Heart Failure

ORLANDO — Cardiac resynchronization therapy improves key clinical outcomes in patients with mild heart failure, a randomized trial has shown.

In the European cohort of the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial, patients with cardiac synchronization therapy switched on had a 62% relative risk reduction in the combined end point of heart failure hospitalization or death compared with those assigned to CRT-off, at 24 months' follow-up, Dr. Cecilia Linde said at the annual meeting of the American College of Cardiology.

Patients with the CRT device turned on also had significantly improved left ventricular function, as reflected in their ejection fraction and end-diastolic and end-systolic volumes (see box). All these outcomes combined suggest that reverse ventricular remodeling had occurred, added Dr. Linde, professor of cardiology at Karolinska Hospital, Stockholm.

The European follow-up analysis, prespecified in the double-blind prospective REVERSE study, involved 262 patients who underwent implantation of a biventricular pacemaker and were then randomized 2:1 to have CRT switched on or off.

All subjects had New York Heart Association class II or previously symptomatic class I heart failure, a left ventricular ejection fraction of 40% or less, and a wide QRS interval of at least 120 ms. All were on optimal guideline-recommended medical therapy.

The goal of REVERSE was to learn whether heart failure patients who improved with medications to the point of being asymptomatic or mildly symptomatic could maintain that status with CRT. The answer, Dr. Linde said, is yes.

There was a 10% major complication rate related to the CRT devices in REVERSE. Lead dislocation, perforation of the coronary sinus, and other complications were concentrated in the left ventricular lead during the first year and the right lead in year 2.

The 12-month REVERSE results, presented last year, showed only a nonsignificant trend favoring better outcomes in the CRT-on group. Why the difference a year later?

“It takes time to have an effect in patients with asymptomatic or mildly symptomatic heart failure, so of course when you follow patients for 24 months you're going to find more than if you follow them for 12 months,” she observed.

Today CRT is indicated for patients with class III or ambulatory class IV heart failure. Dr. Linde predicted that if the new REVERSE findings are confirmed in the Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy (MADIT-CRT) trial and Rythmol SR Atrial Fibrillation Trial (RAFT), the indications for CRT will broaden to incorporate the large population of patients with class I and II heart failure along with a low ejection fraction and wide QRS interval.

Discussant Richard L. Page said he found it difficult to reconcile the enhanced LV function and improved clinical outcomes seen with CRT in REVERSE with the observed lack of functional and symptomatic improvement. The CRT on and off groups did not differ significantly at 24 months in the 6-minute walk test, Minnesota Living With Heart Failure Questionnaire, or NYHA class, noted Dr. Page, professor of medicine at the University of Washington, Seattle.

Dr. Jean-Claude Daubert of the REVERSE steering committee replied that since most patients were asymptomatic or mildly symptomatic at entry, there was little room for functional or symptomatic improvement.

“We suspect that to show functional benefit we'll need a much longer follow-up,” said Dr. Daubert, professor of cardiology at Central University Hospital, Rennes, France.

REVERSE was sponsored by Medtronic. Dr. Linde and Dr. Daubert are consultants to, and are on the speakers bureaus for, Medtronic and St. Jude Medical.

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Cardiac resynchronization therapy improves key clinical outcomes in patients with mild heart failure, a randomized trial has shown.

In the European cohort of the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial, patients with cardiac synchronization therapy switched on had a 62% relative risk reduction in the combined end point of heart failure hospitalization or death compared with those assigned to CRT-off, at 24 months' follow-up, Dr. Cecilia Linde said at the annual meeting of the American College of Cardiology.

Patients with the CRT device turned on also had significantly improved left ventricular function, as reflected in their ejection fraction and end-diastolic and end-systolic volumes (see box). All these outcomes combined suggest that reverse ventricular remodeling had occurred, added Dr. Linde, professor of cardiology at Karolinska Hospital, Stockholm.

The European follow-up analysis, prespecified in the double-blind prospective REVERSE study, involved 262 patients who underwent implantation of a biventricular pacemaker and were then randomized 2:1 to have CRT switched on or off.

All subjects had New York Heart Association class II or previously symptomatic class I heart failure, a left ventricular ejection fraction of 40% or less, and a wide QRS interval of at least 120 ms. All were on optimal guideline-recommended medical therapy.

The goal of REVERSE was to learn whether heart failure patients who improved with medications to the point of being asymptomatic or mildly symptomatic could maintain that status with CRT. The answer, Dr. Linde said, is yes.

There was a 10% major complication rate related to the CRT devices in REVERSE. Lead dislocation, perforation of the coronary sinus, and other complications were concentrated in the left ventricular lead during the first year and the right lead in year 2.

The 12-month REVERSE results, presented last year, showed only a nonsignificant trend favoring better outcomes in the CRT-on group. Why the difference a year later?

“It takes time to have an effect in patients with asymptomatic or mildly symptomatic heart failure, so of course when you follow patients for 24 months you're going to find more than if you follow them for 12 months,” she observed.

Today CRT is indicated for patients with class III or ambulatory class IV heart failure. Dr. Linde predicted that if the new REVERSE findings are confirmed in the Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy (MADIT-CRT) trial and Rythmol SR Atrial Fibrillation Trial (RAFT), the indications for CRT will broaden to incorporate the large population of patients with class I and II heart failure along with a low ejection fraction and wide QRS interval.

Discussant Richard L. Page said he found it difficult to reconcile the enhanced LV function and improved clinical outcomes seen with CRT in REVERSE with the observed lack of functional and symptomatic improvement. The CRT on and off groups did not differ significantly at 24 months in the 6-minute walk test, Minnesota Living With Heart Failure Questionnaire, or NYHA class, noted Dr. Page, professor of medicine at the University of Washington, Seattle.

Dr. Jean-Claude Daubert of the REVERSE steering committee replied that since most patients were asymptomatic or mildly symptomatic at entry, there was little room for functional or symptomatic improvement.

“We suspect that to show functional benefit we'll need a much longer follow-up,” said Dr. Daubert, professor of cardiology at Central University Hospital, Rennes, France.

REVERSE was sponsored by Medtronic. Dr. Linde and Dr. Daubert are consultants to, and are on the speakers bureaus for, Medtronic and St. Jude Medical.

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Cardiac resynchronization therapy improves key clinical outcomes in patients with mild heart failure, a randomized trial has shown.

In the European cohort of the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial, patients with cardiac synchronization therapy switched on had a 62% relative risk reduction in the combined end point of heart failure hospitalization or death compared with those assigned to CRT-off, at 24 months' follow-up, Dr. Cecilia Linde said at the annual meeting of the American College of Cardiology.

Patients with the CRT device turned on also had significantly improved left ventricular function, as reflected in their ejection fraction and end-diastolic and end-systolic volumes (see box). All these outcomes combined suggest that reverse ventricular remodeling had occurred, added Dr. Linde, professor of cardiology at Karolinska Hospital, Stockholm.

The European follow-up analysis, prespecified in the double-blind prospective REVERSE study, involved 262 patients who underwent implantation of a biventricular pacemaker and were then randomized 2:1 to have CRT switched on or off.

All subjects had New York Heart Association class II or previously symptomatic class I heart failure, a left ventricular ejection fraction of 40% or less, and a wide QRS interval of at least 120 ms. All were on optimal guideline-recommended medical therapy.

The goal of REVERSE was to learn whether heart failure patients who improved with medications to the point of being asymptomatic or mildly symptomatic could maintain that status with CRT. The answer, Dr. Linde said, is yes.

There was a 10% major complication rate related to the CRT devices in REVERSE. Lead dislocation, perforation of the coronary sinus, and other complications were concentrated in the left ventricular lead during the first year and the right lead in year 2.

The 12-month REVERSE results, presented last year, showed only a nonsignificant trend favoring better outcomes in the CRT-on group. Why the difference a year later?

“It takes time to have an effect in patients with asymptomatic or mildly symptomatic heart failure, so of course when you follow patients for 24 months you're going to find more than if you follow them for 12 months,” she observed.

Today CRT is indicated for patients with class III or ambulatory class IV heart failure. Dr. Linde predicted that if the new REVERSE findings are confirmed in the Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy (MADIT-CRT) trial and Rythmol SR Atrial Fibrillation Trial (RAFT), the indications for CRT will broaden to incorporate the large population of patients with class I and II heart failure along with a low ejection fraction and wide QRS interval.

Discussant Richard L. Page said he found it difficult to reconcile the enhanced LV function and improved clinical outcomes seen with CRT in REVERSE with the observed lack of functional and symptomatic improvement. The CRT on and off groups did not differ significantly at 24 months in the 6-minute walk test, Minnesota Living With Heart Failure Questionnaire, or NYHA class, noted Dr. Page, professor of medicine at the University of Washington, Seattle.

Dr. Jean-Claude Daubert of the REVERSE steering committee replied that since most patients were asymptomatic or mildly symptomatic at entry, there was little room for functional or symptomatic improvement.

“We suspect that to show functional benefit we'll need a much longer follow-up,” said Dr. Daubert, professor of cardiology at Central University Hospital, Rennes, France.

REVERSE was sponsored by Medtronic. Dr. Linde and Dr. Daubert are consultants to, and are on the speakers bureaus for, Medtronic and St. Jude Medical.

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Coupling surgical ventricular reconstruction with coronary artery bypass grafting in patients with severe ischemic heart failure provided no survival or quality of life benefits over surgery alone in the largest randomized trial in cardiac surgery.

“These are definitive findings, and we have to conclude from them that there is no justification to offer [surgical ventricular reconstruction] to these patients, Dr. Robert H. Jones said in presenting the Surgical Treatment for Ischemic Heart Failure (STICH) trial results at the annual meeting of the American College of Cardiology.

STICH, funded by the National Heart, Lung, and Blood Institute, randomized 1,000 patients with left ventricular heart failure, an ejection fraction of 35% or less, and coronary artery disease suitable for coronary artery bypass grafting to CABG alone or CABG plus surgical ventricular reconstruction (SVR), an operation designed to reduce the size of the dilated ventricle and normalize the damaged heart's shape.

During the past decade, SVR has generated excitement among cardiac surgeons, based on the fact that beta-blockers, ACE inhibitors, and other highly effective medications for heart failure make the hypertrophic heart smaller and more normal-shaped. Surgeons reasoned that mechanically reshaping and downsizing the hypertrophic heart might similarly improve clinical outcomes.

“Now we know that it does not,” said Dr. Jones, professor of surgery at Duke University, Durham, N.C. Dr. Jones was the principal investigator for the STICH trial (N. Engl. J. Med. 2009;360:1705-16).

