Author + information
- E. Murat Tuzcu, MD∗ (, )
- Samir R. Kapadia, MD and
- Lars G. Svensson, MD, PhD
- ↵∗Reprint requests and correspondence:
Dr. E. Murat Tuzcu, Department of Cardiology, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, J2-3, Cleveland, Ohio, 44195.
On April 16, 2002, Alain Cribier, MD, raised the flag of innovation in the treatment of valvular heart disease. He performed a transcatheter aortic valve replacement (TAVR) in a desperately-ill patient who was days from death. The patient survived the procedure and died 4 months later from noncardiac causes. Following other successful cases, the subsequent decade was filled with incredible advances in technology, patient selection, operator technique, systematic data collection and analysis. New iterations of the balloon-expandable and self-expanding transcatheter valves allow operators to consistently and safely achieve successful results. The first reported randomized PARTNER (Placement of Aortic Transcatheter Valves) trial demonstrated TAVR’s lifesaving value in patients with symptomatic aortic stenosis (AS) who were unsuitable candidates for surgical treatment (1). Recently, the 5-year follow-up of this study demonstrated this intervention’s durability (2). This and subsequent randomized trials were conducted rigorously, in a true partnership of all stakeholders, setting a new standard in valvular heart disease treatment (Figure 1).
Shortly after the initial reported success of TAVR in inoperable patients, attention turned toward operable but high-risk patients. The PARTNER 1A Trial demonstrated noninferiority of TAVR to surgical aortic valve replacement (SAVR) with the first-generation balloon-expandable valve (3). Another randomized study demonstrated that TAVR with a self-expanding valve was superior to SAVR at 1 year in high-risk patients whose mean predicted 30-day surgical mortality was 7.3% (4).
These encouraging results raised the possibility of using this new technique in lower-risk patients. Two randomized trials, designed to answer the question of safety and efficacy of TAVR in intermediate-risk patients, began enrollment a few years ago. PARTNER 2A, in which patients were randomized to TAVR utilizing a balloon-expandable valve or SAVR, completed enrollment in 2014 with results expected in 2016. The SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation [NCT01586910]) trial, which has a similar design using a self-expanding valve, is continuing enrollment.
Increasing experience and technological advances have led to even better outcomes and continued reassessment of TAVR’s role in treating symptomatic severe AS. Characterization of risk has changed over time. The Society of Thoracic Surgeons (STS) score of contemporary “high-risk” patients is much lower than the mean score of 11.8% in PARTNER A; the mean predicted surgical mortality risk (STS score) in the TVT (Transcatheter Valve Therapies) registry, which includes high-risk or inoperable U.S. patients, is 7.1% (5). As practice changed, investigators evaluated TAVR outcomes in intermediate- and even low-risk patients. In various nonrandomized propensity-matched analyses, TAVR was as efficacious and safe as SAVR in lower-risk patients (6).
In this issue of the Journal, Thyregod et al. (7) aimed to determine whether TAVR and SAVR outcomes are similar in an all-comers population over the age of 70 years. The Danish and Swedish investigators should be congratulated for conducting the first randomized trial in lower-risk AS patients. The NOTION (Nordic Aortic Valve Intervention) trial, funded by the Danish Heart Foundation, retained 96% of patients at 1-year follow-up and used Valve Academic Research Consortium-2 definitions for endpoints.
The combined primary endpoint was all-cause mortality, stroke, and myocardial infarction at 1 year, which was similar in both groups. Individually, all-cause mortality, stroke, myocardial infarction, and new-onset or worsening atrial fibrillation rates were not significantly different but were numerically lower in TAVR patients. Major life-threatening or disabling bleeding, cardiogenic shock, and acute kidney injury were significantly lower in the TAVR group compared with the surgical cohort, but surgery appeared to be safer in terms of major vascular complications and need for permanent pacemaker. Both methods provided symptomatic improvement, measured as a reduction in New York Heart Association functional class, although TAVR patients had more dyspnea after 1 year, possibly related to a higher risk of paravalvular regurgitation. This provocative study suggests that TAVR is an alternative to SAVR in the treatment of severe symptomatic elderly AS patients whose surgical risk is low.
