Aortic Stenosis

1979CHAPTER 261

Bicuspid aortic valve (BAV) disease affects as many as 0.5–1.4% of

the general population and is accompanied by an associated aortopathy in ~30-40% of individuals, a disease process expressed as root or

ascending aortic aneurysm formation or descending thoracic aortic

coarctation. An increasing number of childhood survivors of congenital heart disease present later in life with valvular dysfunction. The

global burden of valvular heart disease will continue to progress.

As is true for many other chronic health conditions, disparities

in access to and quality of care for patients with valvular heart disease have been well documented, especially for those patients with

rheumatic heart disease in low- and middle-income countries. In the

Society for Thoracic Surgeons (STS)/American College of Cardiology

(ACC) Transcatheter Valve Therapy (TVT) registry, blacks comprise

<5% of patients in the United States who have received a transcatheter

valve for AS. Management decisions and outcome differences based

on age, sex, race, and geography require intensification of educational

efforts and prioritization of resources.

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.

AORTIC STENOSIS

Aortic stenosis (AS) is the most common valve lesion among adult

patients with chronic valvular heart disease; the majority of adult

patients with symptomatic, valvular AS are male.

■ ETIOLOGY AND PATHOGENESIS

(Table 261-1) AS in adults is due to degenerative calcification of the

aortic cusps and occurs most commonly on a substrate of congenital

disease (BAV), chronic (trileaflet) deterioration, or previous rheumatic

inflammation. A pathologic study of specimens removed at the time

of aortic valve replacement (AVR) for AS in adults showed that 53%

were bicuspid and 4% were unicuspid. The process of aortic valve

deterioration and calcification is not a passive one, but rather one that

shares many features with vascular atherosclerosis, including endothelial dysfunction, lipid accumulation, inflammatory cell activation,

cytokine release, and upregulation of several signaling pathways

(Fig. 261-3). Eventually, a fibrocalcific response is established

wherein collagen is deposited and valvular myofibroblasts differentiate phenotypically into osteoblasts and actively produce

bone matrix proteins that allow for the deposition of calcium

hydroxyapatite crystals. Genetic polymorphisms involving the

vitamin D receptor, the estrogen receptor in postmenopausal

women, interleukin 10, and apolipoprotein E4 have been linked

to the development of calcific AS, and a strong familial clustering

of cases with trileaflet valves has been reported from western

France. Several traditional atherosclerotic risk factors have also

been associated with the development and progression of calcific AS, including hypertension, low-density lipoprotein (LDL)

cholesterol, lipoprotein a (Lp[a]), diabetes mellitus, smoking,

chronic kidney disease, and the metabolic syndrome. In a Canadian observational cohort study, the incidence of severe AS was

144 per 100,000 person-years. Hypertension, diabetes mellitus,

and dyslipidemia accounted for approximately one-third of the

population-attributable risk for severe AS. The presence of aortic

valve sclerosis (focal thickening and calcification of the leaflets

not severe enough to cause obstruction) is associated with an

excess risk of cardiovascular death and myocardial infarction

(MI) among persons aged >65. Approximately 30% of persons

aged >65 years exhibit some degree of aortic valve sclerosis. Rate and

extent of progression to valve obstruction (stenosis) vary among individual patients.

Rheumatic disease of the aortic leaflets produces commissural fusion,

sometimes resulting in a bicuspid-appearing valve. This condition, in

turn, makes the leaflets more susceptible to trauma and ultimately

leads to fibrosis, calcification, and further narrowing. By the time

obstruction to left ventricular (LV) outflow causes serious clinical disability, the valve is usually a rigid calcified mass, and careful examination may make it difficult or even impossible to determine the etiology

of the underlying process. Rheumatic AS is almost always associated

with involvement of the mitral valve and with aortic regurgitation

(AR). Mediastinal radiation can also result in late scarring, fibrosis, and

calcification of the aortic leaflets.

■ BICUSPID AORTIC VALVE DISEASE

A bicuspid aortic valve (BAV) is the most common congenital heart

valve defect and occurs in 0.5–1.4% of the population with a 2–4:1

male-to-female predominance. The inheritance pattern appears to be

autosomal dominant with incomplete penetrance, although some have

questioned an X-linked component as suggested by the prevalence of

BAV disease among patients with Turner’s syndrome. The prevalence

of BAV disease among first-degree relatives of an affected individual

is ~10%. A single gene defect to explain the majority of cases has not

been identified, although mutations in the NOTCH1, GATA5, and

GATA4 genes have been described in some families. Abnormalities in

endothelial nitric oxide synthase and NKX2.5 have been implicated as

well. Medial degeneration with ascending aortic aneurysm formation

occurs commonly among patients with BAV disease; aortic coarctation

is less frequently encountered. Patients with BAV disease have larger

aortas than patients with comparable tricuspid aortic valve disease. The

aortopathy develops independently of the hemodynamic severity of the

valve lesion, but directional shear forces dictated by the anatomic configuration of the valve appear to influence its expression. For example,

enlargement of the ascending aorta along its greater curvature is most

often associated with right-left cusp fusion, the most common bicuspid

variant. Patients with BAV disease are at risk for aneurysm formation and/or dissection. A BAV can be a component of more complex

congenital heart disease with or without other left heart obstructing

lesions, as seen in Shone’s complex.

■ OTHER FORMS OF OBSTRUCTION TO LEFT

VENTRICULAR OUTFLOW

In addition to valvular AS, three other lesions may be responsible for

obstruction to LV outflow: hypertrophic obstructive cardiomyopathy

(Chap. 259), discrete fibromuscular/membranous subaortic stenosis,

All valve disease

Mitral valve disease

Aortic valve disease

0

2

4

6

8

10

12

14

<45 45–54 53–64 65–74 ≥75

Prevalence of moderate or severe valve

disease (%)

FIGURE 261-2 The burden of moderate or severe mitral and aortic valve disease in the

United States. Prevalence estimates are derived from three population-based studies

comprising a total of 11,911 individuals: The Coronary Artery Risk Development in Young

Adults (CARDIA), the Atherosclerosis Risk in Communities (ARIC), and the Cardiovascular

Health Study (CHS). (Reproduced with permission from VT Nkomo et al: Burden of valvular

heart diseases: A population-based study. Lancet 368:1005, 2006.)

TABLE 261-1 Major Causes of Aortic Stenosis

VALVE LESION ETIOLOGIES

Aortic stenosis Congenital (bicuspid, unicuspid)

Degenerative calcific disease

Rheumatic fever

Radiation

1980 PART 6 Disorders of the Cardiovascular System

and supravalvular AS (Chap. 269). The causes of LV outflow obstruction can be differentiated on the basis of the cardiac examination and

Doppler echocardiographic findings.

