Bruce Jancin

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

b.jancin@elsevier.com

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

b.jancin@elsevier.com

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

b.jancin@elsevier.com

SAN ANTONIO – A novel multigene signature known as the breast cancer index markedly outperformed the widely used Oncotype DX Recurrence Score and IHC4 tools in predicting late recurrences of estrogen receptor-positive/lymph node-negative breast cancer, Dr. Dennis C. Sgroi reported at the annual San Antonio Breast Cancer Symposium.

In a large clinical study, all three tools demonstrated significant prognostic value for early distant recurrences – that is, breast cancers recurring within 5 years of diagnosis. But only the breast cancer index (BCI) had sustained power for predicting distant recurrences arising during years 5-10. Both Oncotype DX and the IHC4 – a test based upon a tumor’s estrogen receptor, progesterone receptor, HER2, and Ki-67 status – lost their prognostic ability at about the 5-year mark, observed Dr. Sgroi of Massachusetts General Hospital, Boston.

More than half of all recurrences of estrogen receptor–positive early-stage breast cancer take place after 5 years of adjuvant tamoxifen or aromatase inhibitor therapy. Thus, the BCI fills a major need: a biomarker capable of identifying those estrogen receptor–positive breast cancer patients at increased risk for recurrence 5-10 years after their diagnosis.

The BCI includes the ratio of HOXB13-to-IL17BR gene expression and a five-gene molecular grade index shown to be predictive beyond tumor grade of distance metastasis. Dr. Sgroi and coinvestigators have previously established that these two biomarkers are complementary in their power to predict recurrences (Clin. Cancer Res. 2008;14:2601-8).

At the San Antonio symposium, Dr. Sgroi presented an analysis of the comparative prognostic performance of the BCI, the Oncotype DX recurrence score, and the IHC4 as applied to baseline tumor samples from 665 hormone receptor-positive participants in the randomized, multicenter TransATAC (Arimedex, Tamoxifen, Alone or Together) trial. The primary endpoint was distant recurrence.

The baseline BCI score differentiated three risk groups over the course of 10 years of follow-up in TransATAC: 58% of women fell into the low-risk group with a 4.2% risk of distant recurrence within 10 years, 25% had an intermediate score with an 18% risk, and 17% had a high score with a 30% risk.

In the first 5 years of follow-up, patients with a low- or intermediate-risk BCI had a distant recurrence risk of 1.3% and 5.6%, respectively. Thus, the BCI identified 83% of study participants as having, on average, a 5-year distant recurrence risk of less than 5%. In contrast, women with a high BCI score had a 5-year recurrence risk of 18%.

Among patients who remained disease free at 5 years, the 61% with a low baseline BCI score had a 3.5% rate of distant recurrence during years 5-10. Those with an intermediate or high BCI had a 13.4% rate.

In a multivariate analysis adjusted for the clinical treatment score – an algorithm based upon nodal status, tumor size and grade, age, and treatment (J. Clin. Oncol. 2011;29:4273-8) – the BCI, IHC4, and Oncotype DX displayed similar prognostic performance for distant recurrences in years 0-5. But the latter two tests lost their predictive capability in years 5-10.

Estrogen receptor–positive/node-negative patients have traditionally been considered at low risk. But, as shown in the TransATAC analysis, applying the BCI to primary tumor specimens from such patients enables physicians to identify two groups at the time of diagnosis: those who are at low risk for recurrence within the next 5 years and who are adequately treated with endocrine therapy alone; and a high-risk subgroup who should be considered for chemotherapy or some other additional therapy along with endocrine therapy, Dr. Sgroi concluded.

Moreover, the BCI score at diagnosis also permits identification of two distinct groups among patients remaining disease free at 5 years of follow up: those at low risk of late recurrence and who don’t need subsequent therapy; and those at roughly a threefold greater risk of late recurrence and are therefore candidates for further systemic adjuvant therapy.

"What that additional treatment should be is something we don’t know at this point. It might be extended adjuvant hormonal therapy alone or in combination with another therapeutic agent," he added.

In response to an audience question, Dr. Sgroi admitted that the exact biologic role of the genes incorporated in the BCI is "still a bit of a mystery," although it’s clear that they’re not solely involved in proliferation.

The TransATAC study was funded by AstraZeneca. Dr. Sgroi’s BCI work is supported by the National Institutes of Health, the U.S. Department of Defense, the Avon Foundation, and the Susan G. Komen for the Cure.

SAN ANTONIO – A novel multigene signature known as the breast cancer index markedly outperformed the widely used Oncotype DX Recurrence Score and IHC4 tools in predicting late recurrences of estrogen receptor-positive/lymph node-negative breast cancer, Dr. Dennis C. Sgroi reported at the annual San Antonio Breast Cancer Symposium.

In a large clinical study, all three tools demonstrated significant prognostic value for early distant recurrences – that is, breast cancers recurring within 5 years of diagnosis. But only the breast cancer index (BCI) had sustained power for predicting distant recurrences arising during years 5-10. Both Oncotype DX and the IHC4 – a test based upon a tumor’s estrogen receptor, progesterone receptor, HER2, and Ki-67 status – lost their prognostic ability at about the 5-year mark, observed Dr. Sgroi of Massachusetts General Hospital, Boston.

More than half of all recurrences of estrogen receptor–positive early-stage breast cancer take place after 5 years of adjuvant tamoxifen or aromatase inhibitor therapy. Thus, the BCI fills a major need: a biomarker capable of identifying those estrogen receptor–positive breast cancer patients at increased risk for recurrence 5-10 years after their diagnosis.

The BCI includes the ratio of HOXB13-to-IL17BR gene expression and a five-gene molecular grade index shown to be predictive beyond tumor grade of distance metastasis. Dr. Sgroi and coinvestigators have previously established that these two biomarkers are complementary in their power to predict recurrences (Clin. Cancer Res. 2008;14:2601-8).

At the San Antonio symposium, Dr. Sgroi presented an analysis of the comparative prognostic performance of the BCI, the Oncotype DX recurrence score, and the IHC4 as applied to baseline tumor samples from 665 hormone receptor-positive participants in the randomized, multicenter TransATAC (Arimedex, Tamoxifen, Alone or Together) trial. The primary endpoint was distant recurrence.

The baseline BCI score differentiated three risk groups over the course of 10 years of follow-up in TransATAC: 58% of women fell into the low-risk group with a 4.2% risk of distant recurrence within 10 years, 25% had an intermediate score with an 18% risk, and 17% had a high score with a 30% risk.

In the first 5 years of follow-up, patients with a low- or intermediate-risk BCI had a distant recurrence risk of 1.3% and 5.6%, respectively. Thus, the BCI identified 83% of study participants as having, on average, a 5-year distant recurrence risk of less than 5%. In contrast, women with a high BCI score had a 5-year recurrence risk of 18%.

Among patients who remained disease free at 5 years, the 61% with a low baseline BCI score had a 3.5% rate of distant recurrence during years 5-10. Those with an intermediate or high BCI had a 13.4% rate.

In a multivariate analysis adjusted for the clinical treatment score – an algorithm based upon nodal status, tumor size and grade, age, and treatment (J. Clin. Oncol. 2011;29:4273-8) – the BCI, IHC4, and Oncotype DX displayed similar prognostic performance for distant recurrences in years 0-5. But the latter two tests lost their predictive capability in years 5-10.

Estrogen receptor–positive/node-negative patients have traditionally been considered at low risk. But, as shown in the TransATAC analysis, applying the BCI to primary tumor specimens from such patients enables physicians to identify two groups at the time of diagnosis: those who are at low risk for recurrence within the next 5 years and who are adequately treated with endocrine therapy alone; and a high-risk subgroup who should be considered for chemotherapy or some other additional therapy along with endocrine therapy, Dr. Sgroi concluded.

Moreover, the BCI score at diagnosis also permits identification of two distinct groups among patients remaining disease free at 5 years of follow up: those at low risk of late recurrence and who don’t need subsequent therapy; and those at roughly a threefold greater risk of late recurrence and are therefore candidates for further systemic adjuvant therapy.

"What that additional treatment should be is something we don’t know at this point. It might be extended adjuvant hormonal therapy alone or in combination with another therapeutic agent," he added.

In response to an audience question, Dr. Sgroi admitted that the exact biologic role of the genes incorporated in the BCI is "still a bit of a mystery," although it’s clear that they’re not solely involved in proliferation.

The TransATAC study was funded by AstraZeneca. Dr. Sgroi’s BCI work is supported by the National Institutes of Health, the U.S. Department of Defense, the Avon Foundation, and the Susan G. Komen for the Cure.

SAN ANTONIO – A novel multigene signature known as the breast cancer index markedly outperformed the widely used Oncotype DX Recurrence Score and IHC4 tools in predicting late recurrences of estrogen receptor-positive/lymph node-negative breast cancer, Dr. Dennis C. Sgroi reported at the annual San Antonio Breast Cancer Symposium.

In a large clinical study, all three tools demonstrated significant prognostic value for early distant recurrences – that is, breast cancers recurring within 5 years of diagnosis. But only the breast cancer index (BCI) had sustained power for predicting distant recurrences arising during years 5-10. Both Oncotype DX and the IHC4 – a test based upon a tumor’s estrogen receptor, progesterone receptor, HER2, and Ki-67 status – lost their prognostic ability at about the 5-year mark, observed Dr. Sgroi of Massachusetts General Hospital, Boston.

More than half of all recurrences of estrogen receptor–positive early-stage breast cancer take place after 5 years of adjuvant tamoxifen or aromatase inhibitor therapy. Thus, the BCI fills a major need: a biomarker capable of identifying those estrogen receptor–positive breast cancer patients at increased risk for recurrence 5-10 years after their diagnosis.

The BCI includes the ratio of HOXB13-to-IL17BR gene expression and a five-gene molecular grade index shown to be predictive beyond tumor grade of distance metastasis. Dr. Sgroi and coinvestigators have previously established that these two biomarkers are complementary in their power to predict recurrences (Clin. Cancer Res. 2008;14:2601-8).

At the San Antonio symposium, Dr. Sgroi presented an analysis of the comparative prognostic performance of the BCI, the Oncotype DX recurrence score, and the IHC4 as applied to baseline tumor samples from 665 hormone receptor-positive participants in the randomized, multicenter TransATAC (Arimedex, Tamoxifen, Alone or Together) trial. The primary endpoint was distant recurrence.

The baseline BCI score differentiated three risk groups over the course of 10 years of follow-up in TransATAC: 58% of women fell into the low-risk group with a 4.2% risk of distant recurrence within 10 years, 25% had an intermediate score with an 18% risk, and 17% had a high score with a 30% risk.

In the first 5 years of follow-up, patients with a low- or intermediate-risk BCI had a distant recurrence risk of 1.3% and 5.6%, respectively. Thus, the BCI identified 83% of study participants as having, on average, a 5-year distant recurrence risk of less than 5%. In contrast, women with a high BCI score had a 5-year recurrence risk of 18%.

Among patients who remained disease free at 5 years, the 61% with a low baseline BCI score had a 3.5% rate of distant recurrence during years 5-10. Those with an intermediate or high BCI had a 13.4% rate.

In a multivariate analysis adjusted for the clinical treatment score – an algorithm based upon nodal status, tumor size and grade, age, and treatment (J. Clin. Oncol. 2011;29:4273-8) – the BCI, IHC4, and Oncotype DX displayed similar prognostic performance for distant recurrences in years 0-5. But the latter two tests lost their predictive capability in years 5-10.

Estrogen receptor–positive/node-negative patients have traditionally been considered at low risk. But, as shown in the TransATAC analysis, applying the BCI to primary tumor specimens from such patients enables physicians to identify two groups at the time of diagnosis: those who are at low risk for recurrence within the next 5 years and who are adequately treated with endocrine therapy alone; and a high-risk subgroup who should be considered for chemotherapy or some other additional therapy along with endocrine therapy, Dr. Sgroi concluded.

Moreover, the BCI score at diagnosis also permits identification of two distinct groups among patients remaining disease free at 5 years of follow up: those at low risk of late recurrence and who don’t need subsequent therapy; and those at roughly a threefold greater risk of late recurrence and are therefore candidates for further systemic adjuvant therapy.

"What that additional treatment should be is something we don’t know at this point. It might be extended adjuvant hormonal therapy alone or in combination with another therapeutic agent," he added.

In response to an audience question, Dr. Sgroi admitted that the exact biologic role of the genes incorporated in the BCI is "still a bit of a mystery," although it’s clear that they’re not solely involved in proliferation.

The TransATAC study was funded by AstraZeneca. Dr. Sgroi’s BCI work is supported by the National Institutes of Health, the U.S. Department of Defense, the Avon Foundation, and the Susan G. Komen for the Cure.

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

b.jancin@elsevier.com

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

b.jancin@elsevier.com

SNOWMASS, COLO. – The relentless national emphasis on reducing door-to-balloon times for ST-elevation myocardial infarction patients at percutaneous coronary intervention centers may have gotten out of hand, Dr. Bernard J. Gersh asserted at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

"It’s very difficult for me to stand up here and preach longer door-to-balloon times. It’s an un-American act, really. But I do think we’re getting door-to-balloon times so short that we’re starting to miss the big picture. We’re going to have to rethink this and not be penalized because we divert the patient to the coronary care unit just for 15 minutes to talk to the patient and try to answer some questions," said Dr. Gersh, professor of medicine at the Mayo Clinic, Rochester, Minn.

