Aortic Regurgitation

Background: Primary disease of the aortic valve leaflets, the wall of the aortic root, or
both may cause aortic regurgitation (AR). With the decline in the incidence of syphilitic
aortitis and rheumatic valvulitis in the second half of the 20th century, various aortic root
disorders such as Marfan disease and degeneration of bicuspid aortic valves have
become the most common causes of AR.

Pathophysiology: Chronic AR produces left ventricular (LV) volume overload that

leads to a series of compensatory changes, including LV enlargement and eccentric
hypertrophy. The enlarged ventricle is more compliant and is well suited to deliver a
large stroke volume. This occurs through rearrangement of myocardial fibers with the
addition of new sarcomeres in series, causing the individual myocardial fibers to
become longer. The dilated left ventricle can accommodate increased end-diastolic
volume and deliver a larger stroke volume to compensate for the regurgitant aortic flow.

Wall thickness must increase to compensate for the increased ventricular dimensions.
These compensatory changes are necessary to minimize or normalize wall stress
according to the Laplace law (ie, wall tension/stress is related to the product of
intraventricular pressure and radius divided by wall thickness). Increased wall thickness
results from increased fiber diameter achieved by an increased number of sarcomeres
in parallel. This type of hypertrophy observed in a volume-overload state usually is
eccentric, as opposed to concentric hypertrophy observed in a pressure-overload state
(ie, aortic stenosis). The increased myocardial mass in a hypertrophic heart enables
individual sarcomeres to shorten to a normal degree.

As long as LV wall stress is maintained in the normal range, the LV preload reserve,
contractility, and ejection fraction (EF) remain within the normal range. This is the
chronic compensated stage. During this phase of the disease, most patients remain
asymptomatic for decades because chronic AR generally is a slow and insidious
disease with very low morbidity during a long asymptomatic phase.

With time, transition from a compensated to a decompensated state marks the

progression of the disease. Progressive LV enlargement beyond that required by the
valvular regurgitation occurs and is associated with a change of the left ventricle from
an elliptical shape to a spherical shape.

The cause of this pathologic dilatation is not well understood, but loss of the collagen
support system that acts as a skeleton for the heart may play a substantial role. These
maladaptive changes in the interstitium of the heart are an intricate part of the LV
hypertrophy process. In addition, diminished coronary flow reserve in this hypertrophied
ventricle is thought to result in chronic subendocardial ischemia, even in the absence of
epicardial coronary artery disease (CAD). Eventually, subendocardial necrosis and
fibrosis occur, along with disruption of the collagen support system, with loss of LV
systolic function. The neurohormonal response complicates the disease state further by
its excessive growth stimuli, which are thought to be partially responsible for apoptosis
(programmed cell death) of the remaining functional myocytes.

The vicious cycle continues until the decompensated stage develops over many years.
Progressive LV enlargement, spherical LV shape, increased wall stress, decline in the
contractility and EF, increased afterload, and decreased diastolic compliance with a rise
in end-diastolic pressure characterize this stage. Frequently, development of congestive
symptoms heralds this stage, but an insidious deterioration of ventricular function may
occur without overt clinical signs.

In acute AR, the normal-sized left ventricle poorly tolerates the sudden large volume
imposed on it. The left ventricle poorly accommodates the abrupt increase in end-
diastolic volume, and diastolic filling pressure increases rapidly and dramatically. This
leads to an acute decrease in forward stroke volume, and, although tachycardia
develops as a compensatory mechanism to maintain cardiac output, this often is
insufficient. The rise in LV filling pressure is transmitted to the left atrium, pulmonary
veins, and pulmonary capillaries, leading to pulmonary edema and congestion. Acute
AR usually is severe and rapidly leads to LV decompensation and/or failure and
cardiogenic shock.

Frequency:

• In the US: With the advent of Doppler echocardiogram studies, many cases of
mild AR have been identified in the general population. In some studies, up to
8.5% of women and 13% of men were found to have some degree of AR. In
surgical literature, up to 20% of all aortic valve surgeries are performed because
of pure AR; however, aortic stenosis remains the most frequent indication for
aortic valve replacement (AVR). Multiple logistic regression analysis revealed
age and male gender to be predictors of AR.

Mortality/Morbidity: A long asymptomatic period with a relatively rapid downhill course

after the onset of cardiac symptoms characterizes the natural history of chronic AR.
Data from several studies concerning the natural history of chronic severe AR with
normal LV function found the rate of progression to symptoms and/or LV dysfunction
(LV ejection fraction [LVEF] <0.50) to be approximately 4.5% per year. The incidence
rate of sudden cardiac death was very low, at less than 0.2% per year. Sudden cardiac
death has generally not been considered an important risk for patients with AR who are
asymptomatic and have normal LV function at rest. AVR can be postponed safely until
the appearance of cardiac symptoms and/or LV dysfunction (LVEF <0.50) at rest. The
prognosis of severe AR in asymptomatic patients with normal LV function remains
excellent, but extra vigilance is required in monitoring these patients to ensure that the
optimal time for surgical intervention is not overlooked. The risks associated with
chronic severe AR are as
follows:

• In asymptomatic patients with normal LV systolic function, the rate of progression

to symptoms and/or LV dysfunction is less than 5% per year, the rate of
progression to asymptomatic LV dysfunction is less than 2% per year, and the
rate of sudden death is less than 0.2% per year.