■ PATHOPHYSIOLOGY

The obstruction to LV outflow produces a systolic pressure gradient

between the LV and aorta. When severe obstruction is suddenly produced experimentally, the LV responds by dilation and reduction of

stroke volume. However, in some patients, the obstruction may be present at birth and/or increase gradually over the course of many years, and

LV contractile performance is maintained by the presence of concentric

LV hypertrophy. Initially, this serves as an adaptive mechanism because it

reduces toward normal the systolic stress developed by the myocardium,

as predicted by the Laplace relation (S = Pr/h, where S = systolic wall

stress, P = pressure, r = radius, and h = wall thickness). A large transaortic valve pressure gradient may exist for many years without a reduction

in cardiac output (CO) or the development of LV dilation. Ultimately,

however, excessive hypertrophy becomes maladaptive, LV systolic function declines because of afterload mismatch, abnormalities of diastolic

function progress, and irreversible myocardial fibrosis develops.

A mean systolic pressure gradient >40 mmHg with a normal CO

or an effective aortic orifice area of ~<1 cm2

 (or ~<0.6 cm2

/m2

 body

surface area in a normal-sized adult)—i.e., less than approximately

one-third of the normal orifice area—is generally considered to represent severe obstruction to LV outflow. The elevated LV end-diastolic

pressure observed in many patients with severe AS and preserved ejection fraction (EF) signifies the presence of diminished compliance of

the hypertrophied LV. Although the CO at rest is within normal limits

in most patients with severe AS, it usually fails to rise normally during

exercise. Loss of an appropriately timed, vigorous atrial contraction,

as occurs in atrial fibrillation (AF) or atrioventricular dissociation,

may cause rapid progression of symptoms. Late in the course, contractile function deteriorates because of afterload excess, the CO and

LV–aortic pressure gradient decline, and the mean left atrial (LA),

pulmonary artery (PA), and right ventricular (RV) pressures rise. LV

performance can be further compromised by superimposed epicardial

coronary artery disease (CAD). Stroke volume (and thus CO) can

also be reduced in patients with significant hypertrophy and a small

LV cavity despite a normal EF. Low-flow (defined as a stroke volume

index <35 mL/m2

), low-gradient (defined as a mean pressure gradient

<40 mmHg) AS (with either reduced or normal LV systolic function)

is both a diagnostic and therapeutic challenge.

The hypertrophied LV causes an increase in myocardial oxygen

requirements. In addition, even in the absence of obstructive CAD,

coronary blood flow is impaired to the extent that ischemia can be

precipitated under conditions of excess demand. Capillary density is

reduced relative to wall thickness, compressive forces are increased,

and the elevated LV end-diastolic pressure reduces the coronary driving pressure. The subendocardium is especially vulnerable to ischemia

by this mechanism.

■ SYMPTOMS

AS is rarely of clinical importance until the valve orifice has narrowed

to ~1 cm2

. Even severe AS may exist for many years without producing any symptoms because of the ability of the hypertrophied LV to

generate the elevated intraventricular pressures required to maintain a

Lipid infiltration

Radiation

Mechanical stress

Lipid-derived species

Cytokines

Inflammation Fibro-calcific response

Lipids

Calcium

hydroxyapatite

Blood

vessel

Osteoprogenitor

cell

Apoptosis

Osteogenic transition

Monocyte

Collagen

Fibrosis

Mineralization

Leukotrienes Prostaglandins

VIC

AA

LPAR

ATX

ATX

sPLA2

Ox-LDL

Ox-PL Lp-PLA2

IysoPC

IysoPA

MMPs

VEGF TNF

IL-1β

TGFβ

IL-6

WNT3a

BMP2

5-LO COX2

A2AR

NT5E

ENPP1

ATP

ALP

Pi

Adenosine

+Pi

AMP

+PPi

RUNX2

MSX2

Time

Mastocyte

T cell

Macrophage

Calcifying

microvesicles

VEGF LDL

Lp(a) LDL

NOS

uncoupling

ROS

ACE

RANKL

TNF

Chymase

Angiotensin I

Angiotensin II

inflammation

FIGURE 261-3 Pathogenesis of calcific aortic stenosis. Lipid and inflammatory cell infiltration occurs across damaged endothelium. A cascade of events follows that leads

eventually to formation of disorganized collagen (fibrosis) and calcium hydroxyapatite (bone) deposition. Valvular interstitial cells (VIC) are critical participants in this active

process. AA, arachidonic acid; ACE, angiotensin-converting enzyme; ALP, alkaline phosphatase; ApoB, apolipoprotein B; AMP, adenosine monophosphate; ATP, adenosine

triphosphate; ATX, autotaxin; A2AR, adenosine A2A receptor; BMP, bone morphogenetic protein; COX2, cyclo-oxygenase 2; ENPP, ectonucleotide pyrophosphatase/

phosphodiesterase; IL, interleukin; 5-LO, 5-lipoxygenase; LDL, low-density lipoprotein; Lp(a), lipoprotein(a); LPAR, lysophosphatidic acid receptor; Lp-PLA2, lipoproteinassociated phospholipase A2; lysoPA, lysophosphatidic acid; lysoPC, lysophosphatidylcholine; MMP, matrix metalloproteinase; NOS, nitric oxide synthase; Ox-PL, oxidized

phospholipid; Ox-LDL, oxidized LDL; RANKL, receptor activator of nuclear factor-κB ligand; ROS, reactive oxygen species; RUNX2, runt-related transcription factor 2; sPLA2,

secreted PLA2; TGFβ , transforming growth factor-β ; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor; VIC, valvular interstitial cell. (Reproduced with

permission from B Lindman et al: Calcific aortic stenosis. Nat Rev Dis Primers 2:16006, 2016.)

Aortic Stenosis

1981CHAPTER 261

normal stroke volume. Once symptoms occur, or the LV ejection fraction falls below normal, valve replacement is indicated.

Most patients with pure or predominant AS have gradually increasing obstruction over years but do not become symptomatic until the

sixth to eighth decades. Adult patients with BAV disease, however,

develop significant valve dysfunction and symptoms one to two

decades sooner. Exertional dyspnea, angina pectoris, and syncope are

the three cardinal symptoms. Often, there is a history of insidious progression of fatigue and dyspnea associated with gradual curtailment of

activities and reduced effort tolerance. Dyspnea results primarily from

elevation of the pulmonary capillary pressure caused by elevations of

LV diastolic pressures secondary to impaired relaxation and reduced

LV compliance. Angina pectoris usually develops somewhat later

and reflects an imbalance between the increased myocardial oxygen

requirements and reduced oxygen availability. CAD may or may not

be present, although its coexistence is common among AS patients age

>65. Exertional syncope may result from a decline in arterial pressure

caused by vasodilation in exercising muscles and inadequate vasoconstriction in nonexercising muscles in the face of a fixed CO, or from a

sudden fall in CO produced by an arrhythmia.

