Heart Failure

STOCKHOLM — A β-blocker and an ACE inhibitor, the two mainstays of heart failure treatment, can be started in either order and be safe and effective, according to results from more than 1,000 patients.

Until now, treatment of patients with heart failure usually began with an ACE inhibitor or an angiotensin-receptor blocker, primarily for historic reasons: ACE inhibitors were proven effective for treating heart failure first. But results from a head-to-head trial now show that both options are equivalent. An ACE inhibitor or a β-blocker can be started first, followed by the other drug, and patients have similar outcomes, Ronnie Willenheimer, M.D., reported at the annual congress of the European Society of Cardiology.

“I think this will possibly change practice. The data support using a β-blocker first in selected patients,” commented Kenneth Dickstein, M.D., a cardiologist at the University of Bergen (Norway). “It remains a clinical question [as to] who should get a β-blocker first and who should first get an ACE inhibitor or angiotensin-receptor blocker.”

“The results suggest free choice. A physician can start treatment based on individual judgment of each patient,” said Dr. Willenheimer, a cardiologist at University Hospital Malmö (Sweden). “For patients with tachycardia or ischemic cardiomyopathy, I'd start with a β-blocker,” he told this newspaper.

Dr. Willenheimer has received honoraria from the German division of Merck, which sponsored the study and markets a formulation of the β-blocker bisoprolol (Concor) that is approved in many countries (but not the United States) for treating heart failure. In the United States, generic bisoprolol and its trade formulation (Zebeta) are approved only for treating hypertension. β-Blockers approved for treating heart failure in the United States are carvedilol (Coreg) and metoprolol succinate (Toprol-XL).

The study enrolled 1,010 patients aged 65 years or older (the mean age was 72 years) with New York Heart Association class II or III heart failure at 128 centers in 20 countries. Their average left ventricular ejection fraction was 29%. Patients were randomized to start treatment with either 1.25 mg of bisoprolol once daily or 2.5 mg of the ACE inhibitor enalapril b.i.d. Their monotherapy dosage was increased every 2 weeks until the bisoprolol dosage was 10 mg once daily or the enalapril dosage was 10 mg b.i.d. Monotherapy was continued to a total duration of 6 months, after which the second drug was begun with a similar up-titration scheme. Patients were followed for an average of 1.2 years.

By all efficacy measures used, the bisoprolol-first strategy was not inferior to the enalapril-first regimen. The study's primary end point was the time to first all-cause death or all-cause hospitalization. During follow-up on an intention-to-treat basis, these events occurred in 35.2% of patients in the bisoprolol-first arm and in 36.8% of those in the enalapril-first arm. On a per-protocol basis, the event rates were 32.4% in the bisoprolol-first patients and 33.1% in the enalapril-first group (Circulation 2005;112:2426–35).

The incidence of treatment-related adverse events was also similar in both groups. However, in patients treated with bisoprolol first, the results showed a trend toward an improved survival benefit and a trend toward a higher frequency of worsening heart failure requiring hospitalization, especially early in the study.

These findings are probably class effects, Dr. Willenheimer said. In both treatment groups, the drug that was started first was given in higher dosages during the combined therapy phase. The study was limited by several factors, Dr. Dickstein noted. It was done on an open-label basis, it did not include patients with class IV disease, and patients were maintained on monotherapy for the relatively long period of 6 months. Nonetheless, he said that on the basis of the results, he believes that the two strategies probably have comparable efficacy and safety.

A physician can start treatment based on individual judgment of each patient. DR. WILLENHEIMER

STOCKHOLM — A β-blocker and an ACE inhibitor, the two mainstays of heart failure treatment, can be started in either order and be safe and effective, according to results from more than 1,000 patients.

Until now, treatment of patients with heart failure usually began with an ACE inhibitor or an angiotensin-receptor blocker, primarily for historic reasons: ACE inhibitors were proven effective for treating heart failure first. But results from a head-to-head trial now show that both options are equivalent. An ACE inhibitor or a β-blocker can be started first, followed by the other drug, and patients have similar outcomes, Ronnie Willenheimer, M.D., reported at the annual congress of the European Society of Cardiology.

“I think this will possibly change practice. The data support using a β-blocker first in selected patients,” commented Kenneth Dickstein, M.D., a cardiologist at the University of Bergen (Norway). “It remains a clinical question [as to] who should get a β-blocker first and who should first get an ACE inhibitor or angiotensin-receptor blocker.”

“The results suggest free choice. A physician can start treatment based on individual judgment of each patient,” said Dr. Willenheimer, a cardiologist at University Hospital Malmö (Sweden). “For patients with tachycardia or ischemic cardiomyopathy, I'd start with a β-blocker,” he told this newspaper.

Dr. Willenheimer has received honoraria from the German division of Merck, which sponsored the study and markets a formulation of the β-blocker bisoprolol (Concor) that is approved in many countries (but not the United States) for treating heart failure. In the United States, generic bisoprolol and its trade formulation (Zebeta) are approved only for treating hypertension. β-Blockers approved for treating heart failure in the United States are carvedilol (Coreg) and metoprolol succinate (Toprol-XL).

The study enrolled 1,010 patients aged 65 years or older (the mean age was 72 years) with New York Heart Association class II or III heart failure at 128 centers in 20 countries. Their average left ventricular ejection fraction was 29%. Patients were randomized to start treatment with either 1.25 mg of bisoprolol once daily or 2.5 mg of the ACE inhibitor enalapril b.i.d. Their monotherapy dosage was increased every 2 weeks until the bisoprolol dosage was 10 mg once daily or the enalapril dosage was 10 mg b.i.d. Monotherapy was continued to a total duration of 6 months, after which the second drug was begun with a similar up-titration scheme. Patients were followed for an average of 1.2 years.

By all efficacy measures used, the bisoprolol-first strategy was not inferior to the enalapril-first regimen. The study's primary end point was the time to first all-cause death or all-cause hospitalization. During follow-up on an intention-to-treat basis, these events occurred in 35.2% of patients in the bisoprolol-first arm and in 36.8% of those in the enalapril-first arm. On a per-protocol basis, the event rates were 32.4% in the bisoprolol-first patients and 33.1% in the enalapril-first group (Circulation 2005;112:2426–35).

The incidence of treatment-related adverse events was also similar in both groups. However, in patients treated with bisoprolol first, the results showed a trend toward an improved survival benefit and a trend toward a higher frequency of worsening heart failure requiring hospitalization, especially early in the study.

These findings are probably class effects, Dr. Willenheimer said. In both treatment groups, the drug that was started first was given in higher dosages during the combined therapy phase. The study was limited by several factors, Dr. Dickstein noted. It was done on an open-label basis, it did not include patients with class IV disease, and patients were maintained on monotherapy for the relatively long period of 6 months. Nonetheless, he said that on the basis of the results, he believes that the two strategies probably have comparable efficacy and safety.

A physician can start treatment based on individual judgment of each patient. DR. WILLENHEIMER

STOCKHOLM — A β-blocker and an ACE inhibitor, the two mainstays of heart failure treatment, can be started in either order and be safe and effective, according to results from more than 1,000 patients.

Until now, treatment of patients with heart failure usually began with an ACE inhibitor or an angiotensin-receptor blocker, primarily for historic reasons: ACE inhibitors were proven effective for treating heart failure first. But results from a head-to-head trial now show that both options are equivalent. An ACE inhibitor or a β-blocker can be started first, followed by the other drug, and patients have similar outcomes, Ronnie Willenheimer, M.D., reported at the annual congress of the European Society of Cardiology.

“I think this will possibly change practice. The data support using a β-blocker first in selected patients,” commented Kenneth Dickstein, M.D., a cardiologist at the University of Bergen (Norway). “It remains a clinical question [as to] who should get a β-blocker first and who should first get an ACE inhibitor or angiotensin-receptor blocker.”

“The results suggest free choice. A physician can start treatment based on individual judgment of each patient,” said Dr. Willenheimer, a cardiologist at University Hospital Malmö (Sweden). “For patients with tachycardia or ischemic cardiomyopathy, I'd start with a β-blocker,” he told this newspaper.

Dr. Willenheimer has received honoraria from the German division of Merck, which sponsored the study and markets a formulation of the β-blocker bisoprolol (Concor) that is approved in many countries (but not the United States) for treating heart failure. In the United States, generic bisoprolol and its trade formulation (Zebeta) are approved only for treating hypertension. β-Blockers approved for treating heart failure in the United States are carvedilol (Coreg) and metoprolol succinate (Toprol-XL).

The study enrolled 1,010 patients aged 65 years or older (the mean age was 72 years) with New York Heart Association class II or III heart failure at 128 centers in 20 countries. Their average left ventricular ejection fraction was 29%. Patients were randomized to start treatment with either 1.25 mg of bisoprolol once daily or 2.5 mg of the ACE inhibitor enalapril b.i.d. Their monotherapy dosage was increased every 2 weeks until the bisoprolol dosage was 10 mg once daily or the enalapril dosage was 10 mg b.i.d. Monotherapy was continued to a total duration of 6 months, after which the second drug was begun with a similar up-titration scheme. Patients were followed for an average of 1.2 years.

By all efficacy measures used, the bisoprolol-first strategy was not inferior to the enalapril-first regimen. The study's primary end point was the time to first all-cause death or all-cause hospitalization. During follow-up on an intention-to-treat basis, these events occurred in 35.2% of patients in the bisoprolol-first arm and in 36.8% of those in the enalapril-first arm. On a per-protocol basis, the event rates were 32.4% in the bisoprolol-first patients and 33.1% in the enalapril-first group (Circulation 2005;112:2426–35).

The incidence of treatment-related adverse events was also similar in both groups. However, in patients treated with bisoprolol first, the results showed a trend toward an improved survival benefit and a trend toward a higher frequency of worsening heart failure requiring hospitalization, especially early in the study.

