Introductory Chapter: Aortic Valve Disease – Recent Advances

1. Introduction

The title of the book “Aortic Valve Disease” was selected with the intent to discuss etiologic, diagnostic, and therapeutic aspects of aortic valve disease with a focus on recent advances. Selected clinicians and investigators were invited to submit chapter proposals, once received, suitable proposals were accepted. The purpose of this chapter is to introduce the subject, describe the normal anatomy of the aortic valve apparatus, review the prevalence of different types of aortic valve diseases, and address topics not adequately dealt with in the other chapters in the book.

Several advances in the understanding of the anatomy of the aortic valve, the development of investigative tests to diagnose and quantitate the magnitude of aortic valve disease, and multiple modalities to treat the aortic valve disease have occurred over the last five decades. The objective of this book was to bring some of these advances to the attention of the reader. While surgical therapy of aortic valve disease has been in vogue since the early 1950s, catheter-based interventional techniques introduced in the early 1980s became initial management options at many institutions. This book will address the anatomy of the normal and diseased aortic valve; explore the utility of diagnostic tests such as echocardiogram, Doppler interrogation, magnetic resonance imaging, computed tomography, cardiac catheterization, and selective cine angiography; and review the relative usefulness of catheter-based vs. surgical techniques in addressing the aortic valve disease. Finally, a discussion of both short-term and long-term results of catheter interventional and surgical therapeutic modalities was included.

2. Normal anatomy of the aortic valve apparatus

The functional unit of a normal aortic root is made up of three aortic sinuses of Valsalva. They are formed by the aortic wall and the aortic valve leaflets, which are attached to the corresponding sinus. This establishes three pocket-like spaces. They are divided by commissural spaces and interleaflet triangles, the so-called trigone [1, 2]. The sum of the zones of the valve leaflets is larger than the cross-sectional region of the aortic root and this in addition to valve leaflet tissue pliability permits for a competent valve closure during the diastolic phase and unhindered valve opening to allow forward flow during the systolic phase of the cardiac cycle. While tricuspid valve leaflets are the most common morphologic structure of the aortic valve, unicuspid, bicuspid, and quadricuspid morphologic variants are also seen, the later in aortic valve or truncal disease states.

3. Prevalence

3.1 Congenital valvar AS

The incidence of congenital valvar aortic stenosis (AS) is 5–6% of all congenital heart defects (CHDs). Given the prevalence of CHDs in 0.8% of live births [3, 4], the population prevalence of AS is estimated to be 0.5–0.6% (5 to 6 per 1000) of live births. AS’s occurrence is more frequent in males than in females.

3.2 Bicuspid aortic valve

The prevalence of bicuspid aortic valve is generally thought to be 1–2% of population [5, 6]. More recent studies indicated a slightly lower prevalence. A study that reviewed echocardiograms of 24,265 subjects with a gender distribution of 47% males and 53% females revealed a 0.6% prevalence of bicuspid aortic valves [7]. Screening echocardiograms of 1742 teenage athletes with male preponderance (67% male and 33% female) revealed a 0.5% incidence of bicuspid aortic valves [7]. In another study of 2273 competitive athletes, aged 8–60 years, bicuspid aortic valves were present in 2.5% [8], higher than seen in the previous study. An echocardiogram of 1075 neonates revealed a prevalence of 0.46%; there was a higher (0.71%) prevalence in male babies than in female infants (0.19%) [9]. Studies do confirm a high level of accuracy of echocardiography in diagnosing bicuspid aortic valve [10]. Variations from 0.5 to 2.5% in the prevalence of bicuspid aortic valve appear to be related to the types of study cohorts selected in each study.

3.3 Calcific AS

In a study published in 2013, the prevalence of calcific AS in the elderly has ranged between 2.8 and 4.6% [11]. In a more recent study examining the global epidemiology of valvular heart disease, calcific AS among adults is age-dependent, older the subject, and more frequent, is its prevalence; the highest is in the older adults: 1000 per 100,000 (1%) in 75–79 year-olds and 1400 per 100,000 (1.4%) in 80–85 year-olds [12]. These prevalences are lower than those described in the above study [11]. There was nearly an equal gender distribution [12]. By contrast, rheumatic heart disease is more common in low-income countries with prevalence rates of 400–500 per 100,000 with similar distribution among all adult age groups [12]. The gender distribution of rheumatic heart disease is also similar in all age groups [12].