Average door-to-balloon times (DBTs) at percutaneous coronary intervention (PCI) centers have dropped substantially over the past decade. And DBT is a useful surrogate for overall care. But further reductions in DBT are not going to improve mortality. Moreover, they’ll have adverse consequences in terms of patient safety and health care costs, according to the cardiologist.

Dr. Gersh and his colleagues showed in a secondary analysis of 4,548 STEMI patients in the HORIZONS-AMI and CADILLAC trials that short DBTs of 90 minutes or less were associated with significantly lower 1-year mortality in subjects presenting to PCI centers within the first 90 minutes of ischemia, but had less impact for patients presenting with longer ischemia times (J. Am. Coll. Cardiol. 2010;56:407-13). And most patients in real-world clinical practice, as in these two trials, do present later.

"As we look to the future for further improvements in STEMI outcome, the focus is going to be outside the PCI hospital. It probably won’t be on new stents or new drugs. Transfer times are going to be a target. We’ll need coordinated reperfusion networks and development of protocols, and communication delays will have to be looked at," he said.

Another key strategy in improving STEMI outcomes will require shortening the time from symptom onset to first medical contact through greater public awareness and willingness to seek help quickly. That’s far easier said than done. "This is the most difficult part. This has been the Achilles heel of reperfusion therapy, and nothing really has worked to date," Dr. Gersh noted.

The counterproductive repercussions of pushing for faster and faster DBTs are illustrated by a report on 1,335 patients with suspected STEMI transferred to the Minneapolis Heart Institute for possible primary PCI from 30 outside hospitals in a regional network. At coronary angiography, 14% had no culprit lesion and 9.5% had no significant coronary artery disease. Among the subgroup of patients with left bundle branch block, these figures were threefold greater (JAMA 2007;298:2754-60).

More recent studies suggest false-activation cardiac catheterization laboratory rates may be even higher than in the Minneapolis report. For example, among 411 consecutive patients referred for primary PCI for suspected STEMI after presenting to the emergency departments at two Boston-area primary PCI-capable hospitals, 36% were found to not actually have STEMI (Arch. Intern. Med. 2012;172:864-71).

"There is merit in taking perhaps 10 minutes to just examine the patient before we put them on the catheterization table," Dr. Gersh observed. "Do they have pericarditis? Is this an aortic dissection? Is there intracranial pathology? Do they have a pacemaker? Is this an MI or is it really noncardiac pain?"

The other unwanted fallout from rushing to minimize DBTs is that all too often cardiologists are implanting drug-eluting stents without knowing whether a patient is capable of complying with the requirement of 12 months of dual antiplatelet therapy or can afford it. Furthermore, cardiologists don’t know what the renal function is, or whether the patient plans to have noncardiac surgery, which becomes more vexing in the setting of dual antiplatelet therapy.

Dr. Gersh believes the way forward in achieving further improvement in STEMI outcomes requires greater emphasis upon DIDO, or door-in to door-out time, defined as the time interval between patient arrival to discharge at the first or referring hospital. This is now a Centers for Medicare and Medicaid Services–mandated performance measure, with a recommended DIDO time of 30 minutes or less.

"This is a very good metric because it shares accountability. It puts the onus on the hospital transferring the patient, not just the referral center. It emphasizes a joint responsibility involving what they do at the receiving hospital and what we do at the primary PCI center," he explained.

The most recent report from the National Cardiovascular Data Registry’s ACTION Registry–Get With the Guidelines database underscores the enormous room for improvement in DIDO times. In a review of nearly 15,000 STEMI patients transferred for primary PCI to 298 referral centers, the median DIDO time was 68 minutes. Only 11% of patients met the recommended DIDO benchmark of 30 minutes or less. In-hospital mortality in those patients was 2.7%, compared with 5.9% in those with DIDOs greater than 30 minutes, a highly significant difference (JAMA 2011;305:2540-7).

Dr. Gersh reported that he serves as a consultant to Abbott, Boston Scientific, GE Healthcare, and other companies.

b.jancin@elsevier.com

SNOWMASS, COLO. – A structured frailty assessment has become an important tool for cardiologists in individualizing decisions regarding referral of elderly patients for heart procedures.

The frailty assessment aids in determining whether the procedure is likely to improve the individual’s long-term outcome, or if instead, multiple converging limitations unrelated to the cardiac condition are pushing the patient toward early functional losses and mortality from noncardiovascular causes.

More than 20 multidimensional frailty scales have been developed in the geriatrics literature during the past decade. For busy cardiologists, two of the simplest, fastest, and least expensive are walking speed and the Dalhousie Clinical Frailty Scale, Dr. Karen P. Alexander said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Walking speed can be assessed by a nonphysician with a stopwatch and two marks on the hallway floor 4-6 meters apart, noted Dr. Alexander, a cardiologist with a special interest in geriatrics at Duke University, Durham, N.C.

The first prospective study of walking speed as a predictor of mortality and major morbidity in elderly patients scheduled for cardiac surgery involved 131 subjects at four university hospitals. Those classified as slow walkers as defined by taking 6 seconds or longer to cover 5 meters in the clinic hallway had a threefold increased rate of the composite endpoint of in-hospital mortality, stroke, renal failure, prolonged infection, deep sternal wound infection, or reoperation. That was true even after adjusting for the widely used Society of Thoracic Surgeons risk score.

Patients with a high STS risk score, of 15% or more, plus a 5-meter walk speed of 6 seconds or longer, had a 43% incidence of mortality or major morbidity. Those with an STS risk score below 15% and a walking speed of less than 6 seconds had an event rate of only 6% (J. Am. Coll. Cardiol. 2010;56:1668-76).

More recently, a pooled analysis of 9 cohort studies totaling nearly 35,000 community-dwelling seniors followed for 6-21 years concluded that gait speed was significantly associated with remaining years of life in both men and women.

Lead investigator Dr. Stephanie Studenski, director of research in the division of geriatric medicine at the University of Pittsburgh, noted that each 0.1-meter/second increment in walking speed was associated with a 12% increase in survival. A walking speed of 0.8 meters/second was associated with the median life expectancy for persons in that age category. She proposed that a walking speed of 0.6 meters/second would be a reasonable threshold for increased risk of early mortality, that a speed faster than 1.0 meters/second suggests better than average life expectancy, and a gait speed above 1.2 meters/second suggests exceptional life expectancy (JAMA 2011;305:50-8).

Dr. Alexander said the Clinical Frailty Scale developed by Dr. Kenneth Rockwood and his coworkers at Dalhousie University in Halifax, Nova Scotia, allows physicians to quickly judge where an individual patient fits on a nine-point frailty scale.

"It gets raters on the same page and improves upon the ‘I know frailty when I see it’ eyeball test," she added.

It appears, however, that cardiologists may be underutilizing frailty assessments. When session moderator Dr. Rick A. Nishimura of the Mayo Clinic, Rochester, Minn., asked for an audience show of hands as to how many routinely make a comment about frailty in elderly patients’ charts, only about 40% responded affirmatively.

Panelist Michael J. Mack, a surgeon who has played a major role in the introduction of transcatheter aortic valve replacement (TAVR) in the United States, said he views frailty assessment as indispensable in deciding whether a patient with aortic stenosis is best served by TAVR, surgical replacement, or no procedure.

"On our heart team we spend a lot of time sorting out this matter of futility, where you can have a successful procedure but the patient dies anyway. We’re trying to sort out the patients who are dying with aortic stenosis from those that are dying from aortic stenosis," explained Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

At the Baylor heart team clinic, patients with aortic stenosis get a complete work-up in 1 day. It includes echocardiography, a CT scan, pulmonary function testing, determination of the STS risk score, and frailty testing. Four frailty tests are done routinely: a 5-meter walk test, grip strength, the Katz Activities of Daily Living, and a serum albumin. Then the surgeon and the cardiologist see the patient together.

"We have a pretty good idea before we ever walk into the room what the patient is a candidate for, on the basis of not only on the echo and CT scan, but also the frailty testing. This used to take a long time, but we see virtually eye to eye now and it requires no consultation outside the patient’s view to decide what we think the best option is," Dr. Mack said. "I see the ceiling coming down. We are denying patients now that 2 or 3 years ago we didn’t, because we realize that although they can get through the procedure successfully, their functional quality outcomes and survival at 1 year are not great."

Dr. Mack reported that he is the recipient of a research grant from Edwards Lifesciences. Dr. Alexander disclosed that she serves as a consultant to Gilead and Pozen.

SNOWMASS, COLO. – A structured frailty assessment has become an important tool for cardiologists in individualizing decisions regarding referral of elderly patients for heart procedures.

The frailty assessment aids in determining whether the procedure is likely to improve the individual’s long-term outcome, or if instead, multiple converging limitations unrelated to the cardiac condition are pushing the patient toward early functional losses and mortality from noncardiovascular causes.

More than 20 multidimensional frailty scales have been developed in the geriatrics literature during the past decade. For busy cardiologists, two of the simplest, fastest, and least expensive are walking speed and the Dalhousie Clinical Frailty Scale, Dr. Karen P. Alexander said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Walking speed can be assessed by a nonphysician with a stopwatch and two marks on the hallway floor 4-6 meters apart, noted Dr. Alexander, a cardiologist with a special interest in geriatrics at Duke University, Durham, N.C.

The first prospective study of walking speed as a predictor of mortality and major morbidity in elderly patients scheduled for cardiac surgery involved 131 subjects at four university hospitals. Those classified as slow walkers as defined by taking 6 seconds or longer to cover 5 meters in the clinic hallway had a threefold increased rate of the composite endpoint of in-hospital mortality, stroke, renal failure, prolonged infection, deep sternal wound infection, or reoperation. That was true even after adjusting for the widely used Society of Thoracic Surgeons risk score.

Patients with a high STS risk score, of 15% or more, plus a 5-meter walk speed of 6 seconds or longer, had a 43% incidence of mortality or major morbidity. Those with an STS risk score below 15% and a walking speed of less than 6 seconds had an event rate of only 6% (J. Am. Coll. Cardiol. 2010;56:1668-76).

More recently, a pooled analysis of 9 cohort studies totaling nearly 35,000 community-dwelling seniors followed for 6-21 years concluded that gait speed was significantly associated with remaining years of life in both men and women.

Lead investigator Dr. Stephanie Studenski, director of research in the division of geriatric medicine at the University of Pittsburgh, noted that each 0.1-meter/second increment in walking speed was associated with a 12% increase in survival. A walking speed of 0.8 meters/second was associated with the median life expectancy for persons in that age category. She proposed that a walking speed of 0.6 meters/second would be a reasonable threshold for increased risk of early mortality, that a speed faster than 1.0 meters/second suggests better than average life expectancy, and a gait speed above 1.2 meters/second suggests exceptional life expectancy (JAMA 2011;305:50-8).

Dr. Alexander said the Clinical Frailty Scale developed by Dr. Kenneth Rockwood and his coworkers at Dalhousie University in Halifax, Nova Scotia, allows physicians to quickly judge where an individual patient fits on a nine-point frailty scale.

"It gets raters on the same page and improves upon the ‘I know frailty when I see it’ eyeball test," she added.

It appears, however, that cardiologists may be underutilizing frailty assessments. When session moderator Dr. Rick A. Nishimura of the Mayo Clinic, Rochester, Minn., asked for an audience show of hands as to how many routinely make a comment about frailty in elderly patients’ charts, only about 40% responded affirmatively.

Panelist Michael J. Mack, a surgeon who has played a major role in the introduction of transcatheter aortic valve replacement (TAVR) in the United States, said he views frailty assessment as indispensable in deciding whether a patient with aortic stenosis is best served by TAVR, surgical replacement, or no procedure.

"On our heart team we spend a lot of time sorting out this matter of futility, where you can have a successful procedure but the patient dies anyway. We’re trying to sort out the patients who are dying with aortic stenosis from those that are dying from aortic stenosis," explained Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

At the Baylor heart team clinic, patients with aortic stenosis get a complete work-up in 1 day. It includes echocardiography, a CT scan, pulmonary function testing, determination of the STS risk score, and frailty testing. Four frailty tests are done routinely: a 5-meter walk test, grip strength, the Katz Activities of Daily Living, and a serum albumin. Then the surgeon and the cardiologist see the patient together.

"We have a pretty good idea before we ever walk into the room what the patient is a candidate for, on the basis of not only on the echo and CT scan, but also the frailty testing. This used to take a long time, but we see virtually eye to eye now and it requires no consultation outside the patient’s view to decide what we think the best option is," Dr. Mack said. "I see the ceiling coming down. We are denying patients now that 2 or 3 years ago we didn’t, because we realize that although they can get through the procedure successfully, their functional quality outcomes and survival at 1 year are not great."

