European Heart Journal Advance Access originally published online on January 26, 2007
European Heart Journal 2007 28(2):230-268; doi:10.1093/eurheartj/ehl428
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Guidelines on the management of valvular heart disease
The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology
Authors/Task Force Members,
Paris, ( France)
Vienna ( Austria)
Leiden ( The Netherlands)
Cardiff ( UK)
Leiden ( The Netherlands)
Athens ( Greece)
Erlangen ( Germany)
Norwich ( UK)
Paris ( France)
Lodz ( Poland)
Paris ( France)
Barcelona ( Spain)
Milan ( Italy)
Leiden ( The Netherlands)
ESC Committee for Practice Guidelines (CPG),
Italy
France
Poland
UK
France
The Netherlands
Norway
Greece
France
Italy
Portugal
Germany
Spain
Spain
Document Reviewers,
Spain
Italy
Portugal
Spain
Germany
France
UK
USA
Belgium
Spain
UK
Austria
Portugal
Spain
* Corresponding author. Chairperson: Alec Vahanian, Service de Cardiologie, Hôpital Bichat AP-HP, 46 rue Henri Huchard, 75018 Paris, France. Tel: +33 1 40 25 67 60; fax: +33 1 40 25 67 32. E-mail address: alec.vahanian{at}bch.aphp.fr
 |
Preamble |
|---|
Top
Preamble
IntroductionGuidelines and Expert Consensus Documents aim to present management recommendations based on all of the relevant evidence on a particular subject in order to help physicians select the best possible management strategies for the individual patient suffering from a specific condition, taking into account the impact on outcome and also the risk–benefit ratio of a particular diagnostic or therapeutic procedure. Numerous studies have demonstrated that patient outcomes improve when guideline recommendations, based on the rigorous assessment of evidence-based research, are applied in clinical practice.
A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and also by other organizations or related societies. The profusion of documents can put at stake the authority and credibility of guidelines, particularly if discrepancies appear between different documents on the same issue, as this can lead to confusion in the minds of physicians. In order to avoid these pitfalls, the ESC and other organizations have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents. The ESC recommendations for guidelines production can be found on the ESC website.1 It is beyond the scope of this preamble to recall all but the basic rules.
In brief, the ESC appoints experts in the field to carry out a comprehensive review of the literature, with a view to making a critical evaluation of the use of diagnostic and therapeutic procedures and assessing the risk–benefit ratio of the therapies recommended for management and/or prevention of a given condition. Estimates of expected health outcomes are included, where data exist. The strength of evidence for or against particular procedures or treatments is weighed according to predefined scales for grading recommendations and levels of evidence, as outlined in what follows.
The Task Force members of the writing panels, as well as the document reviewers, are asked to provide disclosure statements of all relationships they may have which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC, and can be made available by written request to the ESC President. Any changes in conflict of interest that arise during the writing period must be notified to the ESC.
Guidelines and recommendations are presented in formats that are easy to interpret. They should help physicians make clinical decisions in their daily routine practice by describing the range of generally acceptable approaches to diagnosis and treatment. However, the ultimate judgement regarding the care of an individual patient must be made by the physician in charge of the patient care.
The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups, or consensus panels. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.
Once the document has been finalized and approved by all the experts involved in the Task Force, it is submitted to outside specialists for review. In some cases, the document can be presented to a panel of key opinion leaders in Europe, specialists in the relevant condition in question, for discussion and critical review. If necessary, the document is revised once more and finally approved by the CPG and selected members of the Board of the ESC and subsequently published.
After publication, dissemination of the message is of paramount importance. Publication of executive summaries and the production of pocket-sized and PDA-downloadable versions of the recommendations are helpful. However, surveys have shown that the intended end-users are often not aware of the existence of guidelines or simply do not put them into practice. Implementation programmes are thus necessary and form an important component of the dissemination of knowledge. Meetings are organized by the ESC and directed towards its member National Societies and key opinion leaders in Europe. Implementation meetings can also be undertaken at a national level, once the guidelines have been endorsed by the ESC member societies, and translated into the local language, when necessary.
All in all, the task of writing Guidelines or Expert Consensus Document covers not only the integration of the most recent research, but also the creation of educational tools, and implementation programmes for the recommendations. The loop between clinical research, writing of guidelines, and implementing them into clinical practice can then only be completed if surveys and registries are organized to verify that actual clinical practice is in keeping with what is recommended in the guidelines. Such surveys and registries also make it possible to check the impact of strict implementation of the guidelines on patient outcome.
|
Introduction |
|---|
Why do we need guidelines on valvular heart disease?
Although valvular heart disease (VHD) is less common in industrialized countries than coronary disease, heart failure, or hypertension, guidelines are of interest in this field for several reasons:
- VHD is common and often requires intervention
- Substantial advances have been made in the understanding of its pathophysiology
- In recent years, the patient population has changed. The continuous decline of acute rheumatic fever owing to better prophylaxis of streptococcus infections explains the decrease in the incidence of rheumatic valve disease, whereas increased life expectancy partially accounts for the increase in the incidence of degenerative valvular diseases in industrialized countries. The incidence of endocarditis remains stable and other causes of valve disease are rare.2,3 Because of the predominance of degenerative valve disease, the two most frequent valve diseases are now calcific aortic stenosis (AS) and mitral regurgitation (MR), whereas aortic regurgitation (AR) and mitral stenosis (MS) have become less common.3 Older age is associated with a higher frequency of comorbidity, which contributes to increased operative risk and renders decision-making for intervention more complex. Another important aspect of contemporary heart valve disease is the growing proportion of previously operated patients who present with further problems.3 Conversely, rheumatic valve disease still remains a major public health problem in developing countries, where it predominantly affects young adults.4 However, rheumatic heart disease is still present in industrialized countries owing to immigration and sequelae of rheumatic fever in older patients.
- Diagnosis is now dominated by echocardiography, which has become the standard to evaluate valve structure and function.
