- Email: [email protected]
Watching a Procedure Evolve: Sequential Findings From the TVT Registry
EDITORIALS
Watching a Procedure Evolve: Sequential Findings From the TVT Registry Michael J. Reardon, MD, and Neal S. Kleiman, MD Department of Cardiovascular Surgery, Houston Methodist DeBakey Heart & Vascular Center, Houston; and Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas
T
ranscatheter aortic valve replacement (TAVR) has rapidly expanded in the United States and worldwide. The approval of the first 2 TAVR prostheses in the United States is based on data from randomized trials showing survival rates superior to conservative medical therapy in nonoperable patients [1, 2] and comparable or superior to surgical aortic valve replacement (SAVR) for patients at high surgical risk [3, 4]. Data from these trials have now been extended to 5-year outcomes for the PARTNER (Placement of Aortic Transcatheter Valves) trial and 2-year outcomes for the CoreValve trial, and continue to confirm the initial findings [5–8]. These trials represent some of the most robust clinical investigations available in the field of valvular heart disease. However, it has long been recognized that observations from clinical trials are not necessarily reflective of outcomes and practices in the broader population, often referred to as “the real world” [9]. For related article, see page 789 The TVT (Transcatheter Valve Therapies) Registry was created to address this concern. It arose from a close collaboration between the U.S. Center for Medicare & Medicaid Services (CMS), the American College of Cardiology, and the Society of Thoracic Surgeons (STS). Specifically, the goal of the TVT Registry was to provide a data repository and reporting structure independent from industry to monitor the safety and effectiveness of approved TAVR devices [10]. The majority of patients receiving TAVR are covered by Medicare, and enrollment in the registry is mandatory for physicians and institutions to receive payment for TAVR from CMS. It is thus anticipated that the registry will capture nearly all commercially funded cases of TAVR and will involve every U.S. physician implanting transcatheter valves, including the authors. The initial in-hospital outcomes of the TVT Registry were reported by Mack and colleagues
Drs Reardon and Kleiman both serve on the publications committee for the TVT Registry. Dr Reardon has served on an advisory board for Medtronic. Dr Kleiman provides educational services for Medtronic. This article is copublished in The Annals of Thoracic Surgery and the Journal of the American College of Cardiology. Address correspondence to Dr Reardon, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin St, MS Smith 1401, Houston, TX 77030; email: [email protected].
Ó 2016 by The Society of Thoracic Surgeons and the American College of Cardiology Foundation Published by Elsevier
[11] in 2013 and the 1-year outcomes by Holmes and colleagues [12]. In this issue of The Annals, Holmes and colleagues [13] provide further updates of the TVT Registry. The predominant theme of the current report is that the field of TAVR is exceptionally dynamic. The report captures a total of 26,414 TAVR procedures from 348 centers in 48 states between 2012 and December 31, 2014, and thus allows comparison of the first 3 years of commercial TAVR implantation. During this timeframe, we have seen a dramatic surge in the number of centers implanting transcatheter valves (the number of participating sites more than doubled between 2012 and 2014), as well as U.S. Food and Drug Administration approval of new devices and CMS approval of new access routes. Patient outcomes remain extremely encouraging: the procedural success of device implantation in the proper position is excellent at 97.4%, with 95% of these having a mean residual gradient <20 mm Hg; mortality (4.4%), myocardial infarction (0.4%), renal injury stage 3 (2.2%), and stroke (2.2%) are low; and conversion to open surgery remains highly unusual at 1.3%. Equally important, the report provides insight into how the procedure is evolving. Patient characteristics seem to suggest a rightward shift in the selection of patients