Heart Failure

BARCELONA — Researchers moved a step closer toward proving that correcting the anemia that often occurs in patients with heart failure improves outcomes, with results from three phase II studies that tested two different ways to boost hemoglobin levels.

Reports from two controlled studies that compared darbepoetin alfa with placebo in 475 patients showed that the treatment was safe, that it produced improvements in patients' exercise capacity that were tied to boosts in hemoglobin levels, and that the drug could cut the rate of death or hospitalization for heart failure at a rate that approached statistical significance, Dr. William T. Abraham reported at a joint meeting of the European Society of Cardiology and the World Heart Federation.

And results from the first randomized, observer-blinded test of intravenous iron in 35 patients with heart failure and low iron levels supported the idea that iron repletion is safe and associated with improvement in exercise capacity and heart failure symptoms, Dr. Stefan D. Anker said in a separate report at the meeting.

Anemia is a common complication of heart failure, but just how common depends on how it's defined. In data collected from one recent, large heart failure treatment trial, 30% of women and 16% of men had anemia if it was defined as a serum hemoglobin level of less than 12.5 g/dL. With a more conservative definition of less than 11.5 g/dL, the prevalence was 10% among women and 8% among men, said Dr. Anker, a cardiologist and professor of medicine at Charité University in Berlin.

These hemoglobin levels would not be severe enough to warrant drug interventions if they occurred in otherwise healthy people, in whom the hemoglobin level would have to be less than 10 g/dL to make drug intervention reasonable, Dr. Anker said in an interview. But in the context of heart failure, experts have hypothesized that higher hemoglobin levels might lead to clinically important improvements in exercise capacity and quality of life, and to a significant drop in heart failure hospitalizations.

The two most obvious ways to correct anemia are treatment with an erythropoietin agent and treatment with iron supplementation. These approaches could also be used together.

Three phase II studies of darbepoetin alfa, a long-acting erythropoietin, were recently completed, and results from the two largest of these studies were reported at the meeting. All three studies were sponsored by Amgen, which markets darbepoetin (Aranesp). Dr. Abraham has received research support from Amgen.

One trial involved 319 patients with New York Heart Association class II-IV heart failure and a serum hemoglobin level of 9.0–12.5 g/dL; their average baseline hemoglobin level was 11.35 g/dL. Of the 319 patients, 157 were randomized to receive placebo and 162 received darbepoetin alfa at a starting dosage of 0.75 mcg/kg administered subcutaneously every 2 weeks. The dosage was titrated to produce a rise in hemoglobin of 0.5–1.5 g/dL every 3 weeks and then to maintain a hemoglobin level of 13.0–15.0 g/dL. All patients also received supplemental iron, given as an oral dosage of 200 mg/day.

The primary end point for this study was the change in exercise capacity from baseline after 6 months of treatment, measured as time spent walking on a treadmill.

The regimen produced an average hemoglobin level of 13.5 g/dL in patients who were treated with darbepoetin alfa and no change in the patients treated with placebo.

The change in treadmill-exercise time was an average of 46.5 seconds in placebo patients and 57.3 seconds in the darbepoetin alfa-treated patients, a nonsignificant difference, reported Dr. Abraham, professor of medicine and director of the division of cardiovascular medicine at Ohio State University, Columbus.

However, a post hoc analysis of these data showed a promising and statistically significant link between the rise in serum hemoglobin level and improvements in exercise time (see graph). More than 80% of patients treated with darbepoetin alfa had a “robust response to treatment,” with a hemoglobin rise of more than 1 g/dL, and these patients had substantial improvements in their exercise time, Dr. Abraham noted.

A prespecified end point for the two largest of the trials was a combined analysis to assess safety and efficacy measured by the incidence of all-cause death or first hospitalization for heart failure after 1 year of treatment. This combined the results from the 319-patient study described above and the results from a study with 165 patients. The second study randomized 55 patients to placebo, 56 to a weight-based dosage of darbepoetin that was the same as was used in the larger study, and 54 patients to a fixed-dosage regimen of the drug that used 50 mcg every 2 weeks. The results showed no difference between the effects of the weight-based and fixed dosages.

Data for the combined analysis were available for 209 patients who received placebo and 266 who received darbepoetin alfa.

The 1-year incidence of death or hospitalization for heart failure was reduced by 33% in the patients treated with darbepoetin, compared with those who received placebo, a difference that neared statistical significance (P = .064).

Darbepoetin alfa treatment was also associated with trends in improved quality of life and in the patients' global self-assessment.

The incidence of serious adverse events was similar in the placebo and drug-treated arms, and treatment with darbepoetin alfa showed no evidence of any increases in the events that are of particular concern in patients who receive erythropoietin-type drugs, such as hypertension or thrombotic events.

Supplementation with oral iron in patients with anemia is often ineffective in routine practice, because the supplements taste bad and patients stop taking them, which makes an intravenous supplement an attractive alternative, Dr. Anker said.

The results that he reported were collected from 18 heart failure patients with anemia (hemoglobin less than 12.5 g/dL) and 17 patients with no anemia (hemoglobin 12.5–14.5 g/dL) but with iron deficiency as measured by their serum ferritin or transferrin saturation levels. Twelve patients from each of these two subgroups were randomized to treatment with weekly infusions of iron sucrose (Venofer), and the remaining 11 were treated with placebo. Patients were treated for 3 months. The study's primary end point was the change from baseline to the end of the study in peak oxygen consumption.

In the anemic patients, iron supplementation was associated with a significant 204 mL/min greater increase in oxygen consumption over baseline, compared with the placebo group. In the nonanemic patients, iron supplementation did not lead to a notable change in oxygen consumption, compared with the placebo group, Dr. Anker reported.

By other measures, iron supplementation was also linked to improvements in exercise duration and heart failure class. The treatment was also safe, with no difference in adverse event rates between the intervention and control groups.

ELSEVIER GLOBAL MEDICAL NEWS

BARCELONA — Researchers moved a step closer toward proving that correcting the anemia that often occurs in patients with heart failure improves outcomes, with results from three phase II studies that tested two different ways to boost hemoglobin levels.

Reports from two controlled studies that compared darbepoetin alfa with placebo in 475 patients showed that the treatment was safe, that it produced improvements in patients' exercise capacity that were tied to boosts in hemoglobin levels, and that the drug could cut the rate of death or hospitalization for heart failure at a rate that approached statistical significance, Dr. William T. Abraham reported at a joint meeting of the European Society of Cardiology and the World Heart Federation.

And results from the first randomized, observer-blinded test of intravenous iron in 35 patients with heart failure and low iron levels supported the idea that iron repletion is safe and associated with improvement in exercise capacity and heart failure symptoms, Dr. Stefan D. Anker said in a separate report at the meeting.

Anemia is a common complication of heart failure, but just how common depends on how it's defined. In data collected from one recent, large heart failure treatment trial, 30% of women and 16% of men had anemia if it was defined as a serum hemoglobin level of less than 12.5 g/dL. With a more conservative definition of less than 11.5 g/dL, the prevalence was 10% among women and 8% among men, said Dr. Anker, a cardiologist and professor of medicine at Charité University in Berlin.

These hemoglobin levels would not be severe enough to warrant drug interventions if they occurred in otherwise healthy people, in whom the hemoglobin level would have to be less than 10 g/dL to make drug intervention reasonable, Dr. Anker said in an interview. But in the context of heart failure, experts have hypothesized that higher hemoglobin levels might lead to clinically important improvements in exercise capacity and quality of life, and to a significant drop in heart failure hospitalizations.

The two most obvious ways to correct anemia are treatment with an erythropoietin agent and treatment with iron supplementation. These approaches could also be used together.

Three phase II studies of darbepoetin alfa, a long-acting erythropoietin, were recently completed, and results from the two largest of these studies were reported at the meeting. All three studies were sponsored by Amgen, which markets darbepoetin (Aranesp). Dr. Abraham has received research support from Amgen.

One trial involved 319 patients with New York Heart Association class II-IV heart failure and a serum hemoglobin level of 9.0–12.5 g/dL; their average baseline hemoglobin level was 11.35 g/dL. Of the 319 patients, 157 were randomized to receive placebo and 162 received darbepoetin alfa at a starting dosage of 0.75 mcg/kg administered subcutaneously every 2 weeks. The dosage was titrated to produce a rise in hemoglobin of 0.5–1.5 g/dL every 3 weeks and then to maintain a hemoglobin level of 13.0–15.0 g/dL. All patients also received supplemental iron, given as an oral dosage of 200 mg/day.

The primary end point for this study was the change in exercise capacity from baseline after 6 months of treatment, measured as time spent walking on a treadmill.

The regimen produced an average hemoglobin level of 13.5 g/dL in patients who were treated with darbepoetin alfa and no change in the patients treated with placebo.

The change in treadmill-exercise time was an average of 46.5 seconds in placebo patients and 57.3 seconds in the darbepoetin alfa-treated patients, a nonsignificant difference, reported Dr. Abraham, professor of medicine and director of the division of cardiovascular medicine at Ohio State University, Columbus.

However, a post hoc analysis of these data showed a promising and statistically significant link between the rise in serum hemoglobin level and improvements in exercise time (see graph). More than 80% of patients treated with darbepoetin alfa had a “robust response to treatment,” with a hemoglobin rise of more than 1 g/dL, and these patients had substantial improvements in their exercise time, Dr. Abraham noted.

A prespecified end point for the two largest of the trials was a combined analysis to assess safety and efficacy measured by the incidence of all-cause death or first hospitalization for heart failure after 1 year of treatment. This combined the results from the 319-patient study described above and the results from a study with 165 patients. The second study randomized 55 patients to placebo, 56 to a weight-based dosage of darbepoetin that was the same as was used in the larger study, and 54 patients to a fixed-dosage regimen of the drug that used 50 mcg every 2 weeks. The results showed no difference between the effects of the weight-based and fixed dosages.

Data for the combined analysis were available for 209 patients who received placebo and 266 who received darbepoetin alfa.

The 1-year incidence of death or hospitalization for heart failure was reduced by 33% in the patients treated with darbepoetin, compared with those who received placebo, a difference that neared statistical significance (P = .064).

Darbepoetin alfa treatment was also associated with trends in improved quality of life and in the patients' global self-assessment.

The incidence of serious adverse events was similar in the placebo and drug-treated arms, and treatment with darbepoetin alfa showed no evidence of any increases in the events that are of particular concern in patients who receive erythropoietin-type drugs, such as hypertension or thrombotic events.

Supplementation with oral iron in patients with anemia is often ineffective in routine practice, because the supplements taste bad and patients stop taking them, which makes an intravenous supplement an attractive alternative, Dr. Anker said.

The results that he reported were collected from 18 heart failure patients with anemia (hemoglobin less than 12.5 g/dL) and 17 patients with no anemia (hemoglobin 12.5–14.5 g/dL) but with iron deficiency as measured by their serum ferritin or transferrin saturation levels. Twelve patients from each of these two subgroups were randomized to treatment with weekly infusions of iron sucrose (Venofer), and the remaining 11 were treated with placebo. Patients were treated for 3 months. The study's primary end point was the change from baseline to the end of the study in peak oxygen consumption.

In the anemic patients, iron supplementation was associated with a significant 204 mL/min greater increase in oxygen consumption over baseline, compared with the placebo group. In the nonanemic patients, iron supplementation did not lead to a notable change in oxygen consumption, compared with the placebo group, Dr. Anker reported.

By other measures, iron supplementation was also linked to improvements in exercise duration and heart failure class. The treatment was also safe, with no difference in adverse event rates between the intervention and control groups.

ELSEVIER GLOBAL MEDICAL NEWS

BARCELONA — Researchers moved a step closer toward proving that correcting the anemia that often occurs in patients with heart failure improves outcomes, with results from three phase II studies that tested two different ways to boost hemoglobin levels.

Reports from two controlled studies that compared darbepoetin alfa with placebo in 475 patients showed that the treatment was safe, that it produced improvements in patients' exercise capacity that were tied to boosts in hemoglobin levels, and that the drug could cut the rate of death or hospitalization for heart failure at a rate that approached statistical significance, Dr. William T. Abraham reported at a joint meeting of the European Society of Cardiology and the World Heart Federation.

And results from the first randomized, observer-blinded test of intravenous iron in 35 patients with heart failure and low iron levels supported the idea that iron repletion is safe and associated with improvement in exercise capacity and heart failure symptoms, Dr. Stefan D. Anker said in a separate report at the meeting.