Because the CO at rest is usually well maintained until late in the

course, marked fatigability, weakness, peripheral cyanosis, cachexia,

and other clinical manifestations of a low CO are usually not prominent until this stage is reached. Orthopnea, paroxysmal nocturnal

dyspnea, and pulmonary edema, i.e., symptoms of LV failure, also

occur only in the advanced stages of the disease. Severe pulmonary

hypertension leading to RV failure and systemic venous hypertension,

hepatomegaly, AF, and tricuspid regurgitation (TR) are usually late

findings in patients with isolated severe AS.

When AS and mitral stenosis (MS) coexist, the reduction in flow

(CO) caused by MS lowers the pressure gradient across the aortic valve

and, thereby, masks many of the clinical findings produced by AS. The

transaortic pressure gradient can be increased in patients with concomitant AR due to higher aortic valve flow rates.

■ PHYSICAL FINDINGS

The heart rhythm is generally regular until late in the course; at other

times, AF should suggest the possibility of associated mitral valve disease.

Hypertension occurs commonly among older adults with AS. In the late

stages, however, when stroke volume declines, the systolic pressure may

fall and the pulse pressure narrow. The carotid arterial pulse rises slowly

to a delayed peak (pulsus parvus et tardus). A thrill or anacrotic “shudder” may be palpable over the carotid arteries, more commonly the left.

In the elderly, the stiffening of the arterial wall may mask this important

physical sign. In many patients, the a wave in the jugular venous pulse

is accentuated. This results from the diminished distensibility of the RV

cavity caused by the bulging, hypertrophied interventricular septum.

The LV impulse is sometimes displaced laterally in the later stages

of the disease. A double apical impulse (with a palpable S4

) may be

appreciated, particularly with the patient in the left lateral recumbent

position. A systolic thrill may be present at the base of the heart to the

right of the sternum when leaning forward or in the suprasternal notch.

Auscultation An early systolic ejection sound is frequently audible

in children, adolescents, and young adults with congenital BAV disease. This sound usually disappears when the valve becomes calcified

and rigid. As AS increases in severity, LV systole may become prolonged so that the aortic valve closure sound no longer precedes the

pulmonic valve closure sound, and the two components may become

synchronous, or aortic valve closure may even follow pulmonic valve

closure, causing paradoxical splitting of S2 (Chap. 239). The sound

of aortic valve closure can be heard most frequently in patients with

AS who have pliable valves, and calcification diminishes the intensity

of this sound. Frequently, an S4

 is audible at the apex and reflects the

presence of LV hypertrophy and an elevated LV end-diastolic pressure;

an S3

 generally occurs late in the course, when the LV dilates and its

systolic function becomes severely compromised.

The murmur of AS is described as an ejection (mid) systolic murmur

that commences shortly after the S1

, increases in intensity to reach a peak

toward the middle of ejection, and ends just before aortic valve closure. It is

characteristically low-pitched, rough, and rasping in character, and loudest

at the base of the heart, most commonly in the second right intercostal

space. It is transmitted upward along the carotid arteries. Occasionally it

is transmitted downward and to the apex, where it may be confused with

the systolic murmur of mitral regurgitation (MR) (Gallavardin effect). In

almost all patients with severe obstruction and preserved CO, the murmur

is at least grade III/VI. In patients with mild degrees of obstruction or in

those with severe stenosis with heart failure and low CO in whom the

stroke volume and, therefore, the transvalvular flow rate are reduced, the

murmur may be relatively soft and brief.

■ LABORATORY EXAMINATION

ECG In most patients with severe AS, there is LV hypertrophy. In

advanced cases, ST-segment depression and T-wave inversion (LV

“strain”) in standard leads I and aVL and in the left precordial leads are

evident. However, there is no close correlation between the ECG and the

hemodynamic severity of obstruction, and the absence of ECG signs of

LV hypertrophy does not exclude severe obstruction. Systemic hypertension can coexist and also contribute to the development of hypertrophy.

Echocardiogram The key findings on transthoracic echocardiogram are thickening, calcification, and reduced systolic opening of the

valve leaflets and LV hypertrophy. Eccentric closure of the aortic valve

cusps is characteristic of congenitally bicuspid valves. Transesophageal

echocardiography imaging can display the obstructed orifice extremely

well, but it is not routinely required for accurate characterization of AS.

The valve gradient and aortic valve area can be estimated by Doppler

measurement of the transaortic velocity. Severe AS is defined by a valve

area <1 cm2

, whereas moderate AS is defined by a valve area of 1–1.5 cm2

and mild AS by a valve area of 1.5–2 cm2

. Aortic valve sclerosis, conversely, is accompanied by a jet velocity of <2.5 m/s (peak gradient

<25 mmHg). LV dilation and reduced systolic shortening reflect

impairment of LV function. There is a robust experience with the use

of longitudinal strain to characterize earlier changes in LV systolic

function, before a decline in EF can be appreciated. Doppler indices of

impaired diastolic function are frequently seen.

Echocardiography is useful for identifying coexisting valvular

abnormalities, differentiating valvular AS from other forms of LV

outflow obstruction, and measuring the aortic root and proximal

ascending aortic dimensions. These aortic measurements are particularly important for patients with BAV disease. Dobutamine stress

echocardiography is useful for the evaluation of patients with AS and

severe LV systolic dysfunction (low-flow, low-gradient, severe AS with

reduced EF), in whom the severity of the AS can often be difficult to

judge. Patients with severe AS (i.e., valve area <1 cm2

) with a relatively

low mean gradient (<40 mmHg) despite a normal EF (low-flow, lowgradient, severe AS with normal EF) are often hypertensive, and efforts

to control their systemic blood pressure should be optimized before

Doppler echocardiography is repeated. The use of dobutamine stress

echocardiography in this setting is generally not advised. When there

is continued uncertainty regarding the severity of AS in patients with

reduced CO, quantitative analysis of the amount of aortic valve calcium

with chest computed tomography (CT) can be helpful. There is increasing use of chest CT angiography to assess aortic valve morphology

and function. It has become the imaging method of choice to plan for

transcatheter aortic valve implantation (TAVI). Finally, the use of cardiac magnetic resonance (CMR) imaging to screen for the presence of

myocardial fibrosis with late gadolinium enhancement in patients with

severe AS is an area of active investigation.