- Treatment has not only developed through the continuing progress in prosthetic valve technology, but has also been reoriented by the development of conservative surgical approaches and the introduction of percutaneous interventional techniques.
When compared with other heart diseases, there are few trials in the field of VHD, and randomized clinical trials are particularly scarce.
The same is true with guidelines: there is only one set of guidelines in the field of VHD in the USA5 and four national guidelines in Europe.6–9 Moreover, published guidelines are not always consistent due to the lack of randomized clinical trials as well as the constant evolution of practice. Finally, data from the recent Euro Heart Survey on VHD show that there is a real gap between the existing guidelines and their effective application.3
It is for this reason that the ESC has produced these guidelines, which are the first European guidelines on this topic.
Contents of these guidelines
The guidelines focus on VHD in adults and adolescents, are oriented towards management, and will not deal with endocarditis and congenital valve diseases in adults and adolescents, since recent guidelines have been produced by the ESC on these topics.10,11 Finally, these guidelines are not intended to include detailed information covered in ESC Guidelines on other topics, ESC Expert Consensus Documents, recommendations from the working group on VHD, and the specific sections of the ESC Textbook on Cardiology.12–15
How to use these guidelines
The committee emphasizes the fact that many factors ultimately determine the most appropriate treatment in individual patients within a given community. These factors include availability of diagnostic equipment, the expertise of interventional cardiologists and surgeons, especially in the field of conservative techniques, and, notably, the wishes of well-informed patients. Furthermore, owing to the lack of evidence-based data in the field of VHD, most recommendations are largely the result of expert consensus opinion. Therefore, deviations from these guidelines may be appropriate in certain clinical circumstances.
Method of review
A literature review was performed using Medline (PubMed) for peer-reviewed published literature focusing on the studies published within the last 10 years. The use of abstracts was avoided in these guidelines.
Definition of levels of recommendation
The Task Force has classified and ranked the usefulness or efficacy of the recommended procedures and/or treatments and the level of evidence as indicated in Table 1. The levels of recommendation were graded on the basis of the ESC recommendations.1 Unlike in the ACC/AHA levels of recommendation, class III (‘conditions for which there is evidence and/or general agreement that the procedure is not useful/effective and in some cases may be harmful’) is usually not used in the ESC guidelines.
|
|
General comments |
|---|
The aims of the evaluation of patients with VHD are to diagnose, quantify, and assess the mechanism of VHD as well as its consequences. The consistency between the results of investigations and clinical findings should be checked at each step. Indications for interventions rely mainly on the comparative assessment of spontaneous prognosis and the results of intervention according to the characteristics of VHD and comorbidities.
Patient evaluation
Diagnosis and evaluation of the severity of VHD should be based on the combined analysis of clinical findings and the results of investigations.
Clinical evaluation
The aim of analysing case history is to assess present and past symptoms, as well as looking for associated comorbidity. The patient is questioned on her/his lifestyle to detect progressive changes in the daily activity in order to limit the subjectivity of symptom analysis, in particular, in the elderly.13 Questioning the patient is also important to check the quality of follow-up, the effectiveness of prophylaxis of endocarditis and, where applicable, of rheumatic fever. In patients receiving chronic anticoagulant therapy, it is necessary to assess the stability of anticoagulation and look for thrombo-embolism or bleeding.
Clinical examination plays a major role in the detection of VHD in asymptomatic patients. It is the first step in the diagnosis of VHD and the assessment of its severity. In patients with a heart valve prosthesis, it is necessary to be aware of any change in murmur or prosthetic sounds.
An electrocardiogram and chest X-ray are usually carried out alongside clinical examination. Besides cardiac enlargement, analysis of pulmonary vascularization on the chest X-ray is useful when interpreting dyspnoea or clinical signs of heart failure.16
Echocardiography
In addition to clinical findings, echocardiography is the key technique to confirm the diagnosis of VHD, as well as to assess its severity and prognosis. It is indicated in any patient with a murmur when valve disease is suspected, the only possible exception being young patients who only have a trivial (grade 1/6) mid-systolic murmur.
The evaluation of the severity of stenotic VHD should combine the assessment of valve area and flow-dependent indices such as mean gradient and/or maximal flow velocity.17 Flow-dependent indices such as mean gradient or maximal flow velocity add further information and have a prognostic value.18
The assessment of valvular regurgitation should combine different indices including quantitative Doppler echocardiography, such as the effective regurgitant orifice area (ERO), which is less dependent on flow conditions than colour Doppler jet size.19 However, all quantitative evaluations, such as the continuity equation or flow convergence, have limitations. In particular, they combine a number of measurements and are highly sensitive to errors of measurement; therefore, their use requires experience.
Thus, when assessing the severity of VHD, it is necessary to check consistency between the different echocardiographic measurements as well as with the anatomy and mechanisms of VHD. It is also necessary to check their consistency with clinical assessment. In Table 2, this is illustrated as it applies to the quantification of severe regurgitation.
|
Echocardiography should include a comprehensive evaluation of all valves, looking for associated valve diseases and that of the ascending aorta.
Indices of left ventricular (LV) enlargement and function are strong prognostic factors in AR and MR and, thus, play an important role in decision-making. It is also important to index LV dimensions to body surface area (BSA) to take into account patient's body size. However, the validity of indexed values is uncertain for extreme body size.
Transoesophageal echocardiography (TEE) should be considered when transthoracic examination is of suboptimal quality or when thrombosis, prosthetic dysfunction, or endocarditis is suspected. It should be performed intraoperatively to monitor the results of valve repair or complex procedures.
Three-dimensional echocardiography is a promising technique, particularly for the evaluation of valve anatomy. However, its incremental usefulness in decision-making has not been validated so far.
Fluoroscopy
Fluoroscopy can be used to assess annular or valvular calcification, which enables calcification to be distinguished from fibrosis with a higher specificity than echocardiography. Fluoroscopy is also useful to assess the kinetics of the mobile part of a mechanical prosthesis.
