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With the Food and Drug Administration’s approval of two different pairs of transcatheter aortic valve replacement systems for patients at low surgical risk, U.S. case volume for the procedure should markedly rise given that patients at low surgical risk form the largest risk subgroup among patients with aortic stenosis severe enough to warrant valve replacement.
But even as transcatheter aortic valve replacement (TAVR) now becomes the predominant approach for fixing severely stenotic aortic valves regardless of a patient’s risk level, the procedure remains less optimal than surgical aortic valve replacement (SAVR) in selected patients, putting an onus on clinicians to identify and alert patients for whom the transcatheter approach is questionable.
The anticipated surge in TAVR cases for low-risk patients after the FDA’s Aug. 16, 2019, decision will also likely lead to more hospitals offering TAVR. That development will test whether recently enacted rules from the Centers for Medicare & Medicaid Services on procedure-volume minimums for TAVR programs – at least 20 cases a year (or 40 within 2 years) at centers that also perform at least 300 percutaneous coronary interventions annually – lead to outcomes at lower-volume centers that come reasonably close to the outcomes at higher-volume programs for low-risk patients.
“The paradigm has definitely shifted from SAVR as the gold standard to TAVR as the primary treatment for aortic stenosis. This opens TAVR to the vast majority of patients with aortic stenosis,” roughly three-quarters of patients with aortic valve stenosis severe enough to need valve replacement, said Joseph C. Cleveland Jr., MD, a cardiothoracic surgeon and professor of surgery at the University of Colorado at Denver, Aurora.
The actual, immediate increase in TAVR patients may not be quite as large as this fraction suggests. That’s in part because many patients in the low-risk category based on their surgical risk score already have been judged to have higher-risk features by heart-valve teams that has allowed such patients to undergo TAVR, said John D. Carroll, MD, professor of medicine and director of interventional cardiology at the University of Colorado.
For several years, U.S. rates of TAVR have exceeded SAVR, he noted, and in 2018 U.S. programs performed roughly 58,000 TAVR procedures and about 25,000 SAVRs, according to data collected by the Transcatheter Valve Therapy (TVT) Registry run by the Society of Thoracic Surgeons and the American College of Cardiology. Dr. Carroll is vice chair of the steering committee for this registry, which was mandated by the FDA in 2011 when the agency first allowed TAVR onto the U.S. market and is designed to capture every TAVR case performed in routine U.S. practice.
Despite this caveat, “there will be substantial growth in TAVR. Going forward, there will be more of a shift from SAVR to TAVR. That is what the results of the low-risk trials did,” Dr. Carroll predicted. In addition, the coming growth in TAVR numbers will stem from more than just low-risk patients whom a month ago would have undergone SAVR but now undergo TAVR instead. The availability of TAVR as an option for a wider range of patients should help boost public awareness that a nonsurgical way exists to treat severe aortic stenosis, plus the aging of baby boomers is on the verge of generating a substantial wave of new patients, a wave so high that Dr. Carroll called it a looming “tsunami” of patients needing TAVR.
How will low-risk TAVR affect lower-volume sites?
More TAVR patients will inevitably mean more U.S. sites offering the procedure, experts agreed. “We anticipate more low-volume programs,” Dr. Carroll said.
“Approval of TAVR for low-risk patients will result in a significant increase in the number of programs offering it. Approximately 1,100 U.S. programs offer SAVR, and as of now about 600 of these programs also offer TAVR. Health systems face the risk of losing patients if they don’t offer TAVR now that low-risk patients can be treated,” observed Sreekanth Vemulapalli, MD, a cardiologist at Duke University, Durham, N.C. who has run several studies using TVT Registry data and serves as liaison between the registry and its analytic center at Duke.
One of these studies, published earlier in 2019, showed that, among more than 96,000 registry patients who underwent transfemoral TAVR during 2015-2017 at 554 U.S. centers, those treated at sites that fell into the bottom quartile for case volume had an adjusted 30-day mortality rate that was 21% higher relative to patients treated at centers in the top quartile, a statistically significant difference (N Engl J Med. 2019 Jun 27;380[26]:2541-50). The absolute difference in adjusted 30-day mortality between the lowest and highest quartiles was 0.54%, roughly 1 additional death for every 200 patients. The TAVR centers in the lowest-volume quartile performed 5-36 cases/year, averaging 27 TAVRs/year; those in the highest quartile performed 86-371 TAVRs annually with an overall quartile average of 143 procedures/year.