These findings are probably class effects, Dr. Willenheimer said. In both treatment groups, the drug that was started first was given in higher dosages during the combined therapy phase. The study was limited by several factors, Dr. Dickstein noted. It was done on an open-label basis, it did not include patients with class IV disease, and patients were maintained on monotherapy for the relatively long period of 6 months. Nonetheless, he said that on the basis of the results, he believes that the two strategies probably have comparable efficacy and safety.

A physician can start treatment based on individual judgment of each patient. DR. WILLENHEIMER

STOCKHOLM — Body temperature gauged prognosis in a retrospective analysis of patients hospitalized for heart failure.

Patients hospitalized for heart failure with hypothermia (a body temperature of 96.5°F or less) at admission were fourfold more likely to die during follow-up as were normathermic patients, Mihai Gheorghiade, M.D., said at the annual congress of the European Society of Cardiology.

“This is the first report [of the link with hypothermia], so it needs validation before making any conclusion that temperature is a prognostic factor,” said Dr. Gheorghiade, professor of medicine at Northwestern University, Chicago.

The correlation was made by reviewing data collected in a study designed to test the safety and efficacy of tolvaptan, an oral vasopressin receptor antagonist, in patients with systolic dysfunction who were hospitalized for worsening heart failure. Of 319 patients enrolled, body temperature readings on admission were available for 315.

Of those patients, 32 had hypothermia. At 60 days, mortality was 9.4% in patients with hypothermia and 5.9% in those with normothermia. After adjustment for baseline differences in blood urea nitrogen, age, and tolvaptan treatment, the patients with hypothermia were 3.9 times more likely to die.

In clinical trials, body temperature should be measured at admission and daily to correlate temperature and heart failure status, Dr. Gheorghiade said.

STOCKHOLM — Body temperature gauged prognosis in a retrospective analysis of patients hospitalized for heart failure.

Patients hospitalized for heart failure with hypothermia (a body temperature of 96.5°F or less) at admission were fourfold more likely to die during follow-up as were normathermic patients, Mihai Gheorghiade, M.D., said at the annual congress of the European Society of Cardiology.

“This is the first report [of the link with hypothermia], so it needs validation before making any conclusion that temperature is a prognostic factor,” said Dr. Gheorghiade, professor of medicine at Northwestern University, Chicago.

The correlation was made by reviewing data collected in a study designed to test the safety and efficacy of tolvaptan, an oral vasopressin receptor antagonist, in patients with systolic dysfunction who were hospitalized for worsening heart failure. Of 319 patients enrolled, body temperature readings on admission were available for 315.

Of those patients, 32 had hypothermia. At 60 days, mortality was 9.4% in patients with hypothermia and 5.9% in those with normothermia. After adjustment for baseline differences in blood urea nitrogen, age, and tolvaptan treatment, the patients with hypothermia were 3.9 times more likely to die.

In clinical trials, body temperature should be measured at admission and daily to correlate temperature and heart failure status, Dr. Gheorghiade said.

STOCKHOLM — Body temperature gauged prognosis in a retrospective analysis of patients hospitalized for heart failure.

Patients hospitalized for heart failure with hypothermia (a body temperature of 96.5°F or less) at admission were fourfold more likely to die during follow-up as were normathermic patients, Mihai Gheorghiade, M.D., said at the annual congress of the European Society of Cardiology.

“This is the first report [of the link with hypothermia], so it needs validation before making any conclusion that temperature is a prognostic factor,” said Dr. Gheorghiade, professor of medicine at Northwestern University, Chicago.

The correlation was made by reviewing data collected in a study designed to test the safety and efficacy of tolvaptan, an oral vasopressin receptor antagonist, in patients with systolic dysfunction who were hospitalized for worsening heart failure. Of 319 patients enrolled, body temperature readings on admission were available for 315.

Of those patients, 32 had hypothermia. At 60 days, mortality was 9.4% in patients with hypothermia and 5.9% in those with normothermia. After adjustment for baseline differences in blood urea nitrogen, age, and tolvaptan treatment, the patients with hypothermia were 3.9 times more likely to die.

In clinical trials, body temperature should be measured at admission and daily to correlate temperature and heart failure status, Dr. Gheorghiade said.

STOCKHOLM — Treatment with the ACE inhibitor perindopril cut the incidence of left ventricular remodeling following myocardial infarction in a study with more than 1,200 elderly patients with preserved left ventricular function.

Perindopril, at a dosage of 8 mg/day, “may be suggested as standard treatment in this clinical setting,” Roberto Ferrari, M.D., said at the annual congress of the European Society of Cardiology.

Based on the results of the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study and those of seven previous studies, “we now have convincing evidence that all patients with coronary artery disease should get treated with an ACE inhibitor,” commented Nicolas Danchin, M.D., a professor of medicine at the European Hospital Georges Pompidou in Paris.

The PREAMI study enrolled 1,252 patients, average age 72 years, at 109 centers in five European countries. All had a left ventricular ejection fraction of at least 40%; the average ejection fraction was 59%. About 80% of patients had New York Heart Association class I heart failure.

Patients were enrolled 7–20 days (a mean of 11 days) after their MI. Patients who had already begun treatment with an ACE inhibitor were withdrawn from the drug for at least 24 hours before entering the study. Three-quarters were on a β-blocker, which they continued to take.

Patients were randomized to treatment with either 4-mg perindopril daily or placebo for the first month of the study, after which the drug dosage was raised to 8 mg daily. Patients were followed for a total of 12 months. The study's primary end point was the combined incidence of death, hospitalization for heart failure, or left ventricular remodeling. Remodeling was defined as a rise of at least 8% in left ventricular and diastolic volumes. Echocardiographs were available a year after treatment started for 455 perindopril and 441 placebo patients.

The incidence of the primary end point was cut by 38% in patients on perindopril, compared with those on placebo, a statistically significant difference, reported Dr. Ferrari, head of cardiology at the University of Ferrara (Italy). But the result was driven entirely by a 46% relative drop in the rate of ventricular remodeling in the perindopril-treated patients (28%), compared with the controls (51%). There was no difference in the mortality rate.

The study was sponsored by Servier, marketer of perindopril (Coversyl) in Europe and elsewhere. In the United States, perindopril is marketed as Aceon by a partnership of Solvay Pharmaceuticals Inc. and CV Therapeutics Inc.

STOCKHOLM — Treatment with the ACE inhibitor perindopril cut the incidence of left ventricular remodeling following myocardial infarction in a study with more than 1,200 elderly patients with preserved left ventricular function.

Perindopril, at a dosage of 8 mg/day, “may be suggested as standard treatment in this clinical setting,” Roberto Ferrari, M.D., said at the annual congress of the European Society of Cardiology.

Based on the results of the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study and those of seven previous studies, “we now have convincing evidence that all patients with coronary artery disease should get treated with an ACE inhibitor,” commented Nicolas Danchin, M.D., a professor of medicine at the European Hospital Georges Pompidou in Paris.

The PREAMI study enrolled 1,252 patients, average age 72 years, at 109 centers in five European countries. All had a left ventricular ejection fraction of at least 40%; the average ejection fraction was 59%. About 80% of patients had New York Heart Association class I heart failure.

Patients were enrolled 7–20 days (a mean of 11 days) after their MI. Patients who had already begun treatment with an ACE inhibitor were withdrawn from the drug for at least 24 hours before entering the study. Three-quarters were on a β-blocker, which they continued to take.

Patients were randomized to treatment with either 4-mg perindopril daily or placebo for the first month of the study, after which the drug dosage was raised to 8 mg daily. Patients were followed for a total of 12 months. The study's primary end point was the combined incidence of death, hospitalization for heart failure, or left ventricular remodeling. Remodeling was defined as a rise of at least 8% in left ventricular and diastolic volumes. Echocardiographs were available a year after treatment started for 455 perindopril and 441 placebo patients.

The incidence of the primary end point was cut by 38% in patients on perindopril, compared with those on placebo, a statistically significant difference, reported Dr. Ferrari, head of cardiology at the University of Ferrara (Italy). But the result was driven entirely by a 46% relative drop in the rate of ventricular remodeling in the perindopril-treated patients (28%), compared with the controls (51%). There was no difference in the mortality rate.

The study was sponsored by Servier, marketer of perindopril (Coversyl) in Europe and elsewhere. In the United States, perindopril is marketed as Aceon by a partnership of Solvay Pharmaceuticals Inc. and CV Therapeutics Inc.

STOCKHOLM — Treatment with the ACE inhibitor perindopril cut the incidence of left ventricular remodeling following myocardial infarction in a study with more than 1,200 elderly patients with preserved left ventricular function.

Perindopril, at a dosage of 8 mg/day, “may be suggested as standard treatment in this clinical setting,” Roberto Ferrari, M.D., said at the annual congress of the European Society of Cardiology.

Based on the results of the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) study and those of seven previous studies, “we now have convincing evidence that all patients with coronary artery disease should get treated with an ACE inhibitor,” commented Nicolas Danchin, M.D., a professor of medicine at the European Hospital Georges Pompidou in Paris.

The PREAMI study enrolled 1,252 patients, average age 72 years, at 109 centers in five European countries. All had a left ventricular ejection fraction of at least 40%; the average ejection fraction was 59%. About 80% of patients had New York Heart Association class I heart failure.

Patients were enrolled 7–20 days (a mean of 11 days) after their MI. Patients who had already begun treatment with an ACE inhibitor were withdrawn from the drug for at least 24 hours before entering the study. Three-quarters were on a β-blocker, which they continued to take.

Patients were randomized to treatment with either 4-mg perindopril daily or placebo for the first month of the study, after which the drug dosage was raised to 8 mg daily. Patients were followed for a total of 12 months. The study's primary end point was the combined incidence of death, hospitalization for heart failure, or left ventricular remodeling. Remodeling was defined as a rise of at least 8% in left ventricular and diastolic volumes. Echocardiographs were available a year after treatment started for 455 perindopril and 441 placebo patients.

The incidence of the primary end point was cut by 38% in patients on perindopril, compared with those on placebo, a statistically significant difference, reported Dr. Ferrari, head of cardiology at the University of Ferrara (Italy). But the result was driven entirely by a 46% relative drop in the rate of ventricular remodeling in the perindopril-treated patients (28%), compared with the controls (51%). There was no difference in the mortality rate.

