Thoracic Surgery News (Archived)

It should not come as a surprise that approximately half of the acute coronary syndromes that recur within 3 years of an index ACS treated percutaneously involve a different lesion that was visualized on angiography at that time but was not severe enough to require treatment, as has been recently reported in the New England Journal of Medicine.

“Pathologic studies … have illustrated that plaques when ruptured were substantially bulky and associated with thin fibrous caps. These lesions at the time of diagnosis may not have been sizable but grow at a faster rate to become eligible for rupture,” Dr. Jagat Narula, who is chief of cardiology at the University of California in Irvine, said in an interview.

The bigger question concerns the potential role for newly available radiofrequency intravascular ultrasonography (RF IVUS) in early assessment of patients with ACS.

The study in question showed that the rate of recurrent major adverse cardiovascular events was 20% in this multicenter prospective study involving 697 patients with ACS who were successfully treated with PCI and medical therapy, then followed for 3 years, reported Dr. Gregg W. Stone of Columbia University Medical Center/New York Presbyterian Hospital and the Cardiovascular Research Foundation, New York, and his associates.

The Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study was conducted at 37 medical centers in the United States and Europe.

Study subjects were enrolled after undergoing successful and uncomplicated PCI for all coronary lesions thought to be responsible for their index ACS. At that time, the subjects underwent angiography, then conventional gray-scale intravascular ultrasonography and the newly available RF IVUS of the left main coronary artery and the proximal 6-8 cm of each of the major epicardial coronary arteries.

The median age of the study subjects was 58 years; 24% were women, and 17% had diabetes.

“We found that approximately one in five patients with [ACS] ... had recurrent major adverse cardiovascular events within 3 years. Events were nearly equally divided between those related to initially treated lesions and those related to previously untreated lesions,” Dr. Stone and his colleagues said.

“Most events were rehospitalizations for unstable or progressive angina; death from cardiac causes, cardiac arrest, and MI were less common,” they noted.

“Despite [certain] caveats, PROSPECT study has contributed immensely to understanding plaque anatomy, plaque composition and the prognostic relevance of the atherosclerotic lesions,” said Dr. Narula.

RF IVUS at baseline revealed that most of the “nonculprit” coronary lesions - those that had been considered mild on the index angiography and were not treated at that time - were characterized by a large plaque burden, a small luminal area, or both. Half of them also were thin-cap fibroatheromas. These traits had not been visible on conventional angiography.

“I think the major message is that the angiogram is a very poor discriminator of how much atherosclerosis is present and which type of atherosclerosis is going to go on and cause unexpected events,” Dr. Stone said in an interview. “Radiofrequency IVUS provides significantly more information than just regular gray-scale IVUS in helping differentiate the nature of these plaques and which ones are going to progress.”

Conventional gray-scale IVUS works by sending out ultrasound waves and the resulting reflection signal can reveal structural information. Gray-scale IVUS measures only the amplitude of the reflected waves. However, RF IVUS also interprets frequency information from the reflected waves.

“That radiofrequency signal has been mapped pixel by pixel to actual histology from human pathologic specimens.” So a four-color coded map with four different types of tissue can be created to map plaque composition.

“RF IVUS has a much higher signal-to-noise ratio because it's a catheter that is right next to the coronary plaque. So the resolution is much greater and you can see plaque composition the way that noninvasive modalities currently can't,” Dr. Stone said.

However, “there are several reasons why the methods we have used are not currently suitable for clinical application as a means of identifying sites in the coronary vasculature for potential intervention,” the investigators noted (N. Engl. J. Med. 2011:364:226-35).

First, this method lacks specificity at present. RF IVUS identified a total of 595 thin-cap atheromas in these subjects, but only 26 of them caused recurrent ACS. Similarly, fewer than 10% of the lesions that carried plaque burdens of 70% or more and the lesions with a 4-mm or smaller luminal area caused recurrent ACS.

“Even when all three predictive variables were present, the event rate rose to only 18%,” they said.

Second, catheters used for this type of ultrasonography could only access the proximal 6-8 cm of the coronary tree. This meant that only 51 of the 106 “nonculprit” lesions seen on angiography could be evaluated by RF IVUS.

Third, the technique was associated with very serious adverse events in 11 patients in this study: 10 coronary dissections and 1 perforation, which in turn caused 4 nonfatal MIs.

While the ability of RF IVUS to assess luminal stenosis, plaque burden and positive remodeling is a useful tool, there are other diagnostic modalities to consider as well, said Dr. Narula. “Optical coherence tomography is the only technique that may accurately measure the cap thickness [and] CT angiography allows an assessment of both positive remodeling and the magnitude of necrotic cores.”

Intravascular optical coherence tomography (OCT) is similar to IVUS but light is used instead and resolution is greater. OCT uses a single fiberoptic wire that emits light and records the reflection as it is rotated and pulled back along the artery. OCT can be used to guide interventions, assess the lumen, visualize thrombi and dissections. It can also allow physicians to evaluate lesion cap thickness.

The advent of multislice CT - 264 slices and even greater - offers better and better resolution for non-invasive CT angiography. CTA can identify the presence of positive vessel remodeling and low-attenuation plaques, which along with a necrotic core, are thought to be associated with subsequent plaque rupture.

In the PROSPECT study, they also found that no major events arose from arterial segments with a plaque burden that blocked less than 40% of the lumen. And nonfibroatheromas rarely caused such events, regardless of their plaque burden or the luminal area they blocked.

These study findings suggest that thin-cap fibroatheromas, lesions with a large plaque burden, and lesions with a small luminal area are particularly prone to cause recurrent ACS.

For now though, the early identification of such lesions needs to be validated in randomized trials and is limited by unclear therapeutical options.

“We need to answer two questions,” said Dr. Narula. “First, can we define the high-risk lesions especially when of intermediate angiographic severity? Second, even if it is possible, are we justified in recommending widespread imaging studies, especially when only a small fraction of nonculprit vessel plaques progress to acute events … plaques form, rupture, and heal all the time, and it would be difficult to precisely identify a high-risk plaque associated with a major event, let alone identify it in a treatable proximity to an event.”

Dr. Stone agreed. “We haven't yet done the randomized trials to say that if we find one of these lesions that the patients are better off if we then treat them. If so, what do we treat them with?”

“For now, statins remain the cornerstone of management of the non-obstructive disease. Whether new agents targeted at inflammation … or non-injurious stent implantation become worthy of clinical application, would depend upon the capability of imaging techniques to identify temporo-spatial proclivity of lesions for the occurrence of events, as also the demonstration of the virtue and benign nature of the intervention,” said Dr. Narula.

PROSPECT was funded by Abbott Vascular and Volcano. Abbott participated in the study design, site selection, data collection, and data analysis.

Dr. Stone reports receiving grant support, consulting fees, and/or lecture fees from numerous pharmaceutical and device firms, including Abbott Vascular, TherOx, the Medicines Company, and Boston Scientific. Other investigators reported financial relationships with Abbott Vascular, Boston Scientific, Volcano, Bristol-Myers Squibb, Sanofi-Aventis, the Medicines Company, and others.

It should not come as a surprise that approximately half of the acute coronary syndromes that recur within 3 years of an index ACS treated percutaneously involve a different lesion that was visualized on angiography at that time but was not severe enough to require treatment, as has been recently reported in the New England Journal of Medicine.

“Pathologic studies … have illustrated that plaques when ruptured were substantially bulky and associated with thin fibrous caps. These lesions at the time of diagnosis may not have been sizable but grow at a faster rate to become eligible for rupture,” Dr. Jagat Narula, who is chief of cardiology at the University of California in Irvine, said in an interview.

The bigger question concerns the potential role for newly available radiofrequency intravascular ultrasonography (RF IVUS) in early assessment of patients with ACS.

The study in question showed that the rate of recurrent major adverse cardiovascular events was 20% in this multicenter prospective study involving 697 patients with ACS who were successfully treated with PCI and medical therapy, then followed for 3 years, reported Dr. Gregg W. Stone of Columbia University Medical Center/New York Presbyterian Hospital and the Cardiovascular Research Foundation, New York, and his associates.

The Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study was conducted at 37 medical centers in the United States and Europe.

Study subjects were enrolled after undergoing successful and uncomplicated PCI for all coronary lesions thought to be responsible for their index ACS. At that time, the subjects underwent angiography, then conventional gray-scale intravascular ultrasonography and the newly available RF IVUS of the left main coronary artery and the proximal 6-8 cm of each of the major epicardial coronary arteries.

The median age of the study subjects was 58 years; 24% were women, and 17% had diabetes.

“We found that approximately one in five patients with [ACS] ... had recurrent major adverse cardiovascular events within 3 years. Events were nearly equally divided between those related to initially treated lesions and those related to previously untreated lesions,” Dr. Stone and his colleagues said.

“Most events were rehospitalizations for unstable or progressive angina; death from cardiac causes, cardiac arrest, and MI were less common,” they noted.

“Despite [certain] caveats, PROSPECT study has contributed immensely to understanding plaque anatomy, plaque composition and the prognostic relevance of the atherosclerotic lesions,” said Dr. Narula.

RF IVUS at baseline revealed that most of the “nonculprit” coronary lesions - those that had been considered mild on the index angiography and were not treated at that time - were characterized by a large plaque burden, a small luminal area, or both. Half of them also were thin-cap fibroatheromas. These traits had not been visible on conventional angiography.

“I think the major message is that the angiogram is a very poor discriminator of how much atherosclerosis is present and which type of atherosclerosis is going to go on and cause unexpected events,” Dr. Stone said in an interview. “Radiofrequency IVUS provides significantly more information than just regular gray-scale IVUS in helping differentiate the nature of these plaques and which ones are going to progress.”

Conventional gray-scale IVUS works by sending out ultrasound waves and the resulting reflection signal can reveal structural information. Gray-scale IVUS measures only the amplitude of the reflected waves. However, RF IVUS also interprets frequency information from the reflected waves.

“That radiofrequency signal has been mapped pixel by pixel to actual histology from human pathologic specimens.” So a four-color coded map with four different types of tissue can be created to map plaque composition.

“RF IVUS has a much higher signal-to-noise ratio because it's a catheter that is right next to the coronary plaque. So the resolution is much greater and you can see plaque composition the way that noninvasive modalities currently can't,” Dr. Stone said.

However, “there are several reasons why the methods we have used are not currently suitable for clinical application as a means of identifying sites in the coronary vasculature for potential intervention,” the investigators noted (N. Engl. J. Med. 2011:364:226-35).

First, this method lacks specificity at present. RF IVUS identified a total of 595 thin-cap atheromas in these subjects, but only 26 of them caused recurrent ACS. Similarly, fewer than 10% of the lesions that carried plaque burdens of 70% or more and the lesions with a 4-mm or smaller luminal area caused recurrent ACS.

“Even when all three predictive variables were present, the event rate rose to only 18%,” they said.

Second, catheters used for this type of ultrasonography could only access the proximal 6-8 cm of the coronary tree. This meant that only 51 of the 106 “nonculprit” lesions seen on angiography could be evaluated by RF IVUS.

Third, the technique was associated with very serious adverse events in 11 patients in this study: 10 coronary dissections and 1 perforation, which in turn caused 4 nonfatal MIs.