During a median follow-up of 48 months, the primary study end point of all-cause mortality or cardiac hospitalization occurred in 58% of the CABG-plus- SVR group and 59% of those who underwent CABG alone.

The STICH trial included an in-depth quality of life assessment led by Dr. Daniel Mark, director of outcomes research at the Duke Clinical Research Institute.

“We looked at a variety of different ways of assessing quality of life, including heart failure-specific quality of life, and found no evidence that the patients who received SVR on top of their bypass operation did any better or were in any way different in their long-term outcome out to 3 years compared to patients who got bypass surgery alone,” he said.

Hospital costs averaged more than $14,500 higher in the SVR-plus-bypass group, mostly because they spent more time in intensive care, Dr. Mark added.

STICH is a milestone study not only because of its size and clarity, but also because it's the first major comparative effectiveness study examining two different cardiac surgical strategies, he said.

” The tendency of cardiac surgery and, I think, other forms of surgery has been to evolve in an anecdotal fashion,” Dr. Mark said.

Discussant Marvin A. Konstam said that the amount of reduction in end systolic volume achieved in the SVR recipients clearly indicates the STICH surgeons did an effective job of decreasing ventricular wall stress. It is noteworthy that this did not translate into improved outcomes, considering the abundant evidence that doing so pharmacologically does, he said.

This suggests that pharmacologic reduction of end systolic volume by reducing the amount of pathologic myocyte hypertrophy is a very good thing, but when a reduction in end systolic volume is achieved simply structurally it might not have the same benefit, said Dr. Konstam, chief of cardiology at Tufts Medical Center, Boston.

The STICH trial continues, with another 1,212 ischemic heart failure patients who have been randomized to intensive medical therapy alone or in conjunction with CABG. They will be followed for another 2 years. This study has potentially far-reaching impact for all of cardiovascular medicine, Dr. Jones stressed.

“If we find in another 2 years that intensive medical therapy has gotten so good that there's not much room for surgery to further improve outcomes, it's going to change a whole lot of cardiology,” from noninvasive testing to how many cardiac caths get done, he said.

Surgical ventricular reconstruction methods shown here are Dor (A), Jatene (B), McCarthy (C), and Mickleborough (D). ©Elsevier; Reprinted from J. Thorac. Cardiovasc. Surg.; Semin. Thorac. Cardiovasc. Surg.; Ann. Thorac. Surg.

ORLANDO — Coupling surgical ventricular reconstruction with coronary artery bypass grafting in patients with severe ischemic heart failure provided no survival or quality of life benefits over surgery alone in the largest randomized trial in cardiac surgery.

“These are definitive findings, and we have to conclude from them that there is no justification to offer [surgical ventricular reconstruction] to these patients, Dr. Robert H. Jones said in presenting the Surgical Treatment for Ischemic Heart Failure (STICH) trial results at the annual meeting of the American College of Cardiology.

STICH, funded by the National Heart, Lung, and Blood Institute, randomized 1,000 patients with left ventricular heart failure, an ejection fraction of 35% or less, and coronary artery disease suitable for coronary artery bypass grafting to CABG alone or CABG plus surgical ventricular reconstruction (SVR), an operation designed to reduce the size of the dilated ventricle and normalize the damaged heart's shape.

During the past decade, SVR has generated excitement among cardiac surgeons, based on the fact that beta-blockers, ACE inhibitors, and other highly effective medications for heart failure make the hypertrophic heart smaller and more normal-shaped. Surgeons reasoned that mechanically reshaping and downsizing the hypertrophic heart might similarly improve clinical outcomes.

“Now we know that it does not,” said Dr. Jones, professor of surgery at Duke University, Durham, N.C. Dr. Jones was the principal investigator for the STICH trial (N. Engl. J. Med. 2009;360:1705-16).

During a median follow-up of 48 months, the primary study end point of all-cause mortality or cardiac hospitalization occurred in 58% of the CABG-plus- SVR group and 59% of those who underwent CABG alone.

The STICH trial included an in-depth quality of life assessment led by Dr. Daniel Mark, director of outcomes research at the Duke Clinical Research Institute.

“We looked at a variety of different ways of assessing quality of life, including heart failure-specific quality of life, and found no evidence that the patients who received SVR on top of their bypass operation did any better or were in any way different in their long-term outcome out to 3 years compared to patients who got bypass surgery alone,” he said.

Hospital costs averaged more than $14,500 higher in the SVR-plus-bypass group, mostly because they spent more time in intensive care, Dr. Mark added.

STICH is a milestone study not only because of its size and clarity, but also because it's the first major comparative effectiveness study examining two different cardiac surgical strategies, he said.

” The tendency of cardiac surgery and, I think, other forms of surgery has been to evolve in an anecdotal fashion,” Dr. Mark said.

Discussant Marvin A. Konstam said that the amount of reduction in end systolic volume achieved in the SVR recipients clearly indicates the STICH surgeons did an effective job of decreasing ventricular wall stress. It is noteworthy that this did not translate into improved outcomes, considering the abundant evidence that doing so pharmacologically does, he said.

This suggests that pharmacologic reduction of end systolic volume by reducing the amount of pathologic myocyte hypertrophy is a very good thing, but when a reduction in end systolic volume is achieved simply structurally it might not have the same benefit, said Dr. Konstam, chief of cardiology at Tufts Medical Center, Boston.

The STICH trial continues, with another 1,212 ischemic heart failure patients who have been randomized to intensive medical therapy alone or in conjunction with CABG. They will be followed for another 2 years. This study has potentially far-reaching impact for all of cardiovascular medicine, Dr. Jones stressed.

“If we find in another 2 years that intensive medical therapy has gotten so good that there's not much room for surgery to further improve outcomes, it's going to change a whole lot of cardiology,” from noninvasive testing to how many cardiac caths get done, he said.

Surgical ventricular reconstruction methods shown here are Dor (A), Jatene (B), McCarthy (C), and Mickleborough (D). ©Elsevier; Reprinted from J. Thorac. Cardiovasc. Surg.; Semin. Thorac. Cardiovasc. Surg.; Ann. Thorac. Surg.

ORLANDO — Coupling surgical ventricular reconstruction with coronary artery bypass grafting in patients with severe ischemic heart failure provided no survival or quality of life benefits over surgery alone in the largest randomized trial in cardiac surgery.

“These are definitive findings, and we have to conclude from them that there is no justification to offer [surgical ventricular reconstruction] to these patients, Dr. Robert H. Jones said in presenting the Surgical Treatment for Ischemic Heart Failure (STICH) trial results at the annual meeting of the American College of Cardiology.

STICH, funded by the National Heart, Lung, and Blood Institute, randomized 1,000 patients with left ventricular heart failure, an ejection fraction of 35% or less, and coronary artery disease suitable for coronary artery bypass grafting to CABG alone or CABG plus surgical ventricular reconstruction (SVR), an operation designed to reduce the size of the dilated ventricle and normalize the damaged heart's shape.

During the past decade, SVR has generated excitement among cardiac surgeons, based on the fact that beta-blockers, ACE inhibitors, and other highly effective medications for heart failure make the hypertrophic heart smaller and more normal-shaped. Surgeons reasoned that mechanically reshaping and downsizing the hypertrophic heart might similarly improve clinical outcomes.

“Now we know that it does not,” said Dr. Jones, professor of surgery at Duke University, Durham, N.C. Dr. Jones was the principal investigator for the STICH trial (N. Engl. J. Med. 2009;360:1705-16).

During a median follow-up of 48 months, the primary study end point of all-cause mortality or cardiac hospitalization occurred in 58% of the CABG-plus- SVR group and 59% of those who underwent CABG alone.

The STICH trial included an in-depth quality of life assessment led by Dr. Daniel Mark, director of outcomes research at the Duke Clinical Research Institute.

“We looked at a variety of different ways of assessing quality of life, including heart failure-specific quality of life, and found no evidence that the patients who received SVR on top of their bypass operation did any better or were in any way different in their long-term outcome out to 3 years compared to patients who got bypass surgery alone,” he said.

Hospital costs averaged more than $14,500 higher in the SVR-plus-bypass group, mostly because they spent more time in intensive care, Dr. Mark added.

STICH is a milestone study not only because of its size and clarity, but also because it's the first major comparative effectiveness study examining two different cardiac surgical strategies, he said.

” The tendency of cardiac surgery and, I think, other forms of surgery has been to evolve in an anecdotal fashion,” Dr. Mark said.

Discussant Marvin A. Konstam said that the amount of reduction in end systolic volume achieved in the SVR recipients clearly indicates the STICH surgeons did an effective job of decreasing ventricular wall stress. It is noteworthy that this did not translate into improved outcomes, considering the abundant evidence that doing so pharmacologically does, he said.

This suggests that pharmacologic reduction of end systolic volume by reducing the amount of pathologic myocyte hypertrophy is a very good thing, but when a reduction in end systolic volume is achieved simply structurally it might not have the same benefit, said Dr. Konstam, chief of cardiology at Tufts Medical Center, Boston.

The STICH trial continues, with another 1,212 ischemic heart failure patients who have been randomized to intensive medical therapy alone or in conjunction with CABG. They will be followed for another 2 years. This study has potentially far-reaching impact for all of cardiovascular medicine, Dr. Jones stressed.

“If we find in another 2 years that intensive medical therapy has gotten so good that there's not much room for surgery to further improve outcomes, it's going to change a whole lot of cardiology,” from noninvasive testing to how many cardiac caths get done, he said.

Surgical ventricular reconstruction methods shown here are Dor (A), Jatene (B), McCarthy (C), and Mickleborough (D). ©Elsevier; Reprinted from J. Thorac. Cardiovasc. Surg.; Semin. Thorac. Cardiovasc. Surg.; Ann. Thorac. Surg.

The use of brain natriuretic peptide levels to guide heart failure therapy did not reduce hospitalizations or improve quality of life in a study comparing that intensified approach against standard symptom-guided treatment.

In the Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIMECHF), researchers found that contrary to their hypothesis, the new strategy was not helpful overall and was actually harmful in the subgroup of the oldest patients.

The findings indicate that despite the “undisputed diagnostic and prognostic importance” of brain natriuretic peptide (BNP) levels, they are no better than clinical symptom-based judgment for managing heart failure, said Dr. Matthias Pfisterer of University Hospital Basel (Switzerland) and his associates.