Chest X-Ray The chest x-ray may show no or little overall cardiac

enlargement for many years. Hypertrophy without dilation may produce some rounding of the cardiac apex in the frontal projection and

slight backward displacement in the lateral view. A dilated proximal

ascending aorta may be seen along the upper right heart border in the

frontal view. Aortic valve calcification may be discernible in the lateral

view, but it is usually readily apparent on fluoroscopic examination

or by echocardiography; the absence of valvular calcification on fluoroscopy in an adult suggests that severe valvular AS is not present.

In later stages of the disease, as the LV dilates, there is increasing

1982 PART 6 Disorders of the Cardiovascular System

roentgenographic evidence of LV enlargement, pulmonary congestion,

and enlargement of the LA, PA, and right-sided heart chambers.

Catheterization Right- and left-sided heart catheterization for

invasive assessment of AS is performed infrequently but can be useful

when there is a discrepancy between the clinical and noninvasive findings. Concern has been raised that attempts to cross the aortic valve

for measurement of LV pressures are associated with a risk of cerebral

embolization. Catheterization can also be useful in three distinct categories of patients: (1) patients with multivalvular disease, in whom

the role played by each valvular deformity should be defined to aid in

the planning of operative treatment; (2) young, asymptomatic patients

with noncalcific congenital AS, to define the severity of obstruction

to LV outflow, because operation or percutaneous aortic balloon valvuloplasty (PABV) may be indicated in these patients if severe AS is

present, even in the absence of symptoms; and (3) patients in whom it

is suspected that the obstruction to LV outflow may not be at the level of

the aortic valve but rather at the sub- or supravalvular level.

Coronary angiography is indicated to screen for CAD in appropriate

patients with severe AS who are being considered for surgical or transcatheter valve intervention. Angiography can be performed invasively

at the time of catheterization for hemodynamic assessment or with

noninvasive CT techniques. Decision-making regarding the need for

coronary artery revascularization at the time of aortic valve intervention is individualized.

■ NATURAL HISTORY

Death in patients with severe AS occurs most commonly in the seventh

and eighth decades. Based on data obtained at postmortem examination

in patients before surgical treatment became widely available, the average time to death after the onset of various symptoms was as follows:

angina pectoris, 3 years; syncope, 3 years; dyspnea, 2 years; heart failure,

1.5–2 years. Moreover, in >80% of patients who died with AS, symptoms

had existed for <4 years. Among adults dying with valvular AS, sudden

death, which presumably resulted from an arrhythmia, occurred in

10–20%; however, most sudden deaths occurred in patients who had

previously been symptomatic. Sudden death as the first manifestation

of severe AS is very uncommon (~1% per year) in asymptomatic adult

patients. Calcific AS is a progressive disease, with an annual reduction

in valve area averaging 0.1 cm2

 and annual increases in peak jet velocity

and mean valve gradient averaging 0.3 m/s and 7 mmHg, respectively.

TREATMENT

Aortic Stenosis (Fig. 261-4)

MEDICAL TREATMENT

In patients with severe AS (valve area <1 cm2

), strenuous physical

activity and competitive sports should be avoided, even in the

asymptomatic stage. Care must be taken to avoid dehydration and

hypovolemia to protect against a significant reduction in CO. Medications used for the treatment of hypertension or CAD, including

beta blockers and angiotensin-converting enzyme (ACE) inhibitors,

are generally safe for asymptomatic patients with preserved LV systolic function. Nitroglycerin is helpful in relieving angina pectoris

in patients with CAD. Neither HMG-CoA reductase inhibitors

(“statins”) nor inhibitors of the renin-angiotensin-aldosterone system slow the rate of progression of AS. The use of statin medications

should be driven by considerations regarding primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD)

events. The need for endocarditis prophylaxis is restricted to AS

patients with a prior history of endocarditis.

SURGICAL TREATMENT

Asymptomatic patients with calcific AS and severe obstruction

should be followed carefully for the development of symptoms

and by serial echocardiograms for evidence of deteriorating LV

function. Operation is indicated in patients with severe AS (valve

area <1 cm2

 or 0.6 cm2

/m2

 body surface area) who are symptomatic,

those who exhibit LV systolic dysfunction (EF <50%), and those

with AS due to BAV disease and an aneurysmal root or ascending

aorta (maximal dimension >5.5 cm). Operation for aneurysm

disease is recommended at smaller aortic diameters (4.5–5.0 cm)

for patients with a family history of an aortic catastrophe and

for patients who exhibit rapid aneurysm growth (>0.5 cm/year).

Patients with asymptomatic moderate or severe AS who are referred

for coronary artery bypass grafting surgery should also have AVR.

In patients without heart failure, the operative risk of surgical AVR

(SAVR) (including patients with AS or AR) is ~2% (Table 261-2)

but increases as a function of age and the need for concomitant

aortic or other heart valve surgery or coronary bypass grafting. The

indications for SAVR in the asymptomatic patient have been the

subject of intense debate, as surgical outcomes in selected patients

have continued to improve. Relative indications for which surgery

can be considered include an abnormal response to treadmill

exercise; rapid progression of AS, especially when urgent access to

medical care might be compromised; very severe AS, defined by an

aortic valve jet velocity >5 m/s or mean gradient >60 mmHg and

low operative risk; and excessive LV hypertrophy in the absence of

systemic hypertension. Exercise testing can be safely performed in

asymptomatic patients, as many as one-third of whom will show

signs of functional impairment. In a small randomized controlled

trial (RCT) of early surgery versus conservative care for asymptomatic patients with very severe AS (defined by a transaortic valve jet

velocity ≥4.5 m/s, mean gradient ≥50 mmHg, or aortic valve area

≤0.75 cm2

), the rate of operative death or death from cardiovascular causes during follow-up was reduced with early surgery. In the

conservative care group, the cumulative incidence of sudden death

was 4% at 4 years and 14% at 8 years.

Operation should be carried out promptly (1–3 months) after

symptom onset. Clinical decision-making is straightforward for

patients with normal flow (>35 mL/m2

), high gradient (≥40 mmHg)

severe AS. In patients with low-flow, low-gradient severe AS with

reduced LVEF, perioperative mortality rates are high (15–20%), and

evidence of LV dysfunction usually persists even after a technically

successful operation. Long-term postoperative survival correlates

with preoperative LV function. Nonetheless, in view of the even

worse prognosis of such patients when they are treated medically,

there is usually little choice but to advise valve replacement, especially in patients in whom flow reserve can be demonstrated by

dobutamine stress echocardiography (defined by a ≥20% increase

in stroke volume after dobutamine challenge). Patients in this high

surgical risk group are usually treated with TAVI (see below), but

robust data from RCTs in this subpopulation of severe AS patients

are lacking. The management of patients with low-flow, low-gradient severe AS with normal LVEF is also challenging. Outcomes are

improved with surgery or TAVI compared with conservative medical care for symptomatic patients with this type of “paradoxical”

low-flow AS, but more research is needed to guide therapeutic decision making for individual patients. In patients in whom severe AS

and CAD coexist, relief of the AS and revascularization may sometimes result in striking clinical and hemodynamic improvement.

