161. Norwood WI, Lang P, Casteneda AR, et al. Experience with operations for hypoplastic left heart

syndrome. J Thorac Cardiovasc Surg 1981; 82(4):511–519.

162. Gutgesell HP, Gibson J. Management of hypoplastic left heart syndrome in the 1990s. Am J Cardiol

2002;89(7):842–846.

163. Azakie A, Martinez D, Sapru A, et al. Impact of right ventricle to pulmonary artery conduit on

outcome of the modified Norwood procedure. Ann Thorac Surg 2004;77(5):1727–1733.

164. Mair R, Tulzer G, Sames E, et al. Right ventricular to pulmonary artery conduit instead of modified

Blalock-Taussig shunt improves postoperative hemodynamics in newborns after the Norwood

operation. J Thorac Cardiovasc Surg 2003;126(5):1378–1384.

165. Pizarro C, Malec E, Maher KO, et al. Right ventricle to pulmonary artery conduit improves

outcome after stage I Norwood for hypoplastic left heart syndrome. Circulation 2003;108(Suppl

1):II155–II160.

166. Sano S, Ishino K, Kawada M, et al. Right ventricle-pulmonary artery shunt in first-stage palliation

of hypoplastic left heart syndrome. J Thorac Cardiovasc Surg 2003;126(2):504–509; discussion

509–510.

167. Hirsch JC, Gurney JG, Donohue JE, et al. Hospital mortality for Norwood and arterial switch

operations as a function of institutional volume. Pediatr Cardiol 2008;29(4):713–717.

168. Douglas WI, Goldberg CS, Mosca RS, et al. Hemi-Fontan procedure for hypoplastic left heart

syndrome: outcome and suitability for Fontan. Ann Thorac Surg 1999;68(4):1361–1367; discussion

1368.

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Chapter 82

Valvular Heart Disease and Cardiac Tumors

Tomislav Mihaljevic, Craig M. Jarrett, Husain T. AlQattan, Shehab Ahmad Redha AlAnsari, Haris Riaz,

Marijan Koprivanac, and A. Marc Gillinov

Key Points

1 The most common cause of aortic stenosis (AS) is degenerative calcific disease, followed by

congenital AS due to bicuspid valve anatomy.

2 Two-dimensional (2D) echocardiography with Doppler allows precise real-time analysis of valvular

anatomy and function, and is the study of choice for the diagnosis and management of valvular

lesions.

3 The current indication for cardiac catheterization in patients with valvular heart disease is limited to

preoperative evaluation of coronary artery disease.

4 There is no effective medical therapy for patients with severe AS. Mechanical relief of the

obstruction to blood flow is the only effective treatment.

5 The most common causes of aortic regurgitation (AR) include bicuspid valve disease, rheumatic

fever, and endocarditis.

6 Mitral stenosis (MS) is almost exclusively caused by rheumatic fever.

7 The most common cause of mitral regurgitation is degenerative mitral valve disease. Other causes

include rheumatic valve disease, endocarditis, certain drugs, and collagen vascular diseases.

8 The most common cardiac tumors are secondary tumors, which usually originate from the lung in

men and from the breast in women.

VALVULAR HEART DISEASE

Valvular Anatomy

The basic structural framework of all heart valves is provided by the fibrous cardiac skeleton (Fig. 82-

1). The skeleton is a collection of dense connective tissue in the shape of four interconnected rings in

the plane between the atria and the ventricles. The interconnecting areas include the right fibrous

trigone, which is between the aortic and tricuspid rings and contiguous with the membranous septum,

and the left trigone and fibrous continuity, which are between the aortic and mitral rings and form the

posterior wall of the left ventricular (LV) outflow tract. The cardiac skeleton maintains the integrity of

the valve orifices and provides points of attachment for the valve leaflets. It also serves as a partition by

electrically isolating the atria and ventricles except at the atrioventricular bundle, which passes through

the right fibrous trigone near the septal leaflet of the tricuspid valve (TV).

The normal aortic valve (AV) consists of three semilunar leaflets or cusps projecting outward and

upward into the lumen of the ascending aorta (Fig. 82-2). The space between the free edge of each

leaflet and the points of attachment to the aorta comprise the sinuses of Valsalva. Since the coronary

arteries arise from two of the three sinuses, the sinuses and the respective leaflets are named the right

coronary, left coronary, and noncoronary (or posterior) sinuses and leaflets.

The properties of the AV ensure minimal obstruction to flow when open and minimal flow reversal

when closed. Opening and closing of the valve are passive, as it functions only in response to pressure

differences between the left ventricle and aorta during the cardiac cycle. The pressure generated from

ventricular contraction forces the valve open, and the subsequent recoil of blood from the aorta fills the

sinuses of Valsalva and forces the leaflets closed.