for TAVR, such that fewer extremely high-risk and more intermediate- to high-risk patients are undergoing the procedure. There are subtle but significant decrements in patient age and baseline risk. The median age decreased from 84 to 83 years, and the median STS predicted risk of mortality among enrolled patients fell from 7.05% to 6.69%, accompanied by a small decrement in the proportion of patients with STS risk scores 15%. Only about 1 in 5 patients had risk scores <4%. Noncardiac morbidities, such as the proportion on home oxygen, tended to decrease as did measures of frailty. Thus, although not completely alleviating early concern about “creep” of the procedure into inappropriately low-risk patient populations, this study shows that the patients remain elderly and at high risk, and are symptomatic and frail. These observations suggest that patient selection for TAVR in the United States has remained reasonable, with excellent efficacy and continued safety. The observations concerning procedure performance are particularly interesting. Although it is difficult within the registry to distinguish between overall trends and more conservative practices by physicians new to TAVR and to the registry, several observations are apparent. Over time, TAVR implanters have become more adept at Ann Thorac Surg 2016;101:417–8 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.11.031
418
EDITORIAL REARDON AND KLEIMAN SEQUENTIAL FINDINGS FROM THE TVT REGISTRY
integrating computed tomography angiogram data (used to assess the aortic annulus in 27.9% in the first cohort vs. 51.9% in the second cohort). Notably, the proportion of patients receiving moderate sedation rather than general anesthesia rose from 1.6% to 5.1% and the proportion of percutaneous TAVR rose from 21.1% to 40.8%, whereas the proportion of transapical and other nonfemoral access use declined. As TAVR enters the mainstream of clinical practice, the registry must embrace new challenges, but will also be able to provide new opportunities. First, only the first 3 years of TAVR are currently included in the registry. Although 5-year results from the PARTNER trial show no indication of structural valve degeneration, surgical experience has shown that in many cases, structural valve degeneration can become apparent fairly abruptly after this period. Second, the recent National Coverage Decision by CMS specifies the requisite operator and institutional requirements, particularly with respect to open surgical volume, to develop a TAVR program. Paradoxically, if the current trials of TAVR in patients at intermediate risk for SAVR, such as SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) (NCT01586910) and PARTNER II (NCT01314313), demonstrate adequate long-term outcomes for these lower-risk patients following TAVR, the number of SAVRs will drop and meeting the current CMS requirements will become more difficult. Accordingly, the registry will become more useful in elucidating the relationship among operator experience, institutional volume, and the likelihood of achieving satisfactory clinical outcomes. The TVT Registry also can be used with other national registries such as the U.K. Registry [14], GARY (German Aortic Valve Registry) [15], and France II Registry [16] to achieve very high-volume data for unusual occurrences with TAVR. Finally, the TVT Registry offers another unique set of opportunities. TVT played an important role in the acceptance and CMS approval of direct aortic access for TAVR. In Sweden, the TASTE (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) investigators demonstrated that simple clinical questions concerning currently available therapy, such as intracoronary thrombectomy during primary percutaneous coronary intervention, can be answered using a randomized trial with data collection performed using an existing registry (SCAAR [Swedish Coronary Angiography and Angioplasty Registry]) [17]. Important questions remain to be resolved, particularly in regard to antithrombotic therapies, in patients who have undergone TAVR. Use of the registry is likely to become a useful mechanism to resolve these questions in a broad national population.