The investigators compared the two treatment approaches in 622 outpatients aged 60 and older who were followed for 18 months at 15 medical centers in Switzerland and Germany. Compared with symptom-guided treatment, intensified therapy guided by centrally obtained BNP levels did not improve survival free of hospitalization, the primary end point of the study. The rates of hospitalization-free survival were 41% and 40%, respectively.

Overall survival also did not differ significantly between patients who received BNP-guided therapy (84%) and those who received standard treatment (78%).

Patients aged 60–74 years showed some benefit with the intensified treatment approach, while those aged 75 and older did not (JAMA 2009;301:383–92).

BNP levels are no better than clinical symptom-based judgment for managing heart failure. DR. PFISTERER

The use of brain natriuretic peptide levels to guide heart failure therapy did not reduce hospitalizations or improve quality of life in a study comparing that intensified approach against standard symptom-guided treatment.

In the Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIMECHF), researchers found that contrary to their hypothesis, the new strategy was not helpful overall and was actually harmful in the subgroup of the oldest patients.

The findings indicate that despite the “undisputed diagnostic and prognostic importance” of brain natriuretic peptide (BNP) levels, they are no better than clinical symptom-based judgment for managing heart failure, said Dr. Matthias Pfisterer of University Hospital Basel (Switzerland) and his associates.

The investigators compared the two treatment approaches in 622 outpatients aged 60 and older who were followed for 18 months at 15 medical centers in Switzerland and Germany. Compared with symptom-guided treatment, intensified therapy guided by centrally obtained BNP levels did not improve survival free of hospitalization, the primary end point of the study. The rates of hospitalization-free survival were 41% and 40%, respectively.

Overall survival also did not differ significantly between patients who received BNP-guided therapy (84%) and those who received standard treatment (78%).

Patients aged 60–74 years showed some benefit with the intensified treatment approach, while those aged 75 and older did not (JAMA 2009;301:383–92).

BNP levels are no better than clinical symptom-based judgment for managing heart failure. DR. PFISTERER

The use of brain natriuretic peptide levels to guide heart failure therapy did not reduce hospitalizations or improve quality of life in a study comparing that intensified approach against standard symptom-guided treatment.

In the Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIMECHF), researchers found that contrary to their hypothesis, the new strategy was not helpful overall and was actually harmful in the subgroup of the oldest patients.

The findings indicate that despite the “undisputed diagnostic and prognostic importance” of brain natriuretic peptide (BNP) levels, they are no better than clinical symptom-based judgment for managing heart failure, said Dr. Matthias Pfisterer of University Hospital Basel (Switzerland) and his associates.

The investigators compared the two treatment approaches in 622 outpatients aged 60 and older who were followed for 18 months at 15 medical centers in Switzerland and Germany. Compared with symptom-guided treatment, intensified therapy guided by centrally obtained BNP levels did not improve survival free of hospitalization, the primary end point of the study. The rates of hospitalization-free survival were 41% and 40%, respectively.

Overall survival also did not differ significantly between patients who received BNP-guided therapy (84%) and those who received standard treatment (78%).

Patients aged 60–74 years showed some benefit with the intensified treatment approach, while those aged 75 and older did not (JAMA 2009;301:383–92).

BNP levels are no better than clinical symptom-based judgment for managing heart failure. DR. PFISTERER

SAN FRANCISCO — Heart transplant recipients who were bridged to transplant with an implantable left ventricular assist device showed similar survival to patients who were treated with inotrope-only support, in a retrospective study.

From 1994 to 2007, 173 status 1 patients received orthotopic heart transplants after inotrope-only (IO) support, and 86 patients received transplants after support with an LVAD used as a bridge to transplant, Dr. Jay D. Pal reported at the annual meeting of the Society of Thoracic Surgeons.

Baseline characteristics were similar between the IO and the LVAD patients at the time of transplant. But prior to LVAD implantation, this group of patients had significantly worse hemodynamics. “During the period of LVAD support, cardiopulmonary status improved to become equivalent to the inotropic-bridged patients,” noted Dr. Pal and his colleagues at Duke University, Durham, N.C.

Survival at 1 year after transplant was similar in both groups (88% in the IO patients vs. 85% in the LVAD group) and at 5 years (76% of IO vs. 73% of LVAD). Infectious complications after transplant were also similar in both groups.

The likelihood of a rejection episode during the first year post transplant was also similar (44% IO vs. 52% LVAD).

“Bridge to transplant with an implantable LVAD device provides comparable outcomes to status 1 patients who were stabilized on inotrope infusion only,” the researchers said. This is despite the fact that patients bridged to transplant with an LVAD represent a subset of patients who deteriorated on maximal medical therapy, according to Dr. Pal, who had no disclosures to report.

SAN FRANCISCO — Heart transplant recipients who were bridged to transplant with an implantable left ventricular assist device showed similar survival to patients who were treated with inotrope-only support, in a retrospective study.

From 1994 to 2007, 173 status 1 patients received orthotopic heart transplants after inotrope-only (IO) support, and 86 patients received transplants after support with an LVAD used as a bridge to transplant, Dr. Jay D. Pal reported at the annual meeting of the Society of Thoracic Surgeons.

Baseline characteristics were similar between the IO and the LVAD patients at the time of transplant. But prior to LVAD implantation, this group of patients had significantly worse hemodynamics. “During the period of LVAD support, cardiopulmonary status improved to become equivalent to the inotropic-bridged patients,” noted Dr. Pal and his colleagues at Duke University, Durham, N.C.

Survival at 1 year after transplant was similar in both groups (88% in the IO patients vs. 85% in the LVAD group) and at 5 years (76% of IO vs. 73% of LVAD). Infectious complications after transplant were also similar in both groups.

The likelihood of a rejection episode during the first year post transplant was also similar (44% IO vs. 52% LVAD).

“Bridge to transplant with an implantable LVAD device provides comparable outcomes to status 1 patients who were stabilized on inotrope infusion only,” the researchers said. This is despite the fact that patients bridged to transplant with an LVAD represent a subset of patients who deteriorated on maximal medical therapy, according to Dr. Pal, who had no disclosures to report.

SAN FRANCISCO — Heart transplant recipients who were bridged to transplant with an implantable left ventricular assist device showed similar survival to patients who were treated with inotrope-only support, in a retrospective study.

From 1994 to 2007, 173 status 1 patients received orthotopic heart transplants after inotrope-only (IO) support, and 86 patients received transplants after support with an LVAD used as a bridge to transplant, Dr. Jay D. Pal reported at the annual meeting of the Society of Thoracic Surgeons.

Baseline characteristics were similar between the IO and the LVAD patients at the time of transplant. But prior to LVAD implantation, this group of patients had significantly worse hemodynamics. “During the period of LVAD support, cardiopulmonary status improved to become equivalent to the inotropic-bridged patients,” noted Dr. Pal and his colleagues at Duke University, Durham, N.C.

Survival at 1 year after transplant was similar in both groups (88% in the IO patients vs. 85% in the LVAD group) and at 5 years (76% of IO vs. 73% of LVAD). Infectious complications after transplant were also similar in both groups.

The likelihood of a rejection episode during the first year post transplant was also similar (44% IO vs. 52% LVAD).

“Bridge to transplant with an implantable LVAD device provides comparable outcomes to status 1 patients who were stabilized on inotrope infusion only,” the researchers said. This is despite the fact that patients bridged to transplant with an LVAD represent a subset of patients who deteriorated on maximal medical therapy, according to Dr. Pal, who had no disclosures to report.

NEW ORLEANS — The annual number of Americans aged 65 or older hospitalized for heart failure jumped more than 230% between 1980 and 2006.

“Heart failure has reached epidemic levels. The prevention and treatment of heart failure have become an urgent public health need with national implications,” Dr. Longjian Liu declared in presenting his analysis of 27 years' worth of National Hospital Discharge Surveys.

And the peak of the epidemic has yet to come.

As steep as the rise in heart failure cases has been since 1980, the rate of increase will become even more pronounced in the near future, Dr. Liu said at the annual scientific sessions of the American Heart Association.

This trend is due to a combination of factors, including the explosive growth in the prevalences of diabetes, obesity, and chronic kidney disease; improved survival after myocardial infarction; and the graying of America.

Indeed, the aging of the baby boomers will have an enormous impact on the heart failure epidemic. In Dr. Liu's study of the 1980–2006 U.S. experience, which included more than 2.2 million hospitalized patients over age 65 years, individuals aged 75–84 had an adjusted 2.3-fold greater rate of hospitalization for heart failure than those aged 65–69. Those aged 85 and up had a 4.1-fold greater rate than the 65- to 69-year-olds, and these oldest of the elderly constitute the fastest-growing segment of the U.S. population.

“The reality about heart failure is that the burden of disease will definitely increase for the next 1, 2, and 3 decades,” observed Dr. Liu of the Drexel University School of Public Health, Philadelphia.

For men aged 65 and older, the rate of hospitalization for heart failure rose from 16.6 hospitalizations per 1,000 in 1980 to 22.9 in 2006. Among women, the rate was 13.9 per 1,000 in 1980 and 19.6 in 2006. The age-adjusted rate of hospitalization for heart failure increased by an average of 1.2% annually in men and 1.55% per year in women.

Men were an adjusted 16% more likely than women to be hospitalized for heart failure. But because women have a longer life expectancy and hence a greater opportunity to develop heart failure, the absolute number of women hospitalized for the disease in any given year was substantially greater, the physician explained.

The relative risk of being hospitalized for heart failure among seniors alive during the last 5 years of the study period was 37% greater than for those living in 1980–1984.

The American Heart Association estimates that at present 660,000 new cases of heart failure are diagnosed per year, and 5.3 million Americans are living with the disease. Heart failure is the number one cause of hospitalization in the Medicare population.

NEW ORLEANS — The annual number of Americans aged 65 or older hospitalized for heart failure jumped more than 230% between 1980 and 2006.

“Heart failure has reached epidemic levels. The prevention and treatment of heart failure have become an urgent public health need with national implications,” Dr. Longjian Liu declared in presenting his analysis of 27 years' worth of National Hospital Discharge Surveys.

And the peak of the epidemic has yet to come.

As steep as the rise in heart failure cases has been since 1980, the rate of increase will become even more pronounced in the near future, Dr. Liu said at the annual scientific sessions of the American Heart Association.

This trend is due to a combination of factors, including the explosive growth in the prevalences of diabetes, obesity, and chronic kidney disease; improved survival after myocardial infarction; and the graying of America.

