Heart Failure

Major Finding: Community-dwelling older adults in the highest quartile for their serum cardiac troponin T level, as measured with a high-sensitivity assay, had a two- to threefold increased risk for new-onset heart failure and for cardiovascular death during a median follow-up of 12 years.

Data Source: The 4,221 unselected U.S. residents age 65 or older (median age of 71) enrolled in the Cardiovascular Health Study.

Disclosures: The study was partially funded by Roche Diagnostics, which markets a high-sensitivity cardiac troponin T assay. Dr. deFilippi said that he has served as a consultant to and has received honoraria and grant support from Roche Diagnostics and from Siemens Healthcare Diagnostics. He has also been a consultant to and received grant support from Critical Diagnostics and BG Medicine.

CHICAGO — Higher serum concentrations of cardiac troponin T independently predicted an increased rate of new-onset heart failure and cardiovascular death in a longitudinal study of more than 4,000 elderly, community-dwelling Americans with a median follow-up of 12 years.

“Measurement of cTnT [cardiac troponin T] may be useful in cardiovascular risk stratification in older adults,” Dr. Christopher R. deFilippi said at the scientific sessions.

Assessing cTnT's role as a risk predictor became possible with the recent availability of high-sensitivity assays. Previous studies using conventional cTnT assays found roughly 4% of the general elderly population had detectable levels; in Dr. deFilippi's new study, 66% of community-dwelling U.S. adults with a median age of 71 had detectable cTnT levels. The high-sensitivity test produces “about a 10-fold increase in the number of people with detectable cTnT; that's what gives us a dynamic range,” said Dr. deFilippi, a cardiologist at the University of Maryland in Baltimore.

Results from two other studies presented at the meeting and a third study published in early December showed similar links between high levels of cTnT and cardiovascular events, cardiac structure, and death (see box).

The consistent findings from all these studies show that cTnT “is a pretty good risk predictor. Cardiac troponin offers a very easy way for a physician to say that a person is at high risk” for new-onset heart failure, cardiovascular death, or other cardiovascular disease events, Dr. deFilippi said in an interview.

“I look at cardiac troponin T as early biochemical evidence of pathology. Finding a high level in a person could be a wake-up call. It gives some of the earliest, direct evidence with a cardiac-specific molecule that pathology is taking place,” independent of traditional risk markers, he said.

“Cardiac troponin T could be the summation of all other risk factors. We use cholesterol level as a motivator, even though it is much less effective for measuring risk,” Dr. deFilippi explained.

Another attractive feature of measuring cTnT is that the evidence collected by Dr. deFilippi and his associates suggest that in some people high levels are reversible, and when levels drop a person's risk drops.

In the analyses so far, the strongest correlation with a lowered serum level of cTnT has been a person's level of activity and exercise, he said.

The high-sensitivity cardiac troponin T test has not yet received marketing approval from the Food and Drug Administration, but is commercially available in Europe.

To examine the prognostic ability of cTnT, Dr. deFilippi and his associates used serum specimens collected from 4,221 community-dwelling Americans aged 65 or older enrolled in the Cardiovascular Health Study.

At baseline, 2,794 (66%) of the participants had a detectable level of cTnT, at least 3 pg/mL, and their median age was 71.

During a median follow-up of almost 12 years, the incidence of heart failure and cardiovascular death tracked along with baseline levels of cTnT. Among the one-third of patients with an undetectable level at baseline the rate of new-onset heart failure during follow-up averaged 1.6% per year. Among people in the highest quintile of cTnT level, greater than 12.9 pg/mL, the incident heart failure rate averaged 6.4% per year. “It's a huge difference,” he said.

In an analysis that adjusted for demographic differences and traditional risk factors including systolic blood pressure, smoking status, serum creatinine, and left ventricular size, people with baseline cTnT levels above the median all had a significantly increased risk for both end points.

The quintile of people with the highest cardiac troponin T level had a 2.5-fold increased risk of new-onset heart failure and a threefold increased risk of cardiovascular death compared with those who had an undetectable level at baseline.

Even when also adjusted for baseline levels of NT-pro brain natriuretic peptide and C-reactive protein, people in the highest quintile for baseline level had about a twofold higher rate of heart failure and cardiovascular death during follow-up, Dr. deFilippi reported.

Records on follow-up cTnT levels, measured 2-3 years after baseline in 86% of the study participants, showed that among those with a detectable cTnT level at baseline, nearly two-thirds stayed at about the same level, 22% increased by more than 50%, and 14% decreased by more than 50%.

The high increasers had their subsequent heart failure and cardiovascular death rates rise by about 50% compared with people with more moderate changes.

In contrast, among those whose levels fell by more than 50% during follow-up subsequent event rates dropped by about 25% compared with those with less change in their cTnT level.

Concurrent with Dr. deFilippi's talk at the meeting the findings also appeared in an article published online in JAMA (2010; 304:doi:10.1001/jama.2010.1708).

The results also identified some people with very high levels at baseline that then fell to an undetectable level at their second cTnT measurement. Few people showed this kind of change, but it occurred often enough for Dr. deFilippi to speculate that certain actions can effectively lower serum cardiac troponin T levels.

The source of the cTnT isn't clear. Dr. deFilippi believes it's caused by a chronic process, although the specifics remain unknown. “It's unlikely an ischemic cause,” he said. “The issue is, once you see [a high level] can you intervene? Right now, that's an open question.”

Over 12 years, the rates of heart failure and cardiac death tracked along with baseline cTnT levels.

Source DR. DEFILIPPI

Other Studies Using High-Sensitivity Test Support cTnT's Risk-Marker Role

CHICAGO – In addition to the report by Dr. deFilippi, three other research groups recently reported finding significant links between elevated serum levels of cardiac troponin T and an increased risk for cardiovascular events:

▸ Researchers measured cardiac troponin T (cTnT) using a high-sensitivity assay in 10,820 Americans aged 53-75 without prevalent cardiovascular disease enrolled in the Atherosclerosis Risk in Communities (ARIC) study. In these people, with an average age of 63 years, 61% had a detectable level of serum cTnT at baseline using the high-sensitivity test. During an average follow-up of 10 years, Researchers found a significant link between detectable levels at baseline and death and hospitalization for heart failure during follow-up, Dr. Justin T. Saunders from Baylor College of Medicine in Houston reported at the scientific sessions.

▸ In a second, independent study, researchers measured serum cTnT with the high-sensitivity assay in women enrolled in the Women's Health Study. The current analysis focused on 512 women with diabetes at the time of their serum sampling and 564 women without diabetes. Among the women with diabetes, detectable levels of cTnT excisted in 56% of those who had cardiovascular disease events during follow-up and in 42% of the women who did not later have an event, a statistically significant difference. The event that seemed most responsible for this difference was cardiovascular disease death. Among the women without diabetes, detectable levels of cTnT appeared to have no significant relationship to subsequent cardiovascular disease events. Detectable cTnT appeared in 34% of the women with a subsequent event and in 30% of those without a later event, Dr. Brendan M. Everett from Brigham and Women's Hospital in Boston reported at the scientific sessions.

▸ In the third study, researchers ran high-sensitivity cTnT measures on 3,546 people aged 30-65 enrolled in the Dallas Heart Study. They found detectable levels in 25% of the participants. The prevalence of detectable levels depended on age and gender. People younger than 40 had a prevalence rate of 14% compared with a prevalence of 58% in people aged 65 or older. Men had a prevalence rate of 37%, compared with a rate of 13% in women. During a median follow-up of 6.4 years, in an analysis that adjusted for a series of baseline variables and risk factors, people in the highest quintile for serum cTnT level had a statistically significant, greater than fourfold increased risk for both all-cause death and cardiovascular death, said Dr. James A. de Lemos, from the University of Texas Southwestern Medical Center, and his associates in a report published in the Dec. 8, 2010, issue of JAMA (2010;304:2503-12).

Dr. Saunders had no disclosures.

Dr. Everett said he had received research grants from Roche Diagnostics.

Dr. de Lemos said that he has received research grants from Roche Diagnostics and Biosite, and consulting fees, lecture honoraria, or both from Tethys Biomedical, Johnson & Johnson, Roche Diagnostics, Biosite/Invemess, Siemens, AstraZeneca, Pfizer, Bristol Myers Squibb/Sanofi Aventis, and Merck.

– Mitchel L. Zoler

Major Finding: Community-dwelling older adults in the highest quartile for their serum cardiac troponin T level, as measured with a high-sensitivity assay, had a two- to threefold increased risk for new-onset heart failure and for cardiovascular death during a median follow-up of 12 years.

Data Source: The 4,221 unselected U.S. residents age 65 or older (median age of 71) enrolled in the Cardiovascular Health Study.

Disclosures: The study was partially funded by Roche Diagnostics, which markets a high-sensitivity cardiac troponin T assay. Dr. deFilippi said that he has served as a consultant to and has received honoraria and grant support from Roche Diagnostics and from Siemens Healthcare Diagnostics. He has also been a consultant to and received grant support from Critical Diagnostics and BG Medicine.

CHICAGO — Higher serum concentrations of cardiac troponin T independently predicted an increased rate of new-onset heart failure and cardiovascular death in a longitudinal study of more than 4,000 elderly, community-dwelling Americans with a median follow-up of 12 years.

“Measurement of cTnT [cardiac troponin T] may be useful in cardiovascular risk stratification in older adults,” Dr. Christopher R. deFilippi said at the scientific sessions.

Assessing cTnT's role as a risk predictor became possible with the recent availability of high-sensitivity assays. Previous studies using conventional cTnT assays found roughly 4% of the general elderly population had detectable levels; in Dr. deFilippi's new study, 66% of community-dwelling U.S. adults with a median age of 71 had detectable cTnT levels. The high-sensitivity test produces “about a 10-fold increase in the number of people with detectable cTnT; that's what gives us a dynamic range,” said Dr. deFilippi, a cardiologist at the University of Maryland in Baltimore.

Results from two other studies presented at the meeting and a third study published in early December showed similar links between high levels of cTnT and cardiovascular events, cardiac structure, and death (see box).

The consistent findings from all these studies show that cTnT “is a pretty good risk predictor. Cardiac troponin offers a very easy way for a physician to say that a person is at high risk” for new-onset heart failure, cardiovascular death, or other cardiovascular disease events, Dr. deFilippi said in an interview.

“I look at cardiac troponin T as early biochemical evidence of pathology. Finding a high level in a person could be a wake-up call. It gives some of the earliest, direct evidence with a cardiac-specific molecule that pathology is taking place,” independent of traditional risk markers, he said.

