Etiology
Aortic regurgitation (AR) rarely occurs as an isolated lesion, but is a common finding in patients with concomitant congenital heart lesions. It can result from primary disease of the aortic leaflets or secondary to pathology of the aortic root and surrounding structures ( Table 37.1 ).
| Aortic Valve Disease | Pathologic Process |
|---|---|
| Rheumatic fever | Cusps become infiltrated with fibrous tissue and retract, a process that prevents cusp coaptation and leads to central AR |
| Infective endocarditis | Infection causing perforation/deformity of a leaflet, or vegetation preventing leaflet coaptation |
| Bicuspid aortic valve |
|
| VSD | Prolapse of cusp(s) into the ventricular outflow tract |
| Membranous subaortic stenosis | Distortion of aortic cusp(s) from jet acceleration cause by the subvalvular obstruction |
| Secondary to percutaneous aortic balloon valvulotomy in congenital aortic stenosis | Sequela of repetitive balloon dilation that leads to valve damage and leaflet degeneration |
| Sinus of Valsalva aneurysm | Rupture of sinus of Valsalva aneurysm into right ventricle or right atrium can be the cause of AR |
| Tetralogy of Fallot | Secondary to dilation of the aortic root and subsequent change in shape and coaptation of aortic valve cusps |
| Unicuspid/quadricuspid valve or rupture of a congenitally fenestrated valve | Primary pathology of a congenitally malformed valve |
| Aortic root pathology secondary inherited diseases (Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, bicuspid aortopathy) | Aortic wall weakened by cystic media degeneration with subsequent aortic wall dilation that leads to lack of aortic leaflets coaptation |
| Aortic root pathology secondary to acquired disease (systemic lupus erythematosus, ankylosing spondylitis, Takayasu disease, etc.) | Dilation of the aortic root and change in shape results in failure of coaptation of aortic valve leaflets |
| Postoperative | Damaged aortic valve after a Ross procedure or arterial switch operation |
A bicuspid aortic valve (BAV) is the most common cause of primary AR. BAV may be divided into type 0, type 1, and type 2, according to whether there is no raphe, 1 raphe, or 2 raphes, respectively. Furthermore, BAV is characterized by heterogeneous cusp and sinus morphology, heavy and asymmetric calcifications, long commissural distance, aortic root angulation (horizontal aorta), aortopathy, and coarctation of the aorta.
AR also occurs in children with aortic root pathology secondary to inherited diseases, but is more common in adults in association with progressive aortic root dilation. Rheumatic heart disease was a principal cause in the past, but is now uncommon in developed countries. Other associated conditions include Turner syndrome, osteogenesis imperfecta, subaortic stenosis, prolapse of an aortic cusp due to a ventricular septal defect (VSD; typically membranous), tetralogy of Fallot (TOF), and truncus arteriosus.
Primary Aortic Valve Abnormality
AR occurs in up to two-thirds of patients with congenital BAV. In most cases this is related to intrinsic abnormality of the valve structure and concomitant associated aortopathy. In patients with a BAV and aortic coarctation, AR might increase secondary to the high afterload inherent to the coarctation itself and associated reduced aortic compliance. Monocuspid or quadricuspid valves have been described in the literature and may be a cause of AR.
Aortic Root Pathology
Secondary AR related to diseases of the aortic root is more prevalent than primary AR related to intrinsic abnormality of the valve. Dilation of the aortic root and sinotubular junction usually occurs in association with a number of forms of congenital and acquired heart disease. These include Marfan syndrome (mutation in Fibrillin-1), Loeys-Dietz syndrome (mutation in TGFBR1 and 2), Ehlers-Danlos syndrome type IV (deficient Type III collagen), and familial/thoracic aortic aneurysm syndrome. In this sense, AR often develops secondary to ascending aortic dilation, which leads to bowing and displacement of the commissures outward, preventing adequate leaflet coaptation. Spontaneous dissection of the aorta is more often the principal clinical concern and can present with acute AR.
Aortic Regurgitation Associated With Other Congenital Lesions
In patients with fibromuscular subaortic stenosis, the discrete fibrous ring creates a jet that may distort the aortic valve cusps, and hemodynamically significant AR occurs in about 20% of patients, especially when the peak instantaneous Doppler left ventricular outflow tract (LVOT) gradient reaches 50 mm Hg or more. Moreover, these patients are at risk for endocarditis, which will contribute to worsening AR.
In the presence of a membranous or subpulmonic VSD, the aortic valve cusps are inadequately supported and may prolapse into the right ventricular outflow tract. The subsequent malcoaptation of the valve cusps leads to progressive AR. In contrast to other causes of AR, early repair is indicated to prevent further valve damage.
