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Transcatheter Aortic Valve Implantation
JACC: CARDIOVASCULAR INTERVENTIONS
VOL. 4, NO. 1, 2011
© 2011 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-8798/$36.00
PUBLISHED BY ELSEVIER INC.
DOI: 10.1016/j.jcin.2010.12.002
ACC INTERVENTIONAL SCIENTIFIC COUNCIL: NEWS AND VIEWS
Transcatheter Aortic Valve Implantation Lessons From the PARTNER (Placement of Aortic Transcatheter Valves) Trial Jon C. George, MD,* Vincent Varghese, DO,* George Dangas, MD,† Jeffrey J. Popma, MD‡ Browns Mills, New Jersey; New York, New York; and Boston, Massachusetts
The PARTNER (Placement of Aortic Transcatheter Valves) trial, recently published (1) and presented at the 2010 Transcatheter Cardiovascular Therapeutics conference, investigated the safety and efficacy of transcatheter aortic-valve implantation (TAVI) in patients deemed unsuitable for surgical aortic valve replacement. Severe calcific aortic stenosis (AS) is an increasingly prevalent disease in elderly persons, with a high and rapid rate of mortality in untreated patients, approaching 50% mortality over the first 2 years (2). Aortic valve replacement is the current gold standard of treatment and has been proven to prolong and improve quality of life in good operative candidates; however, in patients with multiple or severe comorbidities and high operative risk, surgery is often prohibitive (3,4). Transcatheter aortic-valve implantation is a newer and less invasive alternative approach that has demonstrated favorable results and low mortality in these highsurgical-risk patients in the PARTNER trial. Trial Summary The PARTNER trial was a prospective, multicenter, randomized clinical trial designed to compare the outcomes of patients with symptomatic severe AS (defined as an aortic valve area of ⬍0.8 cm2, a mean transvalvular gradient of at least 40 mm Hg, or a peak aortic velocity of at least 4 m/s) by treatment with either TAVI or standard medical therapy. Patients selected were considered unsuitable candidates for aortic valve replacement due to an From the *Division of Interventional Cardiology and Endovascular Medicine, Deborah Heart and Lung Center, Browns Mills, New Jersey; †Division of Interventional Cardiology, Mount Sinai Medical Center, New York, New York; and the ‡Interventional Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Dr. George is a consultant for Boston Scientific and ev3 Endovascular. Dr. Popma has received research grants from Medtronic, Cordis, Boston Scientific, Abbott Vascular, and is a consultant for Cordis, Medtronic, St. Jude, and Abbott. All other authors have reported that they have no relationships to disclose.
exceedingly high surgical risk, as determined by the Society of Thoracic Surgeons risk score. A total of 358 patients were enrolled across 21 sites and followed for at least 1 year. The Edwards SAPIEN heart-valve system (Edwards Lifesciences, Inc., Irvine, California) was the bioprosthetic aortic valve used for TAVI, consisting of a trileaflet bovine pericardial valve and a balloonexpandable stainless steel support frame. Standard medical therapy included balloon aortic valvuloplasty, which was performed in almost 65% of the patients in the control arm within the first 30 days after randomization. The primary end point was the rate of death from any cause at 30 days and 1 year, and secondary end points included the rate of death from cardiovascular causes, New York Heart Association functional class status, rates of myocardial infarction, stroke, bleeding, and vascular complications. The reported rate of death from any cause at 30 days was nonsignificantly higher in the TAVI-treated group in comparison with the standard medical therapy group (5.0% vs. 2.8%, respectively, p ⫽ 0.41). However, at 1-year follow-up, the rate of death from any cause was significantly lower in the TAVI group compared with the medical treatment group (30.7% vs. 50.7%, p ⬍ 0.001). In addition, the rate of death from cardiovascular causes was also lower in the TAVI arm versus the medical therapy arm (20.5% vs. 44.6%, respectively, p ⬍ 0.001). Major strokes, although nonsignificant, were more common in patients who underwent TAVI at 30 days (5.0% vs. 1.1%, p ⫽ 0.06) and 1 year (7.8% vs. 3.9%, p ⫽ 0.18). Additionally, major bleeding events and vascular complications were significantly increased in the TAVI treatment group versus the medically treated group at 30 days and at 1 year. Study Comparisons The observed 30-day mortality rate of 5.0% in the TAVI treatment arm is lower than previously reported studies, which range from 8.6% to 11.3%