Dr. Mack reported that he is the recipient of a research grant from Edwards Lifesciences. Dr. Alexander disclosed that she serves as a consultant to Gilead and Pozen.

SNOWMASS, COLO. – A structured frailty assessment has become an important tool for cardiologists in individualizing decisions regarding referral of elderly patients for heart procedures.

The frailty assessment aids in determining whether the procedure is likely to improve the individual’s long-term outcome, or if instead, multiple converging limitations unrelated to the cardiac condition are pushing the patient toward early functional losses and mortality from noncardiovascular causes.

More than 20 multidimensional frailty scales have been developed in the geriatrics literature during the past decade. For busy cardiologists, two of the simplest, fastest, and least expensive are walking speed and the Dalhousie Clinical Frailty Scale, Dr. Karen P. Alexander said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Walking speed can be assessed by a nonphysician with a stopwatch and two marks on the hallway floor 4-6 meters apart, noted Dr. Alexander, a cardiologist with a special interest in geriatrics at Duke University, Durham, N.C.

The first prospective study of walking speed as a predictor of mortality and major morbidity in elderly patients scheduled for cardiac surgery involved 131 subjects at four university hospitals. Those classified as slow walkers as defined by taking 6 seconds or longer to cover 5 meters in the clinic hallway had a threefold increased rate of the composite endpoint of in-hospital mortality, stroke, renal failure, prolonged infection, deep sternal wound infection, or reoperation. That was true even after adjusting for the widely used Society of Thoracic Surgeons risk score.

Patients with a high STS risk score, of 15% or more, plus a 5-meter walk speed of 6 seconds or longer, had a 43% incidence of mortality or major morbidity. Those with an STS risk score below 15% and a walking speed of less than 6 seconds had an event rate of only 6% (J. Am. Coll. Cardiol. 2010;56:1668-76).

More recently, a pooled analysis of 9 cohort studies totaling nearly 35,000 community-dwelling seniors followed for 6-21 years concluded that gait speed was significantly associated with remaining years of life in both men and women.

Lead investigator Dr. Stephanie Studenski, director of research in the division of geriatric medicine at the University of Pittsburgh, noted that each 0.1-meter/second increment in walking speed was associated with a 12% increase in survival. A walking speed of 0.8 meters/second was associated with the median life expectancy for persons in that age category. She proposed that a walking speed of 0.6 meters/second would be a reasonable threshold for increased risk of early mortality, that a speed faster than 1.0 meters/second suggests better than average life expectancy, and a gait speed above 1.2 meters/second suggests exceptional life expectancy (JAMA 2011;305:50-8).

Dr. Alexander said the Clinical Frailty Scale developed by Dr. Kenneth Rockwood and his coworkers at Dalhousie University in Halifax, Nova Scotia, allows physicians to quickly judge where an individual patient fits on a nine-point frailty scale.

"It gets raters on the same page and improves upon the ‘I know frailty when I see it’ eyeball test," she added.

It appears, however, that cardiologists may be underutilizing frailty assessments. When session moderator Dr. Rick A. Nishimura of the Mayo Clinic, Rochester, Minn., asked for an audience show of hands as to how many routinely make a comment about frailty in elderly patients’ charts, only about 40% responded affirmatively.

Panelist Michael J. Mack, a surgeon who has played a major role in the introduction of transcatheter aortic valve replacement (TAVR) in the United States, said he views frailty assessment as indispensable in deciding whether a patient with aortic stenosis is best served by TAVR, surgical replacement, or no procedure.

"On our heart team we spend a lot of time sorting out this matter of futility, where you can have a successful procedure but the patient dies anyway. We’re trying to sort out the patients who are dying with aortic stenosis from those that are dying from aortic stenosis," explained Dr. Mack, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at the Heart Hospital in Plano, Tex.

At the Baylor heart team clinic, patients with aortic stenosis get a complete work-up in 1 day. It includes echocardiography, a CT scan, pulmonary function testing, determination of the STS risk score, and frailty testing. Four frailty tests are done routinely: a 5-meter walk test, grip strength, the Katz Activities of Daily Living, and a serum albumin. Then the surgeon and the cardiologist see the patient together.

"We have a pretty good idea before we ever walk into the room what the patient is a candidate for, on the basis of not only on the echo and CT scan, but also the frailty testing. This used to take a long time, but we see virtually eye to eye now and it requires no consultation outside the patient’s view to decide what we think the best option is," Dr. Mack said. "I see the ceiling coming down. We are denying patients now that 2 or 3 years ago we didn’t, because we realize that although they can get through the procedure successfully, their functional quality outcomes and survival at 1 year are not great."

Dr. Mack reported that he is the recipient of a research grant from Edwards Lifesciences. Dr. Alexander disclosed that she serves as a consultant to Gilead and Pozen.

LOS ANGELES – A strategy of catheter ablation–based rhythm control in patients with long-standing persistent atrial fibrillation plus heart failure improved cardiopulmonary exercise capacity, quality of life, and neurohormonal status, compared with pharmacologic rate control in a single-center randomized trial.

The majority of improvement seen in these endpoints in the ARC-HF (Catheter Ablation Versus Medical Rate Control for Atrial Fibrillation in Patients With Heart Failure) trial occurred 3-12 months after the initial ablation procedure, Dr. David G. Jones reported at the annual scientific sessions of the American Heart Association.

"This may reflect progressive amelioration of the heart failure syndrome. And our findings may also have prognostic significance," said Dr. Jones of Imperial College London.

Indeed, although clinical outcomes weren’t included in the relatively small ARC-HF study, they were reported in the recently published 1,620-patient HF-ACTION (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure) trial (Circ. Heart Fail. 2012;5:579-85). And HF-ACTION showed that every 6% increase in peak oxygen uptake (VO₂) was associated with an 8% lower risk of the combined endpoint of cardiovascular mortality or heart failure hospitalization and a 7% reduction in all-cause mortality.

"By comparison, ours was close to a 20% increase in peak VO₂ at 1 year with ablation therapy," Dr. Jones observed.

The ARC-HF trial included 51 patients with continuous persistent atrial fibrillation (AF) for an average of 24 months, symptomatic systolic heart failure, and a left ventricular ejection fraction of 35% or less. Because it has been unclear whether restoration of sinus rhythm or pharmacologic rate control is the optimal management strategy in patients with AF and the common comorbidity of heart failure, the investigators randomized participants to catheter ablation of the arrhythmia or to rate control.

The primary endpoint was the change in peak VO₂ at 12 months from a baseline of roughly 17 mL/kg per minute. Peak VO₂ increased by a mean of 2.0 mL/kg per minute in the 25 patients in the ablation group while declining over time in the rate control group, for an impressive 12-month intergroup difference of 3.07 mL/kg per minute.

The ablation group also displayed significant improvements in quality of life as measured by the Minnesota Living With Heart Failure Questionnaire, as well as neurohormonal status as reflected in a reduction in brain natriuretic peptide levels. Data on other cardiac biomarkers are still being analyzed.

A significant reduction in baseline left atrial dilation was documented in the ablation group at 6 months and maintained at 12 months. The ablation group showed a nonsignificant trend toward improved left ventricular ejection fraction.

Dr. Jones stressed that the ablation procedures were long and challenging. They averaged 333 minutes in duration, including mapping, with fully 80 minutes of fluoroscopy time and 82 minutes of actual ablation.

Seven patients experienced recurrent atrial arrhythmias post ablation; five of them underwent a second ablation procedure and one had a third. The single-procedure success rate in achieving sinus rhythm at 12 months was 72%, with a multiprocedure success rate of 92%.

Of the 26 patients in the rate control group, 2 were in sinus rhythm at 12 months (including 1 patient who crossed over to catheter ablation), and 23 of the remaining 24 were optimally rate controlled, with a resting heart rate below 80 beats per minute and a maximum heart rate below 110 bpm during a 6-minute walk test.

Discussant Dr. Karl-Heinz Kuck called the ARC-HF results "remarkable." So much so, in fact, that he doesn’t think catheter ablation can be recommended for now in patients with long-standing persistent AF and heart failure, because the single-center ARC-HF results are out of step with those reported in observational series. Better, he said, to wait for the results of ongoing, much larger multicenter randomized trials, including CASTLE-AF as well as AMICA, for which he serves as principal investigator.

Among Dr. Kuck’s concerns was the whopping 2.0-mL/kg per minute increase in peak VO₂ reported in ARC-HF. To put that in perspective, the major randomized trials of cardiac resynchronization therapy and cardiac contractility modulation therapy for heart failure achieved increases of only 0.7-1.0 mL/kg per minute.

Also, a recent report from Dr. Kuck and his coinvestigators in the Hamburg Sequential Ablation Group, which involved 202 patients who underwent catheter ablation for long-standing persistent AF, showed only 36% were in sinus rhythm at 12 months after a single procedure and 60% after multiple procedures. Those success rates are substantially lower than in ARC-HF, noted Dr. Kuck, head of the cardiology department at St. Georg Hospital, Hamburg, Germany.

The 5-year success rates in the large Hamburg series were 20% and 45% after single and multiple ablation procedures, respectively. Success rates were far better in patients with a history of less than 2 years of persistent AF than in those who were arrhythmic for longer (J. Am. Coll. Cardiol. 2012;60:1921-9).

The ARC-HF study was supported by research grants from the Royal Brompton & Harefield NHS Foundation Trust. Dr. Jones reported having no financial conflicts. Dr. Kuck is on the speakers bureaus for Biosense Webster, Medtronic, St. Jude Medical, Abbott, Cardiofocus, and Biotronik.

b.jancin@elsevier.com

LOS ANGELES – A strategy of catheter ablation–based rhythm control in patients with long-standing persistent atrial fibrillation plus heart failure improved cardiopulmonary exercise capacity, quality of life, and neurohormonal status, compared with pharmacologic rate control in a single-center randomized trial.

The majority of improvement seen in these endpoints in the ARC-HF (Catheter Ablation Versus Medical Rate Control for Atrial Fibrillation in Patients With Heart Failure) trial occurred 3-12 months after the initial ablation procedure, Dr. David G. Jones reported at the annual scientific sessions of the American Heart Association.

"This may reflect progressive amelioration of the heart failure syndrome. And our findings may also have prognostic significance," said Dr. Jones of Imperial College London.

Indeed, although clinical outcomes weren’t included in the relatively small ARC-HF study, they were reported in the recently published 1,620-patient HF-ACTION (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure) trial (Circ. Heart Fail. 2012;5:579-85). And HF-ACTION showed that every 6% increase in peak oxygen uptake (VO₂) was associated with an 8% lower risk of the combined endpoint of cardiovascular mortality or heart failure hospitalization and a 7% reduction in all-cause mortality.

"By comparison, ours was close to a 20% increase in peak VO₂ at 1 year with ablation therapy," Dr. Jones observed.

The ARC-HF trial included 51 patients with continuous persistent atrial fibrillation (AF) for an average of 24 months, symptomatic systolic heart failure, and a left ventricular ejection fraction of 35% or less. Because it has been unclear whether restoration of sinus rhythm or pharmacologic rate control is the optimal management strategy in patients with AF and the common comorbidity of heart failure, the investigators randomized participants to catheter ablation of the arrhythmia or to rate control.

The primary endpoint was the change in peak VO₂ at 12 months from a baseline of roughly 17 mL/kg per minute. Peak VO₂ increased by a mean of 2.0 mL/kg per minute in the 25 patients in the ablation group while declining over time in the rate control group, for an impressive 12-month intergroup difference of 3.07 mL/kg per minute.

The ablation group also displayed significant improvements in quality of life as measured by the Minnesota Living With Heart Failure Questionnaire, as well as neurohormonal status as reflected in a reduction in brain natriuretic peptide levels. Data on other cardiac biomarkers are still being analyzed.

A significant reduction in baseline left atrial dilation was documented in the ablation group at 6 months and maintained at 12 months. The ablation group showed a nonsignificant trend toward improved left ventricular ejection fraction.

Dr. Jones stressed that the ablation procedures were long and challenging. They averaged 333 minutes in duration, including mapping, with fully 80 minutes of fluoroscopy time and 82 minutes of actual ablation.

Seven patients experienced recurrent atrial arrhythmias post ablation; five of them underwent a second ablation procedure and one had a third. The single-procedure success rate in achieving sinus rhythm at 12 months was 72%, with a multiprocedure success rate of 92%.

Of the 26 patients in the rate control group, 2 were in sinus rhythm at 12 months (including 1 patient who crossed over to catheter ablation), and 23 of the remaining 24 were optimally rate controlled, with a resting heart rate below 80 beats per minute and a maximum heart rate below 110 bpm during a 6-minute walk test.

Discussant Dr. Karl-Heinz Kuck called the ARC-HF results "remarkable." So much so, in fact, that he doesn’t think catheter ablation can be recommended for now in patients with long-standing persistent AF and heart failure, because the single-center ARC-HF results are out of step with those reported in observational series. Better, he said, to wait for the results of ongoing, much larger multicenter randomized trials, including CASTLE-AF as well as AMICA, for which he serves as principal investigator.