Dr. Vemulapalli and others cautioned that TAVR case volume is currently serving as a surrogate, and imperfect, marker for program quality until TAVR programs generate enough data to allow a directly measured, risk-adjusted, outcome-driven assessment of performance. In the study he and his associates published in June, the 140 TAVR programs in the lowest-volume quartile showed a “high” level of variability in their adjusted mortality rates. Despite this limitation, the prospect that new TAVR programs will soon open to meet growing TAVR demand from low-risk patients poses the question of how these programs will perform during their start-up days (and possibly beyond), when case volumes may be light, especially if sites open in more remote sections of the United States.
“Will the real-world results of TAVR in low-risk patients match the fantastic results in the two low-risk TAVR trials?” wondered Dr. Carroll, referring to the PARTNER 3 (N Engl J Med. 2019 May 2;380[18]:1695-1705) and Evolut Low-Risk Patients trial (N Engl J Med. 2019 May 2;380[18]:1706-15). “It’s unknown whether a site just starting to do TAVRs will get the same results. The sites that participated in the low-risk trials were mostly high-volume sites.” On the other hand, TVT Registry data have shown that patients with surgical risk that was judged prohibitive, high, or intermediate all have had overall real-world outcomes that match what was seen in the relevant TAVR trials.
In addition, some experts view a modest drop in 30-day survival among patients treated at lower-volume TAVR sites as a reasonable trade-off for easier access for patients seeking this life-changing treatment.
“We need to ensure that patients have access to this treatment option,” said Catherine M. Otto, MD, professor of medicine and director of the Heart Valve Clinic at the University of Washington, Seattle. The potentially better outcomes produced at larger TAVR programs “need to be balanced against having a greater number of programs to ensure access for more patients and allow patients to be treated closer to home,” she said in an interview. She suggested that the potential exists to use telemedicine to link larger and more experienced TAVR programs with smaller and newer programs to help boost their performance.
“There is no perfect solution or metric to ensure high quality while also allowing for adequate access. As indications for TAVR expand we need to maintain vigilance and accountability as the therapy is dispersed to more patients at more centers,” said Brian R. Lindman, MD, medical director of the Structural Heat and Valve Center at Vanderbilt University, Nashville, Tenn. “We also need to insure that certain groups of patients have adequate access to this therapy. Adequate access to TAVR and high-quality clinical outcomes are both important goals.”
Plus, “the volume relationship may be less important,” in lower-risk patients, suggested Dr. Cleveland in an interview. Low-risk patients are younger and have fewer comorbidities and less vascular disease. “Low-volume centers should be able to treat these patients,” he said. Despite that, he personally supported the higher volume minimum for TAVR of 50 cases/year that the ACC, STS, and other U.S. professional societies recommended to CMS during public comment on the proposed rules. “We’ll see whether the increased access is worth this volume minimum.”
Who still gets SAVR?
Given the inherent attraction TAVR holds over SAVR for patients, heart-valve teams will need to convey the right message to patients who may be better served with surgical replacement despite the added trauma and recovery time it produces.
“The decision to perform TAVR or SAVR should now be based on a patient’s expected longevity as well as patient preferences and values, and not on the patient’s estimated surgical risk, except for the highest-risk patients in whom TAVR is recommended,” said Dr. Otto. A patient’s age, comorbidities, and overall life expectancy now move to center stage when deciding the TAVR or SAVR question, along with individual anatomic considerations, the possible need for concurrent procedures, and of course what the patient prefers including their willingness and ability to remain on lifelong anticoagulation if they receive a durable mechanical valve. Dr. Otto outlined this new landscape of the heart-valve team’s decision making process in an editorial she recently published (N Engl J Med. 2019 May 2;380[18]: 1769-70) that accompanied publication of PARTNER 3 and the Evolut Low-Risk Patients trial.
“For some patients there will be clear benefit from one approach, but for many patients, particularly those at low surgical risk, both TAVR and SAVR are technically feasible. For these patients it’s essential that the heart-valve team provide unbiased information to guide patients,” Dr. Otto said. The ideal person to provide this unbiased presentation of the pros and cons would be a cardiologist experienced with valve disease but not actively involved in performing valve-replacement procedures.
A big issue younger patients must confront is what remains unknown about long-term durability of TAVR valves. Dr. Otto called this “the most important missing piece of information. We only have robust data out to about 5 years. If TAVR valve will be durable for 15-20 years, then TAVR will become preferred even in younger patients.”
Even after TAVR became available to intermediate-risk patients in 2016, the median age of U.S. patients undergoing TAVR hardly budged, and has recently stood at about 81 years, Dr. Carroll noted. “With low-risk patients, we expect to see this change,” as more patients now who are in their 70s, 60s, and younger start to routinely undergo TAVR. As more younger patients with life expectancies on the order of 30 years consider TAVR, issues of valve durability “enter the discussion,” he said. “We need data to 10, 15 years,” and in its low-risk approval the FDA mandated manufacturers to follow these patients for at least 10 years. Although valve-in-valve replacement of failed TAVR valves is an option, it’s not always a smooth fix with the potential for prosthesis-patient mismatch (J Am Coll Cardiol. 2018 Dec 4;72[22]:2701-11) and resulting hemodynamic problems, Dr. Carroll said.
