Aortic insufficiency pathophysiology


 * Associate Editor-in-Chief: Varun Kumar, M.B.B.S., Lakshmi Gopalakrishnan, M.B.B.S., Mohammed A. Sbeih, M.D. [mailto:msbeih@perfuse.org]

Overview
Aortic insufficiency is defined as retrograde (backward) flow of blood across an incompetent (leaky) aortic valve during diastole. In general, aortic insufficiency is due to abnormalities of either the aortic valve itself or the aortic root.

Pathophysiology
Normally, the aortic valve is only open when the pressure in the left ventricle exceeds the pressure in the aorta. This allows the blood to be ejected from the left ventricle into the aorta during ventricular systole. The amount of blood that is ejected by the heart is known as the stroke volume. Under normal conditions, 50–70% of the blood in a filled left ventricle is ejected into the aorta to be used by the body (called the ejection fraction). In aortic insufficiency (AI), when the pressure in the left ventricle falls below the pressure in the aorta, the aortic valve leaks, and blood flows from the aorta into the left ventricle. As a result there is volume overload of the left ventricle.

Widened Pulse Pressure
The percentage of blood that regurgitates back through the aortic valve due to AI is known as the regurgitant fraction. This regurgitant flow causes a decrease in the diastolic blood pressure in the aorta, and therefore a widening or increase in the pulse pressure (systolic pressure - diastolic pressure). As a result, the physical examination will often reveal a bounding pulse, especially in the radial artery. There is decreased effective forward flow in aortic insufficiency.

Activation of the Renin-Angiotensin-Aldosterone Axis
Note that while diastolic blood pressure is diminished and the pulse pressure widens, systolic blood pressure generally remains normal or can even be slightly elevated. This is because sympathetic nervous system and the renin-angiotensin-aldosterone axis of the kidneys compensate for the decreased cardiac output. Catecholamines will increase the heart rate and increase the strength of ventricular contraction, directly increasing cardiac output. Catecholamines will also cause peripheral vasoconstriction, which causes increased systemic vascular resistance and ensures that core organs are adequately perfused. Renin, a proteolytic enzyme, cleaves angiotensinogen to angiotensin I, which is converted to angiotensin II, which is also a potent vasoconstrictor. In chronic aortic insufficiency with resultant cardiac remodeling, heart failure may develop, and as a result, the systolic blood pressure will decline.

Volume Overload and Pressure Overload
Aortic insufficiency causes both volume overload (elevated preload) and pressure overload (elevated afterload due to the increased stroke volume) of the heart. Regurgitation of blood into the left ventricle causes volume overload and a rise in preload. The pressure overload causes left ventricular hypertrophy (LVH). There is both concentric hypertrophy and eccentric hypertrophy in AI. The concentric hypertrophy is due to the increased left ventricular systolic pressures associated with AI, while the eccentric hypertrophy is due to volume overload caused by the regurgitant fraction.

Aortic Valve vs Aortic Root Causes
In general, aortic insufficiency is due to abnormalities of either the aortic valve itself or the aortic root.

Aortic Valve Disease
A complete list of causes of aortic insufficiency can be found on the page dedicated to the the causes of aortic insufficiency.

Rheumatic Fever
One of the most common causes of aortic valvular disease in the past has been rheumatic fever in which case the aortic cusps are infiltrated with fibrous tissue. This then leads to retraction of the cusps and prevents their apposition during diastole. The cusps may also fuse and this may cause a component of aortic stenosis. It is therefore not uncommon for these patients to have mixed aortic regurgitation and aortic stenosis. Often these patients will have involvement of the mitral valve as well.

Senile or Degenerative Disease
In the modern era, a more common cause of acquired aortic valve regurgitation is degenerative disease of the aorta and aortic valve in which case there is calcification and fibrosis of the cusps. As is the case with rheumatic fever, there is similar retraction of the cusps that results in aortic insufficiency.

Infective Endocarditis
A third not uncommon cause of acquired aortic regurgitation is infective endocarditis. In this disease state, regurgitation develops as a result of a hole or perforation that develops in the leaflet, or alternatively the cusps may not oppose each other due to a vegetation lying between the cusps which prevents their apposition.

Drugs
Drugs such as dopamine agonists cause activation of serotonin -2B receptors (located in aortic valve and mitral valve) resulting in stimulation of fibroblast growth and fibrogenesis, thereby causing aortic insufficiency.

Trauma
A final not uncommon cause of acquired aortic insufficiency is following a blunt chest trauma or a deceleration injury which causes traumatic aortic valve rupture resulting in distortion of the valve architecture leading to failure of the cusps to oppose.

Congenital Causes
Congenital conditions such as congenital bicuspid aortic stenosis or a ventricular septal defect can also result in aortic insufficiency. Patients with bicuspid aortic valve are at increased risk of developing aortic dissection.