The study was sponsored by Servier, marketer of perindopril (Coversyl) in Europe and elsewhere. In the United States, perindopril is marketed as Aceon by a partnership of Solvay Pharmaceuticals Inc. and CV Therapeutics Inc.

BOCA RATON, FLA. — Fixed-dose isosorbide dinitrate and hydralazine significantly reduces left ventricular volume and increases ejection fraction in African American patients with moderate to severe heart failure, according to a subanalysis of the African American Heart Failure Trial.

Decreases in brain natriuretic peptide corresponded with the 6-month improvements in cardiac remodeling.

In the African American Heart Failure Trial (A-HeFT), the drug combination (BiDil, Nitromed Inc.) was associated with a 43% increase in survival for African Americans with moderate to severe heart failure (N. Engl. J. Med. 2004;351:2049–57). The magnitude of this finding surprised some because the A-HeFT patients were already aggressively treated for heart failure: 87% were already taking β-blockers, 78% were on ACE inhibitors, 39% were on aldosterone inhibitors, and 28% were taking angiotensin receptor blockers.

Regarding A-HeFT mortality, “the survival benefit versus placebo became obvious at 6 months or 7 months, and then the curves spread out remarkably after that,” Jay N. Cohn, M.D., said during a late-breaking clinical trial session at the annual meeting of the Heart Failure Society of America. He and his associates performed a subanalysis of the A-HeFT data to determine whether improvements in left ventricular structure and function could explain the improvement in survival. They compared echocardiographic findings and blood levels of brain natriuretic peptide (BNP) taken at baseline and after 6 months of treatment. One cardiologist evaluated all the digitized echocardiograms in blinded fashion.

Of the 1,050 self-identified African Americans enrolled in A-HeFT, 666 had ejection fraction values recorded at baseline and 6 months. Of this group, 329 were treated with combination therapy and 337 with placebo. In addition, there were 678 participants with left ventricular internal diameter in diastole (LVIDd) values taken at baseline and at 6 months. Of this group, 337 were treated with the combination and 341 with placebo.

At 6 months, there was a significant increase in ejection fraction in the combination group versus placebo, said Dr. Cohn, professor of medicine and director, Rasmussen Center for Cardiovascular Disease Prevention, University of Minnesota in Minneapolis. There also was a highly significant difference in LVIDd in the treatment group versus placebo group.

A meeting attendee asked about possible variation with the measurements in the study. “I'm more comfortable with the consistency of the LVIDd measurements, compared with the ejection fraction measurements, which can be interpreted differently,” Dr. Cohn responded.

The mean baseline BNP level was 300 pg/mL. By 6 months, the treatment group had a greater mean decrease, 28 pg/mL, compared with the placebo group, 11 pg/mL. Dr. Cohn called this a “striking difference between groups” that supports the cardiac remodeling improvements.

Another attendee asked how well the BNP values tracked with changes to left ventricular volume. Dr. Cohn said, “We don't know that yet, the tracking between the two is not always perfect. BNP is not always perfect. BNP is a continuum, but the lower the better.”

When asked if remodeling was dose dependent, Dr. Cohn replied, “We haven't looked at that yet.” He and his associates plan to perform subgroup analyses. “I would be surprised if the benefit on remodeling is confined to the African American population,” he said.

“The combination of isosorbide dinitrate and hydralazine induces regression of left ventricular remodeling in patients already treated with neurohormonal inhibitors,” Dr. Cohn said. “These data provide further support for the growing database that favorable effects on outcomes in heart failure can be attributed to favorable effects on left ventricular structural remodeling.”

BOCA RATON, FLA. — Fixed-dose isosorbide dinitrate and hydralazine significantly reduces left ventricular volume and increases ejection fraction in African American patients with moderate to severe heart failure, according to a subanalysis of the African American Heart Failure Trial.

Decreases in brain natriuretic peptide corresponded with the 6-month improvements in cardiac remodeling.

In the African American Heart Failure Trial (A-HeFT), the drug combination (BiDil, Nitromed Inc.) was associated with a 43% increase in survival for African Americans with moderate to severe heart failure (N. Engl. J. Med. 2004;351:2049–57). The magnitude of this finding surprised some because the A-HeFT patients were already aggressively treated for heart failure: 87% were already taking β-blockers, 78% were on ACE inhibitors, 39% were on aldosterone inhibitors, and 28% were taking angiotensin receptor blockers.

Regarding A-HeFT mortality, “the survival benefit versus placebo became obvious at 6 months or 7 months, and then the curves spread out remarkably after that,” Jay N. Cohn, M.D., said during a late-breaking clinical trial session at the annual meeting of the Heart Failure Society of America. He and his associates performed a subanalysis of the A-HeFT data to determine whether improvements in left ventricular structure and function could explain the improvement in survival. They compared echocardiographic findings and blood levels of brain natriuretic peptide (BNP) taken at baseline and after 6 months of treatment. One cardiologist evaluated all the digitized echocardiograms in blinded fashion.

Of the 1,050 self-identified African Americans enrolled in A-HeFT, 666 had ejection fraction values recorded at baseline and 6 months. Of this group, 329 were treated with combination therapy and 337 with placebo. In addition, there were 678 participants with left ventricular internal diameter in diastole (LVIDd) values taken at baseline and at 6 months. Of this group, 337 were treated with the combination and 341 with placebo.

At 6 months, there was a significant increase in ejection fraction in the combination group versus placebo, said Dr. Cohn, professor of medicine and director, Rasmussen Center for Cardiovascular Disease Prevention, University of Minnesota in Minneapolis. There also was a highly significant difference in LVIDd in the treatment group versus placebo group.

A meeting attendee asked about possible variation with the measurements in the study. “I'm more comfortable with the consistency of the LVIDd measurements, compared with the ejection fraction measurements, which can be interpreted differently,” Dr. Cohn responded.

The mean baseline BNP level was 300 pg/mL. By 6 months, the treatment group had a greater mean decrease, 28 pg/mL, compared with the placebo group, 11 pg/mL. Dr. Cohn called this a “striking difference between groups” that supports the cardiac remodeling improvements.

Another attendee asked how well the BNP values tracked with changes to left ventricular volume. Dr. Cohn said, “We don't know that yet, the tracking between the two is not always perfect. BNP is not always perfect. BNP is a continuum, but the lower the better.”

When asked if remodeling was dose dependent, Dr. Cohn replied, “We haven't looked at that yet.” He and his associates plan to perform subgroup analyses. “I would be surprised if the benefit on remodeling is confined to the African American population,” he said.

“The combination of isosorbide dinitrate and hydralazine induces regression of left ventricular remodeling in patients already treated with neurohormonal inhibitors,” Dr. Cohn said. “These data provide further support for the growing database that favorable effects on outcomes in heart failure can be attributed to favorable effects on left ventricular structural remodeling.”

BOCA RATON, FLA. — Fixed-dose isosorbide dinitrate and hydralazine significantly reduces left ventricular volume and increases ejection fraction in African American patients with moderate to severe heart failure, according to a subanalysis of the African American Heart Failure Trial.

Decreases in brain natriuretic peptide corresponded with the 6-month improvements in cardiac remodeling.

In the African American Heart Failure Trial (A-HeFT), the drug combination (BiDil, Nitromed Inc.) was associated with a 43% increase in survival for African Americans with moderate to severe heart failure (N. Engl. J. Med. 2004;351:2049–57). The magnitude of this finding surprised some because the A-HeFT patients were already aggressively treated for heart failure: 87% were already taking β-blockers, 78% were on ACE inhibitors, 39% were on aldosterone inhibitors, and 28% were taking angiotensin receptor blockers.

Regarding A-HeFT mortality, “the survival benefit versus placebo became obvious at 6 months or 7 months, and then the curves spread out remarkably after that,” Jay N. Cohn, M.D., said during a late-breaking clinical trial session at the annual meeting of the Heart Failure Society of America. He and his associates performed a subanalysis of the A-HeFT data to determine whether improvements in left ventricular structure and function could explain the improvement in survival. They compared echocardiographic findings and blood levels of brain natriuretic peptide (BNP) taken at baseline and after 6 months of treatment. One cardiologist evaluated all the digitized echocardiograms in blinded fashion.

Of the 1,050 self-identified African Americans enrolled in A-HeFT, 666 had ejection fraction values recorded at baseline and 6 months. Of this group, 329 were treated with combination therapy and 337 with placebo. In addition, there were 678 participants with left ventricular internal diameter in diastole (LVIDd) values taken at baseline and at 6 months. Of this group, 337 were treated with the combination and 341 with placebo.

At 6 months, there was a significant increase in ejection fraction in the combination group versus placebo, said Dr. Cohn, professor of medicine and director, Rasmussen Center for Cardiovascular Disease Prevention, University of Minnesota in Minneapolis. There also was a highly significant difference in LVIDd in the treatment group versus placebo group.

A meeting attendee asked about possible variation with the measurements in the study. “I'm more comfortable with the consistency of the LVIDd measurements, compared with the ejection fraction measurements, which can be interpreted differently,” Dr. Cohn responded.

The mean baseline BNP level was 300 pg/mL. By 6 months, the treatment group had a greater mean decrease, 28 pg/mL, compared with the placebo group, 11 pg/mL. Dr. Cohn called this a “striking difference between groups” that supports the cardiac remodeling improvements.

Another attendee asked how well the BNP values tracked with changes to left ventricular volume. Dr. Cohn said, “We don't know that yet, the tracking between the two is not always perfect. BNP is not always perfect. BNP is a continuum, but the lower the better.”

When asked if remodeling was dose dependent, Dr. Cohn replied, “We haven't looked at that yet.” He and his associates plan to perform subgroup analyses. “I would be surprised if the benefit on remodeling is confined to the African American population,” he said.

“The combination of isosorbide dinitrate and hydralazine induces regression of left ventricular remodeling in patients already treated with neurohormonal inhibitors,” Dr. Cohn said. “These data provide further support for the growing database that favorable effects on outcomes in heart failure can be attributed to favorable effects on left ventricular structural remodeling.”