Bicuspid-valve replacement with TAVR is another big unknown, largely because these patients were excluded from the TAVR trials. A recently published analysis of the 2,726 patients with a bicuspid aortic valve who underwent TAVR anyway in routine U.S. practice between June 2015 and November 2018 and were in the TVT Registry (about 3% of all TAVR patients during this period) showed that these patients had similar mortality, compared with the tricuspid-valve patients, but a significantly increased stroke rate (JAMA. 2019 Jun 11;321[22]:2193-202). The authors concluded that a prospective, randomized study of TAVR, compared with SAVR, is needed for these patients, and many others in the field agree.
As availability of TAVR grows and public awareness increases, heart-valve teams may find it challenging sometimes to help patients understand the upsides of SAVR for their individual clinical needs when TAVR is superficially so much more attractive.
“The desire to avoid the prolonged hospitalization and recovery from SAVR is a huge driver of patient preference,” noted Dr. Carroll.
“It’s hard to tell a 55 year old to think about another procedure they may need when they are 65 or 70 if they undergo TAVR now rather than SAVR. They don’t want open-heart surgery; I hear that all the time,” Dr. Cleveland said. “If I were a 55-year-old aortic valve patient I’d strongly consider TAVR, too.”
Financial consideration at the site performing the interventions can also be a factor. “Differential costs and payments associated with SAVR and TAVR create different financial incentives for health systems between these two procedures,” noted Dr. Vemulapalli. “There likely needs to be a system that creates equal incentives to do SAVR or TAVR so that the decision between them can come down to just the patient and heart-valve team. We need further data and decision aids to help better define which patients will likely do better with SAVR and which with TAVR.”
What now?
Since the first large TAVR trials started in 2007, their main thrust has been to prove the efficacy and safety of TAVR in patients at sequentially less risk of undergoing SAVR. Now that this series of comparisons has ended, where will TAVR research turn its attention?
In addition to the big outstanding issues of TAVR-valve long-term durability, and the efficacy and safety of TAVR for replacing bicuspid valves, other big questions and issues loom. They include the optimal anticoagulant regimen for preventing leaflet thrombosis, reducing the need for pacemakers, reducing strokes, the applicability of TAVR to patients with less severe aortic stenosis, the impact of treating severe but asymptomatic aortic valve obstruction, optimizing valve-in-valve outcomes, and further improvements to valve design, hemodynamics, and delivery. In short, the question of TAVR’s suitability for patients regardless of their surgical risk may have now been answered, but many questions remain about the best way to use and to optimize this technology.
Dr. Cleveland and Dr. Carroll have participated in TAVR trials but had no personal financial disclosures. Dr. Otto had no disclosures. Dr. Vemulapalli has received personal fees from Janssen, Novella, Premiere, and Zafgen, and research funding from Boston Scientific and Abbott Vascular. Dr. Lindman has been a consultant to Medtronic, has served as an advisor to Roche, and has received research funding from Edwards Lifesciences.
With the Food and Drug Administration’s approval of two different pairs of transcatheter aortic valve replacement systems for patients at low surgical risk, U.S. case volume for the procedure should markedly rise given that patients at low surgical risk form the largest risk subgroup among patients with aortic stenosis severe enough to warrant valve replacement.
But even as transcatheter aortic valve replacement (TAVR) now becomes the predominant approach for fixing severely stenotic aortic valves regardless of a patient’s risk level, the procedure remains less optimal than surgical aortic valve replacement (SAVR) in selected patients, putting an onus on clinicians to identify and alert patients for whom the transcatheter approach is questionable.
The anticipated surge in TAVR cases for low-risk patients after the FDA’s Aug. 16, 2019, decision will also likely lead to more hospitals offering TAVR. That development will test whether recently enacted rules from the Centers for Medicare & Medicaid Services on procedure-volume minimums for TAVR programs – at least 20 cases a year (or 40 within 2 years) at centers that also perform at least 300 percutaneous coronary interventions annually – lead to outcomes at lower-volume centers that come reasonably close to the outcomes at higher-volume programs for low-risk patients.
“The paradigm has definitely shifted from SAVR as the gold standard to TAVR as the primary treatment for aortic stenosis. This opens TAVR to the vast majority of patients with aortic stenosis,” roughly three-quarters of patients with aortic valve stenosis severe enough to need valve replacement, said Joseph C. Cleveland Jr., MD, a cardiothoracic surgeon and professor of surgery at the University of Colorado at Denver, Aurora.
