Heart Failure

Major Finding: Among patients with diabetes who took eplerenone, there was a 46% reduction in the primary end point of death from cardiovascular causes or heart failure hospitalization, compared with those who took placebo.

Data Source: Subanalysis of high-risk groups and follow-up analyses of the phase III EMPHASIS-HF trial.

Disclosures: Pfizer sponsored the trial. Dr. Pitt reports financial relationships with several firms excluding Pfizer. His coauthors report similar relationships including employment with Pfizer.

PARIS – The aldosterone antagonist eplerenone cut cardiovascular events and the need for hospitalization significantly across all risk levels in patients with mild heart failure, according to a subanalysis of the EMPHASIS-HF trial.

Eplerenone (Inspra) was also shown to trim troublesome and costly repeat heart failure hospitalizations in a subset of patients followed for up to 10 additional months after the pivotal, phase III trial closed, Dr. Bertram Pitt reported at the congress.

“Overall efficacy, no matter where we looked, was about the same, and we had the same safety,” he told reporters.

EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) was stopped prematurely last spring after eplerenone in addition to standard therapy demonstrated a 37% (hazard ratio, 0.63) improvement over placebo in the primary end point of death from cardiovascular causes or heart failure hospitalization in 2,637 patients with mild New York Heart Association class II systolic heart failure (N. Engl. J. Med. 2011;364:11-21).

Among 1,597 patients who remained on double-blind therapy after study, the primary end point occurred in 21% on eplerenone and 29% on placebo (HR, 0.66), a significant difference, said Dr. Pitt of the University of Michigan, Ann Arbor.

Repeat hospitalization for heart failure was significantly reduced with eplerenone (rate ratio, 0.62).

“This suggests, to us at least, that this is going to have important cost implications and quality of life implications, as well as important implications on survival, since we know that heart failure hospitalization relates to target-organ damage and survival,” he said.

The benefits of eplerenone were particularly compelling in elderly patients and those with diabetes and renal dysfunction, three high-risk populations in whom clinicians are hesitant to use adjuvant aldosterone blockade because of fears of inducing hyperkalemia, Dr. Pitt said. He pointed out that recent head-to-head data show that the aldosterone antagonist spironolactone (Aldactone) raises hemoglobin A1_c and cortisol levels and reduces adiponectin in patients with diabetes, whereas eplerenone does not.

When Dr. Pitt and colleagues looked at patients with diabetes in the subanalysis, the benefit was stronger than that observed in the overall EMPHASIS-HF cohort, with a 46% reduction in the primary end point (HR, 0.54).

Dr. Pitt noted that the current American Heart Association, American College of Cardiology and European Society of Cardiology guidelines for aldosterone blockade do not specify a particular agent, but look at the agents as a class.

“We believe with [these] data, that in the next guidelines there should at least be some consideration for the specific use of eplerenone, at least in the subset of patients with diabetes,” he said.

Among patients with an estimated glomerular filtration rate less than 60 mL per minute per 1.73 m

The study excluded patients with a baseline serum potassium level above 5.0 mmol/L and estimated GFR below 30 mL per minute per 1.73 m

Among elderly patients at least 75 years old, the benefit on the primary end point with eplerenone reached 34%.

Significant benefits were also observed in patients with a left ventricular ejection fraction less than 30% and with a median systolic blood pressure of less than 123 mm Hg.

As seen in the overall EMPHASIS-HF cohort, the benefits of eplerenone were accompanied by a significant increase in the incidence of serum potassium greater than 5.5 mmol/L in each of the high-risk subgroups.

However, there were no significant increases in the incidence of serum potassium above 6 mmol/L, hospitalization leading to treatment discontinuation, hospitalization for/or deaths due to hyperkalemia, or hospitalizations for worsening renal function, Dr. Pitt said.

Invited discussant Dr. Piotr Ponikowski, with the 4th Military Hospital in Wroclaw, Poland, highlighted as important the benefits of eplerenone in people with diabetes and the reduction in repeat hospitalizations. He noted that up to 50% of heart failure patients are rehospitalized and these visits are associated with significant costs and reduced quality of life and mortality. Still, aldosterone antagonists remain underutilized in heart failure patients in Europe as well as the United States.

Physicians frequently question whether clinical trial data are real, consistent, and clinically meaningful, he said. “With the presented data, we can now say that the answer to all these questions is 'yes.'”

View a video interview with Dr. Pitt with the QR code, or by visiting ecardiologynews.com

This is going to have important implications in terms of cost, quality of life, and survival.

Source DR. PITT

Major Finding: Among patients with diabetes who took eplerenone, there was a 46% reduction in the primary end point of death from cardiovascular causes or heart failure hospitalization, compared with those who took placebo.

Data Source: Subanalysis of high-risk groups and follow-up analyses of the phase III EMPHASIS-HF trial.

Disclosures: Pfizer sponsored the trial. Dr. Pitt reports financial relationships with several firms excluding Pfizer. His coauthors report similar relationships including employment with Pfizer.

PARIS – The aldosterone antagonist eplerenone cut cardiovascular events and the need for hospitalization significantly across all risk levels in patients with mild heart failure, according to a subanalysis of the EMPHASIS-HF trial.

Eplerenone (Inspra) was also shown to trim troublesome and costly repeat heart failure hospitalizations in a subset of patients followed for up to 10 additional months after the pivotal, phase III trial closed, Dr. Bertram Pitt reported at the congress.

“Overall efficacy, no matter where we looked, was about the same, and we had the same safety,” he told reporters.

EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) was stopped prematurely last spring after eplerenone in addition to standard therapy demonstrated a 37% (hazard ratio, 0.63) improvement over placebo in the primary end point of death from cardiovascular causes or heart failure hospitalization in 2,637 patients with mild New York Heart Association class II systolic heart failure (N. Engl. J. Med. 2011;364:11-21).

Among 1,597 patients who remained on double-blind therapy after study, the primary end point occurred in 21% on eplerenone and 29% on placebo (HR, 0.66), a significant difference, said Dr. Pitt of the University of Michigan, Ann Arbor.

Repeat hospitalization for heart failure was significantly reduced with eplerenone (rate ratio, 0.62).

“This suggests, to us at least, that this is going to have important cost implications and quality of life implications, as well as important implications on survival, since we know that heart failure hospitalization relates to target-organ damage and survival,” he said.

The benefits of eplerenone were particularly compelling in elderly patients and those with diabetes and renal dysfunction, three high-risk populations in whom clinicians are hesitant to use adjuvant aldosterone blockade because of fears of inducing hyperkalemia, Dr. Pitt said. He pointed out that recent head-to-head data show that the aldosterone antagonist spironolactone (Aldactone) raises hemoglobin A1_c and cortisol levels and reduces adiponectin in patients with diabetes, whereas eplerenone does not.

When Dr. Pitt and colleagues looked at patients with diabetes in the subanalysis, the benefit was stronger than that observed in the overall EMPHASIS-HF cohort, with a 46% reduction in the primary end point (HR, 0.54).

Dr. Pitt noted that the current American Heart Association, American College of Cardiology and European Society of Cardiology guidelines for aldosterone blockade do not specify a particular agent, but look at the agents as a class.

“We believe with [these] data, that in the next guidelines there should at least be some consideration for the specific use of eplerenone, at least in the subset of patients with diabetes,” he said.

Among patients with an estimated glomerular filtration rate less than 60 mL per minute per 1.73 m

The study excluded patients with a baseline serum potassium level above 5.0 mmol/L and estimated GFR below 30 mL per minute per 1.73 m

Among elderly patients at least 75 years old, the benefit on the primary end point with eplerenone reached 34%.

Significant benefits were also observed in patients with a left ventricular ejection fraction less than 30% and with a median systolic blood pressure of less than 123 mm Hg.

As seen in the overall EMPHASIS-HF cohort, the benefits of eplerenone were accompanied by a significant increase in the incidence of serum potassium greater than 5.5 mmol/L in each of the high-risk subgroups.

However, there were no significant increases in the incidence of serum potassium above 6 mmol/L, hospitalization leading to treatment discontinuation, hospitalization for/or deaths due to hyperkalemia, or hospitalizations for worsening renal function, Dr. Pitt said.

Invited discussant Dr. Piotr Ponikowski, with the 4th Military Hospital in Wroclaw, Poland, highlighted as important the benefits of eplerenone in people with diabetes and the reduction in repeat hospitalizations. He noted that up to 50% of heart failure patients are rehospitalized and these visits are associated with significant costs and reduced quality of life and mortality. Still, aldosterone antagonists remain underutilized in heart failure patients in Europe as well as the United States.

Physicians frequently question whether clinical trial data are real, consistent, and clinically meaningful, he said. “With the presented data, we can now say that the answer to all these questions is 'yes.'”

View a video interview with Dr. Pitt with the QR code, or by visiting ecardiologynews.com

This is going to have important implications in terms of cost, quality of life, and survival.

Source DR. PITT

Major Finding: Among patients with diabetes who took eplerenone, there was a 46% reduction in the primary end point of death from cardiovascular causes or heart failure hospitalization, compared with those who took placebo.

Data Source: Subanalysis of high-risk groups and follow-up analyses of the phase III EMPHASIS-HF trial.

Disclosures: Pfizer sponsored the trial. Dr. Pitt reports financial relationships with several firms excluding Pfizer. His coauthors report similar relationships including employment with Pfizer.

PARIS – The aldosterone antagonist eplerenone cut cardiovascular events and the need for hospitalization significantly across all risk levels in patients with mild heart failure, according to a subanalysis of the EMPHASIS-HF trial.

Eplerenone (Inspra) was also shown to trim troublesome and costly repeat heart failure hospitalizations in a subset of patients followed for up to 10 additional months after the pivotal, phase III trial closed, Dr. Bertram Pitt reported at the congress.

“Overall efficacy, no matter where we looked, was about the same, and we had the same safety,” he told reporters.

EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) was stopped prematurely last spring after eplerenone in addition to standard therapy demonstrated a 37% (hazard ratio, 0.63) improvement over placebo in the primary end point of death from cardiovascular causes or heart failure hospitalization in 2,637 patients with mild New York Heart Association class II systolic heart failure (N. Engl. J. Med. 2011;364:11-21).

Among 1,597 patients who remained on double-blind therapy after study, the primary end point occurred in 21% on eplerenone and 29% on placebo (HR, 0.66), a significant difference, said Dr. Pitt of the University of Michigan, Ann Arbor.

Repeat hospitalization for heart failure was significantly reduced with eplerenone (rate ratio, 0.62).

“This suggests, to us at least, that this is going to have important cost implications and quality of life implications, as well as important implications on survival, since we know that heart failure hospitalization relates to target-organ damage and survival,” he said.

The benefits of eplerenone were particularly compelling in elderly patients and those with diabetes and renal dysfunction, three high-risk populations in whom clinicians are hesitant to use adjuvant aldosterone blockade because of fears of inducing hyperkalemia, Dr. Pitt said. He pointed out that recent head-to-head data show that the aldosterone antagonist spironolactone (Aldactone) raises hemoglobin A1_c and cortisol levels and reduces adiponectin in patients with diabetes, whereas eplerenone does not.

When Dr. Pitt and colleagues looked at patients with diabetes in the subanalysis, the benefit was stronger than that observed in the overall EMPHASIS-HF cohort, with a 46% reduction in the primary end point (HR, 0.54).

Dr. Pitt noted that the current American Heart Association, American College of Cardiology and European Society of Cardiology guidelines for aldosterone blockade do not specify a particular agent, but look at the agents as a class.

“We believe with [these] data, that in the next guidelines there should at least be some consideration for the specific use of eplerenone, at least in the subset of patients with diabetes,” he said.

Among patients with an estimated glomerular filtration rate less than 60 mL per minute per 1.73 m

The study excluded patients with a baseline serum potassium level above 5.0 mmol/L and estimated GFR below 30 mL per minute per 1.73 m

Among elderly patients at least 75 years old, the benefit on the primary end point with eplerenone reached 34%.

Significant benefits were also observed in patients with a left ventricular ejection fraction less than 30% and with a median systolic blood pressure of less than 123 mm Hg.

As seen in the overall EMPHASIS-HF cohort, the benefits of eplerenone were accompanied by a significant increase in the incidence of serum potassium greater than 5.5 mmol/L in each of the high-risk subgroups.

However, there were no significant increases in the incidence of serum potassium above 6 mmol/L, hospitalization leading to treatment discontinuation, hospitalization for/or deaths due to hyperkalemia, or hospitalizations for worsening renal function, Dr. Pitt said.

Invited discussant Dr. Piotr Ponikowski, with the 4th Military Hospital in Wroclaw, Poland, highlighted as important the benefits of eplerenone in people with diabetes and the reduction in repeat hospitalizations. He noted that up to 50% of heart failure patients are rehospitalized and these visits are associated with significant costs and reduced quality of life and mortality. Still, aldosterone antagonists remain underutilized in heart failure patients in Europe as well as the United States.

Physicians frequently question whether clinical trial data are real, consistent, and clinically meaningful, he said. “With the presented data, we can now say that the answer to all these questions is 'yes.'”

View a video interview with Dr. Pitt with the QR code, or by visiting ecardiologynews.com

This is going to have important implications in terms of cost, quality of life, and survival.

Source DR. PITT

SAN DIEGO – Heart failure constitutes a previously unrecognized independent risk factor for major osteoporotic fractures, according to a Canadian cohort study.

"Patients with heart failure have double the 5-year risk of fracture," compared with those without heart failure. And "patients with heart failure have lower bone mineral density at every skeletal site at the time of their first test," compared with those without heart failure. "Finally, neither differences in bone mass nor shared risk factors [are enough] to explain the increased risk," said Dr. Sumit Majumdar at the annual meeting of the American Society for Bone and Mineral Research.

He presented a population-based cohort study that included all Manitobans older than age 50 years who had their first bone mineral density test in 1998-2009. The study earned him the 2011 ASBMR Most Outstanding Clinical Abstract Award.

Overall, 4% of the nearly 46,000 Manitobans who had an initial bone minteral density (BMD) test during the study years were identified as having recent-onset heart failure (that is, heart failure diagnosed within the previous 2 years). There were 2,703 new fractures in the study population during a median 5 years of follow-up. The recent heart failure group had a 10% incidence of major nontraumatic fractures of the upper extremities, vertebrae, and hip during the 5 years following the first BMD test, compared with a 5% incidence in subjects without heart failure.

The median time to first fracture in the heart failure group was 3.6 years. The curves describing fracture incidence started to diverge soon after the first BMD test and continued to widen throughout the maximum 10 years of follow-up, reported Dr. Majumdar, professor of general internal medicine at the University of Alberta, Edmonton.

Patients with heart failure had more of all the standard risk factors for osteoporosis (except weight) than did subjects without heart failure. They were significantly older (mean age, 74 vs. 66 years) and 21% of them had a prior major osteoporotic fracture, compared with 13% of those without heart failure. Some 12% of heart failure patients had been on systemic corticosteroids for longer than 90 days, compared with 4% of those without heart failure.

Moreover, 40% of heart failure patients had osteoporosis at the time of their first BMD measurement (defined as a T score less than –2.5 at any skeletal site), compared with 29% of individuals without heart failure. T scores were significantly lower in the heart failure group at all measured sites.

"A diagnosis of heart failure portends an increased risk of fracture greater than rheumatoid arthritis or prior fracture."

On the other hand, nearly every medication used in treating heart failure has previously been shown to increase BMD and to reduce fracture risk, with the exception of loop diuretics, which reduce BMD.

In addition, osteoporosis and heart failure are common, chronic conditions that share several etiologic risk factors, including older age, postmenopausal status, diabetes, and smoking, he continued.