STOCKHOLM — An oral inotropic drug was safe but not effective in a pair of studies that together enrolled more than 1,800 patients with advanced heart failure.

Although the Studies of Oral Enoximone Therapy in Advanced Heart Failure (ESSENTIAL) failed to show that enoximone could cut the incidence of death or cardiovascular hospitalization, the fact that the drug was safe means that it is eligible for further testing in very sick heart failure patients, Michael Bristow, M.D., said in an interview at the annual congress of the European Society of Cardiology.

“We have a lack of effective medications for very sick patients with decompensated heart failure,” especially those with recurrent episodes of acute decompensation, said Dr. Bristow, codirector of the Cardiovascular Institute at the University of Colorado in Denver. “Enoximone has now been [proved] safe, and we saw a signal of efficacy in the sickest patients.”

The studies enrolled 1,854 patients with New York Heart Association class III or IV heart failure at 211 centers in 16 countries. One study was done in North and South America; the other was done in Europe.

The patients also had a left ventricular ejection fraction (LVEF) of 30% or less and had had at least one hospitalization or two outpatient visits for worsening heart failure during the year before they entered the study. All were already on optimal treatment with both a β-blocker and an ACE inhibitor or an angiotensin-receptor blocker.

The patients were randomized either to placebo or to 25 mg enoximone t.i.d. After 2 weeks, the dosage was raised to 50 mg t.i.d for patients who weighed more than 50 kg and had no adverse effects from the lower dosage. These dosages were substantially lower than were those in previous enoximone studies.

After an average follow-up of 16.4 months, there was no significant difference between the two arms in either all-cause death, the major safety end point, or in all-cause death and cardiovascular hospitalizations, the major efficacy end point, said Marco Metra, M.D., professor of cardiology at the University of Brescia (Italy).

In the American but not the European study, treatment with enoximone was linked with a significant increase in a secondary end point measured by a 6-minute walk test done after 6 months of treatment. The two treatment arms showed no significant difference for the third efficacy end point of the study, patients' self-assessment of symptomatic improvement.

In a prespecified subgroup analysis that assessed efficacy responses in patients with an LVEF below the median for all patients (25%) and in those with an ejection fraction above the median, treatment with enoximone in patients with the worst left ventricular function was associated with a 10% reduction in both all-cause death and in deaths and cardiovascular hospitalizations, compared with placebo.

Enoximone treatment in the subgroup was also linked with a mean gain of 15 m in a 6-minute walk distance, compared with the placebo group. Further analyses of results in the sicker patients also showed enoximone treatment was especially effective for reducing deaths and hospitalizations after the first 16 months of treatment.

Enoximone is in the same inotropic class as milrinone. But enoximone is a pure phosphodiesterase inhibitor, which, along with its use in the setting of β-blocker treatment, may lead to its increased safety, said Dr. Bristow, who is also chief science and medical officer for Myogen, which sponsored ESSENTIAL and markets an intravenous formulation of enoximone (Perfan) in Europe, in an interview.

STOCKHOLM — An oral inotropic drug was safe but not effective in a pair of studies that together enrolled more than 1,800 patients with advanced heart failure.

Although the Studies of Oral Enoximone Therapy in Advanced Heart Failure (ESSENTIAL) failed to show that enoximone could cut the incidence of death or cardiovascular hospitalization, the fact that the drug was safe means that it is eligible for further testing in very sick heart failure patients, Michael Bristow, M.D., said in an interview at the annual congress of the European Society of Cardiology.

“We have a lack of effective medications for very sick patients with decompensated heart failure,” especially those with recurrent episodes of acute decompensation, said Dr. Bristow, codirector of the Cardiovascular Institute at the University of Colorado in Denver. “Enoximone has now been [proved] safe, and we saw a signal of efficacy in the sickest patients.”

The studies enrolled 1,854 patients with New York Heart Association class III or IV heart failure at 211 centers in 16 countries. One study was done in North and South America; the other was done in Europe.

The patients also had a left ventricular ejection fraction (LVEF) of 30% or less and had had at least one hospitalization or two outpatient visits for worsening heart failure during the year before they entered the study. All were already on optimal treatment with both a β-blocker and an ACE inhibitor or an angiotensin-receptor blocker.

The patients were randomized either to placebo or to 25 mg enoximone t.i.d. After 2 weeks, the dosage was raised to 50 mg t.i.d for patients who weighed more than 50 kg and had no adverse effects from the lower dosage. These dosages were substantially lower than were those in previous enoximone studies.

After an average follow-up of 16.4 months, there was no significant difference between the two arms in either all-cause death, the major safety end point, or in all-cause death and cardiovascular hospitalizations, the major efficacy end point, said Marco Metra, M.D., professor of cardiology at the University of Brescia (Italy).

In the American but not the European study, treatment with enoximone was linked with a significant increase in a secondary end point measured by a 6-minute walk test done after 6 months of treatment. The two treatment arms showed no significant difference for the third efficacy end point of the study, patients' self-assessment of symptomatic improvement.

In a prespecified subgroup analysis that assessed efficacy responses in patients with an LVEF below the median for all patients (25%) and in those with an ejection fraction above the median, treatment with enoximone in patients with the worst left ventricular function was associated with a 10% reduction in both all-cause death and in deaths and cardiovascular hospitalizations, compared with placebo.

Enoximone treatment in the subgroup was also linked with a mean gain of 15 m in a 6-minute walk distance, compared with the placebo group. Further analyses of results in the sicker patients also showed enoximone treatment was especially effective for reducing deaths and hospitalizations after the first 16 months of treatment.

Enoximone is in the same inotropic class as milrinone. But enoximone is a pure phosphodiesterase inhibitor, which, along with its use in the setting of β-blocker treatment, may lead to its increased safety, said Dr. Bristow, who is also chief science and medical officer for Myogen, which sponsored ESSENTIAL and markets an intravenous formulation of enoximone (Perfan) in Europe, in an interview.

STOCKHOLM — An oral inotropic drug was safe but not effective in a pair of studies that together enrolled more than 1,800 patients with advanced heart failure.

Although the Studies of Oral Enoximone Therapy in Advanced Heart Failure (ESSENTIAL) failed to show that enoximone could cut the incidence of death or cardiovascular hospitalization, the fact that the drug was safe means that it is eligible for further testing in very sick heart failure patients, Michael Bristow, M.D., said in an interview at the annual congress of the European Society of Cardiology.

“We have a lack of effective medications for very sick patients with decompensated heart failure,” especially those with recurrent episodes of acute decompensation, said Dr. Bristow, codirector of the Cardiovascular Institute at the University of Colorado in Denver. “Enoximone has now been [proved] safe, and we saw a signal of efficacy in the sickest patients.”

The studies enrolled 1,854 patients with New York Heart Association class III or IV heart failure at 211 centers in 16 countries. One study was done in North and South America; the other was done in Europe.

The patients also had a left ventricular ejection fraction (LVEF) of 30% or less and had had at least one hospitalization or two outpatient visits for worsening heart failure during the year before they entered the study. All were already on optimal treatment with both a β-blocker and an ACE inhibitor or an angiotensin-receptor blocker.

The patients were randomized either to placebo or to 25 mg enoximone t.i.d. After 2 weeks, the dosage was raised to 50 mg t.i.d for patients who weighed more than 50 kg and had no adverse effects from the lower dosage. These dosages were substantially lower than were those in previous enoximone studies.

After an average follow-up of 16.4 months, there was no significant difference between the two arms in either all-cause death, the major safety end point, or in all-cause death and cardiovascular hospitalizations, the major efficacy end point, said Marco Metra, M.D., professor of cardiology at the University of Brescia (Italy).

In the American but not the European study, treatment with enoximone was linked with a significant increase in a secondary end point measured by a 6-minute walk test done after 6 months of treatment. The two treatment arms showed no significant difference for the third efficacy end point of the study, patients' self-assessment of symptomatic improvement.

In a prespecified subgroup analysis that assessed efficacy responses in patients with an LVEF below the median for all patients (25%) and in those with an ejection fraction above the median, treatment with enoximone in patients with the worst left ventricular function was associated with a 10% reduction in both all-cause death and in deaths and cardiovascular hospitalizations, compared with placebo.

Enoximone treatment in the subgroup was also linked with a mean gain of 15 m in a 6-minute walk distance, compared with the placebo group. Further analyses of results in the sicker patients also showed enoximone treatment was especially effective for reducing deaths and hospitalizations after the first 16 months of treatment.

Enoximone is in the same inotropic class as milrinone. But enoximone is a pure phosphodiesterase inhibitor, which, along with its use in the setting of β-blocker treatment, may lead to its increased safety, said Dr. Bristow, who is also chief science and medical officer for Myogen, which sponsored ESSENTIAL and markets an intravenous formulation of enoximone (Perfan) in Europe, in an interview.

WASHINGTON — Receipt of a left ventricular assist device at an older age may adversely affect long-term, but not short-term, survival with the device, Evgenij V. Potapov, M.D., reported at the annual conference of the American Society for Artificial Internal Organs.

In a review of 403 patients who have received LVADs at the German Heart Institute, Berlin, since 1987, the 116 patients who were older than 60 years were 2.5 times more likely than younger patients to have a negative long-term outcome, such as no heart transplantation, an inability to wean off the LVAD within 6 months, support for less than 6 months in patients with permanent implants, and failure to continue support for more than 6 months in other patients, said Dr. Potapov, a cardiothoracic surgeon at the institute.

No risk factor significantly predicted a negative long-term outcome in patients older than age 60.

“Postcardiotomy support in older patients should be performed in really selective cases,” he said.

WASHINGTON — Receipt of a left ventricular assist device at an older age may adversely affect long-term, but not short-term, survival with the device, Evgenij V. Potapov, M.D., reported at the annual conference of the American Society for Artificial Internal Organs.