George et al. ACC Interventional Scientific Council
JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 4, NO. 1, 2011 JANUARY 2011:132–3
(5– 8); in contrast, the 1-year mortality of 30.7% in TAVI patients was higher than previously reported studies, ranging from 22% to 26% (5–7). These discrepancies might be due to operator inexperience and/or earlier-generation valve systems as well as incomplete patient follow-up in previous reports. Aortic regurgitation is a common finding after TAVI and is usually mild and paravalvular in nature (8,9). The 30-day and 1-year incidence of moderate or severe paravalvular aortic regurgitation in the PARTNER trial was lower at 11.8% and 10.5%, respectively, in TAVI patients compared with 26% and 14% in other recently published studies (10). Future Direction The PARTNER trial investigated the efficacy and safety of TAVI in otherwise inoperable patients with severe symptomatic AS and further strengthened the momentum toward TAVI in high-risk surgical patients. Continued advancements in delivery systems, valve durability, smaller sheath sizes, and operator experience will continue to make TAVI a viable option for patients with severe AS and prohibitive surgical risk. A second randomized trial from the PARTNER study (PARTNER II) investigating TAVI use with the new 18-F device in patients with high but not prohibitive surgical risk is currently ongoing and offers to shed light on TAVI use in surgical candidates. Further evaluation of transfemoral, transaxillary, and transapical approaches to TAVI in addition to newer devices, including the Medtronic Core Valve system (Medtronic, Minneapolis, Minnesota), might broaden the suitability of TAVI for a wider range of patients. The exclusion of patients with coronary stenoses requiring revascularization, left ventricular ejection fraction ⬍20%, and severe peripheral arterial disease limits the usefulness of the results of the trial in everyday cardiology practice and necessitates further investigation. The current challenge, with the improving technical success of TAVI, is finding the appropriate patient population for whom the procedure is best suited; this could be facilitated by the development of a “TAVI risk score” (11). The threat of major stroke from embolic debris during TAVI remains a concerning dilemma. Although the overall risk of permanent neurologic deficit is low, up to 72.7% of patients had new clinically silent cerebral lesions detected by magnetic resonance imaging in a small prospective study (12). Recent studies have evaluated the feasibility of embolic protection devices during TAVI (13), but their role remains currently undefined. The regulatory pathway for approval in the U.S. of the particular valve used in this trial is likely related to the ancillary economic and quality-of-life analyses, the presentation of the PARTNER cohort A (on high-risk though operable patients who were randomized to TAVI vs. aortic
133
valve surgery) in early 2011, and the interrelated device evolution to the 18-F system that is already used where this valve has been approved for clinical use. Finally, the concept of hospital operator team training in large scale is also important. Furthermore, the futility question, the global health system economic management issues, device evolution steps, further understanding and tackling TAVI complications, and incorporation in the clinical practice in the U.S. are major challenges to be met. Evidently, many steps toward making TAVI possible have been accomplished, but some more are still pending. Reprint requests and correspondence: Dr. Jon C. George, Director of Clinical Research, Division of Interventional Cardiology and Endovascular Medicine, Deborah Heart and Lung Center, 200 Trenton Road, Browns Mills, New Jersey 08015. E-mail: [email protected].