The unadjusted risk of a major osteoporotic fracture was increased 2.45-fold in patients with heart failure. But upon adjustment in a multivariate analysis for nearly 30 potential confounders including age, sex, osteoporosis-related factors, medications, comorbidities, and total hip BMD, heart failure remained independently associated with a highly significant 28% increased risk of major osteoporotic fractures.

A disturbing finding of the study was that a mere 14% of heart failure patients who experienced an osteoporotic fracture were then placed on a bisphosphonate or other bone-protective therapy. Bisphosphonates had no association with mortality in the heart failure group.

"For clinicians, I think our study means we need to start understanding that a diagnosis of heart failure portends an increased risk of fracture greater than rheumatoid arthritis or prior fracture, in our data. And we need to learn that patients with heart failure are easily diagnosed and need much more attention to their bone health," Dr. Majumdar observed.

This study also opens up research opportunities for bench scientists, as the Manitoba database contains no information on patients’ aldosterone, parathyroid hormone, or vitamin D levels, or indeed on any other variables that might provide a mechanistic explanation for the link between heart failure and osteoporotic fractures.

"Ours is an example of bedside-to-bench research," he said.

In that vein, one audience member noted that increased adrenergic drive is a hallmark of heart failure. He wondered if heart failure patients on beta-blocker therapy had a lower fracture risk. Dr. Majumdar replied that he and his coinvestigators had had the same thought. However, when they specifically compared the nearly 35% of heart failure patients who were on a beta-blocker vs. those who weren’t, they found that fracture rates in the two groups weren’t significantly different.

Dr. Majumdar declared having no relevant financial interests.

SAN DIEGO – Heart failure constitutes a previously unrecognized independent risk factor for major osteoporotic fractures, according to a Canadian cohort study.

"Patients with heart failure have double the 5-year risk of fracture," compared with those without heart failure. And "patients with heart failure have lower bone mineral density at every skeletal site at the time of their first test," compared with those without heart failure. "Finally, neither differences in bone mass nor shared risk factors [are enough] to explain the increased risk," said Dr. Sumit Majumdar at the annual meeting of the American Society for Bone and Mineral Research.

He presented a population-based cohort study that included all Manitobans older than age 50 years who had their first bone mineral density test in 1998-2009. The study earned him the 2011 ASBMR Most Outstanding Clinical Abstract Award.

Overall, 4% of the nearly 46,000 Manitobans who had an initial bone minteral density (BMD) test during the study years were identified as having recent-onset heart failure (that is, heart failure diagnosed within the previous 2 years). There were 2,703 new fractures in the study population during a median 5 years of follow-up. The recent heart failure group had a 10% incidence of major nontraumatic fractures of the upper extremities, vertebrae, and hip during the 5 years following the first BMD test, compared with a 5% incidence in subjects without heart failure.

The median time to first fracture in the heart failure group was 3.6 years. The curves describing fracture incidence started to diverge soon after the first BMD test and continued to widen throughout the maximum 10 years of follow-up, reported Dr. Majumdar, professor of general internal medicine at the University of Alberta, Edmonton.

Patients with heart failure had more of all the standard risk factors for osteoporosis (except weight) than did subjects without heart failure. They were significantly older (mean age, 74 vs. 66 years) and 21% of them had a prior major osteoporotic fracture, compared with 13% of those without heart failure. Some 12% of heart failure patients had been on systemic corticosteroids for longer than 90 days, compared with 4% of those without heart failure.

Moreover, 40% of heart failure patients had osteoporosis at the time of their first BMD measurement (defined as a T score less than –2.5 at any skeletal site), compared with 29% of individuals without heart failure. T scores were significantly lower in the heart failure group at all measured sites.

"A diagnosis of heart failure portends an increased risk of fracture greater than rheumatoid arthritis or prior fracture."

On the other hand, nearly every medication used in treating heart failure has previously been shown to increase BMD and to reduce fracture risk, with the exception of loop diuretics, which reduce BMD.

In addition, osteoporosis and heart failure are common, chronic conditions that share several etiologic risk factors, including older age, postmenopausal status, diabetes, and smoking, he continued.

The unadjusted risk of a major osteoporotic fracture was increased 2.45-fold in patients with heart failure. But upon adjustment in a multivariate analysis for nearly 30 potential confounders including age, sex, osteoporosis-related factors, medications, comorbidities, and total hip BMD, heart failure remained independently associated with a highly significant 28% increased risk of major osteoporotic fractures.

A disturbing finding of the study was that a mere 14% of heart failure patients who experienced an osteoporotic fracture were then placed on a bisphosphonate or other bone-protective therapy. Bisphosphonates had no association with mortality in the heart failure group.

"For clinicians, I think our study means we need to start understanding that a diagnosis of heart failure portends an increased risk of fracture greater than rheumatoid arthritis or prior fracture, in our data. And we need to learn that patients with heart failure are easily diagnosed and need much more attention to their bone health," Dr. Majumdar observed.

This study also opens up research opportunities for bench scientists, as the Manitoba database contains no information on patients’ aldosterone, parathyroid hormone, or vitamin D levels, or indeed on any other variables that might provide a mechanistic explanation for the link between heart failure and osteoporotic fractures.

"Ours is an example of bedside-to-bench research," he said.

In that vein, one audience member noted that increased adrenergic drive is a hallmark of heart failure. He wondered if heart failure patients on beta-blocker therapy had a lower fracture risk. Dr. Majumdar replied that he and his coinvestigators had had the same thought. However, when they specifically compared the nearly 35% of heart failure patients who were on a beta-blocker vs. those who weren’t, they found that fracture rates in the two groups weren’t significantly different.

Dr. Majumdar declared having no relevant financial interests.

SAN DIEGO – Heart failure constitutes a previously unrecognized independent risk factor for major osteoporotic fractures, according to a Canadian cohort study.

"Patients with heart failure have double the 5-year risk of fracture," compared with those without heart failure. And "patients with heart failure have lower bone mineral density at every skeletal site at the time of their first test," compared with those without heart failure. "Finally, neither differences in bone mass nor shared risk factors [are enough] to explain the increased risk," said Dr. Sumit Majumdar at the annual meeting of the American Society for Bone and Mineral Research.

He presented a population-based cohort study that included all Manitobans older than age 50 years who had their first bone mineral density test in 1998-2009. The study earned him the 2011 ASBMR Most Outstanding Clinical Abstract Award.

Overall, 4% of the nearly 46,000 Manitobans who had an initial bone minteral density (BMD) test during the study years were identified as having recent-onset heart failure (that is, heart failure diagnosed within the previous 2 years). There were 2,703 new fractures in the study population during a median 5 years of follow-up. The recent heart failure group had a 10% incidence of major nontraumatic fractures of the upper extremities, vertebrae, and hip during the 5 years following the first BMD test, compared with a 5% incidence in subjects without heart failure.

The median time to first fracture in the heart failure group was 3.6 years. The curves describing fracture incidence started to diverge soon after the first BMD test and continued to widen throughout the maximum 10 years of follow-up, reported Dr. Majumdar, professor of general internal medicine at the University of Alberta, Edmonton.

Patients with heart failure had more of all the standard risk factors for osteoporosis (except weight) than did subjects without heart failure. They were significantly older (mean age, 74 vs. 66 years) and 21% of them had a prior major osteoporotic fracture, compared with 13% of those without heart failure. Some 12% of heart failure patients had been on systemic corticosteroids for longer than 90 days, compared with 4% of those without heart failure.

Moreover, 40% of heart failure patients had osteoporosis at the time of their first BMD measurement (defined as a T score less than –2.5 at any skeletal site), compared with 29% of individuals without heart failure. T scores were significantly lower in the heart failure group at all measured sites.

"A diagnosis of heart failure portends an increased risk of fracture greater than rheumatoid arthritis or prior fracture."

On the other hand, nearly every medication used in treating heart failure has previously been shown to increase BMD and to reduce fracture risk, with the exception of loop diuretics, which reduce BMD.

In addition, osteoporosis and heart failure are common, chronic conditions that share several etiologic risk factors, including older age, postmenopausal status, diabetes, and smoking, he continued.

The unadjusted risk of a major osteoporotic fracture was increased 2.45-fold in patients with heart failure. But upon adjustment in a multivariate analysis for nearly 30 potential confounders including age, sex, osteoporosis-related factors, medications, comorbidities, and total hip BMD, heart failure remained independently associated with a highly significant 28% increased risk of major osteoporotic fractures.

A disturbing finding of the study was that a mere 14% of heart failure patients who experienced an osteoporotic fracture were then placed on a bisphosphonate or other bone-protective therapy. Bisphosphonates had no association with mortality in the heart failure group.

"For clinicians, I think our study means we need to start understanding that a diagnosis of heart failure portends an increased risk of fracture greater than rheumatoid arthritis or prior fracture, in our data. And we need to learn that patients with heart failure are easily diagnosed and need much more attention to their bone health," Dr. Majumdar observed.

This study also opens up research opportunities for bench scientists, as the Manitoba database contains no information on patients’ aldosterone, parathyroid hormone, or vitamin D levels, or indeed on any other variables that might provide a mechanistic explanation for the link between heart failure and osteoporotic fractures.

"Ours is an example of bedside-to-bench research," he said.

In that vein, one audience member noted that increased adrenergic drive is a hallmark of heart failure. He wondered if heart failure patients on beta-blocker therapy had a lower fracture risk. Dr. Majumdar replied that he and his coinvestigators had had the same thought. However, when they specifically compared the nearly 35% of heart failure patients who were on a beta-blocker vs. those who weren’t, they found that fracture rates in the two groups weren’t significantly different.

Dr. Majumdar declared having no relevant financial interests.

Many hospitals may be unprepared for a new Medicare requirement to lower readmissions, and could face resulting financial penalties over the next few years, according to a new report from the Dartmouth Atlas Project.

Over a 5-year period, hospitals made little progress in reducing readmissions among Medicare beneficiaries aged 65 years and older. The Dartmouth Atlas researchers found that surgical 30-day readmission rates were 12.7% in both 2004 and 2009, and medical 30-day readmission rates rose from 15.9% in 2004 to 16.1% in 2009.

They found similar trends when they looked at specific conditions. For example, the national readmission rates for hip fractures were 14.3% in 2004, compared with 14.5% in 2009. The rates were also relatively unchanged for congestive heart failure (20.9% vs. 21.2%) and pneumonia (15.1% vs. 15.3%). However, U.S. hospitals showed some improvement in acute myocardial infarctions, reducing 30-day readmissions from 19.4% in 2004 to 18.5% in 2009.

"For a long-standing and well-recognized problem, not much progress has been made," Dr. David C. Goodman, the study’s lead author and director of the Center for Health Policy Research at the Dartmouth Institute for Health Policy and Clinical Practice, said during a press conference to release the findings.

The researchers analyzed data for fee-for-service Medicare beneficiaries aged 65 years and older who lived in 306 Dartmouth Atlas hospital referral regions and had both Part A and Part B Medicare coverage.

Hospital readmissions have garnered significant attention in the health care community since the passage of the Affordable Care Act. The new health law calls on the Centers for Medicare and Medicaid Services to start measuring 30-day hospital readmission rates and to penalize poor performers. In October 2012, hospitals with high readmission rates will face penalties of 1% of their total Medicare billings. The penalty increases to 2% the following year.

Part of the solution to reducing hospital readmissions is good discharge planning, Dr. Goodman said. "This sounds simple but often doesn’t happen."

That planning should include having the care team in the hospital develop a care plan and communicate that plan to the patient and their family. It also means ensuring that the patient has all the necessary prescriptions, understands what medications to take and when, and can get their prescriptions. And health care providers in the hospital should also help patients set up follow-up appointments with their primary care physician, Dr. Goodman said.

But aside from discharge planning, there are also "hidden" factors such as how local patterns of hospital use affect readmission rates. Dr. Goodman and his colleagues found that communities and health care systems with higher underlying admission rates also tended to have higher rates of hospital readmission.

The Dartmouth Atlas Project receives most of its funding from the Robert Wood Johnson Foundation, the National Institute on Aging, the California Healthcare Foundation, the United Healthcare Foundation, and the WellPoint Foundation. The researchers reported no financial conflicts.

Many hospitals may be unprepared for a new Medicare requirement to lower readmissions, and could face resulting financial penalties over the next few years, according to a new report from the Dartmouth Atlas Project.

Over a 5-year period, hospitals made little progress in reducing readmissions among Medicare beneficiaries aged 65 years and older. The Dartmouth Atlas researchers found that surgical 30-day readmission rates were 12.7% in both 2004 and 2009, and medical 30-day readmission rates rose from 15.9% in 2004 to 16.1% in 2009.

They found similar trends when they looked at specific conditions. For example, the national readmission rates for hip fractures were 14.3% in 2004, compared with 14.5% in 2009. The rates were also relatively unchanged for congestive heart failure (20.9% vs. 21.2%) and pneumonia (15.1% vs. 15.3%). However, U.S. hospitals showed some improvement in acute myocardial infarctions, reducing 30-day readmissions from 19.4% in 2004 to 18.5% in 2009.

"For a long-standing and well-recognized problem, not much progress has been made," Dr. David C. Goodman, the study’s lead author and director of the Center for Health Policy Research at the Dartmouth Institute for Health Policy and Clinical Practice, said during a press conference to release the findings.

The researchers analyzed data for fee-for-service Medicare beneficiaries aged 65 years and older who lived in 306 Dartmouth Atlas hospital referral regions and had both Part A and Part B Medicare coverage.

Hospital readmissions have garnered significant attention in the health care community since the passage of the Affordable Care Act. The new health law calls on the Centers for Medicare and Medicaid Services to start measuring 30-day hospital readmission rates and to penalize poor performers. In October 2012, hospitals with high readmission rates will face penalties of 1% of their total Medicare billings. The penalty increases to 2% the following year.

Part of the solution to reducing hospital readmissions is good discharge planning, Dr. Goodman said. "This sounds simple but often doesn’t happen."

That planning should include having the care team in the hospital develop a care plan and communicate that plan to the patient and their family. It also means ensuring that the patient has all the necessary prescriptions, understands what medications to take and when, and can get their prescriptions. And health care providers in the hospital should also help patients set up follow-up appointments with their primary care physician, Dr. Goodman said.

But aside from discharge planning, there are also "hidden" factors such as how local patterns of hospital use affect readmission rates. Dr. Goodman and his colleagues found that communities and health care systems with higher underlying admission rates also tended to have higher rates of hospital readmission.

The Dartmouth Atlas Project receives most of its funding from the Robert Wood Johnson Foundation, the National Institute on Aging, the California Healthcare Foundation, the United Healthcare Foundation, and the WellPoint Foundation. The researchers reported no financial conflicts.

Many hospitals may be unprepared for a new Medicare requirement to lower readmissions, and could face resulting financial penalties over the next few years, according to a new report from the Dartmouth Atlas Project.

Over a 5-year period, hospitals made little progress in reducing readmissions among Medicare beneficiaries aged 65 years and older. The Dartmouth Atlas researchers found that surgical 30-day readmission rates were 12.7% in both 2004 and 2009, and medical 30-day readmission rates rose from 15.9% in 2004 to 16.1% in 2009.

They found similar trends when they looked at specific conditions. For example, the national readmission rates for hip fractures were 14.3% in 2004, compared with 14.5% in 2009. The rates were also relatively unchanged for congestive heart failure (20.9% vs. 21.2%) and pneumonia (15.1% vs. 15.3%). However, U.S. hospitals showed some improvement in acute myocardial infarctions, reducing 30-day readmissions from 19.4% in 2004 to 18.5% in 2009.

"For a long-standing and well-recognized problem, not much progress has been made," Dr. David C. Goodman, the study’s lead author and director of the Center for Health Policy Research at the Dartmouth Institute for Health Policy and Clinical Practice, said during a press conference to release the findings.