• For asymptomatic patients with LV systolic dysfunction, the rate of progression to

cardiac symptoms is higher than 25% per year. In symptomatic patients, the
mortality rate associated with angina is higher than 10% per year and, with
congestive heart failure (CHF), is higher than 20% per year.

• The rates of death, symptoms, or LV dysfunction in patients with LV end-systolic

dimension (LVESD) greater than 55 mm is 19% per year, in patients with an
LVESD of 40-49 mm is 6% per year, and in patients with LVESD less than 40
mm is 0% per year.
 • Because angina and dyspnea have long been considered an indication for
surgery in this patient population, no large-scale recent studies exist of the
natural history of symptomatic AR. These patients remain at high risk and
mortality rates are estimated between 10% and 20%. For these reasons, the
Guidelines for the Management of Patients with Valvular Heart Disease
presented by the American College of Cardiology (ACC) and American Heart
Association (AHA) recommend AVR for patients with class II-IV symptoms of
angina or dyspnea and chronic severe AR.

Race: Incidence of AR is similar across various racial populations.

Sex: AR affects males and females equally.

Age: Significant AR can be found in patients of any age; however, the age at which AR
becomes clinically significant varies based on etiology. Patients with Marfan disease
and those with bicuspid aortic valve problems tend to present earlier in life and
generally are free of disability from LV dysfunction at the time of presentation. If left
untreated, significant cardiac symptoms commonly appear in the fifth decade of life and
beyond, usually after considerable cardiomegaly and myocardial dysfunction have
occurred.

History: The natural history of AR is a slow and insidious disease process, with many
patients remaining asymptomatic for decades. In asymptomatic patients, a cardiac
murmur found during a routine medical examination often leads to diagnosis; however,
once cardiac symptoms develop, clinical deterioration is rapid.

• The principal symptoms associated with severe AR are exertional dyspnea,

orthopnea, and paroxysmal nocturnal dyspnea. These symptoms appear when
pulmonary venous pressure is elevated in association with significant
cardiomegaly and myocardial dysfunction. These changes occur late in the
natural history of the disease.

• Angina pectoris may occur without CAD because coronary perfusion is

inadequate to meet the demands of the enlarged and hypertrophic left ventricle.
Less commonly, aortitis can involve the origin of the coronary arteries, leading to
angina.

• Palpitation is a common complaint associated with a hyperdynamic and

tachycardic left ventricle in significant AR. Palpitation also may be due to
frequent premature ventricular contraction.

• Syncope is an uncommon symptom associated with AR.

• Sudden cardiac deaths have been relatively rare in asymptomatic patients with
normal LV function (<0.2% per y).

• In contrast to chronic AR, symptoms of acute AR (commonly from infective

endocarditis, aortic dissection, or trauma) develop rapidly and are very poorly
tolerated. In acute AR, the normal-sized ventricle is unable to adapt to the
sudden increase in regurgitant volume, in addition to the normal left atrial inflow.
 Thus, patients develop pulmonary congestion associated with LV failure and,
possibly, cardiogenic shock.

Physical:

• Hemodynamically severe AR causes a widened pulse pressure, often greater

than 100 mm Hg, associated with a low diastolic pressure, often less than 60 mm
Hg.

• The de Musset sign is when patients' heads frequently bob with each heartbeat.

• The Corrigan pulse is when patients' pulses are of the water-hammer or

collapsing type, with abrupt distention and quick collapse.

• The Quincke sign is when light transmitted through the patient's fingertip shows
capillary pulsations.

• The Hill sign is when popliteal cuff systolic pressure exceeds brachial cuff
pressure by more than 60 mm Hg.

• The Duroziez sign is when a systolic murmur is heard over the femoral artery
when compressed proximally and when a diastolic murmur is heard when the
femoral artery is compressed distally.

• The Mьller sign is systolic pulsations of the uvula.

• The Traube sign (also called pistol-shot sounds) refers to booming systolic and
diastolic sounds heard over the femoral artery.

• The apical impulse in chronic AR is diffuse, hyperdynamic, and displaced

inferiorly and leftward.

• S3 gallop correlates with development of LV dysfunction.

• The typical diastolic murmur of AR has a decrescendo shape. A high-frequency

early diastolic murmur often occurs in mild AR, whereas a rough holodiastolic or
decrescendo diastolic murmur occurs more commonly in severe AR. The volume
and velocity of blood across the incompetent aortic valve tapers off in mid-to-last
diastole as the aortic and LV pressures equilibrate. The diastolic murmur of AR is
usually best heard adjacent to the sternum in the second to fourth left intercostal
space. A concomitant systolic ejection murmur is common in moderate-to-severe
AR

• The murmur associated with acute AR may not be impressive. If cardiac

decompensation is present, the diastolic murmur of acute AR may be very soft
and surprisingly short.