“Cardiac troponin T could be the summation of all other risk factors. We use cholesterol level as a motivator, even though it is much less effective for measuring risk,” Dr. deFilippi explained.

Another attractive feature of measuring cTnT is that the evidence collected by Dr. deFilippi and his associates suggest that in some people high levels are reversible, and when levels drop a person's risk drops.

In the analyses so far, the strongest correlation with a lowered serum level of cTnT has been a person's level of activity and exercise, he said.

The high-sensitivity cardiac troponin T test has not yet received marketing approval from the Food and Drug Administration, but is commercially available in Europe.

To examine the prognostic ability of cTnT, Dr. deFilippi and his associates used serum specimens collected from 4,221 community-dwelling Americans aged 65 or older enrolled in the Cardiovascular Health Study.

At baseline, 2,794 (66%) of the participants had a detectable level of cTnT, at least 3 pg/mL, and their median age was 71.

During a median follow-up of almost 12 years, the incidence of heart failure and cardiovascular death tracked along with baseline levels of cTnT. Among the one-third of patients with an undetectable level at baseline the rate of new-onset heart failure during follow-up averaged 1.6% per year. Among people in the highest quintile of cTnT level, greater than 12.9 pg/mL, the incident heart failure rate averaged 6.4% per year. “It's a huge difference,” he said.

In an analysis that adjusted for demographic differences and traditional risk factors including systolic blood pressure, smoking status, serum creatinine, and left ventricular size, people with baseline cTnT levels above the median all had a significantly increased risk for both end points.

The quintile of people with the highest cardiac troponin T level had a 2.5-fold increased risk of new-onset heart failure and a threefold increased risk of cardiovascular death compared with those who had an undetectable level at baseline.

Even when also adjusted for baseline levels of NT-pro brain natriuretic peptide and C-reactive protein, people in the highest quintile for baseline level had about a twofold higher rate of heart failure and cardiovascular death during follow-up, Dr. deFilippi reported.

Records on follow-up cTnT levels, measured 2-3 years after baseline in 86% of the study participants, showed that among those with a detectable cTnT level at baseline, nearly two-thirds stayed at about the same level, 22% increased by more than 50%, and 14% decreased by more than 50%.

The high increasers had their subsequent heart failure and cardiovascular death rates rise by about 50% compared with people with more moderate changes.

In contrast, among those whose levels fell by more than 50% during follow-up subsequent event rates dropped by about 25% compared with those with less change in their cTnT level.

Concurrent with Dr. deFilippi's talk at the meeting the findings also appeared in an article published online in JAMA (2010; 304:doi:10.1001/jama.2010.1708).

The results also identified some people with very high levels at baseline that then fell to an undetectable level at their second cTnT measurement. Few people showed this kind of change, but it occurred often enough for Dr. deFilippi to speculate that certain actions can effectively lower serum cardiac troponin T levels.

The source of the cTnT isn't clear. Dr. deFilippi believes it's caused by a chronic process, although the specifics remain unknown. “It's unlikely an ischemic cause,” he said. “The issue is, once you see [a high level] can you intervene? Right now, that's an open question.”

Over 12 years, the rates of heart failure and cardiac death tracked along with baseline cTnT levels.

Source DR. DEFILIPPI

Other Studies Using High-Sensitivity Test Support cTnT's Risk-Marker Role

CHICAGO – In addition to the report by Dr. deFilippi, three other research groups recently reported finding significant links between elevated serum levels of cardiac troponin T and an increased risk for cardiovascular events:

▸ Researchers measured cardiac troponin T (cTnT) using a high-sensitivity assay in 10,820 Americans aged 53-75 without prevalent cardiovascular disease enrolled in the Atherosclerosis Risk in Communities (ARIC) study. In these people, with an average age of 63 years, 61% had a detectable level of serum cTnT at baseline using the high-sensitivity test. During an average follow-up of 10 years, Researchers found a significant link between detectable levels at baseline and death and hospitalization for heart failure during follow-up, Dr. Justin T. Saunders from Baylor College of Medicine in Houston reported at the scientific sessions.

▸ In a second, independent study, researchers measured serum cTnT with the high-sensitivity assay in women enrolled in the Women's Health Study. The current analysis focused on 512 women with diabetes at the time of their serum sampling and 564 women without diabetes. Among the women with diabetes, detectable levels of cTnT excisted in 56% of those who had cardiovascular disease events during follow-up and in 42% of the women who did not later have an event, a statistically significant difference. The event that seemed most responsible for this difference was cardiovascular disease death. Among the women without diabetes, detectable levels of cTnT appeared to have no significant relationship to subsequent cardiovascular disease events. Detectable cTnT appeared in 34% of the women with a subsequent event and in 30% of those without a later event, Dr. Brendan M. Everett from Brigham and Women's Hospital in Boston reported at the scientific sessions.

▸ In the third study, researchers ran high-sensitivity cTnT measures on 3,546 people aged 30-65 enrolled in the Dallas Heart Study. They found detectable levels in 25% of the participants. The prevalence of detectable levels depended on age and gender. People younger than 40 had a prevalence rate of 14% compared with a prevalence of 58% in people aged 65 or older. Men had a prevalence rate of 37%, compared with a rate of 13% in women. During a median follow-up of 6.4 years, in an analysis that adjusted for a series of baseline variables and risk factors, people in the highest quintile for serum cTnT level had a statistically significant, greater than fourfold increased risk for both all-cause death and cardiovascular death, said Dr. James A. de Lemos, from the University of Texas Southwestern Medical Center, and his associates in a report published in the Dec. 8, 2010, issue of JAMA (2010;304:2503-12).

Dr. Saunders had no disclosures.

Dr. Everett said he had received research grants from Roche Diagnostics.

Dr. de Lemos said that he has received research grants from Roche Diagnostics and Biosite, and consulting fees, lecture honoraria, or both from Tethys Biomedical, Johnson & Johnson, Roche Diagnostics, Biosite/Invemess, Siemens, AstraZeneca, Pfizer, Bristol Myers Squibb/Sanofi Aventis, and Merck.

– Mitchel L. Zoler

Major Finding: Community-dwelling older adults in the highest quartile for their serum cardiac troponin T level, as measured with a high-sensitivity assay, had a two- to threefold increased risk for new-onset heart failure and for cardiovascular death during a median follow-up of 12 years.

Data Source: The 4,221 unselected U.S. residents age 65 or older (median age of 71) enrolled in the Cardiovascular Health Study.

Disclosures: The study was partially funded by Roche Diagnostics, which markets a high-sensitivity cardiac troponin T assay. Dr. deFilippi said that he has served as a consultant to and has received honoraria and grant support from Roche Diagnostics and from Siemens Healthcare Diagnostics. He has also been a consultant to and received grant support from Critical Diagnostics and BG Medicine.

CHICAGO — Higher serum concentrations of cardiac troponin T independently predicted an increased rate of new-onset heart failure and cardiovascular death in a longitudinal study of more than 4,000 elderly, community-dwelling Americans with a median follow-up of 12 years.

“Measurement of cTnT [cardiac troponin T] may be useful in cardiovascular risk stratification in older adults,” Dr. Christopher R. deFilippi said at the scientific sessions.

Assessing cTnT's role as a risk predictor became possible with the recent availability of high-sensitivity assays. Previous studies using conventional cTnT assays found roughly 4% of the general elderly population had detectable levels; in Dr. deFilippi's new study, 66% of community-dwelling U.S. adults with a median age of 71 had detectable cTnT levels. The high-sensitivity test produces “about a 10-fold increase in the number of people with detectable cTnT; that's what gives us a dynamic range,” said Dr. deFilippi, a cardiologist at the University of Maryland in Baltimore.

Results from two other studies presented at the meeting and a third study published in early December showed similar links between high levels of cTnT and cardiovascular events, cardiac structure, and death (see box).

The consistent findings from all these studies show that cTnT “is a pretty good risk predictor. Cardiac troponin offers a very easy way for a physician to say that a person is at high risk” for new-onset heart failure, cardiovascular death, or other cardiovascular disease events, Dr. deFilippi said in an interview.

“I look at cardiac troponin T as early biochemical evidence of pathology. Finding a high level in a person could be a wake-up call. It gives some of the earliest, direct evidence with a cardiac-specific molecule that pathology is taking place,” independent of traditional risk markers, he said.

“Cardiac troponin T could be the summation of all other risk factors. We use cholesterol level as a motivator, even though it is much less effective for measuring risk,” Dr. deFilippi explained.

Another attractive feature of measuring cTnT is that the evidence collected by Dr. deFilippi and his associates suggest that in some people high levels are reversible, and when levels drop a person's risk drops.

In the analyses so far, the strongest correlation with a lowered serum level of cTnT has been a person's level of activity and exercise, he said.

The high-sensitivity cardiac troponin T test has not yet received marketing approval from the Food and Drug Administration, but is commercially available in Europe.

To examine the prognostic ability of cTnT, Dr. deFilippi and his associates used serum specimens collected from 4,221 community-dwelling Americans aged 65 or older enrolled in the Cardiovascular Health Study.

At baseline, 2,794 (66%) of the participants had a detectable level of cTnT, at least 3 pg/mL, and their median age was 71.

During a median follow-up of almost 12 years, the incidence of heart failure and cardiovascular death tracked along with baseline levels of cTnT. Among the one-third of patients with an undetectable level at baseline the rate of new-onset heart failure during follow-up averaged 1.6% per year. Among people in the highest quintile of cTnT level, greater than 12.9 pg/mL, the incident heart failure rate averaged 6.4% per year. “It's a huge difference,” he said.

In an analysis that adjusted for demographic differences and traditional risk factors including systolic blood pressure, smoking status, serum creatinine, and left ventricular size, people with baseline cTnT levels above the median all had a significantly increased risk for both end points.

The quintile of people with the highest cardiac troponin T level had a 2.5-fold increased risk of new-onset heart failure and a threefold increased risk of cardiovascular death compared with those who had an undetectable level at baseline.

Even when also adjusted for baseline levels of NT-pro brain natriuretic peptide and C-reactive protein, people in the highest quintile for baseline level had about a twofold higher rate of heart failure and cardiovascular death during follow-up, Dr. deFilippi reported.

Records on follow-up cTnT levels, measured 2-3 years after baseline in 86% of the study participants, showed that among those with a detectable cTnT level at baseline, nearly two-thirds stayed at about the same level, 22% increased by more than 50%, and 14% decreased by more than 50%.

The high increasers had their subsequent heart failure and cardiovascular death rates rise by about 50% compared with people with more moderate changes.

In contrast, among those whose levels fell by more than 50% during follow-up subsequent event rates dropped by about 25% compared with those with less change in their cTnT level.

