Over the last century the pathophysiology of valvular heart disease has changed dramatically. Aortic stenosis has become the most common valvular disease among patients referred to hospital, and affects approximately 3% of patients over the age of 75.1 Whilst rheumatic heart disease has been on the decline in Western countries, calcific, degenerative aortic stenosis has been on the increase.

In 2003, the European Society of Cardiology commissioned the Euro Heart Survey2 to provide quantitative information on the burden of cardiovascular disease in Europe. The majority of patients with severe symptomatic aortic stenosis were over 70 years old at the time of surgical aortic valve replacement, and, as expected, had several comorbidities. The reasons for not advising intervention in patients with severe valvular heart disease could be grouped into cardiac, extra cardiac or both. Some patients were not referred to a cardiac surgeon as they had improvement of their symptoms on medical therapy. Others had poor left ventricular function and were, therefore, considered by their physician to be at too high risk for surgical intervention. Of particular concern was the fact that age alone was the most frequently cited comorbidity that precluded surgical consideration. In total, 31.8% of patients with severe single valve disease did not undergo intervention. This was despite (or perhaps resulted in) an excellent 3.1% mortality at 30 days in those patients undergoing aortic valve replacement. The prognosis of symptomatic severe aortic stenosis with medical therapy alone is poor, with an average survival of one to three years.3

The future burden of degenerative aortic stenosis is likely to be significant. In 2012, Iung and Valhanian1 revisited the demographic trends 10 years after the initial Euro Heart Survey. The prevalence of aortic stenosis was found to be very low (<0.2%) before the age of 65 years and increases steadily thereafter. There is predicted to be an ageing population in Europe over the next 50 years, with the numbers of over 75 year olds in France, for example, likely to double to 16.2% by 2060. Based on estimations from the European series, this would result in the number of over 75 year old patients in France with aortic stenosis increasing from 159,600 in 2010 to 333,200 in 2060. This trend is expected to be reflected throughout Europe over the next 50 years.

Transcatheter aortic valve implantation-the procedure

The concept of percutaneous valve replacement began in the 1980s when elderly patients with degenerative calcific aortic stenosis were often considered to be at too high risk of significant morbidity and mortality to be offered surgical aortic valve replacement. The French cardiologist Professor Alain Cribier is widely credited as being the pioneer in the TAVI field. His work with balloon aortic valvuloplasty showed good improvements in quality of life in patients presenting with severe symptomatic aortic stenosis, but the beneficial effects were short lived, hampered by the lack of survival benefit and recurrence rate of 80% at one year.4 Initial post-mortem studies trialling a stented bioprosthetic valve were promising, with the first clinical implantation taking place in 2002. After further refinement and development, two TAVI valves, one balloon expandable and one self-expanding, received CE mark approval in 2007 and thus became available for widespread commercial use in Europe.

The TAVI procedure itself has been under continual development over the last six years. In essence, a bioprosthetic valve is crimped onto a delivery system that is introduced into the arterial tree. The most common routes for this introduction are transfemoral, transapical (through a small submammary thoracotomy) or transaortic (through a paramedian incision in the right chest). The route of choice is via the femoral artery as this reduces the post-procedural discomfort and analgesia requirement. However, transfemoral access requires a suitable calibre of peripheral vessel, and the absence of significant calcification or aneurysm formation and is thus not suitable in all patients. The size of the introducer sheath has reduced considerably over time and is likely to continue to do so as the technology improves further. The bioprosthetic valve is then advanced across the native aortic valve and positioned using fluoroscopic and transoesophageal echo guidance. A temporary pacing wire is placed in the right ventricular apex to allow a period of rapid pacing during valve deployment. This is designed to prevent the left ventricle from ejecting and displacing the valve before it is firmly surrounded by the native annulus. One significant benefit of TAVI over surgical AVR is that it can be performed on a beating heart, removing the need for cardio-pulmonary bypass and the complications thereof. Although the procedure is usually carried out under general anaesthesia in the UK, many European centres use local anaesthetic and sedation for those undergoing transfemoral TAVI. The typical inpatient stay following an uncomplicated procedure is between three and five days.

Evidence for TAVI

The adoption of TAVI technology in the US was delayed by the requirement of the regulatory bodies to have outcome data from randomised controlled trials. The Placement of AoRtic TraNscathetER Valves (PARTNER) trials5-7 were the first randomised multicentre studies, and are arguably amongst the finest examples of medical trial design and execution to date. PARTNER B compared TAVI with medical management (with or without balloon aortic valvuloplasty) in patients that were considered to be surgically inoperable. PARTNER A compared TAVI with surgical AVR in patients considered to be high risk surgical candidates. When compared with medical management (even in patients who received a balloon aortic valvuloplasty) there was a 20% reduction in mortality in the TAVI cohort at one year and an even greater benefit at two years. The comparison of surgery versus TAVI showed TAVI to be non-inferior in those at high operative risk. These results are even more remarkable when it is considered that they also represent the early generation of TAVI devices.

