TAVR Showed Increased Neurologic Events

PHILADELPHIA - The percutaneous, transcatheter replacement of stenotic aortic valves has captured attention as an option for patients who are either too sick to undergo aortic valve replacement by conventional open surgery, or who are surgical candidates but would prefer to avoid sternotomy.

Despite early success with the use of transcatheter aortic valve repair (TAVR) in the two parts of a recent pivotal trial, Dr. D. Craig Miller said the approach has two important limitations: the poorly defined long-term durability of aortic valves placed percutaneously (which thus far have track records of less than 3 years) and the significantly increased risk of a neurologic event from TAVR, compared with conventional open aortic valve repair (AVR).

Courtesy of Catherine Harrell/Elsevier.

A summary analysis of neurologic events following TAVR in the Placement of Aortic Transcatheter Valve (PARTNER) trial showed a total, 1-year event rate of 6% in the as-treated TAVR patients who received their valves via the transfemoral route, compared with a 2% rate in the open AVR patients, a statistically significant difference, Dr. Miller said at the annual meeting of the American Association for Thoracic Surgery.

As-treated patients who received a TAVR via the transapical route had a 1-year neurologic event rate of 14%, compared with a 10% rate in patients treated with open AVR, also a statistically significant difference. The substantially higher rate of events in patients assigned to the transapical arm of the study related to the higher atherosclerotic burden in these patients, both those who underwent TAVR and those who had open AVR.

More than half of the neurologic event risk seen with TAVR occurred during the first 2 weeks after treatment, suggesting a periprocedural cause, said Dr. Miller, FACS, professor of cardiovascular surgery at Stanford (Calif.) University.

"The early neurologic events are undoubtedly due to particulate embolization, although we can't prove it," he said. "A cerebral protection device, such as a deflector across the ostium, may reduce the event rate." He cited a report on initial clinical experience using a percutaneously deployed deflector in three patients undergoing TAVR (J. Am. Coll. Cardiol. Intv. 2010;3:1133-8). Other changes to TAVR that might reduce neurologic event rates include improved antiplatelet and antithrombotic therapy with clopidogrel, aspirin, warfarin, and dabigatran. Development of smaller TAVR devices might also further reduce neurologic events, he said.

Analysis of the correlates of the early neurologic events showed that they significantly linked with a lower aortic valve area index. In other words, patients with smaller, tighter aortic valves were more likely to experience an early event.

During the late, nonperiprocedural phase, the risk for neurologic events was increased for patients with a higher NYHA heart failure stage, those who had had a stroke or transient ischemic attack within the prior 12 months, or those who were not candidates for TAVR via the transfemoral route.

Patients enrolled in the randomized portion of the trial had a low rate of major strokes, with a total of 29 events (18 in the TAVR patients and 11 in those undergoing open AVR), a difference that was not statistically significant. The analysis therefore also included minor strokes and transient ischemic attacks to total an adequate number of events to potentially show a statistical significant difference between the TAVR and open AVR subgroups, Dr. Miller said.

The data Dr. Miller reported came from cohort A of the PARTNER trial, the cohort that focused on patients who could be randomized to either TAVR or open AVR. The primary end point of all-cause mortality in this cohort, reported in April at the American College of Cardiology Scientific Sessions, showed that 1-year survival following TAVR was not inferior to open AVR. A prior report, for cohort B (patients considered too sick to undergo open AVR), had shown that TAVR produced superior outcomes, compared with conven- tional medical management ( N. Engl. J. Med. 2010; 363:1597-607).

The considerable interest in transcatheter aortic valve replacement among patients and physicians alike suggests that it may fall on payers to set limits on which patients undergo this procedure, and on heart-valve teams to ensure that procedures are done appropriately and safely.

"How might we prevent a runaway train [of transcatheter aortic valve replacement], as seen now in Germany, where 20%-25% of all aortic valve replacements are done percutaneously? This will be up to payers," Dr. D. Craig Miller said as he presented new data on the neurologic adverse events in the Placement of Aortic Transcatheter Valves (PARTNER) trial. "I'm personally disappointed with what's happened in Europe. There are no restrictions [on the use of transcatheter aortic valve replacement], and the results are not as good as in PARTNER.