Concurrent with Dr. deFilippi's talk at the meeting the findings also appeared in an article published online in JAMA (2010; 304:doi:10.1001/jama.2010.1708).

The results also identified some people with very high levels at baseline that then fell to an undetectable level at their second cTnT measurement. Few people showed this kind of change, but it occurred often enough for Dr. deFilippi to speculate that certain actions can effectively lower serum cardiac troponin T levels.

The source of the cTnT isn't clear. Dr. deFilippi believes it's caused by a chronic process, although the specifics remain unknown. “It's unlikely an ischemic cause,” he said. “The issue is, once you see [a high level] can you intervene? Right now, that's an open question.”

Over 12 years, the rates of heart failure and cardiac death tracked along with baseline cTnT levels.

Source DR. DEFILIPPI

Other Studies Using High-Sensitivity Test Support cTnT's Risk-Marker Role

CHICAGO – In addition to the report by Dr. deFilippi, three other research groups recently reported finding significant links between elevated serum levels of cardiac troponin T and an increased risk for cardiovascular events:

▸ Researchers measured cardiac troponin T (cTnT) using a high-sensitivity assay in 10,820 Americans aged 53-75 without prevalent cardiovascular disease enrolled in the Atherosclerosis Risk in Communities (ARIC) study. In these people, with an average age of 63 years, 61% had a detectable level of serum cTnT at baseline using the high-sensitivity test. During an average follow-up of 10 years, Researchers found a significant link between detectable levels at baseline and death and hospitalization for heart failure during follow-up, Dr. Justin T. Saunders from Baylor College of Medicine in Houston reported at the scientific sessions.

▸ In a second, independent study, researchers measured serum cTnT with the high-sensitivity assay in women enrolled in the Women's Health Study. The current analysis focused on 512 women with diabetes at the time of their serum sampling and 564 women without diabetes. Among the women with diabetes, detectable levels of cTnT excisted in 56% of those who had cardiovascular disease events during follow-up and in 42% of the women who did not later have an event, a statistically significant difference. The event that seemed most responsible for this difference was cardiovascular disease death. Among the women without diabetes, detectable levels of cTnT appeared to have no significant relationship to subsequent cardiovascular disease events. Detectable cTnT appeared in 34% of the women with a subsequent event and in 30% of those without a later event, Dr. Brendan M. Everett from Brigham and Women's Hospital in Boston reported at the scientific sessions.

▸ In the third study, researchers ran high-sensitivity cTnT measures on 3,546 people aged 30-65 enrolled in the Dallas Heart Study. They found detectable levels in 25% of the participants. The prevalence of detectable levels depended on age and gender. People younger than 40 had a prevalence rate of 14% compared with a prevalence of 58% in people aged 65 or older. Men had a prevalence rate of 37%, compared with a rate of 13% in women. During a median follow-up of 6.4 years, in an analysis that adjusted for a series of baseline variables and risk factors, people in the highest quintile for serum cTnT level had a statistically significant, greater than fourfold increased risk for both all-cause death and cardiovascular death, said Dr. James A. de Lemos, from the University of Texas Southwestern Medical Center, and his associates in a report published in the Dec. 8, 2010, issue of JAMA (2010;304:2503-12).

Dr. Saunders had no disclosures.

Dr. Everett said he had received research grants from Roche Diagnostics.

Dr. de Lemos said that he has received research grants from Roche Diagnostics and Biosite, and consulting fees, lecture honoraria, or both from Tethys Biomedical, Johnson & Johnson, Roche Diagnostics, Biosite/Invemess, Siemens, AstraZeneca, Pfizer, Bristol Myers Squibb/Sanofi Aventis, and Merck.

– Mitchel L. Zoler

Major Finding: Addition of CRT to an ICD significantly reduced the rate of death and heart failure hospitalization by 25% in patients with NYHA class II or III heart failure.

Data Source: Randomized trial in 1,798 patients with mild to moderate heart failure.

Disclosures: RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Yancy said he had no financial conflicts of interest.

CHICAGO – for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials, including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009;361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

Major Finding: Addition of CRT to an ICD significantly reduced the rate of death and heart failure hospitalization by 25% in patients with NYHA class II or III heart failure.

Data Source: Randomized trial in 1,798 patients with mild to moderate heart failure.

Disclosures: RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Yancy said he had no financial conflicts of interest.

CHICAGO – for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials, including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009;361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

Major Finding: Addition of CRT to an ICD significantly reduced the rate of death and heart failure hospitalization by 25% in patients with NYHA class II or III heart failure.

Data Source: Randomized trial in 1,798 patients with mild to moderate heart failure.

Disclosures: RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Yancy said he had no financial conflicts of interest.

CHICAGO – for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials, including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009;361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

STOCKHOLM – Suboptimal glycemic control is an independent risk factor for a linear increase in the rate of new-onset heart failure in patients with type 2 diabetes, a large Scottish prospective case-control study indicates.

Moreover, in type 2 diabetes patients who already have established heart failure, poor glycemic control is independently associated with increased mortality, Dr. Chim Choy Lang reported at the congress.

These were the key findings in a new analysis from the Tayside Study, which is directed by Dr. Lang. The ongoing project provides an unusual opportunity to prospectively follow an entire Scottish community, population 400,000.

“We can track patients with diabetes mellitus, looking at mean [hemoglobin A_1c] over time, and see who develops heart failure,” Dr. Lang said in an interview.

“Our bioinformatics platform allows us to track all sorts of biologic variables, prescribing information, and outcomes data,” he explained.

The analysis of Tayside Study data was performed because controversy has arisen surrounding the relationship between glycemic control in type 2 diabetes and heart failure.

Some recent evidence has suggested that tight metabolic control in type 2 diabetes is actually associated with worse survival of patients in the setting of heart failure.

“It should be noted that most of these studies were based on a single measure of HbA_1c,” observed Dr. Lang, a cardiologist at the University of Dundee. “I think there's always cause for concern about that kind of analysis,” he added.

Dr. Lang reported on more than 9,000 Tayside residents with type 2 diabetes, 841 of whom developed heart failure during the period from 1991 to 2008. Each diabetic heart failure patient was matched by age, gender, and date of diagnosis of diabetes to five controls.

When Dr. Lang and his coinvestigators conducted a multivariate logistic regression analysis, they found that the mean HbA1c _level during the study period was associated in linear fashion with the risk of later developing heart failure.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure after the researchers controlled for patients' mean arterial pressure and use of thiazoli-dinediones.

Further, in type 2 diabetic patients who were diagnosed with heart failure, each 1% increase in mean HbA1_c was independently associated with an adjusted 16% increase in all-cause mortality, according to Dr. Lang.

“I think our findings are an argument for tight glycemic control in diabetic patients with heart failure. The question is how to achieve that. I'm a big believer in metformin for that purpose,” the cardiologist said.

When Dr. Lang was asked whether the increased risk of mortality documented in diabetic patients with poor glycemic control and heart failure is a marker for poor adherence to standard heart failure medications or is due to the adverse effects of high blood glucose, he said that's a key unsettled question.

“We have the ability to look at treatment adherence in this cohort and are doing so at the moment,” Dr. Lang noted.

He declared that he had no financial conflicts in connection with the study, which was conducted free of industry involvement.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure.

Source DR. LANG

STOCKHOLM – Suboptimal glycemic control is an independent risk factor for a linear increase in the rate of new-onset heart failure in patients with type 2 diabetes, a large Scottish prospective case-control study indicates.

Moreover, in type 2 diabetes patients who already have established heart failure, poor glycemic control is independently associated with increased mortality, Dr. Chim Choy Lang reported at the congress.

These were the key findings in a new analysis from the Tayside Study, which is directed by Dr. Lang. The ongoing project provides an unusual opportunity to prospectively follow an entire Scottish community, population 400,000.

“We can track patients with diabetes mellitus, looking at mean [hemoglobin A_1c] over time, and see who develops heart failure,” Dr. Lang said in an interview.

“Our bioinformatics platform allows us to track all sorts of biologic variables, prescribing information, and outcomes data,” he explained.

The analysis of Tayside Study data was performed because controversy has arisen surrounding the relationship between glycemic control in type 2 diabetes and heart failure.

Some recent evidence has suggested that tight metabolic control in type 2 diabetes is actually associated with worse survival of patients in the setting of heart failure.

“It should be noted that most of these studies were based on a single measure of HbA_1c,” observed Dr. Lang, a cardiologist at the University of Dundee. “I think there's always cause for concern about that kind of analysis,” he added.

Dr. Lang reported on more than 9,000 Tayside residents with type 2 diabetes, 841 of whom developed heart failure during the period from 1991 to 2008. Each diabetic heart failure patient was matched by age, gender, and date of diagnosis of diabetes to five controls.

When Dr. Lang and his coinvestigators conducted a multivariate logistic regression analysis, they found that the mean HbA1c _level during the study period was associated in linear fashion with the risk of later developing heart failure.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure after the researchers controlled for patients' mean arterial pressure and use of thiazoli-dinediones.

Further, in type 2 diabetic patients who were diagnosed with heart failure, each 1% increase in mean HbA1_c was independently associated with an adjusted 16% increase in all-cause mortality, according to Dr. Lang.

“I think our findings are an argument for tight glycemic control in diabetic patients with heart failure. The question is how to achieve that. I'm a big believer in metformin for that purpose,” the cardiologist said.

When Dr. Lang was asked whether the increased risk of mortality documented in diabetic patients with poor glycemic control and heart failure is a marker for poor adherence to standard heart failure medications or is due to the adverse effects of high blood glucose, he said that's a key unsettled question.

“We have the ability to look at treatment adherence in this cohort and are doing so at the moment,” Dr. Lang noted.

He declared that he had no financial conflicts in connection with the study, which was conducted free of industry involvement.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure.

Source DR. LANG

STOCKHOLM – Suboptimal glycemic control is an independent risk factor for a linear increase in the rate of new-onset heart failure in patients with type 2 diabetes, a large Scottish prospective case-control study indicates.

Moreover, in type 2 diabetes patients who already have established heart failure, poor glycemic control is independently associated with increased mortality, Dr. Chim Choy Lang reported at the congress.

These were the key findings in a new analysis from the Tayside Study, which is directed by Dr. Lang. The ongoing project provides an unusual opportunity to prospectively follow an entire Scottish community, population 400,000.

“We can track patients with diabetes mellitus, looking at mean [hemoglobin A_1c] over time, and see who develops heart failure,” Dr. Lang said in an interview.

“Our bioinformatics platform allows us to track all sorts of biologic variables, prescribing information, and outcomes data,” he explained.