Among Dr. Kuck’s concerns was the whopping 2.0-mL/kg per minute increase in peak VO₂ reported in ARC-HF. To put that in perspective, the major randomized trials of cardiac resynchronization therapy and cardiac contractility modulation therapy for heart failure achieved increases of only 0.7-1.0 mL/kg per minute.

Also, a recent report from Dr. Kuck and his coinvestigators in the Hamburg Sequential Ablation Group, which involved 202 patients who underwent catheter ablation for long-standing persistent AF, showed only 36% were in sinus rhythm at 12 months after a single procedure and 60% after multiple procedures. Those success rates are substantially lower than in ARC-HF, noted Dr. Kuck, head of the cardiology department at St. Georg Hospital, Hamburg, Germany.

The 5-year success rates in the large Hamburg series were 20% and 45% after single and multiple ablation procedures, respectively. Success rates were far better in patients with a history of less than 2 years of persistent AF than in those who were arrhythmic for longer (J. Am. Coll. Cardiol. 2012;60:1921-9).

The ARC-HF study was supported by research grants from the Royal Brompton & Harefield NHS Foundation Trust. Dr. Jones reported having no financial conflicts. Dr. Kuck is on the speakers bureaus for Biosense Webster, Medtronic, St. Jude Medical, Abbott, Cardiofocus, and Biotronik.

b.jancin@elsevier.com

LOS ANGELES – A strategy of catheter ablation–based rhythm control in patients with long-standing persistent atrial fibrillation plus heart failure improved cardiopulmonary exercise capacity, quality of life, and neurohormonal status, compared with pharmacologic rate control in a single-center randomized trial.

The majority of improvement seen in these endpoints in the ARC-HF (Catheter Ablation Versus Medical Rate Control for Atrial Fibrillation in Patients With Heart Failure) trial occurred 3-12 months after the initial ablation procedure, Dr. David G. Jones reported at the annual scientific sessions of the American Heart Association.

"This may reflect progressive amelioration of the heart failure syndrome. And our findings may also have prognostic significance," said Dr. Jones of Imperial College London.

Indeed, although clinical outcomes weren’t included in the relatively small ARC-HF study, they were reported in the recently published 1,620-patient HF-ACTION (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure) trial (Circ. Heart Fail. 2012;5:579-85). And HF-ACTION showed that every 6% increase in peak oxygen uptake (VO₂) was associated with an 8% lower risk of the combined endpoint of cardiovascular mortality or heart failure hospitalization and a 7% reduction in all-cause mortality.

"By comparison, ours was close to a 20% increase in peak VO₂ at 1 year with ablation therapy," Dr. Jones observed.

The ARC-HF trial included 51 patients with continuous persistent atrial fibrillation (AF) for an average of 24 months, symptomatic systolic heart failure, and a left ventricular ejection fraction of 35% or less. Because it has been unclear whether restoration of sinus rhythm or pharmacologic rate control is the optimal management strategy in patients with AF and the common comorbidity of heart failure, the investigators randomized participants to catheter ablation of the arrhythmia or to rate control.

The primary endpoint was the change in peak VO₂ at 12 months from a baseline of roughly 17 mL/kg per minute. Peak VO₂ increased by a mean of 2.0 mL/kg per minute in the 25 patients in the ablation group while declining over time in the rate control group, for an impressive 12-month intergroup difference of 3.07 mL/kg per minute.

The ablation group also displayed significant improvements in quality of life as measured by the Minnesota Living With Heart Failure Questionnaire, as well as neurohormonal status as reflected in a reduction in brain natriuretic peptide levels. Data on other cardiac biomarkers are still being analyzed.

A significant reduction in baseline left atrial dilation was documented in the ablation group at 6 months and maintained at 12 months. The ablation group showed a nonsignificant trend toward improved left ventricular ejection fraction.

Dr. Jones stressed that the ablation procedures were long and challenging. They averaged 333 minutes in duration, including mapping, with fully 80 minutes of fluoroscopy time and 82 minutes of actual ablation.

Seven patients experienced recurrent atrial arrhythmias post ablation; five of them underwent a second ablation procedure and one had a third. The single-procedure success rate in achieving sinus rhythm at 12 months was 72%, with a multiprocedure success rate of 92%.

Of the 26 patients in the rate control group, 2 were in sinus rhythm at 12 months (including 1 patient who crossed over to catheter ablation), and 23 of the remaining 24 were optimally rate controlled, with a resting heart rate below 80 beats per minute and a maximum heart rate below 110 bpm during a 6-minute walk test.

Discussant Dr. Karl-Heinz Kuck called the ARC-HF results "remarkable." So much so, in fact, that he doesn’t think catheter ablation can be recommended for now in patients with long-standing persistent AF and heart failure, because the single-center ARC-HF results are out of step with those reported in observational series. Better, he said, to wait for the results of ongoing, much larger multicenter randomized trials, including CASTLE-AF as well as AMICA, for which he serves as principal investigator.

Among Dr. Kuck’s concerns was the whopping 2.0-mL/kg per minute increase in peak VO₂ reported in ARC-HF. To put that in perspective, the major randomized trials of cardiac resynchronization therapy and cardiac contractility modulation therapy for heart failure achieved increases of only 0.7-1.0 mL/kg per minute.

Also, a recent report from Dr. Kuck and his coinvestigators in the Hamburg Sequential Ablation Group, which involved 202 patients who underwent catheter ablation for long-standing persistent AF, showed only 36% were in sinus rhythm at 12 months after a single procedure and 60% after multiple procedures. Those success rates are substantially lower than in ARC-HF, noted Dr. Kuck, head of the cardiology department at St. Georg Hospital, Hamburg, Germany.

The 5-year success rates in the large Hamburg series were 20% and 45% after single and multiple ablation procedures, respectively. Success rates were far better in patients with a history of less than 2 years of persistent AF than in those who were arrhythmic for longer (J. Am. Coll. Cardiol. 2012;60:1921-9).

The ARC-HF study was supported by research grants from the Royal Brompton & Harefield NHS Foundation Trust. Dr. Jones reported having no financial conflicts. Dr. Kuck is on the speakers bureaus for Biosense Webster, Medtronic, St. Jude Medical, Abbott, Cardiofocus, and Biotronik.

b.jancin@elsevier.com

LOS ANGELES – A low-carbohydrate diet produced greater weight loss than did a low-fat diet and reduced systemic inflammation to a similar extent, according to results from a 6-month randomized trial.

The finding that both types of weight-loss diets produced similar reductions in inflammatory markers should help put to rest the concern that a low-carbohydrate diet’s higher fat content might have a negative impact on cardiovascular health, explained Kerry J. Stewart, Ed.D., at the annual scientific sessions of the American Heart Association.

"The concern about the low-carbohydrate diet is coming from the biomedical community. That’s why we did this study, to challenge that whole bias against this approach," explained Dr. Stewart, professor of cardiology and director of clinical research on exercise physiology at Johns Hopkins University, Baltimore.

"We’ve been told for the last 30-40 years, especially by the AHA and other groups, that high fat in the diet raises cholesterol and that all the other things that go along with that have harmful effects on the vasculature," he noted. "But we’ve previously shown no adverse effects on endothelial function or vascular stiffness, [as well as] significant improvements in blood pressure and cholesterol levels, with a low-carbohydrate diet."

Dr. Stewart reported on 60 middle-age overweight or obese patients who participated in a lifestyle intervention consisting of an exercise program plus randomization to a low-fat diet or an isocaloric low-carbohydrate diet.

From a mean baseline body weight of 97.1 kg, patients in the low-carbohydrate-diet group lost an average of 13.1 kg over 6 months, compared with 8.2 kg in the patients on the low-fat diet. From a mean baseline of 43.3%, total body fat dropped by an absolute 6.8% in the low-carb group, a significantly better result than the 4.0% decrease in the low-fat group. From a baseline mean body mass index of 34.2 kg/m², BMI improved by 4.7 kg/m² in the low-carbohydrate diet group, compared with 2.9 kg/m² with the low-fat diet.

High-sensitivity C-reactive protein levels fell by a mean of 1.8 mg/L in both groups, from 5.2 mg/L at baseline. The other markers of systemic inflammation measured in the study – levels of interleukin-6 and tumor necrosis factor-alpha – also improved to a similar degree in both study arms.

"It’s important to keep in mind that this was a weight-loss study. If someone is normal- or underweight and eats this kind of low-carbohydrate diet, I’m not exactly sure what would happen," Dr. Stewart observed. "But in the context of a weight-loss program, it seems like the weight loss is an overwhelming benefit that overcomes any possible risks from eating more fat."

One audience member who had helped run a study of an Atkins-type low-carb/high-fat diet said he and his coinvestigators found deleterious effects on arterial flow-mediated dilation over the course of a year. But Dr. Stewart was unconvinced.

"We’ve looked at that literature. It’s a real mixed bag. Some studies show just what you say, others show just the opposite," he replied. "It’s very hard to draw any conclusions from these feeding studies. We’ve done some of them ourselves and found just the opposite of what you said."

Also, as another audience member pointed out, the low-carbohydrate diet employed in this study wasn’t an Atkins-type diet that’s high in total and saturated fat. Dr. Stewart agreed. "The patients really didn’t eat more fat, compared to the typical American diet," he noted.

Indeed, the roughly 1,700 Kcal/day low-carbohydrate diet consisted of 28% of energy from carbohydrates, 29% from protein, and 39% from fat. The isocaloric low-fat diet was 49% carbohydrate, 21% protein, and 29% fat.

Dr. Stewart reported having no financial conflicts.

LOS ANGELES – A low-carbohydrate diet produced greater weight loss than did a low-fat diet and reduced systemic inflammation to a similar extent, according to results from a 6-month randomized trial.

The finding that both types of weight-loss diets produced similar reductions in inflammatory markers should help put to rest the concern that a low-carbohydrate diet’s higher fat content might have a negative impact on cardiovascular health, explained Kerry J. Stewart, Ed.D., at the annual scientific sessions of the American Heart Association.

"The concern about the low-carbohydrate diet is coming from the biomedical community. That’s why we did this study, to challenge that whole bias against this approach," explained Dr. Stewart, professor of cardiology and director of clinical research on exercise physiology at Johns Hopkins University, Baltimore.

"We’ve been told for the last 30-40 years, especially by the AHA and other groups, that high fat in the diet raises cholesterol and that all the other things that go along with that have harmful effects on the vasculature," he noted. "But we’ve previously shown no adverse effects on endothelial function or vascular stiffness, [as well as] significant improvements in blood pressure and cholesterol levels, with a low-carbohydrate diet."

Dr. Stewart reported on 60 middle-age overweight or obese patients who participated in a lifestyle intervention consisting of an exercise program plus randomization to a low-fat diet or an isocaloric low-carbohydrate diet.

From a mean baseline body weight of 97.1 kg, patients in the low-carbohydrate-diet group lost an average of 13.1 kg over 6 months, compared with 8.2 kg in the patients on the low-fat diet. From a mean baseline of 43.3%, total body fat dropped by an absolute 6.8% in the low-carb group, a significantly better result than the 4.0% decrease in the low-fat group. From a baseline mean body mass index of 34.2 kg/m², BMI improved by 4.7 kg/m² in the low-carbohydrate diet group, compared with 2.9 kg/m² with the low-fat diet.

High-sensitivity C-reactive protein levels fell by a mean of 1.8 mg/L in both groups, from 5.2 mg/L at baseline. The other markers of systemic inflammation measured in the study – levels of interleukin-6 and tumor necrosis factor-alpha – also improved to a similar degree in both study arms.

"It’s important to keep in mind that this was a weight-loss study. If someone is normal- or underweight and eats this kind of low-carbohydrate diet, I’m not exactly sure what would happen," Dr. Stewart observed. "But in the context of a weight-loss program, it seems like the weight loss is an overwhelming benefit that overcomes any possible risks from eating more fat."

One audience member who had helped run a study of an Atkins-type low-carb/high-fat diet said he and his coinvestigators found deleterious effects on arterial flow-mediated dilation over the course of a year. But Dr. Stewart was unconvinced.

"We’ve looked at that literature. It’s a real mixed bag. Some studies show just what you say, others show just the opposite," he replied. "It’s very hard to draw any conclusions from these feeding studies. We’ve done some of them ourselves and found just the opposite of what you said."

Also, as another audience member pointed out, the low-carbohydrate diet employed in this study wasn’t an Atkins-type diet that’s high in total and saturated fat. Dr. Stewart agreed. "The patients really didn’t eat more fat, compared to the typical American diet," he noted.

Indeed, the roughly 1,700 Kcal/day low-carbohydrate diet consisted of 28% of energy from carbohydrates, 29% from protein, and 39% from fat. The isocaloric low-fat diet was 49% carbohydrate, 21% protein, and 29% fat.

Dr. Stewart reported having no financial conflicts.

LOS ANGELES – A low-carbohydrate diet produced greater weight loss than did a low-fat diet and reduced systemic inflammation to a similar extent, according to results from a 6-month randomized trial.

The finding that both types of weight-loss diets produced similar reductions in inflammatory markers should help put to rest the concern that a low-carbohydrate diet’s higher fat content might have a negative impact on cardiovascular health, explained Kerry J. Stewart, Ed.D., at the annual scientific sessions of the American Heart Association.