The researchers analyzed data for fee-for-service Medicare beneficiaries aged 65 years and older who lived in 306 Dartmouth Atlas hospital referral regions and had both Part A and Part B Medicare coverage.

Hospital readmissions have garnered significant attention in the health care community since the passage of the Affordable Care Act. The new health law calls on the Centers for Medicare and Medicaid Services to start measuring 30-day hospital readmission rates and to penalize poor performers. In October 2012, hospitals with high readmission rates will face penalties of 1% of their total Medicare billings. The penalty increases to 2% the following year.

Part of the solution to reducing hospital readmissions is good discharge planning, Dr. Goodman said. "This sounds simple but often doesn’t happen."

That planning should include having the care team in the hospital develop a care plan and communicate that plan to the patient and their family. It also means ensuring that the patient has all the necessary prescriptions, understands what medications to take and when, and can get their prescriptions. And health care providers in the hospital should also help patients set up follow-up appointments with their primary care physician, Dr. Goodman said.

But aside from discharge planning, there are also "hidden" factors such as how local patterns of hospital use affect readmission rates. Dr. Goodman and his colleagues found that communities and health care systems with higher underlying admission rates also tended to have higher rates of hospital readmission.

The Dartmouth Atlas Project receives most of its funding from the Robert Wood Johnson Foundation, the National Institute on Aging, the California Healthcare Foundation, the United Healthcare Foundation, and the WellPoint Foundation. The researchers reported no financial conflicts.

Major Finding: One intervention to facilitate the transition from hospitalization to home care cut the 30-day readmission rate by 48%; the other cut the rate by 36%.

Data Source: A prospective pilot study of readmission in 56 heart failure patients participating in a 3-month intervention, and a prospective cohort study of readmission in 257 patients with a variety of disorders who participated in a different, 1-month intervention.

Disclosures: Dr. Stauffer's study was supported by the Baylor Health Care System, Dallas. Ms. Voss's study was funded by the Centers for Medicare & Medicaid Services. Both research groups reported no financial conflicts of interest.

Two interventions to improve the transition from hospital discharge to home care, and to thereby reduce readmissions, were effective in the first attempts to implement them in real-world settings.

Both interventions had been effective in the comparatively controlled conditions of several randomized controlled trials, but until now it wasn't known whether that success would translate into real-world practice.

The first report was a pilot study at a single medical center involving patients with heart failure. The 3-month intervention was a traditional care program in which advanced practice nurses educated patients and families about symptoms and self-management strategies, improved communication patterns with care providers, and marshaled caregiver and community resources to facilitate adherence to treatment and improve quality of life. It included at least eight home visits, beginning within 72 hours of hospital admission, as well as 24-hour phone availability.

A total of 140 Medicare fee-for-service patients with heart failure were eligible, and 56 enrolled in the study.

The 30-day readmission rate was 48% lower after the intervention was implemented than it had been before. No such reduction in readmissions was noted at other medical centers in the same area during the study period, said Dr. Brett D. Stauffer of the Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, and his associates.

Total direct costs were lower for patients who participated in the intervention than for those who did not; however, the cost of the intervention itself was not recovered by the hospital.

In the second report, a Medicare demonstration project following the Care Transitions Intervention (CTI) model was assessed in 257 adults in the Medicare fee-for-service program who were hospitalized for a variety of diagnoses at six Rhode Island medical centers during an 18-month period. The facilities included community hospitals, teaching hospitals, and a tertiary care center, and their size ranged from 129 to 719 beds, said Rachel Voss of Quality Partners of Rhode Island, the Medicare Quality Improvement Organization for Rhode Island, and her associates.

The CTI is a 1-month program designed to help patients on the verge of discharge and their families to manage their health more actively and to communicate more effectively with their providers. Nurses or social workers act as “coaches” who conduct a hospital visit, a home visit within 3 days of discharge, a phone visit within 7-10 days, and a final phone visit within 30 days.

At these visits, the coaches review a booklet in which patients record their health problems, medications, and questions for providers; troubleshoot problems with outpatient care; ensure patients understand the signs and symptoms of any worsening of their condition; and help patients locate other sources of continued support.

Before implementation of the CTI program, the average 30-day readmission rate at the six participating hospitals was 21%. In comparison, the rate was only 12.8% in patients who participated in the intervention.

The primary outcome measure was the difference between the readmission rate among the study participants (12.8%) and a control group of similar patients who did not participate (20%). This represents a 36% reduction in readmissions with intervention, a significant decrease, Ms. Voss and her colleagues said (Arch. Intern. Med. 2011;171:1232-7).

Only 55% of eligible patients who were approached agreed to participate in the intervention, and the attrition rate among those who initially agreed to a home visit was 75%.

View on the News

It is comforting to read about “two successful real-world translations of interventions shown to be effective in reducing hospitalizations in randomized controlled trials.” But other aspects of these real-world successes are sobering, said Dr. Mitchell H. Katz.

Both studies had low participation rates. And in the study by Voss et al, only 14% of the patients who were approached would agree to a home visit. With such a small proportion of patients willing to try such interventions, these programs cannot have a major impact on readmission rates, he noted.

Moreover, they can only reduce health care costs if the savings from the decreased readmissions outweighs the cost of the intervention program. Under the current system that reimburses hospitals 100% for every readmission, this cannot happen.

DR. KATZ is in the Los Angeles County Department of Health Services. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying the two reports (Arch. Intern. Med. 2011;171:1230).

Major Finding: One intervention to facilitate the transition from hospitalization to home care cut the 30-day readmission rate by 48%; the other cut the rate by 36%.

Data Source: A prospective pilot study of readmission in 56 heart failure patients participating in a 3-month intervention, and a prospective cohort study of readmission in 257 patients with a variety of disorders who participated in a different, 1-month intervention.

Disclosures: Dr. Stauffer's study was supported by the Baylor Health Care System, Dallas. Ms. Voss's study was funded by the Centers for Medicare & Medicaid Services. Both research groups reported no financial conflicts of interest.

Two interventions to improve the transition from hospital discharge to home care, and to thereby reduce readmissions, were effective in the first attempts to implement them in real-world settings.

Both interventions had been effective in the comparatively controlled conditions of several randomized controlled trials, but until now it wasn't known whether that success would translate into real-world practice.

The first report was a pilot study at a single medical center involving patients with heart failure. The 3-month intervention was a traditional care program in which advanced practice nurses educated patients and families about symptoms and self-management strategies, improved communication patterns with care providers, and marshaled caregiver and community resources to facilitate adherence to treatment and improve quality of life. It included at least eight home visits, beginning within 72 hours of hospital admission, as well as 24-hour phone availability.

A total of 140 Medicare fee-for-service patients with heart failure were eligible, and 56 enrolled in the study.

The 30-day readmission rate was 48% lower after the intervention was implemented than it had been before. No such reduction in readmissions was noted at other medical centers in the same area during the study period, said Dr. Brett D. Stauffer of the Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, and his associates.

Total direct costs were lower for patients who participated in the intervention than for those who did not; however, the cost of the intervention itself was not recovered by the hospital.

In the second report, a Medicare demonstration project following the Care Transitions Intervention (CTI) model was assessed in 257 adults in the Medicare fee-for-service program who were hospitalized for a variety of diagnoses at six Rhode Island medical centers during an 18-month period. The facilities included community hospitals, teaching hospitals, and a tertiary care center, and their size ranged from 129 to 719 beds, said Rachel Voss of Quality Partners of Rhode Island, the Medicare Quality Improvement Organization for Rhode Island, and her associates.

The CTI is a 1-month program designed to help patients on the verge of discharge and their families to manage their health more actively and to communicate more effectively with their providers. Nurses or social workers act as “coaches” who conduct a hospital visit, a home visit within 3 days of discharge, a phone visit within 7-10 days, and a final phone visit within 30 days.

At these visits, the coaches review a booklet in which patients record their health problems, medications, and questions for providers; troubleshoot problems with outpatient care; ensure patients understand the signs and symptoms of any worsening of their condition; and help patients locate other sources of continued support.

Before implementation of the CTI program, the average 30-day readmission rate at the six participating hospitals was 21%. In comparison, the rate was only 12.8% in patients who participated in the intervention.

The primary outcome measure was the difference between the readmission rate among the study participants (12.8%) and a control group of similar patients who did not participate (20%). This represents a 36% reduction in readmissions with intervention, a significant decrease, Ms. Voss and her colleagues said (Arch. Intern. Med. 2011;171:1232-7).

Only 55% of eligible patients who were approached agreed to participate in the intervention, and the attrition rate among those who initially agreed to a home visit was 75%.

View on the News

It is comforting to read about “two successful real-world translations of interventions shown to be effective in reducing hospitalizations in randomized controlled trials.” But other aspects of these real-world successes are sobering, said Dr. Mitchell H. Katz.

Both studies had low participation rates. And in the study by Voss et al, only 14% of the patients who were approached would agree to a home visit. With such a small proportion of patients willing to try such interventions, these programs cannot have a major impact on readmission rates, he noted.

Moreover, they can only reduce health care costs if the savings from the decreased readmissions outweighs the cost of the intervention program. Under the current system that reimburses hospitals 100% for every readmission, this cannot happen.

DR. KATZ is in the Los Angeles County Department of Health Services. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying the two reports (Arch. Intern. Med. 2011;171:1230).

Major Finding: One intervention to facilitate the transition from hospitalization to home care cut the 30-day readmission rate by 48%; the other cut the rate by 36%.

Data Source: A prospective pilot study of readmission in 56 heart failure patients participating in a 3-month intervention, and a prospective cohort study of readmission in 257 patients with a variety of disorders who participated in a different, 1-month intervention.

Disclosures: Dr. Stauffer's study was supported by the Baylor Health Care System, Dallas. Ms. Voss's study was funded by the Centers for Medicare & Medicaid Services. Both research groups reported no financial conflicts of interest.

Two interventions to improve the transition from hospital discharge to home care, and to thereby reduce readmissions, were effective in the first attempts to implement them in real-world settings.

Both interventions had been effective in the comparatively controlled conditions of several randomized controlled trials, but until now it wasn't known whether that success would translate into real-world practice.

The first report was a pilot study at a single medical center involving patients with heart failure. The 3-month intervention was a traditional care program in which advanced practice nurses educated patients and families about symptoms and self-management strategies, improved communication patterns with care providers, and marshaled caregiver and community resources to facilitate adherence to treatment and improve quality of life. It included at least eight home visits, beginning within 72 hours of hospital admission, as well as 24-hour phone availability.

A total of 140 Medicare fee-for-service patients with heart failure were eligible, and 56 enrolled in the study.

The 30-day readmission rate was 48% lower after the intervention was implemented than it had been before. No such reduction in readmissions was noted at other medical centers in the same area during the study period, said Dr. Brett D. Stauffer of the Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, and his associates.

Total direct costs were lower for patients who participated in the intervention than for those who did not; however, the cost of the intervention itself was not recovered by the hospital.

In the second report, a Medicare demonstration project following the Care Transitions Intervention (CTI) model was assessed in 257 adults in the Medicare fee-for-service program who were hospitalized for a variety of diagnoses at six Rhode Island medical centers during an 18-month period. The facilities included community hospitals, teaching hospitals, and a tertiary care center, and their size ranged from 129 to 719 beds, said Rachel Voss of Quality Partners of Rhode Island, the Medicare Quality Improvement Organization for Rhode Island, and her associates.

The CTI is a 1-month program designed to help patients on the verge of discharge and their families to manage their health more actively and to communicate more effectively with their providers. Nurses or social workers act as “coaches” who conduct a hospital visit, a home visit within 3 days of discharge, a phone visit within 7-10 days, and a final phone visit within 30 days.

At these visits, the coaches review a booklet in which patients record their health problems, medications, and questions for providers; troubleshoot problems with outpatient care; ensure patients understand the signs and symptoms of any worsening of their condition; and help patients locate other sources of continued support.

Before implementation of the CTI program, the average 30-day readmission rate at the six participating hospitals was 21%. In comparison, the rate was only 12.8% in patients who participated in the intervention.

The primary outcome measure was the difference between the readmission rate among the study participants (12.8%) and a control group of similar patients who did not participate (20%). This represents a 36% reduction in readmissions with intervention, a significant decrease, Ms. Voss and her colleagues said (Arch. Intern. Med. 2011;171:1232-7).

Only 55% of eligible patients who were approached agreed to participate in the intervention, and the attrition rate among those who initially agreed to a home visit was 75%.

View on the News

It is comforting to read about “two successful real-world translations of interventions shown to be effective in reducing hospitalizations in randomized controlled trials.” But other aspects of these real-world successes are sobering, said Dr. Mitchell H. Katz.

Both studies had low participation rates. And in the study by Voss et al, only 14% of the patients who were approached would agree to a home visit. With such a small proportion of patients willing to try such interventions, these programs cannot have a major impact on readmission rates, he noted.

Moreover, they can only reduce health care costs if the savings from the decreased readmissions outweighs the cost of the intervention program. Under the current system that reimburses hospitals 100% for every readmission, this cannot happen.

DR. KATZ is in the Los Angeles County Department of Health Services. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying the two reports (Arch. Intern. Med. 2011;171:1230).

Major Finding: The incidence of heart failure in type 1 diabetes patients rose as HbA_1c levels did, from 1.42 to 5.20 per 1,000 patient-years in patients with HbA_1c levels of below 6.5% and at least 10.5%, respectively.

Data Source: An analysis of 20,985 type 1 diabetes patients aged at least 18 with no known heart failure in the Swedish national diabetes registry, who were registered during 1998-2003 and followed through 2009.

Disclosures: The study was supported by an unrestricted grant from AstraZeneca, Novo Nordisk Scandinavia, the Swedish Heart and Lung Foundation, and the Swedish Research Council. Dr. Lind has received honoraria from or been a consultant for Bayer, Eli Lilly, Novartis, Novo Nordisk Scandinavia, Medtronic, Pfizer, and Sanofi-Aventis; and has been a member of an advisory board for Novo Nordisk Scandinavia.

SAN DIEGO – Tight control of hemoglobin A_1c levels significantly reduces the risk of heart failure in patients with type 1 diabetes, results from a large, long-term study show.

In fact, patients with very poor glycemic control were four times as likely to experience heart failure, compared with their counterparts with optimal glycemic control.

“Because treatment for heart failure improves survival and quality of life, clinicians should be observant of signs of heart failure in management of patients with type 1 diabetes, starting at an early stage,” lead author Dr. Marcus Lind wrote in the study, which was presented at the meeting and simultaneously published onlinei “Echocardiography might be warranted, especially in the presence of poor glycemic control, long duration of diabetes, or an adverse risk factor profile.”

Dr. Lind of the department of medicine at Uddevalla (Sweden) Hospital and his associates used the Swedish national diabetes registry to identify 20,985 patients aged 18 years or older with type 1 disease who had no known heart failure and who were registered between January 1998 and December 2003. They followed the cohort until hospital admission for heart failure, death, or end of follow-up on Dec. 31, 2009 (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)60471-6]).

The incidence of heart failure was determined by dividing the number of patient-years of follow-up in a particular HbA_1c category, reported as events per 1,000 years of follow-up. The six HbA_1c categories were less than 6.5%, from 6.5% to less than 7.5%, from 7.5% to less than 8.5%, from 8.5% to less than 9.5%, from 9.5% to less than 10.5%, and 10.5% or greater. Cox regression analysis was used to study possible associations between heart failure and patients' characteristics.

The mean age of patients was 39 years, and 45% were female; they had had diabetes for a mean of 14 years, and their mean body mass index was 25 kg/m

After adjustment for age, sex, duration of diabetes, cardiovascular disease risk factors, acute myocardial infarction, and other comorbidities, a Cox regression analysis revealed that patients with an HbA_1c level of 10.5% or higher were four times more likely to develop heart failure than were those who had an HbA_1c level of less than 6.5%.

