AHA Scientific Sessions 2010

CHICAGO – Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

"This was a definitively negative trial," Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.

The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

"I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn’t make therapeutic decisions based on phase II trials," he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis "remains alive," but the focus should shift to stem cell–based therapies, which show great promise.

Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It’s possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn’t changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.

Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO – Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

"This was a definitively negative trial," Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.

The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

"I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn’t make therapeutic decisions based on phase II trials," he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis "remains alive," but the focus should shift to stem cell–based therapies, which show great promise.

Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It’s possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn’t changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.

Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO – Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

"This was a definitively negative trial," Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.

The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

"I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn’t make therapeutic decisions based on phase II trials," he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis "remains alive," but the focus should shift to stem cell–based therapies, which show great promise.

Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It’s possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn’t changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.

Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO – Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

"This was a definitively negative trial," Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.

The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

"I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn’t make therapeutic decisions based on phase II trials," he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis "remains alive," but the focus should shift to stem cell–based therapies, which show great promise.

Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It’s possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn’t changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.

Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO – Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

"This was a definitively negative trial," Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.

The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

"I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn’t make therapeutic decisions based on phase II trials," he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis "remains alive," but the focus should shift to stem cell–based therapies, which show great promise.

Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It’s possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn’t changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.

Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO – Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

"This was a definitively negative trial," Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.

The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

"I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn’t make therapeutic decisions based on phase II trials," he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis "remains alive," but the focus should shift to stem cell–based therapies, which show great promise.

Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It’s possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn’t changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.

Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO – Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

"This was a definitively negative trial," Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.

The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

"I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn’t make therapeutic decisions based on phase II trials," he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis "remains alive," but the focus should shift to stem cell–based therapies, which show great promise.

Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It’s possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn’t changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.

Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO – Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

"This was a definitively negative trial," Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.

The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

"I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn’t make therapeutic decisions based on phase II trials," he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis "remains alive," but the focus should shift to stem cell–based therapies, which show great promise.

Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It’s possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn’t changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.

Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO – Gene therapy proved ineffective in critical limb ischemia patients with ischemic skin lesions unsuitable for revascularization in the largest-ever clinical trial of gene therapy for this application.

Results of the phase III, randomized, double-blind, 525-patient TAMARIS study showed a 37% rate of death or major amputation at 1 year in recipients of the gene controlling for the expression of angiogenic fibroblast growth factor 1, compared with a 33% rate in placebo-treated controls.

"This was a definitively negative trial," Dr. William R. Hiatt declared in presenting the TAMARIS results at the annual scientific sessions of the American Heart Association.

The TAMARIS findings are particularly disappointing in light of the earlier, highly impressive results of the phase II TALISMAN study. In that 125-patient study, the same gene delivery system, known as NV1FGF, resulted in a 56% reduction in the combined end point of death or major amputation at 1 year, said Dr. Hiatt, professor of medicine and cardiology at the University of Colorado, Denver.

The delivered gene, FGF1, codes for heparin-binding growth factor 1, which is a known angiogenic factor.

"I would merely say that this confirms the importance of large, well-conducted, randomized controlled trials. You really shouldn’t make therapeutic decisions based on phase II trials," he said.

Gene therapy recipients received four 4-mg intramuscular injections of NV1FGF over a 6-week period.

Dr. Hiatt said the concept of therapeutic angiogenesis "remains alive," but the focus should shift to stem cell–based therapies, which show great promise.

Indeed, elsewhere at the meeting Dr. Douglas W. Losordo presented the results of a phase II study of autologous CD34+ cells for critical limb ischemia unsuitable for surgical or percutaneous revascularization. In that 28-patient study, cell therapy recipients had a 74% greater amputation-free survival rate at 1 year than did placebo-treated controls.

Dr. Losordo, the designated discussant for the TAMARIS trial, said one possible explanation for the divergent results relative to the earlier phase II TALISMAN study is that TAMARIS was conducted in 30 countries on multiple continents, whereas TALISMAN was carried out in a more genetically homogeneous European population. It’s possible, he theorized, that there are genetic differences in critical limb ischemia and in the response to gene therapy.

New treatments for critical limb ischemia with tissue loss are desperately needed. There are 100,000 amputations per year in the United States for this condition. The amputation rate hasn’t changed in 3 decades, noted Dr. Losordo, professor of medicine and director of the Feinberg Cardiovascular Research Institute at Northwestern University, Chicago.