Ann Thorac Surg 2016;101:417–8
References 1. Leon MB, Smith CR, Mack M, et al. Transcatheter aorticvalve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597–607. 2. Popma JJ, Adams DH, Reardon MJ, et al. Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery. J Am Coll Cardiol 2014;63:1972–81. 3. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187–98. 4. Adams DH, Popma JJ, Reardon MJ. Transcatheter aorticvalve replacement with a self-expanding prosthesis. N Engl J Med 2014;371:967–8. 5. Yakubov SJ, Adams DH, Watson DR, et al. 2-year outcomes after iliofemoral self-expanding transcatheter aortic valve replacement in patients with severe aortic stenosis deemed extreme risk for surgery. J Am Coll Cardiol 2015;66:1327–34. 6. 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. 7. Kapadia SR, Leon MB, Makkar RR, et al, for the PARTNER 1 Trial Investigators. 5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 2015;385:2485–91. 8. Mack MJ, Leon MB, Smith CR, et al, for the PARTNER 1 Trial Investigators. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 2015;385:2477–84. 9. Nallamothu BK, Hayward RA, Bates ER. Beyond the randomized clinical trial: the role of effectiveness studies in evaluating cardiovascular therapies. Circulation 2008;118: 1294–303. 10. Rumsfeld JS, Holmes DR Jr, Stough WG, et al. Insights from the early experience of the Society of Thoracic Surgeons/ American College of Cardiology Transcatheter Valve Therapy Registry. J Am Coll Cardiol Intv 2015;8:377–81. 11. Mack MJ, Brennan JM, Brindis R, et al. Outcomes following transcatheter aortic valve replacement in the United States. JAMA 2013;310:2069–77. 12. Holmes DR Jr, Brennan JM, Rumsfeld JS, et al. Clinical outcomes at 1 year following transcatheter aortic valve replacement. JAMA 2015;313:1019–28. 13. Holmes DR Jr, Nishimura RA, Grover FL, et al, for the STS/ ACC TVT Registry. Annual outcomes with transcatheter valve therapy: from the STS/ACC TVT Registry. Ann Thorac Surg 2016;101:789–800. 14. Duncan A, Ludman P, Banya W, et al. Long-term outcomes after transcatheter aortic valve replacement in high-risk patients with severe aortic stenosis: the U.K. Transcatheter Aortic Valve Implantation Registry. J Am Coll Cardiol Intv 2015;8:645–53. 15. Walther T, Hamm CW, Schuler G, et al. Perioperative results and complications in 15,964 transcatheter aortic valve replacements: prospective data from the GARY Registry. J Am Coll Cardiol 2015;65:2173–80. 16. Gilard M, Eltchaninoff H, Iung B, et al. Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med 2012;366:1705–15. 17. Lagerqvist B, Fr€ obert O, Olivecrona GK, et al. Outcomes 1 year after thrombus aspiration for myocardial infarction. N Engl J Med 2014;371:1111–20.
Watching a Procedure Evolve: Sequential Findings From the TVT Registry Michael J. Reardon, MD, and Neal S. Kleiman, MD Department of Cardiovascular Surgery, Houston Methodist DeBakey Heart & Vascular Center, Houston; and Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas
T
ranscatheter aortic valve replacement (TAVR) has rapidly expanded in the United States and worldwide. The approval of the first 2 TAVR prostheses in the United States is based on data from randomized trials showing survival rates superior to conservative medical therapy in nonoperable patients [1, 2] and comparable or superior to surgical aortic valve replacement (SAVR) for patients at high surgical risk [3, 4]. Data from these trials have now been extended to 5-year outcomes for the PARTNER (Placement of Aortic Transcatheter Valves) trial and 2-year outcomes for the CoreValve trial, and continue to confirm the initial findings [5–8]. These trials represent some of the most robust clinical investigations available in the field of valvular heart disease. However, it has long been recognized that observations from clinical trials are not necessarily reflective of outcomes and practices in the broader population, often referred to as “the real world” [9]. For related article, see page 789 The TVT (Transcatheter Valve Therapies) Registry was created to address this concern. It arose from a close collaboration between the U.S. Center for Medicare & Medicaid Services (CMS), the American College of Cardiology, and the Society of Thoracic Surgeons (STS). Specifically, the goal of the TVT Registry was to provide a data repository and reporting structure independent from industry to monitor the safety and effectiveness of approved TAVR devices [10]. The majority of patients receiving TAVR are covered by Medicare, and enrollment in the registry is mandatory for physicians and institutions to receive payment for TAVR from CMS. It is thus anticipated that the registry will capture nearly all commercially funded cases of TAVR and will involve every U.S. physician implanting transcatheter valves, including the authors. The initial in-hospital outcomes of the TVT Registry were reported by Mack and colleagues
Drs Reardon and Kleiman both serve on the publications committee for the TVT Registry. Dr Reardon has served on an advisory board for Medtronic. Dr Kleiman provides educational services for Medtronic. This article is copublished in The Annals of Thoracic Surgery and the Journal of the American College of Cardiology. Address correspondence to Dr Reardon, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin St, MS Smith 1401, Houston, TX 77030; email: [email protected].
