Acquired Cardiovascular Disease

Neither aspirin nor simvastatin improved outcomes for patients with pulmonary arterial hypertension in a phase II safety and efficacy trial published in Circulation and simultaneously presented at the annual meeting of the American Thoracic Society.

The primary end point of 6-minute walk distance did not increase after 6 months of aspirin therapy and actually decreased after 6 months of simvastatin therapy, indicating that neither agent should be used as an add-on therapy in PAH, said Dr. Steven M. Kawut of Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, and his associates.

A recent animal study showed that aspirin decreased pulmonary artery pressure, reduced right ventricular hypertrophy, and improved survival, and several recent studies showed that statins were effective in animal models of pulmonary hypertension. Dr. Kawut and his associates in the ASA-STAT Study Group designed their phase II clinical trial to test the safety and efficacy of both agents against matching placebos, intending to enroll 100 subjects with PAH.

The study, however, was terminated after only 65 subjects had been randomized because an interim analysis showed "a high likelihood of not rejecting the null hypothesis for the simvastatin arm even if fully recruited," they wrote. The investigators reported their findings for those 65 subjects.

The patients’ mean age was 50 years, and 86% were women. Approximately 52% had idiopathic PAH, 19% had PAH associated with systemic sclerosis, 15% had PAH associated with other connective tissue diseases, 9% had congenital systemic-to-pulmonary shunts, and 5% had heritable PAH.

The primary outcome measure was 6-minute walk distance after 6 months of treatment, after adjustment for 6-minute walk distance at baseline.

Patients who received aspirin therapy showed no improvement in this measure, compared with those who received placebo. They also showed no improvement in median Borg dyspnea scores after the walk test, in any scales of the SF-36, or in World Health Organization functional class. And there was no difference between the two groups in time to clinical worsening, Dr. Kawut and his associates said.

Similarly, patients who received simvastatin showed no improvement in 6-minute walk distance after 6 months of treatment, compared with those who received placebo. In fact, the active drug may have reduced this distance, although the number of subjects was not sufficient to detect a statistically significant difference. Moreover, the median Borg dyspnea scores after the walk test tended to be higher in subjects who took simvastatin than in those who took placebo, suggesting greater breathlessness.

As with aspirin, there were no differences on any scales of the SF-36 or in WHO functional class between the subjects who took simvastatin and those who took placebo (Circulation 2011 May 19 [doi:10.1161/CIRCULATIONAHA.110.015693]).

"There was a possible increased risk of major bleeding associated with aspirin use," they noted, but again, the number of subjects was not sufficient to make this determination definitively.

"On the basis of these findings, neither drug can be recommended for the treatment of PAH," Dr. Kawut and his colleagues said.

The study was funded by the National Institutes of Health and the National Center for Research Resources. Aspirin and matching placebo were provided free of charge by Bayer Healthcare. Additional support was provided by Merck. Dr. Kawut and his associates reported ties to numerous industry sources.

Neither aspirin nor simvastatin improved outcomes for patients with pulmonary arterial hypertension in a phase II safety and efficacy trial published in Circulation and simultaneously presented at the annual meeting of the American Thoracic Society.

The primary end point of 6-minute walk distance did not increase after 6 months of aspirin therapy and actually decreased after 6 months of simvastatin therapy, indicating that neither agent should be used as an add-on therapy in PAH, said Dr. Steven M. Kawut of Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, and his associates.

A recent animal study showed that aspirin decreased pulmonary artery pressure, reduced right ventricular hypertrophy, and improved survival, and several recent studies showed that statins were effective in animal models of pulmonary hypertension. Dr. Kawut and his associates in the ASA-STAT Study Group designed their phase II clinical trial to test the safety and efficacy of both agents against matching placebos, intending to enroll 100 subjects with PAH.

The study, however, was terminated after only 65 subjects had been randomized because an interim analysis showed "a high likelihood of not rejecting the null hypothesis for the simvastatin arm even if fully recruited," they wrote. The investigators reported their findings for those 65 subjects.

The patients’ mean age was 50 years, and 86% were women. Approximately 52% had idiopathic PAH, 19% had PAH associated with systemic sclerosis, 15% had PAH associated with other connective tissue diseases, 9% had congenital systemic-to-pulmonary shunts, and 5% had heritable PAH.

The primary outcome measure was 6-minute walk distance after 6 months of treatment, after adjustment for 6-minute walk distance at baseline.

Patients who received aspirin therapy showed no improvement in this measure, compared with those who received placebo. They also showed no improvement in median Borg dyspnea scores after the walk test, in any scales of the SF-36, or in World Health Organization functional class. And there was no difference between the two groups in time to clinical worsening, Dr. Kawut and his associates said.

Similarly, patients who received simvastatin showed no improvement in 6-minute walk distance after 6 months of treatment, compared with those who received placebo. In fact, the active drug may have reduced this distance, although the number of subjects was not sufficient to detect a statistically significant difference. Moreover, the median Borg dyspnea scores after the walk test tended to be higher in subjects who took simvastatin than in those who took placebo, suggesting greater breathlessness.

As with aspirin, there were no differences on any scales of the SF-36 or in WHO functional class between the subjects who took simvastatin and those who took placebo (Circulation 2011 May 19 [doi:10.1161/CIRCULATIONAHA.110.015693]).

"There was a possible increased risk of major bleeding associated with aspirin use," they noted, but again, the number of subjects was not sufficient to make this determination definitively.

"On the basis of these findings, neither drug can be recommended for the treatment of PAH," Dr. Kawut and his colleagues said.

The study was funded by the National Institutes of Health and the National Center for Research Resources. Aspirin and matching placebo were provided free of charge by Bayer Healthcare. Additional support was provided by Merck. Dr. Kawut and his associates reported ties to numerous industry sources.

Neither aspirin nor simvastatin improved outcomes for patients with pulmonary arterial hypertension in a phase II safety and efficacy trial published in Circulation and simultaneously presented at the annual meeting of the American Thoracic Society.

The primary end point of 6-minute walk distance did not increase after 6 months of aspirin therapy and actually decreased after 6 months of simvastatin therapy, indicating that neither agent should be used as an add-on therapy in PAH, said Dr. Steven M. Kawut of Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, and his associates.

A recent animal study showed that aspirin decreased pulmonary artery pressure, reduced right ventricular hypertrophy, and improved survival, and several recent studies showed that statins were effective in animal models of pulmonary hypertension. Dr. Kawut and his associates in the ASA-STAT Study Group designed their phase II clinical trial to test the safety and efficacy of both agents against matching placebos, intending to enroll 100 subjects with PAH.

The study, however, was terminated after only 65 subjects had been randomized because an interim analysis showed "a high likelihood of not rejecting the null hypothesis for the simvastatin arm even if fully recruited," they wrote. The investigators reported their findings for those 65 subjects.

The patients’ mean age was 50 years, and 86% were women. Approximately 52% had idiopathic PAH, 19% had PAH associated with systemic sclerosis, 15% had PAH associated with other connective tissue diseases, 9% had congenital systemic-to-pulmonary shunts, and 5% had heritable PAH.

The primary outcome measure was 6-minute walk distance after 6 months of treatment, after adjustment for 6-minute walk distance at baseline.

Patients who received aspirin therapy showed no improvement in this measure, compared with those who received placebo. They also showed no improvement in median Borg dyspnea scores after the walk test, in any scales of the SF-36, or in World Health Organization functional class. And there was no difference between the two groups in time to clinical worsening, Dr. Kawut and his associates said.

Similarly, patients who received simvastatin showed no improvement in 6-minute walk distance after 6 months of treatment, compared with those who received placebo. In fact, the active drug may have reduced this distance, although the number of subjects was not sufficient to detect a statistically significant difference. Moreover, the median Borg dyspnea scores after the walk test tended to be higher in subjects who took simvastatin than in those who took placebo, suggesting greater breathlessness.

As with aspirin, there were no differences on any scales of the SF-36 or in WHO functional class between the subjects who took simvastatin and those who took placebo (Circulation 2011 May 19 [doi:10.1161/CIRCULATIONAHA.110.015693]).

"There was a possible increased risk of major bleeding associated with aspirin use," they noted, but again, the number of subjects was not sufficient to make this determination definitively.

"On the basis of these findings, neither drug can be recommended for the treatment of PAH," Dr. Kawut and his colleagues said.

The study was funded by the National Institutes of Health and the National Center for Research Resources. Aspirin and matching placebo were provided free of charge by Bayer Healthcare. Additional support was provided by Merck. Dr. Kawut and his associates reported ties to numerous industry sources.

NEW YORK - Mitral valve repair surgery was associated with very low operative mortality and acceptable morbidity in a database analysis of 903 patients at 16 centers in Virginia presented at the 2011 Mitral Conclave.

Mitral valve repair (MVR) rather than replacement has become the favored surgical approach for mitral insufficiency over the last 2 decades. The recent emergence of transcatheter approaches to repair has focused attention on the outcomes for surgical approaches. In the EVEREST II trial, published earlier this year, worse short-term outcomes were seen with surgical MVR or replacement, compared with percutaneous MVR using the MitraClip device. Among 279 patients, composite major event rates at 30 days were 15% for percutaneous repair, compared with 48% for surgery (N. Engl. J. Med. 2011;364:1395-406).

The current study was undertaken to analyze contemporary outcomes for surgical mitral repair within a multiinstitutional cohort of patients to better establish a benchmark for future comparisons of treatments for mitral valve insufficiency, Dr. Damien J. LaPar said.