REFERENCES
1. 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– 607. 2. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008;52:e1–142. 3. Schwarz F, Baumann P, Manthey J, et al. The effect of aortic valve replacement on survival. Circulation 1982;66:1105–10. 4. Murphy ES, Lawson RM, Starr A, Rahimtoola SH. Severe aortic stenosis in patients 60 years of age or older: left ventricular function and 10-year survival after valve replacement. Circulation 1981;64:II184 – 8. 5. Rodes-Cabau J, Webb JG, Cheung A, et al. Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk. J Am Coll Cardiol 2010;55:1081–90. 6. Himbert D, Descoutures F, Al-Attar N, et al. Results of transfemoral or transapical aortic valve implantation following a uniform assessment in high-risk patients with aortic stenosis. J Am Coll Cardiol 2009;54: 303–11. 7. Webb JG, Altwegg L, Boone R, et al. Transcatheter aortic valve implantation. Impact on clinical and valve-related outcomes. Circulation 2009;119:3009 –16. 8. Rodes-Cabau J, Dumont E, DelaRochelliere R, et al. Feasibility and initial results of percutaneous aortic valve implantation including selection of the transfemoral or transapical approach in patients with severe aortic stenosis. Am J Cardiol 2008;102:1240 – 6. 9. Cribier A, Eltchaninoff H, Tron C, et al. Treatment of calcific aortic stenosis with the percutaneous heart valve. Mid-term follow up from the initial feasibility studies: the French experience. J Am Coll Cardiol 2006;47:1214 –23. 10. Sherif MA, Abdel-Wahab M, Stoker B, et al. Anatomic and procedural predictors of paravalvular aortic regurgitation after implantation of the Medtronic CoreValve bioprosthesis. J Am Coll Cardiol 2010; 56:1623–9. 11. Thomas M. The global experience with percutaneous aortic valve replacement. J Am Coll Cardiol Intv 2010;3:1103–9. 12. Ghanem A, Muller A, Nahle C, et al. Risk and fate of cerebral embolism after transfemoral aortic valve implantation. J Am Coll Cardiol 2010;55:1427–32. 13. Nietlispach F, Wijesinghe N, Gurvitch R, et al. An embolic deflection device for aortic valve interventions. J Am Coll Cardiol Intv 2010;3: 1133– 8.
VOL. 4, NO. 1, 2011
© 2011 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-8798/$36.00
PUBLISHED BY ELSEVIER INC.
DOI: 10.1016/j.jcin.2010.12.002
ACC INTERVENTIONAL SCIENTIFIC COUNCIL: NEWS AND VIEWS
Transcatheter Aortic Valve Implantation Lessons From the PARTNER (Placement of Aortic Transcatheter Valves) Trial Jon C. George, MD,* Vincent Varghese, DO,* George Dangas, MD,† Jeffrey J. Popma, MD‡ Browns Mills, New Jersey; New York, New York; and Boston, Massachusetts
The PARTNER (Placement of Aortic Transcatheter Valves) trial, recently published (1) and presented at the 2010 Transcatheter Cardiovascular Therapeutics conference, investigated the safety and efficacy of transcatheter aortic-valve implantation (TAVI) in patients deemed unsuitable for surgical aortic valve replacement. Severe calcific aortic stenosis (AS) is an increasingly prevalent disease in elderly persons, with a high and rapid rate of mortality in untreated patients, approaching 50% mortality over the first 2 years (2). Aortic valve replacement is the current gold standard of treatment and has been proven to prolong and improve quality of life in good operative candidates; however, in patients with multiple or severe comorbidities and high operative risk, surgery is often prohibitive (3,4). Transcatheter aortic-valve implantation is a newer and less invasive alternative approach that has demonstrated favorable results and low mortality in these highsurgical-risk patients in the PARTNER trial. Trial Summary The PARTNER trial was a prospective, multicenter, randomized clinical trial designed to compare the outcomes of patients with symptomatic severe AS (defined as an aortic valve area of ⬍0.8 cm2, a mean transvalvular gradient of at least 40 mm Hg, or a peak aortic velocity of at least 4 m/s) by treatment with either TAVI or standard medical therapy. Patients selected were considered unsuitable candidates for aortic valve replacement due to an From the *Division of Interventional Cardiology and Endovascular Medicine, Deborah Heart and Lung Center, Browns Mills, New Jersey; †Division of Interventional Cardiology, Mount Sinai Medical Center, New York, New York; and the ‡Interventional Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Dr. George is a consultant for Boston Scientific and ev3 Endovascular. Dr. Popma has received research grants from Medtronic, Cordis, Boston Scientific, Abbott Vascular, and is a consultant for Cordis, Medtronic, St. Jude, and Abbott. All other authors have reported that they have no relationships to disclose.