Indeed, the aging of the baby boomers will have an enormous impact on the heart failure epidemic. In Dr. Liu's study of the 1980–2006 U.S. experience, which included more than 2.2 million hospitalized patients over age 65 years, individuals aged 75–84 had an adjusted 2.3-fold greater rate of hospitalization for heart failure than those aged 65–69. Those aged 85 and up had a 4.1-fold greater rate than the 65- to 69-year-olds, and these oldest of the elderly constitute the fastest-growing segment of the U.S. population.

“The reality about heart failure is that the burden of disease will definitely increase for the next 1, 2, and 3 decades,” observed Dr. Liu of the Drexel University School of Public Health, Philadelphia.

For men aged 65 and older, the rate of hospitalization for heart failure rose from 16.6 hospitalizations per 1,000 in 1980 to 22.9 in 2006. Among women, the rate was 13.9 per 1,000 in 1980 and 19.6 in 2006. The age-adjusted rate of hospitalization for heart failure increased by an average of 1.2% annually in men and 1.55% per year in women.

Men were an adjusted 16% more likely than women to be hospitalized for heart failure. But because women have a longer life expectancy and hence a greater opportunity to develop heart failure, the absolute number of women hospitalized for the disease in any given year was substantially greater, the physician explained.

The relative risk of being hospitalized for heart failure among seniors alive during the last 5 years of the study period was 37% greater than for those living in 1980–1984.

The American Heart Association estimates that at present 660,000 new cases of heart failure are diagnosed per year, and 5.3 million Americans are living with the disease. Heart failure is the number one cause of hospitalization in the Medicare population.

NEW ORLEANS — The annual number of Americans aged 65 or older hospitalized for heart failure jumped more than 230% between 1980 and 2006.

“Heart failure has reached epidemic levels. The prevention and treatment of heart failure have become an urgent public health need with national implications,” Dr. Longjian Liu declared in presenting his analysis of 27 years' worth of National Hospital Discharge Surveys.

And the peak of the epidemic has yet to come.

As steep as the rise in heart failure cases has been since 1980, the rate of increase will become even more pronounced in the near future, Dr. Liu said at the annual scientific sessions of the American Heart Association.

This trend is due to a combination of factors, including the explosive growth in the prevalences of diabetes, obesity, and chronic kidney disease; improved survival after myocardial infarction; and the graying of America.

Indeed, the aging of the baby boomers will have an enormous impact on the heart failure epidemic. In Dr. Liu's study of the 1980–2006 U.S. experience, which included more than 2.2 million hospitalized patients over age 65 years, individuals aged 75–84 had an adjusted 2.3-fold greater rate of hospitalization for heart failure than those aged 65–69. Those aged 85 and up had a 4.1-fold greater rate than the 65- to 69-year-olds, and these oldest of the elderly constitute the fastest-growing segment of the U.S. population.

“The reality about heart failure is that the burden of disease will definitely increase for the next 1, 2, and 3 decades,” observed Dr. Liu of the Drexel University School of Public Health, Philadelphia.

For men aged 65 and older, the rate of hospitalization for heart failure rose from 16.6 hospitalizations per 1,000 in 1980 to 22.9 in 2006. Among women, the rate was 13.9 per 1,000 in 1980 and 19.6 in 2006. The age-adjusted rate of hospitalization for heart failure increased by an average of 1.2% annually in men and 1.55% per year in women.

Men were an adjusted 16% more likely than women to be hospitalized for heart failure. But because women have a longer life expectancy and hence a greater opportunity to develop heart failure, the absolute number of women hospitalized for the disease in any given year was substantially greater, the physician explained.

The relative risk of being hospitalized for heart failure among seniors alive during the last 5 years of the study period was 37% greater than for those living in 1980–1984.

The American Heart Association estimates that at present 660,000 new cases of heart failure are diagnosed per year, and 5.3 million Americans are living with the disease. Heart failure is the number one cause of hospitalization in the Medicare population.

NEW ORLEANS — Preclinical diastolic dysfunction was highly prevalent among patients with diabetes, occurring in 24% of more than 1,700 largely unselected patients in a retrospective study.

Diastolic dysfunction without any clinical manifestations in patients with either type 1 or type 2 diabetes also had substantial clinical consequences, leading to a significantly increased rate of both heart failure and all-cause mortality during up to 5 years of follow-up, Dr. Aaron M. From reported at the annual scientific sessions of the American Heart Association.

Because the increased risk for heart failure in patients with diabetes and diastolic dysfunction was independent of both hypertension and coronary artery disease, “we suspect that the cardiomyopathy may be a direct consequence of diabetes itself,” said Dr. From, a cardiologist at the Mayo Clinic in Rochester, Minn.

He and his associates studied the natural history of preclinical diastolic dysfunction in diabetes patients by reviewing the records of 2,770 patients with type 1 or type 2 diabetes who were residents of Olmsted County, Minn., and who had an echocardiographic exam at the Mayo Clinic during 1996–2006. The analysis excluded 975 patients who were diagnosed with heart failure within 30 days of their echo exam, and 1 patient with severe heart-valve regurgitation, leaving 1,794 in the analysis. The patients' average age was 60, about half were women, their average body mass index was 33 kg/m

Diastolic dysfunction was identified by calculating the ratio of a patient's early mitral filling velocity—the E wave—and the mitral annulus velocity—the e: wave—obtained from the echo results. If the E/e: ratio was more than 15, the patient was deemed to have diastolic dysfunction. Using this criterion, 431 (24%) of the 1,784 patients with diabetes had diastolic dysfunction at the time of their echo exam. Subsequent development of heart failure was identified by finding ICD-9 code 428 in the patient's record.

Clinical follow-up data were available for an average of 2.7 years following the echo exam, and for periods as long as 5 years. During follow-up, the rate of new-onset heart failure was 37% in patients with diastolic dysfunction at baseline and 17% in those without diastolic dysfunction, a statistically significant difference, said Dr. From, who reported that he and his coauthors had no conflicts of interest related to the study.

In a multivariate analysis controlling for baseline differences in age, sex, body mass index, hypertension, coronary disease, ejection fraction, left atrial volume, and deceleration time, diabetes patients with diastolic dysfunction were 67% more likely to develop heart failure.

During up to 5 years of follow-up, the rate of death from any cause was 33% in patients with diastolic dysfunction at baseline and 13% in those without dysfunction, also a significant difference. In a multivariate analysis that controlled for the same baseline variables, patients with diastolic dysfunction had an 88% higher risk of dying from any cause than did patients without dysfunction at the time of their echo exam.

NEW ORLEANS — Preclinical diastolic dysfunction was highly prevalent among patients with diabetes, occurring in 24% of more than 1,700 largely unselected patients in a retrospective study.

Diastolic dysfunction without any clinical manifestations in patients with either type 1 or type 2 diabetes also had substantial clinical consequences, leading to a significantly increased rate of both heart failure and all-cause mortality during up to 5 years of follow-up, Dr. Aaron M. From reported at the annual scientific sessions of the American Heart Association.

Because the increased risk for heart failure in patients with diabetes and diastolic dysfunction was independent of both hypertension and coronary artery disease, “we suspect that the cardiomyopathy may be a direct consequence of diabetes itself,” said Dr. From, a cardiologist at the Mayo Clinic in Rochester, Minn.

He and his associates studied the natural history of preclinical diastolic dysfunction in diabetes patients by reviewing the records of 2,770 patients with type 1 or type 2 diabetes who were residents of Olmsted County, Minn., and who had an echocardiographic exam at the Mayo Clinic during 1996–2006. The analysis excluded 975 patients who were diagnosed with heart failure within 30 days of their echo exam, and 1 patient with severe heart-valve regurgitation, leaving 1,794 in the analysis. The patients' average age was 60, about half were women, their average body mass index was 33 kg/m

Diastolic dysfunction was identified by calculating the ratio of a patient's early mitral filling velocity—the E wave—and the mitral annulus velocity—the e: wave—obtained from the echo results. If the E/e: ratio was more than 15, the patient was deemed to have diastolic dysfunction. Using this criterion, 431 (24%) of the 1,784 patients with diabetes had diastolic dysfunction at the time of their echo exam. Subsequent development of heart failure was identified by finding ICD-9 code 428 in the patient's record.

Clinical follow-up data were available for an average of 2.7 years following the echo exam, and for periods as long as 5 years. During follow-up, the rate of new-onset heart failure was 37% in patients with diastolic dysfunction at baseline and 17% in those without diastolic dysfunction, a statistically significant difference, said Dr. From, who reported that he and his coauthors had no conflicts of interest related to the study.

In a multivariate analysis controlling for baseline differences in age, sex, body mass index, hypertension, coronary disease, ejection fraction, left atrial volume, and deceleration time, diabetes patients with diastolic dysfunction were 67% more likely to develop heart failure.

During up to 5 years of follow-up, the rate of death from any cause was 33% in patients with diastolic dysfunction at baseline and 13% in those without dysfunction, also a significant difference. In a multivariate analysis that controlled for the same baseline variables, patients with diastolic dysfunction had an 88% higher risk of dying from any cause than did patients without dysfunction at the time of their echo exam.

NEW ORLEANS — Preclinical diastolic dysfunction was highly prevalent among patients with diabetes, occurring in 24% of more than 1,700 largely unselected patients in a retrospective study.

Diastolic dysfunction without any clinical manifestations in patients with either type 1 or type 2 diabetes also had substantial clinical consequences, leading to a significantly increased rate of both heart failure and all-cause mortality during up to 5 years of follow-up, Dr. Aaron M. From reported at the annual scientific sessions of the American Heart Association.

Because the increased risk for heart failure in patients with diabetes and diastolic dysfunction was independent of both hypertension and coronary artery disease, “we suspect that the cardiomyopathy may be a direct consequence of diabetes itself,” said Dr. From, a cardiologist at the Mayo Clinic in Rochester, Minn.

He and his associates studied the natural history of preclinical diastolic dysfunction in diabetes patients by reviewing the records of 2,770 patients with type 1 or type 2 diabetes who were residents of Olmsted County, Minn., and who had an echocardiographic exam at the Mayo Clinic during 1996–2006. The analysis excluded 975 patients who were diagnosed with heart failure within 30 days of their echo exam, and 1 patient with severe heart-valve regurgitation, leaving 1,794 in the analysis. The patients' average age was 60, about half were women, their average body mass index was 33 kg/m

Diastolic dysfunction was identified by calculating the ratio of a patient's early mitral filling velocity—the E wave—and the mitral annulus velocity—the e: wave—obtained from the echo results. If the E/e: ratio was more than 15, the patient was deemed to have diastolic dysfunction. Using this criterion, 431 (24%) of the 1,784 patients with diabetes had diastolic dysfunction at the time of their echo exam. Subsequent development of heart failure was identified by finding ICD-9 code 428 in the patient's record.

