Classifications of Aortic Stenosis Severity4
The aortic valve separates the left ventricular outflow tract from the aorta. It is a tricuspid valve consisting of three semilunar cusps and the aortic valve annulus. The aortic valve annulus is a collagenous structure lying at the level of the junction of the aortic valve and the ventricular septum, which is the nadir of the aortic valve complex. This area is also referred to as the aortic ring and serves to provide structural support to the aortic valve complex. The annulus is shaped like a crown and extends to the level of the aortic sinuses. It attaches to the aortic media distally and the membranous and muscular ventricular septum proximally and anteriorly. There are 3 aortic valve cusps, each half-moon shaped or semilunar in appearance. A small dilatation of the proximal aorta is associated with each cusp; collectively, these are referred to as the sinuses of Valsalva or aortic sinuses, named after the Italian anatomist Antonio Valsalva. Their association with the respective coronary ostia identifies them: left, right, and posterior (or noncoronary).
Aortic stenosis (AS) is one of the most common diseases of the aortic valve. The most common causes of AS are degenerative calcification, bicuspid aortic valve and rheumatic etiology. Age – related degenerative calcific AS is currently the most common cause of AS in adults and most frequent reason for aortic valve replacement (AVR). That atherosclerosis is a cause of AS is derived primarily from five pieces of evidence: 1) that patients with familial homozygous hyperlipidemia usually develop calcific deposits on the aortic aspects of their aortic valve cusps at a very young age, usually by the teenage years (These individuals have serum total cholesterol levels
The pathophysiology of valvular aortic stenosis is one of progressive obstruction and the resultant compensatory changes. With increasing left ventricular outflow tract obstruction, there is pressure hypertrophy of the left ventricle. Left ventricular cavity size and systolic function is initially maintained, as the increase in left ventricular wall thickness acts as a compensatory mechanism to normalize wall stress. The development of pressure hypertrophy is initially a beneficial adaptation. However, this hypertrophy may result in reduced coronary flow reserve and oxygen supply–demand mismatch. These hypertrophied hearts are also more sensitive to diffuse subendocardial ischemic injury, which may result in both systolic and diastolic dysfunction. As the obstruction progresses to a critical level, the high afterload “overwhelms” the left ventricle and systolic function begins to decrease. With continued severe afterload excess, myocyte degeneration and fibrosis occurs and produces irreversible left ventricular systolic dysfunction. In these patients, both the high afterload and the intrinsic myocardial disease significantly increase wall stress and a vicious cycle of deterioration in ventricular function ensues.
The evaluation of aortic stenosis is based upon the history, the physical examination, and a comprehensive echocardiography. For most patients, two-dimensional echocardiography readily identifies the calcified stenotic aortic valve, and Doppler echocardiography reliably estimates the severity of aortic stenosis in the majority of patients. Many patients with aortic stenosis will remain asymptomatic for decades. The diagnosis of aortic stenosis is usually made in the asymptomatic patient on the basis of a systolic murmur on auscultation and confirmed by echocardiography. Symptoms, when they occur, usually consist of one or more of the classic triad of exertional dyspnea, angina, and syncope. Following symptom onset, there is a high mortality rate with an average survival of 2–3 years. The development of symptoms therefore is a critical point in the natural history of patients with aortic stenosis. Sudden death rarely is the initial manifestation of severe aortic stenosis, occurring at a rate of less than 1% per year in asymptomatic patients. Two-dimensional and Doppler echocardiography is the imaging modality of choice for the diagnosis and quantification of aortic stenosis. Short-axis images from two-dimensional echocardiography demonstrate the number of aortic cusps and the degree of cusp fusion or restricted cusp opening in valvular aortic stenosis. Two dimensional echocardiography is also useful for determining the status of the left ventricle and the degree of hypertrophy. Left atrial enlargement indicates concomitant diastolic dysfunction. The normal area of the adult aortic valve is 3.0 to 4.0 cm2. Reduction of the normal area usually does not produce symptoms until the valve reaches one-fourth of its normal dimension. The graduation of AS is given in Table 1.