Outcome data

Given the PARTNER results, there were many within the cardiological community calling for a widespread application of the TAVI technology to lower risk patients. This call has largely been resisted as the long-term morbidity and mortality data from the procedure is awaited. To this end, several national and international registries have been compiled to comprehensively record detailed outcome data. The largest of these to date is the SOURCE registry,8 charting the progress of patients receiving the Edwards SAPIEN™ valve. This reported a 93.8% procedural success rate, with a 30 day mortality of 8.5%, well below that predicted by the EuroSCORE (27.6%). The EuroSCORE9 is a well validated risk calculator used prior to cardiac surgery. The rate of permanent pacemaker implantation was 7% and the stroke risk 2.5% at 30 days. The one year survival from the same cohort was between 72.1% and 81.1% with the transfemoral group faring better. This may, however, represent the fact that those requiring a non-transfemoral TAVI were also at greater surgical risk due to more extensive comorbidities. Indeed, half of these deaths after 30 days were attributed to a non-cardiac cause, reflecting the high risk group that is currently offered a transcatheter procedure. There was also a significant improvement in the functional status of patients at one year.

Quality of life in the elderly

Quality of life is obviously a critical outcome when measuring the effectiveness of TAVI in this high risk elderly population. Ussia et al10 studied 149 patients who underwent TAVI in Italy and assessed their physical and mental scores, both of which showed significant improvement at one year. Indeed, these patients had no significant difference in their quality of life scores when compared to the general population over the age of 75 years. Bekeredjian et al11 showed a similar significant clinical benefit from TAVI in a population age over 81 years.

Cost effectiveness

Recent cost effectiveness data does support the use of TAVI in the treatment of high risk surgical candidates as having a cost advantage in length of intensive care stay, rapid mobilisation and early hospital discharge.12,13 This benefit persists post discharge with octogenarian patients reporting a gain in physical and mental functioning, and a reduction in bodily pain.11

Risk stratification

It is often said that the key to a successful TAVI procedure lies in patient selection. Unfortunately, a TAVI specific, multi-factorial, risk assessment score that provides the required robust analysis in even the highest risk patients remains elusive. Central to all programmes providing a TAVI service is the multidisciplinary heart team, comprised of cardiac surgeons, cardiologists, anaesthetists and often physicians with a subspecialist interest in elderly care. It is only with the unanimous agreement of this heart team that a patient is currently offered a TAVI procedure. One unexpected yet welcome effect of the heart MDT is that the number of surgical aortic valve replacements performed in TAVI centres is actually increasing, presumably due to a lower referral threshold for patients at high risk.

Perhaps the most appropriate risk stratification strategy to use in a procedure that has such a benefit over medical management is an attempt to predict those patients who may have either a high procedural mortality or a poor treatment response. Interestingly, it appears that those patients with low gradient aortic stenosis (due to a poor left ventricular function) or those with tricuspid regurgitation have a higher all cause mortality.14 Post procedural paraprosthetic aortic regurgitation was a strong predictor of both mortality and poor treatment response.

Society guidelines

The European Society of Cardiology (ESC) has released two guidelines specifically addressing the use of transcatheter technology in aortic stenosis. The first position paper published in 200815 was updated more recently in the joint guidelines published by the ESC and the European Society for Cardiothoracic Surgery.16 The position at present is that patients with severe symptomatic aortic stenosis who are not surgical candidates, or who are at high risk of surgery, should be considered for TAVI, providing they do not have a separate reason for a compromised life-expectancy in the short term. This consideration should be undertaken by a multidisciplinary heart team that is comprised of both surgeons and cardiologists with a sub-specialist interest in TAVI.

In the UK the British Cardiovascular Intervention Society (BCIS) and the Society of Cardiothoracic Surgeons (SCTS) issued a joint position statement shortly after the two devices in Europe received the CE mark. A group of members of both Societies with experience of the procedure and knowledge of the literature formulated the guidelines. They re-iterated the advice that TAVI should be reserved for patients considered by the heart team to be at high risk of surgical aortic valve replacement (log EuroSCORE >20 or STS >10) but who would otherwise benefit from TAVI. 17

The future of TAVI

As with any technology in its infancy, there are questions that still need to be addressed before TAVI becomes the intervention of choice in all patients with symptomatic, severe aortic stenosis. Surgical aortic valve replacement has a proven track record of mortality and morbidity reduction, together with data attesting to the durability of the implanted prostheses. Such data for TAVI is several years away, but there has been no early signal to date that suggests that the bioprosthetic TAVI valve will be any less durable than its surgical counterpart.

As the TAVI procedure is refined and experience gained, the appropriate expansion to lower risk groups will be inevitable. Indications such as acute aortic regurgitation, valve-in-valve procedures for failing surgical bioprostheses, or transcatheter valves placed in the mitral position will all be considered. The next generation of valves and their delivery systems will become easier to manipulate through smaller sheaths, widening the patient population who might benefit from the preferred transfemoral approach.

The future for transcatheter valve technology appears bright, but each new indication should be carefully considered to avoid replacing the surgical standard with a sub-standard percutaneous alternative.

Conclusion

Transcatheter aortic valve replacement has developed rapidly since the first clinical case 11 years ago. The elderly patient with symptomatic, severe aortic stenosis has much to gain when referred to the heart team for consideration of intervention. In this group, TAVI has been shown to improve quality of life and reduced morbidity and mortality, whist also remaining cost effective. The 30% of patients identified in the Euro Heart Survey that were never referred for consideration of intervention on the aortic valve should now be assessed carefully by the heart team. The landscape of aortic valve intervention is changing rapidly and the prospects look good for the growing numbers of patients we are likely to encounter with aortic stenosis who pose an unacceptable risk for conventional, surgical aortic valve replacement.

 

Conflict of interest: SR Redwood is a proctor for, and has received research funding from, Edwards Lifesciences Inc.

 

References

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