Clinical follow-up data were available for an average of 2.7 years following the echo exam, and for periods as long as 5 years. During follow-up, the rate of new-onset heart failure was 37% in patients with diastolic dysfunction at baseline and 17% in those without diastolic dysfunction, a statistically significant difference, said Dr. From, who reported that he and his coauthors had no conflicts of interest related to the study.

In a multivariate analysis controlling for baseline differences in age, sex, body mass index, hypertension, coronary disease, ejection fraction, left atrial volume, and deceleration time, diabetes patients with diastolic dysfunction were 67% more likely to develop heart failure.

During up to 5 years of follow-up, the rate of death from any cause was 33% in patients with diastolic dysfunction at baseline and 13% in those without dysfunction, also a significant difference. In a multivariate analysis that controlled for the same baseline variables, patients with diastolic dysfunction had an 88% higher risk of dying from any cause than did patients without dysfunction at the time of their echo exam.

NEW ORLEANS — Medicare beneficiaries with heart failure see an average of 16–23 different physicians annually, depending upon the severity of their heart failure.

This finding, based on extrapolation from fiscal year 2005 data on a representative sample of more than 1.7 million Medicare beneficiaries, underscores the need to develop systems and processes of coordinated care for the nation's more than 5 million heart failure patients, Robert L. Page II, Pharm.D., said at the annual scientific sessions of the American Heart Association.

Better-coordinated care is the key to avoiding duplication of services, improving care, and reining in health care costs in the heart failure population. In 2005, patients with heart failure accounted for 37% of all Medicare spending and nearly 50% of all inpatient costs, added Dr. Page of the University of Colorado, Denver.

The overall Medicare population, more than 34 million strong, saw an average of 7.9 different physicians in 2005. In contrast, Medicare beneficiaries with mild heart failure saw an average of 15.9 physicians that year. Those with moderate heart failure saw an average of 18.6 different physicians, while the more than 537,000 patients with severe heart failure saw an average of 23. The average number of physicians who ordered care for these patients ranged from 8.3 to 11.2, depending on heart failure severity.

Heart failure patients saw an average of 5.8–11 different physicians in the inpatient setting over the course of the year. Only 10% of all outpatient physician visits by patients with mild heart failure were specifically for their heart failure. Among patients with moderate or severe heart failure, this figure was 20%. The other 80%-90% of outpatient visits were driven largely by the numerous comorbidities present in the heart failure population. (See box.)

Close to half of all outpatient care for Medicare beneficiaries with heart failure was provided by internists and family physicians. Cardiologists handled 16%-20% of all outpatient visits, with the proportion climbing as severity of heart failure increased.

As severity of heart failure increased, so did total costs of care and the proportion of those costs devoted to inpatient or emergency department care. There were significant racial and sex differences in this spending. For example, total 2005 costs of care in black men with mild, moderate, and severe heart failure averaged $35,106, $43,536, and $55,457, respectively, compared with $26,433, $30,536, and $44,433 in white men. Costs in black women with heart failure were lower than in black men but higher than in white men. Costs in white women were lowest of all.

ELESEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — Medicare beneficiaries with heart failure see an average of 16–23 different physicians annually, depending upon the severity of their heart failure.

This finding, based on extrapolation from fiscal year 2005 data on a representative sample of more than 1.7 million Medicare beneficiaries, underscores the need to develop systems and processes of coordinated care for the nation's more than 5 million heart failure patients, Robert L. Page II, Pharm.D., said at the annual scientific sessions of the American Heart Association.

Better-coordinated care is the key to avoiding duplication of services, improving care, and reining in health care costs in the heart failure population. In 2005, patients with heart failure accounted for 37% of all Medicare spending and nearly 50% of all inpatient costs, added Dr. Page of the University of Colorado, Denver.

The overall Medicare population, more than 34 million strong, saw an average of 7.9 different physicians in 2005. In contrast, Medicare beneficiaries with mild heart failure saw an average of 15.9 physicians that year. Those with moderate heart failure saw an average of 18.6 different physicians, while the more than 537,000 patients with severe heart failure saw an average of 23. The average number of physicians who ordered care for these patients ranged from 8.3 to 11.2, depending on heart failure severity.

Heart failure patients saw an average of 5.8–11 different physicians in the inpatient setting over the course of the year. Only 10% of all outpatient physician visits by patients with mild heart failure were specifically for their heart failure. Among patients with moderate or severe heart failure, this figure was 20%. The other 80%-90% of outpatient visits were driven largely by the numerous comorbidities present in the heart failure population. (See box.)

Close to half of all outpatient care for Medicare beneficiaries with heart failure was provided by internists and family physicians. Cardiologists handled 16%-20% of all outpatient visits, with the proportion climbing as severity of heart failure increased.

As severity of heart failure increased, so did total costs of care and the proportion of those costs devoted to inpatient or emergency department care. There were significant racial and sex differences in this spending. For example, total 2005 costs of care in black men with mild, moderate, and severe heart failure averaged $35,106, $43,536, and $55,457, respectively, compared with $26,433, $30,536, and $44,433 in white men. Costs in black women with heart failure were lower than in black men but higher than in white men. Costs in white women were lowest of all.

ELESEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — Medicare beneficiaries with heart failure see an average of 16–23 different physicians annually, depending upon the severity of their heart failure.

This finding, based on extrapolation from fiscal year 2005 data on a representative sample of more than 1.7 million Medicare beneficiaries, underscores the need to develop systems and processes of coordinated care for the nation's more than 5 million heart failure patients, Robert L. Page II, Pharm.D., said at the annual scientific sessions of the American Heart Association.

Better-coordinated care is the key to avoiding duplication of services, improving care, and reining in health care costs in the heart failure population. In 2005, patients with heart failure accounted for 37% of all Medicare spending and nearly 50% of all inpatient costs, added Dr. Page of the University of Colorado, Denver.

The overall Medicare population, more than 34 million strong, saw an average of 7.9 different physicians in 2005. In contrast, Medicare beneficiaries with mild heart failure saw an average of 15.9 physicians that year. Those with moderate heart failure saw an average of 18.6 different physicians, while the more than 537,000 patients with severe heart failure saw an average of 23. The average number of physicians who ordered care for these patients ranged from 8.3 to 11.2, depending on heart failure severity.

Heart failure patients saw an average of 5.8–11 different physicians in the inpatient setting over the course of the year. Only 10% of all outpatient physician visits by patients with mild heart failure were specifically for their heart failure. Among patients with moderate or severe heart failure, this figure was 20%. The other 80%-90% of outpatient visits were driven largely by the numerous comorbidities present in the heart failure population. (See box.)

Close to half of all outpatient care for Medicare beneficiaries with heart failure was provided by internists and family physicians. Cardiologists handled 16%-20% of all outpatient visits, with the proportion climbing as severity of heart failure increased.

As severity of heart failure increased, so did total costs of care and the proportion of those costs devoted to inpatient or emergency department care. There were significant racial and sex differences in this spending. For example, total 2005 costs of care in black men with mild, moderate, and severe heart failure averaged $35,106, $43,536, and $55,457, respectively, compared with $26,433, $30,536, and $44,433 in white men. Costs in black women with heart failure were lower than in black men but higher than in white men. Costs in white women were lowest of all.

ELESEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — In the largest study of exercise training as part of the management of heart failure to date, a guided exercise program was safe and modestly effective, although investigators acknowledged that patients found it hard to keep up the routine.

The safety of exercise training in heart failure patients, outside of a supervised environment, has been a concern, but this study proved benefits could be obtained without excess risk, said Dr. Christopher M. O'Connor, presenting results of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial at the annual scientific sessions of the American Heart Association.

“Over 30 randomized trials have shown increased exercise capacity and possibly improved survival with exercise training, but these were largely single-center studies that were underpowered or lacked adequate controls and produced limited data on safety,” he noted at a press conference.

HF-ACTION, a randomized, phase III trial sponsored by the National Heart, Lung, and Blood Institute, followed 2,331 heart failure patients at 82 international sites for an average of 2.5 years. The relatively young population, median age 59 years, had an average left ventricular ejection fraction (LVEF) of 25%, indicating moderate HF. History of coronary occlusion and prior myocardial infarction was common.

Patients were randomized to an exercise training program aimed at increasing workout intensity and duration or to usual care, where they were encouraged to exercise, based on the American College of Cardiology/AHA recommendations of 30 minutes of moderate exercise most days of the week. Both groups received optimized medical treatment, patient education, and follow-up phone calls.

The exercise training followed the cardiac rehabilitation model. Patients were prescribed a multistage, guided workout of 36 supervised training sessions of 30 minutes of exercise three times a week. At the 18th session, patients received a treadmill or exercise bicycle for home use, learned how to monitor their heart rate during exercise, and were encouraged to complete five weekly sessions of similar intensity and 40 minutes' duration.

At 4–6 weeks, patients were exercising a median of 95 minutes per week, a little short of the goal of 120 minutes. This was consistent for the first year and then diminished further, reported Dr. O'Connor, professor of medicine and director of the heart center at Duke University Medical Center, Durham, N.C.

The diminished adherence is not surprising, he said, because “lifestyle intervention trials are very difficult. At the completion of a drug trial, for example, 85% of patients would still be on the drug. Here, after 3 years people were exercising for about 50 minutes. We had wanted them to exercise for 120 minutes. So adherence is extremely difficult.”

Exercise training was not associated with a significant reduction in the primary end point, all-cause mortality and hospitalization. Adjusted for heart failure etiology, this group experienced a 7% relative risk reduction that was not statistically significant. Secondary composite end points also failed to reach significance: cardiovascular (CV) mortality plus CV hospitalization was reduced by 8%, and CV mortality plus HF hospitalization was reduced by 13%, Dr. O'Connor reported.

However, improvements in outcomes emerged in the prespecified adjusted analysis that accounted for additional key prognostic variables related to heart failure outcomes. These included exercise duration, LVEF, Beck Depression Inventory score, and history of atrial fibrillation flutter.

In the adjusted analysis, the primary end point was significantly reduced by 11%, and CV mortality plus heart failure hospitalization was significantly reduced by 15%. The reduction in CV mortality plus CV hospitalization remained a nonsignificant 8%.

“The prespecified adjusted analysis is a fair analysis of these data and is probably closest to the truth,” Dr. O'Connor maintained. “Prognostic factors are most important. The reductions in risk were in the range of 11%–15%.”