There are two structures in close proximity to the AV and, therefore, susceptible to injury during AV

surgery (Fig. 82-2). First, the anterior leaflet of the mitral valve (MV) is positioned under the

commissure between the left and noncoronary leaflets. Second, the left bundle of His is positioned

under the commissure between the right and noncoronary leaflets.

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In contrast to the simplistic anatomy and passive opening and closing mechanism of the AV, the

anatomy and active valve mechanism of the MV are more complex. Indeed, proper functioning of the

MV depends on the organized interaction of all components of the MV apparatus, which consists of the

leaflets, annulus, LV papillary muscles, and chordae tendineae.

The normal MV consists of two leaflets: the anterior and posterior leaflets. The anterior leaflet is

semicircular in shape, extends from the anteromedial aspect of the mitral annulus, and encompasses

approximately one-third of the annular circumference. The posterior leaflet is rectangular in shape,

extends from the posterolateral aspect of the mitral annulus, and encompasses approximately two-thirds

of the annular circumference. The leaflets are separated from one another at the annulus by the

posteromedial and anterolateral commissures. Both leaflets are divided by clefts into three scallops,

named laterally to medially A1, A2, and A3, and P1, P2, and P3, and together comprise an average

cross-sectional area of 5 to 11 cm2.

The mitral annulus is formed anteriorly by the confluence of the right, left, and intervalvular fibrous

trigones and posteriorly by a fibrous band. Since the anterior aspect of the mitral annulus is composed

of the fibrous trigones, it has limited flexibility. Conversely, the posterior aspect of the annulus, which

is not surrounded by any rigid structures, has more flexibility. This increased flexibility of the posterior

aspect relative to the anterior aspect has important implications during the cardiac cycle. In systole the

mitral annulus contracts (primarily the posterior aspect) and adopts an elliptical shape (shortening

occurs perpendicular to the line of leaflet coaptation), and in diastole it relaxes and adopts a circular

shape.1,2 This dynamic motion of the annulus provides increased leaflet coaptation during systole and

increased orifice area during diastole.

Figure 82-1. Schematic diagram of the fibrous cardiac skeleton.

Two papillary muscles arise directly from the ventricular wall: the anterolateral and posteromedial

papillary muscles. Importantly, the anterolateral papillary muscle usually is supplied by two coronary

arteries, the left anterior descending artery and branches of the circumflex artery. On the other hand,

the posteromedial papillary muscle is usually supplied by a single coronary artery, either from the right

coronary or the circumflex artery, which makes it twice as likely to rupture from ischemia and

infarction as the anterolateral papillary muscle. The papillary muscles play an important role in the

proper function of the MV. MV closure and appropriate leaflet coaptation are permitted by end-diastolic

and early systolic lengthening of the papillary muscles.3

Chordae tendineae attach the leaflets to the papillary muscles or directly to the ventricular wall and

can be categorized based on the attachments. Primary chordae attach to the leaflets at the free edge to

ensure proper coaptation without prolapse or flail. The secondary chordae attach along the line of

coaptation and are more prominent on the anterior leaflet. Tertiary chordae arise directly from the

ventricle or trabeculae carneae and are only present on the posterior leaflet. Finally, commissural

chordae attach to both leaflets and arise from either papillary muscle.

The structures in close proximity to the MV and, therefore, susceptible to injury during MV surgery

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include the AV, the atrioventricular node, and the circumflex coronary artery (Fig. 82-3).

Figure 82-2. Schematic diagram of the relationship of the aortic valve to the underlying structures.

AORTIC STENOSIS

Prevalence and Etiology

1 Aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries. The most

common cause of AS is degenerative calcific disease, followed by congenital AS due to bicuspid valve

anatomy. Rheumatic AS is becoming exceedingly uncommon in developed countries due to efficient

prevention of rheumatic heart disease.

Figure 82-3. Schematic diagram of the relationship of the mitral valve to the underlying structures.

Degenerative Calcific Aortic Stenosis

The most frequent cause of AS is degenerative calcification of the AV. The prevalence of degenerative

AS in persons older than 65 years, which is the most commonly affected age group, is 2%.4 The

degenerative process that leads to stiffening of the aortic leaflets is the result of proliferative and

inflammatory changes with lipid accumulation and infiltration of macrophages and T lymphocytes.4–9

Fibrosis and calcification initially affect the base of the leaflets, but ultimately progress to

immobilization of the leaflets due to large calcific deposits that can extend deep into the annulus. These

deposits may also extend onto the ventricular surface of the anterior leaflet of the MV, as well as into

the wall of the ascending aorta. The risk factors for the development of calcific AS are similar to those

for atherosclerosis and include elevated serum levels of low-density lipoprotein (LDL) cholesterol,

diabetes, smoking, and hypertension.10,11

Bicuspid Aortic Stenosis

Calcification of bicuspid AVs, which are present in approximately 2% of the general population,