Dr. Hiatt disclosed that he has received a research grant from Sanofi-Aventis, which funded the TAMARIS trial. The CD34+ cell therapy study was sponsored by Baxter Healthcare. Dr. Losordo declared that he was previously a paid consultant to Baxter.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – Closure-device problems did not explain why endovascular closure of patent foramen ovale in patients with a history of cryptogenic stroke failed to produce better outcomes than those of medically-treated patients. The device performed well, Dr. Anthony J. Furlan said at the annual scientific sessions of the American Heart Association.

The problem was patient selection.

"For the vast majority of patients who have had a cryptogenic stroke and a patent foramen ovale [PFO] medical therapy is a good first-choice," said Dr. Furlan, professor and chairman of neurology at Case Western Reserve University in Cleveland. "The challenge now to the endovascular community is to refine the patient selection criteria and not close these holes so liberally."

Based on the results from A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale (CLOSURE I), the first randomized study to compare anticoagulant therapy and endovascular PFO closure, "we should see a significant drop in the number of PFOs that get closed," Dr. Furlan said.

The CLOSURE I investigators selected patients "who are being closed worldwide," he said. "Many patients who have a cryptogenic stroke also have a hole and nothing else, but people don’t look that hard. Assessments tend to stop when they find a PFO, he said.

The CLOSURE I results "clearly showed that in patients with stroke of unknown cause and PFO there is no need for systematic PFO closure because it is not effective and may be associated with major vascular complications, atrial fibrillation, or bleeding," said Dr. Pierre Amarenco, professor and chairman of the department of neurology and stroke center at Bichat Hospital in Paris. "Cryptogenic stroke likely includes a broad range of underlying etiologies that may have diluted the true, causal effect of PFO. These results should now be translated into practice for the million patients with stroke of unknown cause and PFO. On a case-by-case basis, after careful evaluation by a vascular neurologist, there may be some patients for whom closing the PFO can be deemed useful, but these cases are likely very rare."

CLOSURE I enrolled 18- to 60-year-olds who had a cryptogenic stroke or transient ischemic attack (TIA) within the past 6 months, and a PFO documented by transesophageal echocardiography. Investigators at 87 centers in the United States and Canada randomized 909 patients during June 2003–October 2008 to endovascular closure with the STARFlex device or to medical therapy. Patients in the closure group also received aspirin and clopidogrel for 6 months following their procedure, followed by aspirin alone for an additional 18 months. Patients in the medical-treatment arm received warfarin alone, dosed to a target international normalized ratio of 2.0-3.0 (139 patients), warfarin plus aspirin (80 patients), or aspirin alone (243 patients) throughout their follow-up. The average age of the patients was 46; 52% were men. Nearly three-quarters had an index cryptogenic stroke.

"We believe the study population was representative of patients aged 60 or younger with cryptogenic stroke or TIA and a PFO," Dr. Furlan said.

The study’s primary end points were the individual rates of stroke and TIA and the composite rate after 2 years of follow-up on an intent-to-treat basis. The composite rates were 5.9% among the 447 patients in the closure group and 7.7% among 462 patients in the medical-therapy group, a difference that was not statistically significant. The numeric difference was driven primarily by a difference in the TIA rate, 3.3% in the closure group and 4.6% in the medical therapy group, not significantly different. The stroke rates were nearly identical in the two groups, 3.1% and 3.4%. The composite end point showed no significant difference between the two treatment arms regardless of the shunt severity or whether or not the patients had an atrial septal aneurysm.

Roughly 80% of the strokes that occurred during follow-up in both arms of the study had no relationship to paradoxical embolism, suggesting that in many of these patients the PFO may be coincidental, Dr. Furlan said.

In the control arm, the outcomes did not significantly differ regardless of whether patients received warfarin plus aspirin, warfarin alone, or aspirin alone. Dr. Furlan noted that the study was not powered to find significant differences among these three subgroups.

The overall rate of major adverse events was similar, 17%, in both treatment arms (see table). Patients who underwent PFO closure had significantly more major vascular complications and atrial fibrillations. Vascular complications occurred completely secondary to the closures, with none in the medically-managed patients, Dr. Furlan said. The closure procedure achieved technical success in 90% of patients in that arm of the study, with 86% of the PFOs closed at 6 months after treatment based on follow-up echocardiography examinations.

The CLOSURE I study was sponsored by NMT Medical, which markets the STARFlex closure device. Dr. Furlan said that he is a consultant to NMT Medical and was the principal investigator for the trial. Dr. Amarenco said that he has received research grants from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Pfizer.

CHICAGO – "Measurement of cardiac troponin T using a highly sensitive assay may be useful in risk stratification in older adults," Dr. Stephen L. Seliger declared in presenting study findings at the annual scientific sessions of the American Heart Association.

