Introduction. 2 DE Newby et al., Emerging treatments for aortic stenosis: statins, angiotensin converting enzyme inhibitors,

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Introduction

My fascination with aortic stenosis originates from a work shadowing placement, in which I

was fortunate enough to shadow a consultant cardiac surgeon for a week1. In consultations I

witnessed the gravity of the condition first hand, and saw how it could take hold of people’s lives. Aortic stenosis is the most common adult heart valve condition seen in the western

world2, and is said to affect up to 9% of the population which is over 65 years old3. It is

therefore a very serious and widespread problem, in need of a comprehensive solution. The main feasible way to tackle a stenosed aortic valve is to replace it with a healthy one; however during the work experience, I realised that there was more than one method available to carry out such a procedure. I observed both a surgical aortic valve replacement (which I will refer to as SAVR), and a trans-catheter aortic valve implant (or TAVI), and found comparison between the two captivating. Why was one procedure insufficient? To compare the two techniques is to compare that which is traditional, established and reliable (SAVR), with that which is innovative, unknown and potentially erroneous, a discussion

relevant to the entire modernisation of medicine in the 21st century. This project will

therefore be devoted to the question: ‘Will Trans-catheter Aortic Valve Implant ever take the place of Surgical Aortic Valve Replacement, in the treatment of aortic stenosis?’

Answering this question will require an in-depth discussion centred on the strengths and weaknesses of both procedures. After looking at aortic stenosis as a disease, in terms of its characteristics and causes, I will look at each treatment in turn, using published research to discuss the various aspects of the procedures, including efficacy, safety, and financial factors. Once I have evaluated all the contributing issues, I intend to come to an overall conclusion, of whether or not TAVI will ever replace SAVR, as a treatment of aortic valve stenosis.

       1

 Week commencing 15/06/09, Guys and St. Thomas’ NHS Foundation Trust, London.  

2

 DE Newby et al., ‘Emerging treatments for aortic stenosis: statins, angiotensin converting enzyme inhibitors,  or both?’ Heart, 2006;92:729‐734 

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Aortic Stenosis- The Problem to be Solved

In order to understand the various benefits and drawbacks of TAVI and SAVR, it is first necessary to understand the problem that they are attempting to solve; namely, aortic

stenosis; as well as the role of a healthy aortic valve4.

What role does the aortic valve play in this system of blood transport? The role of any valve, be it in industry or in a vein, is to stop the backflow of a particular substance. In the heart, valves exist to stop the backflow of blood. The aortic valve, is situated between the left ventricle and aorta, with the role of stopping the backflow of blood during ventricular

diastole. This allows blood to be pumped around the body in a single direction. The basic definition of aortic stenosis is: ‘the narrowing of the opening of the aortic

valve’5. Whilst stenosis is often, somewhat

ironically, compounded with regurgitation, the disease is problematic because it does not let enough oxygenated blood move from the left ventricle, into systemic circulation. Whilst the definition of aortic stenosis is all encompassing, there are several different founding causes of the narrowed valve.

Rheumatic Aortic Stenosis

Rheumatic fever is rare in modernised countries, however is still prevalent in the developing world. In this auto-immune disease, the body’s immune system damages its own tissues, including the aortic valve. This can cause fibrosis and fusion of the aortic cusps, thus causing stenosis.        4  See Appendix 1‐ The Healthy Heart  5 BMA Illustrated Medical Dictionary, published 2009  Images: http://www.mercyangiography.co.nz/PatientInfo/OurProcedures/PAVR.aspx 

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Congenital Aortic Stenosis

The aortic valve naturally consists of three, equally sized triangular cusps, meeting in the centre of the aortic lumen, to provide a seal. Occasionally (in

around 1-2% of the population6) due to genetic or

developmental malformations, the three cusps may be of different sizes, or there may just be two (bicuspid). Such valves are the most common cause of stenosis in young people; however a deformed valve in itself is not necessarily problematic. The valve may still function, however it does tend to make blood flow more turbulent, inducing more trauma to the leaflets. Over time this may cause fibrosis of the leaflets, ultimately resulting in stenosis. The increased ‘wear and tear’ that the valve undergoes due to a more turbulent blood flow, may also lead to an additional process known as calcification.

Calcific Aortic Stenosis

Calcific aortic stenosis is the most common type of stenosis in older patients. Calcification may occur in otherwise normal, or abnormal, such as bicuspid, valves. It is thought that around 2% of people over 65 years suffer from frank calcific aortic stenosis, and many more

have mild or moderate forms of the disease7.

A calcified aortic valve, is a valve covered in calcific nodules. These are lumps of bone mineral, cholesterol, white blood cells, and collagen fibre fused on to the valve cusps, which stiffen the leaflets, and so prevent the valve from opening to its full diameter. Little is known about the fundamental triggers of calcification, although professional opinion generally agrees that it is similar to the mechanism of atherosclerosis in coronary heart disease. This suggests that calcification is heavily

influenced by cholesterol, however trials involving statins have shown that whilst such drugs do reduce low density lipoprotein concentrations, they do not slow the progression of calcific       

6 Edward J Bayne, Aortic valve‐ Bicuspid, Web article, 13/11/09 www.emedicine.medscape.com 

Images: http://www.heart‐valve‐surgery.com/heart‐surgery‐blog/2009/08/03/pictures‐aortic‐stenosis‐picture‐

mitral‐prolapse/ 

 http://www.mo‐media.com/pathology/ 

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aortic stenosis (although it is conceivable that LDLs only trigger the process, and then play

no further role in the disease progression)8.