Cardiac surgical data were obtained from the 16 participating centers of the Virginia Cardiac Surgery Quality Initiative, which captures approximately 99% of the state?s cardiac operations. Patient exclusions were the same as in the EVEREST II trial: prior valve operations, endocarditis, and mitral stenosis.

The 903 patients had an average age of 57 years; 41% were women. Heart failure was present in 32%, and severe mitral insufficiency in 82%. Most (85%) of the operations were elective, including reconstruction with annuloplasty in 69%, said Dr. LaPar of the University of Virginia, Charlottesville.

Major adverse events occurred in 29%, a lower percentage than reported in EVEREST II. Atrial fibrillation was the most frequent, in 18%. Renal failure occurred in just 1.3%, stroke in 0.9%, and operative mortality in 1.1%. The mean postoperative length of stay was 6 days.

Multivariate predictors of major adverse events included age, preoperative stroke and immunosuppressive therapy, use of an aortic cross-clamp, and cardiopulmonary bypass times. Factors not significantly associated with major adverse events were female sex, renal failure, prior coronary artery bypass grafting, and ejection fraction.

 "These results may help stratify which patients might be best served by emerging approaches to surgery," he said.

This study was funded by a training grant from the National Heart, Lung, and Blood Institute and a research grant from the Thoracic Surgery Foundation for Research and Education. Dr. LaPar stated that he had no disclosures; three of his coinvestigators consult for, and/or received honoraria from Abbott, maker of the MitraClip device used in the study.

NEW YORK - Mitral valve repair surgery was associated with very low operative mortality and acceptable morbidity in a database analysis of 903 patients at 16 centers in Virginia presented at the 2011 Mitral Conclave.

Mitral valve repair (MVR) rather than replacement has become the favored surgical approach for mitral insufficiency over the last 2 decades. The recent emergence of transcatheter approaches to repair has focused attention on the outcomes for surgical approaches. In the EVEREST II trial, published earlier this year, worse short-term outcomes were seen with surgical MVR or replacement, compared with percutaneous MVR using the MitraClip device. Among 279 patients, composite major event rates at 30 days were 15% for percutaneous repair, compared with 48% for surgery (N. Engl. J. Med. 2011;364:1395-406).

The current study was undertaken to analyze contemporary outcomes for surgical mitral repair within a multiinstitutional cohort of patients to better establish a benchmark for future comparisons of treatments for mitral valve insufficiency, Dr. Damien J. LaPar said.

Cardiac surgical data were obtained from the 16 participating centers of the Virginia Cardiac Surgery Quality Initiative, which captures approximately 99% of the state?s cardiac operations. Patient exclusions were the same as in the EVEREST II trial: prior valve operations, endocarditis, and mitral stenosis.

The 903 patients had an average age of 57 years; 41% were women. Heart failure was present in 32%, and severe mitral insufficiency in 82%. Most (85%) of the operations were elective, including reconstruction with annuloplasty in 69%, said Dr. LaPar of the University of Virginia, Charlottesville.

Major adverse events occurred in 29%, a lower percentage than reported in EVEREST II. Atrial fibrillation was the most frequent, in 18%. Renal failure occurred in just 1.3%, stroke in 0.9%, and operative mortality in 1.1%. The mean postoperative length of stay was 6 days.

Multivariate predictors of major adverse events included age, preoperative stroke and immunosuppressive therapy, use of an aortic cross-clamp, and cardiopulmonary bypass times. Factors not significantly associated with major adverse events were female sex, renal failure, prior coronary artery bypass grafting, and ejection fraction.

 "These results may help stratify which patients might be best served by emerging approaches to surgery," he said.

This study was funded by a training grant from the National Heart, Lung, and Blood Institute and a research grant from the Thoracic Surgery Foundation for Research and Education. Dr. LaPar stated that he had no disclosures; three of his coinvestigators consult for, and/or received honoraria from Abbott, maker of the MitraClip device used in the study.

NEW YORK - Mitral valve repair surgery was associated with very low operative mortality and acceptable morbidity in a database analysis of 903 patients at 16 centers in Virginia presented at the 2011 Mitral Conclave.

Mitral valve repair (MVR) rather than replacement has become the favored surgical approach for mitral insufficiency over the last 2 decades. The recent emergence of transcatheter approaches to repair has focused attention on the outcomes for surgical approaches. In the EVEREST II trial, published earlier this year, worse short-term outcomes were seen with surgical MVR or replacement, compared with percutaneous MVR using the MitraClip device. Among 279 patients, composite major event rates at 30 days were 15% for percutaneous repair, compared with 48% for surgery (N. Engl. J. Med. 2011;364:1395-406).

The current study was undertaken to analyze contemporary outcomes for surgical mitral repair within a multiinstitutional cohort of patients to better establish a benchmark for future comparisons of treatments for mitral valve insufficiency, Dr. Damien J. LaPar said.

Cardiac surgical data were obtained from the 16 participating centers of the Virginia Cardiac Surgery Quality Initiative, which captures approximately 99% of the state?s cardiac operations. Patient exclusions were the same as in the EVEREST II trial: prior valve operations, endocarditis, and mitral stenosis.

The 903 patients had an average age of 57 years; 41% were women. Heart failure was present in 32%, and severe mitral insufficiency in 82%. Most (85%) of the operations were elective, including reconstruction with annuloplasty in 69%, said Dr. LaPar of the University of Virginia, Charlottesville.

Major adverse events occurred in 29%, a lower percentage than reported in EVEREST II. Atrial fibrillation was the most frequent, in 18%. Renal failure occurred in just 1.3%, stroke in 0.9%, and operative mortality in 1.1%. The mean postoperative length of stay was 6 days.

Multivariate predictors of major adverse events included age, preoperative stroke and immunosuppressive therapy, use of an aortic cross-clamp, and cardiopulmonary bypass times. Factors not significantly associated with major adverse events were female sex, renal failure, prior coronary artery bypass grafting, and ejection fraction.

 "These results may help stratify which patients might be best served by emerging approaches to surgery," he said.

This study was funded by a training grant from the National Heart, Lung, and Blood Institute and a research grant from the Thoracic Surgery Foundation for Research and Education. Dr. LaPar stated that he had no disclosures; three of his coinvestigators consult for, and/or received honoraria from Abbott, maker of the MitraClip device used in the study.

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

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

Courtesy of Catherine Harrell/Elsevier.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Courtesy of Catherine Harrell/Elsevier.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Courtesy of Catherine Harrell/Elsevier.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

NEW ORLEANS – About 12% of the more than 140,000 Americans who underwent elective coronary artery stenting during 2009-2010 had an inappropriate procedure, based on an analysis of data from a national registry maintained by the American College of Cardiology.

In contrast, the rate of inappropriate procedures was 1% in the larger group of more than 355,000 patients who had an acute need for percutaneous coronary interventions (PCI) during the period studied, Dr. Paul S. Chan said at the annual meeting of the ACC.

The analysis also showed a striking hospital-to-hospital variation in the rate of elective PCI cases flagged as inappropriate. About 25% of the hospitals doing elective cases had a rate below 6%; another quarter had a rate of 17% or higher. Yet some hospitals had inappropriate rates that exceeded 30%.

Starting in May 2011, the ACC will start reporting data from this analysis to each of the more than 1,000 participating U.S. hospitals. By carefully reviewing cases that have been flagged as inappropriate, it is hoped that hospitals will learn from their mistakes and drive down the inappropriate rate, especially for elective PCIs, said Dr. Chan of Saint Luke’s Hospital in Kansas City, Mo.

The ACC collects the PCI data through the CathPCI portion of its National Cardiovascular Data Registry (NCDR). Dr. Chan and his associates rated each procedure they reviewed as appropriate, inappropriate, or uncertain based on comprehensive criteria established by an ACC expert panel (J. Am. Coll. Card. 2009;53:530-53).

"About 25% of the interventional cases in my practice would be categorized as inappropriate," commented Dr. Edward J. McNulty, an interventional cardiologist at Kaiser Permanente in San Francisco. "I get most of my patients from surgeons or other interventional cardiologists who feel the patients are too high risk. I do a lot of left main and multivessel PCI. There is no way that I can explain on the NCDR form why I consider these patients appropriate. The NCDR data don’t allow you to appreciate nuances. The criteria tend to penalize physicians who deviate from the average [by performing] complex cases."

Additionally, the way patients’ drug use gets recorded on the day of hospitalization is problematic, as patients may stop a chronically used drug on the day before entering the hospital and be erroneously recorded as not being on a therapy. Another issue is misclassification of symptoms, such as a patient who perceives ischemic chest pain as shortness of breath.

"I believe that inappropriate PCIs occur, and these results can certainly show signals. But within the ‘inappropriate’ procedures are some cases with mitigating circumstances," Dr. McNulty said in an interview.

The ACC expert panel published appropriateness criteria for 198 different clinical scenarios based on six separate clinical elements in February 2009. They applied the criteria to 500,154 U.S. cases treated with PCI during July 2009 through the end of September 2010. Inappropriate cases were defined as situations where expected negative consequences exceeded expected benefits.

PCI performed for an acute problem (such as high-risk unstable angina or MI) occurred in 71% of the cases. In this group, 99% of the cases were rated as appropriate, 1% as inappropriate, and fewer than 1% as uncertain. The remaining 29% of PCI procedures occurred in elective cases, of which 50% were rated as appropriate, 12% as inappropriate, and 38% as uncertain, Dr. Chan reported.

The three most common reasons for rating a case as inappropriate included patients with no ischemia, patients with mild ischemia, and asymptomatic patients, he said in an interview.

