Section 1: Epidemiology and aetiology
In most people the aortic valve (AV) has three leaflets - the right, left, and non-coronary cusps. The valve opens to an effective orifice area of 3-4 cm2 at the beginning of systole when the left ventricular (LV) pressure exceeds the aortic root pressure. This facilitates blood flow into the aortic root from the LV.
At the end of systole, the aortic leaflets coapt (close) approximately 60 milliseconds after the aortic root pressure exceeds LV pressure, preventing the regurgitation of blood into the LV.
Aortic valve disease consists of either obstruction to LV outflow (such as in aortic stenosis), regurgitation of blood from the aortic root into the LV during diastole (such as in aortic regurgitation), or a mixed pattern of disease with both features.
Valvular aortic stenosis (AS) may be congenital or acquired. The causes of acquired valvular AS are more common and include calcific degeneration, rheumatic heart disease (more commonly affecting the mitral valve), infective endocarditis(IE), radiation, and drugs (such as fenfluramine). Calcific degeneration occurs as a result of mechanical stress across the AV which initiates inflammatory processes that ultimately cause calcium deposition from osteoblasts.
A bicuspid aortic valve (BAV) is the most common cause of congenital AS. The condition has a genetic link, with an autosomal-dominant pattern of inheritance described.1 However, there is variable penetrance, with family members being unpredictably affected. BAV is associated with other conditions such as aortic root dilatation,2 and coarctation of the aorta.3
Aortic stenosis causes obstruction, thereby increasing the workload of the LV (afterload). Compensatory mechanisms react to the pressure overload by stimulating hypertrophy of the ventricle with preserved LV function. Progression of the stenosis may eventually lead to failure of these mechanisms, with reduction in systolic function and dilatation of the ventricle (end-stage AS).
Aortic regurgitation (AR) may be primary (abnormalities of the valve leaflets or annulus), or functional (abnormalities of the aortic root).
Primary causes include calcific degeneration, bicuspid AV, rheumatic heart disease, and IE.4
Abnormalities of the aortic root (functional AR) lead to dilatation of the aortic root and AV annulus, with failure of coaptation of the AV leaflets. This can be secondary to age-related degeneration, arteriosclerosis, hypertension, cystic medial necrosis, aortic dissection, or inflammatory autoimmune diseases. Associated conditions include Marfan’s syndrome, bicuspid AV, syphilis, and ankylosing spondylitis.
In AR, the LV is filled from the left atrium and via regurgitation from the aortic root, causing a volume overload. The increased ventricular end-diastolic volume increases LV contraction through the Frank-Starling mechanism. Progression of the condition leads to eventual failure of contractile fibres and dilatation of the ventricle.
In developed countries, the most common cause of AS is calcific degeneration. Mild calcification occurs in up to 40 per cent of those aged 60 or over, and 75 per cent of those aged over 85.5 Bicuspid AV is more common in males and is present in 0.5-0.8 per cent of large population studies.6 Rheumatic heart disease remains the most common cause in the developing world.
As with AS, the prevalence of AR increases with age. In the Helsinki Ageing Study (n = 552), 29 per cent of all participants (mainly elderly) had some degree of AR, while 13 per cent had severe AR.7
Section 2: Making the diagnosis
The majority of patients with AS are asymptomatic. Onset of symptoms indicates a worse prognosis and is associated with 15-50% mortality at 5 years.8 The cardinal symptoms of severe AS are all typically provoked by exertion.
This is explained by the inability of the fixed LV output to meet the increased demand during exercise, and is compounded by the vasodilatation that accompanies physical activity. There is also an increase in cardiac oxygen requirements from compensatory LV hypertrophy.
Most patients with symptomatic AS experience exertional angina. A proportion of patients develop syncope on exertion, while exertional dyspnoea and other symptoms of heart failure occur late in the disease. Rarely, patients can develop underlying arrhythmia which may present as palpitations or pre-syncopal episodes.
GPs should specifically ask about exertional angina, breathlessness, and dizziness/syncope, and explore any deterioration in functional status or symptoms of heart failure.
Be aware that deterioration in functional capacity occurs over a prolonged period of time, and patients may declare that they are asymptomatic when they have consciously reduced their physical activity to avoid symptoms. It is often useful to ask a close relative their opinion about exertional symptoms.