Anemia is a common complication of heart failure, but just how common depends on how it's defined. In data collected from one recent, large heart failure treatment trial, 30% of women and 16% of men had anemia if it was defined as a serum hemoglobin level of less than 12.5 g/dL. With a more conservative definition of less than 11.5 g/dL, the prevalence was 10% among women and 8% among men, said Dr. Anker, a cardiologist and professor of medicine at Charité University in Berlin.

These hemoglobin levels would not be severe enough to warrant drug interventions if they occurred in otherwise healthy people, in whom the hemoglobin level would have to be less than 10 g/dL to make drug intervention reasonable, Dr. Anker said in an interview. But in the context of heart failure, experts have hypothesized that higher hemoglobin levels might lead to clinically important improvements in exercise capacity and quality of life, and to a significant drop in heart failure hospitalizations.

The two most obvious ways to correct anemia are treatment with an erythropoietin agent and treatment with iron supplementation. These approaches could also be used together.

Three phase II studies of darbepoetin alfa, a long-acting erythropoietin, were recently completed, and results from the two largest of these studies were reported at the meeting. All three studies were sponsored by Amgen, which markets darbepoetin (Aranesp). Dr. Abraham has received research support from Amgen.

One trial involved 319 patients with New York Heart Association class II-IV heart failure and a serum hemoglobin level of 9.0–12.5 g/dL; their average baseline hemoglobin level was 11.35 g/dL. Of the 319 patients, 157 were randomized to receive placebo and 162 received darbepoetin alfa at a starting dosage of 0.75 mcg/kg administered subcutaneously every 2 weeks. The dosage was titrated to produce a rise in hemoglobin of 0.5–1.5 g/dL every 3 weeks and then to maintain a hemoglobin level of 13.0–15.0 g/dL. All patients also received supplemental iron, given as an oral dosage of 200 mg/day.

The primary end point for this study was the change in exercise capacity from baseline after 6 months of treatment, measured as time spent walking on a treadmill.

The regimen produced an average hemoglobin level of 13.5 g/dL in patients who were treated with darbepoetin alfa and no change in the patients treated with placebo.

The change in treadmill-exercise time was an average of 46.5 seconds in placebo patients and 57.3 seconds in the darbepoetin alfa-treated patients, a nonsignificant difference, reported Dr. Abraham, professor of medicine and director of the division of cardiovascular medicine at Ohio State University, Columbus.

However, a post hoc analysis of these data showed a promising and statistically significant link between the rise in serum hemoglobin level and improvements in exercise time (see graph). More than 80% of patients treated with darbepoetin alfa had a “robust response to treatment,” with a hemoglobin rise of more than 1 g/dL, and these patients had substantial improvements in their exercise time, Dr. Abraham noted.

A prespecified end point for the two largest of the trials was a combined analysis to assess safety and efficacy measured by the incidence of all-cause death or first hospitalization for heart failure after 1 year of treatment. This combined the results from the 319-patient study described above and the results from a study with 165 patients. The second study randomized 55 patients to placebo, 56 to a weight-based dosage of darbepoetin that was the same as was used in the larger study, and 54 patients to a fixed-dosage regimen of the drug that used 50 mcg every 2 weeks. The results showed no difference between the effects of the weight-based and fixed dosages.

Data for the combined analysis were available for 209 patients who received placebo and 266 who received darbepoetin alfa.

The 1-year incidence of death or hospitalization for heart failure was reduced by 33% in the patients treated with darbepoetin, compared with those who received placebo, a difference that neared statistical significance (P = .064).

Darbepoetin alfa treatment was also associated with trends in improved quality of life and in the patients' global self-assessment.

The incidence of serious adverse events was similar in the placebo and drug-treated arms, and treatment with darbepoetin alfa showed no evidence of any increases in the events that are of particular concern in patients who receive erythropoietin-type drugs, such as hypertension or thrombotic events.

Supplementation with oral iron in patients with anemia is often ineffective in routine practice, because the supplements taste bad and patients stop taking them, which makes an intravenous supplement an attractive alternative, Dr. Anker said.

The results that he reported were collected from 18 heart failure patients with anemia (hemoglobin less than 12.5 g/dL) and 17 patients with no anemia (hemoglobin 12.5–14.5 g/dL) but with iron deficiency as measured by their serum ferritin or transferrin saturation levels. Twelve patients from each of these two subgroups were randomized to treatment with weekly infusions of iron sucrose (Venofer), and the remaining 11 were treated with placebo. Patients were treated for 3 months. The study's primary end point was the change from baseline to the end of the study in peak oxygen consumption.

In the anemic patients, iron supplementation was associated with a significant 204 mL/min greater increase in oxygen consumption over baseline, compared with the placebo group. In the nonanemic patients, iron supplementation did not lead to a notable change in oxygen consumption, compared with the placebo group, Dr. Anker reported.

By other measures, iron supplementation was also linked to improvements in exercise duration and heart failure class. The treatment was also safe, with no difference in adverse event rates between the intervention and control groups.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO —Measuring N-terminal-proB-type natriuretic peptide in the emergency department facilitated diagnosis of acute heart failure, shortened visits, and saved money, according to results of IMPROVE-CHF, a multicenter randomized-controlled trial of the use of NT-proBNP-guided strategy in the management of suspected acute heart failure.

“Our economic analysis found that adding this test to physician judgment reduced the duration of the emergency department visit from an average of 6.3 hours to an average of 5.6 hours,” Dr. Gordon W. Moe reported at the annual scientific sessions of the American Heart Association.

“In addition, it reduced the number of patients rehospitalized within 60 days from 51 to 33 and reduced costs in 2005 U.S. dollars from $5,592 to $4,631 per patient overall, a savings of $961 per patient,” Dr. Moe said.

The IMPROVE-CHF study included 501 patients who presented to seven Canadian emergency departments with dyspnea. NT-proBNP samples were taken in all patients, but in only about half were the treating physicians made aware of the results. In the other half of patients, physicians utilized standard clinical tools to determine a diagnosis.

Patients were followed for 60 days to determine whether knowledge of NT-proBNP values improved the management of patients with suspected acute heart failure in a publicly funded, universal-access health care setting.

Although the amount of time spent in the ED was significantly reduced, the number of ICU admissions, median duration of ICU stay, and the number of patients requiring hospitalization after their ED visit did not differ between the NT-proBNP group and the usual-care group. By 60 days, 23% of patients enrolled had died or were rehospitalized, with no difference between groups.

Discussant Dr. Margaret M. Redford of the Mayo Clinic in Rochester, Minn., noted that the researchers were not clear on whether the cost savings were caused by more efficient treatment of patients or to less use of other diagnostic testing. It was also unclear whether the test was most helpful in making a diagnosis of heart failure or in excluding heart failure.

She also noted that the setting for IMPROVE-CHF—in Canada, where there is a single-payer system and carefully controlled costs—is both a strength and a limitation of the trial. “In this system costs are already carefully controlled, making it a rigorous testing ground for cost-saving measure … but we cannot assume the savings observed in the Canadian system would necessarily be observed in other health care systems.”

CHICAGO —Measuring N-terminal-proB-type natriuretic peptide in the emergency department facilitated diagnosis of acute heart failure, shortened visits, and saved money, according to results of IMPROVE-CHF, a multicenter randomized-controlled trial of the use of NT-proBNP-guided strategy in the management of suspected acute heart failure.

“Our economic analysis found that adding this test to physician judgment reduced the duration of the emergency department visit from an average of 6.3 hours to an average of 5.6 hours,” Dr. Gordon W. Moe reported at the annual scientific sessions of the American Heart Association.

“In addition, it reduced the number of patients rehospitalized within 60 days from 51 to 33 and reduced costs in 2005 U.S. dollars from $5,592 to $4,631 per patient overall, a savings of $961 per patient,” Dr. Moe said.

The IMPROVE-CHF study included 501 patients who presented to seven Canadian emergency departments with dyspnea. NT-proBNP samples were taken in all patients, but in only about half were the treating physicians made aware of the results. In the other half of patients, physicians utilized standard clinical tools to determine a diagnosis.

Patients were followed for 60 days to determine whether knowledge of NT-proBNP values improved the management of patients with suspected acute heart failure in a publicly funded, universal-access health care setting.

Although the amount of time spent in the ED was significantly reduced, the number of ICU admissions, median duration of ICU stay, and the number of patients requiring hospitalization after their ED visit did not differ between the NT-proBNP group and the usual-care group. By 60 days, 23% of patients enrolled had died or were rehospitalized, with no difference between groups.

Discussant Dr. Margaret M. Redford of the Mayo Clinic in Rochester, Minn., noted that the researchers were not clear on whether the cost savings were caused by more efficient treatment of patients or to less use of other diagnostic testing. It was also unclear whether the test was most helpful in making a diagnosis of heart failure or in excluding heart failure.

She also noted that the setting for IMPROVE-CHF—in Canada, where there is a single-payer system and carefully controlled costs—is both a strength and a limitation of the trial. “In this system costs are already carefully controlled, making it a rigorous testing ground for cost-saving measure … but we cannot assume the savings observed in the Canadian system would necessarily be observed in other health care systems.”

CHICAGO —Measuring N-terminal-proB-type natriuretic peptide in the emergency department facilitated diagnosis of acute heart failure, shortened visits, and saved money, according to results of IMPROVE-CHF, a multicenter randomized-controlled trial of the use of NT-proBNP-guided strategy in the management of suspected acute heart failure.

“Our economic analysis found that adding this test to physician judgment reduced the duration of the emergency department visit from an average of 6.3 hours to an average of 5.6 hours,” Dr. Gordon W. Moe reported at the annual scientific sessions of the American Heart Association.

“In addition, it reduced the number of patients rehospitalized within 60 days from 51 to 33 and reduced costs in 2005 U.S. dollars from $5,592 to $4,631 per patient overall, a savings of $961 per patient,” Dr. Moe said.

The IMPROVE-CHF study included 501 patients who presented to seven Canadian emergency departments with dyspnea. NT-proBNP samples were taken in all patients, but in only about half were the treating physicians made aware of the results. In the other half of patients, physicians utilized standard clinical tools to determine a diagnosis.

Patients were followed for 60 days to determine whether knowledge of NT-proBNP values improved the management of patients with suspected acute heart failure in a publicly funded, universal-access health care setting.

Although the amount of time spent in the ED was significantly reduced, the number of ICU admissions, median duration of ICU stay, and the number of patients requiring hospitalization after their ED visit did not differ between the NT-proBNP group and the usual-care group. By 60 days, 23% of patients enrolled had died or were rehospitalized, with no difference between groups.

Discussant Dr. Margaret M. Redford of the Mayo Clinic in Rochester, Minn., noted that the researchers were not clear on whether the cost savings were caused by more efficient treatment of patients or to less use of other diagnostic testing. It was also unclear whether the test was most helpful in making a diagnosis of heart failure or in excluding heart failure.

She also noted that the setting for IMPROVE-CHF—in Canada, where there is a single-payer system and carefully controlled costs—is both a strength and a limitation of the trial. “In this system costs are already carefully controlled, making it a rigorous testing ground for cost-saving measure … but we cannot assume the savings observed in the Canadian system would necessarily be observed in other health care systems.”

SEATTLE — The Heart Failure Society of America introduced at its annual meeting its 2006 Comprehensive Heart Failure Practice Guidelines, which updates its original 1999 guidelines.

“There wasn't much data available then. It was a good start, but this is a completely different document,” said Dr. JoAnn Lindenfeld, current chair of the heart failure practice guideline committee and director of heart transplantation at the University of Colorado Health Sciences Center, Denver.

The Heart Failure Society of America (HFSA) guidelines are more comprehensive than two other sets of heart failure guidelines put out separately in 2005 by the European Society of Cardiology (ESC) and jointly by the American Heart Association and American College of Cardiology (AHA/ACC), she said.

The AHA/ACC recommendations don't address acute heart failure, and the ESC created separate sets of guidelines for acute and chronic heart failure. The HFSA guidelines include both.

“I think the ESC guidelines go further in [discussion of] subpopulations,” Dr. Kirkwood F. Adams Jr. commented in a discussion session on the HFSA guidelines. “Heart failure [encompasses] about 18 different populations. I think as people look back 100 years from now, they'll be perhaps laughing that we had something called heart failure guidelines when really there are so many different patient varieties.”

One of the values of the HFSA's comprehensive approach is that the guidelines focus attention on the enormous public health problem that heart failure presents, causing more than 1 million U.S. hospitalizations per year, added Dr. Adams, who cochaired the guidelines committee with Dr. Lindenfeld and is director of the heart failure program at the University of North Carolina, Chapel Hill. “It's good to push recognition” of the problem among both specialists and primary care physicians, who manage 80% of patients with heart failure.