In a review of 403 patients who have received LVADs at the German Heart Institute, Berlin, since 1987, the 116 patients who were older than 60 years were 2.5 times more likely than younger patients to have a negative long-term outcome, such as no heart transplantation, an inability to wean off the LVAD within 6 months, support for less than 6 months in patients with permanent implants, and failure to continue support for more than 6 months in other patients, said Dr. Potapov, a cardiothoracic surgeon at the institute.

No risk factor significantly predicted a negative long-term outcome in patients older than age 60.

“Postcardiotomy support in older patients should be performed in really selective cases,” he said.

WASHINGTON — Receipt of a left ventricular assist device at an older age may adversely affect long-term, but not short-term, survival with the device, Evgenij V. Potapov, M.D., reported at the annual conference of the American Society for Artificial Internal Organs.

In a review of 403 patients who have received LVADs at the German Heart Institute, Berlin, since 1987, the 116 patients who were older than 60 years were 2.5 times more likely than younger patients to have a negative long-term outcome, such as no heart transplantation, an inability to wean off the LVAD within 6 months, support for less than 6 months in patients with permanent implants, and failure to continue support for more than 6 months in other patients, said Dr. Potapov, a cardiothoracic surgeon at the institute.

No risk factor significantly predicted a negative long-term outcome in patients older than age 60.

“Postcardiotomy support in older patients should be performed in really selective cases,” he said.

VANCOUVER, B.C. — The latest Cochrane systematic review of digoxin for treatment of heart failure patients in sinus rhythm paints a picture of a more than 200-year-old drug that's still clinically useful, although it has no effect on mortality, William B. Hood Jr., M.D., said at a meeting sponsored by the International Academy of Cardiology.

“It's probably not first-line therapy. It's not very powerful. But it's available for patients who are not fully responsive to other agents that have become first-line treatments—the ACE inhibitors, β-blockers, spironolactone, and the angiotensin receptor blockers,” added Dr. Hood, lead author of the recent Cochrane review and a cardiologist at the University of Washington, Seattle.

The metaanalysis was restricted to randomized, double-blind, placebo-controlled trials involving adults followed for at least 7 weeks. Thirteen trials totaling nearly 7,900 patients qualified, including the largest of all digoxin studies: the 6,800-patient, 3-year Digitalis Investigation Group (DIG) trial (N. Engl. J. Med. 1997;336:525–33).

Why even bother doing a metaanalysis when one trial is so dominant? Dr. Hood explained that the smaller trials are helpful in that each consistently reached the same conclusion as DIG regarding the effect of digoxin on mortality—namely, there is none. The drug didn't lessen mortality, nor did it significantly worsen it.

In the DIG trial, however, there was a nonsignificant trend for fewer deaths from heart failure in digoxin-treated patients and a hint that the inotrope may have caused more arrhythmia deaths, although this wasn't a prespecified study end point.

Digoxin's effect on deterioration in clinical status was much more clearcut in the metaanalysis. The odds ratio for that end point was 0.31, meaning patients randomized to digoxin were 69% less likely to show significant clinical deterioration than were control patients.

Digoxin patients were 32% less likely to experience the end point of hospitalization for worsening heart failure.

Two studies included in the metaanalysis showed that patients on an ACE inhibitor plus digoxin did better than those on an ACE inhibitor plus placebo. However, the effects of digoxin in patients on other agents that have become first-line therapies in heart failure more recently than the ACE inhibitors, including β-blockers and aldosterone antagonists, haven't been systematically studied. For ethical reasons it's highly unlikely such trials will ever be done, Dr. Hood said.

VANCOUVER, B.C. — The latest Cochrane systematic review of digoxin for treatment of heart failure patients in sinus rhythm paints a picture of a more than 200-year-old drug that's still clinically useful, although it has no effect on mortality, William B. Hood Jr., M.D., said at a meeting sponsored by the International Academy of Cardiology.

“It's probably not first-line therapy. It's not very powerful. But it's available for patients who are not fully responsive to other agents that have become first-line treatments—the ACE inhibitors, β-blockers, spironolactone, and the angiotensin receptor blockers,” added Dr. Hood, lead author of the recent Cochrane review and a cardiologist at the University of Washington, Seattle.

The metaanalysis was restricted to randomized, double-blind, placebo-controlled trials involving adults followed for at least 7 weeks. Thirteen trials totaling nearly 7,900 patients qualified, including the largest of all digoxin studies: the 6,800-patient, 3-year Digitalis Investigation Group (DIG) trial (N. Engl. J. Med. 1997;336:525–33).

Why even bother doing a metaanalysis when one trial is so dominant? Dr. Hood explained that the smaller trials are helpful in that each consistently reached the same conclusion as DIG regarding the effect of digoxin on mortality—namely, there is none. The drug didn't lessen mortality, nor did it significantly worsen it.

In the DIG trial, however, there was a nonsignificant trend for fewer deaths from heart failure in digoxin-treated patients and a hint that the inotrope may have caused more arrhythmia deaths, although this wasn't a prespecified study end point.

Digoxin's effect on deterioration in clinical status was much more clearcut in the metaanalysis. The odds ratio for that end point was 0.31, meaning patients randomized to digoxin were 69% less likely to show significant clinical deterioration than were control patients.

Digoxin patients were 32% less likely to experience the end point of hospitalization for worsening heart failure.

Two studies included in the metaanalysis showed that patients on an ACE inhibitor plus digoxin did better than those on an ACE inhibitor plus placebo. However, the effects of digoxin in patients on other agents that have become first-line therapies in heart failure more recently than the ACE inhibitors, including β-blockers and aldosterone antagonists, haven't been systematically studied. For ethical reasons it's highly unlikely such trials will ever be done, Dr. Hood said.

VANCOUVER, B.C. — The latest Cochrane systematic review of digoxin for treatment of heart failure patients in sinus rhythm paints a picture of a more than 200-year-old drug that's still clinically useful, although it has no effect on mortality, William B. Hood Jr., M.D., said at a meeting sponsored by the International Academy of Cardiology.

“It's probably not first-line therapy. It's not very powerful. But it's available for patients who are not fully responsive to other agents that have become first-line treatments—the ACE inhibitors, β-blockers, spironolactone, and the angiotensin receptor blockers,” added Dr. Hood, lead author of the recent Cochrane review and a cardiologist at the University of Washington, Seattle.

The metaanalysis was restricted to randomized, double-blind, placebo-controlled trials involving adults followed for at least 7 weeks. Thirteen trials totaling nearly 7,900 patients qualified, including the largest of all digoxin studies: the 6,800-patient, 3-year Digitalis Investigation Group (DIG) trial (N. Engl. J. Med. 1997;336:525–33).

Why even bother doing a metaanalysis when one trial is so dominant? Dr. Hood explained that the smaller trials are helpful in that each consistently reached the same conclusion as DIG regarding the effect of digoxin on mortality—namely, there is none. The drug didn't lessen mortality, nor did it significantly worsen it.

In the DIG trial, however, there was a nonsignificant trend for fewer deaths from heart failure in digoxin-treated patients and a hint that the inotrope may have caused more arrhythmia deaths, although this wasn't a prespecified study end point.

Digoxin's effect on deterioration in clinical status was much more clearcut in the metaanalysis. The odds ratio for that end point was 0.31, meaning patients randomized to digoxin were 69% less likely to show significant clinical deterioration than were control patients.

Digoxin patients were 32% less likely to experience the end point of hospitalization for worsening heart failure.

Two studies included in the metaanalysis showed that patients on an ACE inhibitor plus digoxin did better than those on an ACE inhibitor plus placebo. However, the effects of digoxin in patients on other agents that have become first-line therapies in heart failure more recently than the ACE inhibitors, including β-blockers and aldosterone antagonists, haven't been systematically studied. For ethical reasons it's highly unlikely such trials will ever be done, Dr. Hood said.

VANCOUVER, B.C. — The recent big therapeutic successes in heart failure have come from implantable electrophysiologic devices—cardiac resynchronization therapy, implantable cardioverter defibrillators—and surgical advances, such as ventricular reduction procedures.

Although attempts to develop new drugs have proved largely disappointing of late, that may be about to change, Robert E. Hobbs, M.D., said at a meeting sponsored by the International Academy of Cardiology.

Many heart failure drugs are working their way through the developmental process. Dr. Hobbs chose to highlight half a dozen, each having a different and novel mechanism of action.

Each of these drugs has shown promise in clinical trials, and each addresses a different hypothesis about the nature of worsening heart failure. And these six interesting drugs constitute only a portion of what's in the pipeline, added Dr. Hobbs of the Cleveland Clinic Foundation.

▸ A xanthine oxidase inhibitor. Oxypurinol, an analogue of allopurinol, inhibits xanthine oxidase, the enzyme that produces uric acid, as well as harmful oxygen free radicals. Xanthine oxidase is upregulated in heart failure. By inhibiting this enzyme, oxypurinol has been shown to improve myocardial energetics and endothelial function.

The Oxypurinol Therapy for Congestive Heart Failure (OPT-CHF) trial is a recently completed 400-patient phase II/III randomized double-blind trial. The data are now being analyzed and are due to be presented this fall at the annual meeting of the American Heart Association.

▸ A unique inotropic agent. Levosimendan's mechanism of action differs from that of other inotropes, such as dobutamine and milrinone. It binds to cardiac troponin C. Levosimendan is categorized as a calcium-sensitizing agent because it enhances myocardial contractility without increasing intracellular calcium concentrations. The drug also acts as a vasodilator through activation of potassium channels. Moreover, it's a weak phosphodiesterase inhibitor as well.

Levosimendan's hemodynamic effects include an increase in cardiac index along with systemic and coronary vasodilation. In heart failure patients, levosimendan reduces elevated intracardiac pressures without increasing myocardial oxygen consumption. Unlike other inotropes, it has low arrhythmic potential, Dr. Hobbs stressed. The drug is approved for use in more than 30 countries as a treatment for patients with decompensated heart failure in need of inotropic support. But not in the United States.

“In the United States, they're reinventing the wheel and taking the drug through repeats of the clinical trials,” the cardiologist said. “I can't believe I'm still talking about levosimendan 10 years later. I was involved in clinical trials of the oral formulation a decade ago.”