Complete List of Aortic Valvular Causes

 * Bicuspid aortic valve
 * Collagen vascular disease
 * Senile or degenerative calcific aortic valve disease
 * Endocarditis
 * Myxomatous aortic valve
 * Rheumatic fever
 * Rheumatoid arthritis
 * Sinus of Valsalva Aneurysm
 * Systemic Lupus Erythematosus
 * Trauma
 * Turner's Syndrome
 * Ventricular Septal Defect
 * Weight loss medications

Aortic Root Disease
Aortic root disease as a cause of aortic insufficiency has overtaken acquired forms of valvular disease and congenital forms of valvular disease as the leading cause of aortic regurgitation. The following is a list of those conditions that lead to dilation of the aortic root and thereby cause aortic insufficiency:
 * Bicuspid aortic valve
 * Collagen vascular disease
 * Senile or degenerative calcific aortic valve disease
 * Endocarditis
 * Myxomatous aortic valve
 * Rheumatic fever
 * Rheumatoid arthritis
 * Sinus of Valsalva Aneurysm
 * Systemic Lupus Erythematosus
 * Trauma
 * Turner's Syndrome
 * Ventricular Septal Defect
 * Weight loss medications

Acute Aortic Insufficiency

 * After aortic valvuloplasty
 * Aortic dissection
 * Bacterial Endocarditis
 * Blunt chest trauma
 * Myxomatous aortic valve
 * Rheumatic Fever

Chronic Aortic Insufficiency

 * Ankylosing Spondylitis
 * Aortic Dissection
 * Arteriosclerosis
 * Bacterial Endocarditis
 * Bechterew's Disease
 * Bicuspid aortic valve
 * Cystic medial necrosis of the aorta
 * Ehlers-Danlos Syndrome
 * Hypertension
 * Marfan Syndrome
 * Myxomatous aortic valve
 * Polymyalgia Rheumatica
 * Pseudoxanthoma Elasticum
 * Reiter's Syndrome
 * Rheumatic Fever
 * Rheumatoid Arthritis
 * Sinus of Valsalva Aneurysm
 * Syphilis
 * Systemic Lupus Erythematosus
 * Turner's Syndrome
 * Ventricular Septal Defect
 * Weight loss medications

Acute aortic insufficiency
Acute aortic insufficiency is often secondary to infective endocarditis, aortic dissection or traumatic aortic rupture.

In acute aortic insufficiency, the left ventricle becomes acutely volume overloaded by the retrograde flow of blood from the aorta. The left ventricle cannot dilate acutely to accommodate this large volume of regurgitant blood. As a result, the left ventricular end diastolic pressure rises abruptly and this rise in pressure is transmitted backward to the pulmonary circulation resulting in pulmonary edema. There is also a sudden decrease in forward cardiac output due to a reduction in stroke volume secondary to regurgitation of blood into left ventricle. The very high left ventricular end diastolic pressure causes reflex tachycardia as does the reduction in stroke volume. As a result of all of the above, hypotension and cardiogenic shock may ensue.

Initially there may be a wide pulse pressure, but as the left ventricle fails, the pulse pressure may narrow as the left ventricular end diastolic pressure rises to equal the diastolic blood pressure, and stroke volume of the left ventricle declines reducing the systolic blood pressure may. In some cases, the sharply rising left ventricular end diastolic pressure causes the mitral valve to close earlier during diastole. This early closure fortunately prevents backward flow of blood into the pulmonary vascular bed and often keeps the aortic diastolic pressure from falling too low and sometimes there may not be a wide pulse pressure.

Chronic Aortic Insufficiency
Chronic aortic insufficiency differs from acute aortic insufficiency in so far as the left ventricle has time to adapt to the chronic volume overload through a series of compensatory changes, namely dilation and eccentric hypertrophy.

Initial left Ventricular Dilation
The increasing regurgitant volume causes the stroke volume to fall. In order to compensate for a fraction of the blood going backwards, the heart compensates by ejecting a larger total volume of blood forward. The ejection fraction is preserved and perhaps even increased to compensate for the regurgitant fraction. In order to eject a larger volume of blood, the left ventricle must dilate. Via the Frank-Starling mechanism, left ventricular dilation up to a point is associated with greater contractility. The way the ventricle dilates is to lengthen the muscle fibers and the way is does this is to add sarcomeres in series. While the heart is normally shaped like a football (lime an ellipse) as it dilates, it begins to assume a more round, globular, and spherical shape. During this initial period, the left ventricle is fairly compliant. The patient is generally asymptomatic during this period.

Initial Eccentric Left Ventricular Hypertrophy
As the heart dilates, there is greater stress on the wall due to Laplace's Law. In order to compensate for the increased wall stress, eccentric hypertrophy develops.

Later Decompensated Phase of Chronic Aortic Insufficicency
While left ventricular dilation is associated with increased cardiac output according to the Frank-Starling mechanism, at a certain point of left ventricular dilation, the left ventricle begins to fail as left ventricular contractility falls. Once wall thickening fails to keep up with the hemodynamic load, end systolic wall stress rises and at this point the left ventricle fails. The dramatic enlargement of the heart that is seen with aortic insufficiency is called cor bovinum. The left ventricle also stiffens over time due to increased interstitial fibrosis.

At this point, the left ventricular ejection fraction falls. The left ventricular end systolic volume begins to rise. Next the left ventricular end diastolic volume begins to rise and this causes dyspnea or frank pulmonary edema. The first symptoms of the rise in left ventricular end diastolic pressure may be an increase in dyspnea on exertion.

Patients with chronic aortic insufficiency may also develop myocardial ischemia. This is due to the fact that they have an increase in demand due to an increased thickness of the left ventricle and also a reduction in the supply due to a lower perfusion pressure during diastole.

It has been said that 'aortic regurgitation begets aortic regurgitation'. The high oscillatory shear associated with aortic regurgitation may lead to further dilation of the aorta, which in turn may lead to further worsening of aortic regurgitation.

The mitral valve ring may also dilate leading to mitral regurgitation which further can progress to the development of left atrium dilatation. Left atrial dilation may in turn cause atrial fibrillation which further reduces left ventricular filling.