The HFSA guidelines comprise 16 sections that include acute or chronic heart failure, disease management, heart failure in special populations, hypertension in heart failure, heart failure with preserved ejection fraction, and more. The recommendations come in four strengths:

▸ Is recommended—part of routine care, with very few exceptions.

▸ Should be considered—the majority of patients should receive the intervention.

▸ May be considered—individualize the therapy to the patient.

▸ Is not recommended—don't use the intervention.

The guidelines also present the level of evidence for recommendations, following routine models for rating evidence with one exception: One randomized trial could constitute the highest level of evidence (A). “That's controversial,” Dr. Adams said.

In some categories, recommendations of the highest level are not based on the highest level of evidence. Although the guidelines on acute decompensated heart failure include many interventions that are “recommended,” none of these are based on level A evidence, for example, Dr. Lindenfeld said.

“This points out how far we have to go in the data and studies of acute decompensated heart failure,” she said.

The HFSA committee elected not to present majority and minority opinions on its recommendations, as some other guidelines do. “I think majority/minority opinions are useless. You go to the guidelines to get a recommendation,” Dr. Adams said.

The HFSA committee plans to update the guidelines yearly. Topics not covered in the current guidelines that may be included in future versions include genetic screening and testing of patients with heart failure, the timing of altering diuretic therapy, and more guidance on implantable devices.

Clinicians can request a free copy of the pocket guidelines or request pricing for multiple copies by contacting info@hfsa.orgwww.heartfailureguideline.com

SEATTLE — The Heart Failure Society of America introduced at its annual meeting its 2006 Comprehensive Heart Failure Practice Guidelines, which updates its original 1999 guidelines.

“There wasn't much data available then. It was a good start, but this is a completely different document,” said Dr. JoAnn Lindenfeld, current chair of the heart failure practice guideline committee and director of heart transplantation at the University of Colorado Health Sciences Center, Denver.

The Heart Failure Society of America (HFSA) guidelines are more comprehensive than two other sets of heart failure guidelines put out separately in 2005 by the European Society of Cardiology (ESC) and jointly by the American Heart Association and American College of Cardiology (AHA/ACC), she said.

The AHA/ACC recommendations don't address acute heart failure, and the ESC created separate sets of guidelines for acute and chronic heart failure. The HFSA guidelines include both.

“I think the ESC guidelines go further in [discussion of] subpopulations,” Dr. Kirkwood F. Adams Jr. commented in a discussion session on the HFSA guidelines. “Heart failure [encompasses] about 18 different populations. I think as people look back 100 years from now, they'll be perhaps laughing that we had something called heart failure guidelines when really there are so many different patient varieties.”

One of the values of the HFSA's comprehensive approach is that the guidelines focus attention on the enormous public health problem that heart failure presents, causing more than 1 million U.S. hospitalizations per year, added Dr. Adams, who cochaired the guidelines committee with Dr. Lindenfeld and is director of the heart failure program at the University of North Carolina, Chapel Hill. “It's good to push recognition” of the problem among both specialists and primary care physicians, who manage 80% of patients with heart failure.

The HFSA guidelines comprise 16 sections that include acute or chronic heart failure, disease management, heart failure in special populations, hypertension in heart failure, heart failure with preserved ejection fraction, and more. The recommendations come in four strengths:

▸ Is recommended—part of routine care, with very few exceptions.

▸ Should be considered—the majority of patients should receive the intervention.

▸ May be considered—individualize the therapy to the patient.

▸ Is not recommended—don't use the intervention.

The guidelines also present the level of evidence for recommendations, following routine models for rating evidence with one exception: One randomized trial could constitute the highest level of evidence (A). “That's controversial,” Dr. Adams said.

In some categories, recommendations of the highest level are not based on the highest level of evidence. Although the guidelines on acute decompensated heart failure include many interventions that are “recommended,” none of these are based on level A evidence, for example, Dr. Lindenfeld said.

“This points out how far we have to go in the data and studies of acute decompensated heart failure,” she said.

The HFSA committee elected not to present majority and minority opinions on its recommendations, as some other guidelines do. “I think majority/minority opinions are useless. You go to the guidelines to get a recommendation,” Dr. Adams said.

The HFSA committee plans to update the guidelines yearly. Topics not covered in the current guidelines that may be included in future versions include genetic screening and testing of patients with heart failure, the timing of altering diuretic therapy, and more guidance on implantable devices.

Clinicians can request a free copy of the pocket guidelines or request pricing for multiple copies by contacting info@hfsa.orgwww.heartfailureguideline.com

SEATTLE — The Heart Failure Society of America introduced at its annual meeting its 2006 Comprehensive Heart Failure Practice Guidelines, which updates its original 1999 guidelines.

“There wasn't much data available then. It was a good start, but this is a completely different document,” said Dr. JoAnn Lindenfeld, current chair of the heart failure practice guideline committee and director of heart transplantation at the University of Colorado Health Sciences Center, Denver.

The Heart Failure Society of America (HFSA) guidelines are more comprehensive than two other sets of heart failure guidelines put out separately in 2005 by the European Society of Cardiology (ESC) and jointly by the American Heart Association and American College of Cardiology (AHA/ACC), she said.

The AHA/ACC recommendations don't address acute heart failure, and the ESC created separate sets of guidelines for acute and chronic heart failure. The HFSA guidelines include both.

“I think the ESC guidelines go further in [discussion of] subpopulations,” Dr. Kirkwood F. Adams Jr. commented in a discussion session on the HFSA guidelines. “Heart failure [encompasses] about 18 different populations. I think as people look back 100 years from now, they'll be perhaps laughing that we had something called heart failure guidelines when really there are so many different patient varieties.”

One of the values of the HFSA's comprehensive approach is that the guidelines focus attention on the enormous public health problem that heart failure presents, causing more than 1 million U.S. hospitalizations per year, added Dr. Adams, who cochaired the guidelines committee with Dr. Lindenfeld and is director of the heart failure program at the University of North Carolina, Chapel Hill. “It's good to push recognition” of the problem among both specialists and primary care physicians, who manage 80% of patients with heart failure.

The HFSA guidelines comprise 16 sections that include acute or chronic heart failure, disease management, heart failure in special populations, hypertension in heart failure, heart failure with preserved ejection fraction, and more. The recommendations come in four strengths:

▸ Is recommended—part of routine care, with very few exceptions.

▸ Should be considered—the majority of patients should receive the intervention.

▸ May be considered—individualize the therapy to the patient.

▸ Is not recommended—don't use the intervention.

The guidelines also present the level of evidence for recommendations, following routine models for rating evidence with one exception: One randomized trial could constitute the highest level of evidence (A). “That's controversial,” Dr. Adams said.

In some categories, recommendations of the highest level are not based on the highest level of evidence. Although the guidelines on acute decompensated heart failure include many interventions that are “recommended,” none of these are based on level A evidence, for example, Dr. Lindenfeld said.

“This points out how far we have to go in the data and studies of acute decompensated heart failure,” she said.

The HFSA committee elected not to present majority and minority opinions on its recommendations, as some other guidelines do. “I think majority/minority opinions are useless. You go to the guidelines to get a recommendation,” Dr. Adams said.

The HFSA committee plans to update the guidelines yearly. Topics not covered in the current guidelines that may be included in future versions include genetic screening and testing of patients with heart failure, the timing of altering diuretic therapy, and more guidance on implantable devices.

Clinicians can request a free copy of the pocket guidelines or request pricing for multiple copies by contacting info@hfsa.orgwww.heartfailureguideline.com

SEATTLE — Blood tests on 507 patients seen in emergency departments for chest pain found resistance to aspirin in 20% of those with a history of heart failure and 12% of patients without heart failure, Dr. Lori B. Daniels reported in a poster presentation at the annual meeting of the Heart Failure Society of America.

“Physicians should be aware of the high rate of aspirin nonresponsiveness in patients with heart failure, since they may be susceptible to thrombotic events” even if treated with aspirin, and may need other antithrombotic therapy, said Dr. Daniels of the University of California, San Diego, and her associates.

Aspirin prevents MI, stroke, or other vascular events by causing platelet dysfunction so that platelets do not aggregate. It irreversibly inhibits platelet cyclooxygenase, a key enzyme in prostaglandin synthesis, so that platelets lose the capacity to synthesize thromboxane A2, an inducer of platelet aggregation with vasoconstrictive properties.

Between 8% and 18% of patients treated with aspirin, however, develop recurrent vascular events within 2 years, a phenomenon described as aspirin resistance “or perhaps more accurately as aspirin nonresponsiveness,” the investigators wrote.

They took blood samples from patients with suspected acute coronary syndromes seen at five medical centers. All were on outpatient aspirin therapy or were given an aspirin when they arrived at the emergency department. The 25% of patients with a history of heart failure were older than those without heart failure (62 vs. 58 years) and were more likely to be taking aspirin as an outpatient (81% vs. 60%), but the two groups did not differ by sex or body mass index.

Blood samples were tested using the Ultegra Rapid Platelet Function Assay on a VerifyNow testing device. The Ultegra assay is a turbidimetric-based optical detection system that measures platelet-induced aggregation as an increase in light transmittance. Aspirin nonresponsiveness was defined as an “aspirin reaction unit” value of at least 550. Results showed a mean of 479 aspirin reaction units in patients with a history of heart failure, compared with 458 units in patients without heart failure.

None of the investigators are associated with Accumetrix, the company that makes the VerifyNow device.

Heart failure patients were more likely to have a history of hypertension, coronary artery disease, MI, diabetes, chronic renal insufficiency, and tobacco use than were non-heart failure patients. Those with heart failure had averaged 4 years of aspirin use, compared with 2 years in patients without prior heart failure, she said.

The high rate of aspirin nonres-ponsiveness in heart failure patients may make them susceptible to thrombotic events. DR. DANIELS

SEATTLE — Blood tests on 507 patients seen in emergency departments for chest pain found resistance to aspirin in 20% of those with a history of heart failure and 12% of patients without heart failure, Dr. Lori B. Daniels reported in a poster presentation at the annual meeting of the Heart Failure Society of America.

“Physicians should be aware of the high rate of aspirin nonresponsiveness in patients with heart failure, since they may be susceptible to thrombotic events” even if treated with aspirin, and may need other antithrombotic therapy, said Dr. Daniels of the University of California, San Diego, and her associates.

Aspirin prevents MI, stroke, or other vascular events by causing platelet dysfunction so that platelets do not aggregate. It irreversibly inhibits platelet cyclooxygenase, a key enzyme in prostaglandin synthesis, so that platelets lose the capacity to synthesize thromboxane A2, an inducer of platelet aggregation with vasoconstrictive properties.

Between 8% and 18% of patients treated with aspirin, however, develop recurrent vascular events within 2 years, a phenomenon described as aspirin resistance “or perhaps more accurately as aspirin nonresponsiveness,” the investigators wrote.

They took blood samples from patients with suspected acute coronary syndromes seen at five medical centers. All were on outpatient aspirin therapy or were given an aspirin when they arrived at the emergency department. The 25% of patients with a history of heart failure were older than those without heart failure (62 vs. 58 years) and were more likely to be taking aspirin as an outpatient (81% vs. 60%), but the two groups did not differ by sex or body mass index.

Blood samples were tested using the Ultegra Rapid Platelet Function Assay on a VerifyNow testing device. The Ultegra assay is a turbidimetric-based optical detection system that measures platelet-induced aggregation as an increase in light transmittance. Aspirin nonresponsiveness was defined as an “aspirin reaction unit” value of at least 550. Results showed a mean of 479 aspirin reaction units in patients with a history of heart failure, compared with 458 units in patients without heart failure.

None of the investigators are associated with Accumetrix, the company that makes the VerifyNow device.

Heart failure patients were more likely to have a history of hypertension, coronary artery disease, MI, diabetes, chronic renal insufficiency, and tobacco use than were non-heart failure patients. Those with heart failure had averaged 4 years of aspirin use, compared with 2 years in patients without prior heart failure, she said.

The high rate of aspirin nonres-ponsiveness in heart failure patients may make them susceptible to thrombotic events. DR. DANIELS

SEATTLE — Blood tests on 507 patients seen in emergency departments for chest pain found resistance to aspirin in 20% of those with a history of heart failure and 12% of patients without heart failure, Dr. Lori B. Daniels reported in a poster presentation at the annual meeting of the Heart Failure Society of America.

“Physicians should be aware of the high rate of aspirin nonresponsiveness in patients with heart failure, since they may be susceptible to thrombotic events” even if treated with aspirin, and may need other antithrombotic therapy, said Dr. Daniels of the University of California, San Diego, and her associates.