• Antegrade flow across the mitral valve is thought to cause an Austin Flint
murmur, which is a mid- and late-diastolic apical low-frequency murmur or
rumble. The rumble occurs during rapid closure of the mitral valve as flow
velocity is increasing across the valve and LV diastolic pressure is rising rapidly
because of severe aortic reflux. Its presence indicates severe AR.
Causes:

• Acute aortic regurgitation

o Infective endocarditis may lead to destruction or perforation of the aortic

valve leaflet. The vegetation can also interfere with proper coaptation of
the valve leaflets and can sometimes lead to frank prolapse or flail of a
leaflet.

o In acute ascending aortic dissection (type A), the retrograde proximal

dissection flap undermines the commissural suspensions of the aortic
valve leaflets. Varying levels of aortic malcoaptation and prolapse occur.

o Prosthetic valve malfunction can lead to AR.

o Chest trauma may lead to a tear in the ascending aorta and disruption of
the aortic valve support apparatus.

• Chronic aortic regurgitation

o While a congenital bicuspid aortic valve often leads to progressive aortic

stenosis, incomplete closure or prolapse can also lead to significant
regurgitant flow across the valve. This common congenial lesion remains
the most common cause of isolated AR requiring aortic valve surgery.
Histologic abnormalities of the bicuspid root frequently lead to proximal
aortic dilatation and further exacerbation of AR.

o Connective tissue disorders syndrome, including Marfan syndrome,

Ehlers-Danlos syndrome, floppy aortic valve, aortic valve prolapse, sinus
of Valsalva aneurysm, and aortic annular fistula can all lead to significant
chronic AR. The use of diet drugs such as fenfluramine and
dexfenfluramine (commonly referred to as Phen-Fen) may lead to chronic
AR, although these data remain controversial at this time.

o Representative of connective tissue disorders, Marfan syndrome is a

common cause of severe AR that requires intervention. This disorder is
associated with dilated sinuses of Valsalva, progressing to aortic dilatation
and AR. These patients are also at very high risk for aortic dissection,
depending on the size of the ascending aorta.

o Rheumatic fever was a common cause of AR in the first half of the 20th
century. The cusps become thickened with fibrous tissues and retract,
which causes central valvular regurgitation. Most commonly, some fusion
of the cusps occurs, resulting in some degree of aortic stenosis and
regurgitation. Associated rheumatic mitral valve disease is also very
common.

o Syphilitic aortitis leads to dilatation of the ascending aorta. The aortic

annulus becomes dilated, and coaptation of the cusps is lost.

o Takayasu arteritis involves the aorta and its major branches. AR may
complicate type I and type III of this disease.
 o Ankylosing spondylitis leads to shortening and thickening of the aortic
valve cusps and dilatation of the aortic root.

o Reiter syndrome presents similarly to ankylosing spondylitis. Dilatation of

the aortic root and associated AR occurs. Reiter syndrome may involve
the coronary ostium rarely, producing angina.

o Rheumatoid arthritis can produce granulomata involving the valve leaflets

and rings. The central portion of the leaflets is usually involved, with
sparing of the peripheral portions.

o Systemic lupus erythematosus (SLE) is associated with Libman-Sacks

endocarditis, and these verrucous vegetations can produce mitral and
aortic regurgitation. Distinct from endocarditis, SLE can produce valvulitis,
leading to thickened, calcific, and dysfunctional valves.

o Behзet disease is a diffuse aortitis, often leading to proximal aortic

dilatation and severe AR.

Lab Studies:

• No specific laboratory blood tests are required in the workup of AR. However,
serologic testing may be required when attempting to distinguish the various
etiologies of AR.

Imaging Studies:

• Two-dimensional echocardiography and Doppler

o M-mode features of AR include the following:

 Diastolic flutter of the mitral valve (can be both anterior and
posterior mitral valve leaflet)
 Diastolic flutter of the aortic valve
 Premature closure of the mitral valve (severe AR)
 Premature opening of the aortic valve (severe elevated LV end-
diastolic pressure)
 Diastolic LV septal fluttering
 LV volume overload (hyperkinesis of the LV walls with LV dilatation)
 LVESD (>55 mm indicates poorer surgical outcome)

o On 2-dimensional echocardiography, look for the following features:

 Flail aortic valve
 Dilatation of the sinuses of Valsalva (particularly in patients with
Marfan syndrome or bicuspid aortic valve problems)
 Ascending aortic aneurysm
 Incomplete closure of the aortic valve cusps on the parasternal
short-axis view of the aortic valve
 High-frequency diastolic fluttering of the anterior leaflet of the mitral
valve during diastole
 Reverse doming of the anterior mitral valve leaflet
 LV volume overload pattern
  Measurements of LV end-diastolic and end-systolic dimensions and
volumes, shortening fractions, and EFs - Critical in determining the
optimal time for valve replacement
 Measurement of aortic regurgitant fraction, regurgitant orifice size,
and regurgitant volumes - Now available with Doppler
echocardiography

o Color-flow Doppler should be used as follows:

 Determine the regurgitant jet height and/or LV outflow tract (LVOT)
height in the parasternal long-axis view (mild [1+] <25%, moderate
[2+] 25-46%, moderately severe [3+] 47-64%, severe [4+] >65%).
 Determine the regurgitant jet area and/or LVOT area in the
parasternal short-axis view of the aortic valve (mild [1+] <20%,
moderate [2+] 20-40%, moderately severe [3+] 40-60%, severe [4+]
>60%).
 Proximal acceleration (flow convergence) indicates aortic
insufficiency is grade 3+ or 4+.

o Continuous-wave Doppler should be used as follows:

 Determine the spectral strength of the regurgitant jet. Grade 1+
produces spectral tracing stain sufficient for detection but is not
enough for clear delineation. In grade 2+, complete spectral tracing
can barely be seen. In grade 3+, distinct darkening of spectral
tracing is visible, but density is less than antegrade flow. Grade 4+
produces dark-stained spectral tracing.
 Determine the slope of the aortic insufficiency spectral display. In
general, steeper slopes indicate more severe aortic insufficiency.
 Determine the pressure half-time of the aortic insufficiency spectral
display. In general, a pressure half-time less than or equal to 300
m/s indicates significant aortic insufficiency.

o Pulsed-wave Doppler should be used as follows:

 The pulse-wave mapping technique is used mostly prior to color
Doppler.
 Velocity of more than 1.5 m/s is consistent with marked AR.
 Mitral inflow has a restrictive filling pattern.
 Reversal of flow in the descending thoracic aorta and/or abdominal
aorta indicates that aortic insufficiency is moderately severe (3+ or
4+). This phenomenon requires careful placement of the sample
volume in the descending aorta, distal to the takeoff of the left
subclavian artery. The flow in the descending aorta may also be
seen with color-flow Doppler, although this method is more prone to
error.

• Radionuclide imaging should be used as follows:

o Radionuclide angiography findings can help determine the AR regurgitant

fraction and the left-to-right ventricular stroke volume ratio. An accurate
noninvasive assessment of the severity of AR can be determined if
concomitant mitral regurgitation, tricuspid regurgitation, or pulmonary
regurgitation is not present.
 o Left-to-right ventricular stroke volume ratio of 2 or more denotes severe
AR.

• MRI or ultrafast CT scanning are as follows:

o These techniques can provide accurate measurements of regurgitant

volumes, ventricular end-systolic and diastolic volumes, ejection fraction,
ventricular mass, and the regurgitant orifice.

o These techniques are not as well validated as echocardiography and may

not be as widely available.

• Chest radiograph findings are as follows:

o In acute AR, little cardiac enlargement may be present, but, in chronic AR,
enlargement is marked.

o Dilatation of the ascending aorta may suggest that aortic root disease is
responsible for AR.

o Pulmonary congestion can be observed in patients who have developed

LV dysfunction or in those with acute AR.

Other Tests:

• Electrocardiography findings can reveal the following, although they are not an
accurate predictor of the severity of AR:

o LV hypertrophy

o Left axis deviation

o Left atrial enlargement

o LV volume overload pattern (prominent Q waves in leads I, aVL, and V3 to

V6 and relatively small r waves in V1)

o LV conduction defect (late in disease process)

• Exercise treadmill testing

o Assessment of functional capacity and symptomatic responses in patients

with a history of equivocal symptoms

o Evaluation of symptoms and functional capacity before participation in

athletic activities

Procedures:

• Cardiac catheterization

o Indications
  This should be performed for coronary angiography studies before
AVR in patients at risk for CAD, including men older than 35 years,
premenopausal women older than 35 years with coronary risk
factors, and postmenopausal women.
 It can be used to assess the severity of regurgitation when
noninvasive test results are inconclusive or discordant with clinical
findings regarding the severity of regurgitation or the need for
surgery.
 Use cardiac catheterization to assess LV function when
noninvasive test results are inconclusive or discordant with clinical
findings regarding LV dysfunction and the need for surgery in
patients with severe AR.

o Qualitative assessment (aortic angiogram)

 In mild AR (1+), a small amount of contrast enters the left ventricle
during diastole and clears with each systole.
 In moderate AR (2+), more contrast enters with each diastole, and
faint opacification of the entire LV chamber occurs.
 In moderately severe AR (3+), the LV chamber is well opacified and
equal in density when compared with the ascending aorta.
 In severe AR (4+), complete dense opacification of the LV chamber
occurs on the first beat and the left ventricle is more densely
opacified than the ascending aorta.

o Simultaneous aortic and LV pressure tracing (signs of severe AR)

 Wide pulse pressure may be present.
 Brisk aortic pressure upstroke can be observed.
 LV diastolic pressure increases rapidly.
 Near equilibration of aortic and LV pressure occurs at diastole.