exceedingly high surgical risk, as determined by the Society of Thoracic Surgeons risk score. A total of 358 patients were enrolled across 21 sites and followed for at least 1 year. The Edwards SAPIEN heart-valve system (Edwards Lifesciences, Inc., Irvine, California) was the bioprosthetic aortic valve used for TAVI, consisting of a trileaflet bovine pericardial valve and a balloonexpandable stainless steel support frame. Standard medical therapy included balloon aortic valvuloplasty, which was performed in almost 65% of the patients in the control arm within the first 30 days after randomization. The primary end point was the rate of death from any cause at 30 days and 1 year, and secondary end points included the rate of death from cardiovascular causes, New York Heart Association functional class status, rates of myocardial infarction, stroke, bleeding, and vascular complications. The reported rate of death from any cause at 30 days was nonsignificantly higher in the TAVI-treated group in comparison with the standard medical therapy group (5.0% vs. 2.8%, respectively, p ⫽ 0.41). However, at 1-year follow-up, the rate of death from any cause was significantly lower in the TAVI group compared with the medical treatment group (30.7% vs. 50.7%, p ⬍ 0.001). In addition, the rate of death from cardiovascular causes was also lower in the TAVI arm versus the medical therapy arm (20.5% vs. 44.6%, respectively, p ⬍ 0.001). Major strokes, although nonsignificant, were more common in patients who underwent TAVI at 30 days (5.0% vs. 1.1%, p ⫽ 0.06) and 1 year (7.8% vs. 3.9%, p ⫽ 0.18). Additionally, major bleeding events and vascular complications were significantly increased in the TAVI treatment group versus the medically treated group at 30 days and at 1 year. Study Comparisons The observed 30-day mortality rate of 5.0% in the TAVI treatment arm is lower than previously reported studies, which range from 8.6% to 11.3%
George et al. ACC Interventional Scientific Council
JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 4, NO. 1, 2011 JANUARY 2011:132–3
(5– 8); in contrast, the 1-year mortality of 30.7% in TAVI patients was higher than previously reported studies, ranging from 22% to 26% (5–7). These discrepancies might be due to operator inexperience and/or earlier-generation valve systems as well as incomplete patient follow-up in previous reports. Aortic regurgitation is a common finding after TAVI and is usually mild and paravalvular in nature (8,9). The 30-day and 1-year incidence of moderate or severe paravalvular aortic regurgitation in the PARTNER trial was lower at 11.8% and 10.5%, respectively, in TAVI patients compared with 26% and 14% in other recently published studies (10). Future Direction The PARTNER trial investigated the efficacy and safety of TAVI in otherwise inoperable patients with severe symptomatic AS and further strengthened the momentum toward TAVI in high-risk surgical patients. Continued advancements in delivery systems, valve durability, smaller sheath sizes, and operator experience will continue to make TAVI a viable option for patients with severe AS and prohibitive surgical risk. A second randomized trial from the PARTNER study (PARTNER II) investigating TAVI use with the new 18-F device in patients with high but not prohibitive surgical risk is currently ongoing and offers to shed light on TAVI use in surgical candidates. Further evaluation of transfemoral, transaxillary, and transapical approaches to TAVI in addition to newer devices, including the Medtronic Core Valve system (Medtronic, Minneapolis, Minnesota), might broaden the suitability of TAVI for a wider range of patients. The exclusion of patients with coronary stenoses requiring revascularization, left ventricular ejection fraction ⬍20%, and severe peripheral arterial disease limits the usefulness of the results of the trial in everyday cardiology practice and necessitates further investigation. The