TAVR Usable in Older, High-Risk Patients

NEW ORLEANS Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was found in conventional surgery for older, high-risk patients who suffered from severe, symptomatic aortic stenosis, according to the results of the PARTNER trial.

All-cause mortality at 30 days favored the use of transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% vs, 27%, respectively). 

The difference at 1 year reached the trial's prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can't tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

However, The stroke rate with TAVR as seen in the in­dustry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, turned out to be twice the rate for these patients as that observed with conventional surgical repair.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). 

When only major strokes were compared, the difference was not significant between TAVR and convential surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York Presby­terian Hospital/Columbia Uni­versity Medical Center in New York City. 

Notably, patients who un?derwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

An examination of echocardiographic findings indicated a small hemodynamic benefit ocurred with TAVR vs. surgery at 1 year, but there was significantly increased paravalvular aortic re­gurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing histo­ry in the making.

"This will prob­ably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lex­ington. 

"If we look back to balloon angio­plasty, the advent of stents and drug-eluting stents, this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was as­sociated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR. These pa­tients were treated using the transfemoral approach in 492 cases and the transapical approach in 207. 

Severe stenosis was defined as an aortic valve area of less than 0.8 cm2 and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. 

The patients in the trial had a New York Heart Association heart failure class II or greater, and they also had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery (STS) score of at least 10.

The mean age of the patients in the study was 83 years, and 94% of them were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was sim­ilar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis sug­gested that there may be a possible benefit found with TAVR in women and in patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be inter­preted cautiously.

Overall, the TAVR mortality of 3.4% at 30 days was the lowest reported in any series, despite the use of an early-gener­ation device and limited previous oper­ator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, Dr. Moliterno said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascu?lar medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, sur­geons, and imaging experts, who con­sulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is ap­proved, I don't think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure. 

Dr. Michael Crawford, chief of clini­cal cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an “amazing effort, particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas Hospital, London. 

The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diam­eter of 7-8 mm. 

The size of catheters has been decreased down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.'s Sapien valve that was used in PARTNER and the Medtronic Inc.'s CoreValve are already approved for commercial use. 

Recruitment began in February for the PARTNER II trial that is evaluating the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary com­pletion in December 2011.

When asked whether the advent of newer, thinner devices will mean adop­tion in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk cate­gories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was found in conventional surgery for older, high-risk patients who suffered from severe, symptomatic aortic stenosis, according to the results of the PARTNER trial.

All-cause mortality at 30 days favored the use of transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% vs, 27%, respectively). 

The difference at 1 year reached the trial's prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can't tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

However, The stroke rate with TAVR as seen in the in­dustry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, turned out to be twice the rate for these patients as that observed with conventional surgical repair.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). 

When only major strokes were compared, the difference was not significant between TAVR and convential surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York Presby­terian Hospital/Columbia Uni­versity Medical Center in New York City. 

Notably, patients who un?derwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

An examination of echocardiographic findings indicated a small hemodynamic benefit ocurred with TAVR vs. surgery at 1 year, but there was significantly increased paravalvular aortic re­gurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing histo­ry in the making.

"This will prob­ably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lex­ington. 

"If we look back to balloon angio­plasty, the advent of stents and drug-eluting stents, this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was as­sociated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR. These pa­tients were treated using the transfemoral approach in 492 cases and the transapical approach in 207. 

Severe stenosis was defined as an aortic valve area of less than 0.8 cm2 and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. 

The patients in the trial had a New York Heart Association heart failure class II or greater, and they also had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery (STS) score of at least 10.

The mean age of the patients in the study was 83 years, and 94% of them were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was sim­ilar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis sug­gested that there may be a possible benefit found with TAVR in women and in patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be inter­preted cautiously.

Overall, the TAVR mortality of 3.4% at 30 days was the lowest reported in any series, despite the use of an early-gener­ation device and limited previous oper­ator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, Dr. Moliterno said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascu?lar medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, sur­geons, and imaging experts, who con­sulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is ap­proved, I don't think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure. 

Dr. Michael Crawford, chief of clini­cal cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an “amazing effort, particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas Hospital, London. 

The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diam­eter of 7-8 mm. 

The size of catheters has been decreased down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.'s Sapien valve that was used in PARTNER and the Medtronic Inc.'s CoreValve are already approved for commercial use. 

Recruitment began in February for the PARTNER II trial that is evaluating the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary com­pletion in December 2011.

When asked whether the advent of newer, thinner devices will mean adop­tion in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk cate­gories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.

NEW ORLEANS Transcatheter aortic valve replacement was associated with the same survival rates at 1 year as was found in conventional surgery for older, high-risk patients who suffered from severe, symptomatic aortic stenosis, according to the results of the PARTNER trial.

All-cause mortality at 30 days favored the use of transcatheter aortic valve replacement (TAVR) at 3.4%, compared with 6.5% for open surgery, and was similar at 1 year (24% vs, 27%, respectively). 

The difference at 1 year reached the trial's prespecified noninferiority margin with a P value of .001.

"We already learned from the previous cohort that TAVR is the standard of care for patients who can't tolerate surgery. So this [finding] opens up a new set of patients who may very well benefit as much with TAVR as with the gold standard surgery," coprincipal investigator Dr. Craig B. Smith said at the annual meeting of the American College of Cardiology.

However, The stroke rate with TAVR as seen in the in­dustry-sponsored PARTNER (Placement of Aortic Transcatheter Valve) trial, turned out to be twice the rate for these patients as that observed with conventional surgical repair.