Radionuclide angiography
Radionuclide angiography provides a reproducible evaluation of LV ejection fraction (EF) in patients in sinus rhythm. This aids decision-making in asymptomatic patients with valvular regurgitation, in particular, when echocardiographic examination is of suboptimal quality.20
Stress testing
Exercise ECG
The primary purpose of exercise testing is to unmask the objective occurrence of symptoms in patients who claim to be asymptomatic. In truly asymptomatic patients, it has an additional value for risk stratification in AS.21,22 Exercise testing will also determine the level of authorized physical activity, including participation in sports.23
Exercise echocardiography
Promising recent reports suggest that the estimation of the prognosis of VHD and indications for intervention may be refined by measuring changes in gradients or degree of regurgitation on exercise.24,25 Echocardiography performed immediately after exercise has shown to be useful to assess the prognosis of degenerative MR.26 However, these preliminary findings need to be confirmed before this can be recommended in practice.
Other stress tests
Low-dose dobutamine stress echocardiography is useful in AS with impaired LV function.27 The use of stress tests to detect coronary artery disease associated with severe VHD is discouraged because of their low diagnostic value.
Other non-invasive imaging techniques
Computed tomography
Preliminary data show that computed tomography (CT) scanning enables valve calcification to be accurately quantified with good reproducibility. Valve calcification is linked to the severity of VHD and provides additional prognostic information.28 In expert centres, multislice CT can be useful to exclude coronary artery disease in patients who are at low risk of atherosclerosis.
Magnetic resonance imaging
At present, magnetic resonance imaging (MRI) is not indicated in VHD in routine clinical practice; however, most measurements usually acquired by Doppler echocardiography can also be acquired with MRI and thus MRI can be used as an alternative technique when echocardiography is not feasible. In particular, quantification of cardiac function, dimensions, and regurgitant volume is very accurate with MRI.29
Biomarkers
Natriuretic peptide serum level, in particular, of the B-type, has been shown to be related to functional class and prognosis, particularly in AS and MR.30,31 However, data regarding their incremental value in risk-stratification so far remain limited.
Coronary angiography
Coronary angiography is widely indicated to detect associated coronary artery disease when surgery is planned (Table 3). Knowledge of coronary anatomy improves risk-stratification and determines whether coronary revascularization is indicated in association with valvular surgery.
|
Coronary angiography can be omitted in young patients with no risk factors and in rare circumstances when its risk outweighs benefit, e.g. in acute aortic dissection, a large aortic vegetation in front of coronary ostia, or occlusive prosthetic thrombosis leading to an unstable haemodynamic condition.
Cardiac catheterization
The measurement of pressures and cardiac output, or the performance of ventricular angiography, is restricted to situations where non-invasive evaluation is inconclusive or discordant with clinical findings. Given its potential risks, cardiac catheterization to assess haemodynamics should not be systematically associated with coronary angiography, although this remains common in current practice.3,32
Assessment of comorbidity
The choice of specific examinations to assess comorbidity is directed by the clinical evaluation. The most frequently encountered are peripheral atherosclerosis, renal failure, and chronic obstructive pulmonary disease.3
Endocarditis prophylaxis
Endocarditis prophylaxis should be considered in any patient with VHD and adapted to the individual patient risk.10
Risk stratification
The Euro Heart Survey has shown that, in current practice, there is general agreement between the decision to operate and the existing guidelines in asymptomatic patients. However, in patients with severe symptoms, intervention is underused for reasons that are often unjustified.3,33 This stresses the importance of the widespread use of careful risk stratification.
In the absence of evidence from randomized clinical trials, the decision to intervene in a patient with VHD relies on an individual risk–benefit analysis, suggesting that improvement of prognosis compared with natural history outweighs the risk of intervention and its potential late consequences, in particular, prosthesis-related complications.
The evaluation of the prognosis of VHD depends on the type of VHD and is derived from studies on natural history, which are frequently old and not always applicable to current presentations of VHD. Only a few contemporary studies enable spontaneous prognosis to be assessed according to patient characteristics.34
Factors predicting operative mortality have been identified from large series of patients undergoing cardiac surgery or, more specifically, heart valve surgery.35–39 They are related to heart disease, the patient's age, comorbidity, and the type of surgery. The easiest way to integrate the weight of the different predictable factors is to combine them in multivariate scores, enabling operative mortality to be estimated. The Euroscore (Table 4) is widely used in this setting. Although it has been elaborated for cardiac surgery in general, it has been validated in valvular surgery.35,39 One recent analysis of a database from the UK led to a simple scoring system, which has been specifically elaborated and validated in patients operated on for VHD.37 However, no scoring systems enable the spontaneous outcome to be assessed.
|
Despite limitations and the need for further validation, the use of these scores reduces the subjectivity of the evaluation of the operative risk and, thus, of the risk–benefit ratio. Of course, this is only one of the elements in decision-making, which should also take into account the patient's life expectancy, quality of life, wishes, as well as local resources, in particular, the availability of valve repair and surgical outcome in the specified centre. Finally, very importantly, the decision to intervene should take into account the decision of the patient and the relatives after they have been thoroughly informed of the risks and benefits of the different therapeutic possibilities.
|
Aortic regurgitation |
|---|
Introduction
AR may be the consequence of diverse aetiologies, the distribution of which has changed over time. The most frequent causes of AR are now those related to aortic root disease and bicuspid aortic valve. The inherent consequence is the frequent involvement of the ascending aorta2,3 which may need surgical treatment.
Evaluation
Initial examination should include a detailed clinical evaluation. AR is diagnosed by the presence of a diastolic murmur. Exaggerated arterial pulsations and low diastolic pressure represent the first and main clinical signs for quantifying AR.15 Peripheral signs are attenuated in acute AR, which contrasts with a poor functional tolerance.
The general principles for the use of invasive and non-invasive investigations follow the recommendations made in the General comments section.
