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1Department of Internal Medicine, Section of Cardiology, Sarver Heart Center, University of Arizona College of Medicine, 1501, N Campbell Avenue, Tucson, AZ 85724, USA
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2Section of Cardiology, Sarver Heart Center, University of Arizona College of Medicine
Correspondence to: R Ramaraj drkutty2@gmail.com
Cite this as: BMJ 2008;336:550-5
<DOI> 10.1136/bmj.39478.498819.AD http://www.bmj.com/content/336/7643/550
Aortic stenosis is the most common valvular lesion in Europe and North America. It primarily presents as calcific aortic stenosis in 2-7% of the population aged >65 years.1 About 80% of adult patients with symptomatic aortic stenosis are male. As 1-2% of the population is born with a congenital bicuspid aortic valve and populations are ageing, aortic stenosis is becoming more common. By 2020, about 3.5 million people in England are expected to have aortic sclerosis and 150 000 will have severe aortic stenosis.2 Here we provide an overview to help diagnosis and a summary of the management of AS and its sequelae. Many of the points made in this review are based on randomised controlled trials. However, observational studies and the guideline recommendations of the American Heart Association and the American College of Cardiology and of the European Society of Cardiology are also included to provide comprehensive overviews that are beyond the scope of this article.
The most common cause of aortic stenosis in adults is calcification of a normal trileaflet (fig 1). Calcific aortic stenosis is thought to be a degenerative process that shares many features with coronary artery disease, such as lipid accumulation, inflammation, and calcification. The abnormal architecture of the bicuspid or unicuspid aortic valve makes the leaflets susceptible to haemodynamic stress, leading to valvular thickening, calcification, and increased rigidity and narrowing of the aortic orifice.
Aortic stenosis may also be secondary to rheumatic inflammation of the valve leaflets. Investigators have found histological similarities between the lesion of aortic stenosis and atheromatous coronary artery disease and have documented an association between traditional atherosclerotic risk factors and the development of calcific aortic valve disease.3 Mature lamellar bone formation and osteopontin bone expression are present in calcified aortic valves. Researchers have also shown that hypercholesterolaemia can induce both cellular proliferation and osteoblast phenotype expression that may lead to progression of aortic valvular disease.4
SOURCES AND SELECTION CRITERIA
The literature search included Medline and PubMed from 2003 to the present. The terms searched were “aortic stenosis”, “diagnosis”, “aortic valve replacement”, and “grading” in various combinations. We scrutinised the articles identified by this search and selected high quality randomised controlled trials and retrospective studies. We examined citation lists from these for further relevant articles. To identify the factors contributing to aortic stenosis, we did a complete search of the Medline database. When appropriate, we also considered publications from before 2003. We included some review articles, websites, and book chapters because they provide comprehensive overviews that are beyond the scope of this article.
SUMMARY POINTS
In 2006 the American Heart Association and the American College of Cardiology jointly provided the guidelines in grading aortic stenosis (box 1) as mild, moderate, and severe (figs 2 and 3) (see www.americanheart.org.)5
Recently, the European Society of Cardiology (ESC) has also published guidelines (a summary is at www.escardio.org).6 Aortic stenosis produces a systolic gradient between the left ventricular outflow tract and the aorta. Aortic sclerosis is distinguished from aortic stenosis by the valve thickening and calcification without obstruction (no significant gradient) (fig 1). However, 16% of patients with aortic sclerosis will progress to aortic stenosis in seven years time.7
Clinical diagnosis
The patient’s history and physical examination are essential in diagnosing aortic stenosis. Identifying symptoms such as exertional shortness of breath, angina, dizziness, or syncope is important for proper management. The characteristic systolic murmur guides further diagnostic investigations. An early peaking murmur is usually associated with a less stenotic valve, whereas a late peaking murmur has a more severe degree of stenosis. This is because a more stenotic valve takes longer for the ventricle to generate the pressures needed to force the blood past the lesion. Occasionally, the murmur may be faint and primary presentation may be heart failure of unknown cause. The disappearance of the second aortic sound is specific to severe aortic stenosis, although not a sensitive sign.7 The murmur of aortic stenosis is often “missed” (or not understood for what it is) in many patients, especially in those who are obese or have underlying obstructive lung diseases (where the murmur is muffled) and in those with left ventricular dysfunction (where the murmur is blunted).