"It behooves us to work with a functional heart-valve team to make sure these complementary techniques [transcatheter aortic valve replacement and open valve replacement] are used appropriately. I don't think that open aortic valve replacement is an endangered species."

Deciding which patients should undergo transcatheter aortic valve replacement (TAVR) will require "defining the line between utility and futility," he said. "You don't want to empty every nursing home in California of patients with aortic stenosis, and on the young side, you don't want the percutaneous option used in patients at low surgical risk." Concern about using TAVR on patients who are good open surgery candidates focuses on the unknown long-term durability of TAVR, and the "high price to pay in neurologic events, at least in the current version of TAVR," he said.

"Patients will always flock to the least invasive approach. That's where the heart-valve team will be very important. This will only work well if surgeons and cardiologists work together to decide whether something should be done about aortic stenosis in a patient and, if so, which treatment is best. TAVR and open replacement are complementary, not competitive.

"You can't let this technology go everywhere," Dr. Miller warned. TAVR is "tricky, and the learning curve is steep and unforgiving. We [at Stanford] still insist on having two surgeons and two interventionalists on every case, because when a case goes south it goes in a hurry. We have done 100 cases, and problems still come up and are, to some extent, unpredictable."

The PARTNER trial was sponsored by Edwards Lifesciences. Dr. Miller said that he has been the Stanford Principal Investigator for PARTNER and has served as an unpaid consultant to Edwards. He has also been a consultant to Abbott Vascular, Medtronic Cardiovascular, and St. Jude Medical.

PHILADELPHIA - The percutaneous, transcatheter replacement of stenotic aortic valves has captured attention as an option for patients who are either too sick to undergo aortic valve replacement by conventional open surgery, or who are surgical candidates but would prefer to avoid sternotomy.

Despite early success with the use of transcatheter aortic valve repair (TAVR) in the two parts of a recent pivotal trial, Dr. D. Craig Miller said the approach has two important limitations: the poorly defined long-term durability of aortic valves placed percutaneously (which thus far have track records of less than 3 years) and the significantly increased risk of a neurologic event from TAVR, compared with conventional open aortic valve repair (AVR).

Courtesy of Catherine Harrell/Elsevier.

A summary analysis of neurologic events following TAVR in the Placement of Aortic Transcatheter Valve (PARTNER) trial showed a total, 1-year event rate of 6% in the as-treated TAVR patients who received their valves via the transfemoral route, compared with a 2% rate in the open AVR patients, a statistically significant difference, Dr. Miller said at the annual meeting of the American Association for Thoracic Surgery.

As-treated patients who received a TAVR via the transapical route had a 1-year neurologic event rate of 14%, compared with a 10% rate in patients treated with open AVR, also a statistically significant difference. The substantially higher rate of events in patients assigned to the transapical arm of the study related to the higher atherosclerotic burden in these patients, both those who underwent TAVR and those who had open AVR.

More than half of the neurologic event risk seen with TAVR occurred during the first 2 weeks after treatment, suggesting a periprocedural cause, said Dr. Miller, FACS, professor of cardiovascular surgery at Stanford (Calif.) University.

"The early neurologic events are undoubtedly due to particulate embolization, although we can't prove it," he said. "A cerebral protection device, such as a deflector across the ostium, may reduce the event rate." He cited a report on initial clinical experience using a percutaneously deployed deflector in three patients undergoing TAVR (J. Am. Coll. Cardiol. Intv. 2010;3:1133-8). Other changes to TAVR that might reduce neurologic event rates include improved antiplatelet and antithrombotic therapy with clopidogrel, aspirin, warfarin, and dabigatran. Development of smaller TAVR devices might also further reduce neurologic events, he said.

Analysis of the correlates of the early neurologic events showed that they significantly linked with a lower aortic valve area index. In other words, patients with smaller, tighter aortic valves were more likely to experience an early event.

During the late, nonperiprocedural phase, the risk for neurologic events was increased for patients with a higher NYHA heart failure stage, those who had had a stroke or transient ischemic attack within the prior 12 months, or those who were not candidates for TAVR via the transfemoral route.

Patients enrolled in the randomized portion of the trial had a low rate of major strokes, with a total of 29 events (18 in the TAVR patients and 11 in those undergoing open AVR), a difference that was not statistically significant. The analysis therefore also included minor strokes and transient ischemic attacks to total an adequate number of events to potentially show a statistical significant difference between the TAVR and open AVR subgroups, Dr. Miller said.