The actual, immediate increase in TAVR patients may not be quite as large as this fraction suggests. That’s in part because many patients in the low-risk category based on their surgical risk score already have been judged to have higher-risk features by heart-valve teams that has allowed such patients to undergo TAVR, said John D. Carroll, MD, professor of medicine and director of interventional cardiology at the University of Colorado.
For several years, U.S. rates of TAVR have exceeded SAVR, he noted, and in 2018 U.S. programs performed roughly 58,000 TAVR procedures and about 25,000 SAVRs, according to data collected by the Transcatheter Valve Therapy (TVT) Registry run by the Society of Thoracic Surgeons and the American College of Cardiology. Dr. Carroll is vice chair of the steering committee for this registry, which was mandated by the FDA in 2011 when the agency first allowed TAVR onto the U.S. market and is designed to capture every TAVR case performed in routine U.S. practice.
Despite this caveat, “there will be substantial growth in TAVR. Going forward, there will be more of a shift from SAVR to TAVR. That is what the results of the low-risk trials did,” Dr. Carroll predicted. In addition, the coming growth in TAVR numbers will stem from more than just low-risk patients whom a month ago would have undergone SAVR but now undergo TAVR instead. The availability of TAVR as an option for a wider range of patients should help boost public awareness that a nonsurgical way exists to treat severe aortic stenosis, plus the aging of baby boomers is on the verge of generating a substantial wave of new patients, a wave so high that Dr. Carroll called it a looming “tsunami” of patients needing TAVR.
How will low-risk TAVR affect lower-volume sites?
More TAVR patients will inevitably mean more U.S. sites offering the procedure, experts agreed. “We anticipate more low-volume programs,” Dr. Carroll said.
“Approval of TAVR for low-risk patients will result in a significant increase in the number of programs offering it. Approximately 1,100 U.S. programs offer SAVR, and as of now about 600 of these programs also offer TAVR. Health systems face the risk of losing patients if they don’t offer TAVR now that low-risk patients can be treated,” observed Sreekanth Vemulapalli, MD, a cardiologist at Duke University, Durham, N.C. who has run several studies using TVT Registry data and serves as liaison between the registry and its analytic center at Duke.
One of these studies, published earlier in 2019, showed that, among more than 96,000 registry patients who underwent transfemoral TAVR during 2015-2017 at 554 U.S. centers, those treated at sites that fell into the bottom quartile for case volume had an adjusted 30-day mortality rate that was 21% higher relative to patients treated at centers in the top quartile, a statistically significant difference (N Engl J Med. 2019 Jun 27;380[26]:2541-50). The absolute difference in adjusted 30-day mortality between the lowest and highest quartiles was 0.54%, roughly 1 additional death for every 200 patients. The TAVR centers in the lowest-volume quartile performed 5-36 cases/year, averaging 27 TAVRs/year; those in the highest quartile performed 86-371 TAVRs annually with an overall quartile average of 143 procedures/year.
Dr. Vemulapalli and others cautioned that TAVR case volume is currently serving as a surrogate, and imperfect, marker for program quality until TAVR programs generate enough data to allow a directly measured, risk-adjusted, outcome-driven assessment of performance. In the study he and his associates published in June, the 140 TAVR programs in the lowest-volume quartile showed a “high” level of variability in their adjusted mortality rates. Despite this limitation, the prospect that new TAVR programs will soon open to meet growing TAVR demand from low-risk patients poses the question of how these programs will perform during their start-up days (and possibly beyond), when case volumes may be light, especially if sites open in more remote sections of the United States.
“Will the real-world results of TAVR in low-risk patients match the fantastic results in the two low-risk TAVR trials?” wondered Dr. Carroll, referring to the PARTNER 3 (N Engl J Med. 2019 May 2;380[18]:1695-1705) and Evolut Low-Risk Patients trial (N Engl J Med. 2019 May 2;380[18]:1706-15). “It’s unknown whether a site just starting to do TAVRs will get the same results. The sites that participated in the low-risk trials were mostly high-volume sites.” On the other hand, TVT Registry data have shown that patients with surgical risk that was judged prohibitive, high, or intermediate all have had overall real-world outcomes that match what was seen in the relevant TAVR trials.
In addition, some experts view a modest drop in 30-day survival among patients treated at lower-volume TAVR sites as a reasonable trade-off for easier access for patients seeking this life-changing treatment.
“We need to ensure that patients have access to this treatment option,” said Catherine M. Otto, MD, professor of medicine and director of the Heart Valve Clinic at the University of Washington, Seattle. The potentially better outcomes produced at larger TAVR programs “need to be balanced against having a greater number of programs to ensure access for more patients and allow patients to be treated closer to home,” she said in an interview. She suggested that the potential exists to use telemedicine to link larger and more experienced TAVR programs with smaller and newer programs to help boost their performance.