The analysis of Tayside Study data was performed because controversy has arisen surrounding the relationship between glycemic control in type 2 diabetes and heart failure.

Some recent evidence has suggested that tight metabolic control in type 2 diabetes is actually associated with worse survival of patients in the setting of heart failure.

“It should be noted that most of these studies were based on a single measure of HbA_1c,” observed Dr. Lang, a cardiologist at the University of Dundee. “I think there's always cause for concern about that kind of analysis,” he added.

Dr. Lang reported on more than 9,000 Tayside residents with type 2 diabetes, 841 of whom developed heart failure during the period from 1991 to 2008. Each diabetic heart failure patient was matched by age, gender, and date of diagnosis of diabetes to five controls.

When Dr. Lang and his coinvestigators conducted a multivariate logistic regression analysis, they found that the mean HbA1c _level during the study period was associated in linear fashion with the risk of later developing heart failure.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure after the researchers controlled for patients' mean arterial pressure and use of thiazoli-dinediones.

Further, in type 2 diabetic patients who were diagnosed with heart failure, each 1% increase in mean HbA1_c was independently associated with an adjusted 16% increase in all-cause mortality, according to Dr. Lang.

“I think our findings are an argument for tight glycemic control in diabetic patients with heart failure. The question is how to achieve that. I'm a big believer in metformin for that purpose,” the cardiologist said.

When Dr. Lang was asked whether the increased risk of mortality documented in diabetic patients with poor glycemic control and heart failure is a marker for poor adherence to standard heart failure medications or is due to the adverse effects of high blood glucose, he said that's a key unsettled question.

“We have the ability to look at treatment adherence in this cohort and are doing so at the moment,” Dr. Lang noted.

He declared that he had no financial conflicts in connection with the study, which was conducted free of industry involvement.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure.

Source DR. LANG

SAN DIEGO – Plasma levels of serotonin were significantly elevated in patients with decompensated systolic heart failure, compared with patients in the compensated state and with normal controls, according to a single-center study.

The finding suggests that serotonin has an active role in the progression of heart failure (HF), researchers led by Dr. Ahmed M. Selim reported during a poster session at the meeting.

“More studies should be done to test the sensitivity, specificity, and prognostic value of serotonin as a marker for congestive heart failure,” wrote the researchers from the department of cardiology at Albert Einstein College of Medicine, New York.

They noted that, while the relationship between HF and the serotoninergic system has been established in previous research, fluctuations in serotonin levels during the course of the disease and its correlation with exacerbation of HF have never been tested.

Dr. Selim and his associates measured plasma serotonin levels in 29 patients admitted with decompensated HF, 61 with stable HF, and 22 normal controls.

Overall, the mean age of patients was 55 years, and 62% were male.

The researchers reported that the mean serotonin level in the control group was 2.4 ng/mL, vs. 4.1 ng/mL in the compensated group and 11.8 ng/mL in the decompensated group. “All results were highly significant,” the researchers wrote.

Dr. Selim and his associates stated that they had no relevant financial conflicts of interest.

SAN DIEGO – Plasma levels of serotonin were significantly elevated in patients with decompensated systolic heart failure, compared with patients in the compensated state and with normal controls, according to a single-center study.

The finding suggests that serotonin has an active role in the progression of heart failure (HF), researchers led by Dr. Ahmed M. Selim reported during a poster session at the meeting.

“More studies should be done to test the sensitivity, specificity, and prognostic value of serotonin as a marker for congestive heart failure,” wrote the researchers from the department of cardiology at Albert Einstein College of Medicine, New York.

They noted that, while the relationship between HF and the serotoninergic system has been established in previous research, fluctuations in serotonin levels during the course of the disease and its correlation with exacerbation of HF have never been tested.

Dr. Selim and his associates measured plasma serotonin levels in 29 patients admitted with decompensated HF, 61 with stable HF, and 22 normal controls.

Overall, the mean age of patients was 55 years, and 62% were male.

The researchers reported that the mean serotonin level in the control group was 2.4 ng/mL, vs. 4.1 ng/mL in the compensated group and 11.8 ng/mL in the decompensated group. “All results were highly significant,” the researchers wrote.

Dr. Selim and his associates stated that they had no relevant financial conflicts of interest.

SAN DIEGO – Plasma levels of serotonin were significantly elevated in patients with decompensated systolic heart failure, compared with patients in the compensated state and with normal controls, according to a single-center study.

The finding suggests that serotonin has an active role in the progression of heart failure (HF), researchers led by Dr. Ahmed M. Selim reported during a poster session at the meeting.

“More studies should be done to test the sensitivity, specificity, and prognostic value of serotonin as a marker for congestive heart failure,” wrote the researchers from the department of cardiology at Albert Einstein College of Medicine, New York.

They noted that, while the relationship between HF and the serotoninergic system has been established in previous research, fluctuations in serotonin levels during the course of the disease and its correlation with exacerbation of HF have never been tested.

Dr. Selim and his associates measured plasma serotonin levels in 29 patients admitted with decompensated HF, 61 with stable HF, and 22 normal controls.

Overall, the mean age of patients was 55 years, and 62% were male.

The researchers reported that the mean serotonin level in the control group was 2.4 ng/mL, vs. 4.1 ng/mL in the compensated group and 11.8 ng/mL in the decompensated group. “All results were highly significant,” the researchers wrote.

Dr. Selim and his associates stated that they had no relevant financial conflicts of interest.

Major Finding: Patients with NYHA stage III or IV heart failure who received gene therapy with MYDICAR had cardiovascular-related hospital stays that averaged 2 fewer days than those who received placebo.

Data Source: A phase II study of 39 patients enrolled in the CUPID trial.

Disclosures: Celladon Corp. funded the trial. Dr. Greenberg said that he had no relevant financial disclosures.

SAN DIEGO – In a phase II study of patients with advanced heart failure, gene therapy with MYDICAR was found to be safe and was associated with benefit in clinical outcomes, symptoms, functional status, and cardiac structure.

Deficiency of the protein SERCA2a is central to the progression of heart failure, resulting in abnormal calcium transfer and impairing myocardial relaxation and contraction, Dr. Barry H. Greenberg said

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A viral vectoridelivers the SERCA2a gene.

The objectives of the study, known as CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease), were to evaluate safety and feasibility and to explore the activity and efficacy of MYDICAR in patients with advanced heart failure, said Dr. Greenberg, professor of medicine and director of the Advanced Heart Failure Treatment Program at the University of California, San Diego.

To be eligible for the trial, patients had to be 18–75 years old, have New York State Heart Association class III or IV heart failure caused by an ischemic or nonischemic etiology, have a maximal oxygen consumption of 20 mL/kg per minute or less, have a left ventricular fraction of 35% or less, and be on a stable, optimized heart failure regimen for 30 days.

Dr. Greenberg and his colleagues randomized 39 patients to one of three MYDICAR doses or to placebo, and all were treated via single intracoronary infusion. All patients were observed for 12 months, with primary analysis after 6 months of therapy.

CUPID's primary efficacy end point was defined as evidence of success in one of four areas: group-level analysis, individual analysis, time-to-event analysis, and duration of cardiovascular-related hospitalization analysis. All were deemed significant (P less than .2).

CUPID met the primary efficacy end point for high-dose MYDICAR treatment group vs. placebo in three of the four areas. In the group-level analysis, significant improvements were seen in the treatment group, compared with the placebo group, in 6-minute walk tests and end systolic volume, with no clinically significant worsening in any end point and numerical superiority to placebo in all other end points.

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group. In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but theidifferencedias not significantce.

In the duration of cardiovascular-related hospitalization analysis, the duration of stay was significantly shorter for the treatment group than for the placebo group (mean, 2 fewer days).

Improvements were seen in the treatment group, vs. placebo, in 6-minute walk tests and end systolic volume.

Source DR. GREENBERG

Major Finding: Patients with NYHA stage III or IV heart failure who received gene therapy with MYDICAR had cardiovascular-related hospital stays that averaged 2 fewer days than those who received placebo.

Data Source: A phase II study of 39 patients enrolled in the CUPID trial.

Disclosures: Celladon Corp. funded the trial. Dr. Greenberg said that he had no relevant financial disclosures.

SAN DIEGO – In a phase II study of patients with advanced heart failure, gene therapy with MYDICAR was found to be safe and was associated with benefit in clinical outcomes, symptoms, functional status, and cardiac structure.

Deficiency of the protein SERCA2a is central to the progression of heart failure, resulting in abnormal calcium transfer and impairing myocardial relaxation and contraction, Dr. Barry H. Greenberg said

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A viral vectoridelivers the SERCA2a gene.

The objectives of the study, known as CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease), were to evaluate safety and feasibility and to explore the activity and efficacy of MYDICAR in patients with advanced heart failure, said Dr. Greenberg, professor of medicine and director of the Advanced Heart Failure Treatment Program at the University of California, San Diego.

To be eligible for the trial, patients had to be 18–75 years old, have New York State Heart Association class III or IV heart failure caused by an ischemic or nonischemic etiology, have a maximal oxygen consumption of 20 mL/kg per minute or less, have a left ventricular fraction of 35% or less, and be on a stable, optimized heart failure regimen for 30 days.

Dr. Greenberg and his colleagues randomized 39 patients to one of three MYDICAR doses or to placebo, and all were treated via single intracoronary infusion. All patients were observed for 12 months, with primary analysis after 6 months of therapy.

CUPID's primary efficacy end point was defined as evidence of success in one of four areas: group-level analysis, individual analysis, time-to-event analysis, and duration of cardiovascular-related hospitalization analysis. All were deemed significant (P less than .2).

CUPID met the primary efficacy end point for high-dose MYDICAR treatment group vs. placebo in three of the four areas. In the group-level analysis, significant improvements were seen in the treatment group, compared with the placebo group, in 6-minute walk tests and end systolic volume, with no clinically significant worsening in any end point and numerical superiority to placebo in all other end points.

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group. In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but theidifferencedias not significantce.

In the duration of cardiovascular-related hospitalization analysis, the duration of stay was significantly shorter for the treatment group than for the placebo group (mean, 2 fewer days).

Improvements were seen in the treatment group, vs. placebo, in 6-minute walk tests and end systolic volume.

Source DR. GREENBERG

Major Finding: Patients with NYHA stage III or IV heart failure who received gene therapy with MYDICAR had cardiovascular-related hospital stays that averaged 2 fewer days than those who received placebo.

Data Source: A phase II study of 39 patients enrolled in the CUPID trial.

Disclosures: Celladon Corp. funded the trial. Dr. Greenberg said that he had no relevant financial disclosures.