Histologic Findings: Histological changes in the left ventricle include fiber hypertrophy
and increased interstitial fibrous tissue. In decompensated LV, disruption of the collagen
support system and subsequent fiber layer slippage occur. In the subendocardium,
evidence of necrosis, replacement fibrosis, and apoptosis is abundant.

Recent data suggest that patients with a wide variety of congenital heart lesions
(including bicuspid aortic valves) have underlying distortion of the aortic root. These
patients were found to have abnormalities of smooth muscle, elastin, collagen, and
ground substance in the ascending aorta over a wide variety of ages. Programmed cell
death (apoptosis) of neural crest derivative cells within the proximal aorta has also been
demonstrated in patients with bicuspid aortic valve problems.

These aortic abnormalities predispose to progressive proximal aortic dilatation,

aneurysm formation, or aortic rupture. These proximal aortic changes occur regardless
of the underlying severity of aortic valvular disease and can be observed in patients with
nonregurgitant bicuspid valves.

Medical Care:
Medical vs Surgical Treatment: Medical therapy is appropriate for many patients with
mild to moderate chronic AR. The appropriate use of vasodilators, as described below,
is associated with improvement in symptoms and is thought to slow the development of
LV enlargement and dysfunction and the need for surgery. That said, physicians
treating patients with chronic AR must be attentive to any changes that suggest
worsening LV function and the need for surgery. Subjective reporting of exercise
tolerance by patients is often unreliable. In patients with borderline AR, formal exercise
testing on an annual basis may be useful. Annual echocardiography to assess LV size
and function is also useful. As with mitral valve regurgitation, patients should be referred
for surgical evaluation before irreversible LF dysfunction has occurred.

Patients with acute, significant AR represent an entirely different group. Surgical

treatment is almost always indicated and medical therapy (typically using intravenous
medications titrated to blood pressure, as described below) is recommended only as an
interim measure.

Medical Care: Vasodilator therapy is designed to optimize LV loading conditions and

achieve a favorable remodeling process through systolic unloading and reduction in
regurgitant volume. Treat asymptomatic patients with chronic severe AR and dilated but
normal LV systolic function medically, and monitor their cases for development of
indications for AVR. Patients with mild AR and normal LV size require no therapy other
than endocarditis prophylaxis.

• Earlier studies revealed that long-term vasodilator therapy with nifedipine

reduces or delays the need for AVR in asymptomatic patients with severe AR
and normal LV function. Nifedipine was also shown to reduce LV size and mass
significantly. However, use of nifedipine in patients with LV dysfunction should be
cautioned because calcium channel blockers generally are contraindicated in
patients with CHF.

• Enalapril therapy achieves significant LV mass regression, LV end-diastolic and

end-systolic volume index reduction, and renin-angiotensin system suppression.
Enalapril may have favorable influence on the natural history of chronic AR by
delaying the need for AVR.
• Digoxin and diuretics can be used to relieve symptoms of congestion.
• Recent publications have yielded conflicting results on the use of vasodilators in
this group. One recent follow-up study confirmed the positive effects of using
nifedipine in severe asymptomatic AR. This study showed that nifedipine delayed
the onset of LV dysfunction and prolonged survival and protected the
myocardium after AVR, even if stopped at surgery. Patients in this study had
moderate to severe hypertension at entry into the study. A separate study
comparing the use of nifedipine, enalapril, and placebo was unable to show a
benefit to vasodilator therapy in a cohort of normotensive patients. In this study,
vasodilator therapy with nifedipine or enalapril did not delay the need for AVR or
improve parameters such as regurgitant volume, LV size, or LV systolic function.
• The main goal of medical therapy is to significantly reduce the systolic
hypertension associated with chronic severe AR.

• Antibiotic prophylaxis for endocarditis is discussed as follows:

o AR leads to damaged endothelial lining of the valve and predisposes the

valve to platelet and fibrin deposition.
o In the presence of bacteremia, colonization of platelets and/or fibrin
deposition can lead to bacterial endocarditis; thus, antibiotic prophylaxis is
important for preventing this serious complication.
 • Acute AR usually is severe and rapidly leads to LV decompensation, failure, and
cardiogenic shock. The treatment of choice for acute AR is AVR. Medical therapy
can be used as a bridge to surgery but should not replace it.

o Dobutamine reduces afterload and assists with forward outflow. It also has
a positive inotropic effect.
o Vasodilators achieve significant LV mass regression, LV end-diastolic and
end-systolic volume index reduction, and renin-angiotensin system
suppression.
o Intra-aortic balloon pump is contraindicated in AR.

• Percutaneous transcatheter implantation of a heart valve prosthesis may be

available in the future, but these techniques are investigational at this time.

Surgical Care: Surgical treatment of AR almost always requires replacement of the

diseased valve with a prosthetic valve. The surgical mortality rate for AVR probably is
3%, although the mortality rate may be higher if patients also need coronary artery
bypass grafts. In addition, the long-term complications of prosthetic valves need to be
considered.

