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Born From Risk: What Made TAVR Possible and the Future of a Transformational Technology
Transcatheter aortic valve replacement (TAVR) exists today because of our perception of the risk associated with surgical aortic valve replacement (SAVR). Historically, those patients at high risk for morbidity and mortality with SAVR (perhaps based on factors such as the Society of Thoracic Surgery [STS] score), were not offered SAVR. Only “lower risk” patients were selected for the operation. Studies from the pre-TAVR era document that roughly 40%-60% of patients with severe aortic stenosis (AS) were not offered SAVR due to this perceived excessive surgical risk.1,2 Historically, the high-risk severe AS cohort was treated with either balloon valvuloplasty or most often with medical palliation alone. It was precisely the unmet need of these high-risk severe AS patients that led to an interest in developing less invasive methods of replacing the aortic valve.
In the late 1980s, the Danish physician H.R. Andersen first developed the concept of a fully percutaneous, non-surgical valve delivery system. Using porcine valves excised at a local butcher shop, Andersen mounted these valves within a stent frame fashioned from stainless-steel sternotomy wires. He was ultimately able to demonstrate the feasibility of his concept with a live porcine implant. Despite publishing his results, however, there was little enthusiasm generated for his creation.3 Andersen’s invention was truly ahead of its time. He ultimately sold his patent to a small American company and the technology initially languished. A few years later in 2002, however, the inventor of balloon valvuloplasty, Alan Cribier in Rouen, France, would successfully implant the first percutaneous transcatheter heart valve based on Andersen’s design into a human. The patent was ultimately bought in 2004 by Edwards Lifesciences, a leading valve manufacturing company, which then steadily refined the technology until it was truly ready for broader human trials. The original TAVR trial (PARTNER) focused exclusively on the high surgical risk and inoperable cohorts with the intent of first meeting their unmet need, before challenging the then prevailing paradigm of performing SAVR in lower surgical risk patients.4,5 Once the technology was honed and proven in the high-risk and inoperable cohorts, TAVR could be tested against SAVR in these other, lower surgical risk candidates. The stepwise rollout of TAVR down the risk continuum was by no means an accident and is in fact a testament to the vision of the architects of the contemporary technology.
Recently, we have seen the publication of two large randomized clinical trials, PARTNER IIA and SURTAVI, that demonstrated the non-inferiority of TAVR to SAVR among intermediate-risk patients.6,7 Thus, the field is now moving to the next set of trials comparing TAVR against SAVR among low-risk patients. While the American audience has patiently awaited these trial series traveling down the risk spectrum, our colleagues across the globe have moved beyond the constraints of the surgical risk construct altogether. For example, the NOTION trial took all-comers regardless of risk and randomized them one-to-one to TAVR vs SAVR, reporting no difference in the primary composite endpoint of death from any cause, stroke, or myocardial infarction at 1 year.8
In the current issue of the Journal of Invasive Cardiology, Garg et al provide a meta-analysis of data comparing TAVR to SAVR among low-to-intermediate risk patients.9 These researchers pooled data from five randomized controlled trials and five propensity-matched observational studies, collecting nearly 7000 low-to-intermediate risk patients. Their analysis found no difference between TAVR and SAVR in all-cause 30-day mortality.9
These encouraging findings in many ways confirm the original vision of the pioneers who launched the field. Now reaching maturity with third-generation devices, TAVR should compete favorably with SAVR even among lower-risk patients. Nevertheless, on a more granular level, these findings highlight some of the strengths and weaknesses of each approach. TAVR suffers from higher rates of significant vascular complications, paravalvular regurgitation, and permanent pacemaker implantation. On the other hand, SAVR suffers from higher rates of major bleeding, acute kidney injury, and atrial fibrillation. The long-term implications of these individual weaknesses have yet to be fully elucidated. While significant paravalvular regurgitation post TAVR has been linked to increased mortality, the definitions of moderate or severe paravalvular regurgitation remain disturbingly subjective and imprecise.10 We have not yet been able to adequately quantitate precisely enough the amount of aortic regurgitation post TAVR that compromises longer-term survival, or that might warrant additional treatments. With respect to vascular complications and permanent pacemaker implantation, robust data on the impact of these events on the longer-term quality of life and survival remain elusive and sparse. The same applies post SAVR with understanding the long-term impact of periprocedural acute kidney injury or atrial fibrillation. These are all areas that require more detailed analysis before we can make definitive judgments about one or the other therapy (TAVR or SAVR) in lower-risk patients. We must also look more closely at areas where each procedure excels. For example, in patients with impediments to post-surgical rehabilitation, TAVR may prove the better option. On the other hand, in patients with severe left ventricular outflow tract calcium, the ability to directly debulk the calcium may give SAVR an advantage.