3.4 Aortic insufficiency

In the Framingham heart study involving 1696 men and 1893 women aged 54 ± 10 years, the prevalence of aortic insufficiency (AI) was found to be 13% in men and 8.5% in women; the subjects were assessed by echocardiography [13].

3.5 Ascending aortic aneurysm

The prevalence of ascending aortic aneurysms is 5 per 100,000 patient-years; this is based on population-based studies [14].

4. Clinical features

4.1 AS in the pediatric patient

Most children with valvar AS are asymptomatic and the AS is usually detected because of a cardiac murmur heard on routine auscultation [15, 16, 17]. Patients with severe AS may exhibit symptoms such as dyspnea, easy fatigability, or chest pain. Syncope may be a presenting complaint in some children with very severe AS. On physical examination, the left ventricular impulse is increased (left ventricular heave) in all but mild cases. A thrill may be felt at the right upper sternal border and/or in the supra-sternal notch. The first heart sound is usually normal. The second heart sound is also normal unless the AS is extremely severe when there may be a paradoxical splitting of the second heart sound. An ejection systolic click is heard best at the apex and left mid and right upper sternal borders and the click does not vary with respiration. An ejection systolic murmur of grade II–V/VI intensity is heard best at the right upper sternal border with radiation into both carotid arteries. The arterial pulses are usually normal.

4.2 Critical AS in neonates

The term critical AS is used to describe very severe aortic valve stenosis who have high peak systolic pressure gradients across the aortic valve, signs and symptoms of congestive heart failure (CHF) are present, and/or a ductal-dependent systemic circulation exists. The pressure gradient across the aortic valve may not be high in some babies because of poor left ventricular function. They usually present during the first 24–48 hours after birth with symptoms of tachypnea, respiratory distress, cyanosis, pallor, lethargy, metabolic acidosis, and oliguria. Physical examination reveals signs of CHF and poor pulses in all four extremities. Ejection systolic click at the apex and ejection systolic murmur at the right upper sternal border may be heard, but not as prominent as non-critical AS patients.

4.3 Mild, moderate, and severe AS in the adult

The clinical features are essentially like those seen in pediatric patients described above, although, the findings are less discernable in obese adult subjects.

4.4 Calcific AS in the elderly

Patients with milder forms of calcific AS are asymptomatic and are usually detected because of a cardiac murmur heard on routine physical examination or by an echocardiographic study performed for an unrelated reason. Moderate to severe forms may present with symptoms of dyspnea on exertion or exercise intolerance. Rarely, the presenting symptoms such as syncope, chest pain, or signs of CHF may appear. Physical examination reveals increased left ventricular impulse; slow upstroke of the pulse (pulsus tardus) and small pulse volume (pulsus parvus), both are better perceived in carotid than in radial and brachial pulses; ejection systolic click at the apex, unless the aortic valve is immobile because of marked calcification; soft aortic component of the second heart sound; and an ejection systolic murmur, heard at the right upper sternal border, radiating to the carotid arteries. Higher grades of the murmur (grade IV) and late peaking in systole suggest more severe obstruction.

4.5 Aortic insufficiency

Most patients with mild to moderate AI are asymptomatic and are detected because of a cardiac murmur. Severe AI patients present with symptoms of easy fatigability, dyspnea on exertion, or chest pain. On physical examination, while the peripheral pulses are normal in mild AI, they are increased and “bounding” in patients with moderate and severe AI. The pulse pressure is increased secondary to increased systolic blood pressure with a concurrent decrease in diastolic pressure. Peripheral signs of AI such as water-hammer pulse (rapid increase and decrease of pulse when palpating the forearm), Corrigan’s pulse (strikingly augmented carotid pulses), Duroziez’s murmur [bruits both in systole and diastole auscultated in the femoral artery region while it is partially occluded], pistol shot sounds (systolic and diastolic vibrations of the arterial wall—Traube’s sign), and Quinke’s pulse (flushing and blanching alternatively of the capillary beds of the tips of finger) are seen in subjects with moderate to severe AI; however, these signs do not inevitably categorize that the AI is severe. The left ventricular impulse is prominent to hyperdynamic. The diastolic thrill of AI is rarely felt. In general, there are no abnormal cardiac sounds. If the AI is due to a bicuspid aortic valve, an aortic systolic click is auscultated. A systolic ejection murmur is heard at the upper right or at mid-left sternal borders; this may be related to the increased volume of blood that has to be pumped back via the aortic valve. Alternatively, the systolic component may be due to associated aortic valve stenosis. An early diastolic decrescendo murmur is auscultated at the right upper and left mid sternal borders. The murmur has a high pitch and is heard better with the diaphragm than the bell of the stethoscope. The murmur begins with the aortic component of the 2nd sound and is better heard when the patient sits up, leans forward, and holds the breath at end-expiration. It may transmit inferiorly to the left lower sternal border. An Austin-Flint type of mid-diastolic murmur may be appreciated at the apex.