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represents the most common form of congenital AS. In patients with bicuspid AVs, the left and right

coronary cusps are usually fused, while the noncoronary cusp is freestanding. Gradual calcification of

the bicuspid valve results in AS with typical onset of symptoms in the fifth or sixth decade of life, in

contrast to degenerative AS, which causes symptoms in elderly individuals. Bicuspid AS is frequently

associated with degenerative changes in the wall of the ascending aorta with resultant dilation or

aneurysm formation.

Rheumatic Aortic Stenosis

Introduction of effective antibiotic therapy has resulted in a decline in the prevalence of rheumatic fever

and rheumatic valve disease. Rheumatic AS is caused by inflammation and thickening of the AV leaflets,

producing a mixture of AS and regurgitation. Rheumatic AS is rarely an isolated disease, and usually

occurs in conjunction with MV stenosis.12

Pathophysiology

Regardless of the etiology of AS, the pathophysiologic consequences are similar. Narrowing of the AV to

one-quarter of its normal area of 3 to 4 cm2 produces a significant pressure gradient between the left

ventricle and aorta. There is a resultant increase in LV workload and compensatory LV hypertrophy.

Even though this hypertrophy is an appropriate response to the increased afterload, there are

numerous harmful effects. First, the increased wall thickness makes the ventricle stiff and less

compliant. This leads to diastolic dysfunction and increased wall tension. In addition to diastolic

dysfunction, systolic dysfunction, typically occurring later in the course of the disease, can develop from

chronic ischemia. All of the following contribute to increased myocardial oxygen demand: increased LV

muscle mass, increased wall tension, increased systolic ventricular pressure, and increased systolic

ejection time. There is also decreased coronary artery perfusion, which occurs during diastole, due to

increased wall tension, increased diastolic ventricular pressure, and decreased diastolic aortic

pressure.13,14 The subsequent ischemia of the subendocardium due to increased oxygen demand and

decreased perfusion leads to cell death and fibrosis. Chronically, this ischemia results in systolic

dysfunction.

Diagnosis

Symptoms

The most common symptoms of AS are angina pectoris, syncope, and heart failure.15 Angina pectoris

occurs in 30% to 50% of patients with severe AS. It is a reflection of myocardial ischemia caused by

increased metabolic demands and decreased coronary perfusion. Coronary artery disease, which affects

more than 70% of elderly patients with degenerative AV disease, causes further deterioration of

myocardial perfusion and lowers the threshold for angina.

Syncope is most commonly due to reduced cerebral perfusion that occurs during exertion. Reduced

cerebral perfusion is a result of decreased mean arterial pressure from peripheral vasodilation in the

presence of a fixed cardiac output. Approximately 15% of patients present with syncope and only 50%

of these survive for 3 years.

Congestive heart failure in patients with severe AS is typically a sign of advanced and longstanding

disease. It is marked by shortness of breath and dyspnea with exertion, and results from ongoing LV

outflow obstruction. Heart failure is a consequence of the aforementioned diastolic and systolic

dysfunction from decreased compliance and ischemia, respectively. In addition, as the left ventricle

becomes less compliant, atrial systole becomes more important for maintaining cardiac output and the

onset of atrial fibrillation may result in worsening of congestive heart failure.

Some patients with severe AS may develop serious gastrointestinal bleeding secondary to

angiodysplasias, occurring predominantly in the right colon, and also in the small bowel and stomach.

These result from shear stress–induced platelet aggregation with reduction in high–molecular-weight

multimers of von Willebrand factor.

Signs

Signs of AS include a loud systolic ejection murmur that radiates to the neck and is often accompanied

by a thrill. “Pulsus parvus et tardus” describes a weak and prolonged arterial pulse characteristic of

advanced AS. The weak pulse is a reflection of a narrowed pulse pressure, while the slow rise in pulse

reflects a prolonged ejection of blood volume through a stenotic valve.16

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Electrocardiogram and Imaging

2 The electrocardiogram typically shows signs of LV hypertrophy, which is found in the majority of

patients with AS. Echocardiography represents the “gold standard” modality for the diagnosis of AS.

Two-dimensional (2D) echocardiography with Doppler allows precise real-time analysis of ventricular

and valvular anatomy and function. The most important objective of echocardiography is correct

assessment of the severity of AS using Doppler echocardiography to calculate jet velocity, mean

transvalvular pressure gradient, and valve orifice area (Table 82-1). It is also used to assess valve

thickening and calcification, as well as reduced leaflet motion. Distinction between bicuspid and TVs is

often possible, particularly when the amount of calcification is small.