Specific issues in AR are as follows:
Echocardiography is the key examination, its aim being to:
- Diagnose and quantify the severity of AR, using colour Doppler (extension or, better, width of regurgitant jet) and continuous-wave Doppler (rate of decline of aortic regurgitant flow and holodiastolic flow reversal in the descending aorta). All these indices are influenced by loading conditions and the compliance of the ascending aorta and the LV. Quantitative Doppler echocardiography, using the continuity equation or analysis of proximal isovelocity surface area, is less sensitive to loading conditions. The criteria for defining severe AR are described in Table 2.19 The evaluation of severity, using quantitative measurements, is less well established than in MR, and consequently, the results of quantitative measurements should be integrated with other data to come to a final conclusion as regards severity.
- Assess the mechanisms of regurgitation, describe the valve anatomy, and determine the feasibility of valve repair.
- Image the aorta at four different levels: annulus, sinuses of Valsalva, sino-tubular junction, and ascending aorta.40 Indexing for BSA could be recommended, especially in patients of small body size and women.41
- Evaluate LV function. LV dimensions should also be indexed as described earlier.42
TEE may be performed to better define the anatomy of the valve and ascending aorta, especially when valve-sparing intervention is considered.
At the present time, clinical decisions should not be based on changes in EF on exercise, nor on data from stress echocardiography because these indices, although potentially interesting, have not been adequately validated.
When available, MRI can be used to assess the severity of regurgitation and LV function, particularly when echocardiographic images are of poor quality.
MRI or CT scanning, according to availability and expertise, is recommended for the evaluation of the aorta in patients with an enlarged aorta as detected by echocardiography, especially in cases of bicuspid valves or Marfan's syndrome.
Natural history
Patients with acute AR have a poor prognosis without intervention owing to the significant increase in diastolic LV pressure, leading to poor haemodynamic tolerance. There is little information in the literature on the progression from mild to severe AR. Patients with severe AR and symptoms have a poor prognosis.43
In asymptomatic patients with severe AR and normal LV function, the number of events during follow-up is low: development of asymptomatic LV dysfunction, < 1.3% per year; sudden death, < 0.2% per year; and symptoms, LV impairment, or death, 4.3% per year. Age, end-systolic diameter or volume, and EF at rest are predictors of outcome. On multivariate analysis, age and end-systolic diameter, when it is > 50 mm, predict a poor outcome.43–46 Recent data suggest that it could be more appropriate to use thresholds related to BSA and the proposed value is an end-systolic diameter > 25 mm/m2 BSA.42
The natural history of aortic root aneurysm has been mainly studied in patients with Marfan's syndrome. The strongest predictors of complication are the diameter of the aortic root at the level of the sinuses of Valsalva and the presence of a family history of cardiovascular events (aortic dissection, sudden cardiac death).40,47–49 When the aorta has reached 6 cm in size, yearly rates of rupture, dissection, and death are, respectively, 3.6, 3.7, and 10.8%. There is a rising incidence of dissection or rupture with the increase in aneurysm size.47–49 Recent data using indexed values show a 4, 8, and > 20% risk of complications, respectively, when the measurements are 2.75, 2.75–4.24, and > 4.25 cm/m2.41 Patients with bicuspid valves50 may also present a rapid progression rate. Less information is available for other aetiologies such as annulo-aortic ectasia.
Results of surgery
Surgical treatment of AR is aortic valve replacement when there is no associated aortic aneurysm. When an aneurysm of the aortic root is associated, surgery also comprises replacement of the ascending aorta with re-implantation of the coronary arteries, combined with either replacement of the valve or valve-sparing techniques. In current practice, valve replacement remains the standard and the other procedures are performed in only a small percentage of patients. Supra-coronary replacement of ascending aorta can be performed when Valsalva sinuses are preserved.
Operative mortality is low (1–3%)3,43,51,52 (Table 5) in asymptomatic patients submitted to isolated aortic valve surgery. In symptomatic patients, in patients with combined aortic valve and root surgery, and in patients with concomitant coronary artery bypass grafting (CABG), operative mortality ranges from 3 to 7%. The strongest preoperative predictors of heart failure or death after surgery are age, preoperative functional class, resting EF < 50% or shortening fraction < 25%, and LV end-systolic diameter > 55 mm.43–45,53–56
|
Immediate and late results of the replacement of the ascending aorta, using a composite graft, are excellent in Marfan's syndrome when performed by experienced teams on an elective basis.40,57 Data on conservative surgery are more limited and come from expert centres. In such settings, recent series have reported an operative mortality of 1.6%, 10 year survival of 88%, freedom from aortic valve replacement of 99%, and freedom from at least moderate AR of 83%.58,59
Indications for surgery
In symptomatic acute AR, urgent intervention is indicated. In chronic AR, the goals of the operation are to improve outcome, to diminish symptoms, to prevent the development of postoperative heart failure and cardiac death, and to avoid aortic complications in patients who present with aortic aneurysm.46,60
On the basis of robust observational evidence, recommended surgical indications are as follows (Table 6, Figure 1):
|
|
Symptom onset is an indication for surgery. Surgery should not be denied in symptomatic patients with LV dysfunction or marked LV dilatation after careful exclusion of other possible causes. Although in these patients postoperative outcome is worse than in patients operated at an earlier stage, acceptable operative mortality, improvement of clinical symptoms, and acceptable long-term survival can be obtained.53,56
Surgery should also be considered in asymptomatic patients with severe AR and impaired LV function at rest [resting EF 
50% and/or LV end-diastolic diameter > 70 mm and/or end-systolic diameter > 50 mm (or > 25 mm/m2 BSA)] since the likelihood of early development of symptoms is high, perioperative mortality low, and postoperative results excellent. A rapid increase in ventricular parameters on serial testing is another reason to consider surgery. Good-quality echocardiograms and data confirmation with repeated measurements are strongly recommended before surgery in asymptomatic patients.