However, several limitations make the findings less than conclusive. During a period of approximately 3.5 years, 1,576 patients in 3 hospitals were evaluated by heart teams, but only 280 patients were included in the study (mean age: 79 years). It is difficult to describe a study that enrolled <20% of screened patients as an all-comers trial. Also, the NOTION study was designed to test TAVR’s superiority with sample size calculated on the assumption that primary outcome would occur 3 times more frequently in the SAVR cohort. Given the similar outcomes, it turns out that NOTION is an underpowered study that provides valuable but not definitive data.
An important difference between the 2 groups was the rate of post-TAVR aortic regurgitation (AR), which was 4 times more frequent after TAVR than SAVR. It is difficult to envision widespread application of TAVR in low-risk patients unless the paravalvular AR issue is addressed effectively. Data from the PARTNER trials and a recent meta-analysis indicate an association between mild AR and increased 1- to 2-year mortality (8,9). Advances in imaging have led to more precise measurement of the aortic annulus and placement of appropriately-sized prosthesis. In the NOTION trial, 3-dimensional imaging of the annulus was not performed, perhaps resulting in higher post-procedural AR.
New-generation transcatheter valves promise to eliminate moderate and severe AR and reduce mild AR cases. Recently, data from the PARTNER Sapien 3 registry provided the first large-scale assessment of lower-risk patient outcomes. At the 2015 American College of Cardiology Scientific Sessions, Kodali et al. (8) presented 30-day outcomes for 1,076 intermediate-risk (STS score 4 to 8) patients treated with the Sapien 3 valve (Edwards Lifesciences, Irvine, California) (89% transfemoral). In this cohort, with an average age of 81.9 years and average STS score of 5.3%, the 30-day rates of all-cause mortality and disabling stroke were 1.1% and 1.0%, respectively. Importantly, AR rates were much lower than previously reported, with moderate and severe AR seen in 3.4% of patients. This concurs with findings of small studies evaluating valves with innovative designs that also indicate that very low AR rates are possible.
In the NOTION trial, 38% of patients required pacemaker implantation within 1 year of TAVR compared with only 2.4% of SAVR patients, a 16-fold difference. It would be difficult to advise a low-risk, AS patient to have TAVR with these odds.
What should practitioners do in light of the NOTION study? The data are not robust enough to support performing TAVR in all patients age ≥70 years and candidates for first-time open heart surgery for isolated aortic valve replacement. We should await the results of the randomized trials of intermediate-risk patients and continue to carefully evaluate outcomes in lower-risk patients, including those treated with new-generation valves. In addition to the registry studies and randomized clinical trials, heart teams should track their own institutional outcomes, local resources, and capabilities while answering the question “What is the best treatment for our patient?”
Rather than performing another industry-sponsored, expensive randomized trial, the recently established STS/American College of Cardiology/TVT registry can be used to further our understanding of TAVR’s role in treating low-risk AS patients. Detailed data are prospectively collected from all but a small number of TAVR procedures performed in the United States. Similarly, STS collects detailed SAVR data from most U.S. centers. These 2 registries can serve as a platform to organize studies to compare the effectiveness of TAVR and SAVR in patient populations that have not yet been studied.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Kapadia S.R.,
- Leon M.B.,
- Makkar R.R.,
- et al.
- Piazza N.,
- Kalesan B.,
- van Mieghem N.,
- et al.
- Thyregod H.G.H.,
- Steinbrüchel D.A.,
- Ihlemann N.,
- et al.
- Kodali S.,
- Pibarot P.,
- Douglas P.S.,
- et al.
- Athappan G.,
- Patvardhan E.,
- Tuzcu E.M.,
- et al.