Important! Where possible, ask relatives about exertional symptoms as patients may have reduced their physical activity to avoid symptoms.
The character of the pulse tends to be of low volume, reflecting the reduction in flow across the narrowed valve. This is most prominent in the carotid region where the pressure on the palpating finger slowly rises to maximum amplitude (slow rising pulse).
Progression of AS causes the systolic pressure to decline until the pulse pressure (the difference between systolic and diastolic blood pressure [BP]) narrows ultimately to less than 20 mmHg.
Unlike in AR, the apical impulse is not usually displaced, as it is pressure - not volume - overloaded. The impulse is felt as a sustained heave due to the prolonged systole required to achieve a normal stroke volume in severe AS.
The harsh crescendo-decrescendo (or ejection systolic) murmur of AS is best heard in expiration in the aortic area, with the patient sitting forwards, and often radiates to the root of the neck. The intensity of the murmur bears no relation to the degree of stenosis and should not be used as an estimate of severity.
The first heart sound (S1) is of normal intensity. The aortic component (louder than the pulmonary component) of the second heart sound (S2) softens with progressive tethering of the valve cusps, until it becomes inaudible in severe AS.
Be aware that in bicuspid valves the intensity of S2 may be preserved despite severe stenosis. Hence, although the disappearance of S2 is used as a marker of severe AS, it lacks sensitivity. A pre-systolic fourth heart sound (S4) may arise from forceful contraction of the LA against increased diastolic pressures in the hypertrophied LV.
Patients with chronic AR are often asymptomatic. Failure of compensatory mechanisms may lead to symptoms. A common symptom in AR is fatigue from the decreased aortic forward flow. Exertional dyspnoea and other symptoms ofheart failure worsen as the disease progresses, resulting in myocardial fibrosis and LV dysfunction. Patients may occasionally have an increased awareness of their heartbeat, often described as palpitations.
Numerous eponymous clinical signs have been described in AR.9 However, these usually occur in severe symptomatic disease and are not in isolation helpful in diagnosis. They are rarely seen in current practice due to the increased sensitivity of diagnostic testing.
The pathophysiological mechanism underlying these signs is the flow reversal in the aorta and major arteries due to severe valvular incompetence, resulting in a rapid decline in diastolic BP. This mechanism also explains many of the other clinical features in AR.
The pulse is high volume and may be collapsing in nature if there is sufficient regurgitation to cause a flow reversal. In compensated AR, the systolic BP is elevated by the increased stroke volume and forceful LV contraction.
However, the diastolic BP often drops too, depending on the severity of AR, resulting in a wide pulse pressure (in contrast to AS). Be aware that end-stage AR with decompensated heart failure may present instead with a low systolic BP.
The apical impulse is often visible and displaced outwardly and inferiorly. The enlarged and hyperdynamic ventricle imparts a forceful impulse to the palpating hand.
The S1 is usually normal while the S2 is closely followed by a blowing early diastolic murmur which is the most useful clinical sign in diagnosing AR. This is heard best in expiration in the aortic area with the patient sitting forwards. Clinicians should focus on the diastolic phase during auscultation to recognise this, which may be an absence of silence rather than a prominent murmur after S2.
A late diastolic murmur is occasionally present as a result of the regurgitant jet displacing the anterior mitral valve leaflet (Austin Flint murmur).
Acute AR may occur secondary to aortic dissection, and patients typically present with haemodynamic compromise and pulmonary oedema. These patients may lack the usual signs associated with the condition.
|Clinical features of aortic valve disease|
|Aortic stenosis||Aortic regurgitation|
|Pulse character||low volume, slow rising||high volume, collapsing|
|Pulse pressure||narrow||wide (in early disease)|
|Murmur||systolic murmur (crescendo-decrescendo)||early diastolic murmur|
|Additional features||soft S2||Austin Flint murmur|
A thorough history and clinical examination is the cornerstone of diagnosis in AV disease. Resting 12-lead ECG may reveal evidence of LV hypertrophy (typically tall R waves in V5-6, and deep S wave in V1-2) in patients with AS, although severe AS without significant LV hypertrophy is a well-recognised entity.10
Calcific degeneration of the aortic root in AS may extend into the nearby interventricular septum, resulting in conduction disturbances, including first degree block (prolonged PR interval). Higher degrees of AV block are less commonly seen. LV hypertrophy may also result in ST-T wave changes, most prominent in the lateral leads (V4-V6, I, aVL).