|Normal||< 2.5||-||3 to 4|
|Mild||2.5 to 2.9||< 25||1.5 to 2|
|Moderate||3 to 4||25 to 40||1 to 1.5|
|Severe||> 4||> 40||< 1|
There is no effective medical therapy for AS. AVR is the only effective treatment for severe aortic stenosis in adults. Following AVR for AS, one can expect resolution of symptoms, left ventricular hypertrophy (LVH) regression, and improved left ventricular (LV) systolic function secondary to reduced afterload. Importantly, postoperative survival is similar to age-matched controls after AVR for AS when performed prior to the development of LV dysfunction or congestive heart failure (CHF). Similarly, incomplete regression of LVH after AVR has been associated with adverse outcomes such as reduced long-term survival. Contrary to the immediate improvement in systolic performance, diastolic dysfunction may persist for several more years after AVR. In fact, Gjertsson et al. recently evaluated diastolic dysfunction in AS and found that the proportion of patients with moderate-to-severe diastolic dysfunction actually increased with time after AVR despite normalization of LV mass and appropriate adjustments for senile diastolic dysfunction. Finally, AVR is associated with improved quality of life scores, particularly among the elderly, and has been found to be similar to age-matched individuals without heart disease. [3,5,6]
The American College of Cardiology (ACC) and the American Heart Association (ACH) have jointly developed guidelines in which they published indications for AVR:
Patients who have severe AS and presented with one or more of its classical symptoms (angina, syncope, heart failure, etc.)
Patients who have severe AS and required coronary artery bypass surgery, surgery on the aorta or other heart valves
Patients who have severe AS and left ventricle systolic dysfunction (ejection fraction less than 50 %)
Patients who have moderate AS and required coronary artery bypass surgery, surgery on the aorta or other heart valves
Asymptomatic patients with severe AS with abnormal exercise test, or an increase in transaortic gradient during exercise, or left ventricle systolic dysfunction (ejection fraction less than 50 %), or left ventricular dilatation, or significantly elevated left ventricular diastolic pressure. 
The European Society of Cardiology (ESC) has also developed guidelines in which they published indications for AVR (Table 2). They strongly recommended early AVR in all symptomatic patients with severe AS.
Management of asymptomatic patients requires careful weighing of benefits against risks. Early elective surgery at these patients 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 decisionmaking more difficult. There is no strict age limit for performance of exercise testing and it is reasonable to propose it in patients > 70 years old who are still highly active.
|Patients with severe AS undergoing coronary artery bypass surgery, surgery of the ascending aorta, or on another valve||IC|
|Asymptomatic patients with severe AS and systolic LV dysfunction (LVEF < 50%) unless due to other cause||IC|
|Asymptomatic patients with severe AS and abnormal exercise test showing symptoms on exercise||IC|
|Asymptomatic patients with severe AS and abnormal exercise test showing fall in blood pressure below baseline||IIaC|
|Patients with moderate AS undergoing coronary artery bypass surgery, surgery of the ascending aorta or another valve||IIaC|
|Asymptomatic patients with severe AS and moderate-to-severe valve calcification, and a rate of peak velocity progression ≥ 0.3 m/s per year||IIaC|
|AS with low gradient (< 40 mmHg) and LV dysfunction with contractile reserve||IIaC|
|Asymptomatic patients with severe AS and abnormal exercise test showing complex ventricular arrhythmias||IIbC|
|Asymptomatic patients with severe AS and excessive LV hypertrophy (≥ 15 mm) unless this is due to hypertension||IIbC|
|AS with low gradient (< 40 mmHg) and LV dysfunction without contractile reserve||IIbC|
In last 50 years, the varieties of prostheses that have become available for use are numerous. An ideal aortic prosthesis would be simple to implant, widely available, possess long-term durability, would have no intrinsic thrombogenicity, would not have a predilection foe endocarditis and would have no residual transvalvular pressure gradient. Such a valve does not currently exist. Currently available options include mechanical valves, stented biological valves, stentless biological valves, allograft valves and pulmonary autograft valves. Commonly in us are mechanical and biological prostheses. When selecting between mechanical and biologic heart valves, the surgeon and patient must balance the risks and benefits of each choice.
