Heart Failure

NEW ORLEANS — Conivaptan was safe and effective for treating hyponatremia in three phase III studies that together involved about 200 evaluable patients.

Based in part on these findings, the Food and Drug Administration issued an approvable letter for conivaptan last December. According to Yamanouchi Pharma America, the company developing the drug, the FDA said that it will license conivaptan for the treatment of hyponatremia if Yamanouchi provides additional safety data and meets certain other conditions. Yamanouchi sponsored the phase III studies.

Currently, no agent has FDA approval for treating hyponatremia, which affects 2%‐3% of all hospitalized patients and is more prevalent among patients with advanced heart failure and in the elderly. Hyponatremia is defined as a serum sodium concentration of less than 136 mEq/L, and is usually managed by restricting fluids.

Conivaptan is an antagonist for the arginine vasopressor receptor. Through this activity, the drug causes aquaresis and reduces vasomotor tone. Patients with heart failure often have abnormally high levels of arginine vasopressin, which promotes water reabsorption and helps produce the edema that often accompanies heart failure. Conivaptan can be administered either orally or intravenously; however, Yamanouchi is only seeking approval to market conivaptan with intravenous administration.

Results from the three studies were presented in posters at the annual scientific sessions of the American Heart Association. One study included 74 men and women at least 18 years old with a serum sodium level of 115‐130 mEq/L who were either hypervolemic or euvolemic. About 43% of the patients had hyponatremia secondary to heart failure, about 20% had idiopathic hyponatremia, and in the remainder it was due to other factors. About 74% of the patients were euvolemic.

Patients were randomized to treatment with 20 mg conivaptan orally b.i.d, 40 mg orally b.i.d, or placebo, and treatment continued for 5 days. Three patients dropped out during the study, one from each treatment group.

During the 5 days of treatment, serum sodium levels increased in the conivaptan group in a dose‐related manner and to levels that were significantly above those reached in the control group, reported Jala K. Ghali, M.D., director of clinical research at Cardiology Centers of Louisiana in Shreveport. The 20‐mg b.i.d dosage boosted sodium levels from a mean of 125 mEq/L at baseline to about 132 mEq/L after 5 days. The 40‐mg b.i.d. dosage raised sodium levels from a mean of 125 mEq/L at baseline to about 133 mEq/L after 5 days. In the placebo group, the starting sodium level averaged 124 mEq/L, which rose to about 127 mEq/L after 5 days.

Conivaptan was effective regardless of whether patients were euvolemic or hypervolemic at baseline, and regardless of the etiologic cause of hyponatremia. Both dosages were well tolerated; the rate of drug‐related adverse events was similar in the three treatment groups, Dr. Ghali reported.

The second study reported at the meeting was very similar in design to the first, except conivaptan was administered intravenously. The study initially treated 84 patients, of whom 66 completed a 4‐day course of treatment. The study enrolled adult men and women with a baseline serum sodium level of 115‐130 mEq/L. Two‐thirds of the patients were euvolemic, and 30% had heart failure as their etiology of hyponatremia. Patients were randomized to treatment with 40 mg/day conivaptan intravenously, 80 mg/day, or placebo.

After 4 days of treatment, serum sodium levels had increased significantly in both treatment groups, compared with the control patients, reported Joseph G. Verbalis, M.D., professor of medicine and chief of the division of endocrinology and metabolism at Georgetown University, Washington. Once again, the increases were dose dependent, and were very similar to those seen with oral dosing. And conivaptan was effective whether patients were euvolemic or hypervolemic, and regardless of the etiology of their hyponatremia.

Both dosages of the intravenous drug were also well tolerated. Although the incidence of drug‐related adverse effects were more than twice as common in patients treated with conivaptan, compared with those who received placebo, the effects were mild to moderate in severity, Dr. Verbalis said. Discontinuations due to adverse effects were similar in all three treatment groups.

The third study closely resembled the first oral‐administration study, but it was run in Europe. It enrolled 89 patients, of whom 72 completed the 5‐day treatment. This study enrolled adult men and women with serum sodium levels of less than 130 mEq/L. About 58% of the patients were euvolemic at baseline, and 30% had heart failure as their cause of hyponatremia. Patients were randomized to receive 20 mg oral conivaptan b.i.d, 40 mg b.i.d., or placebo.

After 5 days of treatment, serum sodium levels were significantly higher in both treatment groups, compared with control patients, said Peter Gross, M.D., professor of medicine and nephrology at the Carl Gustav Carus University Clinic in Dresden, Germany. Sodium levels rose in a dose‐dependent fashion, and the increases were similar to those seen in the two U.S. studies. The effects on sodium levels were similar regardless of volemic status at baseline and hyponatremia etiology. Treatment with conivaptan was well tolerated, with a low rate of drug‐related adverse effects and few discontinuations due to adverse effects.