The data Dr. Miller reported came from cohort A of the PARTNER trial, the cohort that focused on patients who could be randomized to either TAVR or open AVR. The primary end point of all-cause mortality in this cohort, reported in April at the American College of Cardiology Scientific Sessions, showed that 1-year survival following TAVR was not inferior to open AVR. A prior report, for cohort B (patients considered too sick to undergo open AVR), had shown that TAVR produced superior outcomes, compared with conven- tional medical management ( N. Engl. J. Med. 2010; 363:1597-607).

The considerable interest in transcatheter aortic valve replacement among patients and physicians alike suggests that it may fall on payers to set limits on which patients undergo this procedure, and on heart-valve teams to ensure that procedures are done appropriately and safely.

"How might we prevent a runaway train [of transcatheter aortic valve replacement], as seen now in Germany, where 20%-25% of all aortic valve replacements are done percutaneously? This will be up to payers," Dr. D. Craig Miller said as he presented new data on the neurologic adverse events in the Placement of Aortic Transcatheter Valves (PARTNER) trial. "I'm personally disappointed with what's happened in Europe. There are no restrictions [on the use of transcatheter aortic valve replacement], and the results are not as good as in PARTNER.

"It behooves us to work with a functional heart-valve team to make sure these complementary techniques [transcatheter aortic valve replacement and open valve replacement] are used appropriately. I don't think that open aortic valve replacement is an endangered species."

Deciding which patients should undergo transcatheter aortic valve replacement (TAVR) will require "defining the line between utility and futility," he said. "You don't want to empty every nursing home in California of patients with aortic stenosis, and on the young side, you don't want the percutaneous option used in patients at low surgical risk." Concern about using TAVR on patients who are good open surgery candidates focuses on the unknown long-term durability of TAVR, and the "high price to pay in neurologic events, at least in the current version of TAVR," he said.

"Patients will always flock to the least invasive approach. That's where the heart-valve team will be very important. This will only work well if surgeons and cardiologists work together to decide whether something should be done about aortic stenosis in a patient and, if so, which treatment is best. TAVR and open replacement are complementary, not competitive.

"You can't let this technology go everywhere," Dr. Miller warned. TAVR is "tricky, and the learning curve is steep and unforgiving. We [at Stanford] still insist on having two surgeons and two interventionalists on every case, because when a case goes south it goes in a hurry. We have done 100 cases, and problems still come up and are, to some extent, unpredictable."

The PARTNER trial was sponsored by Edwards Lifesciences. Dr. Miller said that he has been the Stanford Principal Investigator for PARTNER and has served as an unpaid consultant to Edwards. He has also been a consultant to Abbott Vascular, Medtronic Cardiovascular, and St. Jude Medical.

PHILADELPHIA - The percutaneous, transcatheter replacement of stenotic aortic valves has captured attention as an option for patients who are either too sick to undergo aortic valve replacement by conventional open surgery, or who are surgical candidates but would prefer to avoid sternotomy.

Despite early success with the use of transcatheter aortic valve repair (TAVR) in the two parts of a recent pivotal trial, Dr. D. Craig Miller said the approach has two important limitations: the poorly defined long-term durability of aortic valves placed percutaneously (which thus far have track records of less than 3 years) and the significantly increased risk of a neurologic event from TAVR, compared with conventional open aortic valve repair (AVR).

Courtesy of Catherine Harrell/Elsevier.

A summary analysis of neurologic events following TAVR in the Placement of Aortic Transcatheter Valve (PARTNER) trial showed a total, 1-year event rate of 6% in the as-treated TAVR patients who received their valves via the transfemoral route, compared with a 2% rate in the open AVR patients, a statistically significant difference, Dr. Miller said at the annual meeting of the American Association for Thoracic Surgery.

As-treated patients who received a TAVR via the transapical route had a 1-year neurologic event rate of 14%, compared with a 10% rate in patients treated with open AVR, also a statistically significant difference. The substantially higher rate of events in patients assigned to the transapical arm of the study related to the higher atherosclerotic burden in these patients, both those who underwent TAVR and those who had open AVR.