• AVR is indicated in patients with normal systolic function (defined as EF >0.50 at

rest) who have New York Heart Association (NYHA) functional class III or IV
symptoms. Also consider patients with Canadian Heart Association functional
class II-IV angina pectoris for surgery. In many patients with NYHA functional
class II dyspnea, the etiology of symptoms often is unclear and clinical judgment
is required.

• Patients with NYHA functional class II, III, or IV symptoms and with mild-to-
moderate LV systolic dysfunction (EF 0.25-0.49) should undergo AVR. Patients
with functional class IV symptoms have worse postoperative survival rates and a
lower likelihood of recovery of systolic function when compared to patients with
less severe symptoms, but AVR improves ventricular loading conditions and
expedites subsequent management of LV dysfunction.

• Symptomatic patients with severe LV dysfunction (EF <0.25) pose difficult

management issues. Most patients develop irreversible myocardial damage and
may not show improved LV function or NYHA functional class after AVR;
however, some patients may gain meaningful recovery of LV function. Surgery
carries an operative mortality rate of approximately 10%, but medical therapy
alone carries a mortality rate of higher than 20% per year; thus, high-risk AVR
may be a viable option when compared to the even worse prognosis associated
with medical therapy alone.

• Asymptomatic patients with evidence of LV systolic dysfunction (EF <0.50)

should undergo AVR. The postoperative recovery of LV function and survival is
strongly associated with preoperative LV function; thus, do not delay AVR for
patients with evidence of LV dysfunction.

• Asymptomatic patients with severe AR and normal LV function but with severe
LV dilatation (end-diastolic dimension >75 mm or end-systolic dimension >55
mm) should undergo AVR. These patients tend to progress to symptomatic or LV
 dysfunction rapidly. Postoperative survival and reduction of LV dimension in this
subgroup of patients are excellent.

• Preoperative predictors of poor postoperative survival and LV function include

the following:

o LVESD greater than 55 mm

o LVEF less than 0.50

o NYHA CHF class III, IV

o Duration of CHF symptoms longer than 12 months

Consultations:

• Cardiologist

• Cardiothoracic surgeon

Diet: Place patients on a low-sodium diet with fluid restriction when CHF symptoms
appear.

Activity: Asymptomatic patients with normal LV systolic function may participate in all
forms of normal daily physical activity, including mild forms of exercise and, in some
cases, competitive athletics; however, isometric exercise (eg, weight lifting) should be
avoided. Patients with evidence of LV dysfunction or low cardiac reserve should not
engage in vigorous sports or heavy exertion.

Vasodilator therapy has reduced severity of AR and LV volume and mass successfully,
postponing the need for surgical intervention.

Drug Category: Angiotensin-converting enzyme inhibitors -- Competitive

inhibitors of angiotensin-converting enzyme (ACE). Reduce angiotensin II levels,
decreasing aldosterone secretion.

Enalapril (Vasotec) -- ACE-I produces a small

increase in EF and significant decrease in LV
Drug Name volume and mass. Effective vasodilator
therapy requires adjustment of dosage to
achieve a decrease in arterial pressure.
5 mg PO bid for 2 wk initially; if
hemodynamically stable, increase to 10 mg
Adult Dose
PO bid for 2 wk, then to 20 mg PO bid
maintenance
Pediatric Dose Not established
Contraindications Documented hypersensitivity; second or third
trimester pregnancy, breastfeeding, history of
angioneurotic edema, significant renal artery
 stenosis
NSAIDs may reduce hypotensive effects; ACE
inhibitors may increase digoxin, lithium, and
allopurinol levels; rifampin decreases levels;
Interactions
probenecid may increase levels; hypotensive
effects of ACE inhibitors may be enhanced
when administered concurrently with diuretics
C - Safety for use during pregnancy has not
Pregnancy
been established.
Pregnancy category D in second and third
trimester of pregnancy; caution in renal
impairment, valvular stenosis, severe CHF, or
Precautions
angioedema; oliguria, seizures, and
unpredictable effects on BP may occur in
children

Drug Category: Calcium channel blockers -- Inhibit movement of calcium ions

across the cell membrane, depressing both impulse formation (automaticity) and
conduction velocity.

Nifedipine (Procardia) -- Produces significant

fall in arterial pressure, reduces LV volume
and mass, increases EF, and delays need for
Drug Name AVR in asymptomatic patients with severe AR
and normal LV systolic function. Effective
vasodilator therapy requires adjustment of
dosage to decrease arterial pressure.
10 mg PO bid initially, then titrate to 20 mg PO
Adult Dose
bid
Pediatric Dose Not established
Documented hypersensitivity; CHF,
Contraindications
cardiogenic shock, acute MI
Alcohol, cimetidine, and ranitidine increase
bioavailability and effect; antihypertensive
medications produce an additive effect; may
Interactions
decrease quinidine levels; may increase
digoxin levels; rifampin, phenobarbital, and
phenytoin decrease effects
C - Safety for use during pregnancy has not
Pregnancy
been established.
Renal or hepatic dysfunction; breastfeeding;
Precautions may cause lower extremity edema; allergic
hepatitis is rare

