe PS, patients

may report exertional dyspnea or early-onset fatigue. Anginal chest

pain from RV oxygen supply-demand mismatch and syncope may

occur with very severe forms of obstruction, particularly in the presence of a destabilizing trigger such as atrial fibrillation, fever, infection,

anemia, or pregnancy.

■ PHYSICAL FINDINGS

The murmur of mild or moderate PS is mid-systolic in timing,

crescendo–decrescendo in configuration, heard best in the left second

interspace, and usually introduced by an ejection sound (click) in

younger adults whose valves are still pliable. The ejection sound is the

only right-sided acoustic event that decreases in intensity with inspiration. This phenomenon reflects premature opening of the pulmonic

valve by the elevated RV end-diastolic (post-atrial a wave) pressure.

The systolic murmur increases in intensity during inspiration. With

progressively severe PS, the ejection sound moves closer to the first

heart sound and eventually becomes inaudible. A right-sided fourth

heart sound may emerge. The systolic murmur peaks later and may

persist through the aortic component of the second heart sound (A2

).

Pulmonic valve closure is delayed, and the pulmonic component of

the second heart sound (P2

) is reduced or absent. A prominent a wave,

indicative of the higher atrial pressure necessary to fill the noncompliant RV, may be seen in the jugular venous pulse. A parasternal or RV

lift can be felt with significant pressure overload. Signs of right heart

failure, such as hepatomegaly, ascites, and edema, are uncommon but

may appear very late in the disease.

■ LABORATORY EXAMINATION

The electrocardiogram (ECG) will show right axis deviation, RVH, and

RA enlargement in adult patients with severe PS. Chest x-ray findings

include poststenotic dilation of the main PA in the frontal plane projection and filling of the retrosternal airspace due to RV enlargement on

Multiple and Mixed Valvular Heart Disease

2005CHAPTER 268

not contain a valve. PA pressures in these individuals are not elevated,

and the diastolic murmur can be misleadingly low pitched and of short

duration despite significant degrees of PR and RV volume overload.

■ LABORATORY EXAMINATION

Depending on both the etiology and severity of PR, the ECG may show

findings of RVH and RA enlargement. On chest x-ray, the RV and RA

may be enlarged. Pulmonic valve morphology and function can be

assessed with transthoracic Doppler echocardiography. RV systolic

pressure can be estimated from the tricuspid valve systolic jet velocity. Cardiac magnetic resonance (CMR) imaging can provide greater

anatomic detail, particularly in patients with repaired congenital heart

disease, and more precise assessment of RV volumes and function. Cardiac catheterization is not routinely necessary but would be performed

as part of a planned transcatheter PV procedure.

TREATMENT

Pulmonic Regurgitation

In patients with functional PR due to PA hypertension and annular dilation, efforts to reduce PA vascular resistance and pressure should be pursued. Such efforts may include pharmacologic/

vasodilator and/or surgical/interventional strategies, depending on

the cause of the PA hypertension (e.g., idiopathic PA hypertension,

left-sided heart valve disease). Diuretics can be used to treat the

manifestations of right heart failure. Surgical valve replacement

for primary, severe, pulmonic valve disease, such as carcinoid or

endocarditis, is rarely undertaken. Transcatheter pulmonic valve

replacement has been successfully performed in many patients with

severe PR after childhood repair of tetralogy of Fallot or pulmonic

valve stenosis or atresia. This procedure was introduced clinically

prior to transcatheter aortic valve replacement.

■ FURTHER READING

Ansari MM et al: Percutaneous pulmonary valve implantation. J Am

Coll Cardiol 66:2246, 2015.

Otto CM et al: 2020 AHA/ACC 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.

Stout KK et al: 2018 ACC/AHA guidelines for the management of

adults with congenital heart disease. J Am Coll Cardiol 73:e81, 2019.

the lateral film. In some patients with RVH, the cardiac apex appears

to be lifted off the left hemidiaphragm. The RA may also be enlarged.