To address this issue, the ACC should develop a "real-time decision aid" to encourage interventionalists to "take a step back" during a catheterization to review a patient’s history and make a more informed decision on the need for PCI. The interventional cardiologist should review the degree of symptoms a patient has had and the evidence of ischemia, and take those findings into account when deciding whether the patient needs PCI.

Dr. Chan and Dr. McNulty said they had no disclosures.

NEW ORLEANS – About 12% of the more than 140,000 Americans who underwent elective coronary artery stenting during 2009-2010 had an inappropriate procedure, based on an analysis of data from a national registry maintained by the American College of Cardiology.

In contrast, the rate of inappropriate procedures was 1% in the larger group of more than 355,000 patients who had an acute need for percutaneous coronary interventions (PCI) during the period studied, Dr. Paul S. Chan said at the annual meeting of the ACC.

The analysis also showed a striking hospital-to-hospital variation in the rate of elective PCI cases flagged as inappropriate. About 25% of the hospitals doing elective cases had a rate below 6%; another quarter had a rate of 17% or higher. Yet some hospitals had inappropriate rates that exceeded 30%.

Starting in May 2011, the ACC will start reporting data from this analysis to each of the more than 1,000 participating U.S. hospitals. By carefully reviewing cases that have been flagged as inappropriate, it is hoped that hospitals will learn from their mistakes and drive down the inappropriate rate, especially for elective PCIs, said Dr. Chan of Saint Luke’s Hospital in Kansas City, Mo.

The ACC collects the PCI data through the CathPCI portion of its National Cardiovascular Data Registry (NCDR). Dr. Chan and his associates rated each procedure they reviewed as appropriate, inappropriate, or uncertain based on comprehensive criteria established by an ACC expert panel (J. Am. Coll. Card. 2009;53:530-53).

"About 25% of the interventional cases in my practice would be categorized as inappropriate," commented Dr. Edward J. McNulty, an interventional cardiologist at Kaiser Permanente in San Francisco. "I get most of my patients from surgeons or other interventional cardiologists who feel the patients are too high risk. I do a lot of left main and multivessel PCI. There is no way that I can explain on the NCDR form why I consider these patients appropriate. The NCDR data don’t allow you to appreciate nuances. The criteria tend to penalize physicians who deviate from the average [by performing] complex cases."

Additionally, the way patients’ drug use gets recorded on the day of hospitalization is problematic, as patients may stop a chronically used drug on the day before entering the hospital and be erroneously recorded as not being on a therapy. Another issue is misclassification of symptoms, such as a patient who perceives ischemic chest pain as shortness of breath.

"I believe that inappropriate PCIs occur, and these results can certainly show signals. But within the ‘inappropriate’ procedures are some cases with mitigating circumstances," Dr. McNulty said in an interview.

The ACC expert panel published appropriateness criteria for 198 different clinical scenarios based on six separate clinical elements in February 2009. They applied the criteria to 500,154 U.S. cases treated with PCI during July 2009 through the end of September 2010. Inappropriate cases were defined as situations where expected negative consequences exceeded expected benefits.

PCI performed for an acute problem (such as high-risk unstable angina or MI) occurred in 71% of the cases. In this group, 99% of the cases were rated as appropriate, 1% as inappropriate, and fewer than 1% as uncertain. The remaining 29% of PCI procedures occurred in elective cases, of which 50% were rated as appropriate, 12% as inappropriate, and 38% as uncertain, Dr. Chan reported.

The three most common reasons for rating a case as inappropriate included patients with no ischemia, patients with mild ischemia, and asymptomatic patients, he said in an interview.

To address this issue, the ACC should develop a "real-time decision aid" to encourage interventionalists to "take a step back" during a catheterization to review a patient’s history and make a more informed decision on the need for PCI. The interventional cardiologist should review the degree of symptoms a patient has had and the evidence of ischemia, and take those findings into account when deciding whether the patient needs PCI.

Dr. Chan and Dr. McNulty said they had no disclosures.

NEW ORLEANS – About 12% of the more than 140,000 Americans who underwent elective coronary artery stenting during 2009-2010 had an inappropriate procedure, based on an analysis of data from a national registry maintained by the American College of Cardiology.

In contrast, the rate of inappropriate procedures was 1% in the larger group of more than 355,000 patients who had an acute need for percutaneous coronary interventions (PCI) during the period studied, Dr. Paul S. Chan said at the annual meeting of the ACC.

The analysis also showed a striking hospital-to-hospital variation in the rate of elective PCI cases flagged as inappropriate. About 25% of the hospitals doing elective cases had a rate below 6%; another quarter had a rate of 17% or higher. Yet some hospitals had inappropriate rates that exceeded 30%.

Starting in May 2011, the ACC will start reporting data from this analysis to each of the more than 1,000 participating U.S. hospitals. By carefully reviewing cases that have been flagged as inappropriate, it is hoped that hospitals will learn from their mistakes and drive down the inappropriate rate, especially for elective PCIs, said Dr. Chan of Saint Luke’s Hospital in Kansas City, Mo.

The ACC collects the PCI data through the CathPCI portion of its National Cardiovascular Data Registry (NCDR). Dr. Chan and his associates rated each procedure they reviewed as appropriate, inappropriate, or uncertain based on comprehensive criteria established by an ACC expert panel (J. Am. Coll. Card. 2009;53:530-53).

"About 25% of the interventional cases in my practice would be categorized as inappropriate," commented Dr. Edward J. McNulty, an interventional cardiologist at Kaiser Permanente in San Francisco. "I get most of my patients from surgeons or other interventional cardiologists who feel the patients are too high risk. I do a lot of left main and multivessel PCI. There is no way that I can explain on the NCDR form why I consider these patients appropriate. The NCDR data don’t allow you to appreciate nuances. The criteria tend to penalize physicians who deviate from the average [by performing] complex cases."

Additionally, the way patients’ drug use gets recorded on the day of hospitalization is problematic, as patients may stop a chronically used drug on the day before entering the hospital and be erroneously recorded as not being on a therapy. Another issue is misclassification of symptoms, such as a patient who perceives ischemic chest pain as shortness of breath.

"I believe that inappropriate PCIs occur, and these results can certainly show signals. But within the ‘inappropriate’ procedures are some cases with mitigating circumstances," Dr. McNulty said in an interview.

The ACC expert panel published appropriateness criteria for 198 different clinical scenarios based on six separate clinical elements in February 2009. They applied the criteria to 500,154 U.S. cases treated with PCI during July 2009 through the end of September 2010. Inappropriate cases were defined as situations where expected negative consequences exceeded expected benefits.

PCI performed for an acute problem (such as high-risk unstable angina or MI) occurred in 71% of the cases. In this group, 99% of the cases were rated as appropriate, 1% as inappropriate, and fewer than 1% as uncertain. The remaining 29% of PCI procedures occurred in elective cases, of which 50% were rated as appropriate, 12% as inappropriate, and 38% as uncertain, Dr. Chan reported.

The three most common reasons for rating a case as inappropriate included patients with no ischemia, patients with mild ischemia, and asymptomatic patients, he said in an interview.

To address this issue, the ACC should develop a "real-time decision aid" to encourage interventionalists to "take a step back" during a catheterization to review a patient’s history and make a more informed decision on the need for PCI. The interventional cardiologist should review the degree of symptoms a patient has had and the evidence of ischemia, and take those findings into account when deciding whether the patient needs PCI.

Dr. Chan and Dr. McNulty said they had no disclosures.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data supported performing coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan-Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only, according to Dr. Velaquez.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Dr. Velasquez.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG.

The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years. STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%).

Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data supported performing coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan-Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only, according to Dr. Velaquez.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Dr. Velasquez.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG.

The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years. STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%).

Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data supported performing coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan-Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only, according to Dr. Velaquez.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Dr. Velasquez.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG.

The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years. STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%).

Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW YORK – Outcomes for the MitraClip procedure were similar for cardiologists and cardiac surgeons in an ongoing study of "real-world" use of the percutaneous mitral valve repair system.

The EVEREST II Continued Access Study, known as REALISM, is a prospective, multicenter data analysis of outcomes with the investigational MitraClip System (Abbott), said Dr. Gorav Allawadi, a CT surgeon at the University of Virginia, Charlottesville.

A total of 433 patients were included in the 30-day follow-up analysis; 47 were treated by 6 cardiothoracic surgeons and 386 by interventional cardiologists. Both patient groups had a mean age over 70 years, two-thirds had NYHA Class III or IV, and over half had functional mitral regurgitation. More than half had coronary artery disease, and nearly two-thirds had atrial fibrillation.

MitraClip procedural results were similar for cardiothoracic surgeons and interventional cardiologists, although there was a trend for the surgeons to use more clips. A single clip was implanted in 49% of the surgeon-treated cohort and in 58% of those treated by interventional cardiologists. Two clips were used in 51% of patients treated by surgeons and in 36% of patients treated by interventional cardiologists. (Clips could not be deployed in 6% of the patients treated by interventional cardiologists.) Mean procedural times were similar, 135 minutes for the surgeons versus 145 minutes for the interventional cardiologists. Post-procedure hospital stays averaged 2.5 days in both groups; 90% of patients were discharged home without the need for home health care, Dr. Allawadi reported.

In-hospital complication rates were low and did not differ significantly between the groups. Deaths occurred in 2.1% of the surgeon-treated patients and in 3.4% of the interventional cardiologist-treated patients. Major stroke occurred in 1.3% in patients treated by interventional cardiologists and in none of the surgeon-treated patients.