The rationale for an aggressive approach in patients with mild AR and aortic dilatation is better defined in patients with Marfan's syndrome than in patients with bicuspid valves, and even more so in annulo-aortic ectasia. In borderline cases, the decision to replace the ascending aorta also relies on perioperative surgical findings as regards the thickness of the aortic wall and the status of the rest of the aorta.
Aortic root dilatation 
55 mm should be a surgical indication, irrespective of the degree of AR. In cases of Marfan's syndrome or bicuspid aortic valves, even lower degrees of root dilatation (45 and 50 mm, respectively) have been proposed as indications for surgery, especially when there is a rapid increase of aortic diameter between serial measurements (5 mm per year) or family history of aortic dissection.48,49
For patients who have an indication for surgery on the aortic valve, lower thresholds can be used for combining surgery on the ascending aorta. Lower thresholds of aortic diameters can also be considered for indicating surgery if valve repair can be performed by experienced surgeons.
The choice of the surgical technique is adapted according to the following factors: associated root aneurysm, characteristics of leaflets, underlying pathology, life expectancy, and desired anticoagulation status.
Medical therapy
Nitroprusside and inotropic agents (dopamine or dobutamine) may be used before surgery in patients with poorly tolerated acute AR to stabilize their clinical condition. In patients with chronic severe AR and heart failure, ACE-inhibitors are the treatment of choice when surgery is contraindicated or in cases with persistent postoperative LV dysfunction.
In asymptomatic patients with high blood pressure, the indication for anti-hypertensive treatment with vasodilators such as ACE-inhibitors or dihydropyridine calcium channel blockers is warranted.
The role of vasodilators in the asymptomatic patients without high blood pressure in order to delay surgery is unproved.61,62
In patients with Marfan's syndrome, beta-blockers slow the progression of the aortic dilatation63 and should also be given after operation. In patients with severe AR, the use of beta-blockers should be very cautious because the lengthening of diastole increases the regurgitant volume. However, they can be used in patients with severe LV dysfunction. Recently, enalapril has also been used to delay aortic dilatation64 in patients with Marfan's syndrome. Whether the same beneficial effect occurs in patients with bicuspid aortic valves is not known.
Patients with AR should be educated on endocarditis prevention and antibiotic prophylaxis.10
In patients with Marfan's syndrome or in young patients with aortic root aneurysm, the family needs to be screened to detect asymptomatic cases.
Serial testing
Patients with mild-to-moderate AR can be seen on a yearly basis and echocardiography performed every 2 years.
All patients with severe AR and normal LV function should be seen for follow-up at 6 months after their initial examination. If LV diameter and/or EF show significant changes, or they become close to the thresholds for intervention, follow-up should continue at 6 month intervals. When parameters are stable, follow-up can be yearly.
In patients with a dilated aortic root, and especially in patients with Marfan's syndrome or with bicuspid aortic valves, examination of the aorta should be performed on a yearly basis, but with closer intervals if aortic enlargement is detected.
Special patient populations
In patients with moderate AR who undergo CABG or mitral valve surgery, the decision to replace the aortic valve should be individualized according to aetiology of AR, age, disease progression, and possibility of valve repair. Concurrent aortic valve replacement is more frequently considered when mitral surgery is prosthetic valve replacement than when it is mitral valve repair.
If AR requiring surgery is associated with severe MR, then both should be operated on. Usually the aortic valve will require replacement and the operation required on the mitral valve will depend on the chances of successful repair. Clearly, if the chances are low and the patient is likely to require anticoagulants because of the aortic surgery, then mitral valve replacement is likely to be preferable. If the associated MR does not demand immediate surgery, the decision is more difficult and needs to be individualized, but if the regurgitation is organic and repair is likely, then concurrent mitral valve surgery is attractive. There will, however, be occasions when the patient's clinical condition mandates the quickest and most simple procedure.
|
Aortic stenosis |
|---|
Introduction
AS has become the most frequent type of VHD in Europe and North America. It primarily presents as calcific AS in adults of advanced age (2–7% of the population > 65 years).2,3,65,66 The second most frequent aetiology, which dominates in the younger age group, is congenital, whereas rheumatic AS has become rare.
Evaluation
Patient history and physical examination remain essential. Careful exploration for the presence of symptoms (exertional shortness of breath, angina, dizziness, or syncope) is critical for proper patient management and must take into account that patients may deny symptoms because they significantly reduce their activities.
The characteristic systolic murmur draws the attention and guides the further diagnostic work in the right direction. Occasionally, the murmur may, however, be faint and primary presentation may be heart failure of unknown cause. The disappearance of the second aortic sound is specific to severe AS, although not a sensitive sign.15
The general principles for the use of invasive and non-invasive investigations follow the recommendations made in the General comments section.
Specific issues that need to be addressed in AS are as follows:
Echocardiography has become the key diagnostic tool. It confirms the presence of AS, assesses the degree of valve calcification, LV function and wall thickness, detects the presence of other associated valve disease, and finally provides prognostic information.
Doppler echocardiography is the preferred technique to assess severity.17 Transvalvular pressure gradients are flow dependent and measurement of valve area represents, from a theoretical point of view, the ideal way to quantify AS.
Nevertheless, it has to be emphasized that valve area measurements also have their potential inaccuracies and are less robust than gradient estimates in clinical practice. Thus, valve area alone with absolute cut-off points cannot be relied upon for clinical decision-making and it should be considered in combination with flow rate, pressure gradient and ventricular function, as well as functional status. AS with a valve area < 1.0 cm2 is considered severe; however, indexing to BSA, with a cut-off value of 0.6 cm2/m2 BSA is helpful, in particular in patients with either unusually small or large BSA.