What's under study today, however, is the intravenous version of levosimendan. The 800-patient phase-III Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE) trial is due to be presented in November at the AHA meeting.

▸ A thyroid hormone analogue. Roughly 30% of patients with advanced heart failure have low T₃ and normal TSH. Giving T₃ to patients with heart failure confers multiple cardiovascular benefits, including positive inotropic effects, improved diastolic relaxation, and stimulation of alpha-myosin heavy chain gene expression. But it also causes tachycardia, largely negating the improved cardiac performance.

Treatment with 3,5-diiodothyropropionic acid (DITPA), a T₃ analogue, offers similar cardiovascular benefits—but without the tachycardia. A 40-center, 34-week randomized trial is underway in 150 patients with class III/IV heart failure, low ejection fraction, low T₃, and normal TSH. Participants are assigned to one of two doses of DITPA or placebo.

▸ An atrial natriuretic peptide. Carperitide, a synthetic atrial natriuretic peptide, is an intravenous vasodilator approved for use in acutely decompensated heart failure in Japan for a decade. Its multiple effects are similar to those of nesiritide (Natrecor), recombinant brain natriuretic peptide.

An ongoing U.S. clinical trial is aimed at determining the safety and efficacy of seven different doses of carperitide in 158 patients.

▸ Adenosine receptor antagonists. These agents cause afferent arteriolar dilatation. They promote diuresis while preserving renal function and maintaining glomerular filtration rate. One agent—known at this point only as KW-3902—is the subject of an ongoing clinical trial in 200 hospitalized heart failure patients with impaired renal function. It's a 4-day treatment study with 30-day follow-up. “These agents look promising, but it's early,” Dr. Hobbs commented.

▸ Vasopressin antagonists. Nicknamed “super diuretics,” these drugs cause profound diuresis without disrupting electrolytes. The target of these drugs—vasopressin—is synthesized by the hypothalamus in response to baroreceptor and osmotic stimuli. It causes vasoconstriction and sodium and water retention.

Two vasopressin antagonists, or “vaptans,” have been tested in clinical trials: conivaptan and tolvaptan. Ongoing is the large multinational phase III Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST). Results are probably several years off, according to Dr. Hobbs.

Udho Thadani, M.D., commented that heart failure patients already have a rather full plate just with today's standard medications, which include a b-blocker, an ACE inhibitor or angiotensin receptor blocker, an aldosterone blocker such as spironolactone, and digoxin.

If even a few of the drugs with novel mechanisms of action that are in the developmental pipeline eventually find their way into routine clinical practice on top of today's standard therapy, compliance issues will become a much more prominent concern, predicted Dr. Thadani, professor emeritus of medicine at the University of Oklahoma, Oklahoma City.

VANCOUVER, B.C. — The recent big therapeutic successes in heart failure have come from implantable electrophysiologic devices—cardiac resynchronization therapy, implantable cardioverter defibrillators—and surgical advances, such as ventricular reduction procedures.

Although attempts to develop new drugs have proved largely disappointing of late, that may be about to change, Robert E. Hobbs, M.D., said at a meeting sponsored by the International Academy of Cardiology.

Many heart failure drugs are working their way through the developmental process. Dr. Hobbs chose to highlight half a dozen, each having a different and novel mechanism of action.

Each of these drugs has shown promise in clinical trials, and each addresses a different hypothesis about the nature of worsening heart failure. And these six interesting drugs constitute only a portion of what's in the pipeline, added Dr. Hobbs of the Cleveland Clinic Foundation.

▸ A xanthine oxidase inhibitor. Oxypurinol, an analogue of allopurinol, inhibits xanthine oxidase, the enzyme that produces uric acid, as well as harmful oxygen free radicals. Xanthine oxidase is upregulated in heart failure. By inhibiting this enzyme, oxypurinol has been shown to improve myocardial energetics and endothelial function.

The Oxypurinol Therapy for Congestive Heart Failure (OPT-CHF) trial is a recently completed 400-patient phase II/III randomized double-blind trial. The data are now being analyzed and are due to be presented this fall at the annual meeting of the American Heart Association.

▸ A unique inotropic agent. Levosimendan's mechanism of action differs from that of other inotropes, such as dobutamine and milrinone. It binds to cardiac troponin C. Levosimendan is categorized as a calcium-sensitizing agent because it enhances myocardial contractility without increasing intracellular calcium concentrations. The drug also acts as a vasodilator through activation of potassium channels. Moreover, it's a weak phosphodiesterase inhibitor as well.

Levosimendan's hemodynamic effects include an increase in cardiac index along with systemic and coronary vasodilation. In heart failure patients, levosimendan reduces elevated intracardiac pressures without increasing myocardial oxygen consumption. Unlike other inotropes, it has low arrhythmic potential, Dr. Hobbs stressed. The drug is approved for use in more than 30 countries as a treatment for patients with decompensated heart failure in need of inotropic support. But not in the United States.

“In the United States, they're reinventing the wheel and taking the drug through repeats of the clinical trials,” the cardiologist said. “I can't believe I'm still talking about levosimendan 10 years later. I was involved in clinical trials of the oral formulation a decade ago.”

What's under study today, however, is the intravenous version of levosimendan. The 800-patient phase-III Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE) trial is due to be presented in November at the AHA meeting.

▸ A thyroid hormone analogue. Roughly 30% of patients with advanced heart failure have low T₃ and normal TSH. Giving T₃ to patients with heart failure confers multiple cardiovascular benefits, including positive inotropic effects, improved diastolic relaxation, and stimulation of alpha-myosin heavy chain gene expression. But it also causes tachycardia, largely negating the improved cardiac performance.

Treatment with 3,5-diiodothyropropionic acid (DITPA), a T₃ analogue, offers similar cardiovascular benefits—but without the tachycardia. A 40-center, 34-week randomized trial is underway in 150 patients with class III/IV heart failure, low ejection fraction, low T₃, and normal TSH. Participants are assigned to one of two doses of DITPA or placebo.

▸ An atrial natriuretic peptide. Carperitide, a synthetic atrial natriuretic peptide, is an intravenous vasodilator approved for use in acutely decompensated heart failure in Japan for a decade. Its multiple effects are similar to those of nesiritide (Natrecor), recombinant brain natriuretic peptide.

An ongoing U.S. clinical trial is aimed at determining the safety and efficacy of seven different doses of carperitide in 158 patients.

▸ Adenosine receptor antagonists. These agents cause afferent arteriolar dilatation. They promote diuresis while preserving renal function and maintaining glomerular filtration rate. One agent—known at this point only as KW-3902—is the subject of an ongoing clinical trial in 200 hospitalized heart failure patients with impaired renal function. It's a 4-day treatment study with 30-day follow-up. “These agents look promising, but it's early,” Dr. Hobbs commented.

▸ Vasopressin antagonists. Nicknamed “super diuretics,” these drugs cause profound diuresis without disrupting electrolytes. The target of these drugs—vasopressin—is synthesized by the hypothalamus in response to baroreceptor and osmotic stimuli. It causes vasoconstriction and sodium and water retention.

Two vasopressin antagonists, or “vaptans,” have been tested in clinical trials: conivaptan and tolvaptan. Ongoing is the large multinational phase III Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST). Results are probably several years off, according to Dr. Hobbs.

Udho Thadani, M.D., commented that heart failure patients already have a rather full plate just with today's standard medications, which include a b-blocker, an ACE inhibitor or angiotensin receptor blocker, an aldosterone blocker such as spironolactone, and digoxin.

If even a few of the drugs with novel mechanisms of action that are in the developmental pipeline eventually find their way into routine clinical practice on top of today's standard therapy, compliance issues will become a much more prominent concern, predicted Dr. Thadani, professor emeritus of medicine at the University of Oklahoma, Oklahoma City.

VANCOUVER, B.C. — The recent big therapeutic successes in heart failure have come from implantable electrophysiologic devices—cardiac resynchronization therapy, implantable cardioverter defibrillators—and surgical advances, such as ventricular reduction procedures.

Although attempts to develop new drugs have proved largely disappointing of late, that may be about to change, Robert E. Hobbs, M.D., said at a meeting sponsored by the International Academy of Cardiology.

Many heart failure drugs are working their way through the developmental process. Dr. Hobbs chose to highlight half a dozen, each having a different and novel mechanism of action.

Each of these drugs has shown promise in clinical trials, and each addresses a different hypothesis about the nature of worsening heart failure. And these six interesting drugs constitute only a portion of what's in the pipeline, added Dr. Hobbs of the Cleveland Clinic Foundation.

▸ A xanthine oxidase inhibitor. Oxypurinol, an analogue of allopurinol, inhibits xanthine oxidase, the enzyme that produces uric acid, as well as harmful oxygen free radicals. Xanthine oxidase is upregulated in heart failure. By inhibiting this enzyme, oxypurinol has been shown to improve myocardial energetics and endothelial function.

The Oxypurinol Therapy for Congestive Heart Failure (OPT-CHF) trial is a recently completed 400-patient phase II/III randomized double-blind trial. The data are now being analyzed and are due to be presented this fall at the annual meeting of the American Heart Association.

▸ A unique inotropic agent. Levosimendan's mechanism of action differs from that of other inotropes, such as dobutamine and milrinone. It binds to cardiac troponin C. Levosimendan is categorized as a calcium-sensitizing agent because it enhances myocardial contractility without increasing intracellular calcium concentrations. The drug also acts as a vasodilator through activation of potassium channels. Moreover, it's a weak phosphodiesterase inhibitor as well.

Levosimendan's hemodynamic effects include an increase in cardiac index along with systemic and coronary vasodilation. In heart failure patients, levosimendan reduces elevated intracardiac pressures without increasing myocardial oxygen consumption. Unlike other inotropes, it has low arrhythmic potential, Dr. Hobbs stressed. The drug is approved for use in more than 30 countries as a treatment for patients with decompensated heart failure in need of inotropic support. But not in the United States.