Outcomes at 30 days were similar, with more than half of both groups achieving 1-plus mitral regurgitation status or better and 90% at 2-plus or below. Similarly, 85% of both groups had improved to NYHA class I or II by 30 days post-procedure.

Dr. Allawadi said that the similarity in outcomes should not discourage a multidisciplinary approach to the treatment of these patients. When the CT surgeon performs the MitraClip procedure at his institution, the cardiologist scrubs as well. And if the interventional cardiologist is doing the procedure, the surgeon is still closely involved.

In response to a question about why the surgeons tended to use more clips, he speculated that it might be because surgeons don’t have as much experience with the device as yet. "We’re still very much on the learning curve."

In May, Abbott undertook a voluntary global recall of MitraClip after receiving three reports of incidents where the radiopaque ring at the tip of the steerable guide catheter detached in the heart following implant. Abbott emphasized that the concern only involves delivery of the device and that patients with previously implanted MitraClip devices are not affected.

Abbott officials expect it will take several months to resume shipments of the system, which is marketed in Europe but is investigational in the U.S. The firm says the recall is not likely to impact anticipated U.S. approval of the device later this year, according to a report in "The Gray Sheet."

Dr. Allawadi disclosed consulting fees and honoraria from Abbott. ☐

Rebecca Kern of "The Gray Sheet" added to this article. "The Gray Sheet" and this publication are both owned by Elsevier.

NEW YORK – Outcomes for the MitraClip procedure were similar for cardiologists and cardiac surgeons in an ongoing study of "real-world" use of the percutaneous mitral valve repair system.

The EVEREST II Continued Access Study, known as REALISM, is a prospective, multicenter data analysis of outcomes with the investigational MitraClip System (Abbott), said Dr. Gorav Allawadi, a CT surgeon at the University of Virginia, Charlottesville.

A total of 433 patients were included in the 30-day follow-up analysis; 47 were treated by 6 cardiothoracic surgeons and 386 by interventional cardiologists. Both patient groups had a mean age over 70 years, two-thirds had NYHA Class III or IV, and over half had functional mitral regurgitation. More than half had coronary artery disease, and nearly two-thirds had atrial fibrillation.

MitraClip procedural results were similar for cardiothoracic surgeons and interventional cardiologists, although there was a trend for the surgeons to use more clips. A single clip was implanted in 49% of the surgeon-treated cohort and in 58% of those treated by interventional cardiologists. Two clips were used in 51% of patients treated by surgeons and in 36% of patients treated by interventional cardiologists. (Clips could not be deployed in 6% of the patients treated by interventional cardiologists.) Mean procedural times were similar, 135 minutes for the surgeons versus 145 minutes for the interventional cardiologists. Post-procedure hospital stays averaged 2.5 days in both groups; 90% of patients were discharged home without the need for home health care, Dr. Allawadi reported.

In-hospital complication rates were low and did not differ significantly between the groups. Deaths occurred in 2.1% of the surgeon-treated patients and in 3.4% of the interventional cardiologist-treated patients. Major stroke occurred in 1.3% in patients treated by interventional cardiologists and in none of the surgeon-treated patients.

Outcomes at 30 days were similar, with more than half of both groups achieving 1-plus mitral regurgitation status or better and 90% at 2-plus or below. Similarly, 85% of both groups had improved to NYHA class I or II by 30 days post-procedure.

Dr. Allawadi said that the similarity in outcomes should not discourage a multidisciplinary approach to the treatment of these patients. When the CT surgeon performs the MitraClip procedure at his institution, the cardiologist scrubs as well. And if the interventional cardiologist is doing the procedure, the surgeon is still closely involved.

In response to a question about why the surgeons tended to use more clips, he speculated that it might be because surgeons don’t have as much experience with the device as yet. "We’re still very much on the learning curve."

In May, Abbott undertook a voluntary global recall of MitraClip after receiving three reports of incidents where the radiopaque ring at the tip of the steerable guide catheter detached in the heart following implant. Abbott emphasized that the concern only involves delivery of the device and that patients with previously implanted MitraClip devices are not affected.

Abbott officials expect it will take several months to resume shipments of the system, which is marketed in Europe but is investigational in the U.S. The firm says the recall is not likely to impact anticipated U.S. approval of the device later this year, according to a report in "The Gray Sheet."

Dr. Allawadi disclosed consulting fees and honoraria from Abbott. ☐

Rebecca Kern of "The Gray Sheet" added to this article. "The Gray Sheet" and this publication are both owned by Elsevier.

NEW YORK – Outcomes for the MitraClip procedure were similar for cardiologists and cardiac surgeons in an ongoing study of "real-world" use of the percutaneous mitral valve repair system.

The EVEREST II Continued Access Study, known as REALISM, is a prospective, multicenter data analysis of outcomes with the investigational MitraClip System (Abbott), said Dr. Gorav Allawadi, a CT surgeon at the University of Virginia, Charlottesville.

A total of 433 patients were included in the 30-day follow-up analysis; 47 were treated by 6 cardiothoracic surgeons and 386 by interventional cardiologists. Both patient groups had a mean age over 70 years, two-thirds had NYHA Class III or IV, and over half had functional mitral regurgitation. More than half had coronary artery disease, and nearly two-thirds had atrial fibrillation.

MitraClip procedural results were similar for cardiothoracic surgeons and interventional cardiologists, although there was a trend for the surgeons to use more clips. A single clip was implanted in 49% of the surgeon-treated cohort and in 58% of those treated by interventional cardiologists. Two clips were used in 51% of patients treated by surgeons and in 36% of patients treated by interventional cardiologists. (Clips could not be deployed in 6% of the patients treated by interventional cardiologists.) Mean procedural times were similar, 135 minutes for the surgeons versus 145 minutes for the interventional cardiologists. Post-procedure hospital stays averaged 2.5 days in both groups; 90% of patients were discharged home without the need for home health care, Dr. Allawadi reported.

In-hospital complication rates were low and did not differ significantly between the groups. Deaths occurred in 2.1% of the surgeon-treated patients and in 3.4% of the interventional cardiologist-treated patients. Major stroke occurred in 1.3% in patients treated by interventional cardiologists and in none of the surgeon-treated patients.

Outcomes at 30 days were similar, with more than half of both groups achieving 1-plus mitral regurgitation status or better and 90% at 2-plus or below. Similarly, 85% of both groups had improved to NYHA class I or II by 30 days post-procedure.

Dr. Allawadi said that the similarity in outcomes should not discourage a multidisciplinary approach to the treatment of these patients. When the CT surgeon performs the MitraClip procedure at his institution, the cardiologist scrubs as well. And if the interventional cardiologist is doing the procedure, the surgeon is still closely involved.

In response to a question about why the surgeons tended to use more clips, he speculated that it might be because surgeons don’t have as much experience with the device as yet. "We’re still very much on the learning curve."

In May, Abbott undertook a voluntary global recall of MitraClip after receiving three reports of incidents where the radiopaque ring at the tip of the steerable guide catheter detached in the heart following implant. Abbott emphasized that the concern only involves delivery of the device and that patients with previously implanted MitraClip devices are not affected.

Abbott officials expect it will take several months to resume shipments of the system, which is marketed in Europe but is investigational in the U.S. The firm says the recall is not likely to impact anticipated U.S. approval of the device later this year, according to a report in "The Gray Sheet."

Dr. Allawadi disclosed consulting fees and honoraria from Abbott. ☐

Rebecca Kern of "The Gray Sheet" added to this article. "The Gray Sheet" and this publication are both owned by Elsevier.

PHILADELPHIA – Outcomes following isolated coronary artery bypass surgery did not differ significantly based on the volume of such procedures that were performed by individual surgeons or at particular institutions in a study of more than 2,000 patients.

In the setting of a university-based, community-hospital, quality-improvement program, excellent surgical results can consistently be obtained even in relatively low-volume programs. Surgical outcomes are not associated with program or surgeon volume, but are directly correlated with focus on quality as manifested by compliance with evidence-based quality standards, according to the study’s lead investigator, Dr. Paul Kurlansky.

He and his colleagues from the Florida Heart Research Institute, Miami, studied 2,218 consecutive patients having isolated CABG from 2007 to 2009 in a university-based quality-improvement program that emphasized involvement of all surgeons in the academic quality endeavor. End points included operative mortality, major morbidity, and National Quality Forum (NQF)-endorsed process measures as defined by the Society of Thoracic Surgeons (STS).

Procedural volume was analyzed as a categorical and a continuous variable using general estimating equations that accounted for clustering effects and were adjusted for STS risk scores, as well as for propensity for operation in a low- vs. high-volume program, Dr. Kurlansky reported at the annual meeting of the American Association for Thoracic Surgery.

The annual program volume ranged from 67 to 292 procedures (median 136), and surgeon volume ranged from 1 to 124 procedures (median 58). Mortality among all hospitals was 0.8% (ranging from 0% to 2.23%); annual observed/expected mortality was 0.41% overall, ranging from 0% to 1.20%.

A comparison of low-volume (less than 200 cases/year) with high-volume centers (at least 200 cases/year) showed no significant difference in mortality (odds ratio 1.08), morbidity (OR 1.34), or any of the medication process measures.

In addition, there was no difference in mortality (OR 1.59), morbidity (OR 1.20), or medication failure (OR 0.57) between high- (at least 87 cases/year) and low-volume surgeons (less than 87 cases).

After adjusting for both STS risk score and for propensity score, the researchers found no association between either hospital or surgeon volume with regard to mortality or morbidity.