Ó 2016 by The Society of Thoracic Surgeons and the American College of Cardiology Foundation Published by Elsevier
[11] in 2013 and the 1-year outcomes by Holmes and colleagues [12]. In this issue of The Annals, Holmes and colleagues [13] provide further updates of the TVT Registry. The predominant theme of the current report is that the field of TAVR is exceptionally dynamic. The report captures a total of 26,414 TAVR procedures from 348 centers in 48 states between 2012 and December 31, 2014, and thus allows comparison of the first 3 years of commercial TAVR implantation. During this timeframe, we have seen a dramatic surge in the number of centers implanting transcatheter valves (the number of participating sites more than doubled between 2012 and 2014), as well as U.S. Food and Drug Administration approval of new devices and CMS approval of new access routes. Patient outcomes remain extremely encouraging: the procedural success of device implantation in the proper position is excellent at 97.4%, with 95% of these having a mean residual gradient <20 mm Hg; mortality (4.4%), myocardial infarction (0.4%), renal injury stage 3 (2.2%), and stroke (2.2%) are low; and conversion to open surgery remains highly unusual at 1.3%. Equally important, the report provides insight into how the procedure is evolving. Patient characteristics seem to suggest a rightward shift in the selection of patients for TAVR, such that fewer extremely high-risk and more intermediate- to high-risk patients are undergoing the procedure. There are subtle but significant decrements in patient age and baseline risk. The median age decreased from 84 to 83 years, and the median STS predicted risk of mortality among enrolled patients fell from 7.05% to 6.69%, accompanied by a small decrement in the proportion of patients with STS risk scores 15%. Only about 1 in 5 patients had risk scores <4%. Noncardiac morbidities, such as the proportion on home oxygen, tended to decrease as did measures of frailty. Thus, although not completely alleviating early concern about “creep” of the procedure into inappropriately low-risk patient populations, this study shows that the patients remain elderly and at high risk, and are symptomatic and frail. These observations suggest that patient selection for TAVR in the United States has remained reasonable, with excellent efficacy and continued safety. The observations concerning procedure performance are particularly interesting. Although it is difficult within the registry to distinguish between overall trends and more conservative practices by physicians new to TAVR and to the registry, several observations are apparent. Over time, TAVR implanters have become more adept at Ann Thorac Surg 2016;101:417–8 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.11.031
418
EDITORIAL REARDON AND KLEIMAN SEQUENTIAL FINDINGS FROM THE TVT REGISTRY
integrating computed tomography angiogram data (used to assess the aortic annulus in 27.9% in the first cohort vs. 51.9% in the second cohort). Notably, the proportion of patients receiving moderate sedation rather than general anesthesia rose from 1.6% to 5.1% and the proportion of percutaneous TAVR rose from 21.1% to 40.8%, whereas the proportion of transapical and other nonfemoral access use declined. As TAVR enters the mainstream of clinical practice, the registry must embrace new challenges, but will also be able to provide new opportunities. First, only the first 3 years of TAVR are currently included in the registry. Although 5-year results from the PARTNER trial show no indication of structural valve degeneration, surgical experience has shown that in many cases, structural valve degeneration can become apparent fairly abruptly after this period. Second, the recent National Coverage Decision by CMS specifies the requisite operator and institutional requirements, particularly with respect to open surgical volume, to develop a TAVR program. Paradoxically, if the current trials of TAVR in patients at intermediate risk for SAVR, such as SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) (NCT01586910) and PARTNER II (NCT01314313), demonstrate adequate long-term outcomes for these lower-risk patients following TAVR, the number of SAVRs will drop and meeting the current CMS requirements will become more difficult. Accordingly, the registry will become more useful in elucidating the relationship among operator experience, institutional volume, and the likelihood of achieving satisfactory clinical outcomes. The TVT Registry also can be used with other national registries such as the U.K. Registry [14], GARY (German Aortic Valve Registry) [15], and France II Registry [16] to achieve very high-volume data for unusual occurrences with TAVR. Finally, the TVT Registry offers another unique set of opportunities. TVT played an important role in the acceptance and CMS approval of direct aortic access for TAVR. In Sweden, the TASTE (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) investigators demonstrated that simple clinical questions concerning currently available therapy, such as intracoronary thrombectomy during primary percutaneous coronary intervention, can be answered using a randomized trial with data collection performed using an existing registry (SCAAR [Swedish Coronary Angiography and Angioplasty Registry]) [17]. Important questions remain to be resolved, particularly in regard to antithrombotic therapies, in patients who have undergone TAVR. Use of the registry is likely to become a useful mechanism to resolve these questions in a broad national population.