Because many patients with calcific AS are elderly, particular

attention must be directed to the adequacy of hepatic, renal, and

pulmonary function before AVR is recommended. Age alone is not

a contraindication to SAVR for AS. The perioperative mortality

rate depends to a substantial extent on the patient’s preoperative

clinical and hemodynamic state. Assessment of frailty is a critical

component of preprocedural evaluation. Treatment decisions for

AS patients who are not at low operative risk are made by a multidisciplinary heart team with representation from general cardiology, interventional cardiology, multimodality imaging, cardiac

surgery, and other subspecialties as needed, including geriatrics.

The 10-year survival rate of older adult patients with SAVR is ~60%.

Recommendations regarding the type of valve prosthesis (biological

or mechanical) must weigh the trade-offs between limited bioprosthetic valve durability and the risks of thromboembolism and bleeding with a mechanical valve and are heavily influenced by patient

age and preferences. Bioprostheses are generally favored for patients

Aortic Stenosis

1983CHAPTER 261

Abnormal aortic valve with

reduced systolic opening

Symptoms due to AS

Severe AS stage D1

• Vmax ≥4 m/s or

• ∆Pmean ≥40 mm Hg

AS stage B

(Vmax 3–3.9 m/s)

AS stage C

(Vmax ≥4 m/s)

Severe AS stage D2

DSE Vmax ≥4 m/s at

any flow rate

Severe AS stage D3

AVA1 ≤0.6 cm2/m2

and SVI <35 mL/m2

AS most likely

cause of symptoms

Rapid disease

progression

Low surgical

risk

or

or

↓ EF to <60%

on 3

serial studies

BNP >3x

normal

Vmax ≥5 m/s

Vmax ≥4 m/s and

AVA ≤1.0 cm2

LV EF <50%

Yes No EF

<50%

Other

cardiac

surgery

Other

cardiac

surgery

ETT with

↓BP or

↓ex. capacity

No AS symptoms

AVR (SAVR or TAVI) (1) AVR (SAVR or TAVI) (1) SAVR (2a) SAVR (2b)

FIGURE 261-4 Management strategy for patients with aortic stenosis. 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. Patients who

do not meet criteria for intervention should be monitored with clinical and echocardiographic follow-up. The class designations refer to the American Heart Association/

American College of Cardiology methodology for treatment recommendations. Class I recommendations should be performed or are indicated; Class IIa recommendations

are considered reasonable to perform; Class IIb recommendations may be considered. The stages refer to the stages of progression of the disease. At disease stage A, risk

factors are present for the development of valve dysfunction; stage B refers to progressive, mild-moderate, asymptomatic valve disease; stage C disease is severe in nature

but clinically asymptomatic; stage C1 characterizes asymptomatic patients with severe valve disease but compensated ventricular function; stage C2 refers to asymptomatic,

severe disease with ventricular decompensation; stage D refers to severe, symptomatic valve disease. With aortic stenosis, stage D1 refers to symptomatic patients with

severe aortic stenosis and a high valve gradient (>40 mmHg mean gradient); stage D2 comprises patients with symptomatic, severe, low-flow, low-gradient aortic stenosis

and low left ventricular ejection fraction (LVEF); and stage D3 characterizes patients with symptomatic, severe, low-flow, low-gradient aortic stenosis and preserved left

ventricular ejection fraction (paradoxical, low-flow, low-gradient severe aortic stenosis). Patients with symptomatic severe AS (left side of the diagram, jet velocity ≥4m/s)

should be referred for AVR (SAVR or TAVI). Asymptomatic patients with severe AS (jet velocity ≥4m/s) should be referred for AVR (SAVR or TAVI) for LVEF <50% or when

other cardiac surgery is needed (e.g., aneurysm repair). There are several findings for which referral for AVR would be reasonable related to results of exercise testing, the

presence of a jet velocity >5 m/s or elevated B-type natriuretic peptide (BNP), provided the patient is considered low risk for complications related to AVR. AS, aortic stenosis;

AVA, aortic valve area; AVR, aortic valve replacement; BP, blood pressure; DSE, dobutamine stress echocardiography; EF, ejection fraction; ETT, exercise treadmill test; ΔPmean,

mean pressure gradient; SAVR, surgical AVR; TAVI, transcatheter aortic valve implantation; Vmax, maximum velocity. (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.)

TABLE 261-2 Mortality Rates After Aortic Valve Surgerya

OPERATION NUMBER

UNADJUSTED OPERATIVE

MORTALITY (%)

AVR (isolated) 25,274 1.9

AVR + CAB 15,855 3.6

a

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.

age >65 years. Shared decision-making with younger patients must

be individualized, although increasing numbers of patients age <65

now opt for a biological valve replacement. Approximately 30%

of bioprosthetic valves evidence primary valve failure by 10 years,

requiring re-replacement (or valve-in-valve TAVI, see below), and

an approximately equal percentage of patients with mechanical

prostheses develop hemorrhagic complications as a consequence

of treatment with vitamin K antagonists. In a large observational

study of patients who underwent SAVR in California between 1996

and 2013, receipt of a biological versus a mechanical prosthesis in

patients <55 years old was associated with an excess hazard of death

over 15 years of follow-up. Homograft AVR is usually reserved for

patients with aortic valve endocarditis.

The Ross procedure involves replacement of the diseased aortic

valve with the autologous pulmonic valve and implantation of a

homograft in the native pulmonic position. It is a technically complex procedure that may be considered in young or middle-aged

adult patients when surgical and institutional expertise are available. Late postoperative complications include aortic root dilation,

AR, and pulmonary homograft stenosis.

1984 PART 6 Disorders of the Cardiovascular System

PERCUTANEOUS AORTIC BALLOON VALVULOPLASTY

This procedure is preferable to operation in many children and

young adults with congenital, noncalcific AS (Chap. 269). It is not

recommended as definitive therapy in adults with severe calcific AS

because of a very high restenosis rate (80% within 1 year) and the

risk of procedural complications, but on occasion, it has been used

successfully as a bridge to operation or TAVI in patients with severe

LV dysfunction and shock. It is performed routinely as part of the

TAVI procedure (see below).