Severe AS is unlikely if cardiac output is normal, and there is a mean pressure gradient < 50 mmHg. In the presence of low flow, usually due to depressed LV function, low pressure gradients may be encountered in patients with severe AS. As soon as mean gradient is < 40 mmHg, even a small valve area does not definitely confirm severe AS since mild-to-moderately diseased valves may not open fully, resulting in a ‘functionally small valve area’ (pseudosevere AS).67
Stress echocardiography using low-dose dobutamine may be helpful in this setting to distinguish truly severe AS from the rare cases of pseudosevere AS.27 Truly severe AS shows only small changes in valve area (increase < 0.2 cm2) with increasing flow rate but significant increase in gradients (maximum value of mean gradient > 50 mmHg), whereas pseudosevere AS shows marked increase in valve area but only minor changes in gradients.27,68 In addition, this test may detect the presence of contractile reserve (increase > 20% of stroke volume during low-dose dobutamine test), which has prognostic implications.27,68
Exercise stress echocardiography has been proposed for risk stratification in asymptomatic severe AS25 but more data are necessary to determine its role.
Echocardiographic evaluation will identify coexistent valvular lesions including mitral annular calcification in degenerative disease and rheumatic mitral valve disease, as well as asymmetric dynamic subvalvular obstruction especially in elderly women.
TEE is rarely needed; however, it may provide images that are good enough to allow valve planimetry and this is useful when transthoracic visualization is poor and leaflets only moderately calcified. TEE will also provide additional evaluation of other mitral valve abnormalities.
Exercise testing is contraindicated in symptomatic patients with AS but is useful for unmasking symptoms and in the risk stratification of asymptomatic patients with severe AS.21,22 In such cases, it is safe, provided it is performed under the supervision of an experienced physician, with symptoms, changes in blood pressure, and ECG closely monitored. In current practice, stress tests are under-used in patients with asymptomatic AS.3
CT and MRI could improve assessment of the ascending aorta, if required. Preliminary data suggest that multislice CT may be useful in quantifying valve calcification, which aids in assessing prognosis,28 as well as in measuring valve area.69 However, more data are required to determine the full role of multislice CT.
Natriuretic peptides have been shown in preliminary studies to predict symptom-free survival in AS.30 However, more data are required before recommending their serial measurement to identify optimal timing of surgery.
Retrograde LV catheterization to assess the severity of AS is seldom needed and should only be used with caution, as it is not without risk.32
Natural history
Calcific AS is a chronic progressive disease. During a long latent period, patients remain asymptomatic.70–72 However, it should be emphasized that duration of the asymptomatic phase varies widely among individuals. Sudden cardiac death is a frequent cause of death in symptomatic patients but appears to be rare in the asymptomatic (1% per year).70–72 Reported average symptom-free survival at 2 years ranges from 20 to more than 50%.21,22,70–72 The lower numbers must be viewed with caution since some patients in these studies underwent surgery without symptoms. Finally, it has been speculated that myocardial fibrosis and severe LV hypertrophy, which may not be reversible after delayed surgery, could preclude an optimal postoperative long-term outcome. However, there are, so far, no data to confirm this hypothesis.
Predictors of the progression of AS and, therefore, of poor outcome in asymptomatic patients have recently been identified. They are:
- Clinical: older age, presence of atherosclerotic risk factors65,66
- Echocardiography: valve calcification, peak aortic jet velocity, LVEF,71,72 haemodynamic progression,71 and increase in gradient with exercise.25 The combination of a markedly calcified valve with a rapid increase in velocity of 0.3 m/s within 1 year has been shown to identify a high-risk group of patients (
80% death or requirement of surgery within 2 years71).
- Exercise testing: symptom development on exercise testing in physically active patients, particularly those younger than 70 years, predicts a very high likelihood of symptom development within 12 months. Recent data demonstrates a lower positive predictive value for abnormal blood pressure response, and even more so for ST-segment depression, than symptoms for poor outcome.22
As soon as symptoms occur, the prognosis is dismal and mortality has been reported to be quite significant even within months of symptom onset,73 which is often not promptly reported by patients.
Results of intervention
Aortic valve replacement is the definitive therapy for severe AS. In contemporary series, operative mortality of isolated aortic valve replacement is 3–5% in patients below 70 years and 5–15% in older adults (Table 5).3,51,52 The following factors increase the risk of operative mortality: older age, associated comorbidities, female gender, higher functional class, emergency operation, LV dysfunction, pulmonary hypertension, coexisting coronary disease, and previous bypass or valve surgery. After successful valve replacement, long-term survival rates are close to those expected in the control population, symptoms are less marked, and quality of life is greatly improved.74 Risk factors for late death include age, comorbidities, severe functional condition, LV dysfunction, ventricular arrhythmias, and untreated coexisting coronary artery disease. In addition, poor postoperative outcome may result from prosthesis-related complications and sub-optimal prosthetic valve haemodynamic performance.75
Balloon valvuloplasty plays an important role in the paediatric population but a very limited role in adults because its efficacy is low, complication rate is high (>10%), and restenosis and clinical deterioration occur within 6–12 months in most patients, resulting in a mid-term and long-term outcome similar to natural history.76 Preliminary reports show that percutaneous aortic valve replacement is feasible, but this procedure is at an early stage and further studies are needed to evaluate its potential role.77
Indications for surgery
Surgical indications are as follows (Table 7, Figure 2):
|
|
Early valve replacement should be strongly recommended in all symptomatic patients with severe AS who are otherwise candidates for surgery. As long as mean gradient is still > 40 mmHg, there is virtually no lower EF limit for surgery.
On the other hand, the management of patients with low-flow, low-gradient AS (severely reduced EF and mean gradient < 40 mmHg) is more controversial. The depressed EF in many patients in this group is predominantly caused by excessive afterload (afterload mismatch), and LV function usually improves after surgery.78,79 Conversely, secondary improvement in LV function is uncertain if the primary cause is scarring due to extensive myocardial infarction. In patients with low gradient and with evidence of contractile reserve, surgery is advised since it carries an acceptable risk and improves long-term outcome in most patients. Conversely, the outcome of patients without contractile reserve is compromised by a high operative mortality despite a trend towards better survival after surgery.27 Surgery can, nonetheless, be performed in these patients but decision-making should take into account clinical condition (in particular, the presence of comorbidity), degree of valve calcification, extent of coronary disease, and feasibility of revascularization.