While the ability of RF IVUS to assess luminal stenosis, plaque burden and positive remodeling is a useful tool, there are other diagnostic modalities to consider as well, said Dr. Narula. “Optical coherence tomography is the only technique that may accurately measure the cap thickness [and] CT angiography allows an assessment of both positive remodeling and the magnitude of necrotic cores.”

Intravascular optical coherence tomography (OCT) is similar to IVUS but light is used instead and resolution is greater. OCT uses a single fiberoptic wire that emits light and records the reflection as it is rotated and pulled back along the artery. OCT can be used to guide interventions, assess the lumen, visualize thrombi and dissections. It can also allow physicians to evaluate lesion cap thickness.

The advent of multislice CT - 264 slices and even greater - offers better and better resolution for non-invasive CT angiography. CTA can identify the presence of positive vessel remodeling and low-attenuation plaques, which along with a necrotic core, are thought to be associated with subsequent plaque rupture.

In the PROSPECT study, they also found that no major events arose from arterial segments with a plaque burden that blocked less than 40% of the lumen. And nonfibroatheromas rarely caused such events, regardless of their plaque burden or the luminal area they blocked.

These study findings suggest that thin-cap fibroatheromas, lesions with a large plaque burden, and lesions with a small luminal area are particularly prone to cause recurrent ACS.

For now though, the early identification of such lesions needs to be validated in randomized trials and is limited by unclear therapeutical options.

“We need to answer two questions,” said Dr. Narula. “First, can we define the high-risk lesions especially when of intermediate angiographic severity? Second, even if it is possible, are we justified in recommending widespread imaging studies, especially when only a small fraction of nonculprit vessel plaques progress to acute events … plaques form, rupture, and heal all the time, and it would be difficult to precisely identify a high-risk plaque associated with a major event, let alone identify it in a treatable proximity to an event.”

Dr. Stone agreed. “We haven't yet done the randomized trials to say that if we find one of these lesions that the patients are better off if we then treat them. If so, what do we treat them with?”

“For now, statins remain the cornerstone of management of the non-obstructive disease. Whether new agents targeted at inflammation … or non-injurious stent implantation become worthy of clinical application, would depend upon the capability of imaging techniques to identify temporo-spatial proclivity of lesions for the occurrence of events, as also the demonstration of the virtue and benign nature of the intervention,” said Dr. Narula.

PROSPECT was funded by Abbott Vascular and Volcano. Abbott participated in the study design, site selection, data collection, and data analysis.

Dr. Stone reports receiving grant support, consulting fees, and/or lecture fees from numerous pharmaceutical and device firms, including Abbott Vascular, TherOx, the Medicines Company, and Boston Scientific. Other investigators reported financial relationships with Abbott Vascular, Boston Scientific, Volcano, Bristol-Myers Squibb, Sanofi-Aventis, the Medicines Company, and others.

It should not come as a surprise that approximately half of the acute coronary syndromes that recur within 3 years of an index ACS treated percutaneously involve a different lesion that was visualized on angiography at that time but was not severe enough to require treatment, as has been recently reported in the New England Journal of Medicine.

“Pathologic studies … have illustrated that plaques when ruptured were substantially bulky and associated with thin fibrous caps. These lesions at the time of diagnosis may not have been sizable but grow at a faster rate to become eligible for rupture,” Dr. Jagat Narula, who is chief of cardiology at the University of California in Irvine, said in an interview.

The bigger question concerns the potential role for newly available radiofrequency intravascular ultrasonography (RF IVUS) in early assessment of patients with ACS.

The study in question showed that the rate of recurrent major adverse cardiovascular events was 20% in this multicenter prospective study involving 697 patients with ACS who were successfully treated with PCI and medical therapy, then followed for 3 years, reported Dr. Gregg W. Stone of Columbia University Medical Center/New York Presbyterian Hospital and the Cardiovascular Research Foundation, New York, and his associates.

The Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study was conducted at 37 medical centers in the United States and Europe.

Study subjects were enrolled after undergoing successful and uncomplicated PCI for all coronary lesions thought to be responsible for their index ACS. At that time, the subjects underwent angiography, then conventional gray-scale intravascular ultrasonography and the newly available RF IVUS of the left main coronary artery and the proximal 6-8 cm of each of the major epicardial coronary arteries.

The median age of the study subjects was 58 years; 24% were women, and 17% had diabetes.

“We found that approximately one in five patients with [ACS] ... had recurrent major adverse cardiovascular events within 3 years. Events were nearly equally divided between those related to initially treated lesions and those related to previously untreated lesions,” Dr. Stone and his colleagues said.

“Most events were rehospitalizations for unstable or progressive angina; death from cardiac causes, cardiac arrest, and MI were less common,” they noted.

“Despite [certain] caveats, PROSPECT study has contributed immensely to understanding plaque anatomy, plaque composition and the prognostic relevance of the atherosclerotic lesions,” said Dr. Narula.

RF IVUS at baseline revealed that most of the “nonculprit” coronary lesions - those that had been considered mild on the index angiography and were not treated at that time - were characterized by a large plaque burden, a small luminal area, or both. Half of them also were thin-cap fibroatheromas. These traits had not been visible on conventional angiography.

“I think the major message is that the angiogram is a very poor discriminator of how much atherosclerosis is present and which type of atherosclerosis is going to go on and cause unexpected events,” Dr. Stone said in an interview. “Radiofrequency IVUS provides significantly more information than just regular gray-scale IVUS in helping differentiate the nature of these plaques and which ones are going to progress.”

Conventional gray-scale IVUS works by sending out ultrasound waves and the resulting reflection signal can reveal structural information. Gray-scale IVUS measures only the amplitude of the reflected waves. However, RF IVUS also interprets frequency information from the reflected waves.

“That radiofrequency signal has been mapped pixel by pixel to actual histology from human pathologic specimens.” So a four-color coded map with four different types of tissue can be created to map plaque composition.

“RF IVUS has a much higher signal-to-noise ratio because it's a catheter that is right next to the coronary plaque. So the resolution is much greater and you can see plaque composition the way that noninvasive modalities currently can't,” Dr. Stone said.

However, “there are several reasons why the methods we have used are not currently suitable for clinical application as a means of identifying sites in the coronary vasculature for potential intervention,” the investigators noted (N. Engl. J. Med. 2011:364:226-35).

First, this method lacks specificity at present. RF IVUS identified a total of 595 thin-cap atheromas in these subjects, but only 26 of them caused recurrent ACS. Similarly, fewer than 10% of the lesions that carried plaque burdens of 70% or more and the lesions with a 4-mm or smaller luminal area caused recurrent ACS.

“Even when all three predictive variables were present, the event rate rose to only 18%,” they said.

Second, catheters used for this type of ultrasonography could only access the proximal 6-8 cm of the coronary tree. This meant that only 51 of the 106 “nonculprit” lesions seen on angiography could be evaluated by RF IVUS.

Third, the technique was associated with very serious adverse events in 11 patients in this study: 10 coronary dissections and 1 perforation, which in turn caused 4 nonfatal MIs.

While the ability of RF IVUS to assess luminal stenosis, plaque burden and positive remodeling is a useful tool, there are other diagnostic modalities to consider as well, said Dr. Narula. “Optical coherence tomography is the only technique that may accurately measure the cap thickness [and] CT angiography allows an assessment of both positive remodeling and the magnitude of necrotic cores.”

Intravascular optical coherence tomography (OCT) is similar to IVUS but light is used instead and resolution is greater. OCT uses a single fiberoptic wire that emits light and records the reflection as it is rotated and pulled back along the artery. OCT can be used to guide interventions, assess the lumen, visualize thrombi and dissections. It can also allow physicians to evaluate lesion cap thickness.

The advent of multislice CT - 264 slices and even greater - offers better and better resolution for non-invasive CT angiography. CTA can identify the presence of positive vessel remodeling and low-attenuation plaques, which along with a necrotic core, are thought to be associated with subsequent plaque rupture.

In the PROSPECT study, they also found that no major events arose from arterial segments with a plaque burden that blocked less than 40% of the lumen. And nonfibroatheromas rarely caused such events, regardless of their plaque burden or the luminal area they blocked.

These study findings suggest that thin-cap fibroatheromas, lesions with a large plaque burden, and lesions with a small luminal area are particularly prone to cause recurrent ACS.

For now though, the early identification of such lesions needs to be validated in randomized trials and is limited by unclear therapeutical options.

“We need to answer two questions,” said Dr. Narula. “First, can we define the high-risk lesions especially when of intermediate angiographic severity? Second, even if it is possible, are we justified in recommending widespread imaging studies, especially when only a small fraction of nonculprit vessel plaques progress to acute events … plaques form, rupture, and heal all the time, and it would be difficult to precisely identify a high-risk plaque associated with a major event, let alone identify it in a treatable proximity to an event.”

Dr. Stone agreed. “We haven't yet done the randomized trials to say that if we find one of these lesions that the patients are better off if we then treat them. If so, what do we treat them with?”

“For now, statins remain the cornerstone of management of the non-obstructive disease. Whether new agents targeted at inflammation … or non-injurious stent implantation become worthy of clinical application, would depend upon the capability of imaging techniques to identify temporo-spatial proclivity of lesions for the occurrence of events, as also the demonstration of the virtue and benign nature of the intervention,” said Dr. Narula.

PROSPECT was funded by Abbott Vascular and Volcano. Abbott participated in the study design, site selection, data collection, and data analysis.

Dr. Stone reports receiving grant support, consulting fees, and/or lecture fees from numerous pharmaceutical and device firms, including Abbott Vascular, TherOx, the Medicines Company, and Boston Scientific. Other investigators reported financial relationships with Abbott Vascular, Boston Scientific, Volcano, Bristol-Myers Squibb, Sanofi-Aventis, the Medicines Company, and others.

It's a simple idea, but it could help save millions of lives: a Web site helping hospitals and surgeons worldwide improve surgical outcomes by making a commitment to implement proven protocols in their operating rooms, to share ideas, and to receive feedback on what works best.

Called ORReady, the grass roots project is the brainchild of Dr. Paul Alan Wetter, founder and chairman of the Society of Laparoendoscopic Surgeons. Inspired by the humble beginnings of Facebook, and the power of collaboration in the Human Genome Project, Dr. Wetter decided that his idea - a global effort to improve surgical outcomes - would be just as feasible because "smart doctors around the world can get together and do it." No bureaucracy. No big dollar budget.

Launched in early 2010, the project is still in its infancy, and the Web site (www.orready.com) is still maturing. But the power of it all, he said in an interview, lies in the number of people who know about it and use it.

"There are many examples of people who have really improved outcomes in surgery with increased use of safety measures," said Dr. Wetter, who is an ob.gyn. in South Miami, Fla., and an internationally recognized leader in the field of minimally invasive surgery.

He hopes that by sharing OR safety information, there will be at least a 2%-3% improvement in outcomes. That's six million lives saved worldwide each year. He hopes that hospitals, medical societies, and surgical centers worldwide sign onto this effort within the coming years.

He admits that it's a lofty goal. But he also believes that the increasing emphasis on improving patient safety will help the initiative take off. Add to that the power of technology and collaboration: "[The] world is becoming a small place and information is disseminated quickly," said Dr. Wetter, who is also clinical professor emeritus at the University of Miami.

ORReady is a nonprofit project run by members and institutions that have volunteered their time and resources. The Web site follows the Creative Commons guidelines. "We encourage you to copy and use any materials that will help improve surgical outcome and create Centers of Merit in Surgery and MIS [minimally invasive surgery]." It encourages hospitals and departments to download and sign an "Outcome Commitment Letter"; to choose from a set of protocols on the Web site that suit their operating rooms; and register as an ORReady Center of Merit.

