The Low-Risk TAVR Trials at ACC.19: Will TAVR Replace SAVR for Aortic Stenosis?
Editor's Note: This Expert Analysis is part of a series presenting perspectives on major ACC.19 trials. Please follow this link for the companion articles.
A paradigm shift has occurred in the treatment of aortic valve disease over the past 13 years. This shift was highlighted at ACC.19 in New Orleans, Louisiana with the final presentation in the trilogy of randomized trials between transcatheter (TAVR) or surgical aortic valve replacement (SAVR) for aortic stenosis (AS). The progression from high-, then intermediate-, and now finally low-risk patients has already led to the widespread use of TAVR in lieu of SAVR for those necessitating treatment for AS. Prior randomized trials have reported equivalent mortality at 5 years in high-risk patients,1,2 and at 2 years in intermediate-risk patients.3,4 These trials have consistently shown increased paravalvular regurgitation (PVR) and the need for permanent pacemaker (PPM) but better hemodynamics in TAVR valves, while SAVR patients have higher rates of bleeding, acute kidney injury and patient-prosthesis mismatch compared with TAVR. However, there remains a paucity of data available for the durability of TAVR valves, as the vast majority of TAVR patients have been older than 80 years and these elderly patients are not expected to outlive the durability of the prosthesis. The SAVR durability data is plagued by inconsistencies of structural valve deterioration definition and a lack of protocolized echocardiographic follow-up.
Surgeons have anticipated a shift of TAVR to lower risk populations. We have relied upon the excellent results of SAVR in low-risk populations to maintain our argument for the efficacy of this treatment option. The first large-scale randomized trials including low-risk patients compared SAVR with the self-expanding (SE) Medtronic Evolut and balloon-expanding (BE) Edwards Sapien 3 valves were presented at ACC.19.5,6 Both trials have shown excellent results for both treatments but an advantage of TAVR over surgery in the short term: lower rates of death and disabling stroke (SE: TAVR 0.8% vs. SAVR 2.6% and BE: TAVR 1.0% vs. 3.3%, both results statistically significant). Recovery was faster in the TAVR groups, with improved 6 minute walk tests, NYHA class and quality of life at 30 days, but did not differ at 12 months. Self-expanding valves had a higher incidence of > moderate PVR compared with SAVR at 1 year (3.6% vs. 0.6%); 37.5% of SE TAVR valves had > mild PVR compared with 3.1% of SAVR valves. Balloon-expandable valves had 0.6% > moderate PVR and 30% > mild at 1 year. At 1 year, permanent pacemakers were required in 19.4% of SE valves (6.7% SAVR) and 7.5% of BE valves (5.5% SAVR).
Careful thought is required to determine which low-risk patients will best be treated with TAVR or SAVR. The average age of patients treated in the trials was ~73-74 years and much lower than the intermediate and high-risk patients from prior studies. It remains unclear whether TAVR as a "first valve" strategy in younger patients who are likely to require another intervention for structural valve deterioration is beneficial as there is no data on the efficacy of TAVR-in-TAVR. TAVR following a prior SAVR valve has proved efficacious provided it is performed in a large sized surgical valve (>23mm) and there is no risk of coronary obstruction.7 There is no data on the results of surgical explant of TAVR valves; in our experience this can be more challenging than re-operative SAVR and may require a root replacement in those with a SE valve.
The best management of patients with co-existing coronary disease is unresolved. Concomitant coronary artery bypass grafting (CABG) was more common in SAVR than percutaneous coronary intervention (PCI) in TAVR (BE trial: CABG 12.8% vs. PCI 6.5%; SE trial CABG 14% vs. PCI 6.9%). Coronary access may be more challenging after TAVR (particularly with SE valves) which has the potential to influence long term outcomes.
Both trials specifically excluded patients with bicuspid aortic valves (BAV) in the randomized trials (but are planning registries in this patient population). These patients tend to present for SAVR at a younger age, have non-circular annular/asymmetric leaflet geometry and often have dilatation of the ascending aorta. While there is no data directly comparing TAVR and SAVR in BAV, we believe that these patients may be best served with surgery in low-risk patients. Furthermore, those with severe left ventricular outflow tract calcification (the main reason for exclusion in the BE trial) may be more safely treated with surgery to prevent annular rupture or significant PVR.
Mild PVR was a predictor of death in high-risk patients undergoing TAVR at 5 years, but this has not been replicated elsewhere or in intermediate risk patients.2 The impact of even mild PVR in a low-risk population should be answered in longer-term follow-up with an adjudicated core-lab analysis. Similarly, there remains conflicting reports on how implantation of a permanent pacemaker may affect long term survival or development of significant tricuspid regurgitation.