TRANSCATHETER AORTIC VALVE IMPLANTATION

TAVI surpassed SAVR for treatment of AS in the United States in 2016

and is now available to symptomatic patients across the entire surgical

risk spectrum (prohibitive, high, intermediate, and low) on the basis of

the favorable results seen in a series of landmark RCTs reported over

the past decade (Fig. 261-5). Application of TAVI in asymptomatic AS

patients is under active investigation. It is most commonly performed

using one of two systems, a balloon-expandable valve or a selfexpanding valve, both of which incorporate a pericardial bioprosthesis

(Fig. 261-6). TAVI is most frequently undertaken via the transfemoral

route, although trans-LV apical, subclavian, carotid, and ascending

aortic routes have been used. Aortic balloon valvuloplasty under rapid

RV (or LV) pacing is performed as a first step to create an orifice of

sufficient size for the prosthesis. Procedural success rates exceed 95%

in appropriately selected patients. Valve performance characteristics

are excellent over 5 years; longer-term durability assessment is ongoing.

Outcomes achieved with this transformative technology have been

very favorable and have allowed the extension of AVR to groups of

patients previously considered at high or prohibitive risk for conventional surgery. Nevertheless, some prohibitive or high surgical risk

patients are not candidates for this procedure because their comorbidity profile and frailty would make its undertaking inappropriate. The

heart team is specifically charged with making challenging decisions

of this nature. The use of these devices for treatment of patients with

structural deterioration of bioprosthetic aortic valves (valve-in-valve

TAVI), as an alternative to reoperative valve replacement, has increased

sharply over the past 5 years. The technology has also been increasingly

applied to BAV patients despite the fact that patients with this anatomy

were excluded from the landmark RCTs.

Compared with SAVR, transfemoral TAVI results in fewer periprocedural deaths and confers lower risks of strokes, major bleeding, and

AF. Hospital lengths of stay are shorter and return to normal activity

more rapid with TAVI. Rates of permanent pacemaker use, perivalvular AR, and vascular complications are lower with SAVR. The

choice between TAVI and SAVR for patients with trileaflet AS who

prefer a biological prosthesis rests on several clinical, imaging, and

technical considerations (Fig. 261-7 and Table 261-3). Because there

100

90

50

60

70

80

40

30

Death, stroke, or rehospitalization (%)

20

10

0

0 3 6

Months since procedure

No. at risk

A

Surgery

TAVR

454

496

408

475

390

467

381

462

377

456

374

451

9 12

20

15

10

5

0

3

4.2

8.5

Hazard ratio, 0.54 (95% CI, 0.37–0.79)

P = 0.001 by log-rank test

15.1

9.3

TAVR

Surgery

0 6 9 12

FIGURE 261-6 Transcatheter aortic valve replacement (TAVR) with a balloon

expandable valve versus surgical aortic valve replacement in low surgical risk

patients. Shown are Kaplan-Meier estimates of the rate of the primary composite

end point including death from any cause, stroke, or rehospitalization. In this

randomized trial, transfemoral TAVR resulted in a marked reduction in the composite

endpoint at 1 year, although the individual components did not differ significantly.

(From MJ Mack et al: Transcatheter aortic-valve replacement with a balloonexpandable valve in low-risk patients. N Engl J Med 380:1695, 2019. Copyright © 2019

Massachusetts Medical Society. Reprinted with permission from Massachusetts

Medical Society.)

FIGURE 261-5 Balloon-expandable (A) and self-expanding (B) valves for transcatheter aortic valve replacement (TAVR). B, inflated balloon; N, nose cone; V, valve. (Part A,

courtesy of Edwards Lifesciences, Irvine, CA; with permission. NovaFlex+ is a trademark of Edwards Lifesciences Corporation. Part B, © Medtronic, Inc. 2015. Medtronic

CoreValve Transcatheter Aortic Valve. CoreValve is a registered trademark of Medtronic, Inc.)

B

V

N

A B

Aortic Stenosis

1985CHAPTER 261

Adult patient with AS

Indication for AVR

Share decision making with

patient and heart valve

team with discussion of

SAVR and TAVI (1)

Risk assessment

Patient age*

Mechanical

AVR (2a)

Pulmonic

autograft3

(2a)

Mechanical or

bioprosthetic (2a)

Bioprosthetic

(2a)

Bioprosthetic

No

No No

YES No

YES No

Age/Life expectancy*

Age <65 yrs

SAVR (1) SAVR (1)

TF TAVI (1)

TF TAVI (1)

SAVR (2a)

TAVI (1) Palliative care

(1)

Age 65-80 Age >80 yrs

Symptomatic severe AS (D1,

D2, D3) or asymptomatic

severe AS with EF <50%

Valve and vascular anatomy

and other factors suitable

for transfemoral TAVI†

Valve and vascular

anatomy suitable for

transfemoral TAVI†

Bioprosthetic

(1)

SAVR

VKA OK

>65 yrs No VKA

Life expectancy with acceptable

QOL >1 yr, patient preferences

and values

Estimated risk not extremely

high or prohibitive

VKA Anticoagulation

• Contraindicated

• Cannot be managed

• Not desired

High or prohibitive surgical risk

• STS >8% or

• >2 frailty measures or

• >2 organ systems or

• Procedure specific impediment

<50 yrs 50–65 yrs

FIGURE 261-7 Choice of surgical aortic valve replacement (SAVR) versus transfemoral transcatheter aortic valve implantation (TAVI) when indications for aortic valve

replacement are met. For patients who are not prohibitive or high surgical risk candidates, TAVI is not recommended for patients age <65 years (left hand side of flow

diagram). For prohibitive or high surgical risk patients, TAVI is preferred over SAVR but is recommended on an individual basis only after multidisciplinary heart team

consensus decision-making in collaboration with the patient and family. Palliative care is recommended when TAVI is considered futile (right side of flow diagram). AS, aortic

stenosis; AVR, aortic valve replacement; EF, ejection fraction; QOL, quality of life; STS, Society of Thoracic Surgeons; VKA, vitamin K antagonist. *

Approximate ages, based

on US Actuarial Life Expectancy tables, are provided for guidance. The balance between expected patient longevity and valve durability varies continuously across the age

range, with more durable valves preferred for patients with a longer life expectancy. Bioprosthetic valve durability is finite (with shorter durability for younger patients),

whereas mechanical valves are very durable but require lifelong anticoagulation. Long-term (20-y) data on outcomes with surgical bioprosthetic valves are available; robust

data on transcatheter bioprosthetic valves extend to only 5 years, leading to uncertainty about longer-term outcomes. The decision about valve type should be individualized

on the basis of patient-specific factors that might affect longevity. †

Placement of a transcatheter valve requires vascular anatomy that allows transfemoral delivery and the

absence of aortic root dilation that would require surgical replacement. Valvular anatomy must be suitable for placement on the specific prosthetic valve, including annulus

size and shape, leaflet number and calcification, and ostial height. (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.)

are scant RCT data on TAVI outcomes in patients <65 years, SAVR is

recommended in this age group. Aortic valve/root anatomy, as well

as the extent, severity, and distribution of calcium, and the distance

of the coronary arteries from the plane of the annulus, may dictate

a surgical approach, as could the need to perform a concomitant

procedure such as ascending aortic replacement. Lastly, inability

to achieve transfemoral access is a relative impediment to TAVI

given the higher complication rates observed when this procedure is

undertaken from other vascular access sites.

