Acquired Cardiovascular Disease

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.

SAN DIEGO - Although the right internal thoracic artery is biologically identical to the left internal thoracic artery, it is rarely used in coronary artery bypass grafting.

In a study comparing the use of different graft sources for coronary artery bypass grafting (CABG), Dr. James Tatoulis and his colleagues found that the right internal thoracic artery (RITA) showed equivalent results to using the left internal thoracic artery (LITA).

Dr. Tatoulis of the Royal Melbourne Hospital and his colleagues evaluated consecutive RITA graft angiograms performed from 1986 to 2008. Patency was examined over time by coronary territory and by whether the RITA was in situ or free, and was compared with other coronary conduits, according to the study presented at the annual meeting of the Society of Thoracic Surgeons.

A total of 5,766 patients had a RITA graft, usually as part of bilateral internal thoracic artery CABG. The operative mortality was 1.1%, and the rate of deep sternal infection was 1.5%. Of the nearly 7,800 coronary conduits studied, 991 RITA conduits were examined at a mean of 100 months postoperatively.

The overall 10-year RITA patency was 90%. RITA graft patency to the left anterior descending artery (n = 149) was 95% at 10 years and 90% at 15 years. Ten-year RITA patency to the circumflex marginal artery was 91% (n = 436), 85% (n = 199) to the right coronary artery (RCA), and 86% (n = 207) to the posterior descending artery (PDA). Ten-year patencies of RITA and LITA to the left anterior descending artery were identical.

In situ RITA (n=451) and free RITA (n=540) had similar 10-year patencies, 89% vs. 91% respectively.

RITA patency was found to be significantly better than radial artery and saphenous vein grafts for the circumflex marginal artery, the RCA, and the PDA. The 10-year survival of patients with RITA and LITA for triple-vessel coronary disease were identical at 89%.

Dr. Tatoulis and his colleagues stated that late patencies of RITA are excellent, equivalent to the LITA for identical territories, and always better than radial artery and saphenous vein grafts.

“Unfortunately, less than 10% of all coronary artery surgery worldwide is performed with two internal thoracic arteries," Dr. Tatoulis said in an interview.
He added that the use of this technique could improve patient outcomes and could offer an even better revascularization alternative to stents, particularly for triple-vessel coronary disease.

Dr. Tatoulis and his colleagues reported that they had no relevant disclosures.

SAN DIEGO - Although the right internal thoracic artery is biologically identical to the left internal thoracic artery, it is rarely used in coronary artery bypass grafting.

In a study comparing the use of different graft sources for coronary artery bypass grafting (CABG), Dr. James Tatoulis and his colleagues found that the right internal thoracic artery (RITA) showed equivalent results to using the left internal thoracic artery (LITA).

Dr. Tatoulis of the Royal Melbourne Hospital and his colleagues evaluated consecutive RITA graft angiograms performed from 1986 to 2008. Patency was examined over time by coronary territory and by whether the RITA was in situ or free, and was compared with other coronary conduits, according to the study presented at the annual meeting of the Society of Thoracic Surgeons.

A total of 5,766 patients had a RITA graft, usually as part of bilateral internal thoracic artery CABG. The operative mortality was 1.1%, and the rate of deep sternal infection was 1.5%. Of the nearly 7,800 coronary conduits studied, 991 RITA conduits were examined at a mean of 100 months postoperatively.

The overall 10-year RITA patency was 90%. RITA graft patency to the left anterior descending artery (n = 149) was 95% at 10 years and 90% at 15 years. Ten-year RITA patency to the circumflex marginal artery was 91% (n = 436), 85% (n = 199) to the right coronary artery (RCA), and 86% (n = 207) to the posterior descending artery (PDA). Ten-year patencies of RITA and LITA to the left anterior descending artery were identical.

In situ RITA (n=451) and free RITA (n=540) had similar 10-year patencies, 89% vs. 91% respectively.

RITA patency was found to be significantly better than radial artery and saphenous vein grafts for the circumflex marginal artery, the RCA, and the PDA. The 10-year survival of patients with RITA and LITA for triple-vessel coronary disease were identical at 89%.

Dr. Tatoulis and his colleagues stated that late patencies of RITA are excellent, equivalent to the LITA for identical territories, and always better than radial artery and saphenous vein grafts.

“Unfortunately, less than 10% of all coronary artery surgery worldwide is performed with two internal thoracic arteries," Dr. Tatoulis said in an interview.
He added that the use of this technique could improve patient outcomes and could offer an even better revascularization alternative to stents, particularly for triple-vessel coronary disease.

Dr. Tatoulis and his colleagues reported that they had no relevant disclosures.