Lack of compliance with NQF measures, however, was significantly and highly predictive of morbidity (OR 1.51), regardless of volume, even after adjustment for predicted risk.

The findings indicate that outcome rather than volume is the metric by which cardiac surgical programs should be evaluated, according to Dr. Kurlansky. In addition, meaningful and active academic involvement may represent a new paradigm for the delivery of quality care at the community hospital level, he said.

"The quality process measures, I believe, are only a surrogate of the entire environment created by the academic affiliation, ones that shift the entire focus of the program toward accountability, education, and excellence: open disclosure, discussion of problems, awareness of advances, and striving toward excellence," he said in an interview.

The policy implications of this study are considerable. "The simple administrative approach of a volume threshold (such as that adopted by the Leapfrog group) may be completely inappropriate. Merely adding volume to a mediocre or poor program will only compound the problem, while potentially removing the excellent service provided to the patients of a high-performing, smaller program," he said.

Dr. Kurlansky pointed out that CABG surgery is unique in that it is a very mature, highly practiced, complex surgical procedure.

Dr. Kurlansky reported he had no disclosures relevant to this presentation. ☐

PHILADELPHIA – Outcomes following isolated coronary artery bypass surgery did not differ significantly based on the volume of such procedures that were performed by individual surgeons or at particular institutions in a study of more than 2,000 patients.

In the setting of a university-based, community-hospital, quality-improvement program, excellent surgical results can consistently be obtained even in relatively low-volume programs. Surgical outcomes are not associated with program or surgeon volume, but are directly correlated with focus on quality as manifested by compliance with evidence-based quality standards, according to the study’s lead investigator, Dr. Paul Kurlansky.

He and his colleagues from the Florida Heart Research Institute, Miami, studied 2,218 consecutive patients having isolated CABG from 2007 to 2009 in a university-based quality-improvement program that emphasized involvement of all surgeons in the academic quality endeavor. End points included operative mortality, major morbidity, and National Quality Forum (NQF)-endorsed process measures as defined by the Society of Thoracic Surgeons (STS).

Procedural volume was analyzed as a categorical and a continuous variable using general estimating equations that accounted for clustering effects and were adjusted for STS risk scores, as well as for propensity for operation in a low- vs. high-volume program, Dr. Kurlansky reported at the annual meeting of the American Association for Thoracic Surgery.

The annual program volume ranged from 67 to 292 procedures (median 136), and surgeon volume ranged from 1 to 124 procedures (median 58). Mortality among all hospitals was 0.8% (ranging from 0% to 2.23%); annual observed/expected mortality was 0.41% overall, ranging from 0% to 1.20%.

A comparison of low-volume (less than 200 cases/year) with high-volume centers (at least 200 cases/year) showed no significant difference in mortality (odds ratio 1.08), morbidity (OR 1.34), or any of the medication process measures.

In addition, there was no difference in mortality (OR 1.59), morbidity (OR 1.20), or medication failure (OR 0.57) between high- (at least 87 cases/year) and low-volume surgeons (less than 87 cases).

After adjusting for both STS risk score and for propensity score, the researchers found no association between either hospital or surgeon volume with regard to mortality or morbidity.

Lack of compliance with NQF measures, however, was significantly and highly predictive of morbidity (OR 1.51), regardless of volume, even after adjustment for predicted risk.

The findings indicate that outcome rather than volume is the metric by which cardiac surgical programs should be evaluated, according to Dr. Kurlansky. In addition, meaningful and active academic involvement may represent a new paradigm for the delivery of quality care at the community hospital level, he said.

"The quality process measures, I believe, are only a surrogate of the entire environment created by the academic affiliation, ones that shift the entire focus of the program toward accountability, education, and excellence: open disclosure, discussion of problems, awareness of advances, and striving toward excellence," he said in an interview.

The policy implications of this study are considerable. "The simple administrative approach of a volume threshold (such as that adopted by the Leapfrog group) may be completely inappropriate. Merely adding volume to a mediocre or poor program will only compound the problem, while potentially removing the excellent service provided to the patients of a high-performing, smaller program," he said.

Dr. Kurlansky pointed out that CABG surgery is unique in that it is a very mature, highly practiced, complex surgical procedure.

Dr. Kurlansky reported he had no disclosures relevant to this presentation. ☐

PHILADELPHIA – Outcomes following isolated coronary artery bypass surgery did not differ significantly based on the volume of such procedures that were performed by individual surgeons or at particular institutions in a study of more than 2,000 patients.

In the setting of a university-based, community-hospital, quality-improvement program, excellent surgical results can consistently be obtained even in relatively low-volume programs. Surgical outcomes are not associated with program or surgeon volume, but are directly correlated with focus on quality as manifested by compliance with evidence-based quality standards, according to the study’s lead investigator, Dr. Paul Kurlansky.

He and his colleagues from the Florida Heart Research Institute, Miami, studied 2,218 consecutive patients having isolated CABG from 2007 to 2009 in a university-based quality-improvement program that emphasized involvement of all surgeons in the academic quality endeavor. End points included operative mortality, major morbidity, and National Quality Forum (NQF)-endorsed process measures as defined by the Society of Thoracic Surgeons (STS).

Procedural volume was analyzed as a categorical and a continuous variable using general estimating equations that accounted for clustering effects and were adjusted for STS risk scores, as well as for propensity for operation in a low- vs. high-volume program, Dr. Kurlansky reported at the annual meeting of the American Association for Thoracic Surgery.

The annual program volume ranged from 67 to 292 procedures (median 136), and surgeon volume ranged from 1 to 124 procedures (median 58). Mortality among all hospitals was 0.8% (ranging from 0% to 2.23%); annual observed/expected mortality was 0.41% overall, ranging from 0% to 1.20%.

A comparison of low-volume (less than 200 cases/year) with high-volume centers (at least 200 cases/year) showed no significant difference in mortality (odds ratio 1.08), morbidity (OR 1.34), or any of the medication process measures.

In addition, there was no difference in mortality (OR 1.59), morbidity (OR 1.20), or medication failure (OR 0.57) between high- (at least 87 cases/year) and low-volume surgeons (less than 87 cases).

After adjusting for both STS risk score and for propensity score, the researchers found no association between either hospital or surgeon volume with regard to mortality or morbidity.

Lack of compliance with NQF measures, however, was significantly and highly predictive of morbidity (OR 1.51), regardless of volume, even after adjustment for predicted risk.

The findings indicate that outcome rather than volume is the metric by which cardiac surgical programs should be evaluated, according to Dr. Kurlansky. In addition, meaningful and active academic involvement may represent a new paradigm for the delivery of quality care at the community hospital level, he said.

"The quality process measures, I believe, are only a surrogate of the entire environment created by the academic affiliation, ones that shift the entire focus of the program toward accountability, education, and excellence: open disclosure, discussion of problems, awareness of advances, and striving toward excellence," he said in an interview.

The policy implications of this study are considerable. "The simple administrative approach of a volume threshold (such as that adopted by the Leapfrog group) may be completely inappropriate. Merely adding volume to a mediocre or poor program will only compound the problem, while potentially removing the excellent service provided to the patients of a high-performing, smaller program," he said.

Dr. Kurlansky pointed out that CABG surgery is unique in that it is a very mature, highly practiced, complex surgical procedure.

Dr. Kurlansky reported he had no disclosures relevant to this presentation. ☐

NEW ORLEANS – The durability and safety of treating mitral regurgitation with a percutaneous device as compared with that of surgical repair or replacement persisted at 2 years, based on an updated analysis of the EVEREST II trial results presented at the annual meeting of the American College of Cardiology.

"Our fundamental finding is that outcomes are very stable between 1 and 2 years of follow-up," Dr. Ted Feldman, principal investigator, announced at a press briefing. The 2-year follow-up results show both approaches reduced MR, and meaningful clinical benefits persisted, said Dr. Feldman of the NorthShore University HealthSystem in Evanston, Ill.

Clinical outcome measures at 2 years showed MR grade and left ventricular (LV) volumes remained stable between 1 and 2 years in both groups. The inter-group comparison showed a more favorable reduction in MR and a greater reduction in LV diastolic volume with surgery at 1 and 2 years, and no difference in systolic volume reduction. Also, NYHA functional class was stable between years 1 and 2. "Interestingly, the inter-group comparison showed a more favorable NYHA class outcome at both years with the clip," he reported.

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) is a prospective, multicenter, randomized controlled phase II trial comparing the safety and efficacy of the MitraClip System with mitral valve surgery in the treatment of MR. The study enrolled 279 patients with 3+ or 4+ MR who were either symptomatic or were asymptomatic with a baseline left ejection fraction of 60%. Approximately half of the patients had New York Heart Association (NYHA) functional class III or IV heart failure.

At the meeting, Dr. Feldman presented two analyses of the 2-year data. The composite primary efficacy endpoint was freedom from death, MV surgery for valve dysfunction (for device patients) or re-operation (for surgery patients), and MR greater than 2+ at 12 months.

In the intention-to-treat analysis, the primary composite endpoint was met at 2 years by 52% of the percutaneous group and by 66% of the surgery group; in the 1-year analysis, these figures were 55% and 73%, respectively.

More patients receiving the clip later underwent MV surgery (22%) compared to the few patients in the surgery arm who required re-operation (3.6%). There was no significant difference in mortality or recurrent MR.

In the second analysis, there was no statistical difference in the effectiveness endpoint between the two arms of the study. "When subsequent surgery within 90 days on device patients is considered a success, we see similarly stable results at 1 and 2 years," he noted.