Drug Category: Cardiac glycosides -- Inhibit sodium-potassium ATPase. Inhibition

of the enzyme leads to an increase in the intracellular concentration of sodium and
calcium. Vagomimetic action leads to reduced activity of sympathetic nervous system.
 Digoxin (Lanoxin) -- Pharmacologic
consequences include an increase in the force
and velocity of myocardial systolic contraction
(positive inotropic action) and slowing of the
heart rate and decreased conduction velocity
Drug Name
through the AV node (vagomimetic effect).
Use in patients with heart failure is associated
with 25% reduction in the frequency of
hospitalization for heart failure. Use is not
associated with mortality benefit.
<70 years and good renal function: 0.25 mg
PO qd general initial dose
>70 years or impaired renal function: 0.125 mg
PO qd general initial dose
Marked renal impairment: 0.0625 mg general
Adult Dose initial dose
0.4-0.6 mg if rapid digitalization with IV loading
is needed; produces detectable effect in 5-30
min; 0.1- to 0.3-mg additional doses may be
administered cautiously at 6- to 8-h intervals
until clinical evidence of an adequate effect
Pediatric Dose Adjust loading and daily maintenance dose by
body weight
Digitalization in infants and children not
generally recommended; suggested doses are
as follows:
TDD
Premature infants: 0.02-0.03 mg/kg if tab;
0.015-0.025 mg/kg if cap, IV, or IM in divided
doses
Full-term infants: 0.025-0.035 mg/kg if tab;
0.02-0.03 if cap, IV, or IM in divided doses
1-24 months: 0.035-0.06 mg/kg if tab; 0.03-
0.05 mg/kg if cap, IV, or IM in divided doses
2-5 years: 0.03-0.04 mg/kg if tab; 0.025-0.035
mg/kg if cap, IV, or IM in divided doses
5-10 years: 0.02-0.035 mg/kg if tab; 0.015-
0.030 mg/kg if cap, IV, or IM in divided doses
>10 years: 0.01-0.015 mg/kg if tab; 0.008-
0.012 if cap, IV, or IM in divided doses
May accomplish digitalization by giving half
TDD in first dose followed by 2 doses that are
one fourth TDD given at 8- to 12-h intervals
Maintenance dose
Premature infants: 0.005-0.0075 mg/kg if tab;
0.004-0.006 mg/kg if cap, IV, or IM divided
q12h
Full-term infants: 0.006-0.01 mg/kg if tab;
0.005-0.008 if cap, IV, or IM divided q12h
1-24 months: 0.010-0.015 mg/kg if tab;
0.0075-0.012 mg/kg if cap, IV, or IM divided
 q12h
2-5 years: 0.0075-0.01 mg/kg if tab; 0.006-
0.009 mg/kg if cap, IV, or IM divided q12h
5-10 years: 0.005-0.01 mg/kg if tab; 0.004-
0.008 mg/kg if cap, IV, or IM divided q12h
>10 years: 0.0025-0.005 mg/kg if tab; 0.002-
0.003 if cap, IV, or IM qd or divided q12h
See prescribing information in PDR for more
detailed information
Documented hypersensitivity (hypersensitivity
reaction to other digitalis preparations usually
Contraindications
constitutes a contraindication to digoxin),
ventricular fibrillation
Potassium-depleting diuretics are a major
contributing factor to digitalis toxicity;
quinidine, verapamil, amiodarone,
propafenone, indomethacin, itraconazole,
Interactions
alprazolam, and spironolactone raise serum
digoxin concentrations because of a reduction
in clearance and/or in volume of distribution of
drug, digitalis intoxication may result
C - Safety for use during pregnancy has not
Pregnancy
been established.
Because digoxin slows sinoatrial and AV
conduction, drug commonly prolongs PR
interval; may cause severe sinus bradycardia
or sinoatrial block in preexisting sinus node
disease, and may cause advanced or
complete heart block in preexisting incomplete
AV block; patients with paroxysmal atrial
fibrillation or flutter and a coexisting accessory
Precautions
AV pathway have developed increased
antegrade conduction across the accessory
pathway bypassing the AV node, leading to a
very rapid ventricular response or ventricular
fibrillation after use; unless conduction down
the accessory pathway has been blocked
(either pharmacologically or by surgery), do
not prescribe digoxin to such patients

Drug Category: Diuretics -- Increase urine flow. These agents are ion transport
inhibitors that decrease the reabsorption of sodium at different sites in the nephron.
Diuretics have major clinical uses in managing disorders involving abnormal fluid
retention (edema) or in treating hypertension, in which their diuretic action causes
decreased blood volume.