An important additional caveat to the Garg et al study is the lack of stratification comparing TAVR versus the increasingly utilized technique of minimally invasive aortic valve replacement.11 There are increasing data supporting minimally invasive aortic valve replacement over standard full sternotomy aortic valve replacement, particularly with respect to blood transfusions, incidence of atrial fibrillation, length of stay, and recovery time.12 Further studies are needed to explore these approaches in appropriately risk-matched patients.
As we approach the TAVR versus SAVR choice among healthier, lower-risk patients, we must keep in mind the other critically important innovation that occurred, the creation of the “Heart Team.” In many ways the creation of the Heart Team, cutting across disciplines, putting aside the individual interests of any particular group so as to serve the best interests of the patients, is one of the more important innovations of our time. What we have learned from the TAVR experience over the last decade is that the skill, intellect, and insight of cardiothoracic surgeons and interventional cardiologists, as well as numerous other disciplines, all working together in a coordinated fashion, contribute to a more thoughtful and complete approach to patient care. The choice of TAVR versus SAVR among lower-risk patients will prove the best test of the Heart Team concept. We will have to consider each case individually, weighing the relative merits of TAVR versus SAVR for a given patient based on his or her clinical circumstances.
Emerging data, including the study by Garg et al reported here, indicate that TAVR should be a viable treatment modality in lower-risk patients. The manner in which this happens may, however, surprise us all. The choice of TAVR versus SAVR may ultimately have little or nothing to do with rigid surgical risk categories. The very nature of the STS score will eventually change over time as fewer high-risk patients undergo SAVR. Although born from surgical risk considerations, TAVR ultimately will not be defined by surgical risk but rather by its own individualized outcomes. As we approach the treatment of severe aortic stenosis among ever lower-risk patients, we, the Heart Team, will need to arm ourselves with both TAVR and SAVR as possible options.
References
1. Pellika PA, Saran ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation. 2005;111:3290-3295.
2. Freed BH, Sugeng L, Furlong K, et al. Reasons for non-adherence to guidelines for aortic valve replacement in patients with severe aortic stenosis and potential solutions. Am J Cardiol. 2010;105:1339-1342.
3. Andersen HR, Knudsen LL, Hasenkam JM. Transluminal implantation of artificial heart valves: description of a new expandable aortic valve and initial results with implantation by catheter technique in closed chest pigs. Eur Heart J. 1992;13:704-708.
4. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597-1607.
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8. Thyregod HGH, Steinbrüchel DA, Ihlemann N, et al. Transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis. J Am Coll Cardiol. 2015;65:2184-2194.
9. Garg A, Rao SV, Visveswaran G, et al. Transcatheter aortic valve replacement versus surgical valve replacement in low-intermediate surgical risk patients: a systematic review and meta-analysis. J Invasive Cardiol. 2017;29:209-216.
10. Kodali S, Pibarot P, Douglas PS, et al. Paravalvular regurgitation after transcatheter aortic valve replacement with the Edwards SAPIEN valve in the PARTNER trial: characterizing patients and impact on outcomes. Eur Heart J. 2015;36:449-456.
11. Nguyen TC, Terwelp MD, Thourani VH, et al. Clinical trends in surgical, minimally invasive and transcatheter aortic valve replacement. Eur J Cardiothorac Surg. 2017 Feb 20 (Epub ahead of print).
12. Gilmanov D, Bevilacqua S, Murzi M, et al. Minimally invasive and conventional aortic valve replacement: a propensity score analysis. Ann Thorac Surg. 2013;96:837-843.
From the McGovern Medical School, University of Texas Health Science Center Houston, Memorial Hermann Hospital-Texas Medical Center, Heart & Vascular Institute, Houston, Texas.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Memorial Hermann Heart & Vascular Institute – Texas Medical Center is a TAVR center, and is the site on ongoing clinical trials sponsored by Edwards Lifesciences Corp. and Abbott Vascular, Inc. The authors report no conflicts of interest regarding the content herein.
Address for correspondence: H. Vernon Anderson, MD, Cardiology Division, University of Texas Health Science Center Houston, 6431 Fannin, Suite 1.246, Houston, TX 77030. Email: h.v.anderson@uth.tmc.edu