Aspirin prevents MI, stroke, or other vascular events by causing platelet dysfunction so that platelets do not aggregate. It irreversibly inhibits platelet cyclooxygenase, a key enzyme in prostaglandin synthesis, so that platelets lose the capacity to synthesize thromboxane A2, an inducer of platelet aggregation with vasoconstrictive properties.

Between 8% and 18% of patients treated with aspirin, however, develop recurrent vascular events within 2 years, a phenomenon described as aspirin resistance “or perhaps more accurately as aspirin nonresponsiveness,” the investigators wrote.

They took blood samples from patients with suspected acute coronary syndromes seen at five medical centers. All were on outpatient aspirin therapy or were given an aspirin when they arrived at the emergency department. The 25% of patients with a history of heart failure were older than those without heart failure (62 vs. 58 years) and were more likely to be taking aspirin as an outpatient (81% vs. 60%), but the two groups did not differ by sex or body mass index.

Blood samples were tested using the Ultegra Rapid Platelet Function Assay on a VerifyNow testing device. The Ultegra assay is a turbidimetric-based optical detection system that measures platelet-induced aggregation as an increase in light transmittance. Aspirin nonresponsiveness was defined as an “aspirin reaction unit” value of at least 550. Results showed a mean of 479 aspirin reaction units in patients with a history of heart failure, compared with 458 units in patients without heart failure.

None of the investigators are associated with Accumetrix, the company that makes the VerifyNow device.

Heart failure patients were more likely to have a history of hypertension, coronary artery disease, MI, diabetes, chronic renal insufficiency, and tobacco use than were non-heart failure patients. Those with heart failure had averaged 4 years of aspirin use, compared with 2 years in patients without prior heart failure, she said.

The high rate of aspirin nonres-ponsiveness in heart failure patients may make them susceptible to thrombotic events. DR. DANIELS

SEATTLE — Low-dose aspirin did not reduce the beneficial effects of ACE inhibitors in patients with atrial fibrillation and a history of heart failure, a subset analysis of 2,031 patients found.

The analysis addressed recurring concerns that aspirin use attenuates the effects of ACE inhibitors in heart failure patients and supported the use of both low-dose aspirin and an ACE inhibitor when indications for both treatments exist, Dr. Akshay S. Desai said at the annual meeting of the Heart Failure Society of America.

Dr. Desai and associates studied data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE-W). The prospective, open-label study randomized patients with atrial fibrillation to combination antiplatelet therapy with clopidogrel and 75–100 mg/day of aspirin or to oral anticoagulation with warfarin. ACTIVE-W was discontinued early because warfarin clearly reduced the risk of MI, vascular events, or death.

Compared with all ACTIVE-W patients, the 2,031 patients with prior heart failure were more likely to be hypertensive or diabetic; have left ventricular dysfunction, a prior MI, or coronary disease; and be on an ACE inhibitor or angiotensin receptor blocker at baseline. Patients with prior heart failure in ACTIVE-W were twice as likely to develop MI, vascular events, or death, as those with no such history.

Notably, however, the relative benefits of antiplatelet or anticoagulant therapy to prevent thromboembolic events did not differ significantly either in ACTIVE-W patients as a whole or in the subset of patients with heart failure, said Dr. Desai of Brigham and Women's Hospital, Boston. The risk of bleeding complications also did not differ between treatment groups.

Looking at the composite end point of death or hospitalization for heart failure, patients with a history of heart failure carried triple the risk, compared with non-heart failure patients, but again there was no significant difference between the antiplatelet and anticoagulant treatment groups.

The investigators stratified patients with heart failure based on whether they did or did not use an ACE inhibitor at baseline, expecting to see a greater relative benefit in the warfarin group if aspirin attenuated the effects of ACE inhibitors. They found no statistically significant differences between the antiplatelet and anticoagulation groups, suggesting no interaction between aspirin and ACE inhibitors.

Some heart failure patients in the warfarin group also were on ACE inhibitors at baseline, which might have limited the power to detect an aspirin-ACE inhibitor interaction, so they repeated the analyses after excluding patients on an ACE inhibitor at baseline who were randomized to warfarin. Again, they found no significant aspirin-ACE inhibitor interaction.

Concerns about such an interaction began with a 1992 hemodynamic study, later confirmed by others, that showed that coadministration of enalapril and aspirin in 18 patients with severe heart failure attenuated some of the hemodynamic effects of ACE inhibitors on vascular resistance. A retrospective analysis of the SOLVD trial suggested that patients on enalapril were more likely to die if they also took aspirin. A similar finding came from a retrospective analysis of the Scandinavian CONSENSUS II study. A large meta-analysis of ACE inhibitor trials, however, found no significant increase in death or hospitalization for heart failure with concurrent use of aspirin, said Dr. Desai, who has no relationships with the companies that make the drugs he discussed.

SEATTLE — Low-dose aspirin did not reduce the beneficial effects of ACE inhibitors in patients with atrial fibrillation and a history of heart failure, a subset analysis of 2,031 patients found.

The analysis addressed recurring concerns that aspirin use attenuates the effects of ACE inhibitors in heart failure patients and supported the use of both low-dose aspirin and an ACE inhibitor when indications for both treatments exist, Dr. Akshay S. Desai said at the annual meeting of the Heart Failure Society of America.

Dr. Desai and associates studied data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE-W). The prospective, open-label study randomized patients with atrial fibrillation to combination antiplatelet therapy with clopidogrel and 75–100 mg/day of aspirin or to oral anticoagulation with warfarin. ACTIVE-W was discontinued early because warfarin clearly reduced the risk of MI, vascular events, or death.

Compared with all ACTIVE-W patients, the 2,031 patients with prior heart failure were more likely to be hypertensive or diabetic; have left ventricular dysfunction, a prior MI, or coronary disease; and be on an ACE inhibitor or angiotensin receptor blocker at baseline. Patients with prior heart failure in ACTIVE-W were twice as likely to develop MI, vascular events, or death, as those with no such history.

Notably, however, the relative benefits of antiplatelet or anticoagulant therapy to prevent thromboembolic events did not differ significantly either in ACTIVE-W patients as a whole or in the subset of patients with heart failure, said Dr. Desai of Brigham and Women's Hospital, Boston. The risk of bleeding complications also did not differ between treatment groups.

Looking at the composite end point of death or hospitalization for heart failure, patients with a history of heart failure carried triple the risk, compared with non-heart failure patients, but again there was no significant difference between the antiplatelet and anticoagulant treatment groups.

The investigators stratified patients with heart failure based on whether they did or did not use an ACE inhibitor at baseline, expecting to see a greater relative benefit in the warfarin group if aspirin attenuated the effects of ACE inhibitors. They found no statistically significant differences between the antiplatelet and anticoagulation groups, suggesting no interaction between aspirin and ACE inhibitors.

Some heart failure patients in the warfarin group also were on ACE inhibitors at baseline, which might have limited the power to detect an aspirin-ACE inhibitor interaction, so they repeated the analyses after excluding patients on an ACE inhibitor at baseline who were randomized to warfarin. Again, they found no significant aspirin-ACE inhibitor interaction.

Concerns about such an interaction began with a 1992 hemodynamic study, later confirmed by others, that showed that coadministration of enalapril and aspirin in 18 patients with severe heart failure attenuated some of the hemodynamic effects of ACE inhibitors on vascular resistance. A retrospective analysis of the SOLVD trial suggested that patients on enalapril were more likely to die if they also took aspirin. A similar finding came from a retrospective analysis of the Scandinavian CONSENSUS II study. A large meta-analysis of ACE inhibitor trials, however, found no significant increase in death or hospitalization for heart failure with concurrent use of aspirin, said Dr. Desai, who has no relationships with the companies that make the drugs he discussed.

SEATTLE — Low-dose aspirin did not reduce the beneficial effects of ACE inhibitors in patients with atrial fibrillation and a history of heart failure, a subset analysis of 2,031 patients found.

The analysis addressed recurring concerns that aspirin use attenuates the effects of ACE inhibitors in heart failure patients and supported the use of both low-dose aspirin and an ACE inhibitor when indications for both treatments exist, Dr. Akshay S. Desai said at the annual meeting of the Heart Failure Society of America.

Dr. Desai and associates studied data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE-W). The prospective, open-label study randomized patients with atrial fibrillation to combination antiplatelet therapy with clopidogrel and 75–100 mg/day of aspirin or to oral anticoagulation with warfarin. ACTIVE-W was discontinued early because warfarin clearly reduced the risk of MI, vascular events, or death.

Compared with all ACTIVE-W patients, the 2,031 patients with prior heart failure were more likely to be hypertensive or diabetic; have left ventricular dysfunction, a prior MI, or coronary disease; and be on an ACE inhibitor or angiotensin receptor blocker at baseline. Patients with prior heart failure in ACTIVE-W were twice as likely to develop MI, vascular events, or death, as those with no such history.

Notably, however, the relative benefits of antiplatelet or anticoagulant therapy to prevent thromboembolic events did not differ significantly either in ACTIVE-W patients as a whole or in the subset of patients with heart failure, said Dr. Desai of Brigham and Women's Hospital, Boston. The risk of bleeding complications also did not differ between treatment groups.

Looking at the composite end point of death or hospitalization for heart failure, patients with a history of heart failure carried triple the risk, compared with non-heart failure patients, but again there was no significant difference between the antiplatelet and anticoagulant treatment groups.

The investigators stratified patients with heart failure based on whether they did or did not use an ACE inhibitor at baseline, expecting to see a greater relative benefit in the warfarin group if aspirin attenuated the effects of ACE inhibitors. They found no statistically significant differences between the antiplatelet and anticoagulation groups, suggesting no interaction between aspirin and ACE inhibitors.

Some heart failure patients in the warfarin group also were on ACE inhibitors at baseline, which might have limited the power to detect an aspirin-ACE inhibitor interaction, so they repeated the analyses after excluding patients on an ACE inhibitor at baseline who were randomized to warfarin. Again, they found no significant aspirin-ACE inhibitor interaction.

Concerns about such an interaction began with a 1992 hemodynamic study, later confirmed by others, that showed that coadministration of enalapril and aspirin in 18 patients with severe heart failure attenuated some of the hemodynamic effects of ACE inhibitors on vascular resistance. A retrospective analysis of the SOLVD trial suggested that patients on enalapril were more likely to die if they also took aspirin. A similar finding came from a retrospective analysis of the Scandinavian CONSENSUS II study. A large meta-analysis of ACE inhibitor trials, however, found no significant increase in death or hospitalization for heart failure with concurrent use of aspirin, said Dr. Desai, who has no relationships with the companies that make the drugs he discussed.

SAN FRANCISCO — Patients with end-stage heart failure who received cardiac injections of autologous endothelial progenitor cells showed significant improvements in function and ejection fraction 3 months later, Dr. Kitipan V. Arom reported.

The stem cell therapy treated 32 patients with ischemic cardiomyopathy and 21 with nonischemic dilated cardiomyopathy. Forty-three patients received the cell injections alone, eight underwent coronary artery bypass grafting with the cell injections, and two had a redo CABG with the cell injections, he said at the annual meeting of the International Society for Minimally Invasive Cardiothoracic Surgery.

One patient died 3 days after treatment, most likely from pulmonary emboli. The rest of the patients improved their New York Heart Association functional class from an average of class III to less than class II, said Dr. Arom of Bangkok Heart Hospital, Thailand, and associates.

The NYHA class improved in patients with ischemic cardiomyopathy from an average of 2.7 before cell injections to 1.4 at the 3-month follow-up. In the dilated cardiomyopathy group, the average improved from class III before treatment to II at the 3-month follow-up. Preoperative left ventricular ejection fractions averaged 26% in the ischemic cardiomyopathy group and 23% in the dilated cardiomyopathy group. Cell injection therapy improved ejection fractions significantly by an absolute 10% and 11%, respectively, he said.

Perfusion defects were seen in 19 patients before treatment and 11 patients at follow-up. Patients were able to walk farther in the 6-minute walk test after treatment, and scores on quality-of-life measures improved. Improvements in regional wall motion after therapy could be seen on cardiac MRI and four-chamber echocardiography.

The results are short term, and no one yet has data on outcomes longer than 2 years after stem cell transplants, Dr. Arom noted. So far, however, results are encouraging. “Hopefully, some time in the future, cell therapy can replace heart transplantation for end-stage heart failure,” he said.

Stem cells can come from many sources; this study used peripheral blood, which has the capacity to self-renew and differentiate into one or more cell types, Dr. Arom said. A week before surgery, patients donated 250 cc of blood that was sent for cell separation and growing. The stem cells produced were returned in 15-cc vials, each containing 1.5 million cells. All patients underwent cardiac MRI, echocardiography, and coronary angiography to help plan the injections.