In this analysis, the primary endpoint was met at 2 years by 63% of the percutaneous group and by 66% of the surgery group. By removing the subsequent need for MV surgery as an end point event, 6.2% of the percutaneous group and 3.6% of the surgery group had MV surgery or re-operation.

There was no difference in the Kaplan-Meier mortality plot for the intention-to-treat analysis at any time point, he stressed. At 1 year, 95% of the patients in each arm were alive; at 2 years, 91% of the surgery arm and 90% of the percutaneous arm were still alive.

Freedom from MV surgery/re-operation, however, favored the surgical arm: 96% versus 78% at 2 years. The "need for surgery in patients in the clip group was almost entirely in the first several months; after 6 months the curves overlapped at 1 and 2 years," he observed. "Importantly, 78% of device patients are free from MV surgery at 2 years." When early failures were excluded, there were no differences in need for MV surgery or reoperation.

At a press conference, Dr. Feldman explained that the two analyses "answer different questions." "The intention-to-treat analysis gives the patient the odds of success with the clip at the end of the year," he said. "It tells them that 78% will be free of the need for surgery at 2 years, and 97% will have NYHA functional class I or II."

The second analysis answers the question, ‘What if I am in the 20% needing surgery?’ It counts the combined strategy of the clip, with surgery as needed.

Dr. Feldman reported consulting and research monies from Abbott Vascular. ☐

NEW ORLEANS – The durability and safety of treating mitral regurgitation with a percutaneous device as compared with that of surgical repair or replacement persisted at 2 years, based on an updated analysis of the EVEREST II trial results presented at the annual meeting of the American College of Cardiology.

"Our fundamental finding is that outcomes are very stable between 1 and 2 years of follow-up," Dr. Ted Feldman, principal investigator, announced at a press briefing. The 2-year follow-up results show both approaches reduced MR, and meaningful clinical benefits persisted, said Dr. Feldman of the NorthShore University HealthSystem in Evanston, Ill.

Clinical outcome measures at 2 years showed MR grade and left ventricular (LV) volumes remained stable between 1 and 2 years in both groups. The inter-group comparison showed a more favorable reduction in MR and a greater reduction in LV diastolic volume with surgery at 1 and 2 years, and no difference in systolic volume reduction. Also, NYHA functional class was stable between years 1 and 2. "Interestingly, the inter-group comparison showed a more favorable NYHA class outcome at both years with the clip," he reported.

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) is a prospective, multicenter, randomized controlled phase II trial comparing the safety and efficacy of the MitraClip System with mitral valve surgery in the treatment of MR. The study enrolled 279 patients with 3+ or 4+ MR who were either symptomatic or were asymptomatic with a baseline left ejection fraction of 60%. Approximately half of the patients had New York Heart Association (NYHA) functional class III or IV heart failure.

At the meeting, Dr. Feldman presented two analyses of the 2-year data. The composite primary efficacy endpoint was freedom from death, MV surgery for valve dysfunction (for device patients) or re-operation (for surgery patients), and MR greater than 2+ at 12 months.

In the intention-to-treat analysis, the primary composite endpoint was met at 2 years by 52% of the percutaneous group and by 66% of the surgery group; in the 1-year analysis, these figures were 55% and 73%, respectively.

More patients receiving the clip later underwent MV surgery (22%) compared to the few patients in the surgery arm who required re-operation (3.6%). There was no significant difference in mortality or recurrent MR.

In the second analysis, there was no statistical difference in the effectiveness endpoint between the two arms of the study. "When subsequent surgery within 90 days on device patients is considered a success, we see similarly stable results at 1 and 2 years," he noted.

In this analysis, the primary endpoint was met at 2 years by 63% of the percutaneous group and by 66% of the surgery group. By removing the subsequent need for MV surgery as an end point event, 6.2% of the percutaneous group and 3.6% of the surgery group had MV surgery or re-operation.

There was no difference in the Kaplan-Meier mortality plot for the intention-to-treat analysis at any time point, he stressed. At 1 year, 95% of the patients in each arm were alive; at 2 years, 91% of the surgery arm and 90% of the percutaneous arm were still alive.

Freedom from MV surgery/re-operation, however, favored the surgical arm: 96% versus 78% at 2 years. The "need for surgery in patients in the clip group was almost entirely in the first several months; after 6 months the curves overlapped at 1 and 2 years," he observed. "Importantly, 78% of device patients are free from MV surgery at 2 years." When early failures were excluded, there were no differences in need for MV surgery or reoperation.

At a press conference, Dr. Feldman explained that the two analyses "answer different questions." "The intention-to-treat analysis gives the patient the odds of success with the clip at the end of the year," he said. "It tells them that 78% will be free of the need for surgery at 2 years, and 97% will have NYHA functional class I or II."

The second analysis answers the question, ‘What if I am in the 20% needing surgery?’ It counts the combined strategy of the clip, with surgery as needed.

Dr. Feldman reported consulting and research monies from Abbott Vascular. ☐

NEW ORLEANS – The durability and safety of treating mitral regurgitation with a percutaneous device as compared with that of surgical repair or replacement persisted at 2 years, based on an updated analysis of the EVEREST II trial results presented at the annual meeting of the American College of Cardiology.

"Our fundamental finding is that outcomes are very stable between 1 and 2 years of follow-up," Dr. Ted Feldman, principal investigator, announced at a press briefing. The 2-year follow-up results show both approaches reduced MR, and meaningful clinical benefits persisted, said Dr. Feldman of the NorthShore University HealthSystem in Evanston, Ill.

Clinical outcome measures at 2 years showed MR grade and left ventricular (LV) volumes remained stable between 1 and 2 years in both groups. The inter-group comparison showed a more favorable reduction in MR and a greater reduction in LV diastolic volume with surgery at 1 and 2 years, and no difference in systolic volume reduction. Also, NYHA functional class was stable between years 1 and 2. "Interestingly, the inter-group comparison showed a more favorable NYHA class outcome at both years with the clip," he reported.

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) is a prospective, multicenter, randomized controlled phase II trial comparing the safety and efficacy of the MitraClip System with mitral valve surgery in the treatment of MR. The study enrolled 279 patients with 3+ or 4+ MR who were either symptomatic or were asymptomatic with a baseline left ejection fraction of 60%. Approximately half of the patients had New York Heart Association (NYHA) functional class III or IV heart failure.

At the meeting, Dr. Feldman presented two analyses of the 2-year data. The composite primary efficacy endpoint was freedom from death, MV surgery for valve dysfunction (for device patients) or re-operation (for surgery patients), and MR greater than 2+ at 12 months.

In the intention-to-treat analysis, the primary composite endpoint was met at 2 years by 52% of the percutaneous group and by 66% of the surgery group; in the 1-year analysis, these figures were 55% and 73%, respectively.

More patients receiving the clip later underwent MV surgery (22%) compared to the few patients in the surgery arm who required re-operation (3.6%). There was no significant difference in mortality or recurrent MR.

In the second analysis, there was no statistical difference in the effectiveness endpoint between the two arms of the study. "When subsequent surgery within 90 days on device patients is considered a success, we see similarly stable results at 1 and 2 years," he noted.

In this analysis, the primary endpoint was met at 2 years by 63% of the percutaneous group and by 66% of the surgery group. By removing the subsequent need for MV surgery as an end point event, 6.2% of the percutaneous group and 3.6% of the surgery group had MV surgery or re-operation.

There was no difference in the Kaplan-Meier mortality plot for the intention-to-treat analysis at any time point, he stressed. At 1 year, 95% of the patients in each arm were alive; at 2 years, 91% of the surgery arm and 90% of the percutaneous arm were still alive.

Freedom from MV surgery/re-operation, however, favored the surgical arm: 96% versus 78% at 2 years. The "need for surgery in patients in the clip group was almost entirely in the first several months; after 6 months the curves overlapped at 1 and 2 years," he observed. "Importantly, 78% of device patients are free from MV surgery at 2 years." When early failures were excluded, there were no differences in need for MV surgery or reoperation.

At a press conference, Dr. Feldman explained that the two analyses "answer different questions." "The intention-to-treat analysis gives the patient the odds of success with the clip at the end of the year," he said. "It tells them that 78% will be free of the need for surgery at 2 years, and 97% will have NYHA functional class I or II."

The second analysis answers the question, ‘What if I am in the 20% needing surgery?’ It counts the combined strategy of the clip, with surgery as needed.

Dr. Feldman reported consulting and research monies from Abbott Vascular. ☐

The first-ever AATS Mitral Conclave was held on May 5^th and 6^th. The world’s leading experts in mitral valve disease convened to discuss management guidelines, imaging, pathology, minimally invasive procedures, percutaneous approaches, surgical techniques, devices, and long-term results.

"With 39 faculty and 250 presentations, including selected abstracts and videos, our goal was to have a comprehensive meeting focused on mitral valve disease that would allow attendees to gain exposure to all of the common approaches used in the top centers throughout the world," said Program Director David H. Adams, MD. "We continue to see tremendous progress in our understanding of mitral disease intervention, and a great interest among surgeons in learning and advancing mitral valve repair strategies," said Dr. Adams, chairman of the department of cardiothoracic surgery at the Mount Sinai Medical Center, New York.

More than 1,000 individuals – including about 800 physicians – from 66 countries participated. Industry support was provided by Edwards Lifesciences LLC (Premier Platinum), Metronic, Inc. (Platinum), Abbott Vascular (Gold), Sorin Heart Valves (Gold), and St. Jude Medical Inc. (Bronze).