Transthoracic echocardiography (TTE) allows definitive diagnosis and

characterization in most cases, with depiction of the valve and assessment of the jet velocity, gradient, RV function, PA pressures (which

should be low), and any associated cardiac lesions. Transesophageal

echocardiography (TEE) may be useful in some patients for improved

delineation of the RV outflow tract (RVOT) and assessment of infundibular hypertrophy. Cardiac catheterization is not usually necessary

for diagnostic purposes, but if performed, pressures should be obtained

from just below and above the pulmonic valve with attention to the

possibility that a dynamic component to the gradient may exist. The

correlation between Doppler assessment of peak instantaneous gradient and catheterization-measured peak-to-peak gradient is weak. The

latter may correlate better with the Doppler mean gradient.

TREATMENT

Pulmonic Stenosis

Diuretics can be used to treat symptoms and signs of right heart

failure. Provided there is less than moderate pulmonic regurgitation (PR), percutaneous pulmonic balloon valvuloplasty is recommended for symptomatic patients with moderate or severe PS

and for asymptomatic patients with a peak gradient >64 mmHg

(or mean gradient >35 mmHg). Surgery may be required when the

valve is dysplastic (as seen in patients with Noonan’s syndrome and

other disorders). A multidisciplinary heart team is best positioned

to make treatment decisions of this nature.

PULMONIC REGURGITATION

PR may develop as a consequence of primary valve pathology, annular

enlargement, or their combination; after surgical treatment of RVOT

obstruction in children with such disorders as tetralogy of Fallot; or

after percutaneous pulmonic balloon valvotomy (Table 267-1). Carcinoid usually causes mixed pulmonic valve disease with PR and PS.

Long-standing severe PA hypertension from any cause can result in

dilation of the pulmonic valve ring and PR.

■ PATHOPHYSIOLOGY

Severe PR results in RV chamber enlargement and eccentric hypertrophy. As is the case for aortic regurgitation (AR), PR is a state of

increased preload and afterload. The reverse pressure gradient from the

PA to the RV, which drives the PR, progressively decreases throughout

diastole and accounts for the decrescendo nature of the diastolic murmur. As RV diastolic pressure increases, the murmur becomes shorter

in duration. The forward CO is preserved during the early stages of the

disease but may not increase normally with exercise and declines over

time. A reduction in RV ejection fraction may be an early indicator

of hemodynamic compromise. In advanced stages, there is significant

enlargement of the RV and RA with marked elevation of the jugular

venous pressure.

■ SYMPTOMS

Mild or moderate degrees of PR do not, by themselves, result in symptoms. Other issues, such as PA hypertension, may dominant the clinical

picture. With progressively severe PR and RV dysfunction, fatigue,

exertional dyspnea, abdominal fullness/bloating, and lower extremity

swelling may be reported.

■ PHYSICAL FINDINGS

The physical examination hallmark of PR is a high-pitched, decrescendo diastolic murmur (Graham Steell murmur) heard along the

left sternal border that can be difficult to distinguish from the more

frequently appreciated murmur of AR. The Graham Steell murmur

may become louder with inspiration and is usually associated with a

loud and sometimes palpable P2

 and an RV lift, as would be expected

in patients with significant PA hypertension of any cause. Survivors

of childhood surgery for tetralogy of Fallot or PS/pulmonary atresia

may have an RV-PA conduit that is freely regurgitant because it does

Many acquired and congenital cardiac lesions may result in stenosis

and/or regurgitation of one or more heart valves. For example, rheumatic heart disease can involve the mitral (mitral stenosis [MS], mitral

regurgitation [MR], or MS and MR), aortic (aortic stenosis [AS], aortic

regurgitation [AR], or AS and AR), and tricuspid (tricuspid stenosis

[TS], tricuspid regurgitation [TR], or TS and TR) valve, alone or in

combination. The common association of functional TR with significant mitral valve disease is discussed in Chap. 266. Severe mitral

annular calcification can result in regurgitation (due to decreased

annular shortening during systole) and mild or moderate stenosis

(caused by extension of the calcification onto the leaflets resulting in

restricted valve opening). Patients with severe AS and LV remodeling

may develop functional MR that may not improve after isolated aortic

268 Multiple and Mixed

Valvular Heart Disease

Patrick T. O’Gara, Joseph Loscalzo