Other independent predictors of heart failure included age (hazard ratio, 1.64 per 10-year increase); duration of diabetes (HR, 1.34 per 10-year increase); BMI (HR, 1.05 per 1-kg/m

“For many years there have been observations that poor glycemic control is linked to heart attack and cardiovascular mortality,” Dr. Sue Kirkman, senior vice president of medical affairs and community information for the American Diabetes Association, said in an interview at the meeting. “This may be the first time that it's been shown to be linked to heart failure in a type 1 population.”

She called the study “hypothesis generating,” and noted that a long-term randomized trial will be needed to confirm the findings. “It is interesting, because it seems that in type 1 diabetes there may be a stronger link between glucose lowering and cardiac outcomes than in type 2 diabetes,” she said.

View On The News

Tight Control 'Essential'

How tightly should glycemia be controlled in diabetes? The clear message from Dr. Lind's and his colleagues' paper is that tight control of glycemia in type 1 diabetes is essential, especially now that they have shown that such control can prevent heart failure, besides other aspects of cardiovascular disease. In the future, even established type 1 diabetes cardiomyopathy might be rescued by gene-activated prosurvival paths, as shown in a mouse model. Only in developing countries, where tight control is often not feasible, could less-strict control be acceptable for type 1 diabetes.

LIONEL H. OPIE, M.D., is director of the Hatter Cardiovascular Research Institute at the University of Cape Town (South Africa). This was adapted from an accompanying commentary published online (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)6078703]). He reported no conflicts of interest.

Major Finding: The incidence of heart failure in type 1 diabetes patients rose as HbA_1c levels did, from 1.42 to 5.20 per 1,000 patient-years in patients with HbA_1c levels of below 6.5% and at least 10.5%, respectively.

Data Source: An analysis of 20,985 type 1 diabetes patients aged at least 18 with no known heart failure in the Swedish national diabetes registry, who were registered during 1998-2003 and followed through 2009.

Disclosures: The study was supported by an unrestricted grant from AstraZeneca, Novo Nordisk Scandinavia, the Swedish Heart and Lung Foundation, and the Swedish Research Council. Dr. Lind has received honoraria from or been a consultant for Bayer, Eli Lilly, Novartis, Novo Nordisk Scandinavia, Medtronic, Pfizer, and Sanofi-Aventis; and has been a member of an advisory board for Novo Nordisk Scandinavia.

SAN DIEGO – Tight control of hemoglobin A_1c levels significantly reduces the risk of heart failure in patients with type 1 diabetes, results from a large, long-term study show.

In fact, patients with very poor glycemic control were four times as likely to experience heart failure, compared with their counterparts with optimal glycemic control.

“Because treatment for heart failure improves survival and quality of life, clinicians should be observant of signs of heart failure in management of patients with type 1 diabetes, starting at an early stage,” lead author Dr. Marcus Lind wrote in the study, which was presented at the meeting and simultaneously published onlinei “Echocardiography might be warranted, especially in the presence of poor glycemic control, long duration of diabetes, or an adverse risk factor profile.”

Dr. Lind of the department of medicine at Uddevalla (Sweden) Hospital and his associates used the Swedish national diabetes registry to identify 20,985 patients aged 18 years or older with type 1 disease who had no known heart failure and who were registered between January 1998 and December 2003. They followed the cohort until hospital admission for heart failure, death, or end of follow-up on Dec. 31, 2009 (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)60471-6]).

The incidence of heart failure was determined by dividing the number of patient-years of follow-up in a particular HbA_1c category, reported as events per 1,000 years of follow-up. The six HbA_1c categories were less than 6.5%, from 6.5% to less than 7.5%, from 7.5% to less than 8.5%, from 8.5% to less than 9.5%, from 9.5% to less than 10.5%, and 10.5% or greater. Cox regression analysis was used to study possible associations between heart failure and patients' characteristics.

The mean age of patients was 39 years, and 45% were female; they had had diabetes for a mean of 14 years, and their mean body mass index was 25 kg/m

After adjustment for age, sex, duration of diabetes, cardiovascular disease risk factors, acute myocardial infarction, and other comorbidities, a Cox regression analysis revealed that patients with an HbA_1c level of 10.5% or higher were four times more likely to develop heart failure than were those who had an HbA_1c level of less than 6.5%.

Other independent predictors of heart failure included age (hazard ratio, 1.64 per 10-year increase); duration of diabetes (HR, 1.34 per 10-year increase); BMI (HR, 1.05 per 1-kg/m

“For many years there have been observations that poor glycemic control is linked to heart attack and cardiovascular mortality,” Dr. Sue Kirkman, senior vice president of medical affairs and community information for the American Diabetes Association, said in an interview at the meeting. “This may be the first time that it's been shown to be linked to heart failure in a type 1 population.”

She called the study “hypothesis generating,” and noted that a long-term randomized trial will be needed to confirm the findings. “It is interesting, because it seems that in type 1 diabetes there may be a stronger link between glucose lowering and cardiac outcomes than in type 2 diabetes,” she said.

View On The News

Tight Control 'Essential'

How tightly should glycemia be controlled in diabetes? The clear message from Dr. Lind's and his colleagues' paper is that tight control of glycemia in type 1 diabetes is essential, especially now that they have shown that such control can prevent heart failure, besides other aspects of cardiovascular disease. In the future, even established type 1 diabetes cardiomyopathy might be rescued by gene-activated prosurvival paths, as shown in a mouse model. Only in developing countries, where tight control is often not feasible, could less-strict control be acceptable for type 1 diabetes.

LIONEL H. OPIE, M.D., is director of the Hatter Cardiovascular Research Institute at the University of Cape Town (South Africa). This was adapted from an accompanying commentary published online (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)6078703]). He reported no conflicts of interest.

Major Finding: The incidence of heart failure in type 1 diabetes patients rose as HbA_1c levels did, from 1.42 to 5.20 per 1,000 patient-years in patients with HbA_1c levels of below 6.5% and at least 10.5%, respectively.

Data Source: An analysis of 20,985 type 1 diabetes patients aged at least 18 with no known heart failure in the Swedish national diabetes registry, who were registered during 1998-2003 and followed through 2009.

Disclosures: The study was supported by an unrestricted grant from AstraZeneca, Novo Nordisk Scandinavia, the Swedish Heart and Lung Foundation, and the Swedish Research Council. Dr. Lind has received honoraria from or been a consultant for Bayer, Eli Lilly, Novartis, Novo Nordisk Scandinavia, Medtronic, Pfizer, and Sanofi-Aventis; and has been a member of an advisory board for Novo Nordisk Scandinavia.

SAN DIEGO – Tight control of hemoglobin A_1c levels significantly reduces the risk of heart failure in patients with type 1 diabetes, results from a large, long-term study show.

In fact, patients with very poor glycemic control were four times as likely to experience heart failure, compared with their counterparts with optimal glycemic control.

“Because treatment for heart failure improves survival and quality of life, clinicians should be observant of signs of heart failure in management of patients with type 1 diabetes, starting at an early stage,” lead author Dr. Marcus Lind wrote in the study, which was presented at the meeting and simultaneously published onlinei “Echocardiography might be warranted, especially in the presence of poor glycemic control, long duration of diabetes, or an adverse risk factor profile.”

Dr. Lind of the department of medicine at Uddevalla (Sweden) Hospital and his associates used the Swedish national diabetes registry to identify 20,985 patients aged 18 years or older with type 1 disease who had no known heart failure and who were registered between January 1998 and December 2003. They followed the cohort until hospital admission for heart failure, death, or end of follow-up on Dec. 31, 2009 (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)60471-6]).

The incidence of heart failure was determined by dividing the number of patient-years of follow-up in a particular HbA_1c category, reported as events per 1,000 years of follow-up. The six HbA_1c categories were less than 6.5%, from 6.5% to less than 7.5%, from 7.5% to less than 8.5%, from 8.5% to less than 9.5%, from 9.5% to less than 10.5%, and 10.5% or greater. Cox regression analysis was used to study possible associations between heart failure and patients' characteristics.

The mean age of patients was 39 years, and 45% were female; they had had diabetes for a mean of 14 years, and their mean body mass index was 25 kg/m

After adjustment for age, sex, duration of diabetes, cardiovascular disease risk factors, acute myocardial infarction, and other comorbidities, a Cox regression analysis revealed that patients with an HbA_1c level of 10.5% or higher were four times more likely to develop heart failure than were those who had an HbA_1c level of less than 6.5%.

Other independent predictors of heart failure included age (hazard ratio, 1.64 per 10-year increase); duration of diabetes (HR, 1.34 per 10-year increase); BMI (HR, 1.05 per 1-kg/m

“For many years there have been observations that poor glycemic control is linked to heart attack and cardiovascular mortality,” Dr. Sue Kirkman, senior vice president of medical affairs and community information for the American Diabetes Association, said in an interview at the meeting. “This may be the first time that it's been shown to be linked to heart failure in a type 1 population.”

She called the study “hypothesis generating,” and noted that a long-term randomized trial will be needed to confirm the findings. “It is interesting, because it seems that in type 1 diabetes there may be a stronger link between glucose lowering and cardiac outcomes than in type 2 diabetes,” she said.

View On The News

Tight Control 'Essential'

How tightly should glycemia be controlled in diabetes? The clear message from Dr. Lind's and his colleagues' paper is that tight control of glycemia in type 1 diabetes is essential, especially now that they have shown that such control can prevent heart failure, besides other aspects of cardiovascular disease. In the future, even established type 1 diabetes cardiomyopathy might be rescued by gene-activated prosurvival paths, as shown in a mouse model. Only in developing countries, where tight control is often not feasible, could less-strict control be acceptable for type 1 diabetes.

LIONEL H. OPIE, M.D., is director of the Hatter Cardiovascular Research Institute at the University of Cape Town (South Africa). This was adapted from an accompanying commentary published online (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)6078703]). He reported no conflicts of interest.

Steroids Should Be Discontinued as Soon as Possible in All Patients

There is a compelling case for taking all heart transplant recipients off corticosteroids as early as possible, and certainly no later than 3 months after transplantation.

Patients undergoing heart transplantation are in essence trading a disease that will kill them for a disease that is more treatable: immunosuppression. But we physicians can control immunosuppression, which begs the question: Can’t we do better?

We use steroids in more than 80% of our patients. Steroids are our security blanket; they are the drugs that make us feel better. As I was told in training, we sleep better when our patients are on steroids, because we tend to think that they are safe.

But there is no denying that steroids can have life-altering adverse effects for our patients. What if steroids were unnecessary? In fact, they are, but we just haven’t recognized that universally. Steroids are not necessary. This is a not a new idea, as is evident from reports dating back to 1985 (Circulation 1990;82[5 suppl.]:IV318-21).

At least 10 studies have shown the safety of stopping steroids early in heart transplant recipients. Additionally, a recurring finding is that survival is, in fact, better with this practice. You could argue that the patients who are not taken off steroids have a better risk profile, but the weight of evidence does not suggest that this is the case. The following are a few of these studies:

• A case-control study among 420 heart transplant recipients found that steroid withdrawal starting 6 months or more post transplantation was associated with a higher rate of rejection over 7 years, but despite this, survival was better (Am. J. Transplant. 2005;5 [4 Pt. 1]:720-8).

• In a prospective study of 33 heart transplant recipients who were given tacrolimus or sirolimus, all patients were taken off steroids within 6 months (J. Heart Lung Transplant. 2007;26:598-603). There was a single treated rejection and no deaths.

• A retrospective single-institution study of 220 patients found that steroid weaning after heart transplantation was an independent predictor of survival, conferring a significant 40% reduction in the risk of death (Transplant Proc. 2006;38:1501-6).

• In the randomized TICTAC (Tacrolimus in Combination, Tacrolimus Alone Compared) trial, which compared tacrolimus with and without mycophenolate mofetil (MMF), steroids were discontinued in all patients by 8-9 weeks (Circ. Heart Fail. 2011;4:129-37). Over a median follow-up of 3-4 years, none has had to resume steroid maintenance. There was a slight nonsignificant increase in rejection with the monotherapy, but survival – the standard – was identical between groups.

One fear when we began this study was that we would pay the price in allograft vasculopathy if we didn’t provide adequate immunosuppression. Over a 5-year period, however, we have not: The patients on monotherapy and the patients on combination therapy (again, all of them steroid free during follow-up) were indistinguishable in terms of this outcome.

So why do we cling to corticosteroids? What are they doing for us? It’s time to finally admit that they are not necessary. Steroids should be discontinued as rapidly possible among all heart transplant recipients – certainly within 3 months post transplant. We now have good evidence proving the safety and efficacy of this approach.

Dr. Baran is the director of heart failure and transplant research at the Newark (N.J.) Beth Israel Medical Center.

Only Selected Patients Benefit From Early Discontinuation of Steroids

Given current evidence, it is extreme and premature to take all patients off corticosteroids within 3 months of heart transplantation.

Steroids have been used since the beginning of heart transplant therapy, and are still among our most useful drugs for achieving immunosuppression.

We all know about their adverse effects. But they are less common today now that we use lower doses (enabled by combination therapy), and we have other means for preventing some of the adverse effects associated with steroids.

Although other classes of immunosuppressants – such as calcineurin inhibitors, MMF, and mTOR (mammalian target of rapamycin) inhibitors – have become available, it is important to remember that they, too, have adverse effects.

The different classes of immunosuppressants have different mechanisms of action, and this is the theoretical basis of triple-drug therapy. Nonreliance on a single drug also allows us to use smaller doses of each.

Nearly all of the major clinical trials in heart transplantation have used corticosteroids (J. Heart Lung Transplant. 2010;29:914-56). And certainly it is now clear that none of the leading causes of death after heart transplantation in adults (except for infection) seems attributable to these drugs (J. Heart Lung Transplant. 2010;29:1089-103). On the contrary, lack of steroid maintenance therapy has been identified as an independent risk factor for death, conferring a doubling of risk (J. Thorac. Cardiovasc. Surg. 2010;140:161-8).

The TICTAC trial was well done and had some important findings. Unfortunately, it was not a clinical trial of steroid discontinuation because there was no group of patients kept on steroids.

Also, when compared with patients in a similar trial who were given tacrolimus-MMF (Am. J. Transplant. 2006;6:1377-86), patients in the TICTAC trial had higher levels of tacrolimus and serum creatinine. These differences are a little worrisome in terms of long-term outcomes.

At my institution, even later withdrawal of steroids (that is, among patients who were on steroids for at least 4 years without any acute rejection episodes) was associated with a 25% incidence of acute rejection (Transplant Proc. 2007;39:2372-4). In Spain, centers typically stop steroids only in patients who have unacceptable adverse effects and a low immunologic risk for rejection.

Only one trial has directly compared early steroid withdrawal with standard steroid therapy in transplant recipients (Am. J. Transplant. 2008;8:307-16). In that study, in kidney transplant patients who either did not receive any steroids or received them for just the first week, acute rejection occurred both earlier and more often than in the standard therapy group. And there were only modest reductions in adverse events.

In heart transplantation, immunosuppressive therapy is not a one-size-fits-all undertaking. Some patients (for example, those who have preexisting osteoporosis, are elderly, or have diabetes) do benefit from early withdrawal of steroids.

Indeed, guidelines recommend steroid weaning in patients who experience significant adverse effects and have not had a recent acute rejection episode (J. Heart Transplant. 2010;29:914-56). But they also note that although several studies have shown that it is feasible and safe to wean most patients by 6-12 months, and that doing so is desirable to reduce adverse effects, there has not been a randomized trial testing this practice.