"The concern about the low-carbohydrate diet is coming from the biomedical community. That’s why we did this study, to challenge that whole bias against this approach," explained Dr. Stewart, professor of cardiology and director of clinical research on exercise physiology at Johns Hopkins University, Baltimore.

"We’ve been told for the last 30-40 years, especially by the AHA and other groups, that high fat in the diet raises cholesterol and that all the other things that go along with that have harmful effects on the vasculature," he noted. "But we’ve previously shown no adverse effects on endothelial function or vascular stiffness, [as well as] significant improvements in blood pressure and cholesterol levels, with a low-carbohydrate diet."

Dr. Stewart reported on 60 middle-age overweight or obese patients who participated in a lifestyle intervention consisting of an exercise program plus randomization to a low-fat diet or an isocaloric low-carbohydrate diet.

From a mean baseline body weight of 97.1 kg, patients in the low-carbohydrate-diet group lost an average of 13.1 kg over 6 months, compared with 8.2 kg in the patients on the low-fat diet. From a mean baseline of 43.3%, total body fat dropped by an absolute 6.8% in the low-carb group, a significantly better result than the 4.0% decrease in the low-fat group. From a baseline mean body mass index of 34.2 kg/m², BMI improved by 4.7 kg/m² in the low-carbohydrate diet group, compared with 2.9 kg/m² with the low-fat diet.

High-sensitivity C-reactive protein levels fell by a mean of 1.8 mg/L in both groups, from 5.2 mg/L at baseline. The other markers of systemic inflammation measured in the study – levels of interleukin-6 and tumor necrosis factor-alpha – also improved to a similar degree in both study arms.

"It’s important to keep in mind that this was a weight-loss study. If someone is normal- or underweight and eats this kind of low-carbohydrate diet, I’m not exactly sure what would happen," Dr. Stewart observed. "But in the context of a weight-loss program, it seems like the weight loss is an overwhelming benefit that overcomes any possible risks from eating more fat."

One audience member who had helped run a study of an Atkins-type low-carb/high-fat diet said he and his coinvestigators found deleterious effects on arterial flow-mediated dilation over the course of a year. But Dr. Stewart was unconvinced.

"We’ve looked at that literature. It’s a real mixed bag. Some studies show just what you say, others show just the opposite," he replied. "It’s very hard to draw any conclusions from these feeding studies. We’ve done some of them ourselves and found just the opposite of what you said."

Also, as another audience member pointed out, the low-carbohydrate diet employed in this study wasn’t an Atkins-type diet that’s high in total and saturated fat. Dr. Stewart agreed. "The patients really didn’t eat more fat, compared to the typical American diet," he noted.

Indeed, the roughly 1,700 Kcal/day low-carbohydrate diet consisted of 28% of energy from carbohydrates, 29% from protein, and 39% from fat. The isocaloric low-fat diet was 49% carbohydrate, 21% protein, and 29% fat.

Dr. Stewart reported having no financial conflicts.

SNOWMASS, COLO. – The once highly attractive notion that boosting HDL cholesterol levels will reduce cardiovascular event rates is now dead, or more generously, it remains unsupported by evidence despite expenditure of billions of dollars on negative clinical trials.

"An iconic concept of HDL has not borne good fruit. It really isn’t what we don’t know that hurts us so much as the things that we think are true but just ain’t so – and that’s the story of HDL," Dr. Robert A. Vogel said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Indeed, it now appears that the relationship between HDL and atherosclerosis is far more complicated than lipidologists thought. Evidence now suggests that HDL mass may not be as important as HDL function, which can switch between being anti- and pro-atherogenic in a matter of hours. And HDL may not even be playing an active role in cardiovascular risk; a low HDL may be associated with an increase in cardiovascular events simply because it is a marker for other cardiovascular risk factors, such as obesity, smoking, and insulin resistance.

"This has been a sea change in thinking for me. HDL is something I thought I understood. But I understood it a lot better 10 years ago than I do now," admitted Dr. Vogel of the University of Colorado, Denver.

HDL-raising drugs from multiple classes have now crashed and burned in large randomized trials with clinical endpoints. Thus, the idea that just because a drug does good things to the lipid profile it follows that the agent will also reduce cardiovascular risk "has to die," the cardiologist continued.

Take, for example, niacin.

"Metabolically, niacin does everything right – if you’re a lipidologist. Absolutely everything. It lowers triglycerides, lowers LDL, raises HDL, lowers total cholesterol, lowers C-reactive protein, and increases the beneficial large HDL particles. You would conclude from this that there would be no way niacin would not reduce cardiovascular risk," he explained.

That’s why the negative results of the National Institutes of Health–sponsored 3,414-patient AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglycerides and Impact on Global Health Outcomes) trial came as such a surprise. In AIM-HIGH, randomization to 1.5-2.0 g of extended-release niacin daily in patients on background simvastatin and, if need be, ezetimibe, had no impact on major cardiovascular events (N. Engl. J. Med. 2011;365:2255-67).

The final nail in niacin’s coffin came a few months ago in the form of Merck’s preliminary announcement of a negative result in the massive phase III Health Protection Study-2 THRIVE trial, in which nearly 26,000 subjects with cardiovascular disease and/or diabetes in the United Kingdom, Scandinavia, and China were randomized to 2 g of extended-release niacin plus the antiflushing agent laropiprant daily or placebo on top of background therapy with simvastatin plus or minus ezetimibe. During 3.9 years of prospective follow-up, niacin boosted HDL levels by 17% and reduced LDL by 20%, but it had no impact upon cardiovascular events and was associated with increased risk of serious adverse events.

"I’m going to say it twice: If you have a patient on niacin, take that patient off. Again, if you have a patient on niacin, take that patient off. There is no evidence base at the present time that a patient should be on niacin to reduce cardiovascular risk," Dr. Vogel stressed.

The investigational cholesterol ester transfer protein (CETP) inhibitors produce whopping increases in HDL but to date have proved to be a crushing disappointment in large clinical trials. In the ILLUMINATE trial, the CETP inhibitor torcetrapib raised HDL by 70% and lowered LDL by 30% – and yet it increased all-cause mortality by 60%. Development of torcetrapib has been discontinued.

In the 15,871-patient dal-OUTCOMES trial, the CETP modulator dalcetrapib also produced salutary effects on HDL and LDL, but with absolutely no change in cardiovascular events (N. Engl. J. Med. 2012;367:2089-99).

The only anti-CETP drug that still has a prayer of ever reaching the marketplace is anacetrapib. In the ongoing 1,625-subject DEFINE trial, it has produced a 140% increase in HDL and a 40% drop in LDL. But whether the drug improves clinical outcomes remains to be seen.

As for the fibrates, a meta-analysis of six major randomized trials showed these HDL-raisers had no impact on coronary heart disease (CHD) mortality.

Even the hallowed and robust inverse relation between HDL level and cardiovascular risk described 27 years ago in the Framingham Heart Study (JAMA 1986;256:2835-8) has come under question. This inverse association wasn’t evident in the dal-OUTCOMES trial, and was of only borderline significance in the 10,001-patient Treating to New Targets (TNT) trial (N. Engl. J. Med. 2007;357:1301-10).

"The Framingham data are not quite so right. In these large clinical trials, the inverse relationship between HDL and cardiovascular events was seen only at very low HDL levels – below 30 mg/dL – and not across the broad spectrum," according to the cardiologist.

The most persuasive challenge to the concept that raising HDL will translate into reduced risk of CHD comes from a recent genetic analysis, Dr. Vogel continued. This ambitious project, sponsored by the National Institutes of Health, the Wellcome Trust, the European Union, the British Heart Foundation, and the German government, tracked the prevalence of 14 genetic variants associated with increased HDL in 20 studies totaling more than 100,000 subjects, including nearly 21,000 with a myocardial infarction. The presence of these HDL-raising genes was not associated with reduced risk of MI (Lancet 2012;380:572-80).

What can physicians committed to evidence-based medicine do at this point to prevent cardiovascular events in their patients with low HDL?

Prescribe a statin, regardless of their LDL level, Dr. Vogel said. A consistent finding in the landmark statin trials was that patients with low baseline HDL levels were at higher risk of coronary events, and therefore statin therapy had its biggest benefit. That benefit wasn’t due to the drugs’ small effect on HDL, but rather to their LDL-lowering.

In addition, considerably weaker evidence suggests fibrates may have a limited role in reducing cardiovascular risk in two selected populations. One is in patients with mild to moderate chronic kidney disease, for whom a recent meta-analysis of 10 clinical trials including nearly 17,000 participants showed fibrate therapy reduced the risk of major cardiovascular events by 30% and the risk of cardiovascular mortality by 40% (J. Am. Coll. Cardiol. 2012;60:2061-71). Dr. Vogel rates this evidence worthy of a level IIb recommendation, meaning "you might consider a fibrate in folks with mild to moderate chronic impairment of renal function."

Another group of patients in which fibrate therapy might reasonably be considered are those with a triglyceride level in excess of 200 mg/dL and an HDL level below 35 mg/dL. In subgroup analyses of virtually all of the major fibrate clinical trials, a benefit was shown in that subgroup. Dr. Vogel gives fibrate therapy in such patients a IIb recommendation as well.

As for lifestyle modification as a means of boosting HDL, moderate alcohol consumption, physical exercise, smoking cessation, and weight loss have all been shown to increase HDL. All of these are healthful behaviors, but there is very little hard data to show whether the cardiovascular benefits come from the increase in HDL or some other mechanism.

"If you want to do something in terms of lifestyle modification, tell your patients to run from bar to bar," he quipped.

Dr. Vogel reported having no financial conflicts.

b.jancin@elsevier.com

SNOWMASS, COLO. – The once highly attractive notion that boosting HDL cholesterol levels will reduce cardiovascular event rates is now dead, or more generously, it remains unsupported by evidence despite expenditure of billions of dollars on negative clinical trials.

"An iconic concept of HDL has not borne good fruit. It really isn’t what we don’t know that hurts us so much as the things that we think are true but just ain’t so – and that’s the story of HDL," Dr. Robert A. Vogel said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Indeed, it now appears that the relationship between HDL and atherosclerosis is far more complicated than lipidologists thought. Evidence now suggests that HDL mass may not be as important as HDL function, which can switch between being anti- and pro-atherogenic in a matter of hours. And HDL may not even be playing an active role in cardiovascular risk; a low HDL may be associated with an increase in cardiovascular events simply because it is a marker for other cardiovascular risk factors, such as obesity, smoking, and insulin resistance.

"This has been a sea change in thinking for me. HDL is something I thought I understood. But I understood it a lot better 10 years ago than I do now," admitted Dr. Vogel of the University of Colorado, Denver.

HDL-raising drugs from multiple classes have now crashed and burned in large randomized trials with clinical endpoints. Thus, the idea that just because a drug does good things to the lipid profile it follows that the agent will also reduce cardiovascular risk "has to die," the cardiologist continued.

Take, for example, niacin.

"Metabolically, niacin does everything right – if you’re a lipidologist. Absolutely everything. It lowers triglycerides, lowers LDL, raises HDL, lowers total cholesterol, lowers C-reactive protein, and increases the beneficial large HDL particles. You would conclude from this that there would be no way niacin would not reduce cardiovascular risk," he explained.

That’s why the negative results of the National Institutes of Health–sponsored 3,414-patient AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglycerides and Impact on Global Health Outcomes) trial came as such a surprise. In AIM-HIGH, randomization to 1.5-2.0 g of extended-release niacin daily in patients on background simvastatin and, if need be, ezetimibe, had no impact on major cardiovascular events (N. Engl. J. Med. 2011;365:2255-67).

The final nail in niacin’s coffin came a few months ago in the form of Merck’s preliminary announcement of a negative result in the massive phase III Health Protection Study-2 THRIVE trial, in which nearly 26,000 subjects with cardiovascular disease and/or diabetes in the United Kingdom, Scandinavia, and China were randomized to 2 g of extended-release niacin plus the antiflushing agent laropiprant daily or placebo on top of background therapy with simvastatin plus or minus ezetimibe. During 3.9 years of prospective follow-up, niacin boosted HDL levels by 17% and reduced LDL by 20%, but it had no impact upon cardiovascular events and was associated with increased risk of serious adverse events.

"I’m going to say it twice: If you have a patient on niacin, take that patient off. Again, if you have a patient on niacin, take that patient off. There is no evidence base at the present time that a patient should be on niacin to reduce cardiovascular risk," Dr. Vogel stressed.

The investigational cholesterol ester transfer protein (CETP) inhibitors produce whopping increases in HDL but to date have proved to be a crushing disappointment in large clinical trials. In the ILLUMINATE trial, the CETP inhibitor torcetrapib raised HDL by 70% and lowered LDL by 30% – and yet it increased all-cause mortality by 60%. Development of torcetrapib has been discontinued.

In the 15,871-patient dal-OUTCOMES trial, the CETP modulator dalcetrapib also produced salutary effects on HDL and LDL, but with absolutely no change in cardiovascular events (N. Engl. J. Med. 2012;367:2089-99).