The investigational assay was an independent predictor of cardiovascular mortality in a longitudinal observational cohort study of 4,221 ambulatory, community-dwelling adults aged 65 years or older without prior heart failure. The cohort participated in the nationwide Cardiovascular Health Study, a National Institutes of Health–funded study of cardiovascular risk in the elderly. During a median 11.8 years of follow-up, 1,100 of them died of cardiovascular causes.

At baseline, serum cardiac troponin T (cTnT) was 3.0 pg/mL or more in 66% of the subjects. Cardiovascular deaths rose with increasing baseline cTnT, from a low of 1.1 cases per 100 person-years in those with undetectable cTnT to a high of 4.8 per 100 person-years in subjects in the top quartile of detectable cTnT, with a level greater than 12.94 pg/mL.

The incidence of cardiovascular mortality was 1.6 per 100 person-years in individuals with a baseline cTnT of 3.00-5.44 pg/mL, 2.3 cases per 100 person-years in those with a value of 5.45-8.16 pg/mL, and 3.0 per 100 person-years in subjects with a cTnT of 8.17-12.94 pg/mL, added Dr. Seliger of the University of Maryland, Baltimore.

A higher baseline cTnT was strongly predictive of cardiovascular mortality independent of the traditional cardiovascular risk factors as well as the widely used biomarkers N-terminal pro-type B natriuretic peptide and C-reactive protein. In a multivariate analysis adjusted for these variables, a cTnT greater than 12.94 pg/mL was associated with a 2.1-fold greater risk of cardiovascular death than was an undetectable level of cTnT. Subjects in quartiles 1-3 for detectable cTnT had adjusted risks that were, respectively, 1.3-, 1.45-, and 1.58-fold greater than in individuals with an undetectable cTnT.

Not only was a higher baseline cTnT associated with increased risk of cardiovascular mortality, but so were changes in cTnT over time, regardless of the absolute baseline level. Among the two-thirds of elderly individuals who had a detectable baseline cTnT, 22% had a 50% or greater increase in cTnT over the next several years; their long-term risk of cardiovascular death was 70% greater than that of subjects without an increase of that magnitude.

In contrast, the 14% of subjects who showed a 50% or greater reduction in cTnT compared with baseline had a 30% lower cardiovascular mortality rate than did those with less than a 50% change in cTnT level over the first several years of follow-up.

The underlying cause of these small elevations in cTnT – changes undetectable using standard assays – remains unclear. It’s possible that the enzyme is being released as a consequence of increased left ventricular mass or perhaps because of chronic hypertension. Preliminary work by Dr. Seliger and his coinvestigators suggests the cTnT release may be due to a metabolic alteration involving changes in fatty acid oxidation patterns.

Dr. Seliger declared he serves as a consultant to Roche Diagnostics, which is developing the highly sensitive cTnT assay.

CHICAGO – "Measurement of cardiac troponin T using a highly sensitive assay may be useful in risk stratification in older adults," Dr. Stephen L. Seliger declared in presenting study findings at the annual scientific sessions of the American Heart Association.

The investigational assay was an independent predictor of cardiovascular mortality in a longitudinal observational cohort study of 4,221 ambulatory, community-dwelling adults aged 65 years or older without prior heart failure. The cohort participated in the nationwide Cardiovascular Health Study, a National Institutes of Health–funded study of cardiovascular risk in the elderly. During a median 11.8 years of follow-up, 1,100 of them died of cardiovascular causes.

At baseline, serum cardiac troponin T (cTnT) was 3.0 pg/mL or more in 66% of the subjects. Cardiovascular deaths rose with increasing baseline cTnT, from a low of 1.1 cases per 100 person-years in those with undetectable cTnT to a high of 4.8 per 100 person-years in subjects in the top quartile of detectable cTnT, with a level greater than 12.94 pg/mL.

The incidence of cardiovascular mortality was 1.6 per 100 person-years in individuals with a baseline cTnT of 3.00-5.44 pg/mL, 2.3 cases per 100 person-years in those with a value of 5.45-8.16 pg/mL, and 3.0 per 100 person-years in subjects with a cTnT of 8.17-12.94 pg/mL, added Dr. Seliger of the University of Maryland, Baltimore.