2. Mechanical prostheses
Charles Hufnagel in 1952. Used aortic valve ball and cage prosthesis heterotopically in the descending aorta to treat aortic insufficiency. The first aortic valve replacement with an intra cardiac mechanical prosthesis, which led to long terms survivors, was performed in 1960. Mechanical valves are classified according to their structure as caged-ball, single-tilting-disk or bileaflet-tilting-disk valves. The Starr-Edwards caged-ball valve has been available since the 1960’s and comprises a silastic ball, which rests on the sewing ring when closed and moves forward into the cage when the valve opens. The single-disk valves, for example, the Bjork-Shiley prosthesis and the Medtronic-Hall prosthesis, contain a disk that tilts between two struts of the orifice housing. The most popular of the mechanical valves at present are the bileaflet valves, of which the St. Jude Medical valve and the Carbomedics valve are widely implanted. Both these devices are implanted within the aortic annulus. The two semi-circular leaflets of the bileaflet valve are connected to the housing by a butterfly hinge mechanism and swing apart during opening of the valve creating three outflow tracts, one central and two peripheral respectively. In contrast to the configuration of the latter, the Carbomedics Top Hat (Sulzer Carbomedics, Austin, TX) bileaflet aortic valve that was introduced in 1993 has a unique supra-annular design with all its components incorporated within the aortic sinuses.[10,11]
Mechanical valves are made from carbon, Teflon, Dacron, titanium and polyester and are very durable. The current designs for the aortic and mitral positions include ball-and-cage valves, single tilting disc prostheses, and bileaflet prostheses. Bileaflet mechanical valves are the standard in current practice, with the St. Jude Medical (St. Jude Medical, Inc., St. Paul, MN) prosthesis the modern prototype, having been first implanted in 1977. Most of these valves are constructed using carbon strengthened with silicon carbide additives. Other examples of bileaflet mechanical valves include those manufactured by CarboMedics (Austin, TX); Advancing the Standard Medical (ATS, Minneapolis, MN); Medtronic, Inc. (Minneapolis, MN); and Medical Carbon Research Institute, LLC (MCRI, Austin, TX).[10,11,12] The On-XR mechanical valve (MCRI) was introduced in Europe in 1996 and differs from other bileaflet mechanical valves in that it is made from pure pyrolytic carbon. The PROACT (Prospective Randomized On-X R Valve Anticoagulation Trial) study is an FDA-approved multicenter trial, sponsored by MCRI, currently enrolling patients to determine whether or not defined patient groups receiving AVR (low versus high risk for TE events) with the On-X R
3. Biological prosthesis
The biological prostheses include a wide variety of devices. Included within this broad category are the bioprostheses, a term which is used for valves with non-viable tissue of biological origin. The bioprostheses include the heterografts, composed of porcine (actual valves of a pig) or bovine tissue (pericardium of a cow) and the allografts, which are preserved human aortic valves. The initial bioprostheses were mounted on stents to which the leaflets and sewing ring were attached but subsequently stentless valves, which are sewn in free hand, have been developed. Stented bioprosthetic valves, which incorporate a semi-rigid external support structure for the valve leaflets, represent the majority of tissue valves implanted in clinical practice. The external support provides accurate valve mounting, improving ease of implantation. Two types of stented bioprosthetic valves are currently available in the United States: porcine aortic valves, which incorporate chemically stabilized porcine valve leaflets mounted on a stented structure or frame, and bovine pericardial valves. The leaflets of the latter valve type are constructed from bovine pericardium and subsequently mounted on a stented frame. Available porcine valves include the Medtronic Mosaic valve (Medtronic Inc., Minneapolis, MN), the St. Jude Medical Biocor and Biocor Supra valves (St. Jude Medical, Inc., St. Paul, MN), and the Carbomedics Mitroflow valve (Carbomedics, Inc., Austin, TX). Bovine pericardial valves include the Carpentier–Edwards (C–E) Perimount (Edward Lifesciences, Irvine, CA) and the CE Perimount Magna valves as well as the Sorin Soprano (Sorin Group, Saluggia, Italy) valves. At present, based on the best available data, no one bioprosthetic valve appears superior with regard to patient outcomes and none requires systemic anticoagulation with warfarin, which is their major advantage. Their major disadvantage is the incidence of structural valve deterioration and subsequent need for reoperation, although the lifespan of the latest generation of tissue valves is unknown. Recent evidence also suggests that stentless biological valves may have better coronary flow reserve compared to stented valves. Additionally, compared with stented bovine pericardial valves, stentless valves have been associated with increased transvalvular EOA and decreased pressure gradients during extended follow-up. However, as seen in other studies, LV mass regression after stentless valve implantation was not different from stented aortic bioprostheses.[3,14]
4. Outcomes after aortic valve replacement
The Ad Hoc Liaison Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity of the American Association of Thoracic Surgery and the Society of Thoracic Surgeons published guidelines during years, which are now widely used in reporting outcomes after valve surgery. They presented a list of developing specific valve-related events during patients remaining lifetime. These valve-related events are:
Structural valvular deterioration
Valvular endocarditis and
Several studies have evaluated independent risk factors for operative mortality after AVR. Five variables predictive of increased mortality risk after AVR are common to each of these analyses: preoperative renal failure, urgency of AVR, preoperative heart failure, presence of CAD or recent MI, and redo cardiac operation. Other factors independently associated with operative mortality from the individual studies include preoperative atrial fibrillation, active endocarditis, preoperative stroke, advanced age, lower body surface area, multiple valve procedures, and hypertension. [39, 40]
5. Factors affecting long-term outcome after AVR
Higher pre-operative NYHA functional class
Pre-operative atrial fibrillation and non-sinus rhythm
Pure aortic regurgitation
Longer cardiopulmonary bypass time
Previous myocardial infarction
Left ventricular structure and functional abnormality
Previous aortic valve surgery
Coronary artery disease (CAD)
Older patients have a lot of comorbiditis and they are at higher risk for valve-related events. Atrial fibrillation is one of the risk factor for thromboembolism, because of that INR levels must be higher (INR 2.5 to 3.5) than regular.[30,34] The majority of patients undergoing AVR have other cardiac lesions, most commonly CAD, and more complex pathology has been associated with increased risk. Combined myocardial revascularization and AVR increases cross-clamp time and has the potential to increase perioperative myocardial infarction and early postoperative mortality compared with patients undergoing isolated AVR.7 In addition to severity of CAD and AS, the multivariate factors for late postoperative mortality include low ejection fraction, severity of LV dysfunction, age greater than 70 years (especially in women), and presence of NYHA functional class IV symptoms.