1986 PART 6 Disorders of the Cardiovascular System

TABLE 261-3 Factors Favoring SAVR, TAVI, or Palliative Care in Patients with Aortic Stenosis

FAVORS SAVR FAVORS TAVI FAVORS PALLIATION

Age/life expectancya • Younger age/longer life expectancy • Older age/fewer expected remaining

years of life

• Limited life expectancy

Valve anatomy • Bicuspid aortic valve

• Subaortic (LVOT) calcification

• Rheumatic valve disease

• Small or large aortic annulusb

• Calcific trileaflet AS

Prosthetic valve

preference

• Mechanical or surgical bioprosthetic valve

preferred

• Concern for patient-prosthesis mismatch (annular

enlargement might be considered)

• Bioprosthetic valve preferred

• Favorable ratio of life expectancy to

valve durability

• TAVI provides larger valve area than

same-sized SAVR

Concurrent cardiac

conditions

• Aortic dilationc

• Severe primary MR

• Severe CAD requiring bypass grafting

• Septal hypertrophy requiring myectomy

• Atrial fibrillation

• Severe calcification of the ascending

aorta (“porcelain” aorta)

• Irreversible severe LV systolic

dysfunction

• Severe MR due to annular

calcification

Noncardiac conditions • Severe lung, liver, or renal disease

• Mobility issues (high risk for

sternotomy)

• Symptoms likely due to noncardiac

conditions

• Severe dementia

• Moderate to severe involvement of 2

or more other organ systems

Frailty • Not frail or few frailty measures • Frailty likely to improve after TAVI • Severe frailty unlikely to improve

after TAVI

Estimated risk of SAVR

or TAVI

• SAVR risk low

• TAVI risk high

• TAVI risk low to medium

• SAVR risk high to prohibitive

• Prohibitive SAVR risk (>15%) or postTAVI life expectancy <1 year

Procedure-specific

impediments

• Valve anatomy, annular size, or low coronary ostial

height precludes TAVI

• Vascular access does not allow transfemoral TAVI

• Previous cardiac surgery with at-risk

coronary grafts

• Previous chest irradiation

• Valve anatomy, annular size, or

coronary ostial height precludes TAVI

• Vascular access does not allow

transfemoral TAVI

Goals of care and patient

preferences and values

• Less uncertainty about valve durability

• Avoid repeat intervention

• Lower risk of permanent pacer

• Life prolongation

• Symptom relief

• Improved long-term exercise capacity and QOL

• Avoid vascular complications

• Accepts longer hospital stay, pain in recovery

period

• Accepts uncertainty about valve

durability and possible repeat

intervention

• Higher risk of permanent pacer

• Life prolongation

• Symptom relief

• Improved exercise capacity and QOL

• Prefers shorter hospital stay, less

postprocedure pain

• Life prolongation not an important

goal

• Avoid futile or unnecessary

diagnostic or therapeutic procedures

• Avoid procedural stroke risk

• Avoid possibility of cardiac pacer

a

Data on bioprosthetic valve durability are more robust for SAVR valves than for TAVI valves. Mechanical valves are very durable but require lifelong anticoagulation.

Choice of prosthesis is a shared decision-making process accounting for individual patient values and preferences. b

Surgical root enlargement can be performed at time of

SAVR to allow a use of a larger prosthesis and reduce the occurrence of prosthesis-patient mismatch. c

Aortic root or ascending aortic enlargement may require surgical

correction at time of SAVR.

Abbreviations: AS, aortic stenosis; CAD, coronary artery disease; LV, left ventricular; LVOT, left ventricular outflow tract; MR, mitral regurgitation; QOL, quality of life;

SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation.

Source: Reproduced with permission from CR Burke et al: Goals of care in patients with severe aortic stenosis. Eur Heart J 41:929, 2020.

■ ETIOLOGY

(Table 262-1) Aortic regurgitation (AR) may be caused by primary

valve disease, aortic root disease, or their combination.

Primary Valve Disease Rheumatic disease results in thickening, deformity, and shortening of the individual aortic valve cusps,

changes that prevent their proper opening during systole and closure

during diastole. A rheumatic origin is much less common in patients

with isolated AR who do not have associated rheumatic mitral valve

disease. Patients with congenital bicuspid aortic valve (BAV) disease

may develop predominant AR, and ~20% of these patients will require

aortic valve surgery between 10 and 40 years of age. Congenital

262 Aortic Regurgitation

Patrick T. O’Gara, Joseph Loscalzo

■ FURTHER READING

Carapetis JR et al: Acute rheumatic fever and rheumatic heart disease.

Nat Rev Dis Primers 2:15084, 2016.

Kang D-H et al: Early surgery or conservative care for asymptomatic

aortic stenosis. N Engl J Med 382:111, 2020.

Lindman B et al: Calcific aortic stenosis. Nat Rev Dis Primers 2:16006, 2016.

Otto CM 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.

Siontis GCM et al: Transcatheter aortic valve implantation versus surgical aortic valve replacement for treatment of symptomatic severe aortic

stenosis: an updated meta-analysis. Eur Heart J 40:3143, 2019.

Watkins DA et al: Global, regional, and national burden of rheumatic

heart disease, 1990-2015. N Engl J Med 377:713, 2017.

Zühlke L et al: Clinical outcomes in 3343 children and adults with

rheumatic heart disease from 14 low- and middle-income countries:

Two-year follow-up of the global Rheumatic Heart Disease Registry

(the REMEDY Study). Circulation 134:1456, 2016.

Aortic Regurgitation

1987CHAPTER 262

regurgitates back into the LV) is increased in patients with AR. In

patients with severe AR, the volume of regurgitant flow may equal the

effective forward stroke volume. In contrast to MR, in which a portion

of the LV stroke volume is delivered into the low-pressure left atrium

(LA), in AR, the entire LV stroke volume is ejected into a high-pressure

zone, the aorta. An increase in the LV end-diastolic volume (increased

preload) constitutes the major hemodynamic compensation for AR.