A higher baseline cTnT was strongly predictive of cardiovascular mortality independent of the traditional cardiovascular risk factors as well as the widely used biomarkers N-terminal pro-type B natriuretic peptide and C-reactive protein. In a multivariate analysis adjusted for these variables, a cTnT greater than 12.94 pg/mL was associated with a 2.1-fold greater risk of cardiovascular death than was an undetectable level of cTnT. Subjects in quartiles 1-3 for detectable cTnT had adjusted risks that were, respectively, 1.3-, 1.45-, and 1.58-fold greater than in individuals with an undetectable cTnT.

Not only was a higher baseline cTnT associated with increased risk of cardiovascular mortality, but so were changes in cTnT over time, regardless of the absolute baseline level. Among the two-thirds of elderly individuals who had a detectable baseline cTnT, 22% had a 50% or greater increase in cTnT over the next several years; their long-term risk of cardiovascular death was 70% greater than that of subjects without an increase of that magnitude.

In contrast, the 14% of subjects who showed a 50% or greater reduction in cTnT compared with baseline had a 30% lower cardiovascular mortality rate than did those with less than a 50% change in cTnT level over the first several years of follow-up.

The underlying cause of these small elevations in cTnT – changes undetectable using standard assays – remains unclear. It’s possible that the enzyme is being released as a consequence of increased left ventricular mass or perhaps because of chronic hypertension. Preliminary work by Dr. Seliger and his coinvestigators suggests the cTnT release may be due to a metabolic alteration involving changes in fatty acid oxidation patterns.

Dr. Seliger declared he serves as a consultant to Roche Diagnostics, which is developing the highly sensitive cTnT assay.

CHICAGO – "Measurement of cardiac troponin T using a highly sensitive assay may be useful in risk stratification in older adults," Dr. Stephen L. Seliger declared in presenting study findings at the annual scientific sessions of the American Heart Association.

The investigational assay was an independent predictor of cardiovascular mortality in a longitudinal observational cohort study of 4,221 ambulatory, community-dwelling adults aged 65 years or older without prior heart failure. The cohort participated in the nationwide Cardiovascular Health Study, a National Institutes of Health–funded study of cardiovascular risk in the elderly. During a median 11.8 years of follow-up, 1,100 of them died of cardiovascular causes.

At baseline, serum cardiac troponin T (cTnT) was 3.0 pg/mL or more in 66% of the subjects. Cardiovascular deaths rose with increasing baseline cTnT, from a low of 1.1 cases per 100 person-years in those with undetectable cTnT to a high of 4.8 per 100 person-years in subjects in the top quartile of detectable cTnT, with a level greater than 12.94 pg/mL.

The incidence of cardiovascular mortality was 1.6 per 100 person-years in individuals with a baseline cTnT of 3.00-5.44 pg/mL, 2.3 cases per 100 person-years in those with a value of 5.45-8.16 pg/mL, and 3.0 per 100 person-years in subjects with a cTnT of 8.17-12.94 pg/mL, added Dr. Seliger of the University of Maryland, Baltimore.

A higher baseline cTnT was strongly predictive of cardiovascular mortality independent of the traditional cardiovascular risk factors as well as the widely used biomarkers N-terminal pro-type B natriuretic peptide and C-reactive protein. In a multivariate analysis adjusted for these variables, a cTnT greater than 12.94 pg/mL was associated with a 2.1-fold greater risk of cardiovascular death than was an undetectable level of cTnT. Subjects in quartiles 1-3 for detectable cTnT had adjusted risks that were, respectively, 1.3-, 1.45-, and 1.58-fold greater than in individuals with an undetectable cTnT.

Not only was a higher baseline cTnT associated with increased risk of cardiovascular mortality, but so were changes in cTnT over time, regardless of the absolute baseline level. Among the two-thirds of elderly individuals who had a detectable baseline cTnT, 22% had a 50% or greater increase in cTnT over the next several years; their long-term risk of cardiovascular death was 70% greater than that of subjects without an increase of that magnitude.

In contrast, the 14% of subjects who showed a 50% or greater reduction in cTnT compared with baseline had a 30% lower cardiovascular mortality rate than did those with less than a 50% change in cTnT level over the first several years of follow-up.

The underlying cause of these small elevations in cTnT – changes undetectable using standard assays – remains unclear. It’s possible that the enzyme is being released as a consequence of increased left ventricular mass or perhaps because of chronic hypertension. Preliminary work by Dr. Seliger and his coinvestigators suggests the cTnT release may be due to a metabolic alteration involving changes in fatty acid oxidation patterns.

Dr. Seliger declared he serves as a consultant to Roche Diagnostics, which is developing the highly sensitive cTnT assay.

