Recently, we have witnessed a breakthrough in the field of interventional cardiology. The CoreValve US pivotal trial for high-risk patients with severe aortic stenosis (AS) demonstrated superiority in one-year survival when compared to surgery. For the first time, transcatheter aortic valve replacement (TAVR) outperformed state-of-the art surgical aortic valve replacement (SAVR) in high-risk patients with AS. The results of this pivotal study were presented at the 2014 American College of Cardiology Scientific Meeting and simultaneously published in the New England Journal of Medicine . In brief, TAVR was associated with lower rates of all-cause mortality at 1-year in the as-treated and the intention-to-treat analysis (14.2% vs 19.1%, p = 0.04 and 13.9% vs 18.7%, p = 0.04, respectively). In addition, TAVR was associated with similar rates of stroke as compared with SAVR at 30-days (4.9% vs 6.2%, p = 0.46) and at 1-year (8.8% vs 12.6%, p = 0.1). Major vascular complications, however, were higher in the TAVR group (5.9% vs 1.7%, p = 0.003). Clearly these results are good news for the Heart Teams, which now can comfortably provide a less invasive procedure with better outcome to this complex, high-risk subset of patients with severe AS.

With the inception of this technology it was clear that the success of a TAVR program and the execution of the pivotal trials depend on an effective and functional Heart Team, which composed of experts from multiple disciplines. The Heart Team is charged with patient screening, identifying the optimal treatment strategy, performing the TAVR or SAVR and finally following the patient. While during the trials it was unclear what will be the optimal modality of valve replacement SAVR or TAVR; the results of the CoreValve high-risk cohort identified a preferred treatment strategy for this patient population. Nevertheless, there are still unanswered questions. 1) Do the results of this study represent a class effect that can be generalized to other valve systems, like balloon-expandable valves or newer generations of transcatheter valves? 2) Will these study results be replicated for intermediate- and low-risk patient cohorts with severe AS? 3) What else can be done to further improve the outcome of SAVR or TAVR procedures?

Within the inoperable patient population the balloon expandable, the Placement of Aortic Transcatheter Valve (PARTNER) trial Cohort B , and the self-expanding valve, CoreValve trial , performed well as compared to the standard for each trial. The PARTNER trial randomized to medical therapy for the standard of care comparison, while the CoreValve trial evaluated this success as compared to a performance goal. However, when comparing the effectiveness of these two types of valves to SAVR for their given primary endpoints for the high surgical risk population, the outcomes are different.

In PARTENR Cohort A for the high surgical risk population, when compared to SAVR , TAVR was associated only with a trend towards lower 30-day mortality (3.4% vs 6.5%, p = 0.07) and with similar rates of mortality at 1-year (24.2% vs 26.8%, p = 0.44). Although the PARTNER and the CoreValve trials were similar in design and patient population, we should refrain from comparing treatment effect results across trials. The question remains why the CoreValve US pivotal trial was statistically better than surgery, while the Edwards SAPIEN valve had similar rates?

First, the Edwards SAPIEN valve utilized in PARTNER cohort A trial had a larger delivery sheath set than that used in the CoreValve trial. This size difference is likely responsible for the different rates of vascular complications seen in each trial, 11% and 5.9% , respectively. Since vascular complications correlates with mortality , it is reasonable to hypothesize that reduction in the sheath size in the CoreValve was an important contributor to the reduction in the mortality in the TAVR arm. The impact of delivery sheath size reduction on vascular complication is also seen with the second-generation Edwards SAPIEN XT transcatheter valve. Specifically, it is associated with reduction of the major vascular events at 30 days when compared with the first generation SAPIEN valve . Further, direct comparison of CoreValve and SAPIEN XT revealed similar vascular complications for both valves and similar cardiovascular mortality at 30 days .

Second, in PARTNER cohort A , TAVR was performed using transfemoral access in 244 (70%) and transapical access in 104 (30%) patients. TAVR and SAVR were associated with similar survival rates at 1 year. However, in the subgroup analysis, the transapical access approach was associated with a non-statistically significant higher rate of all-cause death at 1-year both in the intention-to-treat (29% vs 27%, p = 0.85) and in the as-treated analyses (29.1% vs 25.3%, p = 0.55). In contrast, the CoreValve US pivotal trial used transfemoral approach in 83% of patients and alternative access in the remaining with no transapical access. It is well established that there is an increased mortality risk for patients with severe peripheral vascular disease (PVD). Given this elevated risk in mortality, the pooling transformal and transapcial access delivery may bias the mortality rate when compared to a transformal access only population as one of the reasons for transformal access approach was severe PVD.

Third, in the CoreValve US Pivotal trial , despite rigorous screening, the STS scores were lower STS (mean of 7.3% in the TAVR group and 7.5% in the SAVR group) when compared to PARTNER cohort A trial (mean of 11.8 % in the TAVR group and 11.7% in the SAVR group). This difference is another limitation of treatment assignment comparison across these studies.

The next question for the Heart Team will be to assess the safety and efficacy TAVR compared with SAVR for intermediate to low risk patients. In Europe, patients at intermediate risk have been treated with TAVR yielding good results , and similar 1-year mortality rates when compared to SAVR (TAVR = 16.5% vs SAVR = 16.9%, HR 0.9 [0.57–1.42], p = 0.64). In the US, Edwards Lifesciences completed enrollment in their randomized comparison between TAVR and SAVR in intermediate risk patients; while Medtronic is currently enrolling patients in their intermediate risk randomized trial. For this actively enrolling trial the latest results of the high-risk CoreValve trial have created an enrollment challenge given the fact that the mean STS score of 7.5% in this high-risk trial. Perhaps an all-comers trial, which would include low and intermediate risk comparing TAVR and SAVR, may be the ultimate population to address the most important question of valve durability. This durability question requires resolution before TAVR becomes the primary approach for all patients with severe AS.

Finally, the Heart Team should explore how to continue improving the outcomes of TAVR and SAVR. Continued device innovation should focus on paravalvular leak reduction, device profile reduction, safer closure devices, strategies to minimize stroke with the use of protection devices, optimal anticoagulation therapies, and long-term valve durability. We should not forget the cost-effectiveness and economic challenges as well as the socioeconomic implications that this technology carries. The next generation of devices should address all of the above. While the Heart Team takes a pause to celebrate the results of the CoreValve high-risk trial, it should get ready for the next challenges facing this exciting technology.