NEW ORLEANS — Conivaptan was safe and effective for treating hyponatremia in three phase III studies that together involved about 200 evaluable patients.

Based in part on these findings, the Food and Drug Administration issued an approvable letter for conivaptan last December. According to Yamanouchi Pharma America, the company developing the drug, the FDA said that it will license conivaptan for the treatment of hyponatremia if Yamanouchi provides additional safety data and meets certain other conditions. Yamanouchi sponsored the phase III studies.

Currently, no agent has FDA approval for treating hyponatremia, which affects 2%‐3% of all hospitalized patients and is more prevalent among patients with advanced heart failure and in the elderly. Hyponatremia is defined as a serum sodium concentration of less than 136 mEq/L, and is usually managed by restricting fluids.

Conivaptan is an antagonist for the arginine vasopressor receptor. Through this activity, the drug causes aquaresis and reduces vasomotor tone. Patients with heart failure often have abnormally high levels of arginine vasopressin, which promotes water reabsorption and helps produce the edema that often accompanies heart failure. Conivaptan can be administered either orally or intravenously; however, Yamanouchi is only seeking approval to market conivaptan with intravenous administration.

Results from the three studies were presented in posters at the annual scientific sessions of the American Heart Association. One study included 74 men and women at least 18 years old with a serum sodium level of 115‐130 mEq/L who were either hypervolemic or euvolemic. About 43% of the patients had hyponatremia secondary to heart failure, about 20% had idiopathic hyponatremia, and in the remainder it was due to other factors. About 74% of the patients were euvolemic.

Patients were randomized to treatment with 20 mg conivaptan orally b.i.d, 40 mg orally b.i.d, or placebo, and treatment continued for 5 days. Three patients dropped out during the study, one from each treatment group.

During the 5 days of treatment, serum sodium levels increased in the conivaptan group in a dose‐related manner and to levels that were significantly above those reached in the control group, reported Jala K. Ghali, M.D., director of clinical research at Cardiology Centers of Louisiana in Shreveport. The 20‐mg b.i.d dosage boosted sodium levels from a mean of 125 mEq/L at baseline to about 132 mEq/L after 5 days. The 40‐mg b.i.d. dosage raised sodium levels from a mean of 125 mEq/L at baseline to about 133 mEq/L after 5 days. In the placebo group, the starting sodium level averaged 124 mEq/L, which rose to about 127 mEq/L after 5 days.

Conivaptan was effective regardless of whether patients were euvolemic or hypervolemic at baseline, and regardless of the etiologic cause of hyponatremia. Both dosages were well tolerated; the rate of drug‐related adverse events was similar in the three treatment groups, Dr. Ghali reported.

The second study reported at the meeting was very similar in design to the first, except conivaptan was administered intravenously. The study initially treated 84 patients, of whom 66 completed a 4‐day course of treatment. The study enrolled adult men and women with a baseline serum sodium level of 115‐130 mEq/L. Two‐thirds of the patients were euvolemic, and 30% had heart failure as their etiology of hyponatremia. Patients were randomized to treatment with 40 mg/day conivaptan intravenously, 80 mg/day, or placebo.

After 4 days of treatment, serum sodium levels had increased significantly in both treatment groups, compared with the control patients, reported Joseph G. Verbalis, M.D., professor of medicine and chief of the division of endocrinology and metabolism at Georgetown University, Washington. Once again, the increases were dose dependent, and were very similar to those seen with oral dosing. And conivaptan was effective whether patients were euvolemic or hypervolemic, and regardless of the etiology of their hyponatremia.

Both dosages of the intravenous drug were also well tolerated. Although the incidence of drug‐related adverse effects were more than twice as common in patients treated with conivaptan, compared with those who received placebo, the effects were mild to moderate in severity, Dr. Verbalis said. Discontinuations due to adverse effects were similar in all three treatment groups.

The third study closely resembled the first oral‐administration study, but it was run in Europe. It enrolled 89 patients, of whom 72 completed the 5‐day treatment. This study enrolled adult men and women with serum sodium levels of less than 130 mEq/L. About 58% of the patients were euvolemic at baseline, and 30% had heart failure as their cause of hyponatremia. Patients were randomized to receive 20 mg oral conivaptan b.i.d, 40 mg b.i.d., or placebo.

After 5 days of treatment, serum sodium levels were significantly higher in both treatment groups, compared with control patients, said Peter Gross, M.D., professor of medicine and nephrology at the Carl Gustav Carus University Clinic in Dresden, Germany. Sodium levels rose in a dose‐dependent fashion, and the increases were similar to those seen in the two U.S. studies. The effects on sodium levels were similar regardless of volemic status at baseline and hyponatremia etiology. Treatment with conivaptan was well tolerated, with a low rate of drug‐related adverse effects and few discontinuations due to adverse effects.

NEW ORLEANS — Conivaptan was safe and effective for treating hyponatremia in three phