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To evaluate the current and future role of percutaneous aortic valve replacement, we need to ask three main questions:

1. What is the natural history of the disease and where did we stand after the widespread availability of surgical aortic valve replacement?

2. Where do we currently stand?

3. Where are we going from here?

Regarding the first question, before the advent of surgical aortic valve replacement in the early 1960s, symptomatic severe valvular aortic stenosis was uniformly associated with a poor prognosis, with an average life-expectancy of less than three years similar to that of some malignancies.1,2 Likewise, the quality of life was frequently miserable. Moreover, to the frustration of all caretakers involved, no medical treatment was or, for that matter is, available to either improve survival or quality of life.3 Unlike few other procedures, surgical valve replacement dramatically improved longevity such that, apart from the generally low perioperative mortality rate, survival and quality of life are now comparable to that of an age-matched population without valvular heart disease.1 Therefore, surgical aortic valve replacement has revolutionized the care of these patients as well as those with aortic insufficiency, and has rightfully become the treatment of choice with an expected surgical mortality of 4% or less in the ideal candidate.4 Nevertheless, despite the availability of this well-established treatment, a substantial number of patients with severe symptomatic valvular aortic stenosis and comorbid conditions do not undergo surgical valve replacement due to high surgical morbidity and mortality rates.5,6 Hence, the concept of the less invasive aortic balloon valvuloplasty was developed by Cribier et al7 in 1986 and was more widely adopted until it became clear that it offers only modest hemodynamic and symptomatic improvement, is almost invariably associated with recurrent symptoms, has no proven survival benefit, and is associated with a significant periprocedural risk.8–12 Yet, until recently, this has remained the only alternative treatment option for patients with severe aortic stenosis deemed too high-risk to undergo surgical valve replacement.

Where do we currently stand?

The concept of a valve, mounted on a stent, delivered via a percutaneous route was first entertained by Andersen et al in 1989.13 Subsequently, in the same year, an aortic pig valve was sutured onto a balloon-expandable stent and delivered and implanted via the surgically exposed abdominal aorta to various sites of the ascending and descending aorta in a pig model.13 Implantation at the subcoronary position, however, was unsuccessful due to impingement of the coronary arteries after valve deployment. This early experience demonstrated the feasibility of the percutaneous valve replacement concept, however, due to the size of vascular access required and questionable long-term performance, enthusiasm was limited. Aided by the rapid developments of percutaneous coronary, structural heart and peripheral vascular technology, interest to further explore this concept had reemerged in 2000, and was followed by the first human implantation of a stent-mounted valve into the pulmonary position by Bonhoeffer et al in 200014 and subsequently into the aortic position by Cribier et al in 2002.15 As with most new technology, early complication rates were high. More importantly, however, the feasibility had been demonstrated and ignited new excitement to rapidly improve the technology of this desperately needed alternative. It was immediately clear that the most dreaded complications would be related to vascular access, device migration, malposition, embolization related to aortic atherosclerotic plaque or the native aortic valve, and valvular regurgitation due to incomplete apposition of the stent. In the meantime, many technical refinements have been implemented which allow lower-profile sheaths for valve delivery, and less bulky and somewhat steerable devices are easier to maneuver through the iliac vessels, aortic arch and aortic valve. In addition, early experience has allowed better patient selection for this procedure.

To date, though many different prototypes are currently being studied in animal models and humans, the two most widely evaluated valves are the balloon-expandable Edwards Sapien valve (Edwards Lifesciences, Irvine, California, USA) and the self-expanding CoreValve (CoreValve, Medtronic, Inc., Minneapolis, Minnesota, USA). In this issue, Ben-Dor et al provide us with an excellent detailed description of patient selection taking the clinical, anatomical and technical features into account, as well as the steps required for the performance of the procedure using the Edwards Sapien valve via the transfemoral technique. In addition, the available data using this type of valve are reviewed. These are registry data, however, several important conclusions can be made. First, data on more than a thousand patients are now available. Second, compared to the early experience, in the hands of seasoned operators, the periprocedural complication rate has decreased tremendously in recent years, with a current expected 30-day combined mortality and stroke rate in the range of 10%, which compares favorably with the reported mortality rate in high-risk patients who undergo conventional surgical valve replacement. Third, there appears to be a significant learning curve, emphasizing the importance of rigorous training for individuals who plan to learn this procedure. Fourth, the hemodynamic results are excellent, compare well with the surgical results, and appear to be durable. Finally, the intermediate-term follow-up results are encouraging. Major vascular complication rates and the occurrence of hemodynamically important aortic regurgitation are low. Importantly, as demonstrated by the most recent SOURCE registry data, with careful patient selection and when meticulous care is applied to vascular access techniques, complication rates can be reduced.16 Therefore, based on the available data, it is reasonable to offer a percutaneous approach to patients at very high surgical risk (predicted operative mortality in the 10% range) whose comorbidities would prohibit a conventional surgical approach. The results should optimally be followed as part of a registry for quality assurance. Several of Ben-Dor and colleagues’ described techniques are helpful and deserve special mention. First, the procedures are generally performed in the absence of endotracheal intubation, but with immediate backup by Anesthesiology. Second, the stent is mounted low on the balloon to minimize device embolization risk. Third, prolonged inflations are performed to minimize the risk of aortic regurgitation or the need for repeat balloon inflations. To minimize bleeding after sheath removal and during percutaneous suture closure, a balloon is inflated in the ipsilateral iliac circulation at low pressure and angiography is performed after closure to confirm vessel patency.