“In the United States, they're reinventing the wheel and taking the drug through repeats of the clinical trials,” the cardiologist said. “I can't believe I'm still talking about levosimendan 10 years later. I was involved in clinical trials of the oral formulation a decade ago.”

What's under study today, however, is the intravenous version of levosimendan. The 800-patient phase-III Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE) trial is due to be presented in November at the AHA meeting.

▸ A thyroid hormone analogue. Roughly 30% of patients with advanced heart failure have low T₃ and normal TSH. Giving T₃ to patients with heart failure confers multiple cardiovascular benefits, including positive inotropic effects, improved diastolic relaxation, and stimulation of alpha-myosin heavy chain gene expression. But it also causes tachycardia, largely negating the improved cardiac performance.

Treatment with 3,5-diiodothyropropionic acid (DITPA), a T₃ analogue, offers similar cardiovascular benefits—but without the tachycardia. A 40-center, 34-week randomized trial is underway in 150 patients with class III/IV heart failure, low ejection fraction, low T₃, and normal TSH. Participants are assigned to one of two doses of DITPA or placebo.

▸ An atrial natriuretic peptide. Carperitide, a synthetic atrial natriuretic peptide, is an intravenous vasodilator approved for use in acutely decompensated heart failure in Japan for a decade. Its multiple effects are similar to those of nesiritide (Natrecor), recombinant brain natriuretic peptide.

An ongoing U.S. clinical trial is aimed at determining the safety and efficacy of seven different doses of carperitide in 158 patients.

▸ Adenosine receptor antagonists. These agents cause afferent arteriolar dilatation. They promote diuresis while preserving renal function and maintaining glomerular filtration rate. One agent—known at this point only as KW-3902—is the subject of an ongoing clinical trial in 200 hospitalized heart failure patients with impaired renal function. It's a 4-day treatment study with 30-day follow-up. “These agents look promising, but it's early,” Dr. Hobbs commented.

▸ Vasopressin antagonists. Nicknamed “super diuretics,” these drugs cause profound diuresis without disrupting electrolytes. The target of these drugs—vasopressin—is synthesized by the hypothalamus in response to baroreceptor and osmotic stimuli. It causes vasoconstriction and sodium and water retention.

Two vasopressin antagonists, or “vaptans,” have been tested in clinical trials: conivaptan and tolvaptan. Ongoing is the large multinational phase III Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST). Results are probably several years off, according to Dr. Hobbs.

Udho Thadani, M.D., commented that heart failure patients already have a rather full plate just with today's standard medications, which include a b-blocker, an ACE inhibitor or angiotensin receptor blocker, an aldosterone blocker such as spironolactone, and digoxin.

If even a few of the drugs with novel mechanisms of action that are in the developmental pipeline eventually find their way into routine clinical practice on top of today's standard therapy, compliance issues will become a much more prominent concern, predicted Dr. Thadani, professor emeritus of medicine at the University of Oklahoma, Oklahoma City.

VANCOUVER, B.C. — Baseline echocardiographic evidence of mechanical ventricular dyssynchrony is a powerful predictor of the long-term clinical benefit of cardiac resynchronization therapy in patients with severe heart failure, Maria Vittoria Pitzalis, M.D., said at a meeting sponsored by the International Academy of Cardiology.

Indeed, echocardiographic ventricular dyssynchrony is such a strong predictor that it ought to replace ECG evidence of prolonged QRS duration as a major screening criterion for cardiac resynchronization therapy (CRT) patient eligibility, added Dr. Pitzalis, who did her groundbreaking work in this field while at the University of Bari (Italy).

In the past few years, CRT has emerged as a major therapeutic advance for patients with severe heart failure despite optimal medical management. Studies have shown CRT results in reverse left ventricular remodeling as reflected in increased left ventricular ejection fraction, improved exercise tolerance and New York Heart Association functional class, enhanced quality of life, fewer hospitalizations, and, most recently, in the Cardiac Resynchronization in Heart Failure (CARE-HF) trial, a 36% reduction in all-cause mortality.

However, about one-quarter of treated patients do not benefit from CRT. There is great interest in developing ways to identify them in advance so as to spare them the expense of the device therapy as well as the risks associated with the at-times technically challenging transvenous lead placement.

A prolonged QRS interval has been a requirement for participation in all of the major CRT trials and is routinely used as a screening criterion for CRT eligibility in clinical practice. A long QRS is an ECG marker for ventricular dyssynchrony. But there is increasing dissatisfaction with its use as a screening tool in light of clear evidence that some patients with a normal QRS duration have echocardiographic evidence of mechanical ventricular dyssynchrony while others with a long QRS do not.

Dr. Pitzalis and her Italian coworkers have developed an echocardiographic method of assessing patients for ventricular dyssynchrony using a standard two-dimensional Doppler short-axis view at the papillary muscle level. It is obtained by calculating the shortest interval between the greatest posterior displacement of the septum and the maximum displacement of the left posterior ventricular wall. They call it the septal-to-posterior wall motion delay (SPWMD). It's simple, reproducible, widely available, and doesn't require specialized techniques and equipment, unlike tissue Doppler imaging, an alternative echocardiographic means of assessment for ventricular dyssynchrony.

The cardiologist presented a prospective study involving 60 patients, with severe heart failure and left bundle branch block, who underwent CRT. All had a baseline QRS greater than 130 milliseconds, and all underwent baseline measurement of SPWMD.

During a median 14-month follow-up, 4 patients died of heart failure and 12 others were hospitalized for worsening heart failure. In a multivariate analysis, only baseline SPWMD was significantly associated with subsequent heart failure progression or improvement. A long septal-to-posterior wall motion delay—that is, at least 130 milliseconds—was present in 79% of patients who experienced clinical improvement as defined by an increase in left ventricular ejection fraction along with at least a one-class improvement in New York Heart Association functional class. Only 9% of patients with an SPWMD of less than 130 milliseconds experienced such improvement. Change in QRS duration in response to therapy was unrelated to these outcomes.

“If you think about this result, it's not illogical, because in those patients with a long baseline delay, you're correcting the delay with CRT and therefore you are modifying prognosis. If a delay doesn't exist at baseline, you're not improving anything,” she said.

The investigators also compared the SPWMD results with those of tissue Doppler imaging and found no significant difference between the two echocardiographic techniques in terms of the end point of improved ejection fraction at 6 months.

Audience members inquired how they should manage patients who meet the now-standard prolonged QRS criterion for CRT implantation but have a short SPWMD.

“You can find very different things at the echocardiographic and ECG levels. There is dissociation between the two,” Dr. Pitzalis said. “In my opinion, based on our results, if you don't have any ventricular mechanical dyssynchrony, the possibility that your patient will improve with CRT is very low—just 9%. I'm wondering if the QRS duration criterion could be eliminated in the next few years, because we know there are patients with a narrow QRS that have mechanical dyssynchrony, and if an echo evaluation shows a rather large dyssynchrony, we have to implant them with CRT because they will benefit in clinical and functional terms.”

VANCOUVER, B.C. — Baseline echocardiographic evidence of mechanical ventricular dyssynchrony is a powerful predictor of the long-term clinical benefit of cardiac resynchronization therapy in patients with severe heart failure, Maria Vittoria Pitzalis, M.D., said at a meeting sponsored by the International Academy of Cardiology.

Indeed, echocardiographic ventricular dyssynchrony is such a strong predictor that it ought to replace ECG evidence of prolonged QRS duration as a major screening criterion for cardiac resynchronization therapy (CRT) patient eligibility, added Dr. Pitzalis, who did her groundbreaking work in this field while at the University of Bari (Italy).

In the past few years, CRT has emerged as a major therapeutic advance for patients with severe heart failure despite optimal medical management. Studies have shown CRT results in reverse left ventricular remodeling as reflected in increased left ventricular ejection fraction, improved exercise tolerance and New York Heart Association functional class, enhanced quality of life, fewer hospitalizations, and, most recently, in the Cardiac Resynchronization in Heart Failure (CARE-HF) trial, a 36% reduction in all-cause mortality.

However, about one-quarter of treated patients do not benefit from CRT. There is great interest in developing ways to identify them in advance so as to spare them the expense of the device therapy as well as the risks associated with the at-times technically challenging transvenous lead placement.

A prolonged QRS interval has been a requirement for participation in all of the major CRT trials and is routinely used as a screening criterion for CRT eligibility in clinical practice. A long QRS is an ECG marker for ventricular dyssynchrony. But there is increasing dissatisfaction with its use as a screening tool in light of clear evidence that some patients with a normal QRS duration have echocardiographic evidence of mechanical ventricular dyssynchrony while others with a long QRS do not.

Dr. Pitzalis and her Italian coworkers have developed an echocardiographic method of assessing patients for ventricular dyssynchrony using a standard two-dimensional Doppler short-axis view at the papillary muscle level. It is obtained by calculating the shortest interval between the greatest posterior displacement of the septum and the maximum displacement of the left posterior ventricular wall. They call it the septal-to-posterior wall motion delay (SPWMD). It's simple, reproducible, widely available, and doesn't require specialized techniques and equipment, unlike tissue Doppler imaging, an alternative echocardiographic means of assessment for ventricular dyssynchrony.

The cardiologist presented a prospective study involving 60 patients, with severe heart failure and left bundle branch block, who underwent CRT. All had a baseline QRS greater than 130 milliseconds, and all underwent baseline measurement of SPWMD.

During a median 14-month follow-up, 4 patients died of heart failure and 12 others were hospitalized for worsening heart failure. In a multivariate analysis, only baseline SPWMD was significantly associated with subsequent heart failure progression or improvement. A long septal-to-posterior wall motion delay—that is, at least 130 milliseconds—was present in 79% of patients who experienced clinical improvement as defined by an increase in left ventricular ejection fraction along with at least a one-class improvement in New York Heart Association functional class. Only 9% of patients with an SPWMD of less than 130 milliseconds experienced such improvement. Change in QRS duration in response to therapy was unrelated to these outcomes.