"I figured we might get 250 physicians, and would have considered that a success. This is fantastic," said AATS President Irving L. Kron, MD.

Presentations included lectures, expert video sessions, and "Presentations on Demand," accessible on video screens positioned in the exhibit hall. In a plenary address, Robert O. Bonow, MD, said that current valvular heart disease guidelines are based largely on expert opinion rather than evidence from clinical trials. Referring to the 2008 revised joint guidelines from the American College of Cardiology/American Heart Association and the 2007 European Society of Cardiology guidelines, he said, "Unfortunately, the evidence base underpinning them is limited by an inadequate number of randomized clinical trials. We really need to provide more evidence-based information to devise true guidelines and performance measures."

The question of whether mitral valve repair should be considered in all patients with severe mitral valve regurgitation is still being debated.

"It’s at least likely that certain patient subsets would benefit, but current data are insufficient to determine which ones," said Dr. Bonow, of Northwestern University. As an example of ambiguity, U.S. guidelines recommend that patients considered eligible for repair be referred to an "experienced center," but don’t provide criteria for determining that status. Moreover, individual surgeon volume and experience clearly predict successful mitral repair outcomes, even within one institution.

Dr. Bonow is optimistic that useful data will come from two ongoing trials sponsored by the National Heart, Lung, and Blood Institute via the Cardiothoracic Surgical Trials Network.

Dr. Adams presented the Mitral Conclave Career Achievement Award to the legendary Alain F. Carpentier, MD, whose 1983 landmark paper, "Cardiac Valve Surgery – the ‘French Correction,’ " is credited with heralding the modern era of mitral valve reconstructive surgery. Professor Carpentier delivered the Conclave Honored Lecture.

A series of "mini debates" addressed controversies surrounding the use of annuloplasty rings (flexible versus remodeling versus no ring at all), minimally invasive surgery (for all patients versus for some), and the correct approach for specific clinical scenarios of tricuspid valve disease.

The next Aortic Symposium will be held April 26-27, 2012, and the next Mitral Conclave will take place May 2-3, 2013, both in New York. Proceedings from the 2011 Mitral Conclave will be published in an upcoming supplement to The Journal of Thoracic and Cardiovascular Surgery.n

The first-ever AATS Mitral Conclave was held on May 5^th and 6^th. The world’s leading experts in mitral valve disease convened to discuss management guidelines, imaging, pathology, minimally invasive procedures, percutaneous approaches, surgical techniques, devices, and long-term results.

"With 39 faculty and 250 presentations, including selected abstracts and videos, our goal was to have a comprehensive meeting focused on mitral valve disease that would allow attendees to gain exposure to all of the common approaches used in the top centers throughout the world," said Program Director David H. Adams, MD. "We continue to see tremendous progress in our understanding of mitral disease intervention, and a great interest among surgeons in learning and advancing mitral valve repair strategies," said Dr. Adams, chairman of the department of cardiothoracic surgery at the Mount Sinai Medical Center, New York.

More than 1,000 individuals – including about 800 physicians – from 66 countries participated. Industry support was provided by Edwards Lifesciences LLC (Premier Platinum), Metronic, Inc. (Platinum), Abbott Vascular (Gold), Sorin Heart Valves (Gold), and St. Jude Medical Inc. (Bronze).

"I figured we might get 250 physicians, and would have considered that a success. This is fantastic," said AATS President Irving L. Kron, MD.

Presentations included lectures, expert video sessions, and "Presentations on Demand," accessible on video screens positioned in the exhibit hall. In a plenary address, Robert O. Bonow, MD, said that current valvular heart disease guidelines are based largely on expert opinion rather than evidence from clinical trials. Referring to the 2008 revised joint guidelines from the American College of Cardiology/American Heart Association and the 2007 European Society of Cardiology guidelines, he said, "Unfortunately, the evidence base underpinning them is limited by an inadequate number of randomized clinical trials. We really need to provide more evidence-based information to devise true guidelines and performance measures."

The question of whether mitral valve repair should be considered in all patients with severe mitral valve regurgitation is still being debated.

"It’s at least likely that certain patient subsets would benefit, but current data are insufficient to determine which ones," said Dr. Bonow, of Northwestern University. As an example of ambiguity, U.S. guidelines recommend that patients considered eligible for repair be referred to an "experienced center," but don’t provide criteria for determining that status. Moreover, individual surgeon volume and experience clearly predict successful mitral repair outcomes, even within one institution.

Dr. Bonow is optimistic that useful data will come from two ongoing trials sponsored by the National Heart, Lung, and Blood Institute via the Cardiothoracic Surgical Trials Network.

Dr. Adams presented the Mitral Conclave Career Achievement Award to the legendary Alain F. Carpentier, MD, whose 1983 landmark paper, "Cardiac Valve Surgery – the ‘French Correction,’ " is credited with heralding the modern era of mitral valve reconstructive surgery. Professor Carpentier delivered the Conclave Honored Lecture.

A series of "mini debates" addressed controversies surrounding the use of annuloplasty rings (flexible versus remodeling versus no ring at all), minimally invasive surgery (for all patients versus for some), and the correct approach for specific clinical scenarios of tricuspid valve disease.

The next Aortic Symposium will be held April 26-27, 2012, and the next Mitral Conclave will take place May 2-3, 2013, both in New York. Proceedings from the 2011 Mitral Conclave will be published in an upcoming supplement to The Journal of Thoracic and Cardiovascular Surgery.n

The first-ever AATS Mitral Conclave was held on May 5^th and 6^th. The world’s leading experts in mitral valve disease convened to discuss management guidelines, imaging, pathology, minimally invasive procedures, percutaneous approaches, surgical techniques, devices, and long-term results.

"With 39 faculty and 250 presentations, including selected abstracts and videos, our goal was to have a comprehensive meeting focused on mitral valve disease that would allow attendees to gain exposure to all of the common approaches used in the top centers throughout the world," said Program Director David H. Adams, MD. "We continue to see tremendous progress in our understanding of mitral disease intervention, and a great interest among surgeons in learning and advancing mitral valve repair strategies," said Dr. Adams, chairman of the department of cardiothoracic surgery at the Mount Sinai Medical Center, New York.

More than 1,000 individuals – including about 800 physicians – from 66 countries participated. Industry support was provided by Edwards Lifesciences LLC (Premier Platinum), Metronic, Inc. (Platinum), Abbott Vascular (Gold), Sorin Heart Valves (Gold), and St. Jude Medical Inc. (Bronze).

"I figured we might get 250 physicians, and would have considered that a success. This is fantastic," said AATS President Irving L. Kron, MD.

Presentations included lectures, expert video sessions, and "Presentations on Demand," accessible on video screens positioned in the exhibit hall. In a plenary address, Robert O. Bonow, MD, said that current valvular heart disease guidelines are based largely on expert opinion rather than evidence from clinical trials. Referring to the 2008 revised joint guidelines from the American College of Cardiology/American Heart Association and the 2007 European Society of Cardiology guidelines, he said, "Unfortunately, the evidence base underpinning them is limited by an inadequate number of randomized clinical trials. We really need to provide more evidence-based information to devise true guidelines and performance measures."

The question of whether mitral valve repair should be considered in all patients with severe mitral valve regurgitation is still being debated.

"It’s at least likely that certain patient subsets would benefit, but current data are insufficient to determine which ones," said Dr. Bonow, of Northwestern University. As an example of ambiguity, U.S. guidelines recommend that patients considered eligible for repair be referred to an "experienced center," but don’t provide criteria for determining that status. Moreover, individual surgeon volume and experience clearly predict successful mitral repair outcomes, even within one institution.

Dr. Bonow is optimistic that useful data will come from two ongoing trials sponsored by the National Heart, Lung, and Blood Institute via the Cardiothoracic Surgical Trials Network.

Dr. Adams presented the Mitral Conclave Career Achievement Award to the legendary Alain F. Carpentier, MD, whose 1983 landmark paper, "Cardiac Valve Surgery – the ‘French Correction,’ " is credited with heralding the modern era of mitral valve reconstructive surgery. Professor Carpentier delivered the Conclave Honored Lecture.

A series of "mini debates" addressed controversies surrounding the use of annuloplasty rings (flexible versus remodeling versus no ring at all), minimally invasive surgery (for all patients versus for some), and the correct approach for specific clinical scenarios of tricuspid valve disease.

The next Aortic Symposium will be held April 26-27, 2012, and the next Mitral Conclave will take place May 2-3, 2013, both in New York. Proceedings from the 2011 Mitral Conclave will be published in an upcoming supplement to The Journal of Thoracic and Cardiovascular Surgery.n

The Cardiothoracic Surgery Research Program is an intramural research program within the National Heart, Lung, and Blood Institute at the NIH in Bethesda Md. The Director of the laboratory is Dr. Keith A. Horvath,

Currently the program focuses on three major research areas, represented by sections: cell-based therapy, bioengineering, and transplantation. In their 2010 quadrennial report, the group detailed 4 years of significant translational research"representing the return of cardiothoracic research to the NHLBI after a hiatus since 1990," according to Dr. Horvath.

The Cellular Biology Section is focused on cell-based therapy for myocardial ischemia using adult bone-marrow-derived mesenchymal stem cells (BMSCs).

Their research aims are focused on a large animal model to test the effects of BMSCs on chronic myocardial ischemia, to study the fate and differentiation of BMSCs after administration, and to further investigate gene expression patterns of BMSCs under both normoxic and hypoxic conditions.