However, it is worth noting that these patients often have concomitant coronary artery disease that puts them at high risk of myocardial infarction which may also present with similar ST-T wave changes.
Chest X-ray reveals cardiomegaly in patients with AR (defined as cardiothoracic ratio >0.5 on PA film). Evidence of pulmonary congestion may appear in the late stages of both AS and AR.
Transthoracic echocardiography (TTE) is the investigation of choice and should be arranged for all patients with a new murmur in whom valvular heart disease is a possibility. This allows confirmation of aortic valve disease and grading of the severity.
More detailed investigations should be arranged on advice from a cardiologist. These include stress echocardiography, transoesophageal echocardiography (TOE), cardiac magnetic resonance imaging (MRI), multi-slice computed tomography (CT) and cardiac catheterisation.
Patients who are referred for surgery for aortic valve replacement should undergo coronary angiography. The cardiologist can then also assess for coronary stenoses that may require concomitant coronary artery bypass grafting (CABG).
Patients with a clinical suspicion of aortic valve disease should be referred to a cardiologist (irrespective of symptoms) to aid planning of appropriate long-term management.
|Urgency of referral in aortic valve disease|
|Admit to hospital||
Important! Admit to hospital where there is clinical suspicion of infective endocarditis, haemodynamic instability, or clinical evidence of heart failure in someone with previously diagnosed severe AS/AR
Section 3: Managing the condition
No pharmacological agents provide prognostic benefit in patients with AS. Although previously contraindicated in severe AS, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) are now thought to aid in LV remodelling and may be beneficial if started before valve stenosis has progressed to a severe degree.11,12
Nonetheless, vasodilators such as ACE inhibitors, ARBs, alpha- and beta-adrenergic blockers, calcium channel blockers, and nitrates should be used with caution in hypotensive patients. Patients commenced on these medications require careful titration and frequent monitoring.
Symptomatic patients with chronic severe AR and heart failure with hypertension may benefit from vasodilators (ACE inhibitors or ARBs). There is no evidence that these are of benefit in asymptomatic patients.
There is no role for statin therapy in AS.13-15 Co-existent hypertension or heart failure in patients with AV disease should be treated accordingly. Current NICE guidelines (reviewed in 2015) state that routine antibiotic prophylaxis for infective endocarditis is not indicated in patients with AV disease.16
Open surgical AV replacement is the treatment of choice in patients with severe symptomatic AS/AR. The European Society of Cardiology (ESC) 2012 guidelines for the management of valvular heart disease offer the following indications for AV replacement:
- Aortic stenosis:
- severe AS with symptoms (Class 1B recommendation)
- asymptomatic, severe AS with LV dysfunction (ejection fraction [EF] less than 50%) not due to another cause (Class 1C recommendation)
- asymptomatic, severe AS patients who are undergoing CABG, surgery of the ascending aorta, or another valve (Class 1C recommendation)
- Aortic regurgitation:
- severe AR with symptoms (Class 1B recommendation)
- asymptomatic, severe AR with LV dysfunction (EF ≤50 per cent) (Class 1B recommendation)
- asymptomatic, severe AR with preserved LV function (EF >50 per cent) and severe LV dilatation (left ventricular end diastolic diameter [LVEDD] >70 mm, or left ventricular end systolic diameter [LVESD] >50 mm) (Class 2a C recommendation)
- asymptomatic, severe AR patients who are undergoing CABG, surgery of the ascending aorta, or another valve (Class 1C recommendation)
There are two main types of prosthesis in valve replacement - mechanical and bioprosthetic (see box).
|Types of prosthesis and patient selection characteristics|
|Risk of redo surgery||
|Risk of prosthetic valve degeneration||
Transcatheter aortic valve implantation (TAVI)
TAVI should be considered for AS patients who are deemed high risk candidates for surgical AV replacement. This has been shown to improve health status and quality of life.17 Eligible patients should have a life expectancy of more than 1 year and should be likely to gain improvement in their quality of life from the procedure.