SAN DIEGO – In a phase II study of patients with advanced heart failure, gene therapy with MYDICAR was found to be safe and was associated with benefit in clinical outcomes, symptoms, functional status, and cardiac structure.

Deficiency of the protein SERCA2a is central to the progression of heart failure, resulting in abnormal calcium transfer and impairing myocardial relaxation and contraction, Dr. Barry H. Greenberg said

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A viral vectoridelivers the SERCA2a gene.

The objectives of the study, known as CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease), were to evaluate safety and feasibility and to explore the activity and efficacy of MYDICAR in patients with advanced heart failure, said Dr. Greenberg, professor of medicine and director of the Advanced Heart Failure Treatment Program at the University of California, San Diego.

To be eligible for the trial, patients had to be 18–75 years old, have New York State Heart Association class III or IV heart failure caused by an ischemic or nonischemic etiology, have a maximal oxygen consumption of 20 mL/kg per minute or less, have a left ventricular fraction of 35% or less, and be on a stable, optimized heart failure regimen for 30 days.

Dr. Greenberg and his colleagues randomized 39 patients to one of three MYDICAR doses or to placebo, and all were treated via single intracoronary infusion. All patients were observed for 12 months, with primary analysis after 6 months of therapy.

CUPID's primary efficacy end point was defined as evidence of success in one of four areas: group-level analysis, individual analysis, time-to-event analysis, and duration of cardiovascular-related hospitalization analysis. All were deemed significant (P less than .2).

CUPID met the primary efficacy end point for high-dose MYDICAR treatment group vs. placebo in three of the four areas. In the group-level analysis, significant improvements were seen in the treatment group, compared with the placebo group, in 6-minute walk tests and end systolic volume, with no clinically significant worsening in any end point and numerical superiority to placebo in all other end points.

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group. In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but theidifferencedias not significantce.

In the duration of cardiovascular-related hospitalization analysis, the duration of stay was significantly shorter for the treatment group than for the placebo group (mean, 2 fewer days).

Improvements were seen in the treatment group, vs. placebo, in 6-minute walk tests and end systolic volume.

Source DR. GREENBERG

STOCKHOLM – The absence of signs and symptoms of congestion at discharge in patients hospitalized for acute decompensated heart failure does not predict a favorable prognosis, contrary to the conventional wisdom.

A new secondary analysis of the international EVEREST trial provides an important lesson in the everyday management of acute heart failure: “The fact that a patient improves in-hospital with diuretics and other medications is not sufficient. It's not 'mission accomplished,'” Dr. Mihai Gheorghiade said at the congress.

“There is a dissociation between signs and symptoms of congestion at discharge and outcomes. In spite of having a very low congestion score, the event rate in EVEREST during 10 months of follow-up was astronomical,” said Dr. Gheorghiade, professor of medicine and surgery and associate chief of cardiology at Northwestern University, Chicago.

EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) was a double-blind study that randomized 4,133 patients with worsening heart failure and a left ventricular ejection fraction of 40% or less to the oral vasopressin V2 receptor blocker tolvaptan or placebo within 48 hours of hospitalization.

Standard background therapy in both study arms included diuretics, ACE inhibitor or angiotensin II receptor blocker therapy, a beta-blocker, and an aldosterone antagonist. In the previously reported primary results, tolvaptan proved to have no benefit over placebo during a mean follow-up of 9.9 months (JAMA 2007;297:1319–31).

Dr. Gheorghiade presented a secondary analysis focusing on the 2,061 patients in the placebo arm. At randomization, following initial treatment with diuretics, these patients had a mean congestion score of 4 points based on their degree of jugular vein distention, rales, and peripheral edema.

At discharge, patients had lost a mean 2.8 kg of body weight, and 72% had a congestion score of 0 or 1. Although that appears to be a high rate of short-term treatment success, this large subgroup of patients with minimal or no signs or symptoms of congestion at discharge had a 15% all-cause mortality and a 29% rate of rehospitalization for heart failure during the next 9.9 months.

The adverse event rate was even greater in those with a higher congestion score at discharge. In the overall placebo group, all-cause mortality was 26%, with a 40% rate of rehospitalization for heart failure during follow-up.

“We're dealing with a disorder that has an event rate as high as 50%. There is no other medical condition for which patients are hospitalized and are improving with therapy that has a comparable event rate,” the cardiologist observed.

The new EVEREST analysis contains an important message for clinical trialists: Using signs and symptoms of congestion as a key target for treatment during hospitalization as well as the standard end point in acute heart failure studies, as has been common until now, is a recipe for a negative trial result.

“It's very difficult to beat placebo, because placebo plus standard therapy has a tremendous effect on congestion,” Dr. Gheorghiade said. “Looking for new therapies that improve signs and symptoms of congestion in the whole population is a waste of time unless you're dealing with special populations who don't respond to standard therapies, such as patients with low blood pressure.”

Better surrogate markers than congestion are needed to guide therapy. One possibility is B-type natriuretic peptide (BNP). The mean BNP at admission in the placebo arm of EVEREST was 1,375 pg/mL. At discharge it was still markedly elevated at 948 pg/mL.

“The lesson here is that by treating the signs and symptoms of congestion, you can make patients feel much better, but even though they are now able to walk up a flight of stairs, inside, in terms of renal function and BNP, they are still very sick,” he said.

Until better treatments for acute heart failure are found, the best thing physicians can do for patients is try to identify specific targets amenable to current therapies, such as renal dysfunction or myocardial ischemia, Dr. Gheorghiade said.

The EVEREST trial was sponsored by Otsuka. Dr. Gheorghiade has received research grants and/or served as a consultant to Otsuka and numerous other pharmaceutical companies.

Dr. Mihai Gheorghiade: The event rate in EVEREST was “astronomical.”

Source Bruce Jancin/Elsevier Global Medical News

STOCKHOLM – The absence of signs and symptoms of congestion at discharge in patients hospitalized for acute decompensated heart failure does not predict a favorable prognosis, contrary to the conventional wisdom.

A new secondary analysis of the international EVEREST trial provides an important lesson in the everyday management of acute heart failure: “The fact that a patient improves in-hospital with diuretics and other medications is not sufficient. It's not 'mission accomplished,'” Dr. Mihai Gheorghiade said at the congress.

“There is a dissociation between signs and symptoms of congestion at discharge and outcomes. In spite of having a very low congestion score, the event rate in EVEREST during 10 months of follow-up was astronomical,” said Dr. Gheorghiade, professor of medicine and surgery and associate chief of cardiology at Northwestern University, Chicago.

EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) was a double-blind study that randomized 4,133 patients with worsening heart failure and a left ventricular ejection fraction of 40% or less to the oral vasopressin V2 receptor blocker tolvaptan or placebo within 48 hours of hospitalization.

Standard background therapy in both study arms included diuretics, ACE inhibitor or angiotensin II receptor blocker therapy, a beta-blocker, and an aldosterone antagonist. In the previously reported primary results, tolvaptan proved to have no benefit over placebo during a mean follow-up of 9.9 months (JAMA 2007;297:1319–31).

Dr. Gheorghiade presented a secondary analysis focusing on the 2,061 patients in the placebo arm. At randomization, following initial treatment with diuretics, these patients had a mean congestion score of 4 points based on their degree of jugular vein distention, rales, and peripheral edema.

At discharge, patients had lost a mean 2.8 kg of body weight, and 72% had a congestion score of 0 or 1. Although that appears to be a high rate of short-term treatment success, this large subgroup of patients with minimal or no signs or symptoms of congestion at discharge had a 15% all-cause mortality and a 29% rate of rehospitalization for heart failure during the next 9.9 months.

The adverse event rate was even greater in those with a higher congestion score at discharge. In the overall placebo group, all-cause mortality was 26%, with a 40% rate of rehospitalization for heart failure during follow-up.

“We're dealing with a disorder that has an event rate as high as 50%. There is no other medical condition for which patients are hospitalized and are improving with therapy that has a comparable event rate,” the cardiologist observed.

The new EVEREST analysis contains an important message for clinical trialists: Using signs and symptoms of congestion as a key target for treatment during hospitalization as well as the standard end point in acute heart failure studies, as has been common until now, is a recipe for a negative trial result.

“It's very difficult to beat placebo, because placebo plus standard therapy has a tremendous effect on congestion,” Dr. Gheorghiade said. “Looking for new therapies that improve signs and symptoms of congestion in the whole population is a waste of time unless you're dealing with special populations who don't respond to standard therapies, such as patients with low blood pressure.”

Better surrogate markers than congestion are needed to guide therapy. One possibility is B-type natriuretic peptide (BNP). The mean BNP at admission in the placebo arm of EVEREST was 1,375 pg/mL. At discharge it was still markedly elevated at 948 pg/mL.

“The lesson here is that by treating the signs and symptoms of congestion, you can make patients feel much better, but even though they are now able to walk up a flight of stairs, inside, in terms of renal function and BNP, they are still very sick,” he said.

Until better treatments for acute heart failure are found, the best thing physicians can do for patients is try to identify specific targets amenable to current therapies, such as renal dysfunction or myocardial ischemia, Dr. Gheorghiade said.

The EVEREST trial was sponsored by Otsuka. Dr. Gheorghiade has received research grants and/or served as a consultant to Otsuka and numerous other pharmaceutical companies.

Dr. Mihai Gheorghiade: The event rate in EVEREST was “astronomical.”

Source Bruce Jancin/Elsevier Global Medical News

STOCKHOLM – The absence of signs and symptoms of congestion at discharge in patients hospitalized for acute decompensated heart failure does not predict a favorable prognosis, contrary to the conventional wisdom.

A new secondary analysis of the international EVEREST trial provides an important lesson in the everyday management of acute heart failure: “The fact that a patient improves in-hospital with diuretics and other medications is not sufficient. It's not 'mission accomplished,'” Dr. Mihai Gheorghiade said at the congress.

“There is a dissociation between signs and symptoms of congestion at discharge and outcomes. In spite of having a very low congestion score, the event rate in EVEREST during 10 months of follow-up was astronomical,” said Dr. Gheorghiade, professor of medicine and surgery and associate chief of cardiology at Northwestern University, Chicago.

EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) was a double-blind study that randomized 4,133 patients with worsening heart failure and a left ventricular ejection fraction of 40% or less to the oral vasopressin V2 receptor blocker tolvaptan or placebo within 48 hours of hospitalization.

Standard background therapy in both study arms included diuretics, ACE inhibitor or angiotensin II receptor blocker therapy, a beta-blocker, and an aldosterone antagonist. In the previously reported primary results, tolvaptan proved to have no benefit over placebo during a mean follow-up of 9.9 months (JAMA 2007;297:1319–31).