6. Patient selection
Propter selection of patients for valve replacement can bring us excellent long-term results, long-term survival and low incidence of valve-related complications.
In some studies of patients followed over longer time frames, freedom from all valve-related events and freedom from reoperation were improved in patients with mechanical valve prostheses as compared to patients with biological prostheses. [9,16,25] Key of long-term success of mechanical valve prostheses is anticoagulation. Patients that are inconsistent, noncompliant or incapable of managing medications are not good candidates for long-term chronic anticoagulation.[39,41] Also patients with higher levels of education and those from geographic areas with a good medical infrastructure have better compliance with necessary medications and anticoagulant monitoring.
Many centers used bioprosthetic valves for patients who are older than 70 year, based on data by Akins. In patients younger than 60 years of age, the best solution would be implantation of mechanical valves, based on prosthesis durability and they have low-risk for valve-related events. In decade between 60 and 70 years of age, other factors have to be taken into account.7 According to some studies, patients over 65 years at the time of surgery should receive a biologic valve. Patients under the age of 60 should have a mechanical prosthesis to minimize the risk of structural failure requiring repeat AVR in an octogenarian. Patients between 60 and 65 represent the group in whom there is still considerable debate regarding prosthesis selection. Those patients who have comorbidities such as severe CAD may be less likely to outlive their prosthesis and should receive a biologic valve. A detailed discussion of these risks and benefits of prosthesis selection should occur with all patients and their families prior to entering the operating room. [3,7,22,24,25,37,38]
In the early follow-up period, anticoagulation – related hemorrhage is the most common unwanted event for mechanical valve prostheses. Over the first 10 years of follow-up there is a higher incidence of valve-related events in patients with mechanical prostheses as opposed to those with biologic valves. However, in the next 10 to 20 years after AVR, the incidence of valve failure and valve-related complications are much higher at biologic prostheses than those with mechanical valve prostheses. Some series showed that the time to biologic valve failure was only 7.6 years. This failure rate will increase over time. However, freedom from valve-related events is more strongly influenced by pre-existing comorbidities than the presence of mechanical prostheses., [22, 25, 31]
The elderly patient with severe aortic stenosis poses a therapeutic challenge. In considering elderly patients for aortic valve replacement, important factors include the presence of symptoms, physiologic age, patient expectations, anticipated future activities, and comorbidity. The operation itself carries a higher risk than in younger patients. Extensive calcification of the aorta and annulus as well as fragile tissue presents significant technical difficulties for the surgeon. In addition, particularly in women, the aortic root and annulus may be small and require concomitant enlargement to accommodate the valve prosthesis. Furthermore, protruding arch atheroma occurs in one-fifth of patients
A major deterrent to mechanical valve replacement in the younger patient is the impact of long-term anticoagulation. Mechanical valves are, however, more ideal for younger patients due to their excellent durability characteristics. Most importantly, younger patients (i.e., patients under the age of 50 years) are a low-risk subset for valve related events. These individuals have very few risk factors for TE, and thus anticoagulation can be run at the lower end of the therapeutic target range, decreasing the incidence of anticoagulant-related hemorrhage without altering the incidence of TE. In fact, many infants and children have been managed with only aspirin with quite good long term results. While this is not recommended in patients older than infancy, it is a feasible alternative. A recent study in patients under 50 years of age followed 254 patients for up to 20 years and found an exceedingly low rate of valve related events, an exceptional long-term overall survival of nearly 88%, and event-free survival probability of 92% at 19 years.[3,44,45]
Patients with an absolute requirement for long-term anticoagulation such as atrial fibrillation, previous thromboembolic events, hypercoagulable state, severe LVD, another mechanical heart valve in place, or intracardiac thrombus, should receive a mechanical valve regardless of age. Patients in whom anticoagulation with warfarin is contraindicated, such as women of child-bearing age wishing to become pregnant, patients with other bleeding disorders, or those who refuse anticoagulation should receive a bioprosthesis. There is growing interest in using mechanical prostheses in women of child-bearing age and providing anticoagulation with subcutaneous low-molecular weight heparin injections. Patients with end-stage renal failure were previously believed to have significantly elevated risk for early bioprosthetic structural valve deterioration. However, increased anticoagulation- related complications are also more likely in this group, and the current ACC/AHA guidelines do not recommend routine use of mechanical prostheses in these patients.[3,7,8,9,10]
The decision between bioprosthetic and mechanical valve should be made by the patient with educated input regarding the pros and cons of each option from the patient’s physicians. Today surgeons implant bioprosthetic valves in younger patients who wish to avoid anticoagulation due to lifestyle concerns (e.g. young, active individual, desire to become pregnant, etc.), although surgeons generally will guide patients toward a mechanical option at the time of redo-AVR if their life expectancy exceeds 10–15 years at that time.