The only anti-CETP drug that still has a prayer of ever reaching the marketplace is anacetrapib. In the ongoing 1,625-subject DEFINE trial, it has produced a 140% increase in HDL and a 40% drop in LDL. But whether the drug improves clinical outcomes remains to be seen.

As for the fibrates, a meta-analysis of six major randomized trials showed these HDL-raisers had no impact on coronary heart disease (CHD) mortality.

Even the hallowed and robust inverse relation between HDL level and cardiovascular risk described 27 years ago in the Framingham Heart Study (JAMA 1986;256:2835-8) has come under question. This inverse association wasn’t evident in the dal-OUTCOMES trial, and was of only borderline significance in the 10,001-patient Treating to New Targets (TNT) trial (N. Engl. J. Med. 2007;357:1301-10).

"The Framingham data are not quite so right. In these large clinical trials, the inverse relationship between HDL and cardiovascular events was seen only at very low HDL levels – below 30 mg/dL – and not across the broad spectrum," according to the cardiologist.

The most persuasive challenge to the concept that raising HDL will translate into reduced risk of CHD comes from a recent genetic analysis, Dr. Vogel continued. This ambitious project, sponsored by the National Institutes of Health, the Wellcome Trust, the European Union, the British Heart Foundation, and the German government, tracked the prevalence of 14 genetic variants associated with increased HDL in 20 studies totaling more than 100,000 subjects, including nearly 21,000 with a myocardial infarction. The presence of these HDL-raising genes was not associated with reduced risk of MI (Lancet 2012;380:572-80).

What can physicians committed to evidence-based medicine do at this point to prevent cardiovascular events in their patients with low HDL?

Prescribe a statin, regardless of their LDL level, Dr. Vogel said. A consistent finding in the landmark statin trials was that patients with low baseline HDL levels were at higher risk of coronary events, and therefore statin therapy had its biggest benefit. That benefit wasn’t due to the drugs’ small effect on HDL, but rather to their LDL-lowering.

In addition, considerably weaker evidence suggests fibrates may have a limited role in reducing cardiovascular risk in two selected populations. One is in patients with mild to moderate chronic kidney disease, for whom a recent meta-analysis of 10 clinical trials including nearly 17,000 participants showed fibrate therapy reduced the risk of major cardiovascular events by 30% and the risk of cardiovascular mortality by 40% (J. Am. Coll. Cardiol. 2012;60:2061-71). Dr. Vogel rates this evidence worthy of a level IIb recommendation, meaning "you might consider a fibrate in folks with mild to moderate chronic impairment of renal function."

Another group of patients in which fibrate therapy might reasonably be considered are those with a triglyceride level in excess of 200 mg/dL and an HDL level below 35 mg/dL. In subgroup analyses of virtually all of the major fibrate clinical trials, a benefit was shown in that subgroup. Dr. Vogel gives fibrate therapy in such patients a IIb recommendation as well.

As for lifestyle modification as a means of boosting HDL, moderate alcohol consumption, physical exercise, smoking cessation, and weight loss have all been shown to increase HDL. All of these are healthful behaviors, but there is very little hard data to show whether the cardiovascular benefits come from the increase in HDL or some other mechanism.

"If you want to do something in terms of lifestyle modification, tell your patients to run from bar to bar," he quipped.

Dr. Vogel reported having no financial conflicts.

b.jancin@elsevier.com

SNOWMASS, COLO. – The once highly attractive notion that boosting HDL cholesterol levels will reduce cardiovascular event rates is now dead, or more generously, it remains unsupported by evidence despite expenditure of billions of dollars on negative clinical trials.

"An iconic concept of HDL has not borne good fruit. It really isn’t what we don’t know that hurts us so much as the things that we think are true but just ain’t so – and that’s the story of HDL," Dr. Robert A. Vogel said at the annual cardiovascular conference at Snowmass sponsored by the American College of Cardiology.

Indeed, it now appears that the relationship between HDL and atherosclerosis is far more complicated than lipidologists thought. Evidence now suggests that HDL mass may not be as important as HDL function, which can switch between being anti- and pro-atherogenic in a matter of hours. And HDL may not even be playing an active role in cardiovascular risk; a low HDL may be associated with an increase in cardiovascular events simply because it is a marker for other cardiovascular risk factors, such as obesity, smoking, and insulin resistance.

"This has been a sea change in thinking for me. HDL is something I thought I understood. But I understood it a lot better 10 years ago than I do now," admitted Dr. Vogel of the University of Colorado, Denver.

HDL-raising drugs from multiple classes have now crashed and burned in large randomized trials with clinical endpoints. Thus, the idea that just because a drug does good things to the lipid profile it follows that the agent will also reduce cardiovascular risk "has to die," the cardiologist continued.

Take, for example, niacin.

"Metabolically, niacin does everything right – if you’re a lipidologist. Absolutely everything. It lowers triglycerides, lowers LDL, raises HDL, lowers total cholesterol, lowers C-reactive protein, and increases the beneficial large HDL particles. You would conclude from this that there would be no way niacin would not reduce cardiovascular risk," he explained.

That’s why the negative results of the National Institutes of Health–sponsored 3,414-patient AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglycerides and Impact on Global Health Outcomes) trial came as such a surprise. In AIM-HIGH, randomization to 1.5-2.0 g of extended-release niacin daily in patients on background simvastatin and, if need be, ezetimibe, had no impact on major cardiovascular events (N. Engl. J. Med. 2011;365:2255-67).

The final nail in niacin’s coffin came a few months ago in the form of Merck’s preliminary announcement of a negative result in the massive phase III Health Protection Study-2 THRIVE trial, in which nearly 26,000 subjects with cardiovascular disease and/or diabetes in the United Kingdom, Scandinavia, and China were randomized to 2 g of extended-release niacin plus the antiflushing agent laropiprant daily or placebo on top of background therapy with simvastatin plus or minus ezetimibe. During 3.9 years of prospective follow-up, niacin boosted HDL levels by 17% and reduced LDL by 20%, but it had no impact upon cardiovascular events and was associated with increased risk of serious adverse events.

"I’m going to say it twice: If you have a patient on niacin, take that patient off. Again, if you have a patient on niacin, take that patient off. There is no evidence base at the present time that a patient should be on niacin to reduce cardiovascular risk," Dr. Vogel stressed.

The investigational cholesterol ester transfer protein (CETP) inhibitors produce whopping increases in HDL but to date have proved to be a crushing disappointment in large clinical trials. In the ILLUMINATE trial, the CETP inhibitor torcetrapib raised HDL by 70% and lowered LDL by 30% – and yet it increased all-cause mortality by 60%. Development of torcetrapib has been discontinued.

In the 15,871-patient dal-OUTCOMES trial, the CETP modulator dalcetrapib also produced salutary effects on HDL and LDL, but with absolutely no change in cardiovascular events (N. Engl. J. Med. 2012;367:2089-99).

The only anti-CETP drug that still has a prayer of ever reaching the marketplace is anacetrapib. In the ongoing 1,625-subject DEFINE trial, it has produced a 140% increase in HDL and a 40% drop in LDL. But whether the drug improves clinical outcomes remains to be seen.

As for the fibrates, a meta-analysis of six major randomized trials showed these HDL-raisers had no impact on coronary heart disease (CHD) mortality.

Even the hallowed and robust inverse relation between HDL level and cardiovascular risk described 27 years ago in the Framingham Heart Study (JAMA 1986;256:2835-8) has come under question. This inverse association wasn’t evident in the dal-OUTCOMES trial, and was of only borderline significance in the 10,001-patient Treating to New Targets (TNT) trial (N. Engl. J. Med. 2007;357:1301-10).

"The Framingham data are not quite so right. In these large clinical trials, the inverse relationship between HDL and cardiovascular events was seen only at very low HDL levels – below 30 mg/dL – and not across the broad spectrum," according to the cardiologist.

The most persuasive challenge to the concept that raising HDL will translate into reduced risk of CHD comes from a recent genetic analysis, Dr. Vogel continued. This ambitious project, sponsored by the National Institutes of Health, the Wellcome Trust, the European Union, the British Heart Foundation, and the German government, tracked the prevalence of 14 genetic variants associated with increased HDL in 20 studies totaling more than 100,000 subjects, including nearly 21,000 with a myocardial infarction. The presence of these HDL-raising genes was not associated with reduced risk of MI (Lancet 2012;380:572-80).

What can physicians committed to evidence-based medicine do at this point to prevent cardiovascular events in their patients with low HDL?

Prescribe a statin, regardless of their LDL level, Dr. Vogel said. A consistent finding in the landmark statin trials was that patients with low baseline HDL levels were at higher risk of coronary events, and therefore statin therapy had its biggest benefit. That benefit wasn’t due to the drugs’ small effect on HDL, but rather to their LDL-lowering.

In addition, considerably weaker evidence suggests fibrates may have a limited role in reducing cardiovascular risk in two selected populations. One is in patients with mild to moderate chronic kidney disease, for whom a recent meta-analysis of 10 clinical trials including nearly 17,000 participants showed fibrate therapy reduced the risk of major cardiovascular events by 30% and the risk of cardiovascular mortality by 40% (J. Am. Coll. Cardiol. 2012;60:2061-71). Dr. Vogel rates this evidence worthy of a level IIb recommendation, meaning "you might consider a fibrate in folks with mild to moderate chronic impairment of renal function."

Another group of patients in which fibrate therapy might reasonably be considered are those with a triglyceride level in excess of 200 mg/dL and an HDL level below 35 mg/dL. In subgroup analyses of virtually all of the major fibrate clinical trials, a benefit was shown in that subgroup. Dr. Vogel gives fibrate therapy in such patients a IIb recommendation as well.

As for lifestyle modification as a means of boosting HDL, moderate alcohol consumption, physical exercise, smoking cessation, and weight loss have all been shown to increase HDL. All of these are healthful behaviors, but there is very little hard data to show whether the cardiovascular benefits come from the increase in HDL or some other mechanism.

"If you want to do something in terms of lifestyle modification, tell your patients to run from bar to bar," he quipped.

Dr. Vogel reported having no financial conflicts.

b.jancin@elsevier.com

Curbing the high rates of anal cancer in HIV-infected individuals won’t be accomplished through targeted efforts focused on HIV-positive men who have sex with men, according to Dr. Michel Janier, head of dermatology at Saint Joseph Hospital in Paris and the French representative to the International Union Against Sexually Transmitted Infections – Europe.

Anal cancer rates among HIV-infected persons are indeed highest among men who have sex with men (MSM), but anal cancer rates also are quite high among other HIV-infected men and women, based on results of a large study.

Photo: Cynthia Goldsmith, CDC

The findings take on added significance given the availability of the HPV vaccine, although the efficacy of the vaccine in HIV-positive individuals remains to be seen. In addition, pilot projects testing the benefits of periodic anal histology screening in HIV-infected individuals are underway, Dr. Janier observed at the annual congress of the European Academy of Dermatology and Venereology.

The study by Dr. Michael J. Silverberg of Kaiser Permanente, Oakland, Calif., and the North American AIDS Cohort Collaboration on Research and Design (NA–ACCORD) of IeDEA included 36,189 HIV-infected North Americans and 114,260 uninfected controls followed during 1996-2007. The HIV-positive group comprised 55% MSM, 19% heterosexual men, and 26% women.

The unadjusted anal cancer incidence rates per 100,000 person-years were 131 for HIV-positive MSM, 46 for HIV-infected heterosexual men, and 2 for uninfected men. This translated to a demographically adjusted rate ratio of 80.3 for MSM compared with uninfected men, and to a 26.7-fold increased risk of anal cancer in HIV-infected straight men compared with uninfected heterosexual men.

HIV-infected women had an anal cancer incidence rate of 30 cases per 100,000 person-years. A rate ratio could not be determined because no cases occurred in uninfected women (Clin. Infect. Dis. 2012;54:1026-34).

Among HIV-infected individuals, the adjusted relative risk of anal cancer doubled from 1996-1999 to 2000-2003, then leveled off. This is in line with the findings of the large French Hospital Database Study, which also observed a jump in anal cancer rates among HIV-infected individuals in the late 1990s followed by more recent stabilization in the era of widely available antiretroviral therapy (AIDS 2008;22:1203-11).

The National Institutes of Health was the chief sponsor of the study. Dr. Janier reported having no financial conflicts.

Curbing the high rates of anal cancer in HIV-infected individuals won’t be accomplished through targeted efforts focused on HIV-positive men who have sex with men, according to Dr. Michel Janier, head of dermatology at Saint Joseph Hospital in Paris and the French representative to the International Union Against Sexually Transmitted Infections – Europe.

Anal cancer rates among HIV-infected persons are indeed highest among men who have sex with men (MSM), but anal cancer rates also are quite high among other HIV-infected men and women, based on results of a large study.

Photo: Cynthia Goldsmith, CDC

The findings take on added significance given the availability of the HPV vaccine, although the efficacy of the vaccine in HIV-positive individuals remains to be seen. In addition, pilot projects testing the benefits of periodic anal histology screening in HIV-infected individuals are underway, Dr. Janier observed at the annual congress of the European Academy of Dermatology and Venereology.