SAN DIEGO - Although the right internal thoracic artery is biologically identical to the left internal thoracic artery, it is rarely used in coronary artery bypass grafting.

In a study comparing the use of different graft sources for coronary artery bypass grafting (CABG), Dr. James Tatoulis and his colleagues found that the right internal thoracic artery (RITA) showed equivalent results to using the left internal thoracic artery (LITA).

Dr. Tatoulis of the Royal Melbourne Hospital and his colleagues evaluated consecutive RITA graft angiograms performed from 1986 to 2008. Patency was examined over time by coronary territory and by whether the RITA was in situ or free, and was compared with other coronary conduits, according to the study presented at the annual meeting of the Society of Thoracic Surgeons.

A total of 5,766 patients had a RITA graft, usually as part of bilateral internal thoracic artery CABG. The operative mortality was 1.1%, and the rate of deep sternal infection was 1.5%. Of the nearly 7,800 coronary conduits studied, 991 RITA conduits were examined at a mean of 100 months postoperatively.

The overall 10-year RITA patency was 90%. RITA graft patency to the left anterior descending artery (n = 149) was 95% at 10 years and 90% at 15 years. Ten-year RITA patency to the circumflex marginal artery was 91% (n = 436), 85% (n = 199) to the right coronary artery (RCA), and 86% (n = 207) to the posterior descending artery (PDA). Ten-year patencies of RITA and LITA to the left anterior descending artery were identical.

In situ RITA (n=451) and free RITA (n=540) had similar 10-year patencies, 89% vs. 91% respectively.

RITA patency was found to be significantly better than radial artery and saphenous vein grafts for the circumflex marginal artery, the RCA, and the PDA. The 10-year survival of patients with RITA and LITA for triple-vessel coronary disease were identical at 89%.

Dr. Tatoulis and his colleagues stated that late patencies of RITA are excellent, equivalent to the LITA for identical territories, and always better than radial artery and saphenous vein grafts.

“Unfortunately, less than 10% of all coronary artery surgery worldwide is performed with two internal thoracic arteries," Dr. Tatoulis said in an interview.
He added that the use of this technique could improve patient outcomes and could offer an even better revascularization alternative to stents, particularly for triple-vessel coronary disease.

Dr. Tatoulis and his colleagues reported that they had no relevant disclosures.

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.

SAN DIEGO - Although the right internal thoracic artery is biologically identical to the left internal thoracic artery, it is rarely used in coronary artery bypass grafting.

In a study comparing the use of different graft sources for coronary artery bypass grafting (CABG), Dr. James Tatoulis and his colleagues found that the right internal thoracic artery (RITA) showed equivalent results to using the left internal thoracic artery (LITA).

Dr. Tatoulis of the Royal Melbourne Hospital and his colleagues evaluated consecutive RITA graft angiograms performed from 1986 to 2008. Patency was examined over time by coronary territory and by whether the RITA was in situ or free, and was compared with other coronary conduits, according to the study presented at the annual meeting of the Society of Thoracic Surgeons.

A total of 5,766 patients had a RITA graft, usually as part of bilateral internal thoracic artery CABG. The operative mortality was 1.1%, and the rate of deep sternal infection was 1.5%. Of the nearly 7,800 coronary conduits studied, 991 RITA conduits were examined at a mean of 100 months postoperatively.

The overall 10-year RITA patency was 90%. RITA graft patency to the left anterior descending artery (n = 149) was 95% at 10 years and 90% at 15 years. Ten-year RITA patency to the circumflex marginal artery was 91% (n = 436), 85% (n = 199) to the right coronary artery (RCA), and 86% (n = 207) to the posterior descending artery (PDA). Ten-year patencies of RITA and LITA to the left anterior descending artery were identical.

In situ RITA (n=451) and free RITA (n=540) had similar 10-year patencies, 89% vs. 91% respectively.

RITA patency was found to be significantly better than radial artery and saphenous vein grafts for the circumflex marginal artery, the RCA, and the PDA. The 10-year survival of patients with RITA and LITA for triple-vessel coronary disease were identical at 89%.

Dr. Tatoulis and his colleagues stated that late patencies of RITA are excellent, equivalent to the LITA for identical territories, and always better than radial artery and saphenous vein grafts.

“Unfortunately, less than 10% of all coronary artery surgery worldwide is performed with two internal thoracic arteries," Dr. Tatoulis said in an interview.
He added that the use of this technique could improve patient outcomes and could offer an even better revascularization alternative to stents, particularly for triple-vessel coronary disease.

Dr. Tatoulis and his colleagues reported that they had no relevant disclosures.