In the dilated cardiomyopathy group, surgeons made 30 injections into multiple areas of the left ventricular wall using 0.5 cc per injection. Patients with ischemic cardiomyopathy received injections directly into the scar area and surrounding tissue.

The treatment was the last hope for these patients, who were much sicker than the average patient undergoing CABG is, he said. They had run the course of medical and surgical therapies. They suffered from mitral or tricuspid regurgitation, renal insufficiency, or other problems, and had been turned down for redo CABGs, valve replacements, or other surgeries.

The use of autologous progenitor cells avoids rejection concerns, and so far, there has been no evidence with these cells of the arrhythmogenic side effects seen with bone marrow cell transplant, he said.

SAN FRANCISCO — Patients with end-stage heart failure who received cardiac injections of autologous endothelial progenitor cells showed significant improvements in function and ejection fraction 3 months later, Dr. Kitipan V. Arom reported.

The stem cell therapy treated 32 patients with ischemic cardiomyopathy and 21 with nonischemic dilated cardiomyopathy. Forty-three patients received the cell injections alone, eight underwent coronary artery bypass grafting with the cell injections, and two had a redo CABG with the cell injections, he said at the annual meeting of the International Society for Minimally Invasive Cardiothoracic Surgery.

One patient died 3 days after treatment, most likely from pulmonary emboli. The rest of the patients improved their New York Heart Association functional class from an average of class III to less than class II, said Dr. Arom of Bangkok Heart Hospital, Thailand, and associates.

The NYHA class improved in patients with ischemic cardiomyopathy from an average of 2.7 before cell injections to 1.4 at the 3-month follow-up. In the dilated cardiomyopathy group, the average improved from class III before treatment to II at the 3-month follow-up. Preoperative left ventricular ejection fractions averaged 26% in the ischemic cardiomyopathy group and 23% in the dilated cardiomyopathy group. Cell injection therapy improved ejection fractions significantly by an absolute 10% and 11%, respectively, he said.

Perfusion defects were seen in 19 patients before treatment and 11 patients at follow-up. Patients were able to walk farther in the 6-minute walk test after treatment, and scores on quality-of-life measures improved. Improvements in regional wall motion after therapy could be seen on cardiac MRI and four-chamber echocardiography.

The results are short term, and no one yet has data on outcomes longer than 2 years after stem cell transplants, Dr. Arom noted. So far, however, results are encouraging. “Hopefully, some time in the future, cell therapy can replace heart transplantation for end-stage heart failure,” he said.

Stem cells can come from many sources; this study used peripheral blood, which has the capacity to self-renew and differentiate into one or more cell types, Dr. Arom said. A week before surgery, patients donated 250 cc of blood that was sent for cell separation and growing. The stem cells produced were returned in 15-cc vials, each containing 1.5 million cells. All patients underwent cardiac MRI, echocardiography, and coronary angiography to help plan the injections.

In the dilated cardiomyopathy group, surgeons made 30 injections into multiple areas of the left ventricular wall using 0.5 cc per injection. Patients with ischemic cardiomyopathy received injections directly into the scar area and surrounding tissue.

The treatment was the last hope for these patients, who were much sicker than the average patient undergoing CABG is, he said. They had run the course of medical and surgical therapies. They suffered from mitral or tricuspid regurgitation, renal insufficiency, or other problems, and had been turned down for redo CABGs, valve replacements, or other surgeries.

The use of autologous progenitor cells avoids rejection concerns, and so far, there has been no evidence with these cells of the arrhythmogenic side effects seen with bone marrow cell transplant, he said.

SAN FRANCISCO — Patients with end-stage heart failure who received cardiac injections of autologous endothelial progenitor cells showed significant improvements in function and ejection fraction 3 months later, Dr. Kitipan V. Arom reported.

The stem cell therapy treated 32 patients with ischemic cardiomyopathy and 21 with nonischemic dilated cardiomyopathy. Forty-three patients received the cell injections alone, eight underwent coronary artery bypass grafting with the cell injections, and two had a redo CABG with the cell injections, he said at the annual meeting of the International Society for Minimally Invasive Cardiothoracic Surgery.

One patient died 3 days after treatment, most likely from pulmonary emboli. The rest of the patients improved their New York Heart Association functional class from an average of class III to less than class II, said Dr. Arom of Bangkok Heart Hospital, Thailand, and associates.

The NYHA class improved in patients with ischemic cardiomyopathy from an average of 2.7 before cell injections to 1.4 at the 3-month follow-up. In the dilated cardiomyopathy group, the average improved from class III before treatment to II at the 3-month follow-up. Preoperative left ventricular ejection fractions averaged 26% in the ischemic cardiomyopathy group and 23% in the dilated cardiomyopathy group. Cell injection therapy improved ejection fractions significantly by an absolute 10% and 11%, respectively, he said.

Perfusion defects were seen in 19 patients before treatment and 11 patients at follow-up. Patients were able to walk farther in the 6-minute walk test after treatment, and scores on quality-of-life measures improved. Improvements in regional wall motion after therapy could be seen on cardiac MRI and four-chamber echocardiography.

The results are short term, and no one yet has data on outcomes longer than 2 years after stem cell transplants, Dr. Arom noted. So far, however, results are encouraging. “Hopefully, some time in the future, cell therapy can replace heart transplantation for end-stage heart failure,” he said.

Stem cells can come from many sources; this study used peripheral blood, which has the capacity to self-renew and differentiate into one or more cell types, Dr. Arom said. A week before surgery, patients donated 250 cc of blood that was sent for cell separation and growing. The stem cells produced were returned in 15-cc vials, each containing 1.5 million cells. All patients underwent cardiac MRI, echocardiography, and coronary angiography to help plan the injections.

In the dilated cardiomyopathy group, surgeons made 30 injections into multiple areas of the left ventricular wall using 0.5 cc per injection. Patients with ischemic cardiomyopathy received injections directly into the scar area and surrounding tissue.

The treatment was the last hope for these patients, who were much sicker than the average patient undergoing CABG is, he said. They had run the course of medical and surgical therapies. They suffered from mitral or tricuspid regurgitation, renal insufficiency, or other problems, and had been turned down for redo CABGs, valve replacements, or other surgeries.

The use of autologous progenitor cells avoids rejection concerns, and so far, there has been no evidence with these cells of the arrhythmogenic side effects seen with bone marrow cell transplant, he said.

The discovery of a common polymorphism in the gene for β₁-adrenergic-receptor blocker that predicts response to the β-blocker bucindolol has resurrected interest in the discarded drug.

Bucindolol could be the first genetically targeted cardiovascular drug, said Dr. Michael Bristow, codirector of the Cardiovascular Institute at the University of Colorado. His company, ARCA Discovery Inc. of Denver, intends to file a new drug and diagnostic test application with the Food and Drug Administration. If approved, the drug would be marketed along with a genetic test to identify potential responders.

Subjects with heart failure who were homozygous for the arginine variant of the β₁ AR-389 gene (Arg-389 variant) and who took bucindolol had a 38% reduction in mortality, compared with such patients who were treated with placebo, Dr. Bristow and his colleagues have reported. They also had a 34% reduction in the combined end point of hospitalizations and mortality (PNAS 2006;doi/10.1073/pnas.0509937103).

“This is where the field of pharmacogenetic therapy needs to go in cardiovascular medicine,” Dr. Bristow said in an interview. “Developing therapies that are specifically effective on pharmacogenetic subsets, so patients unlikely to respond to therapy aren't exposed to the risks and costs of treatment.”

The drug could be especially important for blacks, who are twice as likely as whites to develop heart failure, but who also have a poorer response to drugs, he said. The DNA test would target blacks who could benefit from bucindolol. “We wouldn't have to rely on skin color to assign therapy. We could assign therapy based on much better criteria: biology as predicted by a genetic profile.”

The bucindolol study is an exciting one, said Dr. Sidney Goldstein, head, emeritus, of the division of cardiovascular medicine at Henry Ford Hospital in Detroit. “Previous studies trying to link genotypes to β-blocker efficacy have shown some association. This study, which is the largest randomized population that has been looked at, certainly lends further credibility to the thought.”

But it will take more than one DNA study to bring bucindolol to market, he predicted. “It's very intriguing, but in order to get approval we'd need a lot more clinical evidence in this particular population,” said Dr. Goldstein, medical editor of CARDIOLOGY NEWS.

Mainstream research abandoned bucindolol in 1999, when the Beta-Blocker Evaluation of Survival Time study (BEST) was halted for ethical reasons. After a median of 2 years, bucindolol offered no significant survival advantage over placebo, while other β-blockers had long been confirmed as beneficial.

But as the study was further analyzed, substudies using its database emerged, including one using DNA collected from 1,040 BEST subjects. In 1998, Dr. Steve Liggett, BEST's lead investigator, identified several genetic variants of the β₁-adrenergic receptor—the target of β-blocker therapy. In a DNA substudy submitted before BEST ended, Dr. Liggett and Dr. Bristow hypothesized that the Arg-389 variant would predict bucindolol response.

Dr. Bristow and his colleagues reexamined the BEST response data, stratifying survival of placebo and bucindolol-treated patients according to genetic type. Only homozygous Arg-389 variant patients treated with bucindolol showed a significant survival advantage: a hazard ratio of 0.62 for mortality, compared with Arg-389 variant placebo-treated patients.

The polymorphism occurred more frequently in whites than in blacks (51% vs. 35%), Dr. Bristow said—an intriguing finding that probably speaks to bucindolol's better performance among whites in the original BEST study (N. Engl. J. Med. 2001;344:1659–67). “We need more research on this point, but it may be possible that this genetic variant has a great deal to do with why black patients have more heart failure, and worse outcomes, than white patients.”

Bucindolol has a unique pharmacologic profile among β-blockers, not only blocking adrenergic receptors but lowering norepinephrine as well. “It appears that those with the Arg/Arg polymorphism can tolerate the loss of norepinephrine signalling better than those who don't have it,” Dr. Bristow said. “In them, the combination of actions produces a supertherapeutic response.”

It's impossible to extrapolate bucindolol's positive effect on patients with the arginine variant to any other β-blocker, however. One study has already addressed this issue, finding no association between β₁-AR genetic subtype and survival in patients taking metoprolol (Eur. J. Heart Fail. 2003;5:463–78). There are no data available on carvedilol or bisoprolol.

If bucindolol and its accompanying genetic screen are eventually approved, physicians and patients will have to decide if the additional time and expense of genetic testing will be worth the drug's benefit, Dr. Goldstein said. “Metoprolol and carvedilol will probably both be coming out in generic forms pretty quickly. In all probability they will be substantially less expensive than bucindolol, and it's hard to believe bucindolol would be better than those drugs, although it does appear to be just as good for these particular patients.”

The discovery of a common polymorphism in the gene for β₁-adrenergic-receptor blocker that predicts response to the β-blocker bucindolol has resurrected interest in the discarded drug.

Bucindolol could be the first genetically targeted cardiovascular drug, said Dr. Michael Bristow, codirector of the Cardiovascular Institute at the University of Colorado. His company, ARCA Discovery Inc. of Denver, intends to file a new drug and diagnostic test application with the Food and Drug Administration. If approved, the drug would be marketed along with a genetic test to identify potential responders.

Subjects with heart failure who were homozygous for the arginine variant of the β₁ AR-389 gene (Arg-389 variant) and who took bucindolol had a 38% reduction in mortality, compared with such patients who were treated with placebo, Dr. Bristow and his colleagues have reported. They also had a 34% reduction in the combined end point of hospitalizations and mortality (PNAS 2006;doi/10.1073/pnas.0509937103).

“This is where the field of pharmacogenetic therapy needs to go in cardiovascular medicine,” Dr. Bristow said in an interview. “Developing therapies that are specifically effective on pharmacogenetic subsets, so patients unlikely to respond to therapy aren't exposed to the risks and costs of treatment.”

The drug could be especially important for blacks, who are twice as likely as whites to develop heart failure, but who also have a poorer response to drugs, he said. The DNA test would target blacks who could benefit from bucindolol. “We wouldn't have to rely on skin color to assign therapy. We could assign therapy based on much better criteria: biology as predicted by a genetic profile.”

The bucindolol study is an exciting one, said Dr. Sidney Goldstein, head, emeritus, of the division of cardiovascular medicine at Henry Ford Hospital in Detroit. “Previous studies trying to link genotypes to β-blocker efficacy have shown some association. This study, which is the largest randomized population that has been looked at, certainly lends further credibility to the thought.”