Balloon aortic valvuloplasty may be used as bridging therapy to surgery or TAVI in patients who are haemodynamically unstable or require urgent non-cardiac surgery. It can be considered as a palliative measure for selected patients.18
Section 4: Prognosis
Symptomatic deterioration should be carefully monitored. Specific enquiries regarding fever, night sweats, lethargy, andweight loss should be made to rule out infective endocarditis. Clinical examination should focus on features of congestive cardiac failure and infective endocarditis, as well as auscultation of the heart sounds.
Mechanical aortic valves generate a metallic S2, whereas bioprosthetic aortic valves typically cause a loud S2. A systolic flow murmur is common in patients with prosthetic AV. Special care should be taken to exclude prosthetic valve incompetence/regurgitation (early diastolic murmur in the left third to fourth intercostal spaces, with the patient leaning forward while breath is held in expiration).
A full baseline assessment, including transthoracic echocardiography, should be performed at 6-12 weeks postoperatively by the cardiology or cardiac surgery team. Clinical suspicion of prosthetic valve incompetence should be assessed further using TTE.
Routine annual follow up TTE is not indicated in the early postoperative years in the absence of symptoms and unchanging murmur. Annual TTE is arranged after 5 years in young patients with a bioprosthetic valve replacement. However, any suspicion of symptomatic deterioration or infective endocarditis should trigger urgent echocardiographic assessment.
Patients with prosthetic heart valves are usually under annual follow-up with cardiology services. Lifelong anticoagulation is recommended for those with mechanical valves, the INR target of which differs according to the position of the valves, the type of valve, and LV function.
Section 5: References
- McDonald K, Maurer BJ. Familial aortic valve disease: evidence for a genetic influence? Eur Heart J 1989;10(7):676-7.
- Tadros TM, Klein MD, Shapira OM. Ascending aortic dilatation associated with bicuspid aortic valve: pathophysiology, molecular biology, and clinical implications. Circulation 2009;119(6):880-90.
- Warnes CA. Bicuspid aortic valve and coarctation: two villains part of a diffuse problem. Heart 2003;89(9):965-6.
- Lung B, Baron G, Butchart EG et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J 2003;24(13):1231-43.
- Malhotra A. The changing burden of valvular heart disease. June 2012.
- Nistri S, Basso C, Marzari C et al. Frequency of bicuspid aortic valve in young male conscripts by echocardiogram.Am J Cardiol 2005;96(5):718-21.
- Lindroos M, Kupari M, Heikkila J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol 1993;21(5):1220-5.
- Ross J Jr, Braunwald E. Aortic stenosis. Circulation 1968;38(suppl):61-7.
- Ashrafian H. Pulsatile pseudo-proptosis, aortic regurgitation and 31 eponyms. Int J Cardiol 2006;107(3):421-3.
- Seiler C, Jenni R. Severe aortic stenosis without left ventricular hypertrophy: prevalence, predictors, and short-term follow up after aortic valve replacement. Heart (1996); 76(3): 250-5.
- Jao G, Lystash J, Sane D. Angiotensin-converting enzyme inhibitors can increase the transvalvular gradient among patients with aortic stenosis. J Am Coll Cardiol 2012;59(8):777.
- Routledge HC, Townend JN. ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity? J Hum Hypertens 2001;15(10):659-67.
- Chan KL, Teo K, Dumesnil JG et al. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial.Circulation 2010;121(2):306-14.
- Cowell SJ, Newby DE, Prescott RJ et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med 2005;352(23):2389-97.
- Otto CM. Calcific aortic stenosis - time to look more closely at the valve. N Engl J Med 2008;359(13):1395-8.
- National Institute for Health and Care Excellence. Prophylaxis against infective endocarditis: antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures (CG64). NICE, March 2008 [reviewed 2015].
- Gurvitch R, Wood DA, Tay EL et al. Transcatheter aortic valve implantation: durability of clinical and hemodynamic outcomes beyond 3 years in a large patient cohort. Circulation 2010;122(13):1319-27.
- Vahanian A, Alfieri O, Andreotti F et al. Guidelines on the management of valvular heart disease (version 2012).Eur Heart J 2012;33(19):2451-96.
Dr Wern Yew Ding, ST3 Cardiology, Liverpool Heart and Chest Hospital and Dr Unni Krishnan academic clinical lecturer, Cambridge University, and Papworth Hospital, Cambridge
- This is an updated version of an article that was first published in March 2010