5. Echocardiographic diagnosis

5.1 Congenital AS in the pediatric patient

Echocardiographic studies are very useful in the diagnosis of the type of AS (valvar, sub-valvar, and supra-valvar), in characterizing the aortic valve morphology, and in quantitating the degree of obstruction.

5.1.1 Types of AS

Obstruction of the left ventricular outflow tract may be seen at valvar (Figure 1), sub-valvar (subaortic membranous stenosis [Figure 2] and hypertrophic cardiomyopathy [Figure 3]), and supra-valvar (Figure 4) locations [15, 16, 17]. Examples are shown in Figures 1–4.

Figure 1.

Echocardiographic frames from precordial long axis view of the left ventricle (LV) demonstrating valvar AS. Note the thickened and domed aortic valve (AV). Ao, aorta; LA, left atrium; LV, left ventricle. Reproduced from reference [17].

Figure 2.

Echocardiogram in parasternal long axis (A) and apical five-chamber (B) projections demonstrating the subaortic membrane (SAM). The position of the aortic valve (AV) is shown. Continuous wave and color Doppler studies demonstrated elevated Doppler flow velocity across SAM but are not shown in these echo frames. LA, left atrium; LV, left ventricle. Reproduced from reference [18].

Figure 3.

Echocardiograms in parasternal long (A) and short (B) axis projections illustrating severe thickening of the inter-ventricular septum (arrows), suggestive of hypertrophic cardiomyopathy. Continuous wave and color Doppler studies demonstrated elevated Doppler flow velocity across the left ventricular outflow tract at the level of thickened inter-ventricular septum. Ao, aorta; LA, left atrium; LV, left ventricle. Modified from reference [17].

Figure 4.

Echo-Doppler studies in parasternal long axis (A and B) and subcostal (C and D) projections illustrating supra-valvar AS. Note that the stenosis is above the aortic valve as shown with arrows. Color flow imaging shows turbulence in Doppler flow signal as pointed out with arrows (B and D). An increased Doppler flow velocity was recorded superior to the aortic valve but is not illustrated in the above echo frames. LA, left atrium; LV, left ventricle. Reproduced from reference [18].

5.1.2 Characterization of aortic valve morphology

The normal aortic valve is tricuspid as shown in Figure 5. In congenital AS, most commonly, the aortic valve is bicuspid (Figures 6 and 7),

Figure 5.

Selected echo images in parasternal short axis view demonstrating normal tricuspid aortic valve in closed (A) and open (B) positions. LA, left atrium; RA, right atrium; RV, right ventricle.

Figure 6.

Selected echo images in parasternal short axis view demonstrating normal tricuspid aortic valve (A), bicuspid aortic valve with vertical (B) and horizontal (C) commissures. The arrows point to the respective aortic valve leaflets.

Figure 7.

Echo images illustrating a thick (A) and bicuspid (B) aortic valve (BAV) with doming of the aortic valve (AV) (C) pointed out by arrows. Color flow Doppler demonstrates turbulent flow (TF) at the aortic valve (arrow) (D). The Doppler velocity across the AV is low (<2 m/s) (E), suggesting trivial AS with a bicuspid aortic valve. LA, left atrium; LV, left ventricle. Reproduced from reference [18].

The aortic valve leaflets are thickened (Figures 1A, B and 7A,B) and dome during systole (Figures 1B and 7C) in most patients.

5.1.3 Quantification of the degree of obstruction

The flow velocity magnitude across the aortic valve, measured by Doppler, is increased (Figures 7E and 8C) which is used to calculate the systolic pressure gradient across the aortic valve by a modified Bernoulli equation:

$$\text{Peak instantaneous gradient}={\text{4V}}^2$$E1

Figure 8.

Echo-Doppler studies of a patient with severe AS illustrating an aortic valve (AV) which is thick and domed (A). Color flow imaging demonstrates turbulent flow with a narrow jet (NJ) at the AV (arrow) (B). The Doppler velocity via the AV is high (>6 m/s) (C), suggesting very severe AS; the calculated peak instantaneous gradient is 148 mmHg with a mean of 75 mmHg. The patient has a bicuspid AV which is not demonstrated in these echo frames. Ao, ascending aorta; LA, left atrium; LV, left ventricle. Reproduced from reference [18].