But it will take more than one DNA study to bring bucindolol to market, he predicted. “It's very intriguing, but in order to get approval we'd need a lot more clinical evidence in this particular population,” said Dr. Goldstein, medical editor of CARDIOLOGY NEWS.

Mainstream research abandoned bucindolol in 1999, when the Beta-Blocker Evaluation of Survival Time study (BEST) was halted for ethical reasons. After a median of 2 years, bucindolol offered no significant survival advantage over placebo, while other β-blockers had long been confirmed as beneficial.

But as the study was further analyzed, substudies using its database emerged, including one using DNA collected from 1,040 BEST subjects. In 1998, Dr. Steve Liggett, BEST's lead investigator, identified several genetic variants of the β₁-adrenergic receptor—the target of β-blocker therapy. In a DNA substudy submitted before BEST ended, Dr. Liggett and Dr. Bristow hypothesized that the Arg-389 variant would predict bucindolol response.

Dr. Bristow and his colleagues reexamined the BEST response data, stratifying survival of placebo and bucindolol-treated patients according to genetic type. Only homozygous Arg-389 variant patients treated with bucindolol showed a significant survival advantage: a hazard ratio of 0.62 for mortality, compared with Arg-389 variant placebo-treated patients.

The polymorphism occurred more frequently in whites than in blacks (51% vs. 35%), Dr. Bristow said—an intriguing finding that probably speaks to bucindolol's better performance among whites in the original BEST study (N. Engl. J. Med. 2001;344:1659–67). “We need more research on this point, but it may be possible that this genetic variant has a great deal to do with why black patients have more heart failure, and worse outcomes, than white patients.”

Bucindolol has a unique pharmacologic profile among β-blockers, not only blocking adrenergic receptors but lowering norepinephrine as well. “It appears that those with the Arg/Arg polymorphism can tolerate the loss of norepinephrine signalling better than those who don't have it,” Dr. Bristow said. “In them, the combination of actions produces a supertherapeutic response.”

It's impossible to extrapolate bucindolol's positive effect on patients with the arginine variant to any other β-blocker, however. One study has already addressed this issue, finding no association between β₁-AR genetic subtype and survival in patients taking metoprolol (Eur. J. Heart Fail. 2003;5:463–78). There are no data available on carvedilol or bisoprolol.

If bucindolol and its accompanying genetic screen are eventually approved, physicians and patients will have to decide if the additional time and expense of genetic testing will be worth the drug's benefit, Dr. Goldstein said. “Metoprolol and carvedilol will probably both be coming out in generic forms pretty quickly. In all probability they will be substantially less expensive than bucindolol, and it's hard to believe bucindolol would be better than those drugs, although it does appear to be just as good for these particular patients.”

The discovery of a common polymorphism in the gene for β₁-adrenergic-receptor blocker that predicts response to the β-blocker bucindolol has resurrected interest in the discarded drug.

Bucindolol could be the first genetically targeted cardiovascular drug, said Dr. Michael Bristow, codirector of the Cardiovascular Institute at the University of Colorado. His company, ARCA Discovery Inc. of Denver, intends to file a new drug and diagnostic test application with the Food and Drug Administration. If approved, the drug would be marketed along with a genetic test to identify potential responders.

Subjects with heart failure who were homozygous for the arginine variant of the β₁ AR-389 gene (Arg-389 variant) and who took bucindolol had a 38% reduction in mortality, compared with such patients who were treated with placebo, Dr. Bristow and his colleagues have reported. They also had a 34% reduction in the combined end point of hospitalizations and mortality (PNAS 2006;doi/10.1073/pnas.0509937103).

“This is where the field of pharmacogenetic therapy needs to go in cardiovascular medicine,” Dr. Bristow said in an interview. “Developing therapies that are specifically effective on pharmacogenetic subsets, so patients unlikely to respond to therapy aren't exposed to the risks and costs of treatment.”

The drug could be especially important for blacks, who are twice as likely as whites to develop heart failure, but who also have a poorer response to drugs, he said. The DNA test would target blacks who could benefit from bucindolol. “We wouldn't have to rely on skin color to assign therapy. We could assign therapy based on much better criteria: biology as predicted by a genetic profile.”

The bucindolol study is an exciting one, said Dr. Sidney Goldstein, head, emeritus, of the division of cardiovascular medicine at Henry Ford Hospital in Detroit. “Previous studies trying to link genotypes to β-blocker efficacy have shown some association. This study, which is the largest randomized population that has been looked at, certainly lends further credibility to the thought.”

But it will take more than one DNA study to bring bucindolol to market, he predicted. “It's very intriguing, but in order to get approval we'd need a lot more clinical evidence in this particular population,” said Dr. Goldstein, medical editor of CARDIOLOGY NEWS.

Mainstream research abandoned bucindolol in 1999, when the Beta-Blocker Evaluation of Survival Time study (BEST) was halted for ethical reasons. After a median of 2 years, bucindolol offered no significant survival advantage over placebo, while other β-blockers had long been confirmed as beneficial.

But as the study was further analyzed, substudies using its database emerged, including one using DNA collected from 1,040 BEST subjects. In 1998, Dr. Steve Liggett, BEST's lead investigator, identified several genetic variants of the β₁-adrenergic receptor—the target of β-blocker therapy. In a DNA substudy submitted before BEST ended, Dr. Liggett and Dr. Bristow hypothesized that the Arg-389 variant would predict bucindolol response.

Dr. Bristow and his colleagues reexamined the BEST response data, stratifying survival of placebo and bucindolol-treated patients according to genetic type. Only homozygous Arg-389 variant patients treated with bucindolol showed a significant survival advantage: a hazard ratio of 0.62 for mortality, compared with Arg-389 variant placebo-treated patients.

The polymorphism occurred more frequently in whites than in blacks (51% vs. 35%), Dr. Bristow said—an intriguing finding that probably speaks to bucindolol's better performance among whites in the original BEST study (N. Engl. J. Med. 2001;344:1659–67). “We need more research on this point, but it may be possible that this genetic variant has a great deal to do with why black patients have more heart failure, and worse outcomes, than white patients.”

Bucindolol has a unique pharmacologic profile among β-blockers, not only blocking adrenergic receptors but lowering norepinephrine as well. “It appears that those with the Arg/Arg polymorphism can tolerate the loss of norepinephrine signalling better than those who don't have it,” Dr. Bristow said. “In them, the combination of actions produces a supertherapeutic response.”

It's impossible to extrapolate bucindolol's positive effect on patients with the arginine variant to any other β-blocker, however. One study has already addressed this issue, finding no association between β₁-AR genetic subtype and survival in patients taking metoprolol (Eur. J. Heart Fail. 2003;5:463–78). There are no data available on carvedilol or bisoprolol.

If bucindolol and its accompanying genetic screen are eventually approved, physicians and patients will have to decide if the additional time and expense of genetic testing will be worth the drug's benefit, Dr. Goldstein said. “Metoprolol and carvedilol will probably both be coming out in generic forms pretty quickly. In all probability they will be substantially less expensive than bucindolol, and it's hard to believe bucindolol would be better than those drugs, although it does appear to be just as good for these particular patients.”

ATLANTA — Carvedilol proved no better than placebo in the first-ever randomized trial of any therapy for chronic heart failure in children, Dr. Robert E. Shaddy said at the annual meeting of the American College of Cardiology.

Until now, treatment of pediatric heart failure has been based largely on the findings of the landmark heart failure trials in adults, with anecdotal best-guess extrapolation in regard to dosing in children. β-Blocker therapy is standard in adult heart failure. But the results of this first multicenter study emphasize that heart failure in children and adults are in some ways very different conditions, added Dr. Shaddy, professor of pediatric cardiology at the University of Utah, Salt Lake City.

He reported on 161 children with symptomatic systolic heart failure who participated in a 26-center double-blind trial in which they were randomized to one of the following regimens: twice-daily placebo, carvedilol at 0.2 mg/kg b.i.d. to a maximum of 12.5 mg per dose in children weighing more than 62.5 kg, or carvedilol at 0.4 mg/kg b.i.d. to a maximum of 25 mg per dose.

The participants had dilated cardiomyopathy or congenital heart disease. Their median age was 3 years, with a range of 3 months to 17 years. All were on an ACE inhibitor unless they were intolerant. Of the total, 71% had New York Heart Association class II heart failure and 27% had class III disease at baseline, with a median left ventricular ejection fraction of 26%.

The primary study end point was heart failure outcome at 8 months as defined by a composite including death, cardiovascular hospitalization, and change in NYHA class, Ross classification of heart failure, and/or physician global assessment score. The results proved similar in the placebo and combined carvedilol groups because of an unexpectedly robust improvement in the placebo group. (See box.)

In hindsight, this might have been predicted because many think that spontaneous improvement is more frequent in younger children with heart failure—and 45% of the trial participants in this trial were younger than 2 years.

A prespecified secondary analysis showed differential results for β-blocker therapy based on ventricular anatomy. In patients with a systemic left ventricle, the rate of improvement was 51% with placebo and 64% with carvedilol. By contrast, the 41 patients with a systemic ventricle other than the left ventricle had a 64% rate of improvement with placebo, compared with 35% with carvedilol.

But it would be difficult to pursue this finding through further controlled trials restricted to children with a systemic left ventricle. Many parents, physicians, and institutional review boards have reservations about randomizing children with heart failure to placebo, said Dr. Shaddy, who is a consultant to GlaxoSmithKline, which sponsored the trial.

Discussant Dr. JoAnn Lindenfeld said that although this was a negative study, she was impressed with the trends for reduction in the objective end points of death and cardiovascular hospitalization with carvedilol, even though the trends didn't reach statistical significance. Dr. Lindenfeld is professor of medicine at the University of Colorado, Denver.

ELSEVIER GLOBAL MEDICAL NEWS

ATLANTA — Carvedilol proved no better than placebo in the first-ever randomized trial of any therapy for chronic heart failure in children, Dr. Robert E. Shaddy said at the annual meeting of the American College of Cardiology.

Until now, treatment of pediatric heart failure has been based largely on the findings of the landmark heart failure trials in adults, with anecdotal best-guess extrapolation in regard to dosing in children. β-Blocker therapy is standard in adult heart failure. But the results of this first multicenter study emphasize that heart failure in children and adults are in some ways very different conditions, added Dr. Shaddy, professor of pediatric cardiology at the University of Utah, Salt Lake City.

He reported on 161 children with symptomatic systolic heart failure who participated in a 26-center double-blind trial in which they were randomized to one of the following regimens: twice-daily placebo, carvedilol at 0.2 mg/kg b.i.d. to a maximum of 12.5 mg per dose in children weighing more than 62.5 kg, or carvedilol at 0.4 mg/kg b.i.d. to a maximum of 25 mg per dose.

The participants had dilated cardiomyopathy or congenital heart disease. Their median age was 3 years, with a range of 3 months to 17 years. All were on an ACE inhibitor unless they were intolerant. Of the total, 71% had New York Heart Association class II heart failure and 27% had class III disease at baseline, with a median left ventricular ejection fraction of 26%.

The primary study end point was heart failure outcome at 8 months as defined by a composite including death, cardiovascular hospitalization, and change in NYHA class, Ross classification of heart failure, and/or physician global assessment score. The results proved similar in the placebo and combined carvedilol groups because of an unexpectedly robust improvement in the placebo group. (See box.)

In hindsight, this might have been predicted because many think that spontaneous improvement is more frequent in younger children with heart failure—and 45% of the trial participants in this trial were younger than 2 years.

A prespecified secondary analysis showed differential results for β-blocker therapy based on ventricular anatomy. In patients with a systemic left ventricle, the rate of improvement was 51% with placebo and 64% with carvedilol. By contrast, the 41 patients with a systemic ventricle other than the left ventricle had a 64% rate of improvement with placebo, compared with 35% with carvedilol.

But it would be difficult to pursue this finding through further controlled trials restricted to children with a systemic left ventricle. Many parents, physicians, and institutional review boards have reservations about randomizing children with heart failure to placebo, said Dr. Shaddy, who is a consultant to GlaxoSmithKline, which sponsored the trial.

Discussant Dr. JoAnn Lindenfeld said that although this was a negative study, she was impressed with the trends for reduction in the objective end points of death and cardiovascular hospitalization with carvedilol, even though the trends didn't reach statistical significance. Dr. Lindenfeld is professor of medicine at the University of Colorado, Denver.

ELSEVIER GLOBAL MEDICAL NEWS

ATLANTA — Carvedilol proved no better than placebo in the first-ever randomized trial of any therapy for chronic heart failure in children, Dr. Robert E. Shaddy said at the annual meeting of the American College of Cardiology.