AR occurs in a small proportion of patients with TOF. It is more common in patients repaired at a later age and also appears to be related to the severity of pulmonary stenosis. The mechanism is unclear, but increased transaortic flow resulting in dilation of the root and ascending aorta have been postulated. Failure to recognize and correct AR at the time of the initial repair of TOF appears to be an important factor in later morbidity and mortality.
Acquired Aortic Regurgitation
AR may be an acquired lesion following an episode of infectious endocarditis (IE) or intervention for aortic stenosis (AS), such as surgical or balloon valvuloplasty. Among patients with congenital valvular AS who are treated with balloon valvuloplasty, the rate of moderate to severe AR has been reported in 13% of patients after the initial procedure and in 38% of patients at 4 years. This risk is increased in patients undergoing repeat balloon valvuloplasty.
Mild incompetence of the pulmonary autograft is often found after the Ross operation and in the neoaortic valve of patients with transposition of the great arteries after the Jatene procedure (arterial switch operation).
Clinical and Natural Course in Children with Aortic Regurgitation
Few studies are available on the clinical course of AR in congenital heart disease patients because most studies have mainly excluded patients with AR and concomitant congenital heart lesions. Most cases of AR in children are mild, and patients remain stable for many years. Progression occurs in some patients, while IE may cause acute progression.
The natural history of isolated congenital AR was described in seven children who did not have Marfan syndrome. The diagnosis was made in infancy in five. Three patients were asymptomatic through follow-up at 8, 10, and 20 years, whereas four required aortic valve replacement (AVR) at age 3, 10, 15, and 20 years for progressive severity. Dilatation of the aorta is common in children with Marfan syndrome and progresses with time. One report followed 52 patients with Marfan syndrome through childhood and adolescence. Aortic root dilation was present in 43 patients and AR in 13 patients (25%). The AR was diagnosed at a mean age of 14.6 years and was initially mild in all but one patient. At a mean follow-up of 7.9 years, aortic abnormalities progressed in 13 patients, and 10 patients required AVR for aortic root dilation or dissection.
Acute Aortic Regurgitation
Acute AR is most commonly seen in the context of IE, dissection of the aortic root, trauma, or disruption of the valve after percutaneous balloon dilation and transcatheter aortic valve replacement (TAVR). In acute AR, the left ventricle (LV) has no time to adapt to the sudden increase in volume loading and a rapid rise in end-diastolic pressure with reduced ejection fraction (EF) and cardiac failure ensues. AR may be fulminant and associated with tachycardia, peripheral vasoconstriction, pulmonary edema, and cardiogenic shock, and patients appear gravely ill. Transthoracic and/or transesophageal echocardiogram (TTE/TEE) is indispensable in confirming the presence and etiology of AR, although quantification of the regurgitation may be difficult. Short deceleration time on the mitral flow velocity curve and early closure of the mitral valve on M-mode echocardiography are indicators of markedly elevated LV end-diastolic pressure. A short half-time of less than 250 ms on the AR velocity curve indicates rapid equilibration of the aortic and LV diastolic pressures. Without rapid surgical intervention, clinical deterioration is imminent.
Chronic Aortic Regurgitation
Pathophysiology
In most patients with AR, the disease course is chronic and slowly progressive with increasing LV volume overload and LV adaptation via chamber dilation and hypertrophy ( Fig. 37.1 ).
The regurgitant volume (RVol) during diastole results in a portion of the left ventricular stroke volume (SV) leaking back from the aorta into the LV. The added RVol produces an increase in LV end-diastolic volume and an elevation in wall stress. The LV responds with compensatory eccentric hypertrophy. The combination of LV eccentric hypertrophy and chamber enlargement raises the total SV. The net effect is that forward SV and hence cardiac output are initially maintained despite the regurgitant lesion. Although LV volume is increased, end-diastolic pressure remains normal due to an increase in ventricular compliance. Thus, the heart initially adapts well to chronic AR, functioning as a very efficient and compliant high-output pump. However, as AR persists and increases in severity over time, wall thickening fails to keep up with the hemodynamic load, and end-systolic wall stress rises. At this point, afterload mismatch results in a decline in systolic function, and EF drops.
Clinical Presentation
History
Early symptoms are usually exertional dyspnea and fatigue. Patients may complain of angina pectoris related to poor coronary perfusion and increased myocardial oxygen demand.
Physical Examination
Manifestations of severe chronic AR are often the result of widened pulse pressure with diastolic pressures often lower than 50 mm Hg. On palpation, the point of maximal impulse may be hyperdynamic, but is often displaced inferiorly and toward the axilla. Peripheral pulses are prominent or bounding. Auscultation may reveal an S3 gallop if LV dysfunction is present. The murmur of AR occurs in diastole, usually as a high-pitched sound that is loudest at the left sternal border. The duration of the murmur correlates better with the severity of AR than does the loudness of the murmur.