The guidelines suggest three main steps for surgeons and their teams: "Slow Down for Warm Up and Check Lists; Stop for Time Out before you Go." A stoplight on the site sums up the message.

Soon, participants can register with an open-access database that can be used for research to improve outcomes and to provide feedback. The school of biological and health systems engineering at Arizona State University, Tempe, has offered to help create the database. Dr. Wetter said that with the rapidly changing technology and arrival of new procedures, ORReady can be the tool through which surgeons and institutions can quickly share their data and receive feedback on what works best.

Dr. Wetter said that so far he has approached a handful of institutions in the United States and abroad and has received a unanimously positive response.

The project also recently won its first award. The Society of Laparoendoscopic Surgeons won the 2011 Alliance for Continuing Medical Education Great Idea Award in the Medical Specialty Societies Member section for introducing ORReady as a way to encourage surgical facilities to improve CME for improved surgical outcomes.

"We're looking for things that are best practices, are innovative, and that other people may want to replicate, adapt, [and] consider using," Jann Balmer, Ph.D., president of the Alliance, said in an interview.

"It's very exciting to do this and see this great enthusiasm," said Dr. Wetter. "For almost any doctor, the main concern is the safety of their patients."

Dr. Wetter is now focusing on spreading the word and making more surgeons and hospitals aware of and involved in ORReady. "The more people that know about this, the more successful it's going to be."

He hopes to see his project make an impact within the next few years.

It's a simple idea, but it could help save millions of lives: a Web site helping hospitals and surgeons worldwide improve surgical outcomes by making a commitment to implement proven protocols in their operating rooms, to share ideas, and to receive feedback on what works best.

Called ORReady, the grass roots project is the brainchild of Dr. Paul Alan Wetter, founder and chairman of the Society of Laparoendoscopic Surgeons. Inspired by the humble beginnings of Facebook, and the power of collaboration in the Human Genome Project, Dr. Wetter decided that his idea - a global effort to improve surgical outcomes - would be just as feasible because "smart doctors around the world can get together and do it." No bureaucracy. No big dollar budget.

Launched in early 2010, the project is still in its infancy, and the Web site (www.orready.com) is still maturing. But the power of it all, he said in an interview, lies in the number of people who know about it and use it.

"There are many examples of people who have really improved outcomes in surgery with increased use of safety measures," said Dr. Wetter, who is an ob.gyn. in South Miami, Fla., and an internationally recognized leader in the field of minimally invasive surgery.

He hopes that by sharing OR safety information, there will be at least a 2%-3% improvement in outcomes. That's six million lives saved worldwide each year. He hopes that hospitals, medical societies, and surgical centers worldwide sign onto this effort within the coming years.

He admits that it's a lofty goal. But he also believes that the increasing emphasis on improving patient safety will help the initiative take off. Add to that the power of technology and collaboration: "[The] world is becoming a small place and information is disseminated quickly," said Dr. Wetter, who is also clinical professor emeritus at the University of Miami.

ORReady is a nonprofit project run by members and institutions that have volunteered their time and resources. The Web site follows the Creative Commons guidelines. "We encourage you to copy and use any materials that will help improve surgical outcome and create Centers of Merit in Surgery and MIS [minimally invasive surgery]." It encourages hospitals and departments to download and sign an "Outcome Commitment Letter"; to choose from a set of protocols on the Web site that suit their operating rooms; and register as an ORReady Center of Merit.

The guidelines suggest three main steps for surgeons and their teams: "Slow Down for Warm Up and Check Lists; Stop for Time Out before you Go." A stoplight on the site sums up the message.

Soon, participants can register with an open-access database that can be used for research to improve outcomes and to provide feedback. The school of biological and health systems engineering at Arizona State University, Tempe, has offered to help create the database. Dr. Wetter said that with the rapidly changing technology and arrival of new procedures, ORReady can be the tool through which surgeons and institutions can quickly share their data and receive feedback on what works best.

Dr. Wetter said that so far he has approached a handful of institutions in the United States and abroad and has received a unanimously positive response.

The project also recently won its first award. The Society of Laparoendoscopic Surgeons won the 2011 Alliance for Continuing Medical Education Great Idea Award in the Medical Specialty Societies Member section for introducing ORReady as a way to encourage surgical facilities to improve CME for improved surgical outcomes.

"We're looking for things that are best practices, are innovative, and that other people may want to replicate, adapt, [and] consider using," Jann Balmer, Ph.D., president of the Alliance, said in an interview.

"It's very exciting to do this and see this great enthusiasm," said Dr. Wetter. "For almost any doctor, the main concern is the safety of their patients."

Dr. Wetter is now focusing on spreading the word and making more surgeons and hospitals aware of and involved in ORReady. "The more people that know about this, the more successful it's going to be."

He hopes to see his project make an impact within the next few years.

It's a simple idea, but it could help save millions of lives: a Web site helping hospitals and surgeons worldwide improve surgical outcomes by making a commitment to implement proven protocols in their operating rooms, to share ideas, and to receive feedback on what works best.

Called ORReady, the grass roots project is the brainchild of Dr. Paul Alan Wetter, founder and chairman of the Society of Laparoendoscopic Surgeons. Inspired by the humble beginnings of Facebook, and the power of collaboration in the Human Genome Project, Dr. Wetter decided that his idea - a global effort to improve surgical outcomes - would be just as feasible because "smart doctors around the world can get together and do it." No bureaucracy. No big dollar budget.

Launched in early 2010, the project is still in its infancy, and the Web site (www.orready.com) is still maturing. But the power of it all, he said in an interview, lies in the number of people who know about it and use it.

"There are many examples of people who have really improved outcomes in surgery with increased use of safety measures," said Dr. Wetter, who is an ob.gyn. in South Miami, Fla., and an internationally recognized leader in the field of minimally invasive surgery.

He hopes that by sharing OR safety information, there will be at least a 2%-3% improvement in outcomes. That's six million lives saved worldwide each year. He hopes that hospitals, medical societies, and surgical centers worldwide sign onto this effort within the coming years.

He admits that it's a lofty goal. But he also believes that the increasing emphasis on improving patient safety will help the initiative take off. Add to that the power of technology and collaboration: "[The] world is becoming a small place and information is disseminated quickly," said Dr. Wetter, who is also clinical professor emeritus at the University of Miami.

ORReady is a nonprofit project run by members and institutions that have volunteered their time and resources. The Web site follows the Creative Commons guidelines. "We encourage you to copy and use any materials that will help improve surgical outcome and create Centers of Merit in Surgery and MIS [minimally invasive surgery]." It encourages hospitals and departments to download and sign an "Outcome Commitment Letter"; to choose from a set of protocols on the Web site that suit their operating rooms; and register as an ORReady Center of Merit.

The guidelines suggest three main steps for surgeons and their teams: "Slow Down for Warm Up and Check Lists; Stop for Time Out before you Go." A stoplight on the site sums up the message.

Soon, participants can register with an open-access database that can be used for research to improve outcomes and to provide feedback. The school of biological and health systems engineering at Arizona State University, Tempe, has offered to help create the database. Dr. Wetter said that with the rapidly changing technology and arrival of new procedures, ORReady can be the tool through which surgeons and institutions can quickly share their data and receive feedback on what works best.

Dr. Wetter said that so far he has approached a handful of institutions in the United States and abroad and has received a unanimously positive response.

The project also recently won its first award. The Society of Laparoendoscopic Surgeons won the 2011 Alliance for Continuing Medical Education Great Idea Award in the Medical Specialty Societies Member section for introducing ORReady as a way to encourage surgical facilities to improve CME for improved surgical outcomes.

"We're looking for things that are best practices, are innovative, and that other people may want to replicate, adapt, [and] consider using," Jann Balmer, Ph.D., president of the Alliance, said in an interview.

"It's very exciting to do this and see this great enthusiasm," said Dr. Wetter. "For almost any doctor, the main concern is the safety of their patients."

Dr. Wetter is now focusing on spreading the word and making more surgeons and hospitals aware of and involved in ORReady. "The more people that know about this, the more successful it's going to be."

He hopes to see his project make an impact within the next few years.

In the second part of a discussion of the potential integration of Cardiac Surgery and Interventional Cardiology, two "early adopters" - Mathew Williams at New York Presbyterian Hospital-Columbia and Michael Davidson at the Brigham and Women's Hospital - continue their personal perspective on potential problems and training challenges such integration might entail.

Dr. Davidson notes there are some downsides to this new type of practice. “The issues that all of us face that do this - the 'ugly underbelly,' if you will - revolve around competition and turf. It plays out differently in every institution due to differences in reimbursement at each institution, etc.

"But even if reimbursement is not the issue, there are also issues of identity. There is a little element of being in 'no man's land': you are set aside from your cardiac surgery colleagues because you do things that they don't. And on the flipside you have the cardiologists, who are largely supportive, but there is always a little worry about encroachment on turf that you have to be very careful about. I don't think anyone has the ideal solution to this."

Looking to the future and the idea of the integration of cardiac surgery and interventional cardiology, both focused on potential changes in training programs. As a first point, they both noted that a significant amount time is required to master catheter-based skills."We need to accept that it takes more than three months to learn," Dr. Williams said.

Dr. Davidson echoed and expanded on this point: "One of the dangers cardiac surgeons face is that because they have such a high degree of technical skills, they tend to not have enough appreciation for the degree of technical skill that is involved in being a good, competent interventional cardiologists. Sometimes, cardiac surgeons assume that because they have good surgical skills, they can waltz into a cardiac catheterization lab and 'figure it out' in a short period of time and this is simply not true. One actually needs to put in a fair amount of time and do a few hundred cases to gain advanced catheter skills.

"One can get lulled into a sense of ease by doing a couple of easy procedures (e.g. a straightforward aortic stent graft) and then getting a sense that endovascular work is very easy. But in fact when one does more advanced procedures, one sees that it actually does take a lot of technical skill. For a cardiac surgeon to do this right, they have to understand the idea that you can't do a weekend or month-long course and expect to have real endovascular competency. "

"There's a bit of a paradox in that many feel it would be good to have more of a cardiac surgical presence in the cath lab; at the same time you risk having cardiac surgeons who are inadequately trained and may get into trouble assuming their surgical skills translate into endovascular skills."

Both went on to comment on the changes in training that would be necessary if interventional cardiology and cardiac surgery were to merge in the future. "There's a lot of divergence of opinion here. I am in the camp that believes that the separation of interventional cardiology and cardiac surgery is artificial and based on historical models that may not apply anymore. I think we should go more towards disease based treatment but in doing this, there would be a blurring of the lines as to be who should be doing what. One way to avoid the 'turf battles' and to achieve better integration would be to have the training integrated from the beginning," said Dr. Davidson.

"One of the problems that has been brought up is in this country is that often the treatment a patient gets is determined by who they happen to go see - one treatment if they go to a surgeon and one treatment if they go to a cardiologist" for the same disease.

"Ideally, if you train people from the ground up to be disease managers and then further differentiate from that point,"say 'outpatient clinicians' versus 'imaging clinicians' versus those that do 'big procedures' or endovascular procedures but united by their core training, it may reduce the 'turf battles' that are actually not very good for patients. The core should be patient care", Davidson continued.