Management of asymptomatic patients with severe AS remains a matter of controversy.5,13,80 The decision to operate on the asymptomatic patients requires careful weighing of benefits against risks. Early elective surgery, at the asymptomatic stage, can only be recommended in selected patients, at low operative risk. This could be the case in:
- The rare asymptomatic patients with depressed LV function not due to another cause
- Those with echocardiographic predictors of poor outcome suggested by the combination of a markedly calcified valve with a rapid increase in peak aortic velocity of 0.3 m/s per year.
- If the exercise test is abnormal, particularly if it shows symptom development, which is a strong indication for surgery in physically active patients.
- However, on the other hand, breathlessness on exercise may be difficult to interpret in patients with only low physical activity, particularly the elderly, making decision-making more difficult. There is no strict age limit for performance of exercise testing and it is reasonable to propose it in patients > 70 who are still highly active.
Indications for balloon valvuloplasty
This intervention can be considered as a bridge to surgery in haemodynamically unstable patients who are at high risk for surgery (Recommendation Class IIb, Level of evidence C) or in patients with symptomatic severe AS who require urgent major non-cardiac surgery (Recommendation Class IIb Level of evidence C). Occasionally, balloon valvuloplasty could be considered as a palliative measure in individual cases when surgery is contraindicated because of severe comorbidities.
Medical therapy
The progression of degenerative AS is an active process sharing a number of similarities with atherosclerosis.81 Thus, modification of atherosclerotic risk factors must be strongly recommended following the guidelines of secondary prevention in atherosclerosis.
Although several retrospective reports have shown beneficial effects of statins82,83 and ACE-inhibitors,84 data are still conflicting and the only randomized trial assessing the effect of statin therapy is negative.85 It is, therefore, too early for treatment recommendations.
Symptomatic patients require early surgery, as no medical therapy for AS is able to delay the inevitability of surgery. However, patients who are unsuitable candidates for surgery may be treated with digitalis, diuretics, ACE-inhibitors, or angiotensin receptor blockers if they are experiencing heart failure. Beta-blockers should be avoided in these circumstances. In selected patients with pulmonary oedema, nitroprusside can be used under haemodynamic monitoring.
Co-existing hypertension should be treated; however, treatment should be carefully titrated to avoid hypotension and patients more frequently evaluated.
Maintenance of sinus rhythm is particularly important. Endocarditis prophylaxis is indicated in all patients with AS.10
Serial testing
The wide variability of the rate of progression of AS heightens the need for patients to be carefully educated about the importance of follow-up and reporting symptoms as soon as they develop. In the asymptomatic patient, stress tests should determine the recommended level of physical activity. Follow-up visits should include echocardiographic assessment since the rate of haemodynamic progression is important for management decisions. Type and interval of follow-up should be determined on the basis of the initial examination.
In cases of moderate-to-severe calcification of the valve and peak aortic jet velocity > 4 m/s at initial evaluation, patients should be re-evaluated every 6 months for the occurrence of symptoms and change in exercise tolerance or in echo-parameters. If peak aortic jet velocity has increased since the last visit (>0.3 m/s per year) or if other evidence of haemodynamic progression is present, surgery should be considered. If no change has occurred and the patient remains asymptomatic, six monthly clinical and six to 12 monthly clinical and echocardiographic re-evaluations are recommended.
In patients who do not meet these criteria, a clinical yearly follow-up is necessary, follow-up being closer in those with borderline values. The frequency of echocardiographic examinations should be adapted to clinical findings.
Special patient populations
In patients with severe AS and severe coronary disease, the performance of concomitant CABG provides a lower mortality rate than that observed in patients who do not undergo combined bypass surgery. However, combined surgery carries a higher risk than isolated valve replacement in patients without coronary disease. Thus, CABG should be combined whenever possible with valve surgery. On the other hand, aortic valve replacement is not necessary during CABG in patients with only mild AS.
Finally, although there are no prospective randomized trials, data from retrospective analysis indicate that patients with moderate AS (mean gradient in the presence of normal flow 30–50 mmHg, valve area 1.0–1.5 cm2) will in general benefit from valve replacement at the time of coronary surgery.86 However, individual judgement must be recommended considering BSA, individual haemodynamic data, life expectancy, expected progression rate of AS, expected outcome from associated disease (particularly comorbidity), and individual risk of valve replacement or eventual re-operation.
Patients with severe symptomatic AS and diffuse coronary artery disease, which cannot be revascularized, should not be denied aortic valve replacement, even though this is a high-risk group.
Recent studies have suggested the potential use of percutaneous coronary revascularization in place of bypass surgery in patients with AS.87 However, available data are not sufficient to currently recommend this approach, except for selected high-risk patients with acute coronary syndromes or in patients with non-severe AS.
AS is increasingly observed in octogenarians and even in nonagenarians who experience higher morbidity and operative mortality during aortic valve replacement. However, surgery can prolong and improve the quality of life.88 Even though valve replacement is the procedure of choice in this population, a large percentage of suitable candidates currently are, unfortunately, not referred for surgery.3,33 Age, per se, should not be considered a contraindication for surgery. Decisions should be made on an individual basis, taking into account patients’ wishes and cardiac and non-cardiac factors (see also General comments section). In this population, the need for an emergency operation, or at the other end of the clinical spectrum, very early intervention at an asymptomatic stage, should be avoided.
When MR is associated with AS, colour jet size and other Doppler findings may be increased by the high ventricular pressures. As long as there are no morphological abnormalities (flail or prolapse, post-rheumatic changes or signs of infective endocarditis), mitral annulus dilatation, or marked abnormalities of LV geometry, surgical intervention on the mitral valve is in general not necessary, and functional MR often resolves after the aortic valve is replaced.