The study found no excess risk for CV events or fractures with intensive exercise. “Perhaps the most important finding is that exercise training of this degree was safe,” Dr. O'Connor added. There was no increase in CV events or fractures with intensive exercise.

The improvements in outcomes were obtained in a setting of excellent overall cardiac care, he added, as more than 90% of patients received evidence-based medical therapy for their disease. “We achieved an 11%–15% meaningful reduction in clinical end points above that, with a safe intervention,” he emphasized.

Discussant Dr. Philip Poole-Wilson said, “This study stresses that the advice to exercise is correct and important. Now, how to persuade the patient is harder.”

“The study missed the primary end point, and some would say that's the end of it. But that would be wrong,” said Dr. Poole-Wilson, professor of medicine at the Imperial College London. “After adjustments, it met many end points, and this means it was a positive trial. The study supports the use of exercise and will strengthen guidelines for the treatment of heart failure, which has wide implications.”

Dr. Clyde Yancy spoke to the financial implications of the study in an interview. He pointed out that the paradigm for exercise has long been established in the form of the cardiac rehabilitation model in which patients enroll in a program over 9–12 weeks to define a new lifestyle,” he said. “When exercise emanates from a structured rehab program, it quadruples adherence rates.

“The important question is whether the study data are sufficient to say that enrollment in a rehab program should become an evidence-based treatment strategy in heart failure. Because if it is guideline-generated then the expectation is that CMS and payers would cover the cost,” said Dr. Yancy, medical director of Baylor University, Dallas.

NEW ORLEANS — In the largest study of exercise training as part of the management of heart failure to date, a guided exercise program was safe and modestly effective, although investigators acknowledged that patients found it hard to keep up the routine.

The safety of exercise training in heart failure patients, outside of a supervised environment, has been a concern, but this study proved benefits could be obtained without excess risk, said Dr. Christopher M. O'Connor, presenting results of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial at the annual scientific sessions of the American Heart Association.

“Over 30 randomized trials have shown increased exercise capacity and possibly improved survival with exercise training, but these were largely single-center studies that were underpowered or lacked adequate controls and produced limited data on safety,” he noted at a press conference.

HF-ACTION, a randomized, phase III trial sponsored by the National Heart, Lung, and Blood Institute, followed 2,331 heart failure patients at 82 international sites for an average of 2.5 years. The relatively young population, median age 59 years, had an average left ventricular ejection fraction (LVEF) of 25%, indicating moderate HF. History of coronary occlusion and prior myocardial infarction was common.

Patients were randomized to an exercise training program aimed at increasing workout intensity and duration or to usual care, where they were encouraged to exercise, based on the American College of Cardiology/AHA recommendations of 30 minutes of moderate exercise most days of the week. Both groups received optimized medical treatment, patient education, and follow-up phone calls.

The exercise training followed the cardiac rehabilitation model. Patients were prescribed a multistage, guided workout of 36 supervised training sessions of 30 minutes of exercise three times a week. At the 18th session, patients received a treadmill or exercise bicycle for home use, learned how to monitor their heart rate during exercise, and were encouraged to complete five weekly sessions of similar intensity and 40 minutes' duration.

At 4–6 weeks, patients were exercising a median of 95 minutes per week, a little short of the goal of 120 minutes. This was consistent for the first year and then diminished further, reported Dr. O'Connor, professor of medicine and director of the heart center at Duke University Medical Center, Durham, N.C.

The diminished adherence is not surprising, he said, because “lifestyle intervention trials are very difficult. At the completion of a drug trial, for example, 85% of patients would still be on the drug. Here, after 3 years people were exercising for about 50 minutes. We had wanted them to exercise for 120 minutes. So adherence is extremely difficult.”

Exercise training was not associated with a significant reduction in the primary end point, all-cause mortality and hospitalization. Adjusted for heart failure etiology, this group experienced a 7% relative risk reduction that was not statistically significant. Secondary composite end points also failed to reach significance: cardiovascular (CV) mortality plus CV hospitalization was reduced by 8%, and CV mortality plus HF hospitalization was reduced by 13%, Dr. O'Connor reported.

However, improvements in outcomes emerged in the prespecified adjusted analysis that accounted for additional key prognostic variables related to heart failure outcomes. These included exercise duration, LVEF, Beck Depression Inventory score, and history of atrial fibrillation flutter.

In the adjusted analysis, the primary end point was significantly reduced by 11%, and CV mortality plus heart failure hospitalization was significantly reduced by 15%. The reduction in CV mortality plus CV hospitalization remained a nonsignificant 8%.

“The prespecified adjusted analysis is a fair analysis of these data and is probably closest to the truth,” Dr. O'Connor maintained. “Prognostic factors are most important. The reductions in risk were in the range of 11%–15%.”

The study found no excess risk for CV events or fractures with intensive exercise. “Perhaps the most important finding is that exercise training of this degree was safe,” Dr. O'Connor added. There was no increase in CV events or fractures with intensive exercise.

The improvements in outcomes were obtained in a setting of excellent overall cardiac care, he added, as more than 90% of patients received evidence-based medical therapy for their disease. “We achieved an 11%–15% meaningful reduction in clinical end points above that, with a safe intervention,” he emphasized.

Discussant Dr. Philip Poole-Wilson said, “This study stresses that the advice to exercise is correct and important. Now, how to persuade the patient is harder.”

“The study missed the primary end point, and some would say that's the end of it. But that would be wrong,” said Dr. Poole-Wilson, professor of medicine at the Imperial College London. “After adjustments, it met many end points, and this means it was a positive trial. The study supports the use of exercise and will strengthen guidelines for the treatment of heart failure, which has wide implications.”

Dr. Clyde Yancy spoke to the financial implications of the study in an interview. He pointed out that the paradigm for exercise has long been established in the form of the cardiac rehabilitation model in which patients enroll in a program over 9–12 weeks to define a new lifestyle,” he said. “When exercise emanates from a structured rehab program, it quadruples adherence rates.

“The important question is whether the study data are sufficient to say that enrollment in a rehab program should become an evidence-based treatment strategy in heart failure. Because if it is guideline-generated then the expectation is that CMS and payers would cover the cost,” said Dr. Yancy, medical director of Baylor University, Dallas.

NEW ORLEANS — In the largest study of exercise training as part of the management of heart failure to date, a guided exercise program was safe and modestly effective, although investigators acknowledged that patients found it hard to keep up the routine.

The safety of exercise training in heart failure patients, outside of a supervised environment, has been a concern, but this study proved benefits could be obtained without excess risk, said Dr. Christopher M. O'Connor, presenting results of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial at the annual scientific sessions of the American Heart Association.

“Over 30 randomized trials have shown increased exercise capacity and possibly improved survival with exercise training, but these were largely single-center studies that were underpowered or lacked adequate controls and produced limited data on safety,” he noted at a press conference.

HF-ACTION, a randomized, phase III trial sponsored by the National Heart, Lung, and Blood Institute, followed 2,331 heart failure patients at 82 international sites for an average of 2.5 years. The relatively young population, median age 59 years, had an average left ventricular ejection fraction (LVEF) of 25%, indicating moderate HF. History of coronary occlusion and prior myocardial infarction was common.

Patients were randomized to an exercise training program aimed at increasing workout intensity and duration or to usual care, where they were encouraged to exercise, based on the American College of Cardiology/AHA recommendations of 30 minutes of moderate exercise most days of the week. Both groups received optimized medical treatment, patient education, and follow-up phone calls.

The exercise training followed the cardiac rehabilitation model. Patients were prescribed a multistage, guided workout of 36 supervised training sessions of 30 minutes of exercise three times a week. At the 18th session, patients received a treadmill or exercise bicycle for home use, learned how to monitor their heart rate during exercise, and were encouraged to complete five weekly sessions of similar intensity and 40 minutes' duration.

At 4–6 weeks, patients were exercising a median of 95 minutes per week, a little short of the goal of 120 minutes. This was consistent for the first year and then diminished further, reported Dr. O'Connor, professor of medicine and director of the heart center at Duke University Medical Center, Durham, N.C.

The diminished adherence is not surprising, he said, because “lifestyle intervention trials are very difficult. At the completion of a drug trial, for example, 85% of patients would still be on the drug. Here, after 3 years people were exercising for about 50 minutes. We had wanted them to exercise for 120 minutes. So adherence is extremely difficult.”

Exercise training was not associated with a significant reduction in the primary end point, all-cause mortality and hospitalization. Adjusted for heart failure etiology, this group experienced a 7% relative risk reduction that was not statistically significant. Secondary composite end points also failed to reach significance: cardiovascular (CV) mortality plus CV hospitalization was reduced by 8%, and CV mortality plus HF hospitalization was reduced by 13%, Dr. O'Connor reported.

However, improvements in outcomes emerged in the prespecified adjusted analysis that accounted for additional key prognostic variables related to heart failure outcomes. These included exercise duration, LVEF, Beck Depression Inventory score, and history of atrial fibrillation flutter.

In the adjusted analysis, the primary end point was significantly reduced by 11%, and CV mortality plus heart failure hospitalization was significantly reduced by 15%. The reduction in CV mortality plus CV hospitalization remained a nonsignificant 8%.

“The prespecified adjusted analysis is a fair analysis of these data and is probably closest to the truth,” Dr. O'Connor maintained. “Prognostic factors are most important. The reductions in risk were in the range of 11%–15%.”

The study found no excess risk for CV events or fractures with intensive exercise. “Perhaps the most important finding is that exercise training of this degree was safe,” Dr. O'Connor added. There was no increase in CV events or fractures with intensive exercise.

The improvements in outcomes were obtained in a setting of excellent overall cardiac care, he added, as more than 90% of patients received evidence-based medical therapy for their disease. “We achieved an 11%–15% meaningful reduction in clinical end points above that, with a safe intervention,” he emphasized.

Discussant Dr. Philip Poole-Wilson said, “This study stresses that the advice to exercise is correct and important. Now, how to persuade the patient is harder.”

“The study missed the primary end point, and some would say that's the end of it. But that would be wrong,” said Dr. Poole-Wilson, professor of medicine at the Imperial College London. “After adjustments, it met many end points, and this means it was a positive trial. The study supports the use of exercise and will strengthen guidelines for the treatment of heart failure, which has wide implications.”

Dr. Clyde Yancy spoke to the financial implications of the study in an interview. He pointed out that the paradigm for exercise has long been established in the form of the cardiac rehabilitation model in which patients enroll in a program over 9–12 weeks to define a new lifestyle,” he said. “When exercise emanates from a structured rehab program, it quadruples adherence rates.

