Aortic stenosis (AS) is the most commonly occurring heart valve lesion in Western societies. Patients usually develop relevant AS aged 60–80 years. Once symptomatic, in terms of angina pectoris, dyspnea or syncope, patients should undergo treatment. Common therapy for AS is conventional aortic valve replacement (AVR). This standard procedure is performed via median sternotomy by using the heart–lung machine for temporary circulatory support, and cardioplegic cardiac arrest during valve replacement. AVR can be performed in most patients with a low degree of risk and excellent immediate and long-term outcomes; in-hospital mortality rates are as low as 1–3% in most centers, as indicated by large-registry data Citation[1].
Minimally invasive techniques were introduced into routine cardiac surgical practice in the mid-1990s. Conventional AV surgery thus changed towards only using a partial mini-sternotomy. Most patients can be treated by means of this minimized approach at comparable levels of precision and safety Citation[2]. Use of the heart–lung machine and cardiac arrest, however, is still a mainstay of the conventional techniques. Prosthetic heart valves have evolved in parallel during the past few decades: mechanical prostheses as well as third-generation xenografts have reached a high standard, providing easy handling during implantation, good hemodynamic function and sufficient durability for most patients.
Despite the excellent results of conventional AV surgery, patients are not uniquely referred for such therapy. The Euro Heart Survey in 2001 demonstrated that almost a third of patients with AS are not being referred owing to a potentially high-risk profile, which is caused by older age, reduced ejection fraction or risk of stroke Citation[3]. By contrast, some studies have pointed out that medical management is worse for most patients with symptomatic AS Citation[4].
Major technical developments have taken place during the past few years. Particularly for the field of AV surgery, new transcatheter (TC) techniques have been developed, allowing for beating-heart, off-pump AV implantation (AVI). Only minimal access is required with TC-AVI, using a retrograde transfemoral (TF), a retrograde trans-subclavian (TS) or an antegrade transapical (TA) approach. TC-AVI brings with it major differences in comparison with the conventional technique, namely leaving the stenosed and calcified leaflets in situ and stenting a new valve instead of suturing it into position. This allows for off-pump, beating-heart implantation, which is a truly minimally invasive procedure. TC-AVI has the potential to revolutionize the field of AV surgery for years. However, despite all the enthusiasm, at present, only the feasibility of these new approaches has been proven. The new TC techniques are being introduced in increasing numbers into clinical practice. Several questions remain with regard to these exciting approaches and will be discussed in the following sections.
Which patients should be treated?
The basic idea of TC-valve technology was to offer high-risk patients with a substantial risk for conventional surgery an alternative treatment option. In several series, TC-AVI was performed on a compassionate basis, only targeting the so-called ‘nonsurgical candidates’. Currently, the indication for TC-AVI is expanding to high-risk patients with a defined risk profile. As the current guidelines do not yet reflect the indication criteria for TC-AVI, a joint position statement was published by the European Society of Cardiac Surgery, the European Society of Cardiology and the European Society of Percutaneous Intervention to identify high-risk patients where TC-AVI instead of conventional AVR is justified Citation[5]. However, why not broaden the indication to younger and low-risk patients? TC-AVI is an exciting and truly minimally invasive procedure that is changing the field of AV surgery, but we need to be very aware of several factors:
• The development and marketing of TC-AVI is highly driven by the device-manufacturing industry;
• Little long-term data exist on the durability of TC valves, and, even more critically, the course of potential paravalvular leaks that occur frequently following TC-AVI is unclear at present;
• There are no available data from prospectively randomized trials comparing TC-AVI with conventional AVR to prove the superiority of TC-AVI – such data do not even exist for very high-risk subgroups of patients. Thus, TC-AVI should be restricted to selected, elderly, high-risk patients at present.
High risk can be defined by using different scoring systems. Older age and the presence of at least one relevant comorbidity can be considered common criteria. A logistic European system for cardiac operative risk evaluation (EuroSCORE) value of more than 20% or a Society of Thoracic Surgeons score of more than 10% have been used to define high risk. However, the logistic EuroSCORE may overestimate the effective risk Citation[6]. Therefore, division of the percentage by three may be warranted, leading to more realistic results, despite the fact that this has not yet been proven on a scientific basis. Furthermore, technical criteria such as true porcelain aorta or severe adhesions, for example, in patients with previous cardiac surgery and mediastinitis, are accepted indications for TC-AVI.
Will randomized studies comparing the new TC techniques & the conventional ‘gold standard’ be performed?
There is little doubt that randomized studies are needed and would result in more reliable indication criteria. The only study that is currently enrolling is the US Placement of Aortic Transcatheter Valve (PARTNER) trial, which compares the use of TF or TA Edwards-SAPIEN™ (Edwards Lifesciences, CA, USA) to conventional surgery. Unfortunately, the design of this study is not based upon a 1:1 randomization strategy and will probably not allow for direct comparison of TF- versus TA-AVI. An all-comers trial randomizing between TF- versus TA-AVI versus conventional AVR would be the optimal trial design – similar to the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) study, which compared coronary artery bypass grafts with percutaneous coronary interventions.