DIAGNOSIS

Table 82-1 Classification of Aortic Stenosis Severity

Two-dimensional echocardiography is also invaluable in detecting associated MV disease and in

assessing LV hypertrophy, systolic function, and diastolic performance. Ejection fraction is used to

measure LV systolic function. However, a severe decrease in ejection fraction can falsely lower

estimates of severity of AS due to low-pressure gradients. Stress echocardiography with dobutamine

administration may be required to properly assess the severity of valvular disease and to distinguish it

from primary contractile dysfunction with lack of contractile reserve.17

3 Cardiac catheterization with direct measurement of the pressure gradients across the AV to calculate

the severity of stenosis has been replaced by less invasive echocardiography. The current indication for

cardiac catheterization is limited to preoperative evaluation of coronary artery disease.

Natural History

The natural history of AS is marked by a prolonged latent period with few symptoms and minimal

morbidity. Even patients with moderately severe AS have a slow decrease in AV area, generally by

approximately 0.1 cm2 per year.18,19 The natural history of severe AS correlates well with the onset and

severity of symptoms. Life expectancy of patients with severe, untreated AS and angina is

approximately 5 years. Patients presenting with syncope have life expectancies of 3 years. Presence of

congestive heart failure in patients with severe, untreated AS is associated with a worse prognosis, with

the time of death occurring less than 2 years from the onset of symptoms (Fig. 82-4).20

Figure 82-4. Natural history of aortic stenosis without operative treatment. Onset of symptoms identifies patients at high risk of

death over the next 2 to 5 years.

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Figure 82-5. St. Jude Medical Regent Valve.

Treatment

4 There is no effective medical therapy for patients with severe AS. Diuretics and digitalis may improve

the symptoms of congestive heart failure. Mechanical relief of AS is accomplished by surgical AV

replacement (AVR), percutaneous AVR, or percutaneous balloon aortic valvotomy (PBAV).

Surgical Aortic Valve Replacement

The primary indication for surgery is the presence of symptoms in patients with severe AS. AVR is also

indicated in patients with severe AS and reduced LV function and in patients with moderate to severe AS

who also require coronary, other valve, or aortic surgery.17 Recent studies suggest that AVR may also

be beneficial in patients with asymptomatic severe AS and severe LV hypertrophy.21

Choice of valve prosthesis for AVR is primarily influenced by the patient’s age. Mechanical prostheses

are made of carbon, require lifelong anticoagulation, and are very durable (Fig. 82-5). Mechanical

prostheses are therefore indicated in patients younger than 65 years old. Stented biologic prostheses are

most commonly made of bovine pericardium or porcine valve leaflets, do not require anticoagulation,

and have a limited durability of approximately 15 years (Fig. 82-6). Biologic prostheses are used in

elderly patients (older than 65 years) and in younger patients in whom long-term anticoagulation with

warfarin is contraindicated (bleeding diathesis, peptic ulcer disease, etc.).

Percutaneous and Transapical Aortic Valve Replacement

Percutaneous AVR is an emerging therapy for patients previously deemed inoperable due to prohibitive

operative risk. This is a novel treatment utilizing a bioprosthesis sutured to a balloon or self-expandable

stainless steel or nitinol stent (Fig. 82-7). The prosthesis is introduced through the femoral artery

retrogradely into the aorta and placed at the midpart of the native stenotic AV. The radial forces of the

stent push the native AV aside to increase the valve orifice area. The prospective trial (Placement of

Aortic Transcatheter valves: PARTNER) randomized “high-risk” patients (operative mortality >15%) to

either transfemoral AVR (TF-AVR) or conventional AVR.22 Thirty-day mortality was doubled in the

conventional group, but at 1 year, survival was similar. In the “inoperable” subset, TF-AVR was shown

to be significantly superior to optimal medical therapy with improvement in NYHA scores to 1–2 and a

20% improvement in mortality at 5-year follow-up. Hemodynamic benefits and valve integrity also

persisted at 5 years.23 In patients with severe peripheral vascular disease, the retrograde arterial

approach cannot be used. In these patients, similar prostheses can be inserted directly into the beating

heart through the LV apex (transapical approach). This approach has been shown to have a lower rate of

vascular complications, postoperative heart block necessitating permanent pacemaker implantation and

paravalvular regurgitation as compared to the TF-AVR with similar 1-year survival.24–26 In conclusion,

appropriately selected high-risk or inoperable patients can benefit significantly from TF-AVR in both

survival and functional status, and in those where femoral access is not an option, the transapical

technique is warranted.

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