Until now, treatment of pediatric heart failure has been based largely on the findings of the landmark heart failure trials in adults, with anecdotal best-guess extrapolation in regard to dosing in children. β-Blocker therapy is standard in adult heart failure. But the results of this first multicenter study emphasize that heart failure in children and adults are in some ways very different conditions, added Dr. Shaddy, professor of pediatric cardiology at the University of Utah, Salt Lake City.

He reported on 161 children with symptomatic systolic heart failure who participated in a 26-center double-blind trial in which they were randomized to one of the following regimens: twice-daily placebo, carvedilol at 0.2 mg/kg b.i.d. to a maximum of 12.5 mg per dose in children weighing more than 62.5 kg, or carvedilol at 0.4 mg/kg b.i.d. to a maximum of 25 mg per dose.

The participants had dilated cardiomyopathy or congenital heart disease. Their median age was 3 years, with a range of 3 months to 17 years. All were on an ACE inhibitor unless they were intolerant. Of the total, 71% had New York Heart Association class II heart failure and 27% had class III disease at baseline, with a median left ventricular ejection fraction of 26%.

The primary study end point was heart failure outcome at 8 months as defined by a composite including death, cardiovascular hospitalization, and change in NYHA class, Ross classification of heart failure, and/or physician global assessment score. The results proved similar in the placebo and combined carvedilol groups because of an unexpectedly robust improvement in the placebo group. (See box.)

In hindsight, this might have been predicted because many think that spontaneous improvement is more frequent in younger children with heart failure—and 45% of the trial participants in this trial were younger than 2 years.

A prespecified secondary analysis showed differential results for β-blocker therapy based on ventricular anatomy. In patients with a systemic left ventricle, the rate of improvement was 51% with placebo and 64% with carvedilol. By contrast, the 41 patients with a systemic ventricle other than the left ventricle had a 64% rate of improvement with placebo, compared with 35% with carvedilol.

But it would be difficult to pursue this finding through further controlled trials restricted to children with a systemic left ventricle. Many parents, physicians, and institutional review boards have reservations about randomizing children with heart failure to placebo, said Dr. Shaddy, who is a consultant to GlaxoSmithKline, which sponsored the trial.

Discussant Dr. JoAnn Lindenfeld said that although this was a negative study, she was impressed with the trends for reduction in the objective end points of death and cardiovascular hospitalization with carvedilol, even though the trends didn't reach statistical significance. Dr. Lindenfeld is professor of medicine at the University of Colorado, Denver.

ELSEVIER GLOBAL MEDICAL NEWS

MADRID — Patients with acute decompensated heart failure who were treated with nesiritide had an in-hospital mortality rate that appeared to be no worse than that of patients who were treated intravenously with either nitroglycerin or a diuretic, according to data from a registry with more than 100,000 patients.

The findings “warrant prospective confirmation of the mortality risk associated with different therapies for acute decompensated heart failure,” Dr. Maria Rosa Costanzo said at the annual meeting of the International Society for Heart and Lung Transplantation.

“We did not find any signal of increased [in-hospital] mortality in patients treated with either nesiritide or nitroglycerin,” said Dr. Costanzo in an interview. The results of her analysis “confirm the appropriateness of nesiritide treatment in patients for whom it's approved,” specifically single-dose treatment of patients with acute decompensated heart failure and symptoms that lead to hospitalization for heart failure, said Dr. Costanzo, medical director of the Edward Hospital Center for Advanced Heart Failure in Naperville, Ill.

Nesiritide's safety for treating patients with heart failure has been under a cloud since a pair of metaanalyses were published last year that suggested that patients who were treated with a single dose of the drug had an excess rate of worsening renal function and death during the subsequent 30 days.

At least one expert who reviewed the new report found limited reassurance in the findings. “The analyses appear to be well done, and they provide some comfort about the short-term safety of nesiritide,” said Dr. Barry M. Massie in an interview. But the results “are not very helpful because they were only able to examine the in-hospital phase,” and there was no information on renal function or length of hospital stay. The results from other studies with nesiritide have indicated that the excess of worsening renal failure occurred primarily after 7 days, and the trends toward increased mortality were most apparent after 30 days, 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.

The new analysis used data from the Acute Decompensated Heart Failure National Registry (ADHERE), which collected data from more than 180,000 patients who were hospitalized at any of 263 participating hospitals in the United States during October 2001 to March 2006, when the registry closed. The analysis by Dr. Costanzo and her associates used data collected from nearly 135,000 patients who were enrolled through August 2004.

The ADHERE registry was sponsored by Scios Inc., the division of Johnson & Johnson that markets nesiritide (Natrecor). Dr. Costanzo serves on the scientific advisory board of Scios.

The analysis excluded about 35,000 patients from the registry who turned out not to have heart failure, had a delayed diagnosis, or had complicating conditions such as a respiratory infection or MI.

Data collected on the remaining 99,963 patients were further refined using two analytic tools aimed at simulating a prospective, controlled study.

The first tool categorized patients by their “intended primary treatment (IPT),” a method used to “simulate an intention-to-treat analysis,” said Dr. Costanzo in an interview. The IPT was whichever drug or drugs a patient received during the first 2 hours of treatment. By this criterion, the vast majority of patients, more than 74,000, received an intravenous diuretic alone as their IPT. Monotherapy with nesiritide as the IPT occurred in 1,855 patients, intravenous nitroglycerin monotherapy was the IPT in 1,590 patients, and 2,465 patients received an inotrope (dobutamine, dopamine, or milrinone) as monotherapy IPT. The remaining patients received at least two drugs during their first 2 hours of treatment.

Comparisons of the IPT groups were then made using a propensity analysis, a method that matches patients from two unrandomized groups by a variety of demographic and clinical characteristics. In this case, the propensity analysis used more than 55 variables, said Dr. Costanzo. Patients who could not be matched with patients from the comparator group were excluded from the analysis.

“The problem with observational data sets is that most physician-determined interventions are not random and reflect something about the judgment of risk and therefore are confounded by the resulting biases. Propensity-score matching is the favored approach to deal with confounding but is limited by only being able to deal with measured variables,” commented Dr. Massie.

The two main analyses that Dr. Costanzo presented compared the in-hospital mortality rates of patients treated with nesiritide or a diuretic, and those of patients treated with nitroglycerin or a diuretic.

In the first comparison, the mortality rate was 3.6% among 1,701 patients treated with nesiritide and 4.8% among 8,505 patients treated with a diuretic, a statistically significant difference. In the second comparison, in-hospital mortality occurred in 2.7% of 1,488 patients treated with nitroglycerin compared with a 3.0% mortality rate among 7,440 patients treated with a diuretic, a difference that was not statistically significant.

Another analysis focused on patients who received either nesiritide or nitroglycerin as a second drug sometime after the initial 2-hour window that was used to define the IPT. The 1,028 patients who received nesiritide as a second drug (following initial treatment with a diuretic, nitroglycerin, or an inotrope) had an in-hospital mortality rate of 3.4%. By comparison, 1,028 patients who received nitroglycerin as a second drug had a mortality rate of 6.2%, a statistically significant difference.

Data like these are useful, Dr. Costanzo said in an interview, because following publication of the two metaanalyses a year ago, physicians have become more reluctant to prescribe nesiritide to patients with acute decompensated heart failure. “Many physicians have reverted back to using more inotropes, which I'm pretty confident are associated with increased mortality,” she said.

MADRID — Patients with acute decompensated heart failure who were treated with nesiritide had an in-hospital mortality rate that appeared to be no worse than that of patients who were treated intravenously with either nitroglycerin or a diuretic, according to data from a registry with more than 100,000 patients.

The findings “warrant prospective confirmation of the mortality risk associated with different therapies for acute decompensated heart failure,” Dr. Maria Rosa Costanzo said at the annual meeting of the International Society for Heart and Lung Transplantation.

“We did not find any signal of increased [in-hospital] mortality in patients treated with either nesiritide or nitroglycerin,” said Dr. Costanzo in an interview. The results of her analysis “confirm the appropriateness of nesiritide treatment in patients for whom it's approved,” specifically single-dose treatment of patients with acute decompensated heart failure and symptoms that lead to hospitalization for heart failure, said Dr. Costanzo, medical director of the Edward Hospital Center for Advanced Heart Failure in Naperville, Ill.

Nesiritide's safety for treating patients with heart failure has been under a cloud since a pair of metaanalyses were published last year that suggested that patients who were treated with a single dose of the drug had an excess rate of worsening renal function and death during the subsequent 30 days.

At least one expert who reviewed the new report found limited reassurance in the findings. “The analyses appear to be well done, and they provide some comfort about the short-term safety of nesiritide,” said Dr. Barry M. Massie in an interview. But the results “are not very helpful because they were only able to examine the in-hospital phase,” and there was no information on renal function or length of hospital stay. The results from other studies with nesiritide have indicated that the excess of worsening renal failure occurred primarily after 7 days, and the trends toward increased mortality were most apparent after 30 days, 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.

The new analysis used data from the Acute Decompensated Heart Failure National Registry (ADHERE), which collected data from more than 180,000 patients who were hospitalized at any of 263 participating hospitals in the United States during October 2001 to March 2006, when the registry closed. The analysis by Dr. Costanzo and her associates used data collected from nearly 135,000 patients who were enrolled through August 2004.

The ADHERE registry was sponsored by Scios Inc., the division of Johnson & Johnson that markets nesiritide (Natrecor). Dr. Costanzo serves on the scientific advisory board of Scios.

The analysis excluded about 35,000 patients from the registry who turned out not to have heart failure, had a delayed diagnosis, or had complicating conditions such as a respiratory infection or MI.

Data collected on the remaining 99,963 patients were further refined using two analytic tools aimed at simulating a prospective, controlled study.

The first tool categorized patients by their “intended primary treatment (IPT),” a method used to “simulate an intention-to-treat analysis,” said Dr. Costanzo in an interview. The IPT was whichever drug or drugs a patient received during the first 2 hours of treatment. By this criterion, the vast majority of patients, more than 74,000, received an intravenous diuretic alone as their IPT. Monotherapy with nesiritide as the IPT occurred in 1,855 patients, intravenous nitroglycerin monotherapy was the IPT in 1,590 patients, and 2,465 patients received an inotrope (dobutamine, dopamine, or milrinone) as monotherapy IPT. The remaining patients received at least two drugs during their first 2 hours of treatment.

Comparisons of the IPT groups were then made using a propensity analysis, a method that matches patients from two unrandomized groups by a variety of demographic and clinical characteristics. In this case, the propensity analysis used more than 55 variables, said Dr. Costanzo. Patients who could not be matched with patients from the comparator group were excluded from the analysis.

“The problem with observational data sets is that most physician-determined interventions are not random and reflect something about the judgment of risk and therefore are confounded by the resulting biases. Propensity-score matching is the favored approach to deal with confounding but is limited by only being able to deal with measured variables,” commented Dr. Massie.

The two main analyses that Dr. Costanzo presented compared the in-hospital mortality rates of patients treated with nesiritide or a diuretic, and those of patients treated with nitroglycerin or a diuretic.

In the first comparison, the mortality rate was 3.6% among 1,701 patients treated with nesiritide and 4.8% among 8,505 patients treated with a diuretic, a statistically significant difference. In the second comparison, in-hospital mortality occurred in 2.7% of 1,488 patients treated with nitroglycerin compared with a 3.0% mortality rate among 7,440 patients treated with a diuretic, a difference that was not statistically significant.

Another analysis focused on patients who received either nesiritide or nitroglycerin as a second drug sometime after the initial 2-hour window that was used to define the IPT. The 1,028 patients who received nesiritide as a second drug (following initial treatment with a diuretic, nitroglycerin, or an inotrope) had an in-hospital mortality rate of 3.4%. By comparison, 1,028 patients who received nitroglycerin as a second drug had a mortality rate of 6.2%, a statistically significant difference.

Data like these are useful, Dr. Costanzo said in an interview, because following publication of the two metaanalyses a year ago, physicians have become more reluctant to prescribe nesiritide to patients with acute decompensated heart failure. “Many physicians have reverted back to using more inotropes, which I'm pretty confident are associated with increased mortality,” she said.

MADRID — Patients with acute decompensated heart failure who were treated with nesiritide had an in-hospital mortality rate that appeared to be no worse than that of patients who were treated intravenously with either nitroglycerin or a diuretic, according to data from a registry with more than 100,000 patients.

The findings “warrant prospective confirmation of the mortality risk associated with different therapies for acute decompensated heart failure,” Dr. Maria Rosa Costanzo said at the annual meeting of the International Society for Heart and Lung Transplantation.