Stroke plus transient ischemic attack (TIA) rates were significantly more frequent with TAVR than surgery at both 30 days (5.5% vs. 2.4%) and 1 year (8.3% vs. 4.3%). 

When only major strokes were compared, the difference was not significant between TAVR and convential surgery at 30 days (3.8% vs. 2.1%) or 1 year (5.1% vs. 2.4%), said Dr. Smith, chief of cardiothoracic surgery at New York Presby­terian Hospital/Columbia Uni­versity Medical Center in New York City. 

Notably, patients who un?derwent conventional surgery were significantly more likely than TAVR patients to experience major bleeding at 30 days (19.5% vs. 9.3%) and 1 year (26% vs. 15%), as well as new atrial fibrillation at both 30 days (16% vs. 8.6%) and 1 year (17% vs. 12%).

An examination of echocardiographic findings indicated a small hemodynamic benefit ocurred with TAVR vs. surgery at 1 year, but there was significantly increased paravalvular aortic re­gurgitation at 30 days, 6 months, and 1 year.

"TAVR and AVR [aortic valve replacement] are both acceptable therapies in these high-risk patients; differing periprocedural hazards should influence case-based decision making," Dr. Smith said.

Dr. David Moliterno, chair of the intervention program (i2 Summit) at the meeting, told reporters that they were witnessing histo­ry in the making.

"This will prob­ably be seen as one of the biggest steps in cardiovascular medicine, as far as intervention is concerned, potentially in our lifetime," said Dr. Moliterno, chief of cardiovascular medicine at the University of Kentucky, Lex­ington. 

"If we look back to balloon angio­plasty, the advent of stents and drug-eluting stents, this will be seen as the next major turning point."

Last year, the PARTNER trial investigators reported a 20% survival benefit at 1 year in a separate cohort of 358 inoperable patients with severe aortic stenosis who underwent transfemoral TAVR vs. standard therapy, including balloon aortic valvuloplasty (N. Engl. J. Med. 2010;363:1597-607). TAVR was as­sociated with significantly more major vascular complications (16% vs. 1%) and a higher incidence of major strokes (5% vs. 1%).

The current portion of PARTNER randomly assigned 699 patients at 26 centers to surgery or TAVR. These pa­tients were treated using the transfemoral approach in 492 cases and the transapical approach in 207. 

Severe stenosis was defined as an aortic valve area of less than 0.8 cm2 and mean aortic valve gradient of more than 40 mm Hg or a peak aortic jet velocity of more than 4.0 m/second. 

The patients in the trial had a New York Heart Association heart failure class II or greater, and they also had a predicted risk of operative mortality of at least 15% as determined by the site surgeon and cardiologist, coupled with a Society of Thoracic Surgery (STS) score of at least 10.

The mean age of the patients in the study was 83 years, and 94% of them were NYHA class III or IV. In all, 42 patients were not treated as assigned, Dr. Smith said.

All-cause mortality at 1 year was sim­ilar for the transfemoral TAVR subgroup, at 22.2% and 26.4% for surgery, as well as for the transapical TAVR subgroup (29% vs. 28%, respectively).

A preliminary subgroup analysis sug­gested that there may be a possible benefit found with TAVR in women and in patients without prior coronary artery bypass surgery, but Dr. Smith said that those results should be inter­preted cautiously.

Overall, the TAVR mortality of 3.4% at 30 days was the lowest reported in any series, despite the use of an early-gener­ation device and limited previous oper­ator experience, he said, noting that nine of the participating centers had never performed TAVR before the trial.

Symptom improvement, including NYHA class and 6-minute walk distance, favored TAVR at 30 days and was similar to conventional surgery at 1 year, Dr. Moliterno said.

Coinvestigator Dr. Murat Tuzcu, vice chair of the department of cardiovascu?lar medicine at the Cleveland Clinic, stressed that the results were accomplished only through unprecedented teamwork among cardiologists, sur­geons, and imaging experts, who con­sulted on each case in the trial.

"I want to emphasize that if we fail to pay equal attention to what we have done in this trial after the device is ap­proved, I don't think we will be able to replicate the same results," he said.

Several speakers at the press conference noted the balancing act that all clinicians will face regarding public demand for the new procedure. 

Dr. Michael Crawford, chief of clini­cal cardiology at the University of California, San Francisco, observed that centers will face substantial up-front costs in the adoption of TAVR, including hybrid surgical/interventional suites, and that this will restrict initial uptake to high-volume centers of excellence.

The 3.4% mortality rate represents an “amazing effort, particularly in the use of the larger, first-generation device, said invited discussant Dr. Martyn Thomas, clinical director of cardiothoracic services at St. Thomas Hospital, London. 

The delivery catheters used in PARTNER are sized at 22 and 24 French, which corresponds to an outside diam­eter of 7-8 mm. 

The size of catheters has been decreased down to 16-Fr in Europe, where more than 5,000 TAVR procedures have been done and where both the Edwards Lifesciences Corp.'s Sapien valve that was used in PARTNER and the Medtronic Inc.'s CoreValve are already approved for commercial use. 

Recruitment began in February for the PARTNER II trial that is evaluating the smaller Edwards Sapien XT device and the later generation NovaFlex delivery system among inoperable patients with symptomatic severe aortic stenosis. The trial is expected to enroll 600 patients, and is targeted for primary com­pletion in December 2011.

When asked whether the advent of newer, thinner devices will mean adop­tion in patients with lower risk, Dr. Smith replied that the adoption of TAVR will "march steadily down the risk cate­gories."

Edwards Lifesciences sponsored the trial. Dr. Smith and his coauthors reported no conflicts of interest.