“There is no perfect solution or metric to ensure high quality while also allowing for adequate access. As indications for TAVR expand we need to maintain vigilance and accountability as the therapy is dispersed to more patients at more centers,” said Brian R. Lindman, MD, medical director of the Structural Heat and Valve Center at Vanderbilt University, Nashville, Tenn. “We also need to insure that certain groups of patients have adequate access to this therapy. Adequate access to TAVR and high-quality clinical outcomes are both important goals.”
Plus, “the volume relationship may be less important,” in lower-risk patients, suggested Dr. Cleveland in an interview. Low-risk patients are younger and have fewer comorbidities and less vascular disease. “Low-volume centers should be able to treat these patients,” he said. Despite that, he personally supported the higher volume minimum for TAVR of 50 cases/year that the ACC, STS, and other U.S. professional societies recommended to CMS during public comment on the proposed rules. “We’ll see whether the increased access is worth this volume minimum.”
Who still gets SAVR?
Given the inherent attraction TAVR holds over SAVR for patients, heart-valve teams will need to convey the right message to patients who may be better served with surgical replacement despite the added trauma and recovery time it produces.
“The decision to perform TAVR or SAVR should now be based on a patient’s expected longevity as well as patient preferences and values, and not on the patient’s estimated surgical risk, except for the highest-risk patients in whom TAVR is recommended,” said Dr. Otto. A patient’s age, comorbidities, and overall life expectancy now move to center stage when deciding the TAVR or SAVR question, along with individual anatomic considerations, the possible need for concurrent procedures, and of course what the patient prefers including their willingness and ability to remain on lifelong anticoagulation if they receive a durable mechanical valve. Dr. Otto outlined this new landscape of the heart-valve team’s decision making process in an editorial she recently published (N Engl J Med. 2019 May 2;380[18]: 1769-70) that accompanied publication of PARTNER 3 and the Evolut Low-Risk Patients trial.
“For some patients there will be clear benefit from one approach, but for many patients, particularly those at low surgical risk, both TAVR and SAVR are technically feasible. For these patients it’s essential that the heart-valve team provide unbiased information to guide patients,” Dr. Otto said. The ideal person to provide this unbiased presentation of the pros and cons would be a cardiologist experienced with valve disease but not actively involved in performing valve-replacement procedures.
A big issue younger patients must confront is what remains unknown about long-term durability of TAVR valves. Dr. Otto called this “the most important missing piece of information. We only have robust data out to about 5 years. If TAVR valve will be durable for 15-20 years, then TAVR will become preferred even in younger patients.”
Even after TAVR became available to intermediate-risk patients in 2016, the median age of U.S. patients undergoing TAVR hardly budged, and has recently stood at about 81 years, Dr. Carroll noted. “With low-risk patients, we expect to see this change,” as more patients now who are in their 70s, 60s, and younger start to routinely undergo TAVR. As more younger patients with life expectancies on the order of 30 years consider TAVR, issues of valve durability “enter the discussion,” he said. “We need data to 10, 15 years,” and in its low-risk approval the FDA mandated manufacturers to follow these patients for at least 10 years. Although valve-in-valve replacement of failed TAVR valves is an option, it’s not always a smooth fix with the potential for prosthesis-patient mismatch (J Am Coll Cardiol. 2018 Dec 4;72[22]:2701-11) and resulting hemodynamic problems, Dr. Carroll said.
Bicuspid-valve replacement with TAVR is another big unknown, largely because these patients were excluded from the TAVR trials. A recently published analysis of the 2,726 patients with a bicuspid aortic valve who underwent TAVR anyway in routine U.S. practice between June 2015 and November 2018 and were in the TVT Registry (about 3% of all TAVR patients during this period) showed that these patients had similar mortality, compared with the tricuspid-valve patients, but a significantly increased stroke rate (JAMA. 2019 Jun 11;321[22]:2193-202). The authors concluded that a prospective, randomized study of TAVR, compared with SAVR, is needed for these patients, and many others in the field agree.
As availability of TAVR grows and public awareness increases, heart-valve teams may find it challenging sometimes to help patients understand the upsides of SAVR for their individual clinical needs when TAVR is superficially so much more attractive.
“The desire to avoid the prolonged hospitalization and recovery from SAVR is a huge driver of patient preference,” noted Dr. Carroll.
“It’s hard to tell a 55 year old to think about another procedure they may need when they are 65 or 70 if they undergo TAVR now rather than SAVR. They don’t want open-heart surgery; I hear that all the time,” Dr. Cleveland said. “If I were a 55-year-old aortic valve patient I’d strongly consider TAVR, too.”