In making any large-scale change, there are always two options: swift, radical action or more gradual stepwise changes.

"The question becomes should we do this by mass upheaval or incremental steps over time? Hard to know," Dr. Davidson remarked.

There are multiple complexities involved in such a change, he noted: "there are a lot of realities that go into this. For instance, the idea of merging cardiology and cardiac surgery doesn't take into account some practitioners who want to divide their time between cardiac and thoracic surgery. This group is more committed to keeping cardiac and thoracic surgery together and maintaining the general surgery training. So, there is an internal conflict/struggles even within CT surgery; in addition to the potential conflicts between cardiac surgery and cardiology."

On his vision of the future, Dr. Williams commented, "going forward, what I imagine is continued slow evolution - that's not my dream; I would hope for merged departments."

He went on to express concern regarding the future of cardiac surgery training. "Cardiac surgery is moving too slowly, in my opinion. At our institution, for example, we've been starting a six-year training program but given the amount of thoracic and general surgery they are required to do, we are not going to be training the cardiac surgeon of the future. Unless we radically change the training structure, true integration of the fields is never going to happen."

Dr. Williams pointed out that in his experience, the primary force of resistance to the idea of the integration of interventional cardiology and cardiac surgery was not from the medical side: "Actually in my experience, the cardiologists have embraced this a lot more than cardiac surgery.
 
"The resistance is not so much from the medical side as the surgical side. They have been a lot more receptive to this. Cardiothoracic surgeons seem to be more interested in fighting about turf instead of really looking at what the appropriate training is."

In the second part of a discussion of the potential integration of Cardiac Surgery and Interventional Cardiology, two "early adopters" - Mathew Williams at New York Presbyterian Hospital-Columbia and Michael Davidson at the Brigham and Women's Hospital - continue their personal perspective on potential problems and training challenges such integration might entail.

Dr. Davidson notes there are some downsides to this new type of practice. “The issues that all of us face that do this - the 'ugly underbelly,' if you will - revolve around competition and turf. It plays out differently in every institution due to differences in reimbursement at each institution, etc.

"But even if reimbursement is not the issue, there are also issues of identity. There is a little element of being in 'no man's land': you are set aside from your cardiac surgery colleagues because you do things that they don't. And on the flipside you have the cardiologists, who are largely supportive, but there is always a little worry about encroachment on turf that you have to be very careful about. I don't think anyone has the ideal solution to this."

Looking to the future and the idea of the integration of cardiac surgery and interventional cardiology, both focused on potential changes in training programs. As a first point, they both noted that a significant amount time is required to master catheter-based skills."We need to accept that it takes more than three months to learn," Dr. Williams said.

Dr. Davidson echoed and expanded on this point: "One of the dangers cardiac surgeons face is that because they have such a high degree of technical skills, they tend to not have enough appreciation for the degree of technical skill that is involved in being a good, competent interventional cardiologists. Sometimes, cardiac surgeons assume that because they have good surgical skills, they can waltz into a cardiac catheterization lab and 'figure it out' in a short period of time and this is simply not true. One actually needs to put in a fair amount of time and do a few hundred cases to gain advanced catheter skills.

"One can get lulled into a sense of ease by doing a couple of easy procedures (e.g. a straightforward aortic stent graft) and then getting a sense that endovascular work is very easy. But in fact when one does more advanced procedures, one sees that it actually does take a lot of technical skill. For a cardiac surgeon to do this right, they have to understand the idea that you can't do a weekend or month-long course and expect to have real endovascular competency. "

"There's a bit of a paradox in that many feel it would be good to have more of a cardiac surgical presence in the cath lab; at the same time you risk having cardiac surgeons who are inadequately trained and may get into trouble assuming their surgical skills translate into endovascular skills."

Both went on to comment on the changes in training that would be necessary if interventional cardiology and cardiac surgery were to merge in the future. "There's a lot of divergence of opinion here. I am in the camp that believes that the separation of interventional cardiology and cardiac surgery is artificial and based on historical models that may not apply anymore. I think we should go more towards disease based treatment but in doing this, there would be a blurring of the lines as to be who should be doing what. One way to avoid the 'turf battles' and to achieve better integration would be to have the training integrated from the beginning," said Dr. Davidson.

"One of the problems that has been brought up is in this country is that often the treatment a patient gets is determined by who they happen to go see - one treatment if they go to a surgeon and one treatment if they go to a cardiologist" for the same disease.

"Ideally, if you train people from the ground up to be disease managers and then further differentiate from that point,"say 'outpatient clinicians' versus 'imaging clinicians' versus those that do 'big procedures' or endovascular procedures but united by their core training, it may reduce the 'turf battles' that are actually not very good for patients. The core should be patient care", Davidson continued.

In making any large-scale change, there are always two options: swift, radical action or more gradual stepwise changes.

"The question becomes should we do this by mass upheaval or incremental steps over time? Hard to know," Dr. Davidson remarked.

There are multiple complexities involved in such a change, he noted: "there are a lot of realities that go into this. For instance, the idea of merging cardiology and cardiac surgery doesn't take into account some practitioners who want to divide their time between cardiac and thoracic surgery. This group is more committed to keeping cardiac and thoracic surgery together and maintaining the general surgery training. So, there is an internal conflict/struggles even within CT surgery; in addition to the potential conflicts between cardiac surgery and cardiology."

On his vision of the future, Dr. Williams commented, "going forward, what I imagine is continued slow evolution - that's not my dream; I would hope for merged departments."

He went on to express concern regarding the future of cardiac surgery training. "Cardiac surgery is moving too slowly, in my opinion. At our institution, for example, we've been starting a six-year training program but given the amount of thoracic and general surgery they are required to do, we are not going to be training the cardiac surgeon of the future. Unless we radically change the training structure, true integration of the fields is never going to happen."

Dr. Williams pointed out that in his experience, the primary force of resistance to the idea of the integration of interventional cardiology and cardiac surgery was not from the medical side: "Actually in my experience, the cardiologists have embraced this a lot more than cardiac surgery.
 
"The resistance is not so much from the medical side as the surgical side. They have been a lot more receptive to this. Cardiothoracic surgeons seem to be more interested in fighting about turf instead of really looking at what the appropriate training is."

In the second part of a discussion of the potential integration of Cardiac Surgery and Interventional Cardiology, two "early adopters" - Mathew Williams at New York Presbyterian Hospital-Columbia and Michael Davidson at the Brigham and Women's Hospital - continue their personal perspective on potential problems and training challenges such integration might entail.

Dr. Davidson notes there are some downsides to this new type of practice. “The issues that all of us face that do this - the 'ugly underbelly,' if you will - revolve around competition and turf. It plays out differently in every institution due to differences in reimbursement at each institution, etc.

"But even if reimbursement is not the issue, there are also issues of identity. There is a little element of being in 'no man's land': you are set aside from your cardiac surgery colleagues because you do things that they don't. And on the flipside you have the cardiologists, who are largely supportive, but there is always a little worry about encroachment on turf that you have to be very careful about. I don't think anyone has the ideal solution to this."

Looking to the future and the idea of the integration of cardiac surgery and interventional cardiology, both focused on potential changes in training programs. As a first point, they both noted that a significant amount time is required to master catheter-based skills."We need to accept that it takes more than three months to learn," Dr. Williams said.

Dr. Davidson echoed and expanded on this point: "One of the dangers cardiac surgeons face is that because they have such a high degree of technical skills, they tend to not have enough appreciation for the degree of technical skill that is involved in being a good, competent interventional cardiologists. Sometimes, cardiac surgeons assume that because they have good surgical skills, they can waltz into a cardiac catheterization lab and 'figure it out' in a short period of time and this is simply not true. One actually needs to put in a fair amount of time and do a few hundred cases to gain advanced catheter skills.

"One can get lulled into a sense of ease by doing a couple of easy procedures (e.g. a straightforward aortic stent graft) and then getting a sense that endovascular work is very easy. But in fact when one does more advanced procedures, one sees that it actually does take a lot of technical skill. For a cardiac surgeon to do this right, they have to understand the idea that you can't do a weekend or month-long course and expect to have real endovascular competency. "

"There's a bit of a paradox in that many feel it would be good to have more of a cardiac surgical presence in the cath lab; at the same time you risk having cardiac surgeons who are inadequately trained and may get into trouble assuming their surgical skills translate into endovascular skills."

Both went on to comment on the changes in training that would be necessary if interventional cardiology and cardiac surgery were to merge in the future. "There's a lot of divergence of opinion here. I am in the camp that believes that the separation of interventional cardiology and cardiac surgery is artificial and based on historical models that may not apply anymore. I think we should go more towards disease based treatment but in doing this, there would be a blurring of the lines as to be who should be doing what. One way to avoid the 'turf battles' and to achieve better integration would be to have the training integrated from the beginning," said Dr. Davidson.

"One of the problems that has been brought up is in this country is that often the treatment a patient gets is determined by who they happen to go see - one treatment if they go to a surgeon and one treatment if they go to a cardiologist" for the same disease.

"Ideally, if you train people from the ground up to be disease managers and then further differentiate from that point,"say 'outpatient clinicians' versus 'imaging clinicians' versus those that do 'big procedures' or endovascular procedures but united by their core training, it may reduce the 'turf battles' that are actually not very good for patients. The core should be patient care", Davidson continued.

In making any large-scale change, there are always two options: swift, radical action or more gradual stepwise changes.

"The question becomes should we do this by mass upheaval or incremental steps over time? Hard to know," Dr. Davidson remarked.

There are multiple complexities involved in such a change, he noted: "there are a lot of realities that go into this. For instance, the idea of merging cardiology and cardiac surgery doesn't take into account some practitioners who want to divide their time between cardiac and thoracic surgery. This group is more committed to keeping cardiac and thoracic surgery together and maintaining the general surgery training. So, there is an internal conflict/struggles even within CT surgery; in addition to the potential conflicts between cardiac surgery and cardiology."

On his vision of the future, Dr. Williams commented, "going forward, what I imagine is continued slow evolution - that's not my dream; I would hope for merged departments."

He went on to express concern regarding the future of cardiac surgery training. "Cardiac surgery is moving too slowly, in my opinion. At our institution, for example, we've been starting a six-year training program but given the amount of thoracic and general surgery they are required to do, we are not going to be training the cardiac surgeon of the future. Unless we radically change the training structure, true integration of the fields is never going to happen."

Dr. Williams pointed out that in his experience, the primary force of resistance to the idea of the integration of interventional cardiology and cardiac surgery was not from the medical side: "Actually in my experience, the cardiologists have embraced this a lot more than cardiac surgery.
 
"The resistance is not so much from the medical side as the surgical side. They have been a lot more receptive to this. Cardiothoracic surgeons seem to be more interested in fighting about turf instead of really looking at what the appropriate training is."

CHICAGO - Using N-terminal prohormone brain natriuretic peptide levels to guide therapy in patients with systolic heart failure proved superior to standard of care management in terms of cardiovascular event rates, quality of life, and echocardiographic parameters in the randomized prospective PROTECT trial.
 
"If duplicated in larger cohorts, treatment guided by NT-proBNP may represent a new paradigm for heart failure care," Dr. James L. Januzzi Jr. said at the annual scientific sessions of the American Heart Association.
 