Dr. Gheorghiade presented a secondary analysis focusing on the 2,061 patients in the placebo arm. At randomization, following initial treatment with diuretics, these patients had a mean congestion score of 4 points based on their degree of jugular vein distention, rales, and peripheral edema.

At discharge, patients had lost a mean 2.8 kg of body weight, and 72% had a congestion score of 0 or 1. Although that appears to be a high rate of short-term treatment success, this large subgroup of patients with minimal or no signs or symptoms of congestion at discharge had a 15% all-cause mortality and a 29% rate of rehospitalization for heart failure during the next 9.9 months.

The adverse event rate was even greater in those with a higher congestion score at discharge. In the overall placebo group, all-cause mortality was 26%, with a 40% rate of rehospitalization for heart failure during follow-up.

“We're dealing with a disorder that has an event rate as high as 50%. There is no other medical condition for which patients are hospitalized and are improving with therapy that has a comparable event rate,” the cardiologist observed.

The new EVEREST analysis contains an important message for clinical trialists: Using signs and symptoms of congestion as a key target for treatment during hospitalization as well as the standard end point in acute heart failure studies, as has been common until now, is a recipe for a negative trial result.

“It's very difficult to beat placebo, because placebo plus standard therapy has a tremendous effect on congestion,” Dr. Gheorghiade said. “Looking for new therapies that improve signs and symptoms of congestion in the whole population is a waste of time unless you're dealing with special populations who don't respond to standard therapies, such as patients with low blood pressure.”

Better surrogate markers than congestion are needed to guide therapy. One possibility is B-type natriuretic peptide (BNP). The mean BNP at admission in the placebo arm of EVEREST was 1,375 pg/mL. At discharge it was still markedly elevated at 948 pg/mL.

“The lesson here is that by treating the signs and symptoms of congestion, you can make patients feel much better, but even though they are now able to walk up a flight of stairs, inside, in terms of renal function and BNP, they are still very sick,” he said.

Until better treatments for acute heart failure are found, the best thing physicians can do for patients is try to identify specific targets amenable to current therapies, such as renal dysfunction or myocardial ischemia, Dr. Gheorghiade said.

The EVEREST trial was sponsored by Otsuka. Dr. Gheorghiade has received research grants and/or served as a consultant to Otsuka and numerous other pharmaceutical companies.

Dr. Mihai Gheorghiade: The event rate in EVEREST was “astronomical.”

Source Bruce Jancin/Elsevier Global Medical News

Major Finding: Adults with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal levels of vitamin D. They were also 1.45 times as likely to die prematurely, compared with those who had normal levels of vitamin D.

Data Source: A total of 13,131 men and women aged 35 and older enrolled in the prospective cohort of the NHANES III from 1988 to 1994.

Disclosures: The researchers had no relevant financial disclosures to make.

SAN DIEGO — Adults with decreased levels of serum 25-hydroxyvitamin D are significantly more likely to die from heart failure or die prematurely, compared with adults who have normal serum levels of vitamin D, results from a large analysis found.

“This may be additional justification for a study of vitamin D supplementation in appropriate patients to determine if there is causality and if this is a treatable condition,” Dr. Howard J. Eisen said at the meeting.

In a study led by his associate, Dr. Longjian Liu of the department of epidemiology and biostatistics at Drexel University School of Public Health, Philadelphia, the researchers reviewed data from 13,131 individuals (6,130 men and 7,001 women) aged 35 and older who were enrolled in the prospective cohort of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994 and followed for mortality through the year 2000. At baseline, a radioimmunoassay kit was used to measure the serum vitamin D level of each participant.

Vitamin D deficiency was defined as a serum level below 20 ng/mL, and vitamin D insufficiency was defined as a serum level of 20-29 ng/mL. Normal levels were defined as 30 ng/mL or greater, said Dr. Eisen of the department of medicine at Drexel University, Philadelphia.

Premature death was defined as death before the age of 75. The researchers used Cox proportional hazards regression analysis to examine the association between serum levels of vitamin D and mortality risk.

Dr. Eisen reported that more than 60% of African American study participants were vitamin D deficient, compared with 20% of whites and about 40% of Hispanics. “This might be yet another explanation for the high prevalence of heart failure [among African Americans],” he said.

During an average follow-up period of 8 years, there were 3,266 deaths among the 13,131 participants (24.9%), including 101 heart failure deaths (0.8%). Of the total deaths, there were 1,066 premature deaths (33%). Death from cardiovascular disease accounted for as many as 34% of the total premature deaths.

The rate of vitamin D deficiency among heart failure deaths was 37%, compared with 26% among non–heart failure–related deaths, a difference that was statistically significant.

After the researchers adjusted for age, gender, race, and baseline medical conditions, study participants with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 2 times more likely to die from heart failure, compared with those who had normal vitamin D levels.

In addition, study participants with vitamin D deficiency were 1.45 times more likely to die prematurely, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 1.14 times more likely to die prematurely, compared with those who had normal vitamin D levels.

Major Finding: Adults with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal levels of vitamin D. They were also 1.45 times as likely to die prematurely, compared with those who had normal levels of vitamin D.

Data Source: A total of 13,131 men and women aged 35 and older enrolled in the prospective cohort of the NHANES III from 1988 to 1994.

Disclosures: The researchers had no relevant financial disclosures to make.

SAN DIEGO — Adults with decreased levels of serum 25-hydroxyvitamin D are significantly more likely to die from heart failure or die prematurely, compared with adults who have normal serum levels of vitamin D, results from a large analysis found.

“This may be additional justification for a study of vitamin D supplementation in appropriate patients to determine if there is causality and if this is a treatable condition,” Dr. Howard J. Eisen said at the meeting.

In a study led by his associate, Dr. Longjian Liu of the department of epidemiology and biostatistics at Drexel University School of Public Health, Philadelphia, the researchers reviewed data from 13,131 individuals (6,130 men and 7,001 women) aged 35 and older who were enrolled in the prospective cohort of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994 and followed for mortality through the year 2000. At baseline, a radioimmunoassay kit was used to measure the serum vitamin D level of each participant.

Vitamin D deficiency was defined as a serum level below 20 ng/mL, and vitamin D insufficiency was defined as a serum level of 20-29 ng/mL. Normal levels were defined as 30 ng/mL or greater, said Dr. Eisen of the department of medicine at Drexel University, Philadelphia.

Premature death was defined as death before the age of 75. The researchers used Cox proportional hazards regression analysis to examine the association between serum levels of vitamin D and mortality risk.

Dr. Eisen reported that more than 60% of African American study participants were vitamin D deficient, compared with 20% of whites and about 40% of Hispanics. “This might be yet another explanation for the high prevalence of heart failure [among African Americans],” he said.

During an average follow-up period of 8 years, there were 3,266 deaths among the 13,131 participants (24.9%), including 101 heart failure deaths (0.8%). Of the total deaths, there were 1,066 premature deaths (33%). Death from cardiovascular disease accounted for as many as 34% of the total premature deaths.

The rate of vitamin D deficiency among heart failure deaths was 37%, compared with 26% among non–heart failure–related deaths, a difference that was statistically significant.

After the researchers adjusted for age, gender, race, and baseline medical conditions, study participants with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 2 times more likely to die from heart failure, compared with those who had normal vitamin D levels.

In addition, study participants with vitamin D deficiency were 1.45 times more likely to die prematurely, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 1.14 times more likely to die prematurely, compared with those who had normal vitamin D levels.

Major Finding: Adults with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal levels of vitamin D. They were also 1.45 times as likely to die prematurely, compared with those who had normal levels of vitamin D.

Data Source: A total of 13,131 men and women aged 35 and older enrolled in the prospective cohort of the NHANES III from 1988 to 1994.

Disclosures: The researchers had no relevant financial disclosures to make.

SAN DIEGO — Adults with decreased levels of serum 25-hydroxyvitamin D are significantly more likely to die from heart failure or die prematurely, compared with adults who have normal serum levels of vitamin D, results from a large analysis found.

“This may be additional justification for a study of vitamin D supplementation in appropriate patients to determine if there is causality and if this is a treatable condition,” Dr. Howard J. Eisen said at the meeting.

In a study led by his associate, Dr. Longjian Liu of the department of epidemiology and biostatistics at Drexel University School of Public Health, Philadelphia, the researchers reviewed data from 13,131 individuals (6,130 men and 7,001 women) aged 35 and older who were enrolled in the prospective cohort of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994 and followed for mortality through the year 2000. At baseline, a radioimmunoassay kit was used to measure the serum vitamin D level of each participant.

Vitamin D deficiency was defined as a serum level below 20 ng/mL, and vitamin D insufficiency was defined as a serum level of 20-29 ng/mL. Normal levels were defined as 30 ng/mL or greater, said Dr. Eisen of the department of medicine at Drexel University, Philadelphia.

Premature death was defined as death before the age of 75. The researchers used Cox proportional hazards regression analysis to examine the association between serum levels of vitamin D and mortality risk.

Dr. Eisen reported that more than 60% of African American study participants were vitamin D deficient, compared with 20% of whites and about 40% of Hispanics. “This might be yet another explanation for the high prevalence of heart failure [among African Americans],” he said.

During an average follow-up period of 8 years, there were 3,266 deaths among the 13,131 participants (24.9%), including 101 heart failure deaths (0.8%). Of the total deaths, there were 1,066 premature deaths (33%). Death from cardiovascular disease accounted for as many as 34% of the total premature deaths.

The rate of vitamin D deficiency among heart failure deaths was 37%, compared with 26% among non–heart failure–related deaths, a difference that was statistically significant.

After the researchers adjusted for age, gender, race, and baseline medical conditions, study participants with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 2 times more likely to die from heart failure, compared with those who had normal vitamin D levels.

In addition, study participants with vitamin D deficiency were 1.45 times more likely to die prematurely, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 1.14 times more likely to die prematurely, compared with those who had normal vitamin D levels.

Major Finding: People in the highest tertile for plasma level of brain natriuretic peptide had a twofold increased risk for death, heart failure, and myocardial infarction during an average 9 years of follow-up.

Data Source: A randomly selected sample of 1,991 people from Olmsted County, Minn., without heart failure or elevated plasma creatinine at baseline.

Disclosures: Dr. McKie said that he had no disclosures.

STOCKHOLM — High plasma levels of B-type natriuretic peptide linked with a significantly increased risk for heart failure, myocardial infarction, and death during 9 years of follow-up in a group of nearly 2,000 adults from the general U.S. population.

Plasma levels of B-type natriuretic peptide (BNP) “had predictive utility for death, heart failure, and MI, even when adjusted for risk factors and structural abnormalities” of the heart in the general population, Dr. Paul M. McKie said at the congress.