Ann Thorac Surg 2016;101:417–8
References 1. Leon MB, Smith CR, Mack M, et al. Transcatheter aorticvalve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597–607. 2. Popma JJ, Adams DH, Reardon MJ, et al. Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery. J Am Coll Cardiol 2014;63:1972–81. 3. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187–98. 4. Adams DH, Popma JJ, Reardon MJ. Transcatheter aorticvalve replacement with a self-expanding prosthesis. N Engl J Med 2014;371:967–8. 5. Yakubov SJ, Adams DH, Watson DR, et al. 2-year outcomes after iliofemoral self-expanding transcatheter aortic valve replacement in patients with severe aortic stenosis deemed extreme risk for surgery. J Am Coll Cardiol 2015;66:1327–34. 6. 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. 7. Kapadia SR, Leon MB, Makkar RR, et al, for the PARTNER 1 Trial Investigators. 5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 2015;385:2485–91. 8. Mack MJ, Leon MB, Smith CR, et al, for the PARTNER 1 Trial Investigators. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet 2015;385:2477–84. 9. Nallamothu BK, Hayward RA, Bates ER. Beyond the randomized clinical trial: the role of effectiveness studies in evaluating cardiovascular therapies. Circulation 2008;118: 1294–303. 10. Rumsfeld JS, Holmes DR Jr, Stough WG, et al. Insights from the early experience of the Society of Thoracic Surgeons/ American College of Cardiology Transcatheter Valve Therapy Registry. J Am Coll Cardiol Intv 2015;8:377–81. 11. Mack MJ, Brennan JM, Brindis R, et al. Outcomes following transcatheter aortic valve replacement in the United States. JAMA 2013;310:2069–77. 12. Holmes DR Jr, Brennan JM, Rumsfeld JS, et al. Clinical outcomes at 1 year following transcatheter aortic valve replacement. JAMA 2015;313:1019–28. 13. Holmes DR Jr, Nishimura RA, Grover FL, et al, for the STS/ ACC TVT Registry. Annual outcomes with transcatheter valve therapy: from the STS/ACC TVT Registry. Ann Thorac Surg 2016;101:789–800. 14. Duncan A, Ludman P, Banya W, et al. Long-term outcomes after transcatheter aortic valve replacement in high-risk patients with severe aortic stenosis: the U.K. Transcatheter Aortic Valve Implantation Registry. J Am Coll Cardiol Intv 2015;8:645–53. 15. Walther T, Hamm CW, Schuler G, et al. Perioperative results and complications in 15,964 transcatheter aortic valve replacements: prospective data from the GARY Registry. J Am Coll Cardiol 2015;65:2173–80. 16. Gilard M, Eltchaninoff H, Iung B, et al. Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med 2012;366:1705–15. 17. Lagerqvist B, Fr€ obert O, Olivecrona GK, et al. Outcomes 1 year after thrombus aspiration for myocardial infarction. N Engl J Med 2014;371:1111–20.