PROTECT (the ProBNP Outpatient Tailored Chronic Heart Failure Therapy study) was a single-center unblinded trial of 151 patients with systolic heart failure and a mean left ventricular ejection fraction of 27%. They were randomized to standard guideline-driven management on the basis of heart failure signs and symptoms or to the same approach with the added goal of reducing NT-proBNP levels to 1,000 pg/mL or less, a threshold previously shown to predict risk in heart failure patients.

Participants were scheduled for quarterly clinic visits, with extra ones as needed to achieve therapeutic goals, said Dr. Januzzi, director of the cardiac intensive care unit at Massachusetts General Hospital, Boston.

The study was halted early for ethical reasons after 10 months. At that point a total of 100 cardiovascular events - worsening heart failure, heart failure hospitalization, acute coronary syndrome, ventricular arrhythmias, cerebral ischemia, or cardiovascular death - had occurred in the standard-treatment group, compared with 58 events in patients on NT-proBNP-guided therapy. The major difference between the two study arms was the sharply lower likelihood of worsening heart failure or heart failure hospitalization in the NT-proBNP-guided arm. Importantly, the reduction in cardiovascular events was similar in patients over age 75 and in those who were younger.

The secondary outcome of quality of life, assessed using the Minnesota Living with Heart Failure Questionnaire, also showed significantly greater improvement in the guided-treatment arm. In all, 61% of subjects in the NT-proBNP-guided arm achieved at least a 10-point improvement over baseline, considered clinically meaningful, compared with 39% on standard management.

The guided-treatment group also did significantly better in terms of secondary echocardiographic end points, with larger improvements in left ventricular ejection fraction and in ventricular remodeling as reflected by changes in LV end-systolic and end-diastolic volume index, the cardiologist continued.

NT-proBNP-guided therapy proved safe and was well tolerated, with no significant increase in adverse events.

Patients in the guided-treatment arm had a median of six clinic visits, compared with five with standard management. The median baseline NT-proBNP level in the guided-therapy arm was 2,344 pg/mL. It fell to 1,125 pg/mL, with 44% of subjects in the guided-therapy arm attaining an NT-proBNP of 1,000 pg/mL or less.

Up-titration of heart failure medications was common in both study arms, but was significantly greater in the NT-proBNP group. A total of 63% of patients in the guided-therapy arm were placed on an aldosterone blocker, compared with 45% of controls.

Session cochair Dr. Gregg C. Fonarow said in an interview that he views PROTECT as a successful proof-of-concept study. But before biomarker-guided treatment of heart failure becomes part of guideline-recommended, routine outpatient care, it will be necessary to see if the Massachusetts General Hospital experience can be extended to other settings, including primary care practices, where many patients with heart failure receive their treatment. This will require a large multicenter trial with a diverse group of clinicians; randomization by site; and hard clinical end points, including mortality. A proposal for such a study has been presented to the National Heart, Lung, and Blood Institute for funding consideration.

"It's a large and expensive trial, but the impact is potentially profound," said Dr. Fonarow, professor of medicine and director of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles. “Given the costs of heart failure and the tremendous number of outpatient visits for this disease, if we truly had a well-validated guide using biomarkers, that would be a phenomenal advance."

The PROTECT trial was sponsored in part by Roche Diagnostics. Dr. Januzzi declared he serves as a consultant to and speaker for the company.

CHICAGO - Using N-terminal prohormone brain natriuretic peptide levels to guide therapy in patients with systolic heart failure proved superior to standard of care management in terms of cardiovascular event rates, quality of life, and echocardiographic parameters in the randomized prospective PROTECT trial.
 
"If duplicated in larger cohorts, treatment guided by NT-proBNP may represent a new paradigm for heart failure care," Dr. James L. Januzzi Jr. said at the annual scientific sessions of the American Heart Association.
 
PROTECT (the ProBNP Outpatient Tailored Chronic Heart Failure Therapy study) was a single-center unblinded trial of 151 patients with systolic heart failure and a mean left ventricular ejection fraction of 27%. They were randomized to standard guideline-driven management on the basis of heart failure signs and symptoms or to the same approach with the added goal of reducing NT-proBNP levels to 1,000 pg/mL or less, a threshold previously shown to predict risk in heart failure patients.

Participants were scheduled for quarterly clinic visits, with extra ones as needed to achieve therapeutic goals, said Dr. Januzzi, director of the cardiac intensive care unit at Massachusetts General Hospital, Boston.

The study was halted early for ethical reasons after 10 months. At that point a total of 100 cardiovascular events - worsening heart failure, heart failure hospitalization, acute coronary syndrome, ventricular arrhythmias, cerebral ischemia, or cardiovascular death - had occurred in the standard-treatment group, compared with 58 events in patients on NT-proBNP-guided therapy. The major difference between the two study arms was the sharply lower likelihood of worsening heart failure or heart failure hospitalization in the NT-proBNP-guided arm. Importantly, the reduction in cardiovascular events was similar in patients over age 75 and in those who were younger.

The secondary outcome of quality of life, assessed using the Minnesota Living with Heart Failure Questionnaire, also showed significantly greater improvement in the guided-treatment arm. In all, 61% of subjects in the NT-proBNP-guided arm achieved at least a 10-point improvement over baseline, considered clinically meaningful, compared with 39% on standard management.

The guided-treatment group also did significantly better in terms of secondary echocardiographic end points, with larger improvements in left ventricular ejection fraction and in ventricular remodeling as reflected by changes in LV end-systolic and end-diastolic volume index, the cardiologist continued.

NT-proBNP-guided therapy proved safe and was well tolerated, with no significant increase in adverse events.

Patients in the guided-treatment arm had a median of six clinic visits, compared with five with standard management. The median baseline NT-proBNP level in the guided-therapy arm was 2,344 pg/mL. It fell to 1,125 pg/mL, with 44% of subjects in the guided-therapy arm attaining an NT-proBNP of 1,000 pg/mL or less.

Up-titration of heart failure medications was common in both study arms, but was significantly greater in the NT-proBNP group. A total of 63% of patients in the guided-therapy arm were placed on an aldosterone blocker, compared with 45% of controls.

Session cochair Dr. Gregg C. Fonarow said in an interview that he views PROTECT as a successful proof-of-concept study. But before biomarker-guided treatment of heart failure becomes part of guideline-recommended, routine outpatient care, it will be necessary to see if the Massachusetts General Hospital experience can be extended to other settings, including primary care practices, where many patients with heart failure receive their treatment. This will require a large multicenter trial with a diverse group of clinicians; randomization by site; and hard clinical end points, including mortality. A proposal for such a study has been presented to the National Heart, Lung, and Blood Institute for funding consideration.

"It's a large and expensive trial, but the impact is potentially profound," said Dr. Fonarow, professor of medicine and director of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles. “Given the costs of heart failure and the tremendous number of outpatient visits for this disease, if we truly had a well-validated guide using biomarkers, that would be a phenomenal advance."

The PROTECT trial was sponsored in part by Roche Diagnostics. Dr. Januzzi declared he serves as a consultant to and speaker for the company.

CHICAGO - Using N-terminal prohormone brain natriuretic peptide levels to guide therapy in patients with systolic heart failure proved superior to standard of care management in terms of cardiovascular event rates, quality of life, and echocardiographic parameters in the randomized prospective PROTECT trial.
 
"If duplicated in larger cohorts, treatment guided by NT-proBNP may represent a new paradigm for heart failure care," Dr. James L. Januzzi Jr. said at the annual scientific sessions of the American Heart Association.
 
PROTECT (the ProBNP Outpatient Tailored Chronic Heart Failure Therapy study) was a single-center unblinded trial of 151 patients with systolic heart failure and a mean left ventricular ejection fraction of 27%. They were randomized to standard guideline-driven management on the basis of heart failure signs and symptoms or to the same approach with the added goal of reducing NT-proBNP levels to 1,000 pg/mL or less, a threshold previously shown to predict risk in heart failure patients.

Participants were scheduled for quarterly clinic visits, with extra ones as needed to achieve therapeutic goals, said Dr. Januzzi, director of the cardiac intensive care unit at Massachusetts General Hospital, Boston.

The study was halted early for ethical reasons after 10 months. At that point a total of 100 cardiovascular events - worsening heart failure, heart failure hospitalization, acute coronary syndrome, ventricular arrhythmias, cerebral ischemia, or cardiovascular death - had occurred in the standard-treatment group, compared with 58 events in patients on NT-proBNP-guided therapy. The major difference between the two study arms was the sharply lower likelihood of worsening heart failure or heart failure hospitalization in the NT-proBNP-guided arm. Importantly, the reduction in cardiovascular events was similar in patients over age 75 and in those who were younger.

The secondary outcome of quality of life, assessed using the Minnesota Living with Heart Failure Questionnaire, also showed significantly greater improvement in the guided-treatment arm. In all, 61% of subjects in the NT-proBNP-guided arm achieved at least a 10-point improvement over baseline, considered clinically meaningful, compared with 39% on standard management.

The guided-treatment group also did significantly better in terms of secondary echocardiographic end points, with larger improvements in left ventricular ejection fraction and in ventricular remodeling as reflected by changes in LV end-systolic and end-diastolic volume index, the cardiologist continued.

NT-proBNP-guided therapy proved safe and was well tolerated, with no significant increase in adverse events.

Patients in the guided-treatment arm had a median of six clinic visits, compared with five with standard management. The median baseline NT-proBNP level in the guided-therapy arm was 2,344 pg/mL. It fell to 1,125 pg/mL, with 44% of subjects in the guided-therapy arm attaining an NT-proBNP of 1,000 pg/mL or less.

Up-titration of heart failure medications was common in both study arms, but was significantly greater in the NT-proBNP group. A total of 63% of patients in the guided-therapy arm were placed on an aldosterone blocker, compared with 45% of controls.

Session cochair Dr. Gregg C. Fonarow said in an interview that he views PROTECT as a successful proof-of-concept study. But before biomarker-guided treatment of heart failure becomes part of guideline-recommended, routine outpatient care, it will be necessary to see if the Massachusetts General Hospital experience can be extended to other settings, including primary care practices, where many patients with heart failure receive their treatment. This will require a large multicenter trial with a diverse group of clinicians; randomization by site; and hard clinical end points, including mortality. A proposal for such a study has been presented to the National Heart, Lung, and Blood Institute for funding consideration.

"It's a large and expensive trial, but the impact is potentially profound," said Dr. Fonarow, professor of medicine and director of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles. “Given the costs of heart failure and the tremendous number of outpatient visits for this disease, if we truly had a well-validated guide using biomarkers, that would be a phenomenal advance."

The PROTECT trial was sponsored in part by Roche Diagnostics. Dr. Januzzi declared he serves as a consultant to and speaker for the company.

CHICAGO - A novel technique utilizing stapled lung debris could help determine adequate and inadequate surgical margins in resected non-small cell lung cancer, results of a prospective study suggest.

Researchers at Albany (N.Y.) Medical College and the Hospital of St. Raphael in New Haven, Conn., are using cytology to analyze lung tissue taken from spent staple cartridges used during sublobar resection. The staple cartridge is simply mixed with 30 cc of normal saline and serves as the cytologic margin, Dr. Thomas Fabian explained at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

"People have [observed] that certain staples used through cancers can potentially contaminate new tissue planes, so that is how the idea was born," he said in an interview.

Dr. Fabian and his colleagues prospectively compared staple-line cytology with traditional histopathologic evaluation of surgical specimens taken from 97 patients undergoing diagnostic sublobar wedge resection between November 2007 and September 2009. Of the 98 specimens retrieved, 30 were benign and 68 were malignant.
Staple-line cytology was 100% accurate in the evaluation of benign lesions when compared with histology, he said.