Why is Aortic Stenosis Problematic?

The aortic valve stands between the body’s tissues, and oxygenated blood. The blood carries a variety of minerals and other substances such as hormones, which are vital for tissue function, as well as oxygen and glucose around the body, which are primary respiratory substrates. If severe narrowing of the valve occurs, less blood can leave the heart, and so there may be a shortage of oxygenated blood moving around the body, and consequently a shortage of respiration and energy release in tissues. This can lead to clinical symptoms such as dyspnea, and syncope. The greater resistance to the ejection of blood from the left ventricle into the aorta, may also lead to left ventricular hypertrophy, reducing stroke volume, and leading to

pulmonary hypertension and heart failure. The increased volume of cardiac muscle cannot be supported by the reduced cardiac output from the left ventricle.

Diagnosis

Aortic stenosis is largely an asymptomatic disease, as it tends to develop very slowly over time. It is however important that the disease is recognised quickly, as whilst a patient’s survival chances may be good in the first stages, when symptoms appear the two year survival rate drops to around 50%. When a patient presents with syncope, due to aortic stenosis, their life expectancy is just 3 years. It is also thought that those with developing aortic stenosis are at increased risk of atherosclerosis. The symptoms of congenital or rheumatic aortic stenosis appear at the ages 50-60, whereas calcific patients usually become symptomatic some twenty years after this.

When a patient presents with symptoms such as dyspnea, and syncope, and the doctor

suspects a cardiac explanation, it is vital that suitable investigatory procedures are carried out, as to determine the underlying cause. A variety of procedures can be used, including Doppler scanning (if this gradient exceeds 50mmHg, and there is a normal cardiac output, then

       8  DE Newby et al, ‘Emerging treatments for aortic stenosis: statins, angiotensin converting enzyme inhibitors,  or both?’ Heart, 2006;92:729‐734  Images: http://www.pathguy.com/lectures/accdep.htm  http://upload.wikimedia.org/wikipedia/commons/b/ba/Heart_left_ventricular_hypertrophy_sa.jpg 

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stenosis is likely), echocardiography (an adult with an aortic valve area less than 0.8cm squared is said to have severe aortic stenosis), aortograms, and physical examination. If stenosis is diagnosed, action must be taken quickly.

Other Treatments

Once calcific aortic stenosis has begun to develop, there is little that can be done to slow disease progression. The only real action that can be taken is endocarditic prophylaxis. Limited success has been reported in the use of balloon valvuloplasty (an older sister procedure to TAVI) to correct the disease. Its benefits seem short lived, the procedure may induce regurgitation, and it is also believed that balloon aortic valvuloplasty in the elderly,

may have a higher mortality rate than SAVR in the same group9.

The diseased valve must be replaced to achieve a long term, effective solution.

      

9 National Institute for Heath and Clinical Excellence, ‘Interventional procedure overview of balloon 

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Trans-catheter Aortic Valve Implant

TAVI is by far the more recent of the two procedures in question. The first percutaneous

implantation of an aortic valve took place on 16th April 2002, and the procedure has been

used on a commercial level since 2007. The technique has been hailed by some as a

‘miracle’10, and is yet another example of the technological revolution which modern

medicine seems to be experiencing.

It is first necessary to outline what exactly TAVI involves. The procedure is carried out under general anaesthetic, and lasts between sixty and ninety minutes. Although TAVI is seen as a major cardiac procedure, it is not classed as a surgical operation, and so is not carried out in an operating theatre, but rather in a catheter laboratory, by a cardiologist and cardiac surgeon. TAVI does not access the diseased valve via a median sternotomy, as SAVR does, but instead one of two methods is used: the trans-apical approach, where the valve is accessed by the tip of the left ventricle/atrium, using a minithoracotomy (the most invasive version of TAVI); or the trans-luminal approach. In the latter, no incision is made in the thorax, and instead, access to the heart is gained via the femoral artery or femoral vein in the groin. If the route chosen is arterial, then the wires and catheters will be moved through a system of arteries, over the aortic crook, and eventually approach the aortic valve from above. When working via the femoral vein, it is necessary to puncture through the septum between the left and right atria, move down through the mitral valve into the left ventricle, and then approach the aortic valve from below. One of the main factors in choosing a route, is the diameter and condition of the patient’s blood vessels. If they are too narrow to accommodate catheters, then it may be necessary to use the trans-apical approach.

Whichever approach is selected, the format of TAVI is roughly the same. Once the patient is anaesthetised and stable, the primary incision is made. Through this, is inserted the initial guide wire, known as a ‘pigtail’ which is guided through the necessary vessels or incisions, until it reaches the aortic valve.

