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Aortic Regurgitation Topic
Aortic Regurgitation Topic
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 enddiastolic 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.
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.
Sudden cardiac deaths have been relatively rare in asymptomatic patients with
normal LV function (<0.2% per y).
The de Musset sign is when patients' heads frequently bob with each heartbeat.
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 Traube sign (also called pistol-shot sounds) refers to booming systolic and
diastolic sounds heard over the femoral artery.
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:
Chest trauma may lead to a tear in the ascending aorta and disruption of
the aortic valve support apparatus.
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.
Takayasu arteritis involves the aorta and its major branches. AR may
complicate type I and type III of this disease.
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:
In acute AR, little cardiac enlargement may be present, but, in chronic AR,
enlargement is marked.
Dilatation of the ascending aorta may suggest that aortic root disease is
responsible for AR.
Other Tests:
Electrocardiography findings can reveal the following, although they are not an
accurate predictor of the severity of AR:
o
LV hypertrophy
Procedures:
Cardiac catheterization
o
Indications
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.
Dobutamine reduces afterload and assists with forward outflow. It also has
a positive inotropic effect.
Vasodilators achieve significant LV mass regression, LV end-diastolic and
end-systolic volume index reduction, and renin-angiotensin system
suppression.
Intra-aortic balloon pump is contraindicated in AR.
Patients with NYHA functional class II, III, or IV symptoms and with mild-tomoderate 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.
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
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.
Interactions
Pregnancy
Precautions
stenosis
NSAIDs may reduce hypotensive effects; ACE
inhibitors may increase digoxin, lithium, and
allopurinol levels; rifampin decreases levels;
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
been established.
Pregnancy category D in second and third
trimester of pregnancy; caution in renal
impairment, valvular stenosis, severe CHF, or
angioedema; oliguria, seizures, and
unpredictable effects on BP may occur in
children
Drug Name
Adult Dose
Pediatric Dose
q12h
2-5 years: 0.0075-0.01 mg/kg if tab; 0.0060.009 mg/kg if cap, IV, or IM divided q12h
5-10 years: 0.005-0.01 mg/kg if tab; 0.0040.008 mg/kg if cap, IV, or IM divided q12h
>10 years: 0.0025-0.005 mg/kg if tab; 0.0020.003 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
Serial multigated angiogram scans should be performed to monitor the LVEF and
the volume of the left ventricle.
Transfer:
Deterrence/Prevention:
Complications:
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-