“If you think about this result, it's not illogical, because in those patients with a long baseline delay, you're correcting the delay with CRT and therefore you are modifying prognosis. If a delay doesn't exist at baseline, you're not improving anything,” she said.

The investigators also compared the SPWMD results with those of tissue Doppler imaging and found no significant difference between the two echocardiographic techniques in terms of the end point of improved ejection fraction at 6 months.

Audience members inquired how they should manage patients who meet the now-standard prolonged QRS criterion for CRT implantation but have a short SPWMD.

“You can find very different things at the echocardiographic and ECG levels. There is dissociation between the two,” Dr. Pitzalis said. “In my opinion, based on our results, if you don't have any ventricular mechanical dyssynchrony, the possibility that your patient will improve with CRT is very low—just 9%. I'm wondering if the QRS duration criterion could be eliminated in the next few years, because we know there are patients with a narrow QRS that have mechanical dyssynchrony, and if an echo evaluation shows a rather large dyssynchrony, we have to implant them with CRT because they will benefit in clinical and functional terms.”

VANCOUVER, B.C. — Baseline echocardiographic evidence of mechanical ventricular dyssynchrony is a powerful predictor of the long-term clinical benefit of cardiac resynchronization therapy in patients with severe heart failure, Maria Vittoria Pitzalis, M.D., said at a meeting sponsored by the International Academy of Cardiology.

Indeed, echocardiographic ventricular dyssynchrony is such a strong predictor that it ought to replace ECG evidence of prolonged QRS duration as a major screening criterion for cardiac resynchronization therapy (CRT) patient eligibility, added Dr. Pitzalis, who did her groundbreaking work in this field while at the University of Bari (Italy).

In the past few years, CRT has emerged as a major therapeutic advance for patients with severe heart failure despite optimal medical management. Studies have shown CRT results in reverse left ventricular remodeling as reflected in increased left ventricular ejection fraction, improved exercise tolerance and New York Heart Association functional class, enhanced quality of life, fewer hospitalizations, and, most recently, in the Cardiac Resynchronization in Heart Failure (CARE-HF) trial, a 36% reduction in all-cause mortality.

However, about one-quarter of treated patients do not benefit from CRT. There is great interest in developing ways to identify them in advance so as to spare them the expense of the device therapy as well as the risks associated with the at-times technically challenging transvenous lead placement.

A prolonged QRS interval has been a requirement for participation in all of the major CRT trials and is routinely used as a screening criterion for CRT eligibility in clinical practice. A long QRS is an ECG marker for ventricular dyssynchrony. But there is increasing dissatisfaction with its use as a screening tool in light of clear evidence that some patients with a normal QRS duration have echocardiographic evidence of mechanical ventricular dyssynchrony while others with a long QRS do not.

Dr. Pitzalis and her Italian coworkers have developed an echocardiographic method of assessing patients for ventricular dyssynchrony using a standard two-dimensional Doppler short-axis view at the papillary muscle level. It is obtained by calculating the shortest interval between the greatest posterior displacement of the septum and the maximum displacement of the left posterior ventricular wall. They call it the septal-to-posterior wall motion delay (SPWMD). It's simple, reproducible, widely available, and doesn't require specialized techniques and equipment, unlike tissue Doppler imaging, an alternative echocardiographic means of assessment for ventricular dyssynchrony.

The cardiologist presented a prospective study involving 60 patients, with severe heart failure and left bundle branch block, who underwent CRT. All had a baseline QRS greater than 130 milliseconds, and all underwent baseline measurement of SPWMD.

During a median 14-month follow-up, 4 patients died of heart failure and 12 others were hospitalized for worsening heart failure. In a multivariate analysis, only baseline SPWMD was significantly associated with subsequent heart failure progression or improvement. A long septal-to-posterior wall motion delay—that is, at least 130 milliseconds—was present in 79% of patients who experienced clinical improvement as defined by an increase in left ventricular ejection fraction along with at least a one-class improvement in New York Heart Association functional class. Only 9% of patients with an SPWMD of less than 130 milliseconds experienced such improvement. Change in QRS duration in response to therapy was unrelated to these outcomes.

“If you think about this result, it's not illogical, because in those patients with a long baseline delay, you're correcting the delay with CRT and therefore you are modifying prognosis. If a delay doesn't exist at baseline, you're not improving anything,” she said.

The investigators also compared the SPWMD results with those of tissue Doppler imaging and found no significant difference between the two echocardiographic techniques in terms of the end point of improved ejection fraction at 6 months.

Audience members inquired how they should manage patients who meet the now-standard prolonged QRS criterion for CRT implantation but have a short SPWMD.

“You can find very different things at the echocardiographic and ECG levels. There is dissociation between the two,” Dr. Pitzalis said. “In my opinion, based on our results, if you don't have any ventricular mechanical dyssynchrony, the possibility that your patient will improve with CRT is very low—just 9%. I'm wondering if the QRS duration criterion could be eliminated in the next few years, because we know there are patients with a narrow QRS that have mechanical dyssynchrony, and if an echo evaluation shows a rather large dyssynchrony, we have to implant them with CRT because they will benefit in clinical and functional terms.”

WASHINGTON — Measuring markers of inflammation and neurohumoral activation in candidates for implantation with a left ventricular assist device may help predict the probability of right ventricular failure, Evgenij V. Potapov, M.D., reported at the annual conference of the American Society for Artificial Internal Organs.

“The problem is that up to 20% of patients receiving a left ventricular assist device [LVAD] develop right heart failure,” Dr. Potapov, a cardiothoracic surgeon at the Deutsches Herzzentrum Berlin, said in an interview.

Dr. Potapov and his colleagues reviewed the records of patients with chronic end-stage heart failure who received an LVAD during 2002-2004.

They found no differences in preoperative echocardiographic findings or laboratory or hemodynamic parameters between the 102 patients who had normal right ventricular function after LVAD implantation and the 9 patients with right ventricular failure, defined as having at least two of the following within 24 hours of LVAD implantation: mean arterial pressure less than 55 mm Hg, central venous pressure less than 16 mm Hg, mixed venous oxygen saturation less than 55%, cardiac index less than 2 L/min per square meter, and more than 20 inotropic equivalents of inotropic support.

But a subsequent prospective study of 40 patients found that people with normal right ventricular function after left ventricular assist device implantation had significantly lower levels of markers of inflammation (procalcitonin and neopterin) and neurohumoral activation (N-terminal pro-B-type natriuretic peptide and big endothelin-1) than did those who would later develop right ventricular failure, he said in a poster session at the conference.

Patients who are identified as having a high probability of right ventricular failure after implantation of a left ventricular assist device could instead undergo implantation of a biventricular support device or a total artificial heart, Dr. Potapov suggested.

None of the patients who were in either study required a left ventricular assist device for postcardiotomy heart failure.

WASHINGTON — Measuring markers of inflammation and neurohumoral activation in candidates for implantation with a left ventricular assist device may help predict the probability of right ventricular failure, Evgenij V. Potapov, M.D., reported at the annual conference of the American Society for Artificial Internal Organs.

“The problem is that up to 20% of patients receiving a left ventricular assist device [LVAD] develop right heart failure,” Dr. Potapov, a cardiothoracic surgeon at the Deutsches Herzzentrum Berlin, said in an interview.

Dr. Potapov and his colleagues reviewed the records of patients with chronic end-stage heart failure who received an LVAD during 2002-2004.

They found no differences in preoperative echocardiographic findings or laboratory or hemodynamic parameters between the 102 patients who had normal right ventricular function after LVAD implantation and the 9 patients with right ventricular failure, defined as having at least two of the following within 24 hours of LVAD implantation: mean arterial pressure less than 55 mm Hg, central venous pressure less than 16 mm Hg, mixed venous oxygen saturation less than 55%, cardiac index less than 2 L/min per square meter, and more than 20 inotropic equivalents of inotropic support.

But a subsequent prospective study of 40 patients found that people with normal right ventricular function after left ventricular assist device implantation had significantly lower levels of markers of inflammation (procalcitonin and neopterin) and neurohumoral activation (N-terminal pro-B-type natriuretic peptide and big endothelin-1) than did those who would later develop right ventricular failure, he said in a poster session at the conference.

Patients who are identified as having a high probability of right ventricular failure after implantation of a left ventricular assist device could instead undergo implantation of a biventricular support device or a total artificial heart, Dr. Potapov suggested.

None of the patients who were in either study required a left ventricular assist device for postcardiotomy heart failure.

WASHINGTON — Measuring markers of inflammation and neurohumoral activation in candidates for implantation with a left ventricular assist device may help predict the probability of right ventricular failure, Evgenij V. Potapov, M.D., reported at the annual conference of the American Society for Artificial Internal Organs.

“The problem is that up to 20% of patients receiving a left ventricular assist device [LVAD] develop right heart failure,” Dr. Potapov, a cardiothoracic surgeon at the Deutsches Herzzentrum Berlin, said in an interview.

Dr. Potapov and his colleagues reviewed the records of patients with chronic end-stage heart failure who received an LVAD during 2002-2004.

They found no differences in preoperative echocardiographic findings or laboratory or hemodynamic parameters between the 102 patients who had normal right ventricular function after LVAD implantation and the 9 patients with right ventricular failure, defined as having at least two of the following within 24 hours of LVAD implantation: mean arterial pressure less than 55 mm Hg, central venous pressure less than 16 mm Hg, mixed venous oxygen saturation less than 55%, cardiac index less than 2 L/min per square meter, and more than 20 inotropic equivalents of inotropic support.

But a subsequent prospective study of 40 patients found that people with normal right ventricular function after left ventricular assist device implantation had significantly lower levels of markers of inflammation (procalcitonin and neopterin) and neurohumoral activation (N-terminal pro-B-type natriuretic peptide and big endothelin-1) than did those who would later develop right ventricular failure, he said in a poster session at the conference.

Patients who are identified as having a high probability of right ventricular failure after implantation of a left ventricular assist device could instead undergo implantation of a biventricular support device or a total artificial heart, Dr. Potapov suggested.

None of the patients who were in either study required a left ventricular assist device for postcardiotomy heart failure.