Given the costs and logistic obstacles associated with such a trial, we will probably not have hard data available within the next few years. Currently, data from international registries with several hundred patients included have become available. Although, at first glance, 30-day mortality and complication rates seem to be acceptable, incompleteness in the follow-up of some registries may lead to under-reporting of potential complications Citation[7]. Further initiatives to obtain reliable data for meaningful comparisons need to be made by all parties, namely medical societies and the device industry.
Which approach should be chosen: TF-, TA- or TS-AVI?
Feasibility has been proven for three different approaches: TF-, TA- and TS-AVI. At a first glance, TF-AVI seems to be the least invasive method of access, facilitating a truly percutaneous procedure. With the help of femoral suture devices, no surgical incision is needed at all. Thus, TF-AVI allows for AVI in conscious patients who are only under local anesthesia. However, there is a trade-off with a higher rate of peripheral vascular complications that can occur during TF approaches. Furthermore, the retrograde approach seems to be associated with an increased stroke rate (TF: 3–9%) compared with the TA method of access (TA: 0–3%), which is most likely to be due to retrograde crossing of the aortic arch with the deployment systems Citation[8,9]. Regarding vascular access, it became evident that the outcome is clearly linked to the required minimal sheath-size diameter of the delivery systems. The strength of the TA approach lies in the avoidance of the femoral vessel and the antegrade delivery minimizing manipulations around the aortic arch. Thus, TA-AVI is applicable in almost every patient, and the size of the delivery systems is not a key issue. The drawback of TA-AVI is the need for a minithoracotomy and general anesthesia. This may lead to limitations in patients who have a severely impaired respiratory function.
Retrograde AVI using the surgically dissected left subclavian artery (TS) is also feasible, but the reported experience is limited. TS-AVI requires surgical dissection, general anesthesia and retrograde crossing of the aortic arch. Thus, the TS access will most probably be limited to patients with contraindications for TF- or TA-AVI.
At present, the superiority of one approach over the others is not proven. A randomized study should address this issue in the near future. Typically, patients referred for TA-AVI present with severe calcified vessels more often. Care is needed when judging the current results of TA- versus TF-AVI, as peripheral vascular disease has been demonstrated to be a major risk factor significantly affecting clinical outcome in high-risk patients. Differences in the risk profiles of the patients who are included in the different series may have the most important impact upon outcomes.
What is next in T-AVI?
Many companies are currently working on new TC devices to develop second-generation valves and delivery systems that attempt to improve the reliability and ease of implantation, with the ultimate goal of patient safety. Conversely, the huge amount of money invested into these developments clearly reflects the economical expectations of the industry in the field of TC heart valves. The task for clinicians is to maintain the balance between patient care, which is only supported by hard data, and research and business, which are supported by industry.
Currently, the CoreValve® (CoreValve, CA, USA; TF and TS only) and the SAPIEN (TA and TF) prostheses are the only commercially available TC valve systems, and both recently obtained CE-mark approval. Numerous new TC valve projects are emerging on the horizon, most of which are still at the level of the animal laboratory. Human implants have been reported for the Ventor™ system Citation[10], allowing for anatomically correct rotation of the valve, and for retrievable devices, such as the DirectFlow™ Citation[11] and the Sadra Lotus™ Citation[12] valves. For TF- and TS-delivered valves, the required minimal sheath diameter will probably determine outcomes and economical successes of new devices, whereas in systems designed for TA implantation, size is not an issue but modifications that result in less paravalvular leakage would enhance acceptance among the surgical community.
In addition to new valve systems, the hardware for TC valve implantation is evolving rapidly. More and more centers are building, or planning to build, a hybrid operating room providing the optimal environment for TC-AVI. The most critical step in TC-AVI is exact valve positioning. Thus, imaging modalities are of utmost importance. Recently, a new imaging modality was developed to ease valve positioning and implantation – the so-called Dyna-CT™ (Siemens, Germany). After rotational angiography using the regular C-arm, a computed tomography-like image of the aortic root is used for online overlay during valve implantation.
Despite the rapidly evolving technology in TC-AVI, the outcome is still strongly influenced by human factors. A dedicated team with cardiologists, surgeons and anesthetists working closely together is probably more important than the latest ‘high-tech’ equipment.
Another issue with TC-AVI is cost–effectiveness. At present, a TC valve is ten-times more expensive than a conventional tissue valve. At the same time, the superiority and, in particular, cost–effectiveness of TC-AVI compared with the excellent outcomes and cost–effectiveness of conventional AVR is unproven. This has led to controversial discussions regarding health-resource utilization and reimbursement issues.
In summary, TC-AVI is a rapidly evolving field that is unlikely to disappear from clinical practice in the future. Owing to the truly minimally invasive nature of this technique, T-AVI has the potential to become a reliable treatment option in selected high-risk patients. Currently, the superiority of TC-AVI compared with the excellent outcomes associated with conventional AVR is not proven by any randomized trial. Such a trial is definitely needed before we should even start to think about broadening the indication for TC-AVI to younger and lower-risk patients. A close collaboration between cardiac surgeons and interventional cardiologists is mandatory to ensure optimal outcome and patient safety. We should not repeat the inglorious story of coronary artery bypass grafts versus percutaneous coronary interventions but rather combine the key skills of each discipline by building highly specialized TC-valve teams. Patients do not benefit from political discussions or broadened indications that are not supported by evidence-based data.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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