The dilation and eccentric hypertrophy of the LV allow this chamber

to eject a larger stroke volume without requiring any increase in the

relative shortening of each myofibril. Therefore, severe AR may occur

with a normal effective forward stroke volume and a normal LV ejection fraction (LVEF, total [forward plus regurgitant] stroke volume/

end-diastolic volume), together with an elevated LV end-diastolic

pressure and volume. However, through the operation of Laplace’s law,

LV dilation increases the LV systolic tension required to develop any

given level of systolic pressure. Chronic AR is, thus, a state in which

LV preload and afterload are both increased. Ultimately, these adaptive

measures fail. As LV function deteriorates, the end-diastolic volume

rises further and the forward stroke volume and ejection fraction (EF)

decline. Deterioration of LV function often precedes the development

of symptoms. Considerable thickening of the LV wall also occurs with

chronic AR, and at autopsy, the hearts of these patients may be among

the largest encountered, sometimes weighing >1000 g.

The reverse diastolic pressure gradient from aorta to LV, which

drives the AR flow, falls progressively during diastole, accounting for

the typical decrescendo nature of the diastolic murmur. Equilibration

between aortic and LV pressures may occur toward the end of diastole

in patients with chronic severe AR, particularly when the heart rate is

slow. In patients with acute severe AR, the LV is unprepared for the

regurgitant volume load. LV compliance is normal or reduced, and LV

diastolic pressures rise rapidly, occasionally to levels >40 mmHg. The

LV pressure may exceed the LA pressure toward the end of diastole,

and this reversed pressure gradient closes the mitral valve prematurely.

In patients with chronic severe AR, the effective forward cardiac

output (CO) usually is normal or only slightly reduced at rest, but often

it fails to rise normally during exercise. An early sign of LV dysfunction

is a reduction in the EF. In advanced stages, there may be considerable

elevation of the LA, pulmonary artery (PA) wedge, PA, and right ventricular (RV) pressures and lowering of the forward CO at rest.

Myocardial ischemia may occur in patients with AR because myocardial oxygen requirements are elevated by LV dilation, hypertrophy, and

elevated LV systolic tension, and coronary blood flow may be compromised. A large fraction of coronary blood flow occurs during diastole,

when aortic pressure is low, thereby reducing coronary perfusion or driving pressure. This combination of increased oxygen demand and reduced

supply may cause myocardial ischemia, particularly of the subendocardium, even in the absence of epicardial coronary artery disease (CAD).

■ HISTORY

Approximately three-fourths of patients with pure or predominant valvular AR are men; women predominate among patients with primary

valvular AR who have associated rheumatic mitral valve disease. A history compatible with IE may sometimes be elicited from patients with

rheumatic or congenital involvement of the aortic valve, and the infection often precipitates or seriously aggravates preexisting symptoms.

In patients with acute severe AR, as may occur in IE, aortic dissection, or trauma, the LV cannot dilate sufficiently to maintain stroke

volume, and LV diastolic pressure rises rapidly with associated marked

elevations of LA and PA wedge pressures. Pulmonary edema and/or

cardiogenic shock may develop rapidly.

Chronic severe AR may have a long latent period, and patients may

remain relatively asymptomatic for as long as 10–15 years. Uncomfortable awareness of the heartbeat, especially on lying down, may be an

early complaint. Sinus tachycardia, during exertion or with emotion, or

premature ventricular contractions may produce particularly uncomfortable palpitations as well as head pounding. These complaints may

persist for many years before the development of exertional dyspnea,

usually the first symptom of diminished cardiac reserve. The dyspnea

is followed by orthopnea, paroxysmal nocturnal dyspnea, and excessive

TABLE 262-1 Major Causes of Aortic Regurgitation

VALVE LESION ETIOLOGIES

Aortic regurgitation Valvular

Congenital (bicuspid)

Endocarditis

Rheumatic fever

Myxomatous (prolapse)

Radiation

Trauma

Syphilis

Ankylosing spondylitis

Aortic root disease

Aortic dissection

Medial degeneration

Marfan syndrome

Bicuspid aortic valve

Nonsyndromic familial aneurysm

Aortitis

Hypertension

fenestrations of the aortic valve occasionally produce mild AR. Membranous subaortic stenosis results in a high velocity systolic jet that

often leads to thickening and scarring of the aortic valve leaflets and

secondary AR. Prolapse of an aortic cusp, resulting in progressive

chronic AR, occurs in ~15% of patients with ventricular septal defect

(Chap. 269), but may also occur as an isolated phenomenon or as a

consequence of myxomatous degeneration sometimes associated with

mitral and/or tricuspid valve involvement.

AR may result from infective endocarditis (IE), which can develop

on a valve previously affected by rheumatic disease, a congenitally

deformed valve, or on a normal aortic valve, and may lead to perforation or erosion of one or more leaflets. The aortic valve leaflets

may become scarred and retracted during the course of syphilis or

ankylosing spondylitis and contribute further to the AR that derives

primarily from the associated root dilation. Although traumatic rupture or avulsion of an aortic cusp is an uncommon cause of acute AR,

it represents the most frequent serious lesion in patients surviving

nonpenetrating cardiac injuries. The coexistence of hemodynamically

significant aortic stenosis (AS) with AR usually excludes all the rarer

forms of AR because it occurs almost exclusively in patients with rheumatic or congenital AR. In patients with AR due to primary valvular

disease, dilation of the aortic annulus may occur secondarily and lead

to worsening regurgitation.

Primary Aortic Root Disease AR also may be due entirely to

marked aortic annular dilation, i.e., aortic root disease, without primary involvement of the valve leaflets; widening of the aortic annulus

and lack of diastolic coaptation of the aortic leaflets are responsible

for the AR (Chap. 280). Medial degeneration of the ascending aorta,

which may or may not be associated with other manifestations of Marfan syndrome; idiopathic dilation of the aorta; annuloaortic ectasia;

osteogenesis imperfecta; and severe, chronic hypertension may all

widen the aortic annulus and lead to progressive AR. Occasionally

AR is caused by retrograde dissection of the aorta involving the aortic

annulus. Syphilis and ankylosing spondylitis, both of which may also

affect the aortic leaflets, may be associated with cellular infiltration and

scarring of the media of the thoracic aorta, leading to aortic dilation,

aneurysm formation, and severe regurgitation. In syphilis of the aorta

(Chap. 182), now a very rare condition, the involvement of the intima

may narrow the coronary ostia, which in turn may be responsible for

myocardial ischemia. Takayasu’s aortitis and giant cell aortitis can also

result in aneurysm formation and secondary AR.

■ PATHOPHYSIOLOGY

The total stroke volume ejected by the left ventricle (LV) (i.e., the sum

of the effective forward stroke volume and the volume of blood that