In the 68 malignant nodules, initial blinded cytologic evaluation was positive in 7, surgical pathology was positive in 6, and both were positive in 4.

Subsequent unblinded review of both specimens changed the final pathologic interpretation in 4 (6%) of the 68 cases, said Dr. Fabian, chief of thoracic surgery at the Albany Medical Center. The interpretation changed from a negative margin to a positive margin in 3 surgical specimens (7%) and in 1 staple-line cytology specimen (2%).

According to analysis of the unblinded data, staple-line cytology demonstrated an overall accuracy of 96%, with 88% sensitivity, 97% specificity, 70% positive-predictive value, and 99% negative-predictive value.

Dr. Fabian described staple-line cytology as a simple technique that could serve as an adjunct to the gold standard of histopathology, which he said is prone to inaccuracies including both false positives and false negatives.

"We need to reevaluate the techniques that allow us to accurately assess surgical margins - particularly in the setting of sublobar resections, given the growing interest in this technique," according to Dr. Fabian.

"The cytologic technique appears to be sensitive, specific, and accurate, but it does need to be validated at other institutions and with additional studies," he added.

Dr. Fabian acknowledged that by design the study lacked clinical outcome data and said further evaluation is ongoing. The next step is to evaluate the technique in patients undergoing sublobar resection with curative intent.

Of the 68 malignant samples, 43 were diagnosed as adenocarcinoma, 7 as squamous cell carcinoma, 3 as large cell, 1 as small cell, 5 as carcinoid, and 9 as other histologies.

Dr. Fabian disclosed serving as a speaker for, and receiving research funding and honoraria from, Covidien. His coauthors reported no conflicts.

CHICAGO - A novel technique utilizing stapled lung debris could help determine adequate and inadequate surgical margins in resected non-small cell lung cancer, results of a prospective study suggest.

Researchers at Albany (N.Y.) Medical College and the Hospital of St. Raphael in New Haven, Conn., are using cytology to analyze lung tissue taken from spent staple cartridges used during sublobar resection. The staple cartridge is simply mixed with 30 cc of normal saline and serves as the cytologic margin, Dr. Thomas Fabian explained at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

"People have [observed] that certain staples used through cancers can potentially contaminate new tissue planes, so that is how the idea was born," he said in an interview.

Dr. Fabian and his colleagues prospectively compared staple-line cytology with traditional histopathologic evaluation of surgical specimens taken from 97 patients undergoing diagnostic sublobar wedge resection between November 2007 and September 2009. Of the 98 specimens retrieved, 30 were benign and 68 were malignant.
Staple-line cytology was 100% accurate in the evaluation of benign lesions when compared with histology, he said.

In the 68 malignant nodules, initial blinded cytologic evaluation was positive in 7, surgical pathology was positive in 6, and both were positive in 4.

Subsequent unblinded review of both specimens changed the final pathologic interpretation in 4 (6%) of the 68 cases, said Dr. Fabian, chief of thoracic surgery at the Albany Medical Center. The interpretation changed from a negative margin to a positive margin in 3 surgical specimens (7%) and in 1 staple-line cytology specimen (2%).

According to analysis of the unblinded data, staple-line cytology demonstrated an overall accuracy of 96%, with 88% sensitivity, 97% specificity, 70% positive-predictive value, and 99% negative-predictive value.

Dr. Fabian described staple-line cytology as a simple technique that could serve as an adjunct to the gold standard of histopathology, which he said is prone to inaccuracies including both false positives and false negatives.

"We need to reevaluate the techniques that allow us to accurately assess surgical margins - particularly in the setting of sublobar resections, given the growing interest in this technique," according to Dr. Fabian.

"The cytologic technique appears to be sensitive, specific, and accurate, but it does need to be validated at other institutions and with additional studies," he added.

Dr. Fabian acknowledged that by design the study lacked clinical outcome data and said further evaluation is ongoing. The next step is to evaluate the technique in patients undergoing sublobar resection with curative intent.

Of the 68 malignant samples, 43 were diagnosed as adenocarcinoma, 7 as squamous cell carcinoma, 3 as large cell, 1 as small cell, 5 as carcinoid, and 9 as other histologies.

Dr. Fabian disclosed serving as a speaker for, and receiving research funding and honoraria from, Covidien. His coauthors reported no conflicts.

CHICAGO - A novel technique utilizing stapled lung debris could help determine adequate and inadequate surgical margins in resected non-small cell lung cancer, results of a prospective study suggest.

Researchers at Albany (N.Y.) Medical College and the Hospital of St. Raphael in New Haven, Conn., are using cytology to analyze lung tissue taken from spent staple cartridges used during sublobar resection. The staple cartridge is simply mixed with 30 cc of normal saline and serves as the cytologic margin, Dr. Thomas Fabian explained at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

"People have [observed] that certain staples used through cancers can potentially contaminate new tissue planes, so that is how the idea was born," he said in an interview.

Dr. Fabian and his colleagues prospectively compared staple-line cytology with traditional histopathologic evaluation of surgical specimens taken from 97 patients undergoing diagnostic sublobar wedge resection between November 2007 and September 2009. Of the 98 specimens retrieved, 30 were benign and 68 were malignant.
Staple-line cytology was 100% accurate in the evaluation of benign lesions when compared with histology, he said.

In the 68 malignant nodules, initial blinded cytologic evaluation was positive in 7, surgical pathology was positive in 6, and both were positive in 4.

Subsequent unblinded review of both specimens changed the final pathologic interpretation in 4 (6%) of the 68 cases, said Dr. Fabian, chief of thoracic surgery at the Albany Medical Center. The interpretation changed from a negative margin to a positive margin in 3 surgical specimens (7%) and in 1 staple-line cytology specimen (2%).

According to analysis of the unblinded data, staple-line cytology demonstrated an overall accuracy of 96%, with 88% sensitivity, 97% specificity, 70% positive-predictive value, and 99% negative-predictive value.

Dr. Fabian described staple-line cytology as a simple technique that could serve as an adjunct to the gold standard of histopathology, which he said is prone to inaccuracies including both false positives and false negatives.

"We need to reevaluate the techniques that allow us to accurately assess surgical margins - particularly in the setting of sublobar resections, given the growing interest in this technique," according to Dr. Fabian.

"The cytologic technique appears to be sensitive, specific, and accurate, but it does need to be validated at other institutions and with additional studies," he added.

Dr. Fabian acknowledged that by design the study lacked clinical outcome data and said further evaluation is ongoing. The next step is to evaluate the technique in patients undergoing sublobar resection with curative intent.

Of the 68 malignant samples, 43 were diagnosed as adenocarcinoma, 7 as squamous cell carcinoma, 3 as large cell, 1 as small cell, 5 as carcinoid, and 9 as other histologies.

Dr. Fabian disclosed serving as a speaker for, and receiving research funding and honoraria from, Covidien. His coauthors reported no conflicts.

CHICAGO - New data suggest that microscopic vascular invasion may be a more powerful prognosticator in early lung cancer than are the tumor size-based categories suggested in the new TNM staging system.

Italian researchers used histologic and immunohistochemical techniques to identify microscopic vascular invasion (MVI), or the presence of neoplastic structures inside the lumen of a vessel, in one-third (154) of 512 patients with resected, pathologically staged T1a to T3 node-negative non-small cell lung cancer (NSCLC). The 2009 edition of the tumor, node, metastasis (TNM) staging system for lung tumors was used.

MVI was significantly correlated with the presence of tumor-infiltrating lymphocytes (odds ratio 1.65, P value = .03), adenocarcinoma histology (OR 1.32, P = .003), and increased tumor size (OR 1.13, P = .009).

Five-year overall survival was significantly lower for patients with MVI at 50% vs. those without MVI at 66% (P = .001), Dr. Enrico Ruffini said at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

The difference in survival remained significant even in those with squamous cell carcinoma (45% vs. 61%, P = .05), although it was more pronounced in those with adenocarcinoma (56% vs. 70%, P = .03).

"Microscopic vascular invasion is a significant independent negative prognostic factor," he said.

When patients with pT1a-T2b tumors were stratified by T-size category, the presence of MVI resulted in a one-category upstaging for each T category, said Dr. Ruffini of the division of thoracic surgery at the University of Torino (Italy). For example, T1a patients with MVI had a prognosis similar to that of patients with T1b tumors without MVI. The number of T3 cases was too small to stratify.

T size was prognostic of survival in the MVI-negative patients (P = .03) but was not a statistically significant factor in MVI-positive patients (P = .9), indicating that MVI is indeed a more powerful prognosticator, he said.

The 2009 TNM stresses the importance of tumor size as a major prognostic factor, but no TNM edition has so far included MVI as a major determinant in the staging of NSCLC.

In a multivariate survival analysis that included age, sex, histology, grading, T-size determinant, MVI, perineural invasion, and tumor-infiltrating lymphocytes, MVI was a stronger prognostic indicator (hazard ratio 1.43, P = .02) than T-size determinant (HR 1.06, P = .06), Dr. Ruffini said.

"The use of adjuvant chemotherapy in NSCLC patients with MVI may be considered," he said.

Invited discussant Dr. Mark Socinski pointed out that 88% of patients in the analysis had 5 cm or smaller tumors, a category of patients in which the role of adjuvant therapy has been discouraged. He highlighted the recent LACE meta-analysis of 4,584 NSCLC patients in five cisplatin-based adjuvant chemotherapy trials that showed an overall significant survival benefit of 4% at 5 years, but also a potentially negative effect in resected stage 1A (Ann. Oncol. 2010 Oct;21 Suppl. 7:vii196-vii198).

"We need to make sure [MVI] is easily reproducible amongst pathologists, and we also clearly need to demonstrate that adjuvant therapy can overcome the biologic impact of this histopathologic finding," said Dr. Socinski of the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill.

Dr. Ruffini acknowledged that bias could have been introduced into the study through its retrospective design, use of overall survival rather than disease-free survival as an outcome measure, and the long study period of January 1998 to August 2008. Prospective validation of MVI is underway using the prospective International Association for the Study of Lung Cancer database, he said.

The median tumor size among the 512 patients was 3.4 cm, with 164 classified as having T1a (less than 2 cm) tumors, 123 T1b (2-3 cm), 164 T2a (3-5 cm), 50 T2b (5-7 cm), and 11 T3 (greater than 7 cm) tumors.

The researchers and Dr. Socinski disclosed no relevant conflicts.

CHICAGO - New data suggest that microscopic vascular invasion may be a more powerful prognosticator in early lung cancer than are the tumor size-based categories suggested in the new TNM staging system.

Italian researchers used histologic and immunohistochemical techniques to identify microscopic vascular invasion (MVI), or the presence of neoplastic structures inside the lumen of a vessel, in one-third (154) of 512 patients with resected, pathologically staged T1a to T3 node-negative non-small cell lung cancer (NSCLC). The 2009 edition of the tumor, node, metastasis (TNM) staging system for lung tumors was used.

MVI was significantly correlated with the presence of tumor-infiltrating lymphocytes (odds ratio 1.65, P value = .03), adenocarcinoma histology (OR 1.32, P = .003), and increased tumor size (OR 1.13, P = .009).