“We're actively working on trying to narrow down the at-risk population” who are possible candidates for routine BNP screening, said Dr. McKie, a cardiologist at the Mayo Clinic in Rochester, Minn. “We're planning a proof-of-concept intervention trial to see if we can intervene with aggressive risk factor reduction and improve outcomes in people with high BNP levels.” People who may get the most benefit from BNP screening and intervention are those with some level of underlying cardiac risk but no current heart failure, he added.

Results from another analysis recently reported by Dr. McKie and his associates at Mayo showed that relatively high BNP levels could not predict the long-term risk of death or cardiovascular events in people from the general adult population without symptomatic heart failure, elevated plasma creatinine, clinical cardiovascular risk factors (such as hypertension, diabetes, peripheral vascular disease, or MI), or cardiac abnormalities identified by echocardiography (such as left atrial enlargement, wall-motion abnormalities, and valvular dysfunction) (J. Am. Coll. Cardiol. 2010;55:2140-7).

That finding, coupled with the new report, suggests that high BNP is prognostic in the people without heart failure or elevated creatinine but with one or more risk factors or a cardiac structural abnormality, which was found in a majority of the general population studied. Among 2,042 unselected people aged 45 years or older residing in Olmsted County, Minn., and participating in the Rochester Epidemiology Project, 1,288 (63%) had one or more clinical risk factors or an echocardiographic abnormality.

The new analysis began with the 2,042 Olmsted County residents and excluded 45 who had symptomatic heart failure, and 6 with a plasma creatinine of more than 2.0 mg/dL.

The researchers measured plasma levels of BNP (specifically amino-terminal pro-BNP) with an immunoassay. These healthy, normal subjects from the community without symptomatic heart failure or elevated creatinine had BNP levels well below the levels found in patients with heart failure, Dr. McKie indicated.

The analysis examined the risk for death, incident heart failure, or incident MI during an average 9 years of follow-up. People in the highest BNP tertile consistently had double the rates of all three outcomes during follow-up than did people in the lowest tertile after adjustment for age, sex, body mass index, clinical risk factors, or echocardiographic abnormalities, differences that were statistically significant (see box).

The analysis also showed that the link between high BNP levels and adverse outcomes remained significant after adjustment for plasma levels of atrial natriuretic peptide. “BNP is a more robust prognostic marker than atrial natriuretic peptide in the general population without heart failure,” Dr. McKie said.

Disclosures: Dr. McKie said that he had no relevant financial interests.

Vitals

Source Elsevier Global Medical News

Major Finding: People in the highest tertile for plasma level of brain natriuretic peptide had a twofold increased risk for death, heart failure, and myocardial infarction during an average 9 years of follow-up.

Data Source: A randomly selected sample of 1,991 people from Olmsted County, Minn., without heart failure or elevated plasma creatinine at baseline.

Disclosures: Dr. McKie said that he had no disclosures.

STOCKHOLM — High plasma levels of B-type natriuretic peptide linked with a significantly increased risk for heart failure, myocardial infarction, and death during 9 years of follow-up in a group of nearly 2,000 adults from the general U.S. population.

Plasma levels of B-type natriuretic peptide (BNP) “had predictive utility for death, heart failure, and MI, even when adjusted for risk factors and structural abnormalities” of the heart in the general population, Dr. Paul M. McKie said at the congress.

“We're actively working on trying to narrow down the at-risk population” who are possible candidates for routine BNP screening, said Dr. McKie, a cardiologist at the Mayo Clinic in Rochester, Minn. “We're planning a proof-of-concept intervention trial to see if we can intervene with aggressive risk factor reduction and improve outcomes in people with high BNP levels.” People who may get the most benefit from BNP screening and intervention are those with some level of underlying cardiac risk but no current heart failure, he added.

Results from another analysis recently reported by Dr. McKie and his associates at Mayo showed that relatively high BNP levels could not predict the long-term risk of death or cardiovascular events in people from the general adult population without symptomatic heart failure, elevated plasma creatinine, clinical cardiovascular risk factors (such as hypertension, diabetes, peripheral vascular disease, or MI), or cardiac abnormalities identified by echocardiography (such as left atrial enlargement, wall-motion abnormalities, and valvular dysfunction) (J. Am. Coll. Cardiol. 2010;55:2140-7).

That finding, coupled with the new report, suggests that high BNP is prognostic in the people without heart failure or elevated creatinine but with one or more risk factors or a cardiac structural abnormality, which was found in a majority of the general population studied. Among 2,042 unselected people aged 45 years or older residing in Olmsted County, Minn., and participating in the Rochester Epidemiology Project, 1,288 (63%) had one or more clinical risk factors or an echocardiographic abnormality.

The new analysis began with the 2,042 Olmsted County residents and excluded 45 who had symptomatic heart failure, and 6 with a plasma creatinine of more than 2.0 mg/dL.

The researchers measured plasma levels of BNP (specifically amino-terminal pro-BNP) with an immunoassay. These healthy, normal subjects from the community without symptomatic heart failure or elevated creatinine had BNP levels well below the levels found in patients with heart failure, Dr. McKie indicated.

The analysis examined the risk for death, incident heart failure, or incident MI during an average 9 years of follow-up. People in the highest BNP tertile consistently had double the rates of all three outcomes during follow-up than did people in the lowest tertile after adjustment for age, sex, body mass index, clinical risk factors, or echocardiographic abnormalities, differences that were statistically significant (see box).

The analysis also showed that the link between high BNP levels and adverse outcomes remained significant after adjustment for plasma levels of atrial natriuretic peptide. “BNP is a more robust prognostic marker than atrial natriuretic peptide in the general population without heart failure,” Dr. McKie said.

Disclosures: Dr. McKie said that he had no relevant financial interests.

Vitals

Source Elsevier Global Medical News

Major Finding: People in the highest tertile for plasma level of brain natriuretic peptide had a twofold increased risk for death, heart failure, and myocardial infarction during an average 9 years of follow-up.

Data Source: A randomly selected sample of 1,991 people from Olmsted County, Minn., without heart failure or elevated plasma creatinine at baseline.

Disclosures: Dr. McKie said that he had no disclosures.

STOCKHOLM — High plasma levels of B-type natriuretic peptide linked with a significantly increased risk for heart failure, myocardial infarction, and death during 9 years of follow-up in a group of nearly 2,000 adults from the general U.S. population.

Plasma levels of B-type natriuretic peptide (BNP) “had predictive utility for death, heart failure, and MI, even when adjusted for risk factors and structural abnormalities” of the heart in the general population, Dr. Paul M. McKie said at the congress.

“We're actively working on trying to narrow down the at-risk population” who are possible candidates for routine BNP screening, said Dr. McKie, a cardiologist at the Mayo Clinic in Rochester, Minn. “We're planning a proof-of-concept intervention trial to see if we can intervene with aggressive risk factor reduction and improve outcomes in people with high BNP levels.” People who may get the most benefit from BNP screening and intervention are those with some level of underlying cardiac risk but no current heart failure, he added.

Results from another analysis recently reported by Dr. McKie and his associates at Mayo showed that relatively high BNP levels could not predict the long-term risk of death or cardiovascular events in people from the general adult population without symptomatic heart failure, elevated plasma creatinine, clinical cardiovascular risk factors (such as hypertension, diabetes, peripheral vascular disease, or MI), or cardiac abnormalities identified by echocardiography (such as left atrial enlargement, wall-motion abnormalities, and valvular dysfunction) (J. Am. Coll. Cardiol. 2010;55:2140-7).

That finding, coupled with the new report, suggests that high BNP is prognostic in the people without heart failure or elevated creatinine but with one or more risk factors or a cardiac structural abnormality, which was found in a majority of the general population studied. Among 2,042 unselected people aged 45 years or older residing in Olmsted County, Minn., and participating in the Rochester Epidemiology Project, 1,288 (63%) had one or more clinical risk factors or an echocardiographic abnormality.

The new analysis began with the 2,042 Olmsted County residents and excluded 45 who had symptomatic heart failure, and 6 with a plasma creatinine of more than 2.0 mg/dL.

The researchers measured plasma levels of BNP (specifically amino-terminal pro-BNP) with an immunoassay. These healthy, normal subjects from the community without symptomatic heart failure or elevated creatinine had BNP levels well below the levels found in patients with heart failure, Dr. McKie indicated.

The analysis examined the risk for death, incident heart failure, or incident MI during an average 9 years of follow-up. People in the highest BNP tertile consistently had double the rates of all three outcomes during follow-up than did people in the lowest tertile after adjustment for age, sex, body mass index, clinical risk factors, or echocardiographic abnormalities, differences that were statistically significant (see box).

The analysis also showed that the link between high BNP levels and adverse outcomes remained significant after adjustment for plasma levels of atrial natriuretic peptide. “BNP is a more robust prognostic marker than atrial natriuretic peptide in the general population without heart failure,” Dr. McKie said.

Disclosures: Dr. McKie said that he had no relevant financial interests.

Vitals

Source Elsevier Global Medical News

SAN ANTONIO — Six months of continuous positive airway pressure therapy markedly improved adverse left ventricular and atrial remodeling in patients with moderate to severe obstructive sleep apnea in a prospective study.

Diastolic as well as systolic abnormalities were reversed, raising the welcome prospect that CPAP is likely to prevent the development of one of the most dreaded complications of severe obstructive sleep apnea (OSA)—chronic heart failure—although this point remains speculative, Dr. Saleh Al-Mutairi said.

He recruited 32 patients with newly diagnosed moderate to severe OSA for the study, which involved serial follow-up by cardiac magnetic resonance (CMR), echocardiography, and cardiac biomarkers through 6 months of individually titrated CPAP therapy.

The subjects averaged 51 years of age, with a mean baseline apnea-hypopnea index of 53 events/hr and a body mass index of 34.5 kg/m

Other studies have shown improvement in left ventricular dysfunction with CPAP, but they were short-term trials. This is the first study with follow-up as long as 6 months using both CMR and echocardiography, according to Dr. Al-Mutairi of the University of Manitoba, Winnipeg.

He focused on the CMR results because he considers that technology more reliable than echocardiography for assessing ventricular size and function. The echo findings, however, corroborated the CMR results.

Most of the left ventricular measurements followed during the study were abnormal at baseline. The 6-month results included a 25% reduction from baseline in left ventricular end-diastolic volume and a 19% decrease in left ventricular mass. (See chart.)

Dr. Al-Mutairi drew particular attention to the 30% reduction in left atrial volume index, which he considers highly encouraging. “TThis is a very important point, given the association between the left atrial volume and cardiovascular events,” he observed.