Bicuspid valves are common in AS, and there is a clear relationship between the presence of bicuspid valves and abnormalities of the aortic root even in the absence of severe AS. Concomitant treatment of a dilated aorta is, therefore, recommended at the same thresholds as in AR.89
|
Mitral regurgitation |
|---|
MR is now the second most frequent valve disease after AS. The treatment has been re-orientated as a result of the good results of valve repair. This section deals with organic, ischaemic, and functional MR.
Organic mitral regurgitation
Organic MR covers all aetiologies in which leaflet abnormality is the primary cause of the disease, in opposition to ischaemic and functional MR, in which MR is the consequence of LV disease.
Reduced prevalence of rheumatic fever and increased life span in industrialized countries have progressively changed the distribution of aetiologies. Degenerative MR is the most common aetiology in Europe, whereas ischaemic and functional MR are increasingly frequent.3 Endocarditis is dealt with in separate specific ESC guidelines.10
Evaluation
Clinical examination usually provides the first clues that MR is present and may be significant as suggested by the intensity and duration of the systolic murmur and the presence of the third sound.15 The general principles for the use of invasive and non-invasive investigations follow the recommendations made in the General comments section.
The specific issues in MR are as follows:
Echocardiography is the principal examination and must include an assessment of severity, mechanisms and repairability, and, finally, consequences.
Several methods can be used to determine the severity of MR. Colour-flow mapping of the regurgitant jet is the easiest method but its accuracy is limited. The width of the vena contracta—the narrowest part of the jet—correlates with quantitative measurements of MR. The two quantitative methods of evaluating regurgitant volume and calculating ERO are useful in experienced hands.90,91 The criteria for defining severe organic MR are described in Table 2.
It should be emphasized again here that the assessment of severity should not rely entirely on one single parameter, but requires an approach integrating blood flow data from Doppler with morphologic information and careful cross-checking of the validity of such data against the consequences on LV and pulmonary pressures19 (Table 2).
In case of acute severe MR, physical examination and auscultation may be misleading, in particular, with a murmur of low intensity, and colour Doppler flow may underestimate the severity of the lesion. The presence of hyperdynamic function in acute heart failure suggests the presence of severe MR.
Transthoracic echocardiography provides precise anatomical definition of the different lesions, which must be related to the segmental and functional anatomy according to the Carpentier classification in order to subsequently assess the feasibility of repair.92
TEE is frequently carried out before surgery for this purpose,93 although transthoracic echocardiography, in experienced hands and when using recent imaging techniques, can be sufficient when images are of high quality.94 The results of mitral valve repair should be assessed intraoperatively by TEE to enable immediate further surgical correction if necessary.
The consequences of MR are assessed by measuring left atrial diameter, LV diameter and EF, and systolic pulmonary arterial pressure.
Evaluation of contractile reserve may be accomplished by exercise echocardiography, but the usefulness of this method for decision-making requires validation.26
Preliminary series have also suggested the value of elevated BNP levels as predictors of long-term outcome but this also remains to be validated.31
Natural history
Acute MR is poorly tolerated and carries a poor prognosis in the absence of intervention.
Our knowledge of the natural history of chronic MR has greatly improved due to recent observational studies.34,91,95,96
In asymptomatic MR, the estimated 5 year rates (±standard error) of death from any cause, death from cardiac causes, and cardiac events (death from cardiac causes, heart failure, or new AF) with medical management were 22 ± 3, 14 ± 3, and 33 ± 3%, respectively.91
In addition to symptoms, age, atrial fibrillation, degree of MR (particularly ERO), left atrial dilatation, LV dilatation, and low LVEF are all predictors of poor outcome.
In patients with chordal rupture, clinical condition may stabilize after an initial symptomatic period. However, it carries a poor spontaneous prognosis owing to subsequent development of pulmonary hypertension.
Results of surgery
Despite the absence of randomized comparison between the results of valve replacement and repair and the possible inherent biases resulting from this, it is widely accepted that valve repair, when feasible, is the optimal surgical treatment in patients with severe MR. When compared with valve replacement, repair has a lower perioperative mortality (Table 5), improved survival, better preservation of postoperative LV function, and lower long-term morbidity.97–101
Besides symptoms, the most important predictors of postoperative outcome after surgery for MR are age, AF, preoperative LV function, and the reparability of the valve.
The best results of surgery are observed in the patients with a preoperative LVEF > 60%. A preoperative end-systolic diameter < 45 mm (no indexed value has been validated in MR) is also closely correlated with a good postoperative prognosis.93,95–98 However, a value about which postoperative LV dysfunction will not occur has not been demonstrated, rendering prediction of the postoperative dysfunction difficult in the individual patient. In addition to the initial measurements, the temporal changes of LV function should also be taken into account when making decisions about surgery. Progressive development of pulmonary hypertension is also a marker for poor prognosis.
The probability of a durable valve repair is of crucial importance.102,103 Degenerative MR due to segmental valve prolapse can usually be repaired with a low risk of reoperation. The reparability of extensive prolapse, rheumatic lesions, and, even more so, MR with leaflet calcification or extensive annulus calcification is not as consistent even in experienced hands.
The results of valve repair are also highly dependent on the experience of the surgeon; this holds to be even more true as the lesions get more complex.
In current practice, surgical expertise in mitral valve repair is growing and becoming widespread since it is used in almost 50% of patients in registries in Europe3 and the USA and in up to 90% in experienced centres.103
When repair is not feasible, mitral valve replacement with chordal preservation is preferred.
Recently, additional anti-arrhythmic procedures derived from the Cox maze intervention have been proposed in patients with preoperative AF to return them to and maintain sinus rhythm. The data available are still limited and the definitive role of these procedures remains to be determined.104
The first percutaneous mitral valve repairs in man have been performed using either implants introduced via the coronary sinus or stitches mimicking the Alfieri operation (edge-to-edge method) introduced transseptally.105,106 Further evaluation