Five-year overall survival was significantly lower for patients with MVI at 50% vs. those without MVI at 66% (P = .001), Dr. Enrico Ruffini said at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

The difference in survival remained significant even in those with squamous cell carcinoma (45% vs. 61%, P = .05), although it was more pronounced in those with adenocarcinoma (56% vs. 70%, P = .03).

"Microscopic vascular invasion is a significant independent negative prognostic factor," he said.

When patients with pT1a-T2b tumors were stratified by T-size category, the presence of MVI resulted in a one-category upstaging for each T category, said Dr. Ruffini of the division of thoracic surgery at the University of Torino (Italy). For example, T1a patients with MVI had a prognosis similar to that of patients with T1b tumors without MVI. The number of T3 cases was too small to stratify.

T size was prognostic of survival in the MVI-negative patients (P = .03) but was not a statistically significant factor in MVI-positive patients (P = .9), indicating that MVI is indeed a more powerful prognosticator, he said.

The 2009 TNM stresses the importance of tumor size as a major prognostic factor, but no TNM edition has so far included MVI as a major determinant in the staging of NSCLC.

In a multivariate survival analysis that included age, sex, histology, grading, T-size determinant, MVI, perineural invasion, and tumor-infiltrating lymphocytes, MVI was a stronger prognostic indicator (hazard ratio 1.43, P = .02) than T-size determinant (HR 1.06, P = .06), Dr. Ruffini said.

"The use of adjuvant chemotherapy in NSCLC patients with MVI may be considered," he said.

Invited discussant Dr. Mark Socinski pointed out that 88% of patients in the analysis had 5 cm or smaller tumors, a category of patients in which the role of adjuvant therapy has been discouraged. He highlighted the recent LACE meta-analysis of 4,584 NSCLC patients in five cisplatin-based adjuvant chemotherapy trials that showed an overall significant survival benefit of 4% at 5 years, but also a potentially negative effect in resected stage 1A (Ann. Oncol. 2010 Oct;21 Suppl. 7:vii196-vii198).

"We need to make sure [MVI] is easily reproducible amongst pathologists, and we also clearly need to demonstrate that adjuvant therapy can overcome the biologic impact of this histopathologic finding," said Dr. Socinski of the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill.

Dr. Ruffini acknowledged that bias could have been introduced into the study through its retrospective design, use of overall survival rather than disease-free survival as an outcome measure, and the long study period of January 1998 to August 2008. Prospective validation of MVI is underway using the prospective International Association for the Study of Lung Cancer database, he said.

The median tumor size among the 512 patients was 3.4 cm, with 164 classified as having T1a (less than 2 cm) tumors, 123 T1b (2-3 cm), 164 T2a (3-5 cm), 50 T2b (5-7 cm), and 11 T3 (greater than 7 cm) tumors.

The researchers and Dr. Socinski disclosed no relevant conflicts.

CHICAGO - New data suggest that microscopic vascular invasion may be a more powerful prognosticator in early lung cancer than are the tumor size-based categories suggested in the new TNM staging system.

Italian researchers used histologic and immunohistochemical techniques to identify microscopic vascular invasion (MVI), or the presence of neoplastic structures inside the lumen of a vessel, in one-third (154) of 512 patients with resected, pathologically staged T1a to T3 node-negative non-small cell lung cancer (NSCLC). The 2009 edition of the tumor, node, metastasis (TNM) staging system for lung tumors was used.

MVI was significantly correlated with the presence of tumor-infiltrating lymphocytes (odds ratio 1.65, P value = .03), adenocarcinoma histology (OR 1.32, P = .003), and increased tumor size (OR 1.13, P = .009).

Five-year overall survival was significantly lower for patients with MVI at 50% vs. those without MVI at 66% (P = .001), Dr. Enrico Ruffini said at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

The difference in survival remained significant even in those with squamous cell carcinoma (45% vs. 61%, P = .05), although it was more pronounced in those with adenocarcinoma (56% vs. 70%, P = .03).

"Microscopic vascular invasion is a significant independent negative prognostic factor," he said.

When patients with pT1a-T2b tumors were stratified by T-size category, the presence of MVI resulted in a one-category upstaging for each T category, said Dr. Ruffini of the division of thoracic surgery at the University of Torino (Italy). For example, T1a patients with MVI had a prognosis similar to that of patients with T1b tumors without MVI. The number of T3 cases was too small to stratify.

T size was prognostic of survival in the MVI-negative patients (P = .03) but was not a statistically significant factor in MVI-positive patients (P = .9), indicating that MVI is indeed a more powerful prognosticator, he said.

The 2009 TNM stresses the importance of tumor size as a major prognostic factor, but no TNM edition has so far included MVI as a major determinant in the staging of NSCLC.

In a multivariate survival analysis that included age, sex, histology, grading, T-size determinant, MVI, perineural invasion, and tumor-infiltrating lymphocytes, MVI was a stronger prognostic indicator (hazard ratio 1.43, P = .02) than T-size determinant (HR 1.06, P = .06), Dr. Ruffini said.

"The use of adjuvant chemotherapy in NSCLC patients with MVI may be considered," he said.

Invited discussant Dr. Mark Socinski pointed out that 88% of patients in the analysis had 5 cm or smaller tumors, a category of patients in which the role of adjuvant therapy has been discouraged. He highlighted the recent LACE meta-analysis of 4,584 NSCLC patients in five cisplatin-based adjuvant chemotherapy trials that showed an overall significant survival benefit of 4% at 5 years, but also a potentially negative effect in resected stage 1A (Ann. Oncol. 2010 Oct;21 Suppl. 7:vii196-vii198).

"We need to make sure [MVI] is easily reproducible amongst pathologists, and we also clearly need to demonstrate that adjuvant therapy can overcome the biologic impact of this histopathologic finding," said Dr. Socinski of the Lineberger Comprehensive Cancer Center at the University of North Carolina, Chapel Hill.

Dr. Ruffini acknowledged that bias could have been introduced into the study through its retrospective design, use of overall survival rather than disease-free survival as an outcome measure, and the long study period of January 1998 to August 2008. Prospective validation of MVI is underway using the prospective International Association for the Study of Lung Cancer database, he said.

The median tumor size among the 512 patients was 3.4 cm, with 164 classified as having T1a (less than 2 cm) tumors, 123 T1b (2-3 cm), 164 T2a (3-5 cm), 50 T2b (5-7 cm), and 11 T3 (greater than 7 cm) tumors.

The researchers and Dr. Socinski disclosed no relevant conflicts.

LONDON - The daily, long-term use of low-dose aspirin cuts the risk of death from several types of cancer, according to a large meta-analysis.

In a meta-analysis of eight randomized clinical trials involving 25,570 patients, low-dose aspirin taken for 5 years or longer reduced mortality from esophageal, pancreatic, brain, stomach, colorectal, prostate, and even lung cancer, with doses as low as 75 mg/day having an effect.

This is the first time that low-dose aspirin has been linked to a reduction in cancer mortality other than colorectal cancer, said Dr. Peter M. Rothwell, who conceived and coordinated the research.

Dr. Rothwell of the John Radcliffe Hospital and the University of Oxford, United Kingdom, and his associates in October 2010 showed that low-dose aspirin reduced the 20-year risk of new colon cancer cases by approximately one-quarter and deaths by a third (Lancet 2010;376:1741-50).

The current study looked at all deaths from cancer that occurred during or after completion of eight randomized clinical trials that had been performed to look at the effects of daily aspirin vs. control for the primary or secondary prevention of vascular events (Lancet 2010 [doi:10.1016/S0140-6736(10)62110-1]).

Across all eight trials, 674 cancer deaths occurred in 25,570 patients, with aspirin treatment significantly reducing the risk of death, compared with no aspirin treatment (pooled odds ratio [OR] 0.79, 95% confidence interval [CI] 0.68-0.92, P = .003).

Using individual patient data available for seven of the trials and in which 657 cancer deaths occurred in 23,535 patients, the benefit of aspirin therapy was apparent only after 5 years or more of follow-up. The hazard ratio (HR) for death from all types of cancer was 0.66 (95% CI 0.50-0.87, P =.003), with a greater effect seen in patients with gastrointestinal tumors (HR 0.46, 95% CI 0.27-0.77, P =.003).

"We found that within the trials, while people were still on aspirin vs. no aspirin, the aspirin group had about a 30%-40% reduction in cancer deaths between year 5 and the end of the trial," Dr. Rothwell said at a press briefing.

To determine the longer-term effects of aspirin on cancer mortality, the team looked more closely at data from three of the trials. These had all been conducted in the United Kingdom and continued to collect information on cancer deaths via national death certification and cancer registration systems long after the trials had concluded.

In all, individual patient data were obtained on 1,634 cancer deaths that had occurred in 12,659 patients. Aspirin was found to reduce the 20-year risk of death from all solid cancers by 20% (HR 0.80, 95% CI 0.72-0.88, P less than .0001). Again, the effect on gastrointestinal cancer was greater (HR 0.65, 95% CI 0.54-0.78, P less than .0001), but there was no effect on hematologic malignancies.

At least 5 years of therapy were needed to reduce the risk of death from esophageal, pancreatic, brain, or lung cancer, with 10 years or more treatment required to see an effect on stomach and colorectal cancer death rates, and 15 years or more for prostate cancer. With regard to both lung and esophageal cancer, the effect of aspirin was limited to adenocarcinomas.

While the findings do not mean that everyone over the age of 40 years should now start taking daily aspirin to prevent cancer, given the increased risk of bleeding in some individuals, "We should probably stop taking people off aspirin unless they've got side effects," Dr. Rothwell said in an interview, adding "We probably shouldn't discourage those who want to take aspirin as actively as we have been doing."

"There is a fundamental difference between the treatment and the prevention of a disease," said Dr. Peter Elwood, professor of epidemiology at Cardiff University, Wales. Dr. Elwood suggested that deciding to take a daily dose of aspirin to prevent cancer could be another choice patients make once they have all the relevant facts, much as lifestyle changes are advised but not prescribed for cardiovascular disease prevention.

Dr. Rothwell has received honoraria from pharmaceutical companies with an interest in antiplatelet therapy, including AstraZeneca and Bayer.

LONDON - The daily, long-term use of low-dose aspirin cuts the risk of death from several types of cancer, according to a large meta-analysis.

In a meta-analysis of eight randomized clinical trials involving 25,570 patients, low-dose aspirin taken for 5 years or longer reduced mortality from esophageal, pancreatic, brain, stomach, colorectal, prostate, and even lung cancer, with doses as low as 75 mg/day having an effect.

This is the first time that low-dose aspirin has been linked to a reduction in cancer mortality other than colorectal cancer, said Dr. Peter M. Rothwell, who conceived and coordinated the research.

Dr. Rothwell of the John Radcliffe Hospital and the University of Oxford, United Kingdom, and his associates in October 2010 showed that low-dose aspirin reduced the 20-year risk of new colon cancer cases by approximately one-quarter and deaths by a third (Lancet 2010;376:1741-50).

The current study looked at all deaths from cancer that occurred during or after completion of eight randomized clinical trials that had been performed to look at the effects of daily aspirin vs. control for the primary or secondary prevention of vascular events (Lancet 2010 [doi:10.1016/S0140-6736(10)62110-1]).

Across all eight trials, 674 cancer deaths occurred in 25,570 patients, with aspirin treatment significantly reducing the risk of death, compared with no aspirin treatment (pooled odds ratio [OR] 0.79, 95% confidence interval [CI] 0.68-0.92, P = .003).