BOX 1 GRADING OF AORTIC STENOSIS5
Mild stenosis
Moderate stenosis
Severe stenosis
Fig 1 Three dimensional transoesophageal echocardiographic image at the level of the tricuspid aortic valve, displayed from the perspective of the aortic root (looking into the left ventricular cavity) in a patient with a widely patent trileaflet aortic valve (left panel shows diastole, right panel shows systole)
Fig 2 Pulsed wave Doppler echocardiogram in patient with severe aortic stenosis: transthoracic, two dimensional, apical, five chamber view (inset). A pulsed wave Doppler region of interest (sample volume) is placed proximal to the stenotic aortic valve in the left ventricular outflow tract, and the spectral display is shown. At 1.0 m/s, the blood flow velocity in the left ventricular outflow tract is equivalent to a gradient of 4 mm Hg
Radiological diagnosis
Echocardiography has become the key diagnostic tool to confirm the presence of aortic stenosis; assess the degree of valve calcification, left ventricular function, and wall thickness; detect the presence of other associated valve disease; and provide prognostic information. Doppler echocardiography is the preferred technique for assessing severity. Aortic stenosis with a valve area <1.0 cm2 is considered severe; however, when patients have unusually small or large body surface area, a cut-off value of 0.6 cm2/m2 is helpful.8
The process of maintaining cardiac output against the aortic stenosis gradient leads to left ventricular hypertrophy. Increased muscle mass of the left ventricle raises myocardial oxygen consumption. In severe aortic stenosis, even in the absence of narrowing of the coronary arteries, the increased stress on the left ventricular wall and workload demands, coupled with direct ventricular pressure compressing the coronary arteries during diastolic flow, may exceed adequate coronary perfusion pressure and cause myocardial ischaemia and angina. Left ventricular diastolic dysfunction is widespread, and left ventricular systolic dysfunction is not uncommon; both these conditions produce symptoms of congestive cardiac failure.
After the onset of symptoms, the average survival is only two to three years. On the basis of the data obtained at postmortem examination in patients not treated surgically, the average time to death after the onset of various symptoms was as follows: angina, three years; syncope, three years; dyspnoea, two years; and congestive cardiac failure, one and a half to two years. Conversely, asymptomatic patients even with severe aortic stenosis have an excellent prognosis without aortic valve replacement. However, the duration of the asymptomatic phase varies widely among individuals. Unfortunately, at least 1-2% of asymptomatic patients die suddenly or have very rapid rate of progression to symptomatic stage and then to sudden death.9 Among patients with congenital or degenerative disease, progression to valve replacement occurs earliest if the patient has a unicuspid valve, later in the case of a bicuspid valve, and latest with a tricuspid valve.
When symptoms develop, mortality rises sharply, so standard therapeutic guidelines recommend surgery.5, 6 No effective drug treatment exists for severe aortic stenosis, and only a few drugs are available to alleviate symptoms. Patients with evidence of pulmonary congestion can benefit from cautious treatment with digitalis or diuretics, or both. A recent observational, drug withdrawal, single blinded study, with randomisation of the order of tests supports the concept that angiotensin converting enzyme inhibitors are safe and may provide short term benefit to patients with aortic stenosis.10 In patients with aortic stenosis, the afterload reduction caused by angiotensin converting enzyme inhibitors is partially blunted by a parallel increase in the transvalvular pressure gradient. However, angiotensin converting enzyme inhibitors favourably affect stress haemodynamic variables in most hypertensive patients with aortic stenosis. A prospective, single blinded study conducted at Cleveland clinic, Ohio, showed that in patients with acute pulmonary oedema, left ventricular systolic dysfunction, and aortic stenosis nitroprusside infusion may help to reduce congestion and improve symptoms.11 Atrial fibrillation has an adverse effect on atrial pump function and ventricular rate, hence prompt cardioversion is beneficial. Endocarditis prophylaxis is indicated in all patients with aortic stenosis.12
No medical treatment has been proved to prevent or delay the disease process in the aortic valve leaflets. The association of aortic stenosis with clinical features similar to atherosclerosis has led to the hypothesis that aggressive modification of risk factors, as for coronary heart disease, may slow or prevent disease progression in the valve leaflets. Despite this hope, recent reports using statins have shown mixed results: one study failed to show a beneficial effect,13 whereas another study showed that rosuvastatin can slow the haemodynamic progression of aortic stenosis.14
Fig 3 Continuous wave Doppler echocardiogram in patient with severe aortic stenosis (same patient as in figure 2). Transthoracic, two dimensional, apical, five chamber view (inset). A continuous wave Doppler records the maximal velocity across the narrowest point of the stenotic aortic valve and the spectral display is shown. The ratio of the velocity of the blood flow in the left ventricular outflow tract (1 m/s) to the aortic jet velocity (4.5 m/s) is <0.25, which is consistent with severe aortic stenosis
BOX 2 JOINT RECOMMENDATIONS OF AMERICAN HEART ASSOCIATION AND AMERICAN COLLEGE OF CARDIOLOGY FOR AORTIC VALVE REPLACEMENT IN PATIENTS WITH AORTIC STENOSIS 5
Aortic valve replacement indicated
Aortic valve replacement possibly indicated
Aortic stenosis is a mechanical obstruction, hence requires mechanical correction. Studies have shown that once symptoms develop, a patient’s life span is severely shortened unless the valve is replaced (fig 4). In contrast, age corrected 10 year survival rates among patients who had surgery for aortic valve replacement approach the survival rate in the normal population.16 Therefore, in the absence of any serious comorbid conditions, aortic valve replacement is indicated in virtually all symptomatic patients with severe aortic stenosis, even in very elderly people.5 Balloon valvuloplasty is not recommended in adults but can be used as a bridge to surgery in haemodynamically unstable patients who are at high risk of surgery or in patients with symptomatic severe aortic stenosis who require urgent, major non-cardiac surgery. 6
Fig 4 Kaplan-Meier survival curve for patients with severe symptomatic aortic stenosis who had valve replacement and similar patients who declined surgery. Adapted from Schwarz F et al15
BOX 3 RECOMMENDATIONS OF EUROPEAN SOCIETY OF CARDIOLOGY FOR FOLLOW-UP IN PATIENTS WITH AORTIC STENOSIS 6
Most patients aged >40-45 years require coronary angiography before aortic valve replacement to exclude coexistent coronary artery disease. Grading or reconfirmation of aortic stenosis is also possible during this procedure if the diagnosis remains uncertain after echocardiography. About 40% of patients having aortic valve replacement have severe coronary artery disease and require concurrent coronary bypass grafting. Preliminary reports show that percutaneous aortic valve replacement is feasible, but this procedure is not often done yet and further studies are needed to evaluate its potential role.17 Asymptomatic patients with severe aortic stenosis generally have an excellent prognosis without aortic valve replacement. In patients with left ventricular dysfunction and severe aortic stenosis, the outcome after replacement surgery is excellent despite the presence of a reduced ejection fraction preoperatively.18 Excessive afterload may contribute to the left ventricular dysfunction, which often returns to normal once obstruction is relieved.