Financial consideration at the site performing the interventions can also be a factor. “Differential costs and payments associated with SAVR and TAVR create different financial incentives for health systems between these two procedures,” noted Dr. Vemulapalli. “There likely needs to be a system that creates equal incentives to do SAVR or TAVR so that the decision between them can come down to just the patient and heart-valve team. We need further data and decision aids to help better define which patients will likely do better with SAVR and which with TAVR.”
What now?
Since the first large TAVR trials started in 2007, their main thrust has been to prove the efficacy and safety of TAVR in patients at sequentially less risk of undergoing SAVR. Now that this series of comparisons has ended, where will TAVR research turn its attention?
In addition to the big outstanding issues of TAVR-valve long-term durability, and the efficacy and safety of TAVR for replacing bicuspid valves, other big questions and issues loom. They include the optimal anticoagulant regimen for preventing leaflet thrombosis, reducing the need for pacemakers, reducing strokes, the applicability of TAVR to patients with less severe aortic stenosis, the impact of treating severe but asymptomatic aortic valve obstruction, optimizing valve-in-valve outcomes, and further improvements to valve design, hemodynamics, and delivery. In short, the question of TAVR’s suitability for patients regardless of their surgical risk may have now been answered, but many questions remain about the best way to use and to optimize this technology.
Dr. Cleveland and Dr. Carroll have participated in TAVR trials but had no personal financial disclosures. Dr. Otto had no disclosures. Dr. Vemulapalli has received personal fees from Janssen, Novella, Premiere, and Zafgen, and research funding from Boston Scientific and Abbott Vascular. Dr. Lindman has been a consultant to Medtronic, has served as an advisor to Roche, and has received research funding from Edwards Lifesciences.
With the Food and Drug Administration’s approval of two different pairs of transcatheter aortic valve replacement systems for patients at low surgical risk, U.S. case volume for the procedure should markedly rise given that patients at low surgical risk form the largest risk subgroup among patients with aortic stenosis severe enough to warrant valve replacement.
But even as transcatheter aortic valve replacement (TAVR) now becomes the predominant approach for fixing severely stenotic aortic valves regardless of a patient’s risk level, the procedure remains less optimal than surgical aortic valve replacement (SAVR) in selected patients, putting an onus on clinicians to identify and alert patients for whom the transcatheter approach is questionable.
The anticipated surge in TAVR cases for low-risk patients after the FDA’s Aug. 16, 2019, decision will also likely lead to more hospitals offering TAVR. That development will test whether recently enacted rules from the Centers for Medicare & Medicaid Services on procedure-volume minimums for TAVR programs – at least 20 cases a year (or 40 within 2 years) at centers that also perform at least 300 percutaneous coronary interventions annually – lead to outcomes at lower-volume centers that come reasonably close to the outcomes at higher-volume programs for low-risk patients.
“The paradigm has definitely shifted from SAVR as the gold standard to TAVR as the primary treatment for aortic stenosis. This opens TAVR to the vast majority of patients with aortic stenosis,” roughly three-quarters of patients with aortic valve stenosis severe enough to need valve replacement, said Joseph C. Cleveland Jr., MD, a cardiothoracic surgeon and professor of surgery at the University of Colorado at Denver, Aurora.
The actual, immediate increase in TAVR patients may not be quite as large as this fraction suggests. That’s in part because many patients in the low-risk category based on their surgical risk score already have been judged to have higher-risk features by heart-valve teams that has allowed such patients to undergo TAVR, said John D. Carroll, MD, professor of medicine and director of interventional cardiology at the University of Colorado.
For several years, U.S. rates of TAVR have exceeded SAVR, he noted, and in 2018 U.S. programs performed roughly 58,000 TAVR procedures and about 25,000 SAVRs, according to data collected by the Transcatheter Valve Therapy (TVT) Registry run by the Society of Thoracic Surgeons and the American College of Cardiology. Dr. Carroll is vice chair of the steering committee for this registry, which was mandated by the FDA in 2011 when the agency first allowed TAVR onto the U.S. market and is designed to capture every TAVR case performed in routine U.S. practice.
Despite this caveat, “there will be substantial growth in TAVR. Going forward, there will be more of a shift from SAVR to TAVR. That is what the results of the low-risk trials did,” Dr. Carroll predicted. In addition, the coming growth in TAVR numbers will stem from more than just low-risk patients whom a month ago would have undergone SAVR but now undergo TAVR instead. The availability of TAVR as an option for a wider range of patients should help boost public awareness that a nonsurgical way exists to treat severe aortic stenosis, plus the aging of baby boomers is on the verge of generating a substantial wave of new patients, a wave so high that Dr. Carroll called it a looming “tsunami” of patients needing TAVR.
How will low-risk TAVR affect lower-volume sites?
More TAVR patients will inevitably mean more U.S. sites offering the procedure, experts agreed. “We anticipate more low-volume programs,” Dr. Carroll said.