       10

 Madeleine Brindley, Western Mail (Cardiff), 25/05/09, P.20  Images: European Society of Cardiology 

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The doctor cannot physically see where the pigtail is in the patient, but rather relies on regular ‘video X-rays’ taken by a radiologist, whilst contrast dye is released from the wire

into the vessel. 11

The next stage is to prepare the diseased valve to receive the implant, by increasing its diameter, using balloon aortic valvuloplasty. Another catheter, this time containing a collapsed prosthetic aortic valve (often consisting of a metal stent, containing cusps formed from animal pericardium tissue) is then advanced over the pig tail. When this has been manoeuvred into position, the stent to which the valve is attached either automatically expands, or is expanded using another saline balloon. To ensure the new valve is not knocked out of place while expanding (which could prove fatal), pacing wires are used to temporarily pace the heart, to around 200 beats per minute. This reduces cardiac output, meaning that there is little moving blood to interfere with valve placement. When fully expanded, if the valve is of a suitable size, the sides of the stent will press against the folded cusps of the diseased valve, which will in turn push inwards against the stent, and so the implant remains in place, and begins to function immediately. The implantation is not in any way sutured in place (although hooks have been       

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 Images: www.health‐energy‐fitness.com 

www.cookmedical.com   

Entry points for  trans‐ luminal  approach via  femoral arteries  (red) 

Entry points for  trans‐luminal  approach via  femoral veins  (blue)  The target:  Aortic Valve 

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used), which can lead to valve migration issues. The catheters, and guide wire must then be removed, and the incision closed, which may be surgical in the trans-apical and arterial approaches.

Surgical Aortic Valve Replacement

The two techniques are extremely different. Whilst TAVI is minimally invasive, the same cannot be said of its surgical counterpart. SAVR is seen as major open heart surgery, performed in an operating theatre. The length of SAVR is roughly two hours, however this varies, depending on whether other procedures (such as coronary artery bypass graft) are also performed. The relative lengths of SAVR and TAVI have implications; the fact that TAVI is shorter means that the patient is under anaesthetic for less time, and so there is less chance of complications developing (such as aspiration). Also, the surgical team can treat more

patients in a set time when using TAVI, reducing waiting lists, and relieving symptoms faster. It could also be argued that the team’s concentration will be better in shorter

procedures such as TAVI, leading to less avoidable procedural errors. In SAVR, the surgeon’s first task is to access the heart. Once the patient has been wiped in sterilising iodine solution, the layers of skin and fat covering the sternum are separated using a scalpel and diathermy knife. The surgeon then uses a powerful electric saw to cut down the centre of the rib cage, splitting the

sternum in two, and retractors are used to pull apart the two pieces of bone, exposing the chest cavity. By cutting through the pericardium, the surgeon has

complete access to the heart. With the development of medicine, there are emerging forms of SAVR, in which a smaller incision is made, however this procedure is still far more invasive than TAVI.

In order to access the aortic valve, the surgeon will have to make an incision into the aorta. This would lead to extensive bleeding, and cut off the body’s supply of oxygenated blood, and so before accessing the valve, the surgeon must stop the heart, and re-route the patient’s circulation, using a heart lung machine. A suction tube is inserted into the venae cavae, the vessels which deoxygenated blood use to access the heart, and from here it is drawn through a system of chambers, which both filter, and oxygenate the tissue through a semi-permeable membrane. The oxygenated blood is then re-pumped into the body via a tube inserted into one of several places; including the femoral artery, iliac artery, or aorta itself (above where

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the aortic clamp is to be placed). In this manner, the body’s blood supply is rerouted around the heart and lungs, meaning that the heart can now be stopped without detriment to the rest of the body. Before full diversion is made, a cold (around 4 degrees Celsius) cardioplegia solution is infused into the coronary arteries of the heart. Their purpose is to slow metabolic rate, slow the release of energy, and so stop cardiac systole. The heart’s lowered energy requirements mean that the tissue will not be damaged by the oxygen deprivation that will occur from the diversion of blood flow. It is important to note that heart-lung bypass is not used in TAVI. Because the surgeon does not have to cut open the aorta to access the valve, there is no need to stop blood flow, and therefore no need to make the heart dormant, although pacing is used.

Cardiopulmonary bypass is associated with several post operative complications. The variety of chemicals in cardioplegia can lead to electrolyte imbalance in the cardiac tissue; and the cardiac muscle may also have ischemic damage. This damage may lead to arrhythmias or fibrillation (atrial arrhythmia is said to occur in 33% to 65% of patients who have undergone

open heart surgery12). The conduction of blood through a ‘foreign system’ can lead to

inflammation, which may continue after surgery; causing to the increased

permeability of capillaries, and so low blood pressure. Blood flow through the kidneys may also be decreased, reducing their filtering capacity, and allowing the concentration of harmful substances in the blood to increase. Atelectasis is also a very common consequence of bypass (70% of patients). Such side effects can be avoided, or at least their incidence reduced, by not using cardiopulmonary bypass; and so it is conceivable that TAVI is a better choice in this regard. The necessity of restarting the heart after the procedure can also prove problematic.