It is possible that future well-designed studies will show that the risk of rejection is a reasonable price to pay for avoiding the adverse effects of steroids. These studies must have long-term follow-up and assess the key outcomes of graft and patient survival, rather than just rejection.

In conclusion, there are certainly patients who benefit from early withdrawal of steroids, but current evidence does not support the generalization of this practice.

Dr. Crespo-Leiro is with the heart failure and heart transplant unit at the Hospital Universitario a Coruña (Spain).

Steroids Should Be Discontinued as Soon as Possible in All Patients

There is a compelling case for taking all heart transplant recipients off corticosteroids as early as possible, and certainly no later than 3 months after transplantation.

Patients undergoing heart transplantation are in essence trading a disease that will kill them for a disease that is more treatable: immunosuppression. But we physicians can control immunosuppression, which begs the question: Can’t we do better?

We use steroids in more than 80% of our patients. Steroids are our security blanket; they are the drugs that make us feel better. As I was told in training, we sleep better when our patients are on steroids, because we tend to think that they are safe.

But there is no denying that steroids can have life-altering adverse effects for our patients. What if steroids were unnecessary? In fact, they are, but we just haven’t recognized that universally. Steroids are not necessary. This is a not a new idea, as is evident from reports dating back to 1985 (Circulation 1990;82[5 suppl.]:IV318-21).

At least 10 studies have shown the safety of stopping steroids early in heart transplant recipients. Additionally, a recurring finding is that survival is, in fact, better with this practice. You could argue that the patients who are not taken off steroids have a better risk profile, but the weight of evidence does not suggest that this is the case. The following are a few of these studies:

• A case-control study among 420 heart transplant recipients found that steroid withdrawal starting 6 months or more post transplantation was associated with a higher rate of rejection over 7 years, but despite this, survival was better (Am. J. Transplant. 2005;5 [4 Pt. 1]:720-8).

• In a prospective study of 33 heart transplant recipients who were given tacrolimus or sirolimus, all patients were taken off steroids within 6 months (J. Heart Lung Transplant. 2007;26:598-603). There was a single treated rejection and no deaths.

• A retrospective single-institution study of 220 patients found that steroid weaning after heart transplantation was an independent predictor of survival, conferring a significant 40% reduction in the risk of death (Transplant Proc. 2006;38:1501-6).

• In the randomized TICTAC (Tacrolimus in Combination, Tacrolimus Alone Compared) trial, which compared tacrolimus with and without mycophenolate mofetil (MMF), steroids were discontinued in all patients by 8-9 weeks (Circ. Heart Fail. 2011;4:129-37). Over a median follow-up of 3-4 years, none has had to resume steroid maintenance. There was a slight nonsignificant increase in rejection with the monotherapy, but survival – the standard – was identical between groups.

One fear when we began this study was that we would pay the price in allograft vasculopathy if we didn’t provide adequate immunosuppression. Over a 5-year period, however, we have not: The patients on monotherapy and the patients on combination therapy (again, all of them steroid free during follow-up) were indistinguishable in terms of this outcome.

So why do we cling to corticosteroids? What are they doing for us? It’s time to finally admit that they are not necessary. Steroids should be discontinued as rapidly possible among all heart transplant recipients – certainly within 3 months post transplant. We now have good evidence proving the safety and efficacy of this approach.

Dr. Baran is the director of heart failure and transplant research at the Newark (N.J.) Beth Israel Medical Center.

Only Selected Patients Benefit From Early Discontinuation of Steroids

Given current evidence, it is extreme and premature to take all patients off corticosteroids within 3 months of heart transplantation.

Steroids have been used since the beginning of heart transplant therapy, and are still among our most useful drugs for achieving immunosuppression.

We all know about their adverse effects. But they are less common today now that we use lower doses (enabled by combination therapy), and we have other means for preventing some of the adverse effects associated with steroids.

Although other classes of immunosuppressants – such as calcineurin inhibitors, MMF, and mTOR (mammalian target of rapamycin) inhibitors – have become available, it is important to remember that they, too, have adverse effects.

The different classes of immunosuppressants have different mechanisms of action, and this is the theoretical basis of triple-drug therapy. Nonreliance on a single drug also allows us to use smaller doses of each.

Nearly all of the major clinical trials in heart transplantation have used corticosteroids (J. Heart Lung Transplant. 2010;29:914-56). And certainly it is now clear that none of the leading causes of death after heart transplantation in adults (except for infection) seems attributable to these drugs (J. Heart Lung Transplant. 2010;29:1089-103). On the contrary, lack of steroid maintenance therapy has been identified as an independent risk factor for death, conferring a doubling of risk (J. Thorac. Cardiovasc. Surg. 2010;140:161-8).

The TICTAC trial was well done and had some important findings. Unfortunately, it was not a clinical trial of steroid discontinuation because there was no group of patients kept on steroids.

Also, when compared with patients in a similar trial who were given tacrolimus-MMF (Am. J. Transplant. 2006;6:1377-86), patients in the TICTAC trial had higher levels of tacrolimus and serum creatinine. These differences are a little worrisome in terms of long-term outcomes.

At my institution, even later withdrawal of steroids (that is, among patients who were on steroids for at least 4 years without any acute rejection episodes) was associated with a 25% incidence of acute rejection (Transplant Proc. 2007;39:2372-4). In Spain, centers typically stop steroids only in patients who have unacceptable adverse effects and a low immunologic risk for rejection.

Only one trial has directly compared early steroid withdrawal with standard steroid therapy in transplant recipients (Am. J. Transplant. 2008;8:307-16). In that study, in kidney transplant patients who either did not receive any steroids or received them for just the first week, acute rejection occurred both earlier and more often than in the standard therapy group. And there were only modest reductions in adverse events.

In heart transplantation, immunosuppressive therapy is not a one-size-fits-all undertaking. Some patients (for example, those who have preexisting osteoporosis, are elderly, or have diabetes) do benefit from early withdrawal of steroids.

Indeed, guidelines recommend steroid weaning in patients who experience significant adverse effects and have not had a recent acute rejection episode (J. Heart Transplant. 2010;29:914-56). But they also note that although several studies have shown that it is feasible and safe to wean most patients by 6-12 months, and that doing so is desirable to reduce adverse effects, there has not been a randomized trial testing this practice.

It is possible that future well-designed studies will show that the risk of rejection is a reasonable price to pay for avoiding the adverse effects of steroids. These studies must have long-term follow-up and assess the key outcomes of graft and patient survival, rather than just rejection.

In conclusion, there are certainly patients who benefit from early withdrawal of steroids, but current evidence does not support the generalization of this practice.

Dr. Crespo-Leiro is with the heart failure and heart transplant unit at the Hospital Universitario a Coruña (Spain).

Steroids Should Be Discontinued as Soon as Possible in All Patients

There is a compelling case for taking all heart transplant recipients off corticosteroids as early as possible, and certainly no later than 3 months after transplantation.

Patients undergoing heart transplantation are in essence trading a disease that will kill them for a disease that is more treatable: immunosuppression. But we physicians can control immunosuppression, which begs the question: Can’t we do better?

We use steroids in more than 80% of our patients. Steroids are our security blanket; they are the drugs that make us feel better. As I was told in training, we sleep better when our patients are on steroids, because we tend to think that they are safe.

But there is no denying that steroids can have life-altering adverse effects for our patients. What if steroids were unnecessary? In fact, they are, but we just haven’t recognized that universally. Steroids are not necessary. This is a not a new idea, as is evident from reports dating back to 1985 (Circulation 1990;82[5 suppl.]:IV318-21).

At least 10 studies have shown the safety of stopping steroids early in heart transplant recipients. Additionally, a recurring finding is that survival is, in fact, better with this practice. You could argue that the patients who are not taken off steroids have a better risk profile, but the weight of evidence does not suggest that this is the case. The following are a few of these studies:

• A case-control study among 420 heart transplant recipients found that steroid withdrawal starting 6 months or more post transplantation was associated with a higher rate of rejection over 7 years, but despite this, survival was better (Am. J. Transplant. 2005;5 [4 Pt. 1]:720-8).

• In a prospective study of 33 heart transplant recipients who were given tacrolimus or sirolimus, all patients were taken off steroids within 6 months (J. Heart Lung Transplant. 2007;26:598-603). There was a single treated rejection and no deaths.

• A retrospective single-institution study of 220 patients found that steroid weaning after heart transplantation was an independent predictor of survival, conferring a significant 40% reduction in the risk of death (Transplant Proc. 2006;38:1501-6).

• In the randomized TICTAC (Tacrolimus in Combination, Tacrolimus Alone Compared) trial, which compared tacrolimus with and without mycophenolate mofetil (MMF), steroids were discontinued in all patients by 8-9 weeks (Circ. Heart Fail. 2011;4:129-37). Over a median follow-up of 3-4 years, none has had to resume steroid maintenance. There was a slight nonsignificant increase in rejection with the monotherapy, but survival – the standard – was identical between groups.

One fear when we began this study was that we would pay the price in allograft vasculopathy if we didn’t provide adequate immunosuppression. Over a 5-year period, however, we have not: The patients on monotherapy and the patients on combination therapy (again, all of them steroid free during follow-up) were indistinguishable in terms of this outcome.

So why do we cling to corticosteroids? What are they doing for us? It’s time to finally admit that they are not necessary. Steroids should be discontinued as rapidly possible among all heart transplant recipients – certainly within 3 months post transplant. We now have good evidence proving the safety and efficacy of this approach.

Dr. Baran is the director of heart failure and transplant research at the Newark (N.J.) Beth Israel Medical Center.

Only Selected Patients Benefit From Early Discontinuation of Steroids

Given current evidence, it is extreme and premature to take all patients off corticosteroids within 3 months of heart transplantation.

Steroids have been used since the beginning of heart transplant therapy, and are still among our most useful drugs for achieving immunosuppression.

We all know about their adverse effects. But they are less common today now that we use lower doses (enabled by combination therapy), and we have other means for preventing some of the adverse effects associated with steroids.

Although other classes of immunosuppressants – such as calcineurin inhibitors, MMF, and mTOR (mammalian target of rapamycin) inhibitors – have become available, it is important to remember that they, too, have adverse effects.

The different classes of immunosuppressants have different mechanisms of action, and this is the theoretical basis of triple-drug therapy. Nonreliance on a single drug also allows us to use smaller doses of each.

Nearly all of the major clinical trials in heart transplantation have used corticosteroids (J. Heart Lung Transplant. 2010;29:914-56). And certainly it is now clear that none of the leading causes of death after heart transplantation in adults (except for infection) seems attributable to these drugs (J. Heart Lung Transplant. 2010;29:1089-103). On the contrary, lack of steroid maintenance therapy has been identified as an independent risk factor for death, conferring a doubling of risk (J. Thorac. Cardiovasc. Surg. 2010;140:161-8).

The TICTAC trial was well done and had some important findings. Unfortunately, it was not a clinical trial of steroid discontinuation because there was no group of patients kept on steroids.

Also, when compared with patients in a similar trial who were given tacrolimus-MMF (Am. J. Transplant. 2006;6:1377-86), patients in the TICTAC trial had higher levels of tacrolimus and serum creatinine. These differences are a little worrisome in terms of long-term outcomes.

At my institution, even later withdrawal of steroids (that is, among patients who were on steroids for at least 4 years without any acute rejection episodes) was associated with a 25% incidence of acute rejection (Transplant Proc. 2007;39:2372-4). In Spain, centers typically stop steroids only in patients who have unacceptable adverse effects and a low immunologic risk for rejection.

Only one trial has directly compared early steroid withdrawal with standard steroid therapy in transplant recipients (Am. J. Transplant. 2008;8:307-16). In that study, in kidney transplant patients who either did not receive any steroids or received them for just the first week, acute rejection occurred both earlier and more often than in the standard therapy group. And there were only modest reductions in adverse events.

In heart transplantation, immunosuppressive therapy is not a one-size-fits-all undertaking. Some patients (for example, those who have preexisting osteoporosis, are elderly, or have diabetes) do benefit from early withdrawal of steroids.

Indeed, guidelines recommend steroid weaning in patients who experience significant adverse effects and have not had a recent acute rejection episode (J. Heart Transplant. 2010;29:914-56). But they also note that although several studies have shown that it is feasible and safe to wean most patients by 6-12 months, and that doing so is desirable to reduce adverse effects, there has not been a randomized trial testing this practice.

It is possible that future well-designed studies will show that the risk of rejection is a reasonable price to pay for avoiding the adverse effects of steroids. These studies must have long-term follow-up and assess the key outcomes of graft and patient survival, rather than just rejection.

In conclusion, there are certainly patients who benefit from early withdrawal of steroids, but current evidence does not support the generalization of this practice.

Dr. Crespo-Leiro is with the heart failure and heart transplant unit at the Hospital Universitario a Coruña (Spain).

Nesiritide has no effect on 30-day mortality or rehospitalization rates in patients with acute decompensated heart failure, according to results of the ASCEND-HF trial reported in the July 7 issue of the New England Journal of Medicine.

In a large 3-year international clinical trial called by an independent panel "to answer the question of whether nesiritide is effective and safe," the drug also failed to improve self-reported dyspnea at 6 hours or 24 hours. It did not worsen renal function, but it nearly doubled the rates of both symptomatic and asymptomatic hypotension.

"Nesiritide thus cannot be recommended in the broad population of patients with acute decompensated heart failure represented by the study population in this trial," wrote Dr. Christopher M. O’Connor of Duke Clinical Research Institute, Durham, N.C., and his associates in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial.

Nesiritide, a recombinant B-type natriuretic peptide with vasodilatory action, was approved in 2001 for use in patients with acute heart failure, based on separate small studies showing that it reduced pulmonary-capillary wedge pressure and eased dyspnea within 3 hours of administration. Later meta-analyses of these and other small trials, however, indicated that the drug worsened renal function and nearly doubled early mortality.

"In hindsight, nesiritide was approved and swiftly adopted in the United States because of its perceived large benefit in relieving dyspnea and congestion, and then its used markedly decreased because of published meta-analyses reporting a detrimental effect on survival and renal function. Our study showed that neither belief was accurate," Dr. O’Connor and his colleagues noted.

ASCEND-HF involved 7,141 patients treated at 398 medical centers around the world. All the participants received standard therapies including diuretics, morphine, and vasoactive medications. Half also received intravenous nesiritide and half received a placebo for up to 7 days.

The two coprimary end points were change in self-reported dyspnea at 6 and 24 hours and rehospitalization for heart failure or death from any cause within 30 days. There was a slight numerical advantage with nesiritide over placebo for dyspnea (44.5% vs. 42.1%, P = .03), but it did not reach the prespecified level for statistical significance. The rates of the second end point were 9.4% with nesiritide and 10.1% with placebo, another nonsignificant difference.

The two study groups also showed no significant differences in self-reported patient well-being, rehospitalization for cardiovascular causes, death from cardiovascular causes, total days alive and out of the hospital at 1 month, rates of persistent or worsening HF, or death from any cause at 1 month. Rates of renal impairment also were comparable between the two groups, regardless of baseline renal insufficiency, the investigators noted (N. Engl. J. Med. 2011;365:32-43).

Significantly more patients who received nesiritide had an episode of asymptomatic (21.4%) or symptomatic (7.2%) hypotension, compared with patients who received placebo (12.4% and 4.0%, respectively).

"The development of nesiritide poses fundamental questions about the manner in which therapies are developed and assessed. Because nesiritide was not studied in a major outcome trial early in its life cycle, both patients and physicians lacked an appropriate understanding of the proper role of the drug in practice.

"Our findings underscore the fact that systematic overviews with small numbers of events can yield unreliable estimates of the balance of benefits and risks, and interpretation of the data is confounded by these imprecise estimates," Dr. O’Connor and his colleagues wrote.