CHICAGO – "Measurement of cardiac troponin T using a highly sensitive assay may be useful in risk stratification in older adults," Dr. Stephen L. Seliger declared in presenting study findings at the annual scientific sessions of the American Heart Association.

The investigational assay was an independent predictor of cardiovascular mortality in a longitudinal observational cohort study of 4,221 ambulatory, community-dwelling adults aged 65 years or older without prior heart failure. The cohort participated in the nationwide Cardiovascular Health Study, a National Institutes of Health–funded study of cardiovascular risk in the elderly. During a median 11.8 years of follow-up, 1,100 of them died of cardiovascular causes.

At baseline, serum cardiac troponin T (cTnT) was 3.0 pg/mL or more in 66% of the subjects. Cardiovascular deaths rose with increasing baseline cTnT, from a low of 1.1 cases per 100 person-years in those with undetectable cTnT to a high of 4.8 per 100 person-years in subjects in the top quartile of detectable cTnT, with a level greater than 12.94 pg/mL.

The incidence of cardiovascular mortality was 1.6 per 100 person-years in individuals with a baseline cTnT of 3.00-5.44 pg/mL, 2.3 cases per 100 person-years in those with a value of 5.45-8.16 pg/mL, and 3.0 per 100 person-years in subjects with a cTnT of 8.17-12.94 pg/mL, added Dr. Seliger of the University of Maryland, Baltimore.

A higher baseline cTnT was strongly predictive of cardiovascular mortality independent of the traditional cardiovascular risk factors as well as the widely used biomarkers N-terminal pro-type B natriuretic peptide and C-reactive protein. In a multivariate analysis adjusted for these variables, a cTnT greater than 12.94 pg/mL was associated with a 2.1-fold greater risk of cardiovascular death than was an undetectable level of cTnT. Subjects in quartiles 1-3 for detectable cTnT had adjusted risks that were, respectively, 1.3-, 1.45-, and 1.58-fold greater than in individuals with an undetectable cTnT.

Not only was a higher baseline cTnT associated with increased risk of cardiovascular mortality, but so were changes in cTnT over time, regardless of the absolute baseline level. Among the two-thirds of elderly individuals who had a detectable baseline cTnT, 22% had a 50% or greater increase in cTnT over the next several years; their long-term risk of cardiovascular death was 70% greater than that of subjects without an increase of that magnitude.

In contrast, the 14% of subjects who showed a 50% or greater reduction in cTnT compared with baseline had a 30% lower cardiovascular mortality rate than did those with less than a 50% change in cTnT level over the first several years of follow-up.

The underlying cause of these small elevations in cTnT – changes undetectable using standard assays – remains unclear. It’s possible that the enzyme is being released as a consequence of increased left ventricular mass or perhaps because of chronic hypertension. Preliminary work by Dr. Seliger and his coinvestigators suggests the cTnT release may be due to a metabolic alteration involving changes in fatty acid oxidation patterns.

Dr. Seliger declared he serves as a consultant to Roche Diagnostics, which is developing the highly sensitive cTnT assay.

CHICAGO – "Measurement of cardiac troponin T using a highly sensitive assay may be useful in risk stratification in older adults," Dr. Stephen L. Seliger declared in presenting study findings at the annual scientific sessions of the American Heart Association.

The investigational assay was an independent predictor of cardiovascular mortality in a longitudinal observational cohort study of 4,221 ambulatory, community-dwelling adults aged 65 years or older without prior heart failure. The cohort participated in the nationwide Cardiovascular Health Study, a National Institutes of Health–funded study of cardiovascular risk in the elderly. During a median 11.8 years of follow-up, 1,100 of them died of cardiovascular causes.

At baseline, serum cardiac troponin T (cTnT) was 3.0 pg/mL or more in 66% of the subjects. Cardiovascular deaths rose with increasing baseline cTnT, from a low of 1.1 cases per 100 person-years in those with undetectable cTnT to a high of 4.8 per 100 person-years in subjects in the top quartile of detectable cTnT, with a level greater than 12.94 pg/mL.

The incidence of cardiovascular mortality was 1.6 per 100 person-years in individuals with a baseline cTnT of 3.00-5.44 pg/mL, 2.3 cases per 100 person-years in those with a value of 5.45-8.16 pg/mL, and 3.0 per 100 person-years in subjects with a cTnT of 8.17-12.94 pg/mL, added Dr. Seliger of the University of Maryland, Baltimore.