More than half of the neurologic event risk seen with TAVR occurred during the first 2 weeks after treatment, suggesting a periprocedural cause, said Dr. Miller, FACS, professor of cardiovascular surgery at Stanford (Calif.) University.

"The early neurologic events are undoubtedly due to particulate embolization, although we can't prove it," he said. "A cerebral protection device, such as a deflector across the ostium, may reduce the event rate." He cited a report on initial clinical experience using a percutaneously deployed deflector in three patients undergoing TAVR (J. Am. Coll. Cardiol. Intv. 2010;3:1133-8). Other changes to TAVR that might reduce neurologic event rates include improved antiplatelet and antithrombotic therapy with clopidogrel, aspirin, warfarin, and dabigatran. Development of smaller TAVR devices might also further reduce neurologic events, he said.

Analysis of the correlates of the early neurologic events showed that they significantly linked with a lower aortic valve area index. In other words, patients with smaller, tighter aortic valves were more likely to experience an early event.

During the late, nonperiprocedural phase, the risk for neurologic events was increased for patients with a higher NYHA heart failure stage, those who had had a stroke or transient ischemic attack within the prior 12 months, or those who were not candidates for TAVR via the transfemoral route.

Patients enrolled in the randomized portion of the trial had a low rate of major strokes, with a total of 29 events (18 in the TAVR patients and 11 in those undergoing open AVR), a difference that was not statistically significant. The analysis therefore also included minor strokes and transient ischemic attacks to total an adequate number of events to potentially show a statistical significant difference between the TAVR and open AVR subgroups, Dr. Miller said.

The data Dr. Miller reported came from cohort A of the PARTNER trial, the cohort that focused on patients who could be randomized to either TAVR or open AVR. The primary end point of all-cause mortality in this cohort, reported in April at the American College of Cardiology Scientific Sessions, showed that 1-year survival following TAVR was not inferior to open AVR. A prior report, for cohort B (patients considered too sick to undergo open AVR), had shown that TAVR produced superior outcomes, compared with conven- tional medical management ( N. Engl. J. Med. 2010; 363:1597-607).

The considerable interest in transcatheter aortic valve replacement among patients and physicians alike suggests that it may fall on payers to set limits on which patients undergo this procedure, and on heart-valve teams to ensure that procedures are done appropriately and safely.

"How might we prevent a runaway train [of transcatheter aortic valve replacement], as seen now in Germany, where 20%-25% of all aortic valve replacements are done percutaneously? This will be up to payers," Dr. D. Craig Miller said as he presented new data on the neurologic adverse events in the Placement of Aortic Transcatheter Valves (PARTNER) trial. "I'm personally disappointed with what's happened in Europe. There are no restrictions [on the use of transcatheter aortic valve replacement], and the results are not as good as in PARTNER.

"It behooves us to work with a functional heart-valve team to make sure these complementary techniques [transcatheter aortic valve replacement and open valve replacement] are used appropriately. I don't think that open aortic valve replacement is an endangered species."

Deciding which patients should undergo transcatheter aortic valve replacement (TAVR) will require "defining the line between utility and futility," he said. "You don't want to empty every nursing home in California of patients with aortic stenosis, and on the young side, you don't want the percutaneous option used in patients at low surgical risk." Concern about using TAVR on patients who are good open surgery candidates focuses on the unknown long-term durability of TAVR, and the "high price to pay in neurologic events, at least in the current version of TAVR," he said.

"Patients will always flock to the least invasive approach. That's where the heart-valve team will be very important. This will only work well if surgeons and cardiologists work together to decide whether something should be done about aortic stenosis in a patient and, if so, which treatment is best. TAVR and open replacement are complementary, not competitive.

"You can't let this technology go everywhere," Dr. Miller warned. TAVR is "tricky, and the learning curve is steep and unforgiving. We [at Stanford] still insist on having two surgeons and two interventionalists on every case, because when a case goes south it goes in a hurry. We have done 100 cases, and problems still come up and are, to some extent, unpredictable."

The PARTNER trial was sponsored by Edwards Lifesciences. Dr. Miller said that he has been the Stanford Principal Investigator for PARTNER and has served as an unpaid consultant to Edwards. He has also been a consultant to Abbott Vascular, Medtronic Cardiovascular, and St. Jude Medical.