Several large European and Canadian registries have been published, showing excellent short- and midterm results after TAVR using both the TF and TA devices [12, 15]. The largest registry reported to date is the SOURCE (SAPIEN Aortic Bioprosthesis European Outcome) registry [17, 18]. Overall, 1,038 patients were enrolled at 32 European centers and were treated with either a TF (n = 463) or TA approach (n = 575). Patients treated by TA had more comorbidities at baseline than TF patients, resulting in a significantly higher EuroSCORE (29.1 % vs. 25.7 %; P < 0.001). Procedural success was 95.2 and 92.7 %, and 30-day mortality was 6.3 and 10.3 % in the TF and TA populations, respectively. The major limitations of this registry were that more than 70 % of the enrolling centers had no prior experience with TAVR and all adverse events were site-reported without core lab analysis. In early 2011, 1-year results were published, demonstrating a 1-year survival of 76.1 % overall, 72.1 % for TA and 81.1 % for TF patients. Among the surviving patients, 73.5 % were NYHA class I or II [17].

A number of large dedicated CoreValve registries have been reported [14, 16]. Promising 3-year results were recently reported by Ussia et al. [27], and although not yet published, the results of the ADVANCE CoreValve™ registry were presented recently [28]. ADVANCE represents a 100 % monitored “real-world” experience, with a core laboratory and an independent clinical event committee adjudicating events. The registry included 1,015 patients from 44 experienced (>40 prior procedures) centers between March 2010 and July 2011. The mean logistic EuroSCORE was 19.2 %. At 30 days and 6 months, the rate of all-cause mortality was 4.5 and 12.8 %, respectively, with cardiac mortality of 3.4 and 8.4 %, respectively. ADVANCE provides insights into contemporary TAVR data of experienced operators and is a benchmark for comparing outcomes.

In 2011, results from four mixed CoreValve™ and Edwards European national registries have been reported, mostly using the TF and TA routes (Table 2.2) [4, 8, 29, 30]. Overall, patients included in these registries were at high risk according to surgical risk models, mean EuroSCORE 18–30 %. These registries showed 1-year survival rates ranging between 71.9 and 81.6 %. The UK registry reported the longest follow-up; survival was 73.7 % at 2 years [30]. Several of these national initiatives performed access-route comparisons and reported that survival was generally higher in patients treated through the TF route [4, 30]. However, it should be noted that a transfemoral-first approach is often advocated, which may introduce selection bias and an unequal comparison between the two access routes [31].

Recently, the largest registry to date was reported by the FRANCE 2 investigators [32]. They included 3,195 patients treated between January 2010 and December 2011 at 34 centers. The registry reflects contemporary real-life use of available TAVR devices in patients at high surgical risk; the Edwards SAPIEN and the Medtronic CoreValve™ devices were used in, respectively, 66.9 and 33.1 %. The transfemoral approach was most widely used (74.6 %), followed by transapical (17.8 %), subclavian (5.8 %), and 1.8 % by a non-femoral non-apical approach. Procedural success rate was 96.9 % and 1-year survival in patients was 76.0 %.

While registry reports are of crucial value to assess “real-world” use of TAVR, more rigorous assessments are available from the first multicenter, randomized clinical PARTNER trials (Placement of Aortic Transcatheter Valves; ClinicalTrials.gov Identifier: NCT00530894) (Fig. 2.1) [20, 21]. As the first of two parallel trials completed, the results of PARTNER IB showed that TF TAVR was superior to standard therapy in patients not deemed candidates for surgery [20]. The primary endpoint of all-cause mortality was markedly reduced by 46 % (P < 0.001). Recently reported 2-years outcomes showed continued encouraging results (Fig. 2.2a) [33]. At 2 years, the primary endpoint of all-cause mortality was reduced from 67.6 % in the standard treatment arm to 43.3 % in the TAVR arm (P < 0.001).

The PARTNER cohort IA compared TAVR to SAVR and met its non-inferiority endpoint: the all-cause 1-year mortality in the TAVR group was non-inferior to the SAVR group (24.2 % vs. 26.8 %; P = 0.44; P = 0.001 for non-inferiority) [21]. Some concerns were raised with regard to early neurologic events that were higher by TAVR as compared to SAVR at 30 days (5.5 % vs. 2.4 %; P = 0.04) and 1 year (8.3 % vs. 4.3 %; P = 0.04). Although the recently published 2-year results revealed that stroke rates were similar for TAVR and SAVR during 1 and 2 years with a hazard ratio of 1.22 (95 % CI 0.67–2.23, P = 0.52), the issue of stroke warrants further investigation and should not be underestimated (Fig. 2.2b, c) [34]. The rate of the composite of all-cause death and stroke was encouragingly similar after TAVR (37.1 %) and SAVR (36.4 %) at 2 years (P = 0.85).

In the USA, a randomized trial is currently ongoing to evaluate the safety and efficacy of the Medtronic CoreValve™ in the treatment of severe symptomatic AS in patients at high or extreme risk for SAVR (ClinicalTrials.gov Identifier: NCT01240902). The trial consists of two arms. Patients in a high-risk arm will be randomized between SAVR and TAVR; the primary endpoint consists of all-cause mortality at 1 year. An extreme risk arm will function as an observational arm in which a composite of all-cause mortality and major stroke is the primary endpoint.

As a sequel to the PARTNER I trial, a second randomized trial (PARTNER II) is currently ongoing. It was designed to investigate the performance and outcomes after TAVR with the next-generation Edwards SAPIEN XT valve, model 9300TFX, as well as the new low-profile 18-Fr NovaFlex™ delivery catheter in patients deemed non-operable (ClinicalTrials.gov Identifier: NCT01314313) (Fig. 2.3). Given the results of the control arm in PARTNER IB, it has been judged that a study comparing TAVR against a “medical management” control group is no longer ethical [35]. Consequently, an “old device” versus “new device” non-inferiority trial was designed. Enrolment was initiated in January 2011, and it is anticipated that primary endpoint results will be published mid-2013.

In Denmark, a phase 2 randomized trial evaluating TAVR in patients ≥70 years of age started enrollment in December 2009 (ClinicalTrials.gov Identifier: NCT01057173). The trial will randomize a total of 280 patients to TAVR (n = 140) and SAVR (n = 140). The primary endpoint is the composite of all-cause death, myocardial infarction, and stroke at 1 year and is scheduled to be completed late 2013.

In an attempt to expand the indication of TAVR to lower-risk patients, the PARTNER IIA trial will be randomizing patients between TAVR with the SAPIEN XT valve and SAVR in intermediate-risk patients (ClinicalTrials.gov Identifier: NCT01314313) (Fig. 2.3). Similarly, the prospective randomized, international SURTAVR trial will randomize 1,900 intermediate-risk patients between TAVR with the Medtronic CoreValve™ and SAVR at approximately 80 centers throughout the USA, Canada, Europe, and Australia (ClinicalTrials.gov Identifier: NCT01586910).