7. Operative technique
Aortic valve replacement is most frequently done through a median sternotomy, meaning the incision is made by cutting through the sternum. Once the pericardium has been opened, the patient is put on a cardiopulmonary bypass machine. This machine takes over the task of breathing for the patient and pumping their blood around while the surgeon replaces the heart valve.
Once the patient is on bypass, a cut is made in the aorta and a crossclamp applied. The surgeon then removes the patient`s diseased aortic valve and a mechanical or biological valve is put in its place. Once the valve is in place and aorta has been closed, the patient is taken off the heart-lung machine. Transesophageal echocardiogram can be used to verify that the new valve is functioning property. Pacing wires are usually put in place, so that the heart can be manually paced should any complications arise after surgery. Drainage tubes are also inserted to drain fluids from the chest and pericardium following surgery. These are usually removed within 36-48 hours while the pacing wires are generally left in place until right before the patient is discharged from the hospital.
8. Patient-prosthesis mismatch
Prosthesis‐patient mismatch (PPM) is that a smaller than expected effective orifice area (IEOA) in relation to the patient's body surface area (BSA) will result in higher transvalvar gradients. It is condition that occurs when the valve area of a prosthetic valve is less than the area of that patient’s normal valve. Several authors suggest that prosthesis-patient mismatch occurs at an IEOA of 0.85 cm2/m2.[46,47] Transvalvular gradients begin to rise substantially at IEOAs below this value, and these elevated gradients potentially cause increased left ventricular work that prevents adequate regression of left ventricular hypertrophy. Several factors including age, body mass index (BMI), and pre-operative status of left ventricular function may potentially influence the effect of PPM on post-operative outcomes. PPM is associated with a significant reduction in cardiac index during the postoperative course. The incidence of congestive heart failure was significantly higher in patients with PPM. Several studies reported that early mortality is significantly increased in patients with PPM.[47, 48, 49, 50]
The projected indexed EOA should be systematically calculated at the time of the operation to estimate the risk of PPM. PPM can be avoided by using a simple strategy at the time of operation. Pibarot suggested that surgeon first calculate the patient's BSA from his or her weight and height. Than multiply BSA by 0.85 cm2/m2, the result being the minimum EOA that the prosthesis to be implanted should have to avoid PPM, and than choose the prosthesis and the reference values for the different types and sizes of prosthesis.[46, 47]
Due to concerns over PPM, stentless bioprosthetic valves, which generally have a larger EOA sizefor- size compared with mechanical or stented bioprosthetic valves, have been increasingly utilized for AVR. In initial evaluation, stentless valves had better hemodynamics and improved survival rates relative to stented biological or mechanical valves and were more durable than stented biological valves. Stentless valves may be preferred in patients with a small aortic root, and arguments have been made that wider utilization of stentless valves may minimize PPM. Stentless valves also appear to have better hemodynamic profiles than stented valves during exercise testing. Technical reasons for not implanting stentless valves include extensive aortic root calcification, coronary ostia opposed by 180, presence of the two coronary ostia in close proximity, or unusual disproportion between the sinotubular junction and the aortic annulus. Whereas stented valves allow perfect valve mounting within the aortic annulus, thus reducing the risk of implanting an incompetent valve, postoperative AR and limited durability remain a concern with the free-hand stentless valve insertion technique. This issue may be circumvented with full aortic root replacement using a stentless porcine root.[3.49,50]