Once the heart is stopped and emptied of blood, the next step is to cut open the aorta, and remove the stenosed valve, and suture the implant in position. This is evidently very different to TAVI. Incisions made in the aorta itself may increase the probability of post operative internal bleeding, as may the removal of the stenosed valve. The removal of a calcific valve may however prove advantageous in some respects, as it is possible that the surgeon is reducing the risk of post operative stroke and myocardial infarction, in that there will be no remaining nodules to later act as emboli, unlike in TAVI. The nodules may however dislodge during surgery. The fact that the diseased valve is removed, also means that SAVR can be used to correct congenitally defected aortic valves, for instance a bicuspid valve; whereas it may be difficult to implant a stent prosthesis into such an irregularly shaped opening. Similar arguments may be applied to suturing, as it could be seen as SAVR

      

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inflicting yet more trauma on the cardiac tissue; however suturing the new valve in place guarantees that it will remain there. One of the largest problems with TAVI is that the

implant valve has the potential to be deployed in the wrong place, or knocked out of position. This is partially due to the fact that deployment is based on X ray images, and so the doctor cannot see exactly what is happening; but also because the valve is not sutured in place, if it is not exactly the right diameter then it could easily fall down into the left ventricle, or be pushed by blood further up the aorta. In one TAVI trial, 7% (4 of 59 patients) of procedures

had to be converted to SAVR due to implant misplacement13. Perhaps correct and durable

deployment of the valve in SAVR justifies the extra invasion. The problem is that regardless of this theoretical advantage, many patients, especially the elderly, simply cannot withstand any more invasion.

The qualities of the new valve also vary between procedures. The implant vale used in TAVI is perhaps more technical than the one in SAVR, as it consists of collapsible technology; however there is perhaps more variety in SAVR. A patient can receive a bio-prosthetic valve (lasting for ten to fifteen years, and so whilst they may be suitable for the elderly, they are not a practical option for younger patients), a mechanical valve (which are extremely durable, however the patient must take an anticoagulant for life), a homograft, or an autograft (where the patient’s own pulmonary valve is used to replace the aortic valve, meaning that the implant valve is living, and so longer lasting). This array of options does not exist in TAVI (yet), and so the procedure cannot be tailored to fit the patient and their lifestyle, as SAVR can be.

When the new valve is in position, the surgeon must surgically close the aorta, followed by the pericardium, and the sternum (which is pulled together using metal wire). One of the most striking differences between SAVR and TAVI, is the scale of invasion. Whilst TAVI can be performed via a small incision, SAVR relies on much more extensive entry. This of course provides TAVI with several benefits. Firstly, a smaller incision leads to a smaller post operative wound, which is aesthetically superior, and also makes the wound easier to care for, possibly reducing the chances of infection. A smaller wound will also heal faster, meaning that whilst SAVR patients may return home after at least a week in hospital, TAVI patients can return home after two to four days. SAVR patients are required to avoid heavy lifting and physical strain for around two months after the procedure while the sternum heals; but with TAVI, as the sternum is not dissected, this waiting time could be reduced to two weeks. There are of course also benefits to SAVR being more invasive. Full access to the heart allows surgeons to carry out other cardiac procedures such as bypass surgery. Such

additional procedures cannot be performed during TAVI, and bearing in mind that patients

with aortic sclerosis are 50% more likely to suffer a myocardial infarction14, this is an

important factor. If the thorax is open, it also means that the surgeon can see exactly what is        13 Walther et al, ‘Tansapical minimally invasive aortic valve implantation: multicentre experience’, Germany,  Vienna, USA, 2007.  Images: www.istockphoto.com  14 Otto et al.  Association of aortic‐valve sclerosis with cardiovascular mortality and morbidity in the elderly. N  Engl J Med 1999;341: 142‐147 

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happening, rather than relying on X-ray images. This may mean that potential problems can be spotted faster, and that a surgeon can rectify a problem far quicker than in TAVI.

Evidence Based Medicine

Perhaps the best way of comparing the two techniques, is to look at the results of trials involving either procedure. This is somewhat difficult, as for any comparison to be valid, patients receiving either procedure must be as similar as possible (in terms of age, condition, conmorbities...). TAVI has only really been trialled on high risk, elderly patients, so there is little data on any other patient group. There is however little recent data of SAVR outcomes for elderly high risk patients, as such trials would be unethical, when there is an alternative for such patients. I will therefore use a retrospective SAVR study (high risk patients who underwent SAVR before TAVI was available), and compare it to more recent TAVI studies included in NICE’s TAVI guidance. The two studies were selected based on their similar patient profiles, making the comparison of results more valid; and I have also tried to select trials with results typical to that particular procedure.

Pre-operative Characteristics

The TAVI study15 involved the implantation of a balloon mounted valve in the aortic

annulus, to combat a stenosed aortic valve, in 50 patients. In the SAVR trial16, 155 patients

were selected from the 3819 patients who underwent surgical aortic valve replacement to treat aortic stenosis in the years 1990-2000. This trial was retrospective so that the authors could look back and highlight the predictive factors in operative mortality, left ventricular function recovery and long term outcome; which would help medical teams in the future decide whether to treat a patient with SAVR. Whilst this objective is not the same as mine, the trial still provides a useful set of data which I can use to compare the outcomes of TAVI and SAVR.