There was no significant change in C-reactive protein, brain natriuretic peptide, or other cardiac biomarkers during the 6 months of CPAP use.

The mechanism by which OSA is thought to predispose to heart failure involves an exaggerated negative thoracic pressure in response to the apneic episodes. This presumably leads to increased left ventricular systolic transmural pressure, which the left atrium resists, with resultant increased compliance and atrial overstretching, Dr. Al-Mutairi said.

He and his coinvestigators are in the midst of expanding their study to 50 patients in order to strengthen the conclusions.

Disclosures: Dr. Al-Mutairi reported having no financial conflicts.

Source Elsevier Global Medical News

SAN ANTONIO — Six months of continuous positive airway pressure therapy markedly improved adverse left ventricular and atrial remodeling in patients with moderate to severe obstructive sleep apnea in a prospective study.

Diastolic as well as systolic abnormalities were reversed, raising the welcome prospect that CPAP is likely to prevent the development of one of the most dreaded complications of severe obstructive sleep apnea (OSA)—chronic heart failure—although this point remains speculative, Dr. Saleh Al-Mutairi said.

He recruited 32 patients with newly diagnosed moderate to severe OSA for the study, which involved serial follow-up by cardiac magnetic resonance (CMR), echocardiography, and cardiac biomarkers through 6 months of individually titrated CPAP therapy.

The subjects averaged 51 years of age, with a mean baseline apnea-hypopnea index of 53 events/hr and a body mass index of 34.5 kg/m

Other studies have shown improvement in left ventricular dysfunction with CPAP, but they were short-term trials. This is the first study with follow-up as long as 6 months using both CMR and echocardiography, according to Dr. Al-Mutairi of the University of Manitoba, Winnipeg.

He focused on the CMR results because he considers that technology more reliable than echocardiography for assessing ventricular size and function. The echo findings, however, corroborated the CMR results.

Most of the left ventricular measurements followed during the study were abnormal at baseline. The 6-month results included a 25% reduction from baseline in left ventricular end-diastolic volume and a 19% decrease in left ventricular mass. (See chart.)

Dr. Al-Mutairi drew particular attention to the 30% reduction in left atrial volume index, which he considers highly encouraging. “TThis is a very important point, given the association between the left atrial volume and cardiovascular events,” he observed.

There was no significant change in C-reactive protein, brain natriuretic peptide, or other cardiac biomarkers during the 6 months of CPAP use.

The mechanism by which OSA is thought to predispose to heart failure involves an exaggerated negative thoracic pressure in response to the apneic episodes. This presumably leads to increased left ventricular systolic transmural pressure, which the left atrium resists, with resultant increased compliance and atrial overstretching, Dr. Al-Mutairi said.

He and his coinvestigators are in the midst of expanding their study to 50 patients in order to strengthen the conclusions.

Disclosures: Dr. Al-Mutairi reported having no financial conflicts.

Source Elsevier Global Medical News

SAN ANTONIO — Six months of continuous positive airway pressure therapy markedly improved adverse left ventricular and atrial remodeling in patients with moderate to severe obstructive sleep apnea in a prospective study.

Diastolic as well as systolic abnormalities were reversed, raising the welcome prospect that CPAP is likely to prevent the development of one of the most dreaded complications of severe obstructive sleep apnea (OSA)—chronic heart failure—although this point remains speculative, Dr. Saleh Al-Mutairi said.

He recruited 32 patients with newly diagnosed moderate to severe OSA for the study, which involved serial follow-up by cardiac magnetic resonance (CMR), echocardiography, and cardiac biomarkers through 6 months of individually titrated CPAP therapy.

The subjects averaged 51 years of age, with a mean baseline apnea-hypopnea index of 53 events/hr and a body mass index of 34.5 kg/m

Other studies have shown improvement in left ventricular dysfunction with CPAP, but they were short-term trials. This is the first study with follow-up as long as 6 months using both CMR and echocardiography, according to Dr. Al-Mutairi of the University of Manitoba, Winnipeg.

He focused on the CMR results because he considers that technology more reliable than echocardiography for assessing ventricular size and function. The echo findings, however, corroborated the CMR results.

Most of the left ventricular measurements followed during the study were abnormal at baseline. The 6-month results included a 25% reduction from baseline in left ventricular end-diastolic volume and a 19% decrease in left ventricular mass. (See chart.)

Dr. Al-Mutairi drew particular attention to the 30% reduction in left atrial volume index, which he considers highly encouraging. “TThis is a very important point, given the association between the left atrial volume and cardiovascular events,” he observed.

There was no significant change in C-reactive protein, brain natriuretic peptide, or other cardiac biomarkers during the 6 months of CPAP use.

The mechanism by which OSA is thought to predispose to heart failure involves an exaggerated negative thoracic pressure in response to the apneic episodes. This presumably leads to increased left ventricular systolic transmural pressure, which the left atrium resists, with resultant increased compliance and atrial overstretching, Dr. Al-Mutairi said.

He and his coinvestigators are in the midst of expanding their study to 50 patients in order to strengthen the conclusions.

Disclosures: Dr. Al-Mutairi reported having no financial conflicts.

Source Elsevier Global Medical News

ATLANTA — Treatment with hydralazine and isosorbide dinitrate was associated with a mortality benefit in both black and nonblack patients with diastolic heart failure in a large, retrospective, single-center study.

This is an encouraging, albeit nondefinitive, observation, since to date no treatment has been shown effective in decreasing mortality in patients with diastolic heart failure, Dr. Jeremy A. Mazurek noted at the meeting.

Because treatment with hydralazine and isosorbide dinitrate was shown to decrease mortality in black patients with systolic heart failure in the African-American Heart Failure Trial (N. Engl. J. Med. 2004; 351:2049–57), Dr. Mazurek wondered whether it might also be effective in the setting of diastolic heart failure, where there is a huge unmet need for medical therapies. He reviewed the last 10 years' experience with hydralazine/isosorbide dinitrate treatment in patients with diastolic heart failure at Montefiore Medical Center in New York.

The 1-year mortality was 16% in 949 black patients with diastolic heart failure who were treated with the drug compared with 21% in 4,053 who were not.

A significant reduction in mortality was also seen in nonblack patients with diastolic heart failure treated with hydralazine/isosorbide dinitrate, with a 1-year mortality rate of 25% in 634 patients compared with 32% in 5,866 nonblack patients not on the drug.

The limitation of this study is its nonrandomized, retrospective nature. Both black and nonblack diastolic heart failure patients who were placed on hydralazine/isosorbide dinitrate were significantly younger and more likely to be on beta-blocker therapy than were those who were not. On the other hand, they also had a higher prevalence of diabetes, prior MI, and cerebrovascular disease. In any case, these results provide justification for a definitive prospective randomized clinical trial of hydralazine/isosorbide dinitrate in the treatment of diastolic heart failure in patients of all races, according to Dr. Mazurek of Albert Einstein College of Medicine, New York.

He reported having no financial conflicts with regard to this retrospective study, which was conducted free of commercial support.

ATLANTA — Treatment with hydralazine and isosorbide dinitrate was associated with a mortality benefit in both black and nonblack patients with diastolic heart failure in a large, retrospective, single-center study.

This is an encouraging, albeit nondefinitive, observation, since to date no treatment has been shown effective in decreasing mortality in patients with diastolic heart failure, Dr. Jeremy A. Mazurek noted at the meeting.

Because treatment with hydralazine and isosorbide dinitrate was shown to decrease mortality in black patients with systolic heart failure in the African-American Heart Failure Trial (N. Engl. J. Med. 2004; 351:2049–57), Dr. Mazurek wondered whether it might also be effective in the setting of diastolic heart failure, where there is a huge unmet need for medical therapies. He reviewed the last 10 years' experience with hydralazine/isosorbide dinitrate treatment in patients with diastolic heart failure at Montefiore Medical Center in New York.

The 1-year mortality was 16% in 949 black patients with diastolic heart failure who were treated with the drug compared with 21% in 4,053 who were not.

A significant reduction in mortality was also seen in nonblack patients with diastolic heart failure treated with hydralazine/isosorbide dinitrate, with a 1-year mortality rate of 25% in 634 patients compared with 32% in 5,866 nonblack patients not on the drug.

The limitation of this study is its nonrandomized, retrospective nature. Both black and nonblack diastolic heart failure patients who were placed on hydralazine/isosorbide dinitrate were significantly younger and more likely to be on beta-blocker therapy than were those who were not. On the other hand, they also had a higher prevalence of diabetes, prior MI, and cerebrovascular disease. In any case, these results provide justification for a definitive prospective randomized clinical trial of hydralazine/isosorbide dinitrate in the treatment of diastolic heart failure in patients of all races, according to Dr. Mazurek of Albert Einstein College of Medicine, New York.

He reported having no financial conflicts with regard to this retrospective study, which was conducted free of commercial support.

ATLANTA — Treatment with hydralazine and isosorbide dinitrate was associated with a mortality benefit in both black and nonblack patients with diastolic heart failure in a large, retrospective, single-center study.

This is an encouraging, albeit nondefinitive, observation, since to date no treatment has been shown effective in decreasing mortality in patients with diastolic heart failure, Dr. Jeremy A. Mazurek noted at the meeting.

Because treatment with hydralazine and isosorbide dinitrate was shown to decrease mortality in black patients with systolic heart failure in the African-American Heart Failure Trial (N. Engl. J. Med. 2004; 351:2049–57), Dr. Mazurek wondered whether it might also be effective in the setting of diastolic heart failure, where there is a huge unmet need for medical therapies. He reviewed the last 10 years' experience with hydralazine/isosorbide dinitrate treatment in patients with diastolic heart failure at Montefiore Medical Center in New York.

The 1-year mortality was 16% in 949 black patients with diastolic heart failure who were treated with the drug compared with 21% in 4,053 who were not.

A significant reduction in mortality was also seen in nonblack patients with diastolic heart failure treated with hydralazine/isosorbide dinitrate, with a 1-year mortality rate of 25% in 634 patients compared with 32% in 5,866 nonblack patients not on the drug.

The limitation of this study is its nonrandomized, retrospective nature. Both black and nonblack diastolic heart failure patients who were placed on hydralazine/isosorbide dinitrate were significantly younger and more likely to be on beta-blocker therapy than were those who were not. On the other hand, they also had a higher prevalence of diabetes, prior MI, and cerebrovascular disease. In any case, these results provide justification for a definitive prospective randomized clinical trial of hydralazine/isosorbide dinitrate in the treatment of diastolic heart failure in patients of all races, according to Dr. Mazurek of Albert Einstein College of Medicine, New York.

He reported having no financial conflicts with regard to this retrospective study, which was conducted free of commercial support.