The results also "highlight the urgent need for rigorously designed trials with adequate power to provide reliable estimates that can replace incomplete or inadequate evidence as a basis for therapeutic decisions," they added. The ASCEND-HF results were presented at the annual scientific sessions of the American Heart Association in November 2010.

ASCEND-HF was sponsored by Scios, a Johnson & Johnson company, which markets nesiritide (Natrecor). The investigators reported ties to numerous industry sources. Dr. O’Connor has received consulting fees from Medtronic, Forest, Amgen, Medpace, Roche, and Actelion. Two of the authors are employees of Johnson & Johnson.

Nesiritide has no effect on 30-day mortality or rehospitalization rates in patients with acute decompensated heart failure, according to results of the ASCEND-HF trial reported in the July 7 issue of the New England Journal of Medicine.

In a large 3-year international clinical trial called by an independent panel "to answer the question of whether nesiritide is effective and safe," the drug also failed to improve self-reported dyspnea at 6 hours or 24 hours. It did not worsen renal function, but it nearly doubled the rates of both symptomatic and asymptomatic hypotension.

"Nesiritide thus cannot be recommended in the broad population of patients with acute decompensated heart failure represented by the study population in this trial," wrote Dr. Christopher M. O’Connor of Duke Clinical Research Institute, Durham, N.C., and his associates in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial.

Nesiritide, a recombinant B-type natriuretic peptide with vasodilatory action, was approved in 2001 for use in patients with acute heart failure, based on separate small studies showing that it reduced pulmonary-capillary wedge pressure and eased dyspnea within 3 hours of administration. Later meta-analyses of these and other small trials, however, indicated that the drug worsened renal function and nearly doubled early mortality.

"In hindsight, nesiritide was approved and swiftly adopted in the United States because of its perceived large benefit in relieving dyspnea and congestion, and then its used markedly decreased because of published meta-analyses reporting a detrimental effect on survival and renal function. Our study showed that neither belief was accurate," Dr. O’Connor and his colleagues noted.

ASCEND-HF involved 7,141 patients treated at 398 medical centers around the world. All the participants received standard therapies including diuretics, morphine, and vasoactive medications. Half also received intravenous nesiritide and half received a placebo for up to 7 days.

The two coprimary end points were change in self-reported dyspnea at 6 and 24 hours and rehospitalization for heart failure or death from any cause within 30 days. There was a slight numerical advantage with nesiritide over placebo for dyspnea (44.5% vs. 42.1%, P = .03), but it did not reach the prespecified level for statistical significance. The rates of the second end point were 9.4% with nesiritide and 10.1% with placebo, another nonsignificant difference.

The two study groups also showed no significant differences in self-reported patient well-being, rehospitalization for cardiovascular causes, death from cardiovascular causes, total days alive and out of the hospital at 1 month, rates of persistent or worsening HF, or death from any cause at 1 month. Rates of renal impairment also were comparable between the two groups, regardless of baseline renal insufficiency, the investigators noted (N. Engl. J. Med. 2011;365:32-43).

Significantly more patients who received nesiritide had an episode of asymptomatic (21.4%) or symptomatic (7.2%) hypotension, compared with patients who received placebo (12.4% and 4.0%, respectively).

"The development of nesiritide poses fundamental questions about the manner in which therapies are developed and assessed. Because nesiritide was not studied in a major outcome trial early in its life cycle, both patients and physicians lacked an appropriate understanding of the proper role of the drug in practice.

"Our findings underscore the fact that systematic overviews with small numbers of events can yield unreliable estimates of the balance of benefits and risks, and interpretation of the data is confounded by these imprecise estimates," Dr. O’Connor and his colleagues wrote.

The results also "highlight the urgent need for rigorously designed trials with adequate power to provide reliable estimates that can replace incomplete or inadequate evidence as a basis for therapeutic decisions," they added. The ASCEND-HF results were presented at the annual scientific sessions of the American Heart Association in November 2010.

ASCEND-HF was sponsored by Scios, a Johnson & Johnson company, which markets nesiritide (Natrecor). The investigators reported ties to numerous industry sources. Dr. O’Connor has received consulting fees from Medtronic, Forest, Amgen, Medpace, Roche, and Actelion. Two of the authors are employees of Johnson & Johnson.

Nesiritide has no effect on 30-day mortality or rehospitalization rates in patients with acute decompensated heart failure, according to results of the ASCEND-HF trial reported in the July 7 issue of the New England Journal of Medicine.

In a large 3-year international clinical trial called by an independent panel "to answer the question of whether nesiritide is effective and safe," the drug also failed to improve self-reported dyspnea at 6 hours or 24 hours. It did not worsen renal function, but it nearly doubled the rates of both symptomatic and asymptomatic hypotension.

"Nesiritide thus cannot be recommended in the broad population of patients with acute decompensated heart failure represented by the study population in this trial," wrote Dr. Christopher M. O’Connor of Duke Clinical Research Institute, Durham, N.C., and his associates in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial.

Nesiritide, a recombinant B-type natriuretic peptide with vasodilatory action, was approved in 2001 for use in patients with acute heart failure, based on separate small studies showing that it reduced pulmonary-capillary wedge pressure and eased dyspnea within 3 hours of administration. Later meta-analyses of these and other small trials, however, indicated that the drug worsened renal function and nearly doubled early mortality.

"In hindsight, nesiritide was approved and swiftly adopted in the United States because of its perceived large benefit in relieving dyspnea and congestion, and then its used markedly decreased because of published meta-analyses reporting a detrimental effect on survival and renal function. Our study showed that neither belief was accurate," Dr. O’Connor and his colleagues noted.

ASCEND-HF involved 7,141 patients treated at 398 medical centers around the world. All the participants received standard therapies including diuretics, morphine, and vasoactive medications. Half also received intravenous nesiritide and half received a placebo for up to 7 days.

The two coprimary end points were change in self-reported dyspnea at 6 and 24 hours and rehospitalization for heart failure or death from any cause within 30 days. There was a slight numerical advantage with nesiritide over placebo for dyspnea (44.5% vs. 42.1%, P = .03), but it did not reach the prespecified level for statistical significance. The rates of the second end point were 9.4% with nesiritide and 10.1% with placebo, another nonsignificant difference.

The two study groups also showed no significant differences in self-reported patient well-being, rehospitalization for cardiovascular causes, death from cardiovascular causes, total days alive and out of the hospital at 1 month, rates of persistent or worsening HF, or death from any cause at 1 month. Rates of renal impairment also were comparable between the two groups, regardless of baseline renal insufficiency, the investigators noted (N. Engl. J. Med. 2011;365:32-43).

Significantly more patients who received nesiritide had an episode of asymptomatic (21.4%) or symptomatic (7.2%) hypotension, compared with patients who received placebo (12.4% and 4.0%, respectively).

"The development of nesiritide poses fundamental questions about the manner in which therapies are developed and assessed. Because nesiritide was not studied in a major outcome trial early in its life cycle, both patients and physicians lacked an appropriate understanding of the proper role of the drug in practice.

"Our findings underscore the fact that systematic overviews with small numbers of events can yield unreliable estimates of the balance of benefits and risks, and interpretation of the data is confounded by these imprecise estimates," Dr. O’Connor and his colleagues wrote.

The results also "highlight the urgent need for rigorously designed trials with adequate power to provide reliable estimates that can replace incomplete or inadequate evidence as a basis for therapeutic decisions," they added. The ASCEND-HF results were presented at the annual scientific sessions of the American Heart Association in November 2010.

ASCEND-HF was sponsored by Scios, a Johnson & Johnson company, which markets nesiritide (Natrecor). The investigators reported ties to numerous industry sources. Dr. O’Connor has received consulting fees from Medtronic, Forest, Amgen, Medpace, Roche, and Actelion. Two of the authors are employees of Johnson & Johnson.

SAN DIEGO – A new allocation algorithm that is designed to improve regional sharing of donor hearts with sicker patients before they are allocated locally to less-sick patients appears to be having the intended effects, according to a national cohort study.

In the study of nearly 12,000 adult patients who were wait-listed for primary heart transplantation in 2004-2009 in the United States, those who were wait-listed after the new algorithm was implemented were 17% less likely to die on the waiting list or to become too sick for transplantation, Dr. Tajinder P. Singh reported at the meeting.

Moreover, this benefit was achieved without any increase in the rate of in-hospital mortality in transplant recipients, even though they were sicker on average.

“The risk of dying on the heart transplant [waiting list] or becoming too sick for transplant has declined since the change in allocation algorithm in 2006,” said Dr. Singh, a pediatric cardiologist at Children's Hospital Boston. And reassuringly, “the shift in hearts to sicker transplant candidates has not resulted in higher early posttransplant mortality.”

These findings suggest that the new algorithm has been effective “not only from a utilitarian view, which means most benefit for most people, but even from the fairness or justice perspective,” he commented, because the hearts are goint to sicker people.

“The demand for donor hearts continues to exceed their supply,” he said, giving background to the study. “The United Network for Organ Sharing has periodically modified the allocation algorithm in the United States” to improve waiting list outcomes.

The last such modification, implemented in July 2006, expanded the sharing of these scarce organs across a geographic region, making them available first to the sickest patients (those with status 1A or 1B) in a region before allocating them locally to less-sick patients.

The investigators studied all patients aged 18 years or older who were placed on the waiting list for primary heart transplantationbduring July 1004, ane 30, 2009, and who were undergoing transplantation of only a heart.

For comparison, the patients were split according to when they were listed into “era 1” (before the date of implementation of the new algorithm) and “era 2” (after that date). Study results were based on 11,864 patients in total; 38% were listed in era 1 and 62% were listed in era 2.

Patients in the two eras were similar with respect to most sociodemographic and medical factors, except that those in era 2 were more likely to be aged 60 years or older (32% vs. 28%), to receive mechanical support (14% vs. 13%), and to be sicker, as indicated by having a transplantation status of 1A (20% vs. 19%) or 1B (38% vs. 32%), for instance.

Overall, 13% of the patients studied either died or had a worsening of their condition that prevented transplantation while they were on the waiting list, the study's primary end point, Dr. Singh reported.

Before statistical adjustment, patients in era 2 were 14% less likely than those in era 1 to die or worsen while on the wait list (hazard ratio, 0.86). And this benefit was evident in both status 1A patients and status 1B patients individually.

After adjustment for numerous potential confounders, patients in era 2 were 17% less likely to die or worsen while on the wait list (HR, 0.83). This significant benefit was similar in most subgroups, except that by race, it was mainly limited to white patients.

Other risk-reducing factors included having an implantable cardioverter defibrillator (HR, 0.87) and having a continuous-flow left ventricular assist device (HR, 0.56).

Overall, 65% of the patients ultimately underwent transplantation. Compared with those in era 1, era 2 transplant recipients had a significantly shorter median wait time before receiving a heart (55 vs. 63 days) and were more likely to be status 1A at transplantation (48% vs. 37%).

Dr. Singh reported having no conflicts of interest related to the research.

SAN DIEGO – A new allocation algorithm that is designed to improve regional sharing of donor hearts with sicker patients before they are allocated locally to less-sick patients appears to be having the intended effects, according to a national cohort study.

In the study of nearly 12,000 adult patients who were wait-listed for primary heart transplantation in 2004-2009 in the United States, those who were wait-listed after the new algorithm was implemented were 17% less likely to die on the waiting list or to become too sick for transplantation, Dr. Tajinder P. Singh reported at the meeting.

Moreover, this benefit was achieved without any increase in the rate of in-hospital mortality in transplant recipients, even though they were sicker on average.

“The risk of dying on the heart transplant [waiting list] or becoming too sick for transplant has declined since the change in allocation algorithm in 2006,” said Dr. Singh, a pediatric cardiologist at Children's Hospital Boston. And reassuringly, “the shift in hearts to sicker transplant candidates has not resulted in higher early posttransplant mortality.”

These findings suggest that the new algorithm has been effective “not only from a utilitarian view, which means most benefit for most people, but even from the fairness or justice perspective,” he commented, because the hearts are goint to sicker people.

“The demand for donor hearts continues to exceed their supply,” he said, giving background to the study. “The United Network for Organ Sharing has periodically modified the allocation algorithm in the United States” to improve waiting list outcomes.

The last such modification, implemented in July 2006, expanded the sharing of these scarce organs across a geographic region, making them available first to the sickest patients (those with status 1A or 1B) in a region before allocating them locally to less-sick patients.

The investigators studied all patients aged 18 years or older who were placed on the waiting list for primary heart transplantationbduring July 1004, ane 30, 2009, and who were undergoing transplantation of only a heart.

For comparison, the patients were split according to when they were listed into “era 1” (before the date of implementation of the new algorithm) and “era 2” (after that date). Study results were based on 11,864 patients in total; 38% were listed in era 1 and 62% were listed in era 2.

Patients in the two eras were similar with respect to most sociodemographic and medical factors, except that those in era 2 were more likely to be aged 60 years or older (32% vs. 28%), to receive mechanical support (14% vs. 13%), and to be sicker, as indicated by having a transplantation status of 1A (20% vs. 19%) or 1B (38% vs. 32%), for instance.

Overall, 13% of the patients studied either died or had a worsening of their condition that prevented transplantation while they were on the waiting list, the study's primary end point, Dr. Singh reported.

Before statistical adjustment, patients in era 2 were 14% less likely than those in era 1 to die or worsen while on the wait list (hazard ratio, 0.86). And this benefit was evident in both status 1A patients and status 1B patients individually.

After adjustment for numerous potential confounders, patients in era 2 were 17% less likely to die or worsen while on the wait list (HR, 0.83). This significant benefit was similar in most subgroups, except that by race, it was mainly limited to white patients.

Other risk-reducing factors included having an implantable cardioverter defibrillator (HR, 0.87) and having a continuous-flow left ventricular assist device (HR, 0.56).

Overall, 65% of the patients ultimately underwent transplantation. Compared with those in era 1, era 2 transplant recipients had a significantly shorter median wait time before receiving a heart (55 vs. 63 days) and were more likely to be status 1A at transplantation (48% vs. 37%).

Dr. Singh reported having no conflicts of interest related to the research.

SAN DIEGO – A new allocation algorithm that is designed to improve regional sharing of donor hearts with sicker patients before they are allocated locally to less-sick patients appears to be having the intended effects, according to a national cohort study.

In the study of nearly 12,000 adult patients who were wait-listed for primary heart transplantation in 2004-2009 in the United States, those who were wait-listed after the new algorithm was implemented were 17% less likely to die on the waiting list or to become too sick for transplantation, Dr. Tajinder P. Singh reported at the meeting.

Moreover, this benefit was achieved without any increase in the rate of in-hospital mortality in transplant recipients, even though they were sicker on average.

“The risk of dying on the heart transplant [waiting list] or becoming too sick for transplant has declined since the change in allocation algorithm in 2006,” said Dr. Singh, a pediatric cardiologist at Children's Hospital Boston. And reassuringly, “the shift in hearts to sicker transplant candidates has not resulted in higher early posttransplant mortality.”

These findings suggest that the new algorithm has been effective “not only from a utilitarian view, which means most benefit for most people, but even from the fairness or justice perspective,” he commented, because the hearts are goint to sicker people.

“The demand for donor hearts continues to exceed their supply,” he said, giving background to the study. “The United Network for Organ Sharing has periodically modified the allocation algorithm in the United States” to improve waiting list outcomes.

The last such modification, implemented in July 2006, expanded the sharing of these scarce organs across a geographic region, making them available first to the sickest patients (those with status 1A or 1B) in a region before allocating them locally to less-sick patients.

The investigators studied all patients aged 18 years or older who were placed on the waiting list for primary heart transplantationbduring July 1004, ane 30, 2009, and who were undergoing transplantation of only a heart.