The mean age in the TAVI trial was 82±7 years, compared to 72 years (with 36% of patients being over 75) in SAVR trial. This apparent difference in 10 years may have an impact on the results, although there is still a large degree of overlap. Whilst the mean EuroSCORE in the TAVI trial was 28%, no data on SAVR EuroSCOREs is provided. This does mean that comparison of patient’s conditions as a whole is difficult; however the extent of their aortic stenosis is still comparable. It is stated that the mean pre-operative aortic valve area in the

TAVI trial was 0.6±0.2cm², and in the SAVR trial is valve us very similar at 0.6±0.15cm².

Such similarity between the two trials continues, as for TAVI, 90% of patients were situated        15 Webb et al. “Percutaneous transarterial aortic valve replacement in selected high‐risk patients with aortic  stenosis.” 2007. VANCOUVER.  16  Vaquette B, et al. “Valve replacement in patients with critical aortic stenosis and depressed left ventricular  function: predictors of operative risk, left ventricular function recovery, and long term outcome.” Heart. 2005;  1324‐1329. 

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in a NYHA functional class of III or IV; as were 89% of patients for SAVR. Whilst the trans-valvular hemodynamic gradient in TAVI patients had an average of 46±17mmHg, SAVR patients had a mean of 43±13mmHg. There is however a difference in mean left ventricular ejection fraction in the two groups. In the TAVI group, the mean is 53±15% preoperatively, whereas this valve falls to 25±5% in the SAVR group (as all selected patients

had to have a fraction ≤ 30%). This shows that the extent of disease in the SAVR patients

was greater than that in the TAVI group. This severity could impact the results, and make comparison less reliable; especially as we are not able to compare the general health condition of the two groups.

Post Operative Results

The TAVI trial results state that 86% of procedures were successful, and the failures were due to events such as malpositioning of the implant valve (4%), inability to pass the iliac artery (2%), that the stenosis was too severe for equipment to be passed through the valve (6%), and problems with the delivery equipment (2%). The SAVR trial states that the 30 day mortality was 12% (18 patients), however we are not informed of how many of these deaths were intraprocedural. Interestingly, the 30 day mortality in the TAVI trial was also 12% (6 patients), and only one of these deaths (2%) was intraprocedural. This seems to suggest that in terms of short term safety, the two techniques are very similar. It is also interesting to compare the causes of death in the two trials. In the SAVR trial, 78% of deaths in the first 30 days are said to have been due to cardiac cause, whereas 33% of deaths in TAVI were due to cardiac cause. This may suggest that SAVR is more invasive and damaging to the heart as a procedure, however reliable conclusions cannot be drawn from such limited data.

Some data regarding the long term outcomes of both techniques was included in both trials. In the TAVI trial, the death rate for around 359 days is said to be 30%, whilst the 1 year mortality rate for the SAVR trial was roughly 18.6% (68 patients died in the 4.6 years after the procedure- 18 of which died in the first month.

Therefore 1 year mortality rate= 100 . ). Another interesting comparison, is how

these deaths are distributed over the year. In the SAVR trial, approximately 26.5% of the deaths occurred in the first month after the procedure, whilst in the TAVI trial, around 40% of deaths in the first year occurred in the first month after the procedure. This perhaps suggests that problems with TAVI emerge earlier than problems with SAVR, although this difference may be due to patient profile.

Other data is also given as to the efficacy of each procedure. In the TAVI trial, the mean aortic valve area is said to have increased to 1.7±0.4 (there is less than a 0.1% probability that this difference is due to chance alone); however no data is supplied for change in valve area for SAVR. The SAVR trial does state however that in the first year after surgery, 95% of patients decreased by one of more NYHA functional class. This valve is dramatically

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reduced in the TAVI trial to just 50% of patients improving by at least 1 NYHA functional class postoperatively. This suggests that SAVR is more effective at relieving the symptoms or aortic stenosis than TAVI, however we are not told the time frame in which the TAVI data was collected, and so it may be that 100% of patients improved by at least one functional class one year after surgery, and the 50% value was taken immediately after the procedure. It is very difficult to draw solid conclusions from incomplete data.

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Economic Feasibility

I learnt on the work shadowing placement that TAVI as a procedure, was far more expensive than its surgical equivalent. This evidently has further implications as to the feasibility of both treatments within the NHS. The health service’s budget is of course limited, and so it is sometimes forced to evaluative the effectiveness of particular treatments, based on both their clinical utility and financial demands. This is one of NICE’s roles, and QUALYs (Quality Adjusted Life Years) are used to calculate the validity of a treatment’s use in the NHS. They represent the number of years (at a reasonable standard of living) that a patient could gain from a treatment. Cost effectiveness takes both QUALYs and cost into account (the rough cost of SAVR per procedure in 2005 was $60,000). One study suggested that SAVR’s cost effectiveness was less than $20,000 per QUALY for octogenarians, and $27,182 per QUALY

for nonagenarians17. This is around £13,500 and £18,300 per QUALY respectively, which

are both below the £20,000 limit imposed by NICE as a guide to what is, and what is not cost effective, therefore it would appear that SAVR is cost effective for even the most elderly. It is extremely difficult to calculate the cost effectiveness of TAVI, because the implant’s durability is somewhat unknown; due to the youth of the technique, and elderly patients dying before the valve’s lifespan can be seen. It is possible that the inflated prices of TAVI are largely due to the recent nature of the technique. Specialist equipment is more expensive than that which can be produced on mass, and so perhaps the cost of TAVI would decrease if healthcare organisations started to use it more. Equally, the shorter recovery times associated with TAVI mean that patients return home more promptly, and may need less anti infection treatment, then funds can be saved by the NHS.