One of the most frequent reasons for procedural failure or patient exclusion for a percutaneous approach is an unsuitable femoral or iliac vasculature. To allow optimal planning, imaging tools that offer the best resolution, delineation of calcium, diameter measurement and three-dimensional assessment are essential. The most frequently used method is computed tomographic (CT) angiography with three-dimensional reconstruction. However, this technique requires the use of a substantial amount of contrast, with an inherent risk of contrast nephropathy if used conventionally in patients with underlying renal dysfunction. Ben-Dor et al describe an excellent technique that uses CT imaging with percutaneous injection of a limited amount of diluted contrast via a pigtail catheter placed in the aorta. It requires a minimal amount of contrast while maintaining the quality of conventional CT imaging. This technique appears very promising for the frequently encountered patient with severe aortic stenosis and concomitant renal insufficiency and may provide an alternative method for other vascular imaging purposes.

After thorough assessment, not uncommonly, it becomes clear that the femoral or iliac vasculature is unsuitable for device delivery. Under these circumstances, until recently, the direct apical approach with surgical exposure of the heart, left ventriculotomy and direct antegrade valve delivery to the aortic position or surgical exposure of the common iliac artery were the only available options. However, in this issue, Gerckens et al describe their experience with percutaneous valve replacement via the subclavian approach. Though it has been described previously,17–19 this is the first larger series of patients treated via this novel approach and it appears to offer a good alternative for patients whose lower-extremity vasculature prohibits the use of the transfemoral route. The reported procedural success and complication rates are very low.

Where are we going from here?

The encouraging results to date should not deter us from pursuing further technical and procedural refinements. Particular focus should be the reduction of device profiles to facilitate percutaneous access in order to expand the use for patients who are currently excluded due to insufficient iliofemoral vasculature. Furthermore, techniques allowing more precise positioning and the option of repositioning after complete deployment should be explored. More than ten valve prototypes are currently under investigation in animal models and humans including valves with non-biological leaflets that do not require the special preservation and preparation of most other currently available models and can be delivered through considerably smaller introducer sheaths.

At this point, after establishment of the feasibility and demonstration of results comparable to those achieved by surgery in high-risk patients, further studies are needed to confirm our current outcomes and, more importantly, to determine which patients are most appropriate for this procedure. To this effect, the PARTNER IDE trial outlined by Ben-Dor et al is underway. This trial is the first randomized trial comparing percutaneous aortic valve implantation (Edwards Sapien Valve) to conventional surgical replacement in patients with severe symptomatic aortic stenosis with high surgical risk (predicted operative mortality ≥15%). In addition, inoperable patients will be randomized to percutaneous aortic valve replacement versus medical management with or without balloon valvuloplasty. More than 1,000 patients are planned for enrollment. The results are expected to be presented in early 2010. Likewise, a large randomized trial using the CoreValve is planned. Until further data are available, reservation is indicated in young patients because the long-term outcomes with percutaneous devices are not yet clear.

Conclusion

Despite technical limitations and the absence of randomized trial results, the percutaneous treatment option is a promising new tool in our armamentarium and will hopefully soon ameliorate the sense of helplessness experienced when confronted with a patient with severe inoperable symptomatic aortic stenosis who traditionally would face a short survival and frequently a miserable quality of life.

From the CardioVascular Center, Frankfurt, Germany.

Address for correspondence: Prof. Dr. Horst Sievert, CardioVascular Center Frankfurt, Seckbacher Landstrasse 65, 60389 Frankfurt, Germany. E-mail: info@CVCFrankfurt.de