Where V is the peak Doppler velocity across the aortic valve in meters/sec.

The Doppler velocity measurements are made in parasternal, suprasternal notch, and apical views. Most important, however, is to achieve a close alignment of the Doppler signal to the aortic flow. It should be understood that the Doppler peak instantaneous gradient does not accurately reflect the true peak-to-peak systolic pressure gradient obtained in the cardiac catheterization laboratory because of the pressure recovery phenomenon [19]. Consequently, applicable corrections to account for pressure recovery should be made during the calculations of the pressure gradient. Turbulent flow is also demonstrated by color flow Doppler (Figures 7D and 8B).

The echo-Doppler studies in pediatric patients are sufficiently accurate such that there is generally no need for other imaging studies such as magnetic resonance imaging (MRI) and computed tomography (CT).

5.1.4 Other echocardiographic features

Annular hypoplasia and dysplasia of aortic valve leaflets have also been seen, mostly in neonates and young babies.

Left ventricular internal dimension (LVID) in diastole is usually normal for age. However, LVID may be increased in patients with long-standing and severe AS. Such left ventricular enlargements are more common in neonates with critical AS. Hypertrophy of the left ventricular musculature in a concentric manner is seen which is mostly proportionate to the severity of obstruction. The left ventricular shortening fraction may be increased, usually proportional to the degree of narrowing. However, in neonates with critical AS and patients with heart failure, it may be decreased. Post-stenotic dilatation of the aorta (Ao) is observed in most patients; the degree of such dilatation is not related to the degree of aortic valve obstruction [16, 17, 18].

5.2 Congenital AS in the young adults

The echo-Doppler studies in young adults with congenital AS are similar to those described in the preceding section, although an occasional patient with poor acoustic windows may require trans-esophageal echo evaluation or other imaging studies.

5.3 Calcific AS in the elderly

Like AS in the pediatric patient, echocardiographic studies are very useful in characterizing the aortic valve morphology, in quantitating the degree of obstruction, and in assessing left ventricular response to increased afterload. The aortic valve leaflets have increased echo density and decreased valve leaflet motion. It is frequently difficult to discern whether it is a tricuspid or bicuspid aortic valve. The Peak Doppler flow velocity is increased which is used to calculate the systolic pressure gradient across the aortic valve by a modified Bernoulli equation, as reviewed above in the section on “Congenital AS in the Pediatric Patient.” Other disease entities such as hypertrophic cardiomyopathy, mitral valve disease, and CHDs are excluded by echo studies. Left ventricular hypertrophy is usually detected by echo evaluation. Left ventricular ejection fraction can be quantitated; in most cases, it is preserved until late in the disease.

5.4 Aortic insufficiency

Echocardiographic, MRI, and CT features of AI were described in the chapter on “Transcatheter Therapies for Aortic Regurgitation – Where Are We in 2023?” by Shabbir and his associates and will not be repeated in this chapter.

6. Aortic valve surgery without valve replacement

Most chapters in this book deal with surgical or transcatheter replacement of the aortic valve. Other forms of surgery such as commissurotomy, plastic repair of aortic valve, and Ross procedure have not been addressed. These will be reviewed briefly.

6.1 Commissurotomy

Aortic valvotomy via aortotomy under cardiopulmonary bypass has been used with success [20]; however, most institutions currently use balloon aortic valvuloplasty as the initial treatment option.

6.2 Plastic repair of the aortic valve

Neocuspidization (plastic repair of aortic valve) either into a bicuspid or tricuspid aortic valve, as the case may be, with or without prosthetic material (patient’s native leaflet tissue, glutaraldehyde-treated autologous pericardium, non-treated autologous pericardium, expanded polytetrafluoroethylene (ePTFE) membrane, decellularized xenogenic tissue, glutaraldehyde-treated bovine pericardium, or untreated equine pericardium) and cusp augmentation to restore the aortic valve close to its normal structure and function has been used successfully [21, 22, 23, 24].

6.3 Ross procedure

Aortic valve replacement with patient’s own pulmonary valve and inserting a bioprosthetic valve in the pulmonary position [25, 26] has been used successfully to address severe AS cases both in neonates and older patients, although the risk of double valve disease exists [27].