TAVI is generally regarded as cost effective for nonagenarians, as the alternative for such patients is inaction (requiring extensive palliative care), or high risk SAVR (requiring intensive postoperative care). The device’s durability does not pose any problems in this group, as life expectancy is generally short anyway. TAVI’s cost effectiveness in younger patient groups is however, questionable; largely because further treatment later in life may well be necessary.

      

17 

Wu Y, et al. “Cost-effectiveness of aortic valve replacement in the elderly: An introductory study.” The Journal of Thoracic and Cardiovascular Surgery. 2007; 608-613

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Overall

My research and discussion has all been geared towards answering the question: will TAVI ever take the place of SAVR, in the treatment of aortic stenosis in the NHS? TAVI of course shows great promise in the treatment of stenosis, however SAVR, which has been used for around fifty years, is seen by many as an exemplary procedure, with extremely low mortality rates, and high success rates. It is recognised, that like any other new procedure, TAVI is passing through a ‘learning curve’, that is, data are fluctuating greatly, whilst the procedure’s various characteristics emerge. It would therefore be unwise to make a definitive decision on the technique’s value, when so little is known about its long term potential.

The evidence available renders comparison more difficult. Whilst it does sometimes appear that TAVI mortality rates are elevated, this could well be due to the selected patient’s poor condition; as well as the variety of procedural errors such as valve misplacement, or unsuitable sized catheters, which are perhaps not intrinsic faults of the procedure itself, but rather creases that will be ironed out by experience and minor amendments.

Trials show that both SAVR and TAVI are capable of relieving symptomatic aortic stenosis, however there is limited information available on the long term efficacy of TAVI; whereas SAVR (particularly when the prosthetic vale is mechanical) is known to last. A full

comparison will only become possible with further research, when the durability of TAVI is revealed. This also implies however that data must be collected for a variety of patient groups, including younger sufferers. This would at the moment be unethical, due to both the high level of procedural complications, and the unknown lifespan of the valve.

In terms of financial feasibility, it is widely accepted that TAVI is cost effective for the treatment of the elderly, however its cost effectiveness in younger patients is unknown, largely due to the unknown durability of the implant. Costs are also likely to decrease as TAVI becomes more widely utilised.

My conclusion is therefore that TAVI will not, in the short term, replace SAVR as a treatment of aortic stenosis in the NHS. This deduction is based partially on uncertainty which will in time be remedied by further literature on TAVI; however it is also because SAVR and TAVI are so different. They may not be simply different solutions to the very same problem, but perhaps are instead both extremely valid, and promising techniques in their own right, both suited to solving slightly different problems. SAVR is a viable, low risk, effective correction of symptomatic aortic stenosis in the vast majority of cases. Its efficacy has been proved by time, and therefore such a treatment does not need to be

replaced; it is not in any way deficient. SAVR only falls short in the treatment of very high risk patients, with short life expectancies, who cannot withstand such an invasive procedure. It is in the treatment of this very category in which TAVI excels; whereas it is perhaps not a feasible long term solution, for the treatment of younger patients. TAVI’s purpose is primarily to relieve the symptoms of stenosis, to improve the patient’s quality of life, for a relatively short period of time. SAVR’s purpose is to provide long term symptom relief for an extended period.

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TAVI must not be discarded simply on the grounds of turbulent data, which are somewhat inevitable in preliminary trials, especially with a high risk patient profile. In time, TAVI’s full potential as a treatment of aortic stenosis will be seen; but in the mean time, it must not be regarded as a competitor to SAVR. Rather it should be seen as yet another,

complimentary treatment, to tackle a disease with such diverse manifestations, in such a varied patient demography.

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Appendix 1- The Healthy Heart

The heart is essentially made up of two pumps, which are side by side (separated by the septum), and mirror each other’s actions exactly. The right hand side of the heart is

responsible for pulmonary circulation, that is pumping deoxygenated blood from the body to the lungs where it is oxygenated; and the left hand side’s role, is to pump oxygenated blood from the lungs to the body, and in doing so, maintain systemic circulation. It is the left hand side of the heart that aortic stenosis primarily affects. For oxygenated blood in the lung capillaries to reach the rest of the body, it must first travel through the pulmonary vein, into the left atrium (the small chamber of the left side of the heart), down through the mitral valve into the left ventricle (the largest and most powerful chamber of the heart), and on ventricular systole, the blood is pushed up into the aorta by high pressure. The aorta is the body’s largest blood vessel, and the vital link between the heart, and systemic circulation. The cardiac cycle is controlled by nervous impulses, generated in the SAN, which travel through the cardiac tissue, inducing systole.

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Appendix 2- Work Shadowing

I was fortunate enough to spend one week (the week commencing 15/06/09) shadowing a consultant cardiac surgeon and his colleagues, at Guy’s and St Thomas’ NHS Foundation Trust, London. Not only was this experience invaluable for my application to medical schools, but it was also the inspiration to conduct an extended project looking at the different treatments of aortic stenosis.