The study by Dr. Michael J. Silverberg of Kaiser Permanente, Oakland, Calif., and the North American AIDS Cohort Collaboration on Research and Design (NA–ACCORD) of IeDEA included 36,189 HIV-infected North Americans and 114,260 uninfected controls followed during 1996-2007. The HIV-positive group comprised 55% MSM, 19% heterosexual men, and 26% women.

The unadjusted anal cancer incidence rates per 100,000 person-years were 131 for HIV-positive MSM, 46 for HIV-infected heterosexual men, and 2 for uninfected men. This translated to a demographically adjusted rate ratio of 80.3 for MSM compared with uninfected men, and to a 26.7-fold increased risk of anal cancer in HIV-infected straight men compared with uninfected heterosexual men.

HIV-infected women had an anal cancer incidence rate of 30 cases per 100,000 person-years. A rate ratio could not be determined because no cases occurred in uninfected women (Clin. Infect. Dis. 2012;54:1026-34).

Among HIV-infected individuals, the adjusted relative risk of anal cancer doubled from 1996-1999 to 2000-2003, then leveled off. This is in line with the findings of the large French Hospital Database Study, which also observed a jump in anal cancer rates among HIV-infected individuals in the late 1990s followed by more recent stabilization in the era of widely available antiretroviral therapy (AIDS 2008;22:1203-11).

The National Institutes of Health was the chief sponsor of the study. Dr. Janier reported having no financial conflicts.

Curbing the high rates of anal cancer in HIV-infected individuals won’t be accomplished through targeted efforts focused on HIV-positive men who have sex with men, according to Dr. Michel Janier, head of dermatology at Saint Joseph Hospital in Paris and the French representative to the International Union Against Sexually Transmitted Infections – Europe.

Anal cancer rates among HIV-infected persons are indeed highest among men who have sex with men (MSM), but anal cancer rates also are quite high among other HIV-infected men and women, based on results of a large study.

Photo: Cynthia Goldsmith, CDC

The findings take on added significance given the availability of the HPV vaccine, although the efficacy of the vaccine in HIV-positive individuals remains to be seen. In addition, pilot projects testing the benefits of periodic anal histology screening in HIV-infected individuals are underway, Dr. Janier observed at the annual congress of the European Academy of Dermatology and Venereology.

The study by Dr. Michael J. Silverberg of Kaiser Permanente, Oakland, Calif., and the North American AIDS Cohort Collaboration on Research and Design (NA–ACCORD) of IeDEA included 36,189 HIV-infected North Americans and 114,260 uninfected controls followed during 1996-2007. The HIV-positive group comprised 55% MSM, 19% heterosexual men, and 26% women.

The unadjusted anal cancer incidence rates per 100,000 person-years were 131 for HIV-positive MSM, 46 for HIV-infected heterosexual men, and 2 for uninfected men. This translated to a demographically adjusted rate ratio of 80.3 for MSM compared with uninfected men, and to a 26.7-fold increased risk of anal cancer in HIV-infected straight men compared with uninfected heterosexual men.

HIV-infected women had an anal cancer incidence rate of 30 cases per 100,000 person-years. A rate ratio could not be determined because no cases occurred in uninfected women (Clin. Infect. Dis. 2012;54:1026-34).

Among HIV-infected individuals, the adjusted relative risk of anal cancer doubled from 1996-1999 to 2000-2003, then leveled off. This is in line with the findings of the large French Hospital Database Study, which also observed a jump in anal cancer rates among HIV-infected individuals in the late 1990s followed by more recent stabilization in the era of widely available antiretroviral therapy (AIDS 2008;22:1203-11).

The National Institutes of Health was the chief sponsor of the study. Dr. Janier reported having no financial conflicts.

SAN ANTONIO – Metabolic syndrome is a potent independent risk factor for breast cancer recurrence in patients who are otherwise at low risk, based on a widely used 21-gene recurrence score assay.

This novel finding in an observational study underscores how much is riding on the outcome of ongoing randomized clinical trials of metformin and aggressive lifestyle modification through weight loss and exercise for secondary prevention of breast cancer, Dr. Arti Lakhani reported at the annual San Antonio Breast Cancer Symposium. If those interventions ultimately prove effective in reducing the risk of breast cancer recurrence, their success may in part be attributed to their ability to reduce the prevalence of metabolic syndrome.

Dr. Lakhani, of Loyola University Medical Center in Maywood, Ill., presented a single-center study of 322 consecutive women newly diagnosed in 2006-2011 with estrogen receptor–positive/lymph node–negative early-stage breast cancer. All patients’ tumors were analyzed using the Oncotype DX assay, which is used to estimate the risk of recurrence based on the expression of 21 genes.

Of the 322 patients, 89 (27%) met World Health Organization criteria for metabolic syndrome. So far, breast cancer has recurred in 21 patients; 13 (62%) of them had metabolic syndrome.

In a multivariate analysis, patients with a low-risk Oncotype DX score of 0-17 had a 24-fold greater risk of recurrence if they had metabolic syndrome. In intermediate-risk patients having a score of 18-30, metabolic syndrome was independently associated with a fourfold increased risk of recurrence. In patients with higher scores, metabolic syndrome didn’t significantly add to the predictive value of the test result, said Dr. Lakhani.

The impact of metabolic syndrome on recurrence score was independent of tumor grade, size, HER2/neu status, and Ki67, as well as patient age and menopausal status.

During a discussion after the presentation, one physician remarked that if the findings are confirmed in an independent data set with larger numbers, he would feel compelled to recommend chemotherapy in all patients with hormone receptor–positive/lymph node–negative breast cancer and metabolic syndrome.

Another oncologist observed that breast cancer treatment seems to inherently promote metabolic syndrome, with its pear-shaped body habitus. "If my breast cancer patients don’t have metabolic syndrome before they start treatment, they often seem to afterwards."

Dr. Lakhani reported having no financial conflicts.

b.jancin@elsevier.com

SAN ANTONIO – Metabolic syndrome is a potent independent risk factor for breast cancer recurrence in patients who are otherwise at low risk, based on a widely used 21-gene recurrence score assay.

This novel finding in an observational study underscores how much is riding on the outcome of ongoing randomized clinical trials of metformin and aggressive lifestyle modification through weight loss and exercise for secondary prevention of breast cancer, Dr. Arti Lakhani reported at the annual San Antonio Breast Cancer Symposium. If those interventions ultimately prove effective in reducing the risk of breast cancer recurrence, their success may in part be attributed to their ability to reduce the prevalence of metabolic syndrome.

Dr. Lakhani, of Loyola University Medical Center in Maywood, Ill., presented a single-center study of 322 consecutive women newly diagnosed in 2006-2011 with estrogen receptor–positive/lymph node–negative early-stage breast cancer. All patients’ tumors were analyzed using the Oncotype DX assay, which is used to estimate the risk of recurrence based on the expression of 21 genes.

Of the 322 patients, 89 (27%) met World Health Organization criteria for metabolic syndrome. So far, breast cancer has recurred in 21 patients; 13 (62%) of them had metabolic syndrome.

In a multivariate analysis, patients with a low-risk Oncotype DX score of 0-17 had a 24-fold greater risk of recurrence if they had metabolic syndrome. In intermediate-risk patients having a score of 18-30, metabolic syndrome was independently associated with a fourfold increased risk of recurrence. In patients with higher scores, metabolic syndrome didn’t significantly add to the predictive value of the test result, said Dr. Lakhani.

The impact of metabolic syndrome on recurrence score was independent of tumor grade, size, HER2/neu status, and Ki67, as well as patient age and menopausal status.

During a discussion after the presentation, one physician remarked that if the findings are confirmed in an independent data set with larger numbers, he would feel compelled to recommend chemotherapy in all patients with hormone receptor–positive/lymph node–negative breast cancer and metabolic syndrome.

Another oncologist observed that breast cancer treatment seems to inherently promote metabolic syndrome, with its pear-shaped body habitus. "If my breast cancer patients don’t have metabolic syndrome before they start treatment, they often seem to afterwards."

Dr. Lakhani reported having no financial conflicts.

b.jancin@elsevier.com

SAN ANTONIO – Metabolic syndrome is a potent independent risk factor for breast cancer recurrence in patients who are otherwise at low risk, based on a widely used 21-gene recurrence score assay.

This novel finding in an observational study underscores how much is riding on the outcome of ongoing randomized clinical trials of metformin and aggressive lifestyle modification through weight loss and exercise for secondary prevention of breast cancer, Dr. Arti Lakhani reported at the annual San Antonio Breast Cancer Symposium. If those interventions ultimately prove effective in reducing the risk of breast cancer recurrence, their success may in part be attributed to their ability to reduce the prevalence of metabolic syndrome.

Dr. Lakhani, of Loyola University Medical Center in Maywood, Ill., presented a single-center study of 322 consecutive women newly diagnosed in 2006-2011 with estrogen receptor–positive/lymph node–negative early-stage breast cancer. All patients’ tumors were analyzed using the Oncotype DX assay, which is used to estimate the risk of recurrence based on the expression of 21 genes.

Of the 322 patients, 89 (27%) met World Health Organization criteria for metabolic syndrome. So far, breast cancer has recurred in 21 patients; 13 (62%) of them had metabolic syndrome.

In a multivariate analysis, patients with a low-risk Oncotype DX score of 0-17 had a 24-fold greater risk of recurrence if they had metabolic syndrome. In intermediate-risk patients having a score of 18-30, metabolic syndrome was independently associated with a fourfold increased risk of recurrence. In patients with higher scores, metabolic syndrome didn’t significantly add to the predictive value of the test result, said Dr. Lakhani.

The impact of metabolic syndrome on recurrence score was independent of tumor grade, size, HER2/neu status, and Ki67, as well as patient age and menopausal status.

During a discussion after the presentation, one physician remarked that if the findings are confirmed in an independent data set with larger numbers, he would feel compelled to recommend chemotherapy in all patients with hormone receptor–positive/lymph node–negative breast cancer and metabolic syndrome.

Another oncologist observed that breast cancer treatment seems to inherently promote metabolic syndrome, with its pear-shaped body habitus. "If my breast cancer patients don’t have metabolic syndrome before they start treatment, they often seem to afterwards."

Dr. Lakhani reported having no financial conflicts.

b.jancin@elsevier.com

SAN ANTONIO – Breast cancer outcomes haven’t improved to nearly the same impressive extent in older women as in younger women, according to Dr. Hyman B. Muss.

The reasons for this age-related disparity in breast cancer–specific survival include the increased level of comorbidities in the elderly, the underrepresentation of geriatric patients in major clinical trials, and oncologists’ limited geriatric training, he said in his Susan G. Komen for the Cure Brinker Award Lecture for Scientific Distinction in Clinical Research.

While the benefits of chemotherapy are similar in seniors and younger patients, the risks of serious toxicity are greater with age, he noted. Here’s where a pretreatment geriatric assessment to identify clinical predictors of morbidity and mortality can be enormously helpful, said Dr. Muss, professor of medicine and director of the geriatric oncology program at the University of North Carolina, Chapel Hill.

A growing body of data speaks to the importance of determining comorbidities to offer optimal treatment to elderly breast cancer patients. In a soon-to-be-published update of the Cancer and Leukemia Group 9343 trial of more than 600 elderly women with early breast cancer, for example, 51% of participants were still alive at the 12-year follow up. Of those who died, just 3% died of breast cancer; the other 46% died from other causes.

"If an elderly breast cancer patient in your office has high blood pressure or a blood sugar of 300 mg/dL, that’s almost more important than whether or not she gets radiation ... is cancer the patient’s major illness or is it something else, like diabetes or cardiac disease? The key thing we should be thinking of is not ‘How old are you?’ but ‘What’s your life expectancy?’ " he said.

Online tools can aid in those evaluations, including Adjuvant! Online (www.adjuvantonline.com). This tool allows one to factor comorbid conditions into clinical decisions about adjuvant therapy in women with early breast cancer. Also helpful is ePrognosis (www.eprognosis.org), which provides several scales to estimate an older community-dwelling individual’s life expectancy without breast cancer. The ePrognosis tool "can help you make a better decision about how aggressively to treat breast cancer. Some of my colleagues are doing this now in the office. It just takes a few minutes and is very user friendly," Dr. Muss said.

He said he is particularly impressed with a predictive tool developed by Dr. Arti Hurria and coworkers at the City of Hope Comprehensive Cancer Center in Duarte, Calif. This tool incorporates a brief geriatric assessment along with several laboratory test results and patient, tumor, and planned chemotherapy characteristics. The results generate a score that’s predictive of grade 3-5 chemotherapy toxicity. This predictive model performed well when tested in 500 older patients with a variety of cancers in a multicenter, prospective study conducted by the Cancer and Aging Research Group (J. Clin. Oncol. 2011;29:3457-65).

The physician’s portion of this brief geriatric assessment takes about 10 minutes and consists of three items: the Timed Up & Go test, a measure of functional status; the Blessed Orientation-Memory-Concentration test, a screen for cognitive function; and the Karnofksy performance status (KPS), a performance status measure commonly used in oncology.