A higher baseline cTnT was strongly predictive of cardiovascular mortality independent of the traditional cardiovascular risk factors as well as the widely used biomarkers N-terminal pro-type B natriuretic peptide and C-reactive protein. In a multivariate analysis adjusted for these variables, a cTnT greater than 12.94 pg/mL was associated with a 2.1-fold greater risk of cardiovascular death than was an undetectable level of cTnT. Subjects in quartiles 1-3 for detectable cTnT had adjusted risks that were, respectively, 1.3-, 1.45-, and 1.58-fold greater than in individuals with an undetectable cTnT.

Not only was a higher baseline cTnT associated with increased risk of cardiovascular mortality, but so were changes in cTnT over time, regardless of the absolute baseline level. Among the two-thirds of elderly individuals who had a detectable baseline cTnT, 22% had a 50% or greater increase in cTnT over the next several years; their long-term risk of cardiovascular death was 70% greater than that of subjects without an increase of that magnitude.

In contrast, the 14% of subjects who showed a 50% or greater reduction in cTnT compared with baseline had a 30% lower cardiovascular mortality rate than did those with less than a 50% change in cTnT level over the first several years of follow-up.

The underlying cause of these small elevations in cTnT – changes undetectable using standard assays – remains unclear. It’s possible that the enzyme is being released as a consequence of increased left ventricular mass or perhaps because of chronic hypertension. Preliminary work by Dr. Seliger and his coinvestigators suggests the cTnT release may be due to a metabolic alteration involving changes in fatty acid oxidation patterns.

Dr. Seliger declared he serves as a consultant to Roche Diagnostics, which is developing the highly sensitive cTnT assay.

CHICAGO – "Measurement of cardiac troponin T using a highly sensitive assay may be useful in risk stratification in older adults," Dr. Stephen L. Seliger declared in presenting study findings at the annual scientific sessions of the American Heart Association.

The investigational assay was an independent predictor of cardiovascular mortality in a longitudinal observational cohort study of 4,221 ambulatory, community-dwelling adults aged 65 years or older without prior heart failure. The cohort participated in the nationwide Cardiovascular Health Study, a National Institutes of Health–funded study of cardiovascular risk in the elderly. During a median 11.8 years of follow-up, 1,100 of them died of cardiovascular causes.

At baseline, serum cardiac troponin T (cTnT) was 3.0 pg/mL or more in 66% of the subjects. Cardiovascular deaths rose with increasing baseline cTnT, from a low of 1.1 cases per 100 person-years in those with undetectable cTnT to a high of 4.8 per 100 person-years in subjects in the top quartile of detectable cTnT, with a level greater than 12.94 pg/mL.

The incidence of cardiovascular mortality was 1.6 per 100 person-years in individuals with a baseline cTnT of 3.00-5.44 pg/mL, 2.3 cases per 100 person-years in those with a value of 5.45-8.16 pg/mL, and 3.0 per 100 person-years in subjects with a cTnT of 8.17-12.94 pg/mL, added Dr. Seliger of the University of Maryland, Baltimore.

A higher baseline cTnT was strongly predictive of cardiovascular mortality independent of the traditional cardiovascular risk factors as well as the widely used biomarkers N-terminal pro-type B natriuretic peptide and C-reactive protein. In a multivariate analysis adjusted for these variables, a cTnT greater than 12.94 pg/mL was associated with a 2.1-fold greater risk of cardiovascular death than was an undetectable level of cTnT. Subjects in quartiles 1-3 for detectable cTnT had adjusted risks that were, respectively, 1.3-, 1.45-, and 1.58-fold greater than in individuals with an undetectable cTnT.

Not only was a higher baseline cTnT associated with increased risk of cardiovascular mortality, but so were changes in cTnT over time, regardless of the absolute baseline level. Among the two-thirds of elderly individuals who had a detectable baseline cTnT, 22% had a 50% or greater increase in cTnT over the next several years; their long-term risk of cardiovascular death was 70% greater than that of subjects without an increase of that magnitude.

In contrast, the 14% of subjects who showed a 50% or greater reduction in cTnT compared with baseline had a 30% lower cardiovascular mortality rate than did those with less than a 50% change in cTnT level over the first several years of follow-up.

The underlying cause of these small elevations in cTnT – changes undetectable using standard assays – remains unclear. It’s possible that the enzyme is being released as a consequence of increased left ventricular mass or perhaps because of chronic hypertension. Preliminary work by Dr. Seliger and his coinvestigators suggests the cTnT release may be due to a metabolic alteration involving changes in fatty acid oxidation patterns.

Dr. Seliger declared he serves as a consultant to Roche Diagnostics, which is developing the highly sensitive cTnT assay.

