Aortic regurgitation pathophysiology
Aortic Regurgitation Microchapters
Acute Aortic regurgitation
Chronic Aortic regurgitation
Aortic regurgitation pathophysiology On the Web
American Roentgen Ray Society Images of Aortic regurgitation pathophysiology
Aortic insufficiency is the backward flow of blood from the aorta into the left ventricle through the aortic valve during systole due to abnormalities in the aortic valve or the aorta. In aortic insufficiency (AI), when the pressure in the left ventricle falls below the pressure in the aorta, the aortic valve is not able to completely close. This causes a leaking of blood from the aorta into the left ventricle. This means that some of the blood that was already ejected from the heart is regurgitating back into the heart. The percentage of blood that regurgitates back through the aortic valve due to AI is known as the regurgitant fraction. For instance, if an individual with AI has a stroke volume of 100ml and during ventricular diastole 25ml regurgitates back through the aortic valve, the regurgitant fraction is 25%. This regurgitant flow causes a decrease in the diastolic blood pressure in the aorta, and therefore an increase in the pulse pressure (systolic pressure - diastolic pressure). Thus, physical examination will reveal a bounding pulse, especially in the radial artery.
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 the blood flows from the aorta into the left ventricle. As a result there is volume overload of the left ventricle.
In acute aortic insufficiency, there is a sudden decrease in stroke volume and subsequent increase in left ventricular end diastolic volume thereby causing decrease cardiac output with resultant reflex tachycardia. The sharply rising high left ventricular end diastolic pressure and reflex tachycardia causes profound hypotension and cardiogenic shock. Initially, the rising left ventricle end diastolic pressure causes early closure of mitral valve during diastole thereby preventing backward blood flow. But in severe cases, the rapidly rising left ventricular end diastolic pressure equalizes with the aortic end-diastolic pressure leading to backward flow of blood progressing towards development of pulmonary edema.
In chronic aortic insufficiency, initially the left ventricle remains complaint, thereby compensates for increased left ventricular end diastolic volume by progressive left ventricular dilatation and left ventricular hypertrophy, which maintains normal ratio of wall thickness to the cavity radius, thereby maintaining normal wall stress. Overtime, when the left ventricular hypertrophy fails to keep up with chronic volume overload, end systolic wall stress rises and at this point the left ventricle fails and results in left ventricle decompensation causing reduction in the left ventricular wall compliance with resultant congestive heart failure.
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. This pathophysiology is in contrast to that of mitral regurgitation where there is also an increase in preload, but there is a decrease in afterload due to ejection of blood into the low pressure system of the pulmonary circuit.
Aortic Valve vs Aortic Root Causes
Aortic Valve Diseases
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.
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 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.
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 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.
Aortic Root Diseases
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. A complete list of conditions that lead to dilation of the aortic root and thereby cause aortic insufficiency can be found on the page dedicated to the causes of aortic insufficiency.
Hemodynamic Consequences of Aortic Insufficiency
Acute Aortic Insufficiency
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 the stroke volume of the left ventricle declines reducing the systolic blood pressure.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 the 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.
Early Compensated Phase of Chronic Aortic Insufficiency
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. According to 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 it does this is to add sarcomeres in series. While the heart is normally shaped like a football, 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 Left Ventricular Eccentric Hypertrophy
Later Decompensated Phase of Chronic Aortic Insufficiency
While the left ventricular dilation is associated with the 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.
- Okafor I, Raghav V, Midha P, Kumar G, Yoganathan A (2016). "The hemodynamic effects of acute aortic regurgitation into a stiffened left ventricle resulting from chronic aortic stenosis". Am J Physiol Heart Circ Physiol. 310 (11): H1801–7. doi:10.1152/ajpheart.00161.2016. PMID 27106040.
- Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA; et al. (2014). "2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". J Thorac Cardiovasc Surg. 148 (1): e1–e132. doi:10.1016/j.jtcvs.2014.05.014. PMID 24939033.
- Stout KK, Verrier ED (2009). "Acute valvular regurgitation". Circulation. 119 (25): 3232–41. doi:10.1161/CIRCULATIONAHA.108.782292. PMID 19564568.
- Mokadam NA, Stout KK, Verrier ED (2011). "Management of acute regurgitation in left-sided cardiac valves". Tex Heart Inst J. 38 (1): 9–19. PMC 3060740. PMID 21423463.