Using individual patient data available for seven of the trials and in which 657 cancer deaths occurred in 23,535 patients, the benefit of aspirin therapy was apparent only after 5 years or more of follow-up. The hazard ratio (HR) for death from all types of cancer was 0.66 (95% CI 0.50-0.87, P =.003), with a greater effect seen in patients with gastrointestinal tumors (HR 0.46, 95% CI 0.27-0.77, P =.003).

"We found that within the trials, while people were still on aspirin vs. no aspirin, the aspirin group had about a 30%-40% reduction in cancer deaths between year 5 and the end of the trial," Dr. Rothwell said at a press briefing.

To determine the longer-term effects of aspirin on cancer mortality, the team looked more closely at data from three of the trials. These had all been conducted in the United Kingdom and continued to collect information on cancer deaths via national death certification and cancer registration systems long after the trials had concluded.

In all, individual patient data were obtained on 1,634 cancer deaths that had occurred in 12,659 patients. Aspirin was found to reduce the 20-year risk of death from all solid cancers by 20% (HR 0.80, 95% CI 0.72-0.88, P less than .0001). Again, the effect on gastrointestinal cancer was greater (HR 0.65, 95% CI 0.54-0.78, P less than .0001), but there was no effect on hematologic malignancies.

At least 5 years of therapy were needed to reduce the risk of death from esophageal, pancreatic, brain, or lung cancer, with 10 years or more treatment required to see an effect on stomach and colorectal cancer death rates, and 15 years or more for prostate cancer. With regard to both lung and esophageal cancer, the effect of aspirin was limited to adenocarcinomas.

While the findings do not mean that everyone over the age of 40 years should now start taking daily aspirin to prevent cancer, given the increased risk of bleeding in some individuals, "We should probably stop taking people off aspirin unless they've got side effects," Dr. Rothwell said in an interview, adding "We probably shouldn't discourage those who want to take aspirin as actively as we have been doing."

"There is a fundamental difference between the treatment and the prevention of a disease," said Dr. Peter Elwood, professor of epidemiology at Cardiff University, Wales. Dr. Elwood suggested that deciding to take a daily dose of aspirin to prevent cancer could be another choice patients make once they have all the relevant facts, much as lifestyle changes are advised but not prescribed for cardiovascular disease prevention.

Dr. Rothwell has received honoraria from pharmaceutical companies with an interest in antiplatelet therapy, including AstraZeneca and Bayer.

LONDON - The daily, long-term use of low-dose aspirin cuts the risk of death from several types of cancer, according to a large meta-analysis.

In a meta-analysis of eight randomized clinical trials involving 25,570 patients, low-dose aspirin taken for 5 years or longer reduced mortality from esophageal, pancreatic, brain, stomach, colorectal, prostate, and even lung cancer, with doses as low as 75 mg/day having an effect.

This is the first time that low-dose aspirin has been linked to a reduction in cancer mortality other than colorectal cancer, said Dr. Peter M. Rothwell, who conceived and coordinated the research.

Dr. Rothwell of the John Radcliffe Hospital and the University of Oxford, United Kingdom, and his associates in October 2010 showed that low-dose aspirin reduced the 20-year risk of new colon cancer cases by approximately one-quarter and deaths by a third (Lancet 2010;376:1741-50).

The current study looked at all deaths from cancer that occurred during or after completion of eight randomized clinical trials that had been performed to look at the effects of daily aspirin vs. control for the primary or secondary prevention of vascular events (Lancet 2010 [doi:10.1016/S0140-6736(10)62110-1]).

Across all eight trials, 674 cancer deaths occurred in 25,570 patients, with aspirin treatment significantly reducing the risk of death, compared with no aspirin treatment (pooled odds ratio [OR] 0.79, 95% confidence interval [CI] 0.68-0.92, P = .003).

Using individual patient data available for seven of the trials and in which 657 cancer deaths occurred in 23,535 patients, the benefit of aspirin therapy was apparent only after 5 years or more of follow-up. The hazard ratio (HR) for death from all types of cancer was 0.66 (95% CI 0.50-0.87, P =.003), with a greater effect seen in patients with gastrointestinal tumors (HR 0.46, 95% CI 0.27-0.77, P =.003).

"We found that within the trials, while people were still on aspirin vs. no aspirin, the aspirin group had about a 30%-40% reduction in cancer deaths between year 5 and the end of the trial," Dr. Rothwell said at a press briefing.

To determine the longer-term effects of aspirin on cancer mortality, the team looked more closely at data from three of the trials. These had all been conducted in the United Kingdom and continued to collect information on cancer deaths via national death certification and cancer registration systems long after the trials had concluded.

In all, individual patient data were obtained on 1,634 cancer deaths that had occurred in 12,659 patients. Aspirin was found to reduce the 20-year risk of death from all solid cancers by 20% (HR 0.80, 95% CI 0.72-0.88, P less than .0001). Again, the effect on gastrointestinal cancer was greater (HR 0.65, 95% CI 0.54-0.78, P less than .0001), but there was no effect on hematologic malignancies.

At least 5 years of therapy were needed to reduce the risk of death from esophageal, pancreatic, brain, or lung cancer, with 10 years or more treatment required to see an effect on stomach and colorectal cancer death rates, and 15 years or more for prostate cancer. With regard to both lung and esophageal cancer, the effect of aspirin was limited to adenocarcinomas.

While the findings do not mean that everyone over the age of 40 years should now start taking daily aspirin to prevent cancer, given the increased risk of bleeding in some individuals, "We should probably stop taking people off aspirin unless they've got side effects," Dr. Rothwell said in an interview, adding "We probably shouldn't discourage those who want to take aspirin as actively as we have been doing."

"There is a fundamental difference between the treatment and the prevention of a disease," said Dr. Peter Elwood, professor of epidemiology at Cardiff University, Wales. Dr. Elwood suggested that deciding to take a daily dose of aspirin to prevent cancer could be another choice patients make once they have all the relevant facts, much as lifestyle changes are advised but not prescribed for cardiovascular disease prevention.

Dr. Rothwell has received honoraria from pharmaceutical companies with an interest in antiplatelet therapy, including AstraZeneca and Bayer.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

CHICAGO - Last fall, physicians at Vanderbilt University Medical Center began routinely testing all patients who were scheduled for coronary catheterization with a broad genotyping screen that - among other things - would identify whether they had a problem activating clopidogrel. By mid-November, the program had tested about 300 patients, including 10 found to have a poor-metabolizer genotype in the hepatic-enzyme gene CYP2C19 that would likely blunt the efficacy of a conventional clopidogrel dose. Many of the 10 patients received a doubled dose to compensate, whereas others who weren't aged 75 or older received the pricier, alternative agent prasugrel.

This experience marked the first phase of a new Vanderbilt program that will expand over time to include other patients in line to receive a drug with a pharmacogenetic dimension, Dr. Dan M. Roden said at the meeting. The genotyping program will soon expand to include patients who are scheduled for knee- or hip-replacement surgery, anticipating their need to start on warfarin. Genotype data can also help physicians select the best dosage for starting a warfarin regimen, said Dr. Roden, a cardiologist and assistant vice chancellor for personalized medicine at Vanderbilt in Nashville, Tenn.

Subsequent expansion plans are not yet set, but other candidates for genotyping include patients who are either already on or at an increased risk for soon starting tamoxifen, abacavir, azathioprine, 6-mercaptopurine, codeine, or "virtually any antidepressant or most antipsychotics,” Dr. Roden said in an interview.

"In the long perspective, every 50-year-old” is a good bet to eventually receive at least one drug for which a dosage adjustment based on genotype is warranted, but - stopping short of such global use right now - the Vanderbilt program will instead gradually phase in new groups of patients to the offer of genotyping.

"Implementation is a huge challenge. In my opinion, this will only work with preemptive implementation. Electronic records are not just repositories of information, but are nimble enough to provide support at the time of a prescription,” he said. "The way it ought to work is, a physician prescribes a drug and the electronic system recognizes [that] the drug has a genetic element and goes into the patient's record and finds the genotype information” to decide whether to flash a screen alert about the patient's genotype and the implications.

The program, known as PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) launched on Sept. 15. It uses a genotyping panel sold on the U.S. market by Illumina that screens for 184 different genetic polymorphisms in 34 genes that affect the absorption, distribution, metabolism, or excretion of various drugs.

Test results get posted into the record within a day of specimen collection.

So far, Vanderbilt itself has completely funded the program, which involved a year of planning and "a huge amount of money,” said Dr. Roden, adding that the program is the first of its kind worldwide. PREDICT is expected to improve patient outcomes and its developers hope to eventually convince payers to cover the cost.

Dr. Roden stated that he is or has been a consultant to several drug companies and has received royalties from Clinical Data Inc.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.

Gait speed independently predicts both major morbidity and mortality in elderly patients who are about to undergo cardiac surgery, according to a prospective, blinded study reported in the Journal of the American College of Cardiology.

"This simple, rapid, and inexpensive test effectively stratifies patients beyond traditional estimates of risk, which tend to be inaccurate in the elderly," said Dr. Jonathan Afilalo of McGill University, Montreal, and his associates.

Half the cardiac surgeries done in North America involve elderly patients (aged at least 70 years), but scoring systems for estimating operative risk perform poorly in this age group, "overestimating mortality by as much as 250%," they noted.

Dr. Afilalo and his colleagues performed what they described as the first study to test the value of gait speed as a predictor of poor outcomes in elderly cardiac surgery patients. The prospective, blinded study involved 131 patients (mean age, 76 years) who were scheduled to undergo elective coronary artery bypass and/or valve replacement or repair via standard sternotomy at four university-affiliated medical centers across Canada and the United States.

Before surgery, the study subjects were timed as they walked a distance of 5 meters in a well-lit hallway; subjects were permitted to use an aid such as a cane or walker if needed. A time of 6 seconds or longer was classified as a slow gait speed, whereas any time under 6 seconds was classified as a normal gait speed.

The primary composite end point was in-hospital mortality or any of five major complications (stroke, renal failure, prolonged ventilation, deep sternal wound infection, and need for reoperation).

In all, 60 patients (46%) were judged to have slow gait speed before surgery. Interestingly, gait speed did not correlate with the Society of Thoracic Surgeons' risk score, "suggesting that these were representing distinct domains," the investigators said.

After surgery, 30 patients (23%) experienced the primary composite end point.

Slow gait speed was a strong and independent predictor, associated with a 3.17-fold increase in risk of the primary end point. Moreover, adding gait speed to existing risk prediction models improved their performance in predicting which patients would experience an adverse event and which patients would need "to be discharged to a health care facility for ongoing medical care or rehabilitation."

Women with slow gait speed appeared to be at particularly high risk for adverse outcomes.

The study findings have three clinical implications. "First, by refining risk predictions in this challenging group, clinicians can have a more comprehensive assessment of their patient and provide a more accurate estimate of risk to the patient," Dr. Afilalo and his associates said (J. Am. Coll. Cardiol. 2010;56:1668-76).

Second, clinicians can better assess which elderly patients might have better success with less-invasive techniques such as trans-catheter valve implantation.

And third, patients who were found to have slow gait speed might benefit from extra interventions in the perioperative period, such as more intensive monitoring, early mobilization, low-intensity exercise training, or planned discharge to a specialized rehabilitation facility, they said.

The investigators reported no financial conflicts of interest.