current challenge, with the improving technical success of TAVI, is finding the appropriate patient population for whom the procedure is best suited; this could be facilitated by the development of a “TAVI risk score” (11). The threat of major stroke from embolic debris during TAVI remains a concerning dilemma. Although the overall risk of permanent neurologic deficit is low, up to 72.7% of patients had new clinically silent cerebral lesions detected by magnetic resonance imaging in a small prospective study (12). Recent studies have evaluated the feasibility of embolic protection devices during TAVI (13), but their role remains currently undefined. The regulatory pathway for approval in the U.S. of the particular valve used in this trial is likely related to the ancillary economic and quality-of-life analyses, the presentation of the PARTNER cohort A (on high-risk though operable patients who were randomized to TAVI vs. aortic
133
valve surgery) in early 2011, and the interrelated device evolution to the 18-F system that is already used where this valve has been approved for clinical use. Finally, the concept of hospital operator team training in large scale is also important. Furthermore, the futility question, the global health system economic management issues, device evolution steps, further understanding and tackling TAVI complications, and incorporation in the clinical practice in the U.S. are major challenges to be met. Evidently, many steps toward making TAVI possible have been accomplished, but some more are still pending. Reprint requests and correspondence: Dr. Jon C. George, Director of Clinical Research, Division of Interventional Cardiology and Endovascular Medicine, Deborah Heart and Lung Center, 200 Trenton Road, Browns Mills, New Jersey 08015. E-mail: [email protected].
REFERENCES
1. 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– 607. 2. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008;52:e1–142. 3. Schwarz F, Baumann P, Manthey J, et al. The effect of aortic valve replacement on survival. Circulation 1982;66:1105–10. 4. Murphy ES, Lawson RM, Starr A, Rahimtoola SH. Severe aortic stenosis in patients 60 years of age or older: left ventricular function and 10-year survival after valve replacement. Circulation 1981;64:II184 – 8. 5. Rodes-Cabau J, Webb JG, Cheung A, et al. Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk. J Am Coll Cardiol 2010;55:1081–90. 6. Himbert D, Descoutures F, Al-Attar N, et al. Results of transfemoral or transapical aortic valve implantation following a uniform assessment in high-risk patients with aortic stenosis. J Am Coll Cardiol 2009;54: 303–11. 7. Webb JG, Altwegg L, Boone R, et al. Transcatheter aortic valve implantation. Impact on clinical and valve-related outcomes. Circulation 2009;119:3009 –16. 8. Rodes-Cabau J, Dumont E, DelaRochelliere R, et al. Feasibility and initial results of percutaneous aortic valve implantation including selection of the transfemoral or transapical approach in patients with severe aortic stenosis. Am J Cardiol 2008;102:1240 – 6. 9. Cribier A, Eltchaninoff H, Tron C, et al. Treatment of calcific aortic stenosis with the percutaneous heart valve. Mid-term follow up from the initial feasibility studies: the French experience. J Am Coll Cardiol 2006;47:1214 –23. 10. Sherif MA, Abdel-Wahab M, Stoker B, et al. Anatomic and procedural predictors of paravalvular aortic regurgitation after implantation of the Medtronic CoreValve bioprosthesis. J Am Coll Cardiol 2010; 56:1623–9. 11. Thomas M. The global experience with percutaneous aortic valve replacement. J Am Coll Cardiol Intv 2010;3:1103–9. 12. Ghanem A, Muller A, Nahle C, et al. Risk and fate of cerebral embolism after transfemoral aortic valve implantation. J Am Coll Cardiol 2010;55:1427–32. 13. Nietlispach F, Wijesinghe N, Gurvitch R, et al. An embolic deflection device for aortic valve interventions. J Am Coll Cardiol Intv 2010;3: 1133– 8.