Early diastolic murmur (lower pitched and shorter than in chronic AR) may be present in acute AR. An Austin-Flint murmur may be present at the cardiac apex in severe AR; it is a low-pitched, middiastolic rumbling murmur due to blood jets from the AR striking the anterior leaflet of the mitral valve, which results in premature closure of the mitral leaflets.
Associated physical examination findings include the following:
Corrigan pulse or “water-hammer” pulse: abrupt distention and quick collapse on palpation of the peripheral arterial pulse.
de Musset sign: Bobbing motion of the patient’s head with each heartbeat.
Hill sign: Popliteal cuff systolic blood pressure 40 mm Hg higher than brachial cuff systolic blood pressure.
Duroziez sign: Systolic murmur over the femoral artery with proximal compression of the artery, and diastolic murmur over the femoral artery with distal compression of the artery.
Müller sign: Visible systolic pulsations of the uvula.
Quincke sign: Visible pulsations of the fingernail bed with light compression of the fingernail
Traube sign (“pistol-shot” pulse): Booming systolic and diastolic sounds auscultated over the femoral artery.
Becker sign: Visible systolic pulsations of the retinal arterioles and pupils.
Mayne sign: More than a 15 mm Hg decrease in diastolic blood pressure with arm elevation as compared with the value obtained with the arm in the standard position.
Senbach sign: Systolic pulsations of the liver.
Gerhard sign: Systolic pulsations of the spleen.
Testing
Electrocardiography
An electrocardiogram is not indicated for a diagnosis of AR but is commonly included in the evaluation of patients with AR to establish a baseline for future comparison.
The electrocardiogram reflects the adaptive changes that occur in the LV as a result of the volume overload, typically with findings of LV hypertrophy.
Chest Radiography
The cardiac silhouette may be enlarged in severe chronic AR. The ascending aorta may be dilated in patents with aortopathy, and the aortic “knuckle” is typically prominent.
Echocardiography
TTE is indicated in patients with signs or symptoms of AR for accurate diagnosis of the cause of regurgitation, regurgitant severity, LV size, and systolic function, and for determining clinical outcome and timing of valve intervention.
TEE is indicated in patients with dilated aortic sinuses or ascending aorta or with a BAV to evaluate the presence and severity of AR.
Severe chronic AR is considered to be present if one or more of the following findings are present on echocardiography :
- 1.
Central jet width greater than 65% of the LVOT
- 2.
A vena contracta width greater than 6 mm
- 3.
Holodiastolic flow reversal in the abdominal aorta
- 4.
A regurgitant fraction (RF) greater than 50%
- 5.
An RVol greater than 60 mL/beat
- 6.
An effective regurgitant orifice (ERO) area greater than 0.30 cm 2
Cardiac Catheterization
The role of invasive angiography in the assessment of chronic AR is limited in the presence of better imaging modalities like echocardiography and cardiac magnetic resonance (CMR) imaging. Aortic root angiography and cardiac catheterization with measurement of left ventricular pressures may be indicated when noninvasive tests are inconclusive or provide results that differ from clinical findings. Angiography allows assessment of aortic root dimension and associated disorders (eg, dissection, sinus of Valsalva aneurysm), determination of left ventricular size, systolic function, and a semiquantitative assessment of the severity of AR. Severe AR is diagnosed by the presence of 3+ to 4+ regurgitation by Sellers criteria.
Magnetic Resonance Imaging
In the updated American Heart Association/American College of Cardiology (AHA/ACC) guidelines, CMR is a class I indication in patients with moderate or severe AR and suboptimal echocardiographic images for the assessment of LV systolic function, systolic and diastolic volumes, and quantification of AR severity. AR volume and regurgitant orifice area can be quantified by CMR with less variability than echocardiographic measurements and is considered as the gold standard. It is also useful for a detailed assessment of the anatomy of the aortic root and ascending aorta and to exclude other significant cardiac abnormalities, including subaortic membrane and aortic coarctation.
Exercise Testing
Exercise stress testing can be used to assess functional capacity in patients with AR. It is helpful in sedentary patients who report no symptoms with daily life activities, and in assessing objective exercise capacity and symptom status in those with equivocal symptoms.
Stages of Chronic Aortic Regurgitation
Management of patients with AR depends on accurate diagnosis of the cause and stage of the disease process ( Table 37.2 ). As described in the updated AHA/ACC guidelines, the stages of AR range from patients at risk of AR (stage A) or with progressive mild-to-moderate AR (stage B) to severe asymptomatic (stage C) and symptomatic AR (stage D). Each of these stages is defined by valve anatomy, valve hemodynamics, severity of LV dilation, and LV systolic function, as well as by patient symptoms.