I spent roughly half the time observing surgical procedures. This of course included TAVI and SAVR, but I also witnessed coronary artery bypass grafts (a treatment of coronary artery disease), and the correction of an aortic dissection. It was exhilarating to see text book biology brought to life, and I was amazed by the skill and coordination of the surgical team. The highlight of the surgical procedures, was the treatment of an aortic dissection. This operation took roughly nine hours, and combined coronary artery bypass grafting, the replacement of the aortic valve, and the replacement of the ascending aorta. To do this procedure, circulation had to be stopped completely (i.e. off bypass), for around forty minutes. It was the culmination of all my newly acquired knowledge and experience. I also spent time shadowing a registrar on the cardiac ward. Here I was able to observe the recovery of patients after SAVR and similar procedures; as well as gain an insight into a different side of medicine. I realised how, and learnt why strokes are common after cardiac surgery (due to equipment knocking sediment off the walls of vessels/valves, which go on to get lodged in cerebral vessels, leading to ischemic damage), and had many scientific and career based questions answered by the staff.

I decided to look at the treatment of aortic stenosis, rather than say, coronary artery disease/ atherosclerosis, for several reasons. Firstly, the disease was new to me, and so it seemed all the more captivating, whereas we had studied other types of heart disease in biology. Also, I was stuck by the two different methods for treating aortic stenosis, whereas I only witnessed one method for treating generic ‘heart disease’. I also sensed an excitement in the catheter laboratory whilst watching TAVI, as if the staff saw this new treatment as a very positive, promising procedure, and I was keen to see if this was the case, and why.

On returning, I was keen to use my new knowledge in a constructive way, and decided that I wanted to do more research into what I had seen. The extended project has proved to be extremely satisfying, as on commencing research, I began to understand what I had seen on placement even more.

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Glossary

ACE Inhibitors- Angiotensin Converting Enzyme inhibitors, are drugs responsible

for inhibiting the action of an enzyme which produces Angiotensin II, a chemical causing vasoconstriction in blood vessels. Subsequently vessels dilate, reducing blood pressure, and so less damage is done to various tissues in the circulatory system.

Aneurysm- A blood filled swelling at a weakened point of a vessel. Aneurysms may

rupture, causing major internal bleeding/stroke.

Aortic Annulus- A ring of fibrous tissue surrounding the base of the aorta.

Aortic Dissection- A medical condition in which blood forces a tunnel through the

aortic wall, and so flows between the different tissue layers; which consequently dissects the wall of the aorta, and makes aneurysm formation and rupture far more likely.

Aortic regurgitation- A disease in which the aortic valve cusps do not form a tight

seal, and so allow blood to move from the high pressure aorta into the lower pressure left ventricle on ventricular diastole.

Aortic sclerosis- Stiffening of the aortic valve cusps.

Aortogram- A minimally invasive, diagnostic procedure, in which a flexible catheter

is pushed through a patient’s blood vessels, and contrast dye is released in the aortic root, allowing the aorta to be seen with X ray.

Aspiration- The anaesthetised patient’s gag reflex is inactive, and so foreign bodies

such as stomach contents may enter the lungs. Equipment is used to minimise this risk.

Atelectasis- A condition in which part of the lung collapses, often caused by the

inhalation of a foreign body, or an accumulation of mucus.

Atherosclerosis Formation- Damage to the epithelial cells in a vessel (usually an

artery) causes the deposit of low-density lipoproteins in the tissue. If these LDLs are oxidised, they form a cytotoxic substance, capable of triggering an inflammatory response, leading to the build up of lymphocytes; as well as causing mineralisation.

Balloon Valvuloplasty- A balloon catheter is pushed along a patient’s blood vessels

to the diseased valve. Once in position, the balloon is inflated with saline solution, and pushes back the stiffened valve cusps, consequently widening the valve diameter.

Cardiac Output- The volume of blood pumped from the left ventricle in one minute.

This is calculated by the formula: stroke volume x heart rate.

Consultation- An appointment in which a patient discusses their individual condition

with their doctor. It may be pre or post treatment, and often involves a physical examination.

Coronary Artery Bypass Graft- The use of a section of vein/ diversion of an artery

in the wall of the thorax, to bypass a blockage in coronary arteries. This ensures that cardiac muscle has a sufficient supply of blood, and the substances that it carries.

Diastole- Relaxation of the cardiac muscle.

Diathermy- The use of high frequency electrical current/ microwaves to produce

heat. The heat may be used to cut through tissue, and cause electrocoagulation, allowing the surgeon to cut through tissue with minimal blood loss.

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Glossary

Doppler Scanning- A type of ultrasound scan, which relies on the Doppler Effect-

ultrasound waves are reflected from moving blood at different frequencies, allowing a picture of the concerned tissues to be built up.

Dyspnea- Difficulty in breathing.

Endocarditic Prophylaxis- The use of treatments and drugs to prevent inflammation

of the endocardium; which is usually due to micro-organisms.

Endocardium- The thin membrane that coats the heart’s interior, and its valves.

EuroSCORE- European System for Cardiac Operative Risk Evaluation. The figure

takes into account a patient’s individual risk factors, which have different weights, based on previous experience. The percentage is the predictive probability of death. It can be used to gain an insight into the patient’s overall physical condition.