The patient self-report part of the assessment takes 20-30 minutes and consists of validated scales measuring comorbidity, functional status, psychological state, social support, nutrition, and medications.

"If you’re as efficient as I am in the clinic, patients have a lot of time to do this before they see you," Dr. Muss quipped.

Scores of 0-25 are possible on this brief geriatric assessment. In the 500-patient multicenter validation study, grade 3-5 chemotherapy toxicity occurred in 53% of study participants. The incidence was 30% among patients with a score of 0-5, 52% in those with a score of 6-9, 77% with a score of 10 or 11, and 89% with a score of 12-19.

Among the significant predictive variables in this study, five stood out: one or more falls in the past 6 months; hearing impairment; difficulty in walking one block; decreased social activity; and need for assistance in taking medications.

"I’ve read hundreds of history and physical exam reports and I never see those data in there," Dr. Muss observed.

Because many oncologists now rely largely upon the KPS in an effort to predict chemotherapy toxicity, the investigators compared its performance to that of the structured brief geriatric assessment. The KPS paled in comparison.

"We pride ourselves in oncology on our judgment of performance status, but the KPS was just about worthless in predicting this. I think this brief geriatric assessment tool has made a real difference," the oncologist commented.

Indeed, pretreatment brief geriatric assessments are now being incorporated into many ongoing oncology clinical trials applying a new and badly needed focus on elderly patients with a variety of cancers, he added.

Geriatric assessments done in real time in the office "might help you identify certain problems in your patients and intervene before you get them on adjuvant chemotherapy or radiation therapy," Dr. Muss explained.

For example, identifying an elderly patient who is predisposed to falling might generate a referral to physical therapy for balance training prior to adjuvant therapy. That could improve quality of life and functional status and might even extend survival. This prospect is going to be tested in a planned randomized trial with standard care in the control group.

Also under active study are a variety of biomarkers that might predict chemotherapy toxicity and functional loss. Dr. Muss and coworkers are focusing on p16INK4A, also known as cyclin-dependent kinase inhibitor 2A or multiple tumor suppressor 1. Levels of this protein increase dramatically with tissue aging.

"As cells accumulate this protein due to increased gene expression, they become senescent. (That finding applies to) all our cells, from our blood cells to our T cells to our glomerular cells. So this is a wonderful marker of aging and we want to see if it’s an independent predictor of toxicity and functional loss. We’re doing those studies now," he said.

Dr. Muss reported that he serves as a consultant to Pfizer and Eisai.

b.jancin@elsevier.com

SAN ANTONIO – Breast cancer outcomes haven’t improved to nearly the same impressive extent in older women as in younger women, according to Dr. Hyman B. Muss.

The reasons for this age-related disparity in breast cancer–specific survival include the increased level of comorbidities in the elderly, the underrepresentation of geriatric patients in major clinical trials, and oncologists’ limited geriatric training, he said in his Susan G. Komen for the Cure Brinker Award Lecture for Scientific Distinction in Clinical Research.

While the benefits of chemotherapy are similar in seniors and younger patients, the risks of serious toxicity are greater with age, he noted. Here’s where a pretreatment geriatric assessment to identify clinical predictors of morbidity and mortality can be enormously helpful, said Dr. Muss, professor of medicine and director of the geriatric oncology program at the University of North Carolina, Chapel Hill.

A growing body of data speaks to the importance of determining comorbidities to offer optimal treatment to elderly breast cancer patients. In a soon-to-be-published update of the Cancer and Leukemia Group 9343 trial of more than 600 elderly women with early breast cancer, for example, 51% of participants were still alive at the 12-year follow up. Of those who died, just 3% died of breast cancer; the other 46% died from other causes.

"If an elderly breast cancer patient in your office has high blood pressure or a blood sugar of 300 mg/dL, that’s almost more important than whether or not she gets radiation ... is cancer the patient’s major illness or is it something else, like diabetes or cardiac disease? The key thing we should be thinking of is not ‘How old are you?’ but ‘What’s your life expectancy?’ " he said.

Online tools can aid in those evaluations, including Adjuvant! Online (www.adjuvantonline.com). This tool allows one to factor comorbid conditions into clinical decisions about adjuvant therapy in women with early breast cancer. Also helpful is ePrognosis (www.eprognosis.org), which provides several scales to estimate an older community-dwelling individual’s life expectancy without breast cancer. The ePrognosis tool "can help you make a better decision about how aggressively to treat breast cancer. Some of my colleagues are doing this now in the office. It just takes a few minutes and is very user friendly," Dr. Muss said.

He said he is particularly impressed with a predictive tool developed by Dr. Arti Hurria and coworkers at the City of Hope Comprehensive Cancer Center in Duarte, Calif. This tool incorporates a brief geriatric assessment along with several laboratory test results and patient, tumor, and planned chemotherapy characteristics. The results generate a score that’s predictive of grade 3-5 chemotherapy toxicity. This predictive model performed well when tested in 500 older patients with a variety of cancers in a multicenter, prospective study conducted by the Cancer and Aging Research Group (J. Clin. Oncol. 2011;29:3457-65).

The physician’s portion of this brief geriatric assessment takes about 10 minutes and consists of three items: the Timed Up & Go test, a measure of functional status; the Blessed Orientation-Memory-Concentration test, a screen for cognitive function; and the Karnofksy performance status (KPS), a performance status measure commonly used in oncology.

The patient self-report part of the assessment takes 20-30 minutes and consists of validated scales measuring comorbidity, functional status, psychological state, social support, nutrition, and medications.

"If you’re as efficient as I am in the clinic, patients have a lot of time to do this before they see you," Dr. Muss quipped.

Scores of 0-25 are possible on this brief geriatric assessment. In the 500-patient multicenter validation study, grade 3-5 chemotherapy toxicity occurred in 53% of study participants. The incidence was 30% among patients with a score of 0-5, 52% in those with a score of 6-9, 77% with a score of 10 or 11, and 89% with a score of 12-19.

Among the significant predictive variables in this study, five stood out: one or more falls in the past 6 months; hearing impairment; difficulty in walking one block; decreased social activity; and need for assistance in taking medications.

"I’ve read hundreds of history and physical exam reports and I never see those data in there," Dr. Muss observed.

Because many oncologists now rely largely upon the KPS in an effort to predict chemotherapy toxicity, the investigators compared its performance to that of the structured brief geriatric assessment. The KPS paled in comparison.

"We pride ourselves in oncology on our judgment of performance status, but the KPS was just about worthless in predicting this. I think this brief geriatric assessment tool has made a real difference," the oncologist commented.

Indeed, pretreatment brief geriatric assessments are now being incorporated into many ongoing oncology clinical trials applying a new and badly needed focus on elderly patients with a variety of cancers, he added.

Geriatric assessments done in real time in the office "might help you identify certain problems in your patients and intervene before you get them on adjuvant chemotherapy or radiation therapy," Dr. Muss explained.

For example, identifying an elderly patient who is predisposed to falling might generate a referral to physical therapy for balance training prior to adjuvant therapy. That could improve quality of life and functional status and might even extend survival. This prospect is going to be tested in a planned randomized trial with standard care in the control group.

Also under active study are a variety of biomarkers that might predict chemotherapy toxicity and functional loss. Dr. Muss and coworkers are focusing on p16INK4A, also known as cyclin-dependent kinase inhibitor 2A or multiple tumor suppressor 1. Levels of this protein increase dramatically with tissue aging.

"As cells accumulate this protein due to increased gene expression, they become senescent. (That finding applies to) all our cells, from our blood cells to our T cells to our glomerular cells. So this is a wonderful marker of aging and we want to see if it’s an independent predictor of toxicity and functional loss. We’re doing those studies now," he said.

Dr. Muss reported that he serves as a consultant to Pfizer and Eisai.

b.jancin@elsevier.com

SAN ANTONIO – Breast cancer outcomes haven’t improved to nearly the same impressive extent in older women as in younger women, according to Dr. Hyman B. Muss.

The reasons for this age-related disparity in breast cancer–specific survival include the increased level of comorbidities in the elderly, the underrepresentation of geriatric patients in major clinical trials, and oncologists’ limited geriatric training, he said in his Susan G. Komen for the Cure Brinker Award Lecture for Scientific Distinction in Clinical Research.

While the benefits of chemotherapy are similar in seniors and younger patients, the risks of serious toxicity are greater with age, he noted. Here’s where a pretreatment geriatric assessment to identify clinical predictors of morbidity and mortality can be enormously helpful, said Dr. Muss, professor of medicine and director of the geriatric oncology program at the University of North Carolina, Chapel Hill.

A growing body of data speaks to the importance of determining comorbidities to offer optimal treatment to elderly breast cancer patients. In a soon-to-be-published update of the Cancer and Leukemia Group 9343 trial of more than 600 elderly women with early breast cancer, for example, 51% of participants were still alive at the 12-year follow up. Of those who died, just 3% died of breast cancer; the other 46% died from other causes.

"If an elderly breast cancer patient in your office has high blood pressure or a blood sugar of 300 mg/dL, that’s almost more important than whether or not she gets radiation ... is cancer the patient’s major illness or is it something else, like diabetes or cardiac disease? The key thing we should be thinking of is not ‘How old are you?’ but ‘What’s your life expectancy?’ " he said.

Online tools can aid in those evaluations, including Adjuvant! Online (www.adjuvantonline.com). This tool allows one to factor comorbid conditions into clinical decisions about adjuvant therapy in women with early breast cancer. Also helpful is ePrognosis (www.eprognosis.org), which provides several scales to estimate an older community-dwelling individual’s life expectancy without breast cancer. The ePrognosis tool "can help you make a better decision about how aggressively to treat breast cancer. Some of my colleagues are doing this now in the office. It just takes a few minutes and is very user friendly," Dr. Muss said.

He said he is particularly impressed with a predictive tool developed by Dr. Arti Hurria and coworkers at the City of Hope Comprehensive Cancer Center in Duarte, Calif. This tool incorporates a brief geriatric assessment along with several laboratory test results and patient, tumor, and planned chemotherapy characteristics. The results generate a score that’s predictive of grade 3-5 chemotherapy toxicity. This predictive model performed well when tested in 500 older patients with a variety of cancers in a multicenter, prospective study conducted by the Cancer and Aging Research Group (J. Clin. Oncol. 2011;29:3457-65).

The physician’s portion of this brief geriatric assessment takes about 10 minutes and consists of three items: the Timed Up & Go test, a measure of functional status; the Blessed Orientation-Memory-Concentration test, a screen for cognitive function; and the Karnofksy performance status (KPS), a performance status measure commonly used in oncology.

The patient self-report part of the assessment takes 20-30 minutes and consists of validated scales measuring comorbidity, functional status, psychological state, social support, nutrition, and medications.

"If you’re as efficient as I am in the clinic, patients have a lot of time to do this before they see you," Dr. Muss quipped.

Scores of 0-25 are possible on this brief geriatric assessment. In the 500-patient multicenter validation study, grade 3-5 chemotherapy toxicity occurred in 53% of study participants. The incidence was 30% among patients with a score of 0-5, 52% in those with a score of 6-9, 77% with a score of 10 or 11, and 89% with a score of 12-19.

Among the significant predictive variables in this study, five stood out: one or more falls in the past 6 months; hearing impairment; difficulty in walking one block; decreased social activity; and need for assistance in taking medications.

"I’ve read hundreds of history and physical exam reports and I never see those data in there," Dr. Muss observed.

Because many oncologists now rely largely upon the KPS in an effort to predict chemotherapy toxicity, the investigators compared its performance to that of the structured brief geriatric assessment. The KPS paled in comparison.

"We pride ourselves in oncology on our judgment of performance status, but the KPS was just about worthless in predicting this. I think this brief geriatric assessment tool has made a real difference," the oncologist commented.

Indeed, pretreatment brief geriatric assessments are now being incorporated into many ongoing oncology clinical trials applying a new and badly needed focus on elderly patients with a variety of cancers, he added.

Geriatric assessments done in real time in the office "might help you identify certain problems in your patients and intervene before you get them on adjuvant chemotherapy or radiation therapy," Dr. Muss explained.

For example, identifying an elderly patient who is predisposed to falling might generate a referral to physical therapy for balance training prior to adjuvant therapy. That could improve quality of life and functional status and might even extend survival. This prospect is going to be tested in a planned randomized trial with standard care in the control group.

Also under active study are a variety of biomarkers that might predict chemotherapy toxicity and functional loss. Dr. Muss and coworkers are focusing on p16INK4A, also known as cyclin-dependent kinase inhibitor 2A or multiple tumor suppressor 1. Levels of this protein increase dramatically with tissue aging.

"As cells accumulate this protein due to increased gene expression, they become senescent. (That finding applies to) all our cells, from our blood cells to our T cells to our glomerular cells. So this is a wonderful marker of aging and we want to see if it’s an independent predictor of toxicity and functional loss. We’re doing those studies now," he said.

Dr. Muss reported that he serves as a consultant to Pfizer and Eisai.

b.jancin@elsevier.com