A prospective Swedish study and an observational study show that aortic valve replacement improves symptoms and survival in patients with severe aortic stenosis.16, 18 Age is not a contraindication to surgery, with studies showing similar outcomes to those in age matched normal subjects in very elderly people. The operative risks can be estimated with readily available and a well validated online risk calculator from the European System for Cardiac Operative Risk Evaluation (www.euroscore.org).19 Indications for aortic valve replacement (fig 5) are given in the guidelines of the American Heart Association and the American College of Cardiology (box 2)5 and of the European Society of Cardiology.6 Doppler echocardiography should be done for the initial evaluation of patients suspected of having aortic stenosis, as well as in patients with established disease if symptoms develop or physical signs change. Box 3 outlines the European Society of Cardiology’s recommendations for follow-up in patients with aortic stenosis.
Fig 5 Proposed algorithm of treatment of aortic stenosis based on 2006 guidelines of American Heart Association and American College of Cardiology for management of patients with valvular heart disease
TIPS FOR NON-SPECIALISTS
ADDITIONAL EDUCATIONAL RESOURCES
UNANSWERED RESEARCH QUESTIONS
ONGOING RESEARCH
Some of the many trials currently testing the effects of statins in aortic valve disease are listed below.
BOX 4 PREDICTORS OF PROGRESSION OF AORTIC STENOSIS 6
Clinical
Echocardiography
Exercise testing
The rate of progression of aortic stenosis in an individual patient cannot be predicted but is reportedly more rapid in patients with degenerative calcific disease than in those with congenital or rheumatic disease. Some studies suggest that the rate of haemodynamic progression is faster when the patient is aged over 50 years and has severe calcification or concurrent coronary heart disease.20 Preliminary studies have shown that natriuretic peptides predict symptom-free survival in aortic stenosis.21 Box 4 summarises the predictors of the progression of aortic stenosis and therefore of poor outcome in asymptomatic patients.6
The presence of low cardiac output may lead clinicians to an incorrect assessment of the severity of the aortic stenosis. Patients with low cardiac output usually have small aortic valve areas (suggesting severe aortic stenosis) but also low aortic valve gradients (suggesting a mild or moderate condition). This discrepancy can be distinguished by recalculating the valve area after increasing cardiac contractility with inotropic stimulation (usually dobutamine). Truly severe aortic stenosis shows only small changes in valve area (increase <0.2 cm2) with increasing flow rate but a substantialincrease in gradients (mean gradient >50 mm Hg). “Pseudosevere” aortic stenosis, however, shows a marked increase in valve area but only minor changes in gradients.22 Patients with true severe aortic stenosis benefit from aortic valve replacement, but those with pseudosevere aortic stenosis would not benefit and could be harmed. Decreased contractile response (<20% of stroke volume) to inotropic infusion indicates a very poor clinical outcome and high mortality.
Clinicians should aim to diagnose aortic stenosis early in the physical examination, to document the severity with echocardiography while the patient is apparently asymptomatic, and try to predict whether the patient has the highest likelihood of developing symptoms. Elective surgery should be planned at the earliest onset of symptoms and requires careful clinical observation. When the history is unclear or the patient is sedentary, carefully supervised exercise tests should be done to identify the early onset of cardinal symptoms. As explained earlier, age is not a contraindication to aortic valve replacement.
Differences between the European and the US guidelines*
*The guidelines of the European Society of Cardiology, and the joint guidelines of the American Heart Association and American
College of Cardiology.
Contributors: Both authors conceived and designed the article. RR did the literature search and wrote the article. VLS revised the article critically for important intellectual content and also added important figures. Parkavi Chellappa helped to revise the article and suggested modifications for the article. Both authors approved the final version of the manuscript. RR is the guarantor.
Funding: No specific funding.
Competing interests: None declared.
Provenance and peer review: Not commissioned; externally peer reviewed.
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