Fibrosis- The thickening of a tissue.

Heart Rate- The number of cardiac cycles which take place in one minute (one

cardiac cycle consists of both systole and diastole).

Ischaemia- Insufficient blood supply to a particular tissue.

Left Ventricular Ejection Fraction- The fraction of blood within the left ventricle

that is successfully pumped into the aorta during ventricular systole. A normal ejection fraction is 55%-70%.

Left Ventricular Hypertrophy- An enlargement of the cardiac muscle making up

the left ventricle. LVH can follow aortic stenosis as the left ventricle has to contract with more force and at a higher frequency in order to supply the body with enough blood through the stenotic aortic valve. This increased demand leads to the cardiac muscle increasing in size, reducing the ventricular volume, and ultimately leading to heart failure. The enlarged left ventricle may also bulge through the septum, reducing right ventricular volume, and so inducing pulmonary hypertension.

Low-Density Lipoproteins- A type of protein carried in the blood plasma,

responsible for the transport of cholesterol from tissues where it is stored, to circulation. More commonly known as ‘bad cholesterol’.

Median Sternotomy- The process in which the bone in the centre of the rib cage (the

sternum) is cracked, to allow access to the organs lying beneath.

Minithoracotomy- A minimally invasive alternative to a median sternotomy. A

small incision is made in the wall of the thorax, and a rib retractor is used to gain access to the tissues within.

Myocardial Infarction- A heart attack, caused by the shortage of blood reaching

cardiac muscle, often due to a blockage. This prevents the tissue from respiring at an adequate rate, and so leads to an irregular cardiac cycle, and ultimately, tissue death.

NICE- National Institute of Health and Clinical Excellence. This organisation is

responsible for evaluating new treatments, and deciding how the NHS’ clinical budget should be distributed.

NYHA Functional Class- New York Heart Association’s system of categorisation,

used to assess the severity of heart failure in a patient. There are four classes, the first being for those will the least severe heart failure, and the fourth for patients with the most severe symptoms. Patients are categorised based on symptoms which

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Glossary

Pericardium- The membranous bag which contains the heart. A procedure is said to

be ‘open heart’ if incisions are made to this tissue.

Pulmonary Hypertension- High blood pressure in the arteries supplying the lungs.

This can be due to increased resistance to the flow of blood into the left ventricle from the lung capillaries, due to a reduced ventricular volume. This condition may lead to right ventricular hypertrophy, and the failure of the right hand side of the heart.

SAN- The Sino Atrial Node is a bundle of cells situated in the wall of the right

atrium, responsible for generating the electrical impulses which induce cardiac systole.

Statins- Lipid lowering drugs, which are proved to reduce blood cholesterol levels,

and may play a prophylactic role in the treatment of aortic stenosis.

Stroke Volume- The volume of blood pumped into the aorta by the left ventricle in

one contraction.

Suturing- Surgical sewing.

Syncope- Dizziness, often induced by a shortage of respiratory substrates and so a

shortage of energy in the brain.

Systole- Contraction of the cardiac muscle.

Thrombosis- The formation of a blood clot, which may lead to myocardial infarction

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Journals/Periodicals

Baumback A, et al. “Surgical aortic valve replacement in octogenarians: results in patients who could be considered for Trans-catheter aortic valve implantation.” Heart. 2009;95;47 Brodsky AM. “Percutaneous approaches to aortic valve replacement.” Cardiac Interventions. 12/2004; 4-9.

Cribier A, et al. “Treatment of calcific aortic stenosis with the percutaneous heart valve.” Journal of the American College of Cardiology. 2006; 1214-1223

Donnelly AJ, et al. “Cardioplegia Solutions.” The American Journal of Hospital Pharmacy. 1991; 2444-2460

Ferguson JJ, et al. “Balloon Aortic Valvuloplasty: The Texas Heart Institute Experience.” Texas Heart Institute- Journal. 1990; 23-30

Flameng W. “Prosthetic aortic valves.” European Heart Journal. 1997; 1043-1044

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Vaquette B, et al. “Valve replacement in patients with critical aortic stenosis and depressed left ventricular function: predictors of operative risk, left ventricular function recovery and long term outcome.” Heart. 2005; 1324-1329

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National Institute for Health and Clinical Excellence. “Interventional procedure overview of balloon valvuloplasty for aortic valve stenosis.” Pub: 2003, Bazian Ltd. LONDON.

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Sussex Cardiac Centre. “Transcatheter Aortic Valve Implant.” Pub: 05/2009, Brighton and Sussex University Hospitals NHS Trust. BRIGHTON/SUSSEX.

The British Medical Association. “Illustrated Medical Dictionary.” Pub: 2008, Index Books Ltd. LONDON.

The TAVI team. “Trans Catheter Aortic Valve Implantation: Information for Patients.” Pub: 02/2009, Oxford Radcliffe Hospitals NHS Trust. OXFORD.

Zipes et al. “Braunwald’s Heart Disease (A Textbook of Cardiovascular Medicine).” 7th

Edition. Pub: Elsevier Saunders, 2005.

Miscellaneous

One week shadowing Mr V Bapat, Guy’s and St. Thomas’ NHS Foundation Trust. LONDON. Week commencing 15/06/2009.

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