Drug Name Furosemide (Lasix) -- Like torsemide and

bumetanide, is a potent loop diuretic.
Compared to all other classes of diuretics,
these drugs have the highest efficacy in
 mobilizing sodium and chloride from the body.
Loop diuretics inhibit the Na+, K+, and Cl-
cotransport in the ascending limb of the loop of
Henle. Furosemide and other loop diuretics
are indicated in treatment of edema
associated with CHF, cirrhosis of the liver, and
renal disease, including nephrotic syndrome.
May be used to treat hypertension alone or in
combination with other antihypertensive
agents.
Individualize according to patient response to
gain maximal therapeutic response and to
determine the minimal dose needed to
maintain that response
20-80 mg PO administered as a single dose is
Adult Dose usual initial dose; repeat or increase 6-8 h
later if needed; dose may be titrated carefully
up to 600 mg/d in patients with clinically
severe edematous states; at higher doses,
careful clinical observation and close
laboratory monitoring are particularly important
2 mg/kg PO administered as a single dose is
usual dose in infants and children; dosage
Pediatric Dose may be increased by 1-2 mg/kg no sooner
than 6-8 h after previous dose if needed; not to
exceed 6 mg/kg
Contraindications Documented hypersensitivity; anuria
May increase ototoxic potential of
Interactions aminoglycoside antibiotics, especially in
impaired renal function
C - Safety for use during pregnancy has not
Pregnancy
been established.
Excessive diuresis may cause dehydration
and blood volume reduction with circulatory
collapse; observe all patients receiving
Precautions furosemide therapy for signs or symptoms of
fluid or electrolyte imbalance; asymptomatic
hyperuricemia can occur, and gout may be
precipitated

Drug Category: Direct-acting adrenergic agonists -- Act directly on alpha- and

beta-receptors, producing effects similar to those that occur following stimulation of
sympathetic nerves or release of the hormone epinephrine from the adrenal medulla.

Drug Name Dobutamine (Dobutrex) -- Synthetic direct-

acting catecholamine and beta-receptor
agonist. Increases cardiac contractility and
output in CHF. At therapeutic dose, mainly an
inotropic agent, while producing comparatively
 mild chronotropic and vasodilative effects. As
compared to other sympathomimetic drugs,
does not significantly increase myocardial
oxygen demands, which is its major advantage
compared to other direct-acting
catecholamines.
Start at low rate (1 mcg/kg/min IV infusion)
titrated at intervals of few minutes guided by
the patient's response, including systemic
blood pressure, urine flow, frequency of
ectopic activity, heart rate, and, if possible,
Adult Dose
measurement of cardiac output, central
venous pressure, and/or pulmonary capillary
wedge pressure
2-20 mcg/kg/min IV usual range, but clinical
response dictates optimal infusion rate
Pediatric Dose Not established
Documented hypersensitivity, idiopathic
Contraindications
hypertrophic subaortic stenosis
Animal studies indicate that may be ineffective
if patient recently received a beta-blocking
Interactions
drug; in this case, peripheral vascular
resistance may increase
B - Usually safe but benefits must outweigh
Pregnancy
the risks.
During administration, monitor ECG and blood
pressure continuously; monitor pulmonary
Precautions wedge pressure and cardiac output whenever
possible to aid in safety and efficacy of
infusion

Further Inpatient Care:

• Admit for testing and surgical intervention.

Further Outpatient Care:

• Close monitoring for symptom development is warranted.

• Serial echocardiograms should be performed to evaluate LV function, LV

dimensions (end-systolic and end-diastolic), and the severity of AR.

• Serial multigated angiogram scans should be performed to monitor the LVEF and
the volume of the left ventricle.

• Exercise stress testing should be performed to determine functional capacity and

symptomatic response in patients with a history of equivocal symptoms.

• Carefully monitor medication doses and adverse effects.

In/Out Patient Meds:

• Medications include calcium channel blockers and ACE inhibitors.

• Avoid calcium channel blockers in patients with CHF.

• Use digoxin and diuretics for patients with CHF.

Transfer:

• Transfer may be required for further diagnostic evaluation and surgical

intervention.

Deterrence/Prevention:

• Endocarditis prophylaxis is discussed as follows:

o AR leads to damaged endothelial lining of the valve and predisposes the

valve to platelet and fibrin deposition.

o In the presence of bacteremia, colonization of platelets and/or fibrin

deposition can lead to bacterial endocarditis; thus, antibiotic prophylaxis is
important for preventing this serious complication.

• Patients with LV dysfunction or CHF symptoms should not engage in vigorous

sports or heavy exertion.

Complications:

• Congestive heart failure

• Infective endocarditis

• Arrhythmia

• Sudden death

Prognosis:

• Asymptomatic patients with normal LV function have a mortality rate of less than
0.2% per year. The rate of progression to symptoms and/or LV dysfunction is
less than 5% per year.

• Patients with angina have a mortality rate of higher than 10% per year.

• Patients with CHF have a mortality rate of higher than 20% per year.

Patient Education:

Educate patients about symptoms associated with severe AR.

Caption: Picture 1. The light blue jet represents the aortic regurgitant flow on this 2-
dimensional color Doppler echocardiogram showing severe aortic regurgitation.