For comparison, the patients were split according to when they were listed into “era 1” (before the date of implementation of the new algorithm) and “era 2” (after that date). Study results were based on 11,864 patients in total; 38% were listed in era 1 and 62% were listed in era 2.

Patients in the two eras were similar with respect to most sociodemographic and medical factors, except that those in era 2 were more likely to be aged 60 years or older (32% vs. 28%), to receive mechanical support (14% vs. 13%), and to be sicker, as indicated by having a transplantation status of 1A (20% vs. 19%) or 1B (38% vs. 32%), for instance.

Overall, 13% of the patients studied either died or had a worsening of their condition that prevented transplantation while they were on the waiting list, the study's primary end point, Dr. Singh reported.

Before statistical adjustment, patients in era 2 were 14% less likely than those in era 1 to die or worsen while on the wait list (hazard ratio, 0.86). And this benefit was evident in both status 1A patients and status 1B patients individually.

After adjustment for numerous potential confounders, patients in era 2 were 17% less likely to die or worsen while on the wait list (HR, 0.83). This significant benefit was similar in most subgroups, except that by race, it was mainly limited to white patients.

Other risk-reducing factors included having an implantable cardioverter defibrillator (HR, 0.87) and having a continuous-flow left ventricular assist device (HR, 0.56).

Overall, 65% of the patients ultimately underwent transplantation. Compared with those in era 1, era 2 transplant recipients had a significantly shorter median wait time before receiving a heart (55 vs. 63 days) and were more likely to be status 1A at transplantation (48% vs. 37%).

Dr. Singh reported having no conflicts of interest related to the research.

Major Finding: After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the heart failure clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic.

Data Source: Randomized study of 1,119 heart failure patients treated at 18 Danish centers.

Disclosures: Dr. Schou said that he has received research support from Roche Diagnostics Denmark, Roche Diagnostics International, and Merck Sharp & Dohme.

NEW ORLEANS – General practice physicians who managed stable heart failure patients achieved long-term outcomes that matched the outcomes of patients managed in specialized, outpatient heart failure clinics supervised by cardiologists, in a randomized, Danish study with more than 1,100 patients.

Another facet of the same study showed that repeated, serial measurement of blood levels of N-terminal-proB-type natriuretic peptide (NT-proBNP) in heart failure patients did not improve long-term outcomes compared with no routine measurement of the biomarker, Dr. Morten Schou said at the meeting.

“Clinically stable patients with systolic heart failure on optimal medical therapy did not benefit from long-term follow-up in a heart failure clinic,” said Dr. Schou, a cardiologist at Hillerod University Hospital in Copenhagen.

Heart failure clinics with intensive patient management can aid in stabilizing patients, but they are most suited for newly diagnosed patients who are not yet well controlled on an appropriate maintenance regimen, Dr. Schou said in an interview. “Our study is the first to investigate continuing intensive management once a heart failure patient is stable on an optimized regimen. The long-term benefits of heart failure clinics were never tested before.”

The stabilization regimen used by the investigators involved uptitrating the drugs patients received so that their medical treatment used drugs such as ACE inhibitors, beta-blockers, and aldosterone antagonists at dosages comparable to what has been shown effective in clinical trials. Patients also received comprehensive education about their heart failure and optimal management methods. The stabilization process took from 1 month to 1 year, he said, and slightly more than a quarter of the heart failure patients seen at least once at one of the 18 participating Danish heart failure clinics achieved stability and also met the study's other eligibility criteria.

“The key message is that you need to educate and uptitrate patients, and then they can be followed by a general practitioner [GP],” he said.

The second finding of the study, that multiple, serial measures of blood NT-proBNP did not lead to improved outcomes, should prompt a change in U.S. practice, commented Dr. Prakash C. Deedwania, professor of medicine at the University of California, San Francisco, in Fresno.

In current U.S. practice, “BNP is measured about 10 times on patients in the hospital [for heart failure]. I could never understand it. These results show that it wastes time and money to measure BNP” repeatedly, he said in an interview (see View on the News, below).

The NT-proBNP stratified follow-up in outpatient heart failure clinics (NorthStar) trial enrolled patients with New York Heart Association class I-III systolic heart failure and a left ventricular ejection fraction of 45% or less who also fulfilled the study's prespecified criteria for disease stability. The criteria included completion of a heart failure education course, and daily treatment with an evidence-based dosage of an ACE inhibitor or angiotensin II receptor blocker, beta-blocker, and, when appropriate, an aldosterone antagonist. Participants were also taking a stable diuretic dose and had a stable weight, stable heart failure symptoms, and no crackles on lung auscultation. The study randomized 460 patients to ongoing care by a general practitioner and 659 patients to regular care in a heart failure clinic supervised by a cardiologist.

The heart failure clinic patients underwent further assessment at baseline to identify those with a blood level of NT-proBNP that exceeded 1,000 pg/mL. The 407 patients in this group underwent a second randomization, with 208 patients followed without any subsequent, routine measurement of their NT-proBNP level, and 199 patients who underwent a repeat blood check of NT-proBNP at every follow-up visit to the clinic. The clinic staff received a guide detailing clinical factors to investigate in patients who had a rise in their NT-proBNP level of greater than 30% from one clinic visit to the next. The study followed all patients for a median of 2.5 years.

The average age of the patients randomized to GP or heart failure clinic management was 69 years. A quarter of the patients were women, and all patients had an average ejection fraction of about 31%. Among the subgroup of patients with an elevated blood level of NT-proBNP at baseline, the average age was 73 years, a quarter were women, and their average ejection fraction was 30%.

The study's primary end point was the combined rate of all-cause death or cardiovascular hospitalization. After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic. In addition, patients managed in heart failure clinics without routine NT-proBNP monitoring had a combined end-point rate similar to those who underwent routine monitoring, Dr. Schou reported. The results showed no statistically significant difference among the study subgroups for any secondary end points assessed.

'You need to educate and uptitrate patients, and then they can be followed by a general practitioner.'

Source DR. SCHOU

View on the News

Findings Point to Lower Costs

The results from this study show that properly treated heart failure patients on an evidence-based regimen can be effectively managed by a primary care physician. That's a very powerful and important message. In the United States, heart failure management has become a big business. But every heart failure patient cannot be managed by a cardiologist because the number of patients is increasing too quickly. In the Danish study, general practitioners got the heart failure patients after they were stabilized, and the GPs were trained in how to adjust the patients' diuretic dosages.

These results do not discount a role for heart failure disease management. Disease management works. It is important to have a specific regimen for monitoring and treating heart failure patients. But the results show that it doesn't matter who does the monitoring and treating as long as they received training in how to do it.

The results also showed that we waste time and money if we measure B-type natriuretic peptide repeatedly in heart failure patients. BNP is good for making an initial diagnosis of heart failure, to distinguish heart failure from other disorders with similar symptoms. But once an initial measure is made and the diagnosis confirmed, more BNP measurements don't add anything further. Many U.S. heart failure patients undergo serial measurements despite the lack of good evidence that this helps. Current guidelines from the Heart Failure Society of America call for only measuring BNP initially in heart failure patients, especially when the initial diagnosis is uncertain based on clinical presentation (J. Card. Fail. 2010;16:e1-e194).

PRAKASH C. DEEDWANIA, M.D., is professor of medicine at the University of California, San Francisco, in Fresno. His comments were made in an interview. He reported having no disclosures.

Major Finding: After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the heart failure clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic.

Data Source: Randomized study of 1,119 heart failure patients treated at 18 Danish centers.

Disclosures: Dr. Schou said that he has received research support from Roche Diagnostics Denmark, Roche Diagnostics International, and Merck Sharp & Dohme.

NEW ORLEANS – General practice physicians who managed stable heart failure patients achieved long-term outcomes that matched the outcomes of patients managed in specialized, outpatient heart failure clinics supervised by cardiologists, in a randomized, Danish study with more than 1,100 patients.

Another facet of the same study showed that repeated, serial measurement of blood levels of N-terminal-proB-type natriuretic peptide (NT-proBNP) in heart failure patients did not improve long-term outcomes compared with no routine measurement of the biomarker, Dr. Morten Schou said at the meeting.

“Clinically stable patients with systolic heart failure on optimal medical therapy did not benefit from long-term follow-up in a heart failure clinic,” said Dr. Schou, a cardiologist at Hillerod University Hospital in Copenhagen.

Heart failure clinics with intensive patient management can aid in stabilizing patients, but they are most suited for newly diagnosed patients who are not yet well controlled on an appropriate maintenance regimen, Dr. Schou said in an interview. “Our study is the first to investigate continuing intensive management once a heart failure patient is stable on an optimized regimen. The long-term benefits of heart failure clinics were never tested before.”

The stabilization regimen used by the investigators involved uptitrating the drugs patients received so that their medical treatment used drugs such as ACE inhibitors, beta-blockers, and aldosterone antagonists at dosages comparable to what has been shown effective in clinical trials. Patients also received comprehensive education about their heart failure and optimal management methods. The stabilization process took from 1 month to 1 year, he said, and slightly more than a quarter of the heart failure patients seen at least once at one of the 18 participating Danish heart failure clinics achieved stability and also met the study's other eligibility criteria.

“The key message is that you need to educate and uptitrate patients, and then they can be followed by a general practitioner [GP],” he said.

The second finding of the study, that multiple, serial measures of blood NT-proBNP did not lead to improved outcomes, should prompt a change in U.S. practice, commented Dr. Prakash C. Deedwania, professor of medicine at the University of California, San Francisco, in Fresno.

In current U.S. practice, “BNP is measured about 10 times on patients in the hospital [for heart failure]. I could never understand it. These results show that it wastes time and money to measure BNP” repeatedly, he said in an interview (see View on the News, below).

The NT-proBNP stratified follow-up in outpatient heart failure clinics (NorthStar) trial enrolled patients with New York Heart Association class I-III systolic heart failure and a left ventricular ejection fraction of 45% or less who also fulfilled the study's prespecified criteria for disease stability. The criteria included completion of a heart failure education course, and daily treatment with an evidence-based dosage of an ACE inhibitor or angiotensin II receptor blocker, beta-blocker, and, when appropriate, an aldosterone antagonist. Participants were also taking a stable diuretic dose and had a stable weight, stable heart failure symptoms, and no crackles on lung auscultation. The study randomized 460 patients to ongoing care by a general practitioner and 659 patients to regular care in a heart failure clinic supervised by a cardiologist.

The heart failure clinic patients underwent further assessment at baseline to identify those with a blood level of NT-proBNP that exceeded 1,000 pg/mL. The 407 patients in this group underwent a second randomization, with 208 patients followed without any subsequent, routine measurement of their NT-proBNP level, and 199 patients who underwent a repeat blood check of NT-proBNP at every follow-up visit to the clinic. The clinic staff received a guide detailing clinical factors to investigate in patients who had a rise in their NT-proBNP level of greater than 30% from one clinic visit to the next. The study followed all patients for a median of 2.5 years.

The average age of the patients randomized to GP or heart failure clinic management was 69 years. A quarter of the patients were women, and all patients had an average ejection fraction of about 31%. Among the subgroup of patients with an elevated blood level of NT-proBNP at baseline, the average age was 73 years, a quarter were women, and their average ejection fraction was 30%.

The study's primary end point was the combined rate of all-cause death or cardiovascular hospitalization. After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic. In addition, patients managed in heart failure clinics without routine NT-proBNP monitoring had a combined end-point rate similar to those who underwent routine monitoring, Dr. Schou reported. The results showed no statistically significant difference among the study subgroups for any secondary end points assessed.

'You need to educate and uptitrate patients, and then they can be followed by a general practitioner.'

Source DR. SCHOU

View on the News

Findings Point to Lower Costs

The results from this study show that properly treated heart failure patients on an evidence-based regimen can be effectively managed by a primary care physician. That's a very powerful and important message. In the United States, heart failure management has become a big business. But every heart failure patient cannot be managed by a cardiologist because the number of patients is increasing too quickly. In the Danish study, general practitioners got the heart failure patients after they were stabilized, and the GPs were trained in how to adjust the patients' diuretic dosages.

These results do not discount a role for heart failure disease management. Disease management works. It is important to have a specific regimen for monitoring and treating heart failure patients. But the results show that it doesn't matter who does the monitoring and treating as long as they received training in how to do it.

The results also showed that we waste time and money if we measure B-type natriuretic peptide repeatedly in heart failure patients. BNP is good for making an initial diagnosis of heart failure, to distinguish heart failure from other disorders with similar symptoms. But once an initial measure is made and the diagnosis confirmed, more BNP measurements don't add anything further. Many U.S. heart failure patients undergo serial measurements despite the lack of good evidence that this helps. Current guidelines from the Heart Failure Society of America call for only measuring BNP initially in heart failure patients, especially when the initial diagnosis is uncertain based on clinical presentation (J. Card. Fail. 2010;16:e1-e194).

PRAKASH C. DEEDWANIA, M.D., is professor of medicine at the University of California, San Francisco, in Fresno. His comments were made in an interview. He reported having no disclosures.

Major Finding: After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the heart failure clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic.

Data Source: Randomized study of 1,119 heart failure patients treated at 18 Danish centers.

Disclosures: Dr. Schou said that he has received research support from Roche Diagnostics Denmark, Roche Diagnostics International, and Merck Sharp & Dohme.

NEW ORLEANS – General practice physicians who managed stable heart failure patients achieved long-term outcomes that matched the outcomes of patients managed in specialized, outpatient heart failure clinics supervised by cardiologists, in a randomized, Danish study with more than 1,100 patients.

Another facet of the same study showed that repeated, serial measurement of blood levels of N-terminal-proB-type natriuretic peptide (NT-proBNP) in heart failure patients did not improve long-term outcomes compared with no routine measurement of the biomarker, Dr. Morten Schou said at the meeting.

“Clinically stable patients with systolic heart failure on optimal medical therapy did not benefit from long-term follow-up in a heart failure clinic,” said Dr. Schou, a cardiologist at Hillerod University Hospital in Copenhagen.

Heart failure clinics with intensive patient management can aid in stabilizing patients, but they are most suited for newly diagnosed patients who are not yet well controlled on an appropriate maintenance regimen, Dr. Schou said in an interview. “Our study is the first to investigate continuing intensive management once a heart failure patient is stable on an optimized regimen. The long-term benefits of heart failure clinics were never tested before.”

The stabilization regimen used by the investigators involved uptitrating the drugs patients received so that their medical treatment used drugs such as ACE inhibitors, beta-blockers, and aldosterone antagonists at dosages comparable to what has been shown effective in clinical trials. Patients also received comprehensive education about their heart failure and optimal management methods. The stabilization process took from 1 month to 1 year, he said, and slightly more than a quarter of the heart failure patients seen at least once at one of the 18 participating Danish heart failure clinics achieved stability and also met the study's other eligibility criteria.

“The key message is that you need to educate and uptitrate patients, and then they can be followed by a general practitioner [GP],” he said.

The second finding of the study, that multiple, serial measures of blood NT-proBNP did not lead to improved outcomes, should prompt a change in U.S. practice, commented Dr. Prakash C. Deedwania, professor of medicine at the University of California, San Francisco, in Fresno.

In current U.S. practice, “BNP is measured about 10 times on patients in the hospital [for heart failure]. I could never understand it. These results show that it wastes time and money to measure BNP” repeatedly, he said in an interview (see View on the News, below).

The NT-proBNP stratified follow-up in outpatient heart failure clinics (NorthStar) trial enrolled patients with New York Heart Association class I-III systolic heart failure and a left ventricular ejection fraction of 45% or less who also fulfilled the study's prespecified criteria for disease stability. The criteria included completion of a heart failure education course, and daily treatment with an evidence-based dosage of an ACE inhibitor or angiotensin II receptor blocker, beta-blocker, and, when appropriate, an aldosterone antagonist. Participants were also taking a stable diuretic dose and had a stable weight, stable heart failure symptoms, and no crackles on lung auscultation. The study randomized 460 patients to ongoing care by a general practitioner and 659 patients to regular care in a heart failure clinic supervised by a cardiologist.