“The important question is whether the study data are sufficient to say that enrollment in a rehab program should become an evidence-based treatment strategy in heart failure. Because if it is guideline-generated then the expectation is that CMS and payers would cover the cost,” said Dr. Yancy, medical director of Baylor University, Dallas.

NEW ORLEANS — Heart failure patients with preserved systolic function did not benefit from treatment with an angiotensin II receptor blocker, according to results of the I-PRESERVE trial, the world's largest placebo-controlled trial of an ARB.

“Disappointingly, for this large group of patients—almost half the patients with heart failure—there remains no specific evidence-based therapy,” concluded Dr. Barry M. Massie, who presented the results of the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial at the annual scientific sessions of the American Heart Association.

Although no pharmacologic therapy has been shown to be effective in improving outcomes in this type of heart failure, inhibitors of the renin-angiotensin-aldosterone system have been of interest because that system is involved in many of the processes associated with this syndrome, such as hypertension, left ventricular hypertrophy, myocardial fibrosis, and vascular dysfunction. Previous studies have hinted at benefits from ARBs and from ACE inhibitors, but statistically significant improvements have not been established, said Dr. Massie, professor of medicine at the University of California, San Francisco and chief of cardiology at the San Francisco Veterans Affairs Medical Center.

I-PRESERVE included 4,128 patients with class II-IV heart failure and a left ventricular ejection fraction of at least 45%. The population was similar to that seen in prior epidemiologic studies in several important ways. The patients were mostly women, were elderly (median age 72 years), and about 9 of 10 had a history of hypertension. The average left ventricular ejection fraction was 59%.

Patients were randomized to either irbesartan up to 300 mg daily or usual care (placebo). The primary end point was a composite of all-cause death, hospitalization for heart failure, myocardial infarction, unstable angina, arrhythmia, and stroke.

After a mean follow-up of approximately 4 years, the primary outcome rates were nearly identical, occurring in 36% (742 of 2,067) of the irbesartan patients and 37% (763 of 2,061) of the placebo group. Similarly, there were no significant differences in the major secondary end points of cardiovascular death and death or hospitalization due to heart failure, or in any of the eight prespecified subgroups, Dr. Massie reported.

“Irbesartan was unsuccessful in achieving its primary or secondary outcomes,” Dr. Massie announced. The results are consistent with two previous trials in patients with heart failure and preserved ejection fraction that did not show a positive treatment effect with either candesartan or perindopril, he added.

Dr. Massie acknowledged that this was a “very well treated population,” with most patients receiving diuretics and many receiving other medications. “After randomization, there was an intensification of all these therapies,” he observed, explaining that this can confound outcomes.

“For this field to move forward, we need a better understanding of the mechanisms underlying this syndrome, and we need to find potential targets above and beyond those used for low ejection fraction patients. We need to do something. This affects more than 2 million individuals in the United States alone.”

Dr. Margaret M. Redfield, professor of medicine at the Mayo Clinic, Rochester, Minn., called I-PRESERVE, “a very important trial, if only for the fact that ARBs and ACE inhibitors are already widely used for the treatment of heart failure with preserved ejection fraction, even though no randomized trial has shown a benefit. Two huge registries have shown that 60% are treated with these agents despite the lack of evidence.”

In this form of heart failure, she said there is little evidence that activation of the renin-angiotensin system is associated with disease progression, unlike in patients with reduced ejection fractions. “This may be why the trial was negative,” she speculated.

She also observed that patients in I-PRESERVE were largely similar to those in observational studies, but that they had fairly normal hemoglobin levels and renal function, “which is uncommon in the elderly with heart failure,” she pointed out. “Few had concentric hypertrophy, though some had concentric remodeling, and very few had advanced diastolic dysfunction or high filling pressures. So, this was a relatively healthy cohort and not as reflective of this syndrome as we would have hoped.”

The study was funded by Bristol-Myers Squibb Co. and Sanofi-Aventis. The results were simultaneously published online in the New England Journal of Medicine (doi:10.1056/NEJMoa08005450).

NEW ORLEANS — Heart failure patients with preserved systolic function did not benefit from treatment with an angiotensin II receptor blocker, according to results of the I-PRESERVE trial, the world's largest placebo-controlled trial of an ARB.

“Disappointingly, for this large group of patients—almost half the patients with heart failure—there remains no specific evidence-based therapy,” concluded Dr. Barry M. Massie, who presented the results of the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial at the annual scientific sessions of the American Heart Association.

Although no pharmacologic therapy has been shown to be effective in improving outcomes in this type of heart failure, inhibitors of the renin-angiotensin-aldosterone system have been of interest because that system is involved in many of the processes associated with this syndrome, such as hypertension, left ventricular hypertrophy, myocardial fibrosis, and vascular dysfunction. Previous studies have hinted at benefits from ARBs and from ACE inhibitors, but statistically significant improvements have not been established, said Dr. Massie, professor of medicine at the University of California, San Francisco and chief of cardiology at the San Francisco Veterans Affairs Medical Center.

I-PRESERVE included 4,128 patients with class II-IV heart failure and a left ventricular ejection fraction of at least 45%. The population was similar to that seen in prior epidemiologic studies in several important ways. The patients were mostly women, were elderly (median age 72 years), and about 9 of 10 had a history of hypertension. The average left ventricular ejection fraction was 59%.

Patients were randomized to either irbesartan up to 300 mg daily or usual care (placebo). The primary end point was a composite of all-cause death, hospitalization for heart failure, myocardial infarction, unstable angina, arrhythmia, and stroke.

After a mean follow-up of approximately 4 years, the primary outcome rates were nearly identical, occurring in 36% (742 of 2,067) of the irbesartan patients and 37% (763 of 2,061) of the placebo group. Similarly, there were no significant differences in the major secondary end points of cardiovascular death and death or hospitalization due to heart failure, or in any of the eight prespecified subgroups, Dr. Massie reported.

“Irbesartan was unsuccessful in achieving its primary or secondary outcomes,” Dr. Massie announced. The results are consistent with two previous trials in patients with heart failure and preserved ejection fraction that did not show a positive treatment effect with either candesartan or perindopril, he added.

Dr. Massie acknowledged that this was a “very well treated population,” with most patients receiving diuretics and many receiving other medications. “After randomization, there was an intensification of all these therapies,” he observed, explaining that this can confound outcomes.

“For this field to move forward, we need a better understanding of the mechanisms underlying this syndrome, and we need to find potential targets above and beyond those used for low ejection fraction patients. We need to do something. This affects more than 2 million individuals in the United States alone.”

Dr. Margaret M. Redfield, professor of medicine at the Mayo Clinic, Rochester, Minn., called I-PRESERVE, “a very important trial, if only for the fact that ARBs and ACE inhibitors are already widely used for the treatment of heart failure with preserved ejection fraction, even though no randomized trial has shown a benefit. Two huge registries have shown that 60% are treated with these agents despite the lack of evidence.”

In this form of heart failure, she said there is little evidence that activation of the renin-angiotensin system is associated with disease progression, unlike in patients with reduced ejection fractions. “This may be why the trial was negative,” she speculated.

She also observed that patients in I-PRESERVE were largely similar to those in observational studies, but that they had fairly normal hemoglobin levels and renal function, “which is uncommon in the elderly with heart failure,” she pointed out. “Few had concentric hypertrophy, though some had concentric remodeling, and very few had advanced diastolic dysfunction or high filling pressures. So, this was a relatively healthy cohort and not as reflective of this syndrome as we would have hoped.”

The study was funded by Bristol-Myers Squibb Co. and Sanofi-Aventis. The results were simultaneously published online in the New England Journal of Medicine (doi:10.1056/NEJMoa08005450).

NEW ORLEANS — Heart failure patients with preserved systolic function did not benefit from treatment with an angiotensin II receptor blocker, according to results of the I-PRESERVE trial, the world's largest placebo-controlled trial of an ARB.

“Disappointingly, for this large group of patients—almost half the patients with heart failure—there remains no specific evidence-based therapy,” concluded Dr. Barry M. Massie, who presented the results of the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial at the annual scientific sessions of the American Heart Association.

Although no pharmacologic therapy has been shown to be effective in improving outcomes in this type of heart failure, inhibitors of the renin-angiotensin-aldosterone system have been of interest because that system is involved in many of the processes associated with this syndrome, such as hypertension, left ventricular hypertrophy, myocardial fibrosis, and vascular dysfunction. Previous studies have hinted at benefits from ARBs and from ACE inhibitors, but statistically significant improvements have not been established, said Dr. Massie, professor of medicine at the University of California, San Francisco and chief of cardiology at the San Francisco Veterans Affairs Medical Center.

I-PRESERVE included 4,128 patients with class II-IV heart failure and a left ventricular ejection fraction of at least 45%. The population was similar to that seen in prior epidemiologic studies in several important ways. The patients were mostly women, were elderly (median age 72 years), and about 9 of 10 had a history of hypertension. The average left ventricular ejection fraction was 59%.

Patients were randomized to either irbesartan up to 300 mg daily or usual care (placebo). The primary end point was a composite of all-cause death, hospitalization for heart failure, myocardial infarction, unstable angina, arrhythmia, and stroke.

After a mean follow-up of approximately 4 years, the primary outcome rates were nearly identical, occurring in 36% (742 of 2,067) of the irbesartan patients and 37% (763 of 2,061) of the placebo group. Similarly, there were no significant differences in the major secondary end points of cardiovascular death and death or hospitalization due to heart failure, or in any of the eight prespecified subgroups, Dr. Massie reported.

“Irbesartan was unsuccessful in achieving its primary or secondary outcomes,” Dr. Massie announced. The results are consistent with two previous trials in patients with heart failure and preserved ejection fraction that did not show a positive treatment effect with either candesartan or perindopril, he added.

Dr. Massie acknowledged that this was a “very well treated population,” with most patients receiving diuretics and many receiving other medications. “After randomization, there was an intensification of all these therapies,” he observed, explaining that this can confound outcomes.

“For this field to move forward, we need a better understanding of the mechanisms underlying this syndrome, and we need to find potential targets above and beyond those used for low ejection fraction patients. We need to do something. This affects more than 2 million individuals in the United States alone.”

Dr. Margaret M. Redfield, professor of medicine at the Mayo Clinic, Rochester, Minn., called I-PRESERVE, “a very important trial, if only for the fact that ARBs and ACE inhibitors are already widely used for the treatment of heart failure with preserved ejection fraction, even though no randomized trial has shown a benefit. Two huge registries have shown that 60% are treated with these agents despite the lack of evidence.”