CHICAGO – "Measurement of cardiac troponin T using a highly sensitive assay may be useful in risk stratification in older adults," Dr. Stephen L. Seliger declared in presenting study findings at the annual scientific sessions of the American Heart Association.

The investigational assay was an independent predictor of cardiovascular mortality in a longitudinal observational cohort study of 4,221 ambulatory, community-dwelling adults aged 65 years or older without prior heart failure. The cohort participated in the nationwide Cardiovascular Health Study, a National Institutes of Health–funded study of cardiovascular risk in the elderly. During a median 11.8 years of follow-up, 1,100 of them died of cardiovascular causes.

At baseline, serum cardiac troponin T (cTnT) was 3.0 pg/mL or more in 66% of the subjects. Cardiovascular deaths rose with increasing baseline cTnT, from a low of 1.1 cases per 100 person-years in those with undetectable cTnT to a high of 4.8 per 100 person-years in subjects in the top quartile of detectable cTnT, with a level greater than 12.94 pg/mL.

The incidence of cardiovascular mortality was 1.6 per 100 person-years in individuals with a baseline cTnT of 3.00-5.44 pg/mL, 2.3 cases per 100 person-years in those with a value of 5.45-8.16 pg/mL, and 3.0 per 100 person-years in subjects with a cTnT of 8.17-12.94 pg/mL, added Dr. Seliger of the University of Maryland, Baltimore.

A higher baseline cTnT was strongly predictive of cardiovascular mortality independent of the traditional cardiovascular risk factors as well as the widely used biomarkers N-terminal pro-type B natriuretic peptide and C-reactive protein. In a multivariate analysis adjusted for these variables, a cTnT greater than 12.94 pg/mL was associated with a 2.1-fold greater risk of cardiovascular death than was an undetectable level of cTnT. Subjects in quartiles 1-3 for detectable cTnT had adjusted risks that were, respectively, 1.3-, 1.45-, and 1.58-fold greater than in individuals with an undetectable cTnT.

Not only was a higher baseline cTnT associated with increased risk of cardiovascular mortality, but so were changes in cTnT over time, regardless of the absolute baseline level. Among the two-thirds of elderly individuals who had a detectable baseline cTnT, 22% had a 50% or greater increase in cTnT over the next several years; their long-term risk of cardiovascular death was 70% greater than that of subjects without an increase of that magnitude.

In contrast, the 14% of subjects who showed a 50% or greater reduction in cTnT compared with baseline had a 30% lower cardiovascular mortality rate than did those with less than a 50% change in cTnT level over the first several years of follow-up.

The underlying cause of these small elevations in cTnT – changes undetectable using standard assays – remains unclear. It’s possible that the enzyme is being released as a consequence of increased left ventricular mass or perhaps because of chronic hypertension. Preliminary work by Dr. Seliger and his coinvestigators suggests the cTnT release may be due to a metabolic alteration involving changes in fatty acid oxidation patterns.

Dr. Seliger declared he serves as a consultant to Roche Diagnostics, which is developing the highly sensitive cTnT assay.

CHICAGO – "Measurement of cardiac troponin T using a highly sensitive assay may be useful in risk stratification in older adults," Dr. Stephen L. Seliger declared in presenting study findings at the annual scientific sessions of the American Heart Association.

The investigational assay was an independent predictor of cardiovascular mortality in a longitudinal observational cohort study of 4,221 ambulatory, community-dwelling adults aged 65 years or older without prior heart failure. The cohort participated in the nationwide Cardiovascular Health Study, a National Institutes of Health–funded study of cardiovascular risk in the elderly. During a median 11.8 years of follow-up, 1,100 of them died of cardiovascular causes.

At baseline, serum cardiac troponin T (cTnT) was 3.0 pg/mL or more in 66% of the subjects. Cardiovascular deaths rose with increasing baseline cTnT, from a low of 1.1 cases per 100 person-years in those with undetectable cTnT to a high of 4.8 per 100 person-years in subjects in the top quartile of detectable cTnT, with a level greater than 12.94 pg/mL.

The incidence of cardiovascular mortality was 1.6 per 100 person-years in individuals with a baseline cTnT of 3.00-5.44 pg/mL, 2.3 cases per 100 person-years in those with a value of 5.45-8.16 pg/mL, and 3.0 per 100 person-years in subjects with a cTnT of 8.17-12.94 pg/mL, added Dr. Seliger of the University of Maryland, Baltimore.