The heart failure clinic patients underwent further assessment at baseline to identify those with a blood level of NT-proBNP that exceeded 1,000 pg/mL. The 407 patients in this group underwent a second randomization, with 208 patients followed without any subsequent, routine measurement of their NT-proBNP level, and 199 patients who underwent a repeat blood check of NT-proBNP at every follow-up visit to the clinic. The clinic staff received a guide detailing clinical factors to investigate in patients who had a rise in their NT-proBNP level of greater than 30% from one clinic visit to the next. The study followed all patients for a median of 2.5 years.

The average age of the patients randomized to GP or heart failure clinic management was 69 years. A quarter of the patients were women, and all patients had an average ejection fraction of about 31%. Among the subgroup of patients with an elevated blood level of NT-proBNP at baseline, the average age was 73 years, a quarter were women, and their average ejection fraction was 30%.

The study's primary end point was the combined rate of all-cause death or cardiovascular hospitalization. After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic. In addition, patients managed in heart failure clinics without routine NT-proBNP monitoring had a combined end-point rate similar to those who underwent routine monitoring, Dr. Schou reported. The results showed no statistically significant difference among the study subgroups for any secondary end points assessed.

'You need to educate and uptitrate patients, and then they can be followed by a general practitioner.'

Source DR. SCHOU

View on the News

Findings Point to Lower Costs

The results from this study show that properly treated heart failure patients on an evidence-based regimen can be effectively managed by a primary care physician. That's a very powerful and important message. In the United States, heart failure management has become a big business. But every heart failure patient cannot be managed by a cardiologist because the number of patients is increasing too quickly. In the Danish study, general practitioners got the heart failure patients after they were stabilized, and the GPs were trained in how to adjust the patients' diuretic dosages.

These results do not discount a role for heart failure disease management. Disease management works. It is important to have a specific regimen for monitoring and treating heart failure patients. But the results show that it doesn't matter who does the monitoring and treating as long as they received training in how to do it.

The results also showed that we waste time and money if we measure B-type natriuretic peptide repeatedly in heart failure patients. BNP is good for making an initial diagnosis of heart failure, to distinguish heart failure from other disorders with similar symptoms. But once an initial measure is made and the diagnosis confirmed, more BNP measurements don't add anything further. Many U.S. heart failure patients undergo serial measurements despite the lack of good evidence that this helps. Current guidelines from the Heart Failure Society of America call for only measuring BNP initially in heart failure patients, especially when the initial diagnosis is uncertain based on clinical presentation (J. Card. Fail. 2010;16:e1-e194).

PRAKASH C. DEEDWANIA, M.D., is professor of medicine at the University of California, San Francisco, in Fresno. His comments were made in an interview. He reported having no disclosures.

Moderate and severe diastolic dysfunction in patients who have normal systolic function increased all-cause mortality, according to a report in the June 27 issue of the Archives of Internal Medicine.

Such diastolic dysfunction is usually preclinical and often is identified on outpatient echocardiography that was done to assess nonspecific symptoms, ventricular or valvular function, arrhythmia, or ECG abnormalities. Its clinical significance has not been documented until now, said Dr. Carmel M. Halley of the Heart and Vascular Institute at the Cleveland Clinic, and her associates.

"Because the use of echocardiography as a clinical tool in the outpatient setting continues to increase ... our study provides the physician with a prognostic context when diastolic dysfunction is reported, especially because most procedures are requested by noncardiologists," the researchers noted (Arch. Intern. Med. 2011;171:1082-7).

Dr. Halley and her colleagues examined diastolic dysfunction in the absence of systolic dysfunction, because the clinical relevance of the condition has been questioned. Many medical disorders associated with diastolic dysfunction, such as hypertension, coronary artery disease, obesity, and diabetes, are themselves predictors of increased mortality, so it was unclear whether diastolic dysfunction was an independent contributor.

The researchers reviewed the records of consecutive patients who underwent outpatient echocardiography at the Cleveland Clinic and its satellite facilities between 1996 and 2005. They identified 36,261 patients (65,696 echocardiographic tests) who had normal ejection fractions signaling preserved systolic function.

The mean patient age was 58 years, and slightly more than half of the study subjects were women. The subjects were typical of patients usually referred for echocardiography – they frequently had cardiovascular risk factors such as dyslipidemia (35%), hypertension (15%), and diabetes (12%), but usually did not have established CV disease, such as congestive heart failure (4%), peripheral vascular disease (1%), or coronary artery disease (0.6%).

The most frequent indications for ordering the echocardiography were symptom assessment, assessment of ventricular or valvular function, evaluation of suspected or known CAD, and assessment of arrhythmia or ECG abnormalities.

The prevalence of diastolic dysfunction was high, at 65%. The dysfunction was mild in the majority of patients (nearly 60%), moderate in 4.8%, and severe in 0.4%.

During an average follow-up of 6 years, there were 5,789 deaths. Unadjusted all-cause mortality was higher with any degree of diastolic dysfunction than with normal diastolic function: 21% with mild diastolic dysfunction, 24% with moderate diastolic dysfunction, and 39% with severe diastolic dysfunction, compared with 7% in patients who had normal diastolic function.

However, because comorbidities that could confound the analyses were more common among patients with more severe diastolic dysfunction, propensity matching and statistical controlling for comorbidities were performed. Subsequent analysis showed that only moderate and severe diastolic dysfunction raised mortality risk.

Eight-year survival estimates were 78% for patients with normal diastolic function and 72% for mild diastolic dysfunction, compared with 68% for moderate diastolic dysfunction and 58% for severe diastolic dysfunction.

"For the first time, to our knowledge, moderate and severe diastolic dysfunction have been shown to be independent predictors of mortality rate," Dr. Halley and her associates said.

The mechanisms by which diastolic dysfunction raises mortality are not yet known, nor is it known whether therapies targeting such dysfunction can be developed, or whether they would reduce mortality. "However, our results suggest that an increased awareness of the clinical significance of advanced diastolic dysfunction may lead to earlier identification of those patients who are at risk, especially at a preclinical stage," the investigators noted.

They added that this study was limited in that it was retrospective and involved only a single institution.

This new study provides "an important piece of the puzzle," shedding light on the continuum from mild and asymptomatic to severe and symptomatic diastolic dysfunction, said Dr. Ileana L. Piña in remarks taken from her invited commentary that accompanied Dr. Halley’s report (Arch. Intern. Med. 2011;171:1088-9).

The findings that diastolic dysfunction is so common – affecting 65% of this study cohort – and that physicians must be alert to the prognostic value of more severe dysfunction are "novel and important for physicians."

In the future, it will be critical to elucidate the missing link between diagnosis of diastolic dysfunction on echocardiography and the later presentation of older patients, particularly older women, with acute decompensated heart failure in which systolic function is preserved, Dr. Piña of the departments of epidemiology and biostatistics at Case Western Reserve University, Cleveland, added.

One of Dr. Halley’s associates reported ties to GE Healthcare, Philips Healthcare, and Siemens AG. Dr. Piña reported no financial disclosures.

Moderate and severe diastolic dysfunction in patients who have normal systolic function increased all-cause mortality, according to a report in the June 27 issue of the Archives of Internal Medicine.

Such diastolic dysfunction is usually preclinical and often is identified on outpatient echocardiography that was done to assess nonspecific symptoms, ventricular or valvular function, arrhythmia, or ECG abnormalities. Its clinical significance has not been documented until now, said Dr. Carmel M. Halley of the Heart and Vascular Institute at the Cleveland Clinic, and her associates.

"Because the use of echocardiography as a clinical tool in the outpatient setting continues to increase ... our study provides the physician with a prognostic context when diastolic dysfunction is reported, especially because most procedures are requested by noncardiologists," the researchers noted (Arch. Intern. Med. 2011;171:1082-7).

Dr. Halley and her colleagues examined diastolic dysfunction in the absence of systolic dysfunction, because the clinical relevance of the condition has been questioned. Many medical disorders associated with diastolic dysfunction, such as hypertension, coronary artery disease, obesity, and diabetes, are themselves predictors of increased mortality, so it was unclear whether diastolic dysfunction was an independent contributor.

The researchers reviewed the records of consecutive patients who underwent outpatient echocardiography at the Cleveland Clinic and its satellite facilities between 1996 and 2005. They identified 36,261 patients (65,696 echocardiographic tests) who had normal ejection fractions signaling preserved systolic function.

The mean patient age was 58 years, and slightly more than half of the study subjects were women. The subjects were typical of patients usually referred for echocardiography – they frequently had cardiovascular risk factors such as dyslipidemia (35%), hypertension (15%), and diabetes (12%), but usually did not have established CV disease, such as congestive heart failure (4%), peripheral vascular disease (1%), or coronary artery disease (0.6%).

The most frequent indications for ordering the echocardiography were symptom assessment, assessment of ventricular or valvular function, evaluation of suspected or known CAD, and assessment of arrhythmia or ECG abnormalities.

The prevalence of diastolic dysfunction was high, at 65%. The dysfunction was mild in the majority of patients (nearly 60%), moderate in 4.8%, and severe in 0.4%.

During an average follow-up of 6 years, there were 5,789 deaths. Unadjusted all-cause mortality was higher with any degree of diastolic dysfunction than with normal diastolic function: 21% with mild diastolic dysfunction, 24% with moderate diastolic dysfunction, and 39% with severe diastolic dysfunction, compared with 7% in patients who had normal diastolic function.

However, because comorbidities that could confound the analyses were more common among patients with more severe diastolic dysfunction, propensity matching and statistical controlling for comorbidities were performed. Subsequent analysis showed that only moderate and severe diastolic dysfunction raised mortality risk.

Eight-year survival estimates were 78% for patients with normal diastolic function and 72% for mild diastolic dysfunction, compared with 68% for moderate diastolic dysfunction and 58% for severe diastolic dysfunction.

"For the first time, to our knowledge, moderate and severe diastolic dysfunction have been shown to be independent predictors of mortality rate," Dr. Halley and her associates said.

The mechanisms by which diastolic dysfunction raises mortality are not yet known, nor is it known whether therapies targeting such dysfunction can be developed, or whether they would reduce mortality. "However, our results suggest that an increased awareness of the clinical significance of advanced diastolic dysfunction may lead to earlier identification of those patients who are at risk, especially at a preclinical stage," the investigators noted.

They added that this study was limited in that it was retrospective and involved only a single institution.

This new study provides "an important piece of the puzzle," shedding light on the continuum from mild and asymptomatic to severe and symptomatic diastolic dysfunction, said Dr. Ileana L. Piña in remarks taken from her invited commentary that accompanied Dr. Halley’s report (Arch. Intern. Med. 2011;171:1088-9).

The findings that diastolic dysfunction is so common – affecting 65% of this study cohort – and that physicians must be alert to the prognostic value of more severe dysfunction are "novel and important for physicians."

In the future, it will be critical to elucidate the missing link between diagnosis of diastolic dysfunction on echocardiography and the later presentation of older patients, particularly older women, with acute decompensated heart failure in which systolic function is preserved, Dr. Piña of the departments of epidemiology and biostatistics at Case Western Reserve University, Cleveland, added.

One of Dr. Halley’s associates reported ties to GE Healthcare, Philips Healthcare, and Siemens AG. Dr. Piña reported no financial disclosures.

Moderate and severe diastolic dysfunction in patients who have normal systolic function increased all-cause mortality, according to a report in the June 27 issue of the Archives of Internal Medicine.

Such diastolic dysfunction is usually preclinical and often is identified on outpatient echocardiography that was done to assess nonspecific symptoms, ventricular or valvular function, arrhythmia, or ECG abnormalities. Its clinical significance has not been documented until now, said Dr. Carmel M. Halley of the Heart and Vascular Institute at the Cleveland Clinic, and her associates.

"Because the use of echocardiography as a clinical tool in the outpatient setting continues to increase ... our study provides the physician with a prognostic context when diastolic dysfunction is reported, especially because most procedures are requested by noncardiologists," the researchers noted (Arch. Intern. Med. 2011;171:1082-7).

Dr. Halley and her colleagues examined diastolic dysfunction in the absence of systolic dysfunction, because the clinical relevance of the condition has been questioned. Many medical disorders associated with diastolic dysfunction, such as hypertension, coronary artery disease, obesity, and diabetes, are themselves predictors of increased mortality, so it was unclear whether diastolic dysfunction was an independent contributor.

The researchers reviewed the records of consecutive patients who underwent outpatient echocardiography at the Cleveland Clinic and its satellite facilities between 1996 and 2005. They identified 36,261 patients (65,696 echocardiographic tests) who had normal ejection fractions signaling preserved systolic function.

The mean patient age was 58 years, and slightly more than half of the study subjects were women. The subjects were typical of patients usually referred for echocardiography – they frequently had cardiovascular risk factors such as dyslipidemia (35%), hypertension (15%), and diabetes (12%), but usually did not have established CV disease, such as congestive heart failure (4%), peripheral vascular disease (1%), or coronary artery disease (0.6%).

The most frequent indications for ordering the echocardiography were symptom assessment, assessment of ventricular or valvular function, evaluation of suspected or known CAD, and assessment of arrhythmia or ECG abnormalities.

The prevalence of diastolic dysfunction was high, at 65%. The dysfunction was mild in the majority of patients (nearly 60%), moderate in 4.8%, and severe in 0.4%.

During an average follow-up of 6 years, there were 5,789 deaths. Unadjusted all-cause mortality was higher with any degree of diastolic dysfunction than with normal diastolic function: 21% with mild diastolic dysfunction, 24% with moderate diastolic dysfunction, and 39% with severe diastolic dysfunction, compared with 7% in patients who had normal diastolic function.

However, because comorbidities that could confound the analyses were more common among patients with more severe diastolic dysfunction, propensity matching and statistical controlling for comorbidities were performed. Subsequent analysis showed that only moderate and severe diastolic dysfunction raised mortality risk.

Eight-year survival estimates were 78% for patients with normal diastolic function and 72% for mild diastolic dysfunction, compared with 68% for moderate diastolic dysfunction and 58% for severe diastolic dysfunction.

"For the first time, to our knowledge, moderate and severe diastolic dysfunction have been shown to be independent predictors of mortality rate," Dr. Halley and her associates said.

The mechanisms by which diastolic dysfunction raises mortality are not yet known, nor is it known whether therapies targeting such dysfunction can be developed, or whether they would reduce mortality. "However, our results suggest that an increased awareness of the clinical significance of advanced diastolic dysfunction may lead to earlier identification of those patients who are at risk, especially at a preclinical stage," the investigators noted.

They added that this study was limited in that it was retrospective and involved only a single institution.

This new study provides "an important piece of the puzzle," shedding light on the continuum from mild and asymptomatic to severe and symptomatic diastolic dysfunction, said Dr. Ileana L. Piña in remarks taken from her invited commentary that accompanied Dr. Halley’s report (Arch. Intern. Med. 2011;171:1088-9).

The findings that diastolic dysfunction is so common – affecting 65% of this study cohort – and that physicians must be alert to the prognostic value of more severe dysfunction are "novel and important for physicians."

In the future, it will be critical to elucidate the missing link between diagnosis of diastolic dysfunction on echocardiography and the later presentation of older patients, particularly older women, with acute decompensated heart failure in which systolic function is preserved, Dr. Piña of the departments of epidemiology and biostatistics at Case Western Reserve University, Cleveland, added.

One of Dr. Halley’s associates reported ties to GE Healthcare, Philips Healthcare, and Siemens AG. Dr. Piña reported no financial disclosures.