The group has already demonstrated the benefits of direct injection of autologous BMSCs in to chronically ischemic myocardium.

Direct injection of autologous BMSCs into the ischemic myocardium showed regional ventricular wall thickening demonstrating significant improvement after cell treatment, whereas saline treated animals showed no improvement compared to baseline as assessed by echocardiography.

Global function was also improved following BMSC injection and increased vascularity was found in the BMSC group compared to saline injected controls.

BMSCs isolated from transgenic pigs designed to express enhanced green fluorescent proteins as the donors showed that allogeneic injection of the green BMSCs is safe, with no observable side effects or signs of graft versus host disease were observed.

The green cells were found migrating from the injected area into deeper layers of myocardium over the course of 1 to 6 weeks. By immunofluorescent staining, the green cells were associated with smooth muscle actin or vWF positive cells, suggesting that the transplanted cells were contributing to the formation of new vessels.

They found no evidence that these cells were associated with the new generation of cardiac myocytes, which suggests that the benefits of this therapy may be due to angiogenesis not the regeneration of cardiac myocytes. Gene profiling of the cells before and after transplantation showed that genes such as VEGF, HIF1-a, PDGF, ANGPT2 and CXCL14 were significantly up-regulated.

A clinical trial will be conducted at the NIH Heart Center at Suburban Hospital, Bethesda, and will follow the direct injection of BSMCs into ischemic areas in patients after coronary artery bypass grafting (CABG) or transmyocardial revascularization.

The Transplantation Section at CSRP has focused on developing a clinically relevant large animal cardiac xenotransplantation model, using genetically engineered pig hearts place in baboons.

Efforts are being focused on appropriate immunosuppression through drugs, stem cell, and genetic-engineering of donor hearts. These research efforts involve a working collaboration with Mayo Clinic, University of Pittsburgh, University of Maryland, Beth Israel Hospital, NIH Swine Center in Missouri, and Revivicor.

The Bioengineering Section is focused on developing and applying engineering technologies with devices, imaging and robotics with the goal of achieving "state-of-the-art minimally invasive cardiac operations.

"By enhancing precision and consistency, these novel procedures will improve clinical outcomes and expand the cohort of patients that can be treated."

The current work focuses on beating heart aortic valve replacement under real-time MRI guidance. Feasibility studies have been completed and long term animal studies are underway.

Active and passive markers have been added to the prostheses and delivery device to aid visualization and allow placement of the valve with the precision achieved in an open surgical procedure in 1/100th the time. The current goal is to translate this work into a clinical trial.

This column will keep track of these and other research efforts conducted by the CSRP, especially as they move from preclinical to clinical applications of their advanced research.☐

The Cardiothoracic Surgery Research Program is an intramural research program within the National Heart, Lung, and Blood Institute at the NIH in Bethesda Md. The Director of the laboratory is Dr. Keith A. Horvath,

Currently the program focuses on three major research areas, represented by sections: cell-based therapy, bioengineering, and transplantation. In their 2010 quadrennial report, the group detailed 4 years of significant translational research"representing the return of cardiothoracic research to the NHLBI after a hiatus since 1990," according to Dr. Horvath.

The Cellular Biology Section is focused on cell-based therapy for myocardial ischemia using adult bone-marrow-derived mesenchymal stem cells (BMSCs).

Their research aims are focused on a large animal model to test the effects of BMSCs on chronic myocardial ischemia, to study the fate and differentiation of BMSCs after administration, and to further investigate gene expression patterns of BMSCs under both normoxic and hypoxic conditions.

The group has already demonstrated the benefits of direct injection of autologous BMSCs in to chronically ischemic myocardium.

Direct injection of autologous BMSCs into the ischemic myocardium showed regional ventricular wall thickening demonstrating significant improvement after cell treatment, whereas saline treated animals showed no improvement compared to baseline as assessed by echocardiography.

Global function was also improved following BMSC injection and increased vascularity was found in the BMSC group compared to saline injected controls.

BMSCs isolated from transgenic pigs designed to express enhanced green fluorescent proteins as the donors showed that allogeneic injection of the green BMSCs is safe, with no observable side effects or signs of graft versus host disease were observed.

The green cells were found migrating from the injected area into deeper layers of myocardium over the course of 1 to 6 weeks. By immunofluorescent staining, the green cells were associated with smooth muscle actin or vWF positive cells, suggesting that the transplanted cells were contributing to the formation of new vessels.

They found no evidence that these cells were associated with the new generation of cardiac myocytes, which suggests that the benefits of this therapy may be due to angiogenesis not the regeneration of cardiac myocytes. Gene profiling of the cells before and after transplantation showed that genes such as VEGF, HIF1-a, PDGF, ANGPT2 and CXCL14 were significantly up-regulated.

A clinical trial will be conducted at the NIH Heart Center at Suburban Hospital, Bethesda, and will follow the direct injection of BSMCs into ischemic areas in patients after coronary artery bypass grafting (CABG) or transmyocardial revascularization.

The Transplantation Section at CSRP has focused on developing a clinically relevant large animal cardiac xenotransplantation model, using genetically engineered pig hearts place in baboons.

Efforts are being focused on appropriate immunosuppression through drugs, stem cell, and genetic-engineering of donor hearts. These research efforts involve a working collaboration with Mayo Clinic, University of Pittsburgh, University of Maryland, Beth Israel Hospital, NIH Swine Center in Missouri, and Revivicor.

The Bioengineering Section is focused on developing and applying engineering technologies with devices, imaging and robotics with the goal of achieving "state-of-the-art minimally invasive cardiac operations.

"By enhancing precision and consistency, these novel procedures will improve clinical outcomes and expand the cohort of patients that can be treated."

The current work focuses on beating heart aortic valve replacement under real-time MRI guidance. Feasibility studies have been completed and long term animal studies are underway.

Active and passive markers have been added to the prostheses and delivery device to aid visualization and allow placement of the valve with the precision achieved in an open surgical procedure in 1/100th the time. The current goal is to translate this work into a clinical trial.

This column will keep track of these and other research efforts conducted by the CSRP, especially as they move from preclinical to clinical applications of their advanced research.☐

The Cardiothoracic Surgery Research Program is an intramural research program within the National Heart, Lung, and Blood Institute at the NIH in Bethesda Md. The Director of the laboratory is Dr. Keith A. Horvath,

Currently the program focuses on three major research areas, represented by sections: cell-based therapy, bioengineering, and transplantation. In their 2010 quadrennial report, the group detailed 4 years of significant translational research"representing the return of cardiothoracic research to the NHLBI after a hiatus since 1990," according to Dr. Horvath.

The Cellular Biology Section is focused on cell-based therapy for myocardial ischemia using adult bone-marrow-derived mesenchymal stem cells (BMSCs).

Their research aims are focused on a large animal model to test the effects of BMSCs on chronic myocardial ischemia, to study the fate and differentiation of BMSCs after administration, and to further investigate gene expression patterns of BMSCs under both normoxic and hypoxic conditions.

The group has already demonstrated the benefits of direct injection of autologous BMSCs in to chronically ischemic myocardium.

Direct injection of autologous BMSCs into the ischemic myocardium showed regional ventricular wall thickening demonstrating significant improvement after cell treatment, whereas saline treated animals showed no improvement compared to baseline as assessed by echocardiography.

Global function was also improved following BMSC injection and increased vascularity was found in the BMSC group compared to saline injected controls.

BMSCs isolated from transgenic pigs designed to express enhanced green fluorescent proteins as the donors showed that allogeneic injection of the green BMSCs is safe, with no observable side effects or signs of graft versus host disease were observed.

The green cells were found migrating from the injected area into deeper layers of myocardium over the course of 1 to 6 weeks. By immunofluorescent staining, the green cells were associated with smooth muscle actin or vWF positive cells, suggesting that the transplanted cells were contributing to the formation of new vessels.

They found no evidence that these cells were associated with the new generation of cardiac myocytes, which suggests that the benefits of this therapy may be due to angiogenesis not the regeneration of cardiac myocytes. Gene profiling of the cells before and after transplantation showed that genes such as VEGF, HIF1-a, PDGF, ANGPT2 and CXCL14 were significantly up-regulated.

A clinical trial will be conducted at the NIH Heart Center at Suburban Hospital, Bethesda, and will follow the direct injection of BSMCs into ischemic areas in patients after coronary artery bypass grafting (CABG) or transmyocardial revascularization.

The Transplantation Section at CSRP has focused on developing a clinically relevant large animal cardiac xenotransplantation model, using genetically engineered pig hearts place in baboons.

Efforts are being focused on appropriate immunosuppression through drugs, stem cell, and genetic-engineering of donor hearts. These research efforts involve a working collaboration with Mayo Clinic, University of Pittsburgh, University of Maryland, Beth Israel Hospital, NIH Swine Center in Missouri, and Revivicor.

The Bioengineering Section is focused on developing and applying engineering technologies with devices, imaging and robotics with the goal of achieving "state-of-the-art minimally invasive cardiac operations.

"By enhancing precision and consistency, these novel procedures will improve clinical outcomes and expand the cohort of patients that can be treated."

The current work focuses on beating heart aortic valve replacement under real-time MRI guidance. Feasibility studies have been completed and long term animal studies are underway.

Active and passive markers have been added to the prostheses and delivery device to aid visualization and allow placement of the valve with the precision achieved in an open surgical procedure in 1/100th the time. The current goal is to translate this work into a clinical trial.

This column will keep track of these and other research efforts conducted by the CSRP, especially as they move from preclinical to clinical applications of their advanced research.☐