SAN DIEGO - Although the right internal thoracic artery is biologically identical to the left internal thoracic artery, it is rarely used in coronary artery bypass grafting.

In a study comparing the use of different graft sources for coronary artery bypass grafting (CABG), Dr. James Tatoulis and his colleagues found that the right internal thoracic artery (RITA) showed equivalent results to using the left internal thoracic artery (LITA).

Dr. Tatoulis of the Royal Melbourne Hospital and his colleagues evaluated consecutive RITA graft angiograms performed from 1986 to 2008. Patency was examined over time by coronary territory and by whether the RITA was in situ or free, and was compared with other coronary conduits, according to the study presented at the annual meeting of the Society of Thoracic Surgeons.

A total of 5,766 patients had a RITA graft, usually as part of bilateral internal thoracic artery CABG. The operative mortality was 1.1%, and the rate of deep sternal infection was 1.5%. Of the nearly 7,800 coronary conduits studied, 991 RITA conduits were examined at a mean of 100 months postoperatively.

The overall 10-year RITA patency was 90%. RITA graft patency to the left anterior descending artery (n = 149) was 95% at 10 years and 90% at 15 years. Ten-year RITA patency to the circumflex marginal artery was 91% (n = 436), 85% (n = 199) to the right coronary artery (RCA), and 86% (n = 207) to the posterior descending artery (PDA). Ten-year patencies of RITA and LITA to the left anterior descending artery were identical.

In situ RITA (n=451) and free RITA (n=540) had similar 10-year patencies, 89% vs. 91% respectively.

RITA patency was found to be significantly better than radial artery and saphenous vein grafts for the circumflex marginal artery, the RCA, and the PDA. The 10-year survival of patients with RITA and LITA for triple-vessel coronary disease were identical at 89%.

Dr. Tatoulis and his colleagues stated that late patencies of RITA are excellent, equivalent to the LITA for identical territories, and always better than radial artery and saphenous vein grafts.

“Unfortunately, less than 10% of all coronary artery surgery worldwide is performed with two internal thoracic arteries," Dr. Tatoulis said in an interview.
He added that the use of this technique could improve patient outcomes and could offer an even better revascularization alternative to stents, particularly for triple-vessel coronary disease.

Dr. Tatoulis and his colleagues reported that they had no relevant disclosures.

SAN DIEGO - Although the right internal thoracic artery is biologically identical to the left internal thoracic artery, it is rarely used in coronary artery bypass grafting.

In a study comparing the use of different graft sources for coronary artery bypass grafting (CABG), Dr. James Tatoulis and his colleagues found that the right internal thoracic artery (RITA) showed equivalent results to using the left internal thoracic artery (LITA).

Dr. Tatoulis of the Royal Melbourne Hospital and his colleagues evaluated consecutive RITA graft angiograms performed from 1986 to 2008. Patency was examined over time by coronary territory and by whether the RITA was in situ or free, and was compared with other coronary conduits, according to the study presented at the annual meeting of the Society of Thoracic Surgeons.

A total of 5,766 patients had a RITA graft, usually as part of bilateral internal thoracic artery CABG. The operative mortality was 1.1%, and the rate of deep sternal infection was 1.5%. Of the nearly 7,800 coronary conduits studied, 991 RITA conduits were examined at a mean of 100 months postoperatively.

The overall 10-year RITA patency was 90%. RITA graft patency to the left anterior descending artery (n = 149) was 95% at 10 years and 90% at 15 years. Ten-year RITA patency to the circumflex marginal artery was 91% (n = 436), 85% (n = 199) to the right coronary artery (RCA), and 86% (n = 207) to the posterior descending artery (PDA). Ten-year patencies of RITA and LITA to the left anterior descending artery were identical.

In situ RITA (n=451) and free RITA (n=540) had similar 10-year patencies, 89% vs. 91% respectively.

RITA patency was found to be significantly better than radial artery and saphenous vein grafts for the circumflex marginal artery, the RCA, and the PDA. The 10-year survival of patients with RITA and LITA for triple-vessel coronary disease were identical at 89%.

Dr. Tatoulis and his colleagues stated that late patencies of RITA are excellent, equivalent to the LITA for identical territories, and always better than radial artery and saphenous vein grafts.

“Unfortunately, less than 10% of all coronary artery surgery worldwide is performed with two internal thoracic arteries," Dr. Tatoulis said in an interview.
He added that the use of this technique could improve patient outcomes and could offer an even better revascularization alternative to stents, particularly for triple-vessel coronary disease.

Dr. Tatoulis and his colleagues reported that they had no relevant disclosures.

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.

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 - 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.

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.