“Approval of TAVR for low-risk patients will result in a significant increase in the number of programs offering it. Approximately 1,100 U.S. programs offer SAVR, and as of now about 600 of these programs also offer TAVR. Health systems face the risk of losing patients if they don’t offer TAVR now that low-risk patients can be treated,” observed Sreekanth Vemulapalli, MD, a cardiologist at Duke University, Durham, N.C. who has run several studies using TVT Registry data and serves as liaison between the registry and its analytic center at Duke.
One of these studies, published earlier in 2019, showed that, among more than 96,000 registry patients who underwent transfemoral TAVR during 2015-2017 at 554 U.S. centers, those treated at sites that fell into the bottom quartile for case volume had an adjusted 30-day mortality rate that was 21% higher relative to patients treated at centers in the top quartile, a statistically significant difference (N Engl J Med. 2019 Jun 27;380[26]:2541-50). The absolute difference in adjusted 30-day mortality between the lowest and highest quartiles was 0.54%, roughly 1 additional death for every 200 patients. The TAVR centers in the lowest-volume quartile performed 5-36 cases/year, averaging 27 TAVRs/year; those in the highest quartile performed 86-371 TAVRs annually with an overall quartile average of 143 procedures/year.
Dr. Vemulapalli and others cautioned that TAVR case volume is currently serving as a surrogate, and imperfect, marker for program quality until TAVR programs generate enough data to allow a directly measured, risk-adjusted, outcome-driven assessment of performance. In the study he and his associates published in June, the 140 TAVR programs in the lowest-volume quartile showed a “high” level of variability in their adjusted mortality rates. Despite this limitation, the prospect that new TAVR programs will soon open to meet growing TAVR demand from low-risk patients poses the question of how these programs will perform during their start-up days (and possibly beyond), when case volumes may be light, especially if sites open in more remote sections of the United States.
“Will the real-world results of TAVR in low-risk patients match the fantastic results in the two low-risk TAVR trials?” wondered Dr. Carroll, referring to the PARTNER 3 (N Engl J Med. 2019 May 2;380[18]:1695-1705) and Evolut Low-Risk Patients trial (N Engl J Med. 2019 May 2;380[18]:1706-15). “It’s unknown whether a site just starting to do TAVRs will get the same results. The sites that participated in the low-risk trials were mostly high-volume sites.” On the other hand, TVT Registry data have shown that patients with surgical risk that was judged prohibitive, high, or intermediate all have had overall real-world outcomes that match what was seen in the relevant TAVR trials.
In addition, some experts view a modest drop in 30-day survival among patients treated at lower-volume TAVR sites as a reasonable trade-off for easier access for patients seeking this life-changing treatment.
“We need to ensure that patients have access to this treatment option,” said Catherine M. Otto, MD, professor of medicine and director of the Heart Valve Clinic at the University of Washington, Seattle. The potentially better outcomes produced at larger TAVR programs “need to be balanced against having a greater number of programs to ensure access for more patients and allow patients to be treated closer to home,” she said in an interview. She suggested that the potential exists to use telemedicine to link larger and more experienced TAVR programs with smaller and newer programs to help boost their performance.
“There is no perfect solution or metric to ensure high quality while also allowing for adequate access. As indications for TAVR expand we need to maintain vigilance and accountability as the therapy is dispersed to more patients at more centers,” said Brian R. Lindman, MD, medical director of the Structural Heat and Valve Center at Vanderbilt University, Nashville, Tenn. “We also need to insure that certain groups of patients have adequate access to this therapy. Adequate access to TAVR and high-quality clinical outcomes are both important goals.”
Plus, “the volume relationship may be less important,” in lower-risk patients, suggested Dr. Cleveland in an interview. Low-risk patients are younger and have fewer comorbidities and less vascular disease. “Low-volume centers should be able to treat these patients,” he said. Despite that, he personally supported the higher volume minimum for TAVR of 50 cases/year that the ACC, STS, and other U.S. professional societies recommended to CMS during public comment on the proposed rules. “We’ll see whether the increased access is worth this volume minimum.”
Who still gets SAVR?
Given the inherent attraction TAVR holds over SAVR for patients, heart-valve teams will need to convey the right message to patients who may be better served with surgical replacement despite the added trauma and recovery time it produces.
“The decision to perform TAVR or SAVR should now be based on a patient’s expected longevity as well as patient preferences and values, and not on the patient’s estimated surgical risk, except for the highest-risk patients in whom TAVR is recommended,” said Dr. Otto. A patient’s age, comorbidities, and overall life expectancy now move to center stage when deciding the TAVR or SAVR question, along with individual anatomic considerations, the possible need for concurrent procedures, and of course what the patient prefers including their willingness and ability to remain on lifelong anticoagulation if they receive a durable mechanical valve. Dr. Otto outlined this new landscape of the heart-valve team’s decision making process in an editorial she recently published (N Engl J Med. 2019 May 2;380[18]: 1769-70) that accompanied publication of PARTNER 3 and the Evolut Low-Risk Patients trial.