- Enriquez-Sarano M, Tajik AJ (2004). "Clinical practice. Aortic regurgitation". N Engl J Med. 351 (15): 1539–46. doi:10.1056/NEJMcp030912. PMID 15470217.
- Devlin WH, Petrusha J, Briesmiester K, Montgomery D, Starling MR (1999). "Impact of vascular adaptation to chronic aortic regurgitation on left ventricular performance". Circulation. 99 (8): 1027–33. PMID 10051296.
- FRANK MJ, CASANEGRA P, MIGLIORI AJ, LEVINSON GE (1965). "THE CLINICAL EVALUATION OF AORTIC REGURGITATION, WITH SPECIAL REFERENCE TO A NEGLECTED SIGN: THE POPLITEAL-BRACHIAL PRESSURE GRADIENT". Arch Intern Med. 116: 357–65. PMID 14325909.
- Choudhry NK, Etchells EE (1999). "The rational clinical examination. Does this patient have aortic regurgitation?". JAMA. 281 (23): 2231–8. PMID 10376577.
- Bekeredjian, R.; Grayburn, PA. (2005). "Valvular heart disease: aortic regurgitation". Circulation. 112 (1): 125–34. doi:10.1161/CIRCULATIONAHA.104.488825. PMID 15998697. Unknown parameter
- Nishimura, RA. (2002). "Cardiology patient pages. Aortic valve disease". Circulation. 106 (7): 770–2. PMID 12176943. Unknown parameter
- Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA; et al. (2014). "2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. 63 (22): e57–185. doi:10.1016/j.jacc.2014.02.536. PMID 24603191.
- Waller EA, Kaplan J, Heckman MG (2005). "Valvular heart disease in patients taking pergolide". Mayo Clinic Proceedings. Mayo Clinic. 80 (8): 1016–20. PMID 16092580. Retrieved 2011-03-28. Unknown parameter
- Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL (2000). "Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications". Circulation. 102 (23): 2836–41. PMID 11104741. Retrieved 2011-03-28. Unknown parameter
- Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E (2007). "Dopamine agonists and the risk of cardiac-valve regurgitation". The New England Journal of Medicine. 356 (1): 29–38. doi:10.1056/NEJMoa062222. PMID 17202453. Retrieved 2011-03-28. Unknown parameter
- Prêtre R, Faidutti B (1993). "Surgical management of aortic valve injury after nonpenetrating trauma". The Annals of Thoracic Surgery. 56 (6): 1426–31. PMID 8267458. Retrieved 2011-03-28. Unknown parameter
- Onorati F, De Santo LS, Carozza A, De Feo M, Renzulli A, Cotrufo M (2004). "Marfan syndrome as a predisposing factor for traumatic aortic insufficiency". The Annals of Thoracic Surgery. 77 (6): 2192–4. doi:10.1016/S0003-4975(03)01409-7. PMID 15172299. Retrieved 2011-03-28. Unknown parameter
- Fedak PW, Verma S, David TE, Leask RL, Weisel RD, Butany J (2002). "Clinical and pathophysiological implications of a bicuspid aortic valve". Circulation. 106 (8): 900–4. PMID 12186790. Retrieved 2011-03-28. Unknown parameter
- Roberts WC, Ko JM, Moore TR, Jones WH (2006). "Causes of pure aortic regurgitation in patients having isolated aortic valve replacement at a single US tertiary hospital (1993 to 2005)". Circulation. 114 (5): 422–9. doi:10.1161/CIRCULATIONAHA.106.622761. PMID 16864725. Retrieved 2011-03-28. Unknown parameter
- Onorati F, De Santo LS, Carozza A, De Feo M, Renzulli A, Cotrufo M (2004). "Marfan syndrome as a predisposing factor for traumatic aortic insufficiency". The Annals of Thoracic Surgery. 77 (6): 2192–4. doi:10.1016/S0003-4975(03)01409-7. Retrieved 2011-03-28. Unknown parameter
- Regeer MV, Versteegh MI, Ajmone Marsan N, Schalij MJ, Klautz RJ, Bax JJ; et al. (2016). "Left ventricular reverse remodeling after aortic valve surgery for acute versus chronic aortic regurgitation". Echocardiography. 33 (10): 1458–1464. doi:10.1111/echo.13295. PMID 27343211.