“We did not find any signal of increased [in-hospital] mortality in patients treated with either nesiritide or nitroglycerin,” said Dr. Costanzo in an interview. The results of her analysis “confirm the appropriateness of nesiritide treatment in patients for whom it's approved,” specifically single-dose treatment of patients with acute decompensated heart failure and symptoms that lead to hospitalization for heart failure, said Dr. Costanzo, medical director of the Edward Hospital Center for Advanced Heart Failure in Naperville, Ill.

Nesiritide's safety for treating patients with heart failure has been under a cloud since a pair of metaanalyses were published last year that suggested that patients who were treated with a single dose of the drug had an excess rate of worsening renal function and death during the subsequent 30 days.

At least one expert who reviewed the new report found limited reassurance in the findings. “The analyses appear to be well done, and they provide some comfort about the short-term safety of nesiritide,” said Dr. Barry M. Massie in an interview. But the results “are not very helpful because they were only able to examine the in-hospital phase,” and there was no information on renal function or length of hospital stay. The results from other studies with nesiritide have indicated that the excess of worsening renal failure occurred primarily after 7 days, and the trends toward increased mortality were most apparent after 30 days, 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.

The new analysis used data from the Acute Decompensated Heart Failure National Registry (ADHERE), which collected data from more than 180,000 patients who were hospitalized at any of 263 participating hospitals in the United States during October 2001 to March 2006, when the registry closed. The analysis by Dr. Costanzo and her associates used data collected from nearly 135,000 patients who were enrolled through August 2004.

The ADHERE registry was sponsored by Scios Inc., the division of Johnson & Johnson that markets nesiritide (Natrecor). Dr. Costanzo serves on the scientific advisory board of Scios.

The analysis excluded about 35,000 patients from the registry who turned out not to have heart failure, had a delayed diagnosis, or had complicating conditions such as a respiratory infection or MI.

Data collected on the remaining 99,963 patients were further refined using two analytic tools aimed at simulating a prospective, controlled study.

The first tool categorized patients by their “intended primary treatment (IPT),” a method used to “simulate an intention-to-treat analysis,” said Dr. Costanzo in an interview. The IPT was whichever drug or drugs a patient received during the first 2 hours of treatment. By this criterion, the vast majority of patients, more than 74,000, received an intravenous diuretic alone as their IPT. Monotherapy with nesiritide as the IPT occurred in 1,855 patients, intravenous nitroglycerin monotherapy was the IPT in 1,590 patients, and 2,465 patients received an inotrope (dobutamine, dopamine, or milrinone) as monotherapy IPT. The remaining patients received at least two drugs during their first 2 hours of treatment.

Comparisons of the IPT groups were then made using a propensity analysis, a method that matches patients from two unrandomized groups by a variety of demographic and clinical characteristics. In this case, the propensity analysis used more than 55 variables, said Dr. Costanzo. Patients who could not be matched with patients from the comparator group were excluded from the analysis.

“The problem with observational data sets is that most physician-determined interventions are not random and reflect something about the judgment of risk and therefore are confounded by the resulting biases. Propensity-score matching is the favored approach to deal with confounding but is limited by only being able to deal with measured variables,” commented Dr. Massie.

The two main analyses that Dr. Costanzo presented compared the in-hospital mortality rates of patients treated with nesiritide or a diuretic, and those of patients treated with nitroglycerin or a diuretic.

In the first comparison, the mortality rate was 3.6% among 1,701 patients treated with nesiritide and 4.8% among 8,505 patients treated with a diuretic, a statistically significant difference. In the second comparison, in-hospital mortality occurred in 2.7% of 1,488 patients treated with nitroglycerin compared with a 3.0% mortality rate among 7,440 patients treated with a diuretic, a difference that was not statistically significant.

Another analysis focused on patients who received either nesiritide or nitroglycerin as a second drug sometime after the initial 2-hour window that was used to define the IPT. The 1,028 patients who received nesiritide as a second drug (following initial treatment with a diuretic, nitroglycerin, or an inotrope) had an in-hospital mortality rate of 3.4%. By comparison, 1,028 patients who received nitroglycerin as a second drug had a mortality rate of 6.2%, a statistically significant difference.

Data like these are useful, Dr. Costanzo said in an interview, because following publication of the two metaanalyses a year ago, physicians have become more reluctant to prescribe nesiritide to patients with acute decompensated heart failure. “Many physicians have reverted back to using more inotropes, which I'm pretty confident are associated with increased mortality,” she said.

MADRID — The four criteria now used to measure hospitals' performance in treating patients with heart failure also have a significant impact on patient survival, based on a review of more than 2,000 patients.

In 2002, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) set four core measures for the assessment of the quality of heart failure management.

“To our knowledge, this is the first report showing that adherence to the JCAHO heart failure core measures improves 1-year survival following hospitalization for heart failure,” Dr. A.G. Kfoury said at the annual meeting of the International Society for Heart and Lung Transplantation.

“The data show that these four cheap interventions can have an impact on patient outcomes,” said Dr. Kfoury, who is the medical director of the Utah Transplantation Affiliated Hospitals cardiac transplant program, and associate director of the heart failure prevention and treatment program at LDS Hospital in Salt Lake City.

The four performance measures are: discharge instructions to patients on heart failure management, including medications, diet, and weight control; assessment of left ventricular function or scheduling an assessment at discharge; treatment with an ACE inhibitor or angiotensin receptor blocker (ARB) at discharge; and instructions on smoking cessation at discharge.

To determine how the application of these four measures correlated with patient survival, Dr. Kfoury and his associates reviewed the records of 2,144 patients who were discharged with a primary diagnosis of heart failure and left ventricular dysfunction from 20 hospitals within the Intermountain Healthcare system from January 2003 to May 2005. The primary end point of the analysis was death during the 12 months following hospital discharge.

Because 90% of the patients were nonsmokers, one analysis excluded the smoking cessation measure and focused on the application of the other three criteria.

About 43% of patients received all three interventions, and another 39% of the patients received two of the interventions. Some 3% of patients received none of the interventions. When only one intervention was used, it was most often prescription of an ACE inhibitor or ARB.

The second most commonly used intervention was assessment of left ventricular function. Patient education was applied less often.

According to an analysis that adjusted for patients' age, gender, and severity of illness, patients who received none of these three interventions had about a 25% mortality rate during the 12 months following hospital discharge. Patients who received one or two interventions had about a 15% mortality rate, and patients who received all three interventions had about a 10% mortality rate.

When differences between these subgroups were analyzed statistically, patients who received two or three of the JCAHO-prescribed interventions had a significantly improved 12-month survival, compared with the patients who did not, Dr. Kfoury said.

A second analysis looked at the impact of all four interventions, including counseling on smoking cessation. The pattern was quite similar to the previous analysis: Patients who received all four interventions at discharge had a 5% mortality rate over the next 12 months. Those who received none of the interventions had a 25% mortality rate.

“These results should be an impetus to implement these simple but effective measures,” said Dr. Kfoury.

“Most patients get one or more of the interventions, but patients do not always get all of them.”

Treatment with an ACE inhibitor or ARB at discharge has become standard practice, but patient education at discharge is a strategy that's been used only for a few years and needs to become more widely used, he added.

MADRID — The four criteria now used to measure hospitals' performance in treating patients with heart failure also have a significant impact on patient survival, based on a review of more than 2,000 patients.

In 2002, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) set four core measures for the assessment of the quality of heart failure management.

“To our knowledge, this is the first report showing that adherence to the JCAHO heart failure core measures improves 1-year survival following hospitalization for heart failure,” Dr. A.G. Kfoury said at the annual meeting of the International Society for Heart and Lung Transplantation.

“The data show that these four cheap interventions can have an impact on patient outcomes,” said Dr. Kfoury, who is the medical director of the Utah Transplantation Affiliated Hospitals cardiac transplant program, and associate director of the heart failure prevention and treatment program at LDS Hospital in Salt Lake City.

The four performance measures are: discharge instructions to patients on heart failure management, including medications, diet, and weight control; assessment of left ventricular function or scheduling an assessment at discharge; treatment with an ACE inhibitor or angiotensin receptor blocker (ARB) at discharge; and instructions on smoking cessation at discharge.

To determine how the application of these four measures correlated with patient survival, Dr. Kfoury and his associates reviewed the records of 2,144 patients who were discharged with a primary diagnosis of heart failure and left ventricular dysfunction from 20 hospitals within the Intermountain Healthcare system from January 2003 to May 2005. The primary end point of the analysis was death during the 12 months following hospital discharge.

Because 90% of the patients were nonsmokers, one analysis excluded the smoking cessation measure and focused on the application of the other three criteria.

About 43% of patients received all three interventions, and another 39% of the patients received two of the interventions. Some 3% of patients received none of the interventions. When only one intervention was used, it was most often prescription of an ACE inhibitor or ARB.

The second most commonly used intervention was assessment of left ventricular function. Patient education was applied less often.

According to an analysis that adjusted for patients' age, gender, and severity of illness, patients who received none of these three interventions had about a 25% mortality rate during the 12 months following hospital discharge. Patients who received one or two interventions had about a 15% mortality rate, and patients who received all three interventions had about a 10% mortality rate.

When differences between these subgroups were analyzed statistically, patients who received two or three of the JCAHO-prescribed interventions had a significantly improved 12-month survival, compared with the patients who did not, Dr. Kfoury said.

A second analysis looked at the impact of all four interventions, including counseling on smoking cessation. The pattern was quite similar to the previous analysis: Patients who received all four interventions at discharge had a 5% mortality rate over the next 12 months. Those who received none of the interventions had a 25% mortality rate.

“These results should be an impetus to implement these simple but effective measures,” said Dr. Kfoury.

“Most patients get one or more of the interventions, but patients do not always get all of them.”

Treatment with an ACE inhibitor or ARB at discharge has become standard practice, but patient education at discharge is a strategy that's been used only for a few years and needs to become more widely used, he added.

MADRID — The four criteria now used to measure hospitals' performance in treating patients with heart failure also have a significant impact on patient survival, based on a review of more than 2,000 patients.

In 2002, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) set four core measures for the assessment of the quality of heart failure management.

“To our knowledge, this is the first report showing that adherence to the JCAHO heart failure core measures improves 1-year survival following hospitalization for heart failure,” Dr. A.G. Kfoury said at the annual meeting of the International Society for Heart and Lung Transplantation.

“The data show that these four cheap interventions can have an impact on patient outcomes,” said Dr. Kfoury, who is the medical director of the Utah Transplantation Affiliated Hospitals cardiac transplant program, and associate director of the heart failure prevention and treatment program at LDS Hospital in Salt Lake City.

The four performance measures are: discharge instructions to patients on heart failure management, including medications, diet, and weight control; assessment of left ventricular function or scheduling an assessment at discharge; treatment with an ACE inhibitor or angiotensin receptor blocker (ARB) at discharge; and instructions on smoking cessation at discharge.

To determine how the application of these four measures correlated with patient survival, Dr. Kfoury and his associates reviewed the records of 2,144 patients who were discharged with a primary diagnosis of heart failure and left ventricular dysfunction from 20 hospitals within the Intermountain Healthcare system from January 2003 to May 2005. The primary end point of the analysis was death during the 12 months following hospital discharge.

Because 90% of the patients were nonsmokers, one analysis excluded the smoking cessation measure and focused on the application of the other three criteria.

About 43% of patients received all three interventions, and another 39% of the patients received two of the interventions. Some 3% of patients received none of the interventions. When only one intervention was used, it was most often prescription of an ACE inhibitor or ARB.

The second most commonly used intervention was assessment of left ventricular function. Patient education was applied less often.

According to an analysis that adjusted for patients' age, gender, and severity of illness, patients who received none of these three interventions had about a 25% mortality rate during the 12 months following hospital discharge. Patients who received one or two interventions had about a 15% mortality rate, and patients who received all three interventions had about a 10% mortality rate.

When differences between these subgroups were analyzed statistically, patients who received two or three of the JCAHO-prescribed interventions had a significantly improved 12-month survival, compared with the patients who did not, Dr. Kfoury said.

A second analysis looked at the impact of all four interventions, including counseling on smoking cessation. The pattern was quite similar to the previous analysis: Patients who received all four interventions at discharge had a 5% mortality rate over the next 12 months. Those who received none of the interventions had a 25% mortality rate.

“These results should be an impetus to implement these simple but effective measures,” said Dr. Kfoury.

“Most patients get one or more of the interventions, but patients do not always get all of them.”

Treatment with an ACE inhibitor or ARB at discharge has become standard practice, but patient education at discharge is a strategy that's been used only for a few years and needs to become more widely used, he added.