“For some patients there will be clear benefit from one approach, but for many patients, particularly those at low surgical risk, both TAVR and SAVR are technically feasible. For these patients it’s essential that the heart-valve team provide unbiased information to guide patients,” Dr. Otto said. The ideal person to provide this unbiased presentation of the pros and cons would be a cardiologist experienced with valve disease but not actively involved in performing valve-replacement procedures.
A big issue younger patients must confront is what remains unknown about long-term durability of TAVR valves. Dr. Otto called this “the most important missing piece of information. We only have robust data out to about 5 years. If TAVR valve will be durable for 15-20 years, then TAVR will become preferred even in younger patients.”
Even after TAVR became available to intermediate-risk patients in 2016, the median age of U.S. patients undergoing TAVR hardly budged, and has recently stood at about 81 years, Dr. Carroll noted. “With low-risk patients, we expect to see this change,” as more patients now who are in their 70s, 60s, and younger start to routinely undergo TAVR. As more younger patients with life expectancies on the order of 30 years consider TAVR, issues of valve durability “enter the discussion,” he said. “We need data to 10, 15 years,” and in its low-risk approval the FDA mandated manufacturers to follow these patients for at least 10 years. Although valve-in-valve replacement of failed TAVR valves is an option, it’s not always a smooth fix with the potential for prosthesis-patient mismatch (J Am Coll Cardiol. 2018 Dec 4;72[22]:2701-11) and resulting hemodynamic problems, Dr. Carroll said.
Bicuspid-valve replacement with TAVR is another big unknown, largely because these patients were excluded from the TAVR trials. A recently published analysis of the 2,726 patients with a bicuspid aortic valve who underwent TAVR anyway in routine U.S. practice between June 2015 and November 2018 and were in the TVT Registry (about 3% of all TAVR patients during this period) showed that these patients had similar mortality, compared with the tricuspid-valve patients, but a significantly increased stroke rate (JAMA. 2019 Jun 11;321[22]:2193-202). The authors concluded that a prospective, randomized study of TAVR, compared with SAVR, is needed for these patients, and many others in the field agree.
As availability of TAVR grows and public awareness increases, heart-valve teams may find it challenging sometimes to help patients understand the upsides of SAVR for their individual clinical needs when TAVR is superficially so much more attractive.
“The desire to avoid the prolonged hospitalization and recovery from SAVR is a huge driver of patient preference,” noted Dr. Carroll.
“It’s hard to tell a 55 year old to think about another procedure they may need when they are 65 or 70 if they undergo TAVR now rather than SAVR. They don’t want open-heart surgery; I hear that all the time,” Dr. Cleveland said. “If I were a 55-year-old aortic valve patient I’d strongly consider TAVR, too.”
Financial consideration at the site performing the interventions can also be a factor. “Differential costs and payments associated with SAVR and TAVR create different financial incentives for health systems between these two procedures,” noted Dr. Vemulapalli. “There likely needs to be a system that creates equal incentives to do SAVR or TAVR so that the decision between them can come down to just the patient and heart-valve team. We need further data and decision aids to help better define which patients will likely do better with SAVR and which with TAVR.”
What now?
Since the first large TAVR trials started in 2007, their main thrust has been to prove the efficacy and safety of TAVR in patients at sequentially less risk of undergoing SAVR. Now that this series of comparisons has ended, where will TAVR research turn its attention?
In addition to the big outstanding issues of TAVR-valve long-term durability, and the efficacy and safety of TAVR for replacing bicuspid valves, other big questions and issues loom. They include the optimal anticoagulant regimen for preventing leaflet thrombosis, reducing the need for pacemakers, reducing strokes, the applicability of TAVR to patients with less severe aortic stenosis, the impact of treating severe but asymptomatic aortic valve obstruction, optimizing valve-in-valve outcomes, and further improvements to valve design, hemodynamics, and delivery. In short, the question of TAVR’s suitability for patients regardless of their surgical risk may have now been answered, but many questions remain about the best way to use and to optimize this technology.
Dr. Cleveland and Dr. Carroll have participated in TAVR trials but had no personal financial disclosures. Dr. Otto had no disclosures. Dr. Vemulapalli has received personal fees from Janssen, Novella, Premiere, and Zafgen, and research funding from Boston Scientific and Abbott Vascular. Dr. Lindman has been a consultant to Medtronic, has served as an advisor to Roche, and has received research funding from Edwards Lifesciences.