In this form of heart failure, she said there is little evidence that activation of the renin-angiotensin system is associated with disease progression, unlike in patients with reduced ejection fractions. “This may be why the trial was negative,” she speculated.

She also observed that patients in I-PRESERVE were largely similar to those in observational studies, but that they had fairly normal hemoglobin levels and renal function, “which is uncommon in the elderly with heart failure,” she pointed out. “Few had concentric hypertrophy, though some had concentric remodeling, and very few had advanced diastolic dysfunction or high filling pressures. So, this was a relatively healthy cohort and not as reflective of this syndrome as we would have hoped.”

The study was funded by Bristol-Myers Squibb Co. and Sanofi-Aventis. The results were simultaneously published online in the New England Journal of Medicine (doi:10.1056/NEJMoa08005450).

MUNICH — Metformin-treated diabetic patients with heart failure had strikingly lower morbidity and mortality than did those on oral sulfonylureas, in a long-term observational study.

“Our data suggest metformin is probably safe—and potentially effective—in congestive heart failure patients compared to treatment with sulfonylureas alone,” Dr. Chim C. Lang reported at the annual congress of the European Society of Cardiology.

The safety issue is key. Heart failure has long been considered a relative contraindication to metformin because of a supposedly increased risk of drug-related, potentially fatal, lactic acidosis. The concern has its origins in problems with phenformin, another insulin-sensitizing biguanide. But several lines of evidence suggest the concern over metformin has little or no merit, said Dr. Lang of Ninewells Hospital and Medical School, Dundee, Scotland.

How best to manage diabetes in patients with heart failure is a pressing issue, particularly in light of recent problems with the use of thiazolidinediones in this setting. Metformin could be a cheaper and safer alternative in this extremely common clinical situation. The incidence of heart failure in type 2 diabetic patients is 30.9 cases per 1,000 person-years, Dr. Lang noted.

He reported on all 774 type 2 diabetic patients who developed new-onset chronic heart failure in Tayside, Scotland, during 1994–2003. Ninety were managed with metformin monotherapy, 381 with sulfonylurea monotherapy, and 303 with both.

At 10 years of follow-up, 60% of patients in the metformin group were dead, compared with 77% who received sulfonyl-ureas alone and 66% with combination therapy.

Patients managed with sulfonylureas alone tended to be older, to be sicker, and to have worse renal function, and were less likely to be on β-blockers and aspirin, so those differences were adjusted for in a Cox regression analysis. The result: an adjusted 28% relative risk reduction in mortality with metformin alone.

The mortality curves diverged within the first year of follow-up. At 1 year, 90% of patients in the metformin group remained alive. They had an adjusted 55% relative risk reduction in 1-year mortality compared with the sulfonylurea-only group, while patients on both forms of therapy had a 34% relative risk reduction.

The combined risk of death or all-cause hospitalization was reduced by 26% in the metformin group compared with those on sulfonylureas alone. However, there was no significant difference between the sulfonylurea-only and combination therapy groups in the combined end point.

In an interview, Dr. Lang noted that he is conducting an ongoing, double-blind, placebo-controlled, randomized trial assessing whether 4 months of metformin improves exercise capacity, flow-mediated dilatation, and muscle enzyme activity in insulin-resistant patients with heart failure. It's a highly practical question, as poor exercise tolerance is one of the most debilitating aspects of heart failure.

The notion that metformin is safe in the setting of heart failure received a boost from a recent systematic review by investigators at the University of Alberta, Edmonton. They concluded, “Of the current antidiabetic agents, metformin is the only one not associated with any measurable harm in people with diabetes and heart failure and is associated with reduced mortality” (BMJ 2007;335:497).

In addition, the most recent Cochrane review concluded there were no cases of fatal or nonfatal lactic acidosis in 274 studies involving nearly 60,000 patient-years of metformin use (Cochrane Database Syst. Rev. Jan. 25, 2006 [epub doi:10.1002/14651858.CD002967.pub2

The observational Tayside study was funded by the British Heart Foundation. Dr. Lang's ongoing randomized trial is sponsored by the University of Dundee.

MUNICH — Metformin-treated diabetic patients with heart failure had strikingly lower morbidity and mortality than did those on oral sulfonylureas, in a long-term observational study.

“Our data suggest metformin is probably safe—and potentially effective—in congestive heart failure patients compared to treatment with sulfonylureas alone,” Dr. Chim C. Lang reported at the annual congress of the European Society of Cardiology.

The safety issue is key. Heart failure has long been considered a relative contraindication to metformin because of a supposedly increased risk of drug-related, potentially fatal, lactic acidosis. The concern has its origins in problems with phenformin, another insulin-sensitizing biguanide. But several lines of evidence suggest the concern over metformin has little or no merit, said Dr. Lang of Ninewells Hospital and Medical School, Dundee, Scotland.

How best to manage diabetes in patients with heart failure is a pressing issue, particularly in light of recent problems with the use of thiazolidinediones in this setting. Metformin could be a cheaper and safer alternative in this extremely common clinical situation. The incidence of heart failure in type 2 diabetic patients is 30.9 cases per 1,000 person-years, Dr. Lang noted.

He reported on all 774 type 2 diabetic patients who developed new-onset chronic heart failure in Tayside, Scotland, during 1994–2003. Ninety were managed with metformin monotherapy, 381 with sulfonylurea monotherapy, and 303 with both.

At 10 years of follow-up, 60% of patients in the metformin group were dead, compared with 77% who received sulfonyl-ureas alone and 66% with combination therapy.

Patients managed with sulfonylureas alone tended to be older, to be sicker, and to have worse renal function, and were less likely to be on β-blockers and aspirin, so those differences were adjusted for in a Cox regression analysis. The result: an adjusted 28% relative risk reduction in mortality with metformin alone.

The mortality curves diverged within the first year of follow-up. At 1 year, 90% of patients in the metformin group remained alive. They had an adjusted 55% relative risk reduction in 1-year mortality compared with the sulfonylurea-only group, while patients on both forms of therapy had a 34% relative risk reduction.

The combined risk of death or all-cause hospitalization was reduced by 26% in the metformin group compared with those on sulfonylureas alone. However, there was no significant difference between the sulfonylurea-only and combination therapy groups in the combined end point.

In an interview, Dr. Lang noted that he is conducting an ongoing, double-blind, placebo-controlled, randomized trial assessing whether 4 months of metformin improves exercise capacity, flow-mediated dilatation, and muscle enzyme activity in insulin-resistant patients with heart failure. It's a highly practical question, as poor exercise tolerance is one of the most debilitating aspects of heart failure.

The notion that metformin is safe in the setting of heart failure received a boost from a recent systematic review by investigators at the University of Alberta, Edmonton. They concluded, “Of the current antidiabetic agents, metformin is the only one not associated with any measurable harm in people with diabetes and heart failure and is associated with reduced mortality” (BMJ 2007;335:497).

In addition, the most recent Cochrane review concluded there were no cases of fatal or nonfatal lactic acidosis in 274 studies involving nearly 60,000 patient-years of metformin use (Cochrane Database Syst. Rev. Jan. 25, 2006 [epub doi:10.1002/14651858.CD002967.pub2

The observational Tayside study was funded by the British Heart Foundation. Dr. Lang's ongoing randomized trial is sponsored by the University of Dundee.

MUNICH — Metformin-treated diabetic patients with heart failure had strikingly lower morbidity and mortality than did those on oral sulfonylureas, in a long-term observational study.

“Our data suggest metformin is probably safe—and potentially effective—in congestive heart failure patients compared to treatment with sulfonylureas alone,” Dr. Chim C. Lang reported at the annual congress of the European Society of Cardiology.

The safety issue is key. Heart failure has long been considered a relative contraindication to metformin because of a supposedly increased risk of drug-related, potentially fatal, lactic acidosis. The concern has its origins in problems with phenformin, another insulin-sensitizing biguanide. But several lines of evidence suggest the concern over metformin has little or no merit, said Dr. Lang of Ninewells Hospital and Medical School, Dundee, Scotland.

How best to manage diabetes in patients with heart failure is a pressing issue, particularly in light of recent problems with the use of thiazolidinediones in this setting. Metformin could be a cheaper and safer alternative in this extremely common clinical situation. The incidence of heart failure in type 2 diabetic patients is 30.9 cases per 1,000 person-years, Dr. Lang noted.

He reported on all 774 type 2 diabetic patients who developed new-onset chronic heart failure in Tayside, Scotland, during 1994–2003. Ninety were managed with metformin monotherapy, 381 with sulfonylurea monotherapy, and 303 with both.

At 10 years of follow-up, 60% of patients in the metformin group were dead, compared with 77% who received sulfonyl-ureas alone and 66% with combination therapy.

Patients managed with sulfonylureas alone tended to be older, to be sicker, and to have worse renal function, and were less likely to be on β-blockers and aspirin, so those differences were adjusted for in a Cox regression analysis. The result: an adjusted 28% relative risk reduction in mortality with metformin alone.

The mortality curves diverged within the first year of follow-up. At 1 year, 90% of patients in the metformin group remained alive. They had an adjusted 55% relative risk reduction in 1-year mortality compared with the sulfonylurea-only group, while patients on both forms of therapy had a 34% relative risk reduction.

The combined risk of death or all-cause hospitalization was reduced by 26% in the metformin group compared with those on sulfonylureas alone. However, there was no significant difference between the sulfonylurea-only and combination therapy groups in the combined end point.

In an interview, Dr. Lang noted that he is conducting an ongoing, double-blind, placebo-controlled, randomized trial assessing whether 4 months of metformin improves exercise capacity, flow-mediated dilatation, and muscle enzyme activity in insulin-resistant patients with heart failure. It's a highly practical question, as poor exercise tolerance is one of the most debilitating aspects of heart failure.

The notion that metformin is safe in the setting of heart failure received a boost from a recent systematic review by investigators at the University of Alberta, Edmonton. They concluded, “Of the current antidiabetic agents, metformin is the only one not associated with any measurable harm in people with diabetes and heart failure and is associated with reduced mortality” (BMJ 2007;335:497).

In addition, the most recent Cochrane review concluded there were no cases of fatal or nonfatal lactic acidosis in 274 studies involving nearly 60,000 patient-years of metformin use (Cochrane Database Syst. Rev. Jan. 25, 2006 [epub doi:10.1002/14651858.CD002967.pub2

The observational Tayside study was funded by the British Heart Foundation. Dr. Lang's ongoing randomized trial is sponsored by the University of Dundee.