Hemodynamics favoured SE valves compared to SAVR, but did not differ between BE and SAVR. Implanted SAVR valve sizes were > 23mm in 78% and 79% in the SE and BE trials, respectively; root enlargement occurred in 1.6% and 4.6% of SAVR in the SE and BE trials, respectively.
Atrial fibrillation (AF) was present prior to treatment in approximately 16% of patients. Concomitant MAZE was performed in 4.8% (left atrial appendage ligation, LAA, in 9.5%) and 3.5% (LAA 6.2%) in the SE and BE trials, respectively. Patients with AF treated with MAZE may have a survival benefit compared with those untreated and should be considered if SAVR is offered.8 SAVR resulted in increased post-operative AF that persisted to 12 months in both trials. The relative contribution to long term mortality and morbidity is unclear and further thought is required to determine best management in these patients.
SAVR is not dead. Surgeons must embrace TAVR and collaborate with our cardiology colleagues; never before has the heart team been more important. Long term follow-up of these trials is critical and will shed light on the relative efficacy of treatment in various subgroups. There will be increased focus on the durability of TAVR (and SAVR) valves in younger, low-risk patients as currently there is limited data for either treatment strategy. Surgeons must continue to improve SAVR with placement of larger sized valves, more concomitant MAZE and meticulous stroke prevention strategies. We need to improve its appeal with more minimally invasive approaches. Commercial approval of TAVR in low-risk patients is imminent. It is especially important that the results of TAVR be followed carefully by the ACC/STS Transcatheter Valve Therapies (TVT) Registry to ensure 'real-world' results reflect those in these carefully monitored trials.
- Gleason TG, Reardon MJ, Popma JJ, et al. 5-year outcomes of self-expanding transcatheter versus surgical aortic valve replacement in high-risk patients. J Am Coll Cardiol 2018;72:2687-96.
- Mack MJ, Leon MB, Smith CR, et al. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTER 1): a randomised controlled trial. Lancet 2015;385:2477-84.
- Reardon MJ, Adams DH, Kleiman NS, et al. 2-year outcomes in patients undergoing surgical or self-expanding transcatheter aortic valve replacement. J Am Coll Cardiol 2015;66:113-21.
- Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic valve replacement in intermediate-risk patients. N Engl J Med 2016;374:1609-20.
- Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with balloon-expandable valve in low-risk patients. N Engl J Med 2019. [Epub ahead of print]
- Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med 2019. [Epub ahead of print]
- Dvir D, Webb JG, Bleiziffer S, et al. Transcatheter aortic valve implantation in failed bioprosthetic surgical valves. JAMA 2014;312:162-70.
- Musharbash FN, Schill MR, Sinn LA, et al. Performance of the Cox-maxe IV procedure is associated with improved long-term survival in patients with atrial fibrillation undergoing cardiac surgery. J Thorac Cardivasc Surg 2018;155:159-70.
Keywords: Acute Coronary Syndrome, Acute Kidney Injury, Aneurysm, Dissecting, Aortic Aneurysm, Aorta, Aortic Valve Insufficiency, Aortic Valve, Aortic Valve Stenosis, Arrhythmias, Cardiac, Arterial Pressure, Atherosclerosis, Atrial Appendage, Atrial Fibrillation, Bicuspid, Biomarkers, Cardiac Surgical Procedures, Constriction, Pathologic, Constriction, Pathologic, Conversion to Open Surgery, Coronary Artery Bypass, Coronary Disease, Creatinine, Diagnosis, Differential, Disease-Free Survival, Dilatation, Echocardiography, Endovascular Procedures, Factor VII, Follow-Up Studies, Heart Defects, Congenital, Heart Transplantation, Heart Failure, Heart Valve Diseases, Heart Valve Prosthesis, Heart-Assist Devices, Hemodynamics, Hemorrhage, Hospital Mortality, Hospitalization, Hypertension, Hypertension, Pulmonary, Length of Stay, Liver Diseases, Mitral Valve, Mitral Valve Stenosis, Mitral Valve Insufficiency, Pacemaker, Artificial, Patient Selection, Percutaneous Coronary Intervention, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Pulmonary Embolism, Pulmonary Veins, Pulsatile Flow, Quality Improvement, Quality of Life, Referral and Consultation, Registries, Reoperation, Renal Insufficiency, Research Personnel, Respiratory Insufficiency, Risk Factors, Smoking, Sodium, Spinal Cord Ischemia, Stroke, Stroke Volume, Surgeons, Surgical Instruments, Thrombosis, Tomography, X-Ray Computed, Transcatheter Aortic Valve Replacement, Treatment Outcome, Tricuspid Valve Insufficiency, Ventricular Dysfunction, Left, ACC Annual Scientific Session, ACC19
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