A higher baseline cTnT was strongly predictive of cardiovascular mortality independent of the traditional cardiovascular risk factors as well as the widely used biomarkers N-terminal pro-type B natriuretic peptide and C-reactive protein. In a multivariate analysis adjusted for these variables, a cTnT greater than 12.94 pg/mL was associated with a 2.1-fold greater risk of cardiovascular death than was an undetectable level of cTnT. Subjects in quartiles 1-3 for detectable cTnT had adjusted risks that were, respectively, 1.3-, 1.45-, and 1.58-fold greater than in individuals with an undetectable cTnT.

Not only was a higher baseline cTnT associated with increased risk of cardiovascular mortality, but so were changes in cTnT over time, regardless of the absolute baseline level. Among the two-thirds of elderly individuals who had a detectable baseline cTnT, 22% had a 50% or greater increase in cTnT over the next several years; their long-term risk of cardiovascular death was 70% greater than that of subjects without an increase of that magnitude.

In contrast, the 14% of subjects who showed a 50% or greater reduction in cTnT compared with baseline had a 30% lower cardiovascular mortality rate than did those with less than a 50% change in cTnT level over the first several years of follow-up.

The underlying cause of these small elevations in cTnT – changes undetectable using standard assays – remains unclear. It’s possible that the enzyme is being released as a consequence of increased left ventricular mass or perhaps because of chronic hypertension. Preliminary work by Dr. Seliger and his coinvestigators suggests the cTnT release may be due to a metabolic alteration involving changes in fatty acid oxidation patterns.

Dr. Seliger declared he serves as a consultant to Roche Diagnostics, which is developing the highly sensitive cTnT assay.

CHICAGO – "Measurement of cardiac troponin T using a highly sensitive assay may be useful in risk stratification in older adults," Dr. Stephen L. Seliger declared in presenting study findings at the annual scientific sessions of the American Heart Association.

The investigational assay was an independent predictor of cardiovascular mortality in a longitudinal observational cohort study of 4,221 ambulatory, community-dwelling adults aged 65 years or older without prior heart failure. The cohort participated in the nationwide Cardiovascular Health Study, a National Institutes of Health–funded study of cardiovascular risk in the elderly. During a median 11.8 years of follow-up, 1,100 of them died of cardiovascular causes.

At baseline, serum cardiac troponin T (cTnT) was 3.0 pg/mL or more in 66% of the subjects. Cardiovascular deaths rose with increasing baseline cTnT, from a low of 1.1 cases per 100 person-years in those with undetectable cTnT to a high of 4.8 per 100 person-years in subjects in the top quartile of detectable cTnT, with a level greater than 12.94 pg/mL.

The incidence of cardiovascular mortality was 1.6 per 100 person-years in individuals with a baseline cTnT of 3.00-5.44 pg/mL, 2.3 cases per 100 person-years in those with a value of 5.45-8.16 pg/mL, and 3.0 per 100 person-years in subjects with a cTnT of 8.17-12.94 pg/mL, added Dr. Seliger of the University of Maryland, Baltimore.

A higher baseline cTnT was strongly predictive of cardiovascular mortality independent of the traditional cardiovascular risk factors as well as the widely used biomarkers N-terminal pro-type B natriuretic peptide and C-reactive protein. In a multivariate analysis adjusted for these variables, a cTnT greater than 12.94 pg/mL was associated with a 2.1-fold greater risk of cardiovascular death than was an undetectable level of cTnT. Subjects in quartiles 1-3 for detectable cTnT had adjusted risks that were, respectively, 1.3-, 1.45-, and 1.58-fold greater than in individuals with an undetectable cTnT.

Not only was a higher baseline cTnT associated with increased risk of cardiovascular mortality, but so were changes in cTnT over time, regardless of the absolute baseline level. Among the two-thirds of elderly individuals who had a detectable baseline cTnT, 22% had a 50% or greater increase in cTnT over the next several years; their long-term risk of cardiovascular death was 70% greater than that of subjects without an increase of that magnitude.

In contrast, the 14% of subjects who showed a 50% or greater reduction in cTnT compared with baseline had a 30% lower cardiovascular mortality rate than did those with less than a 50% change in cTnT level over the first several years of follow-up.

The underlying cause of these small elevations in cTnT – changes undetectable using standard assays – remains unclear. It’s possible that the enzyme is being released as a consequence of increased left ventricular mass or perhaps because of chronic hypertension. Preliminary work by Dr. Seliger and his coinvestigators suggests the cTnT release may be due to a metabolic alteration involving changes in fatty acid oxidation patterns.

Dr. Seliger declared he serves as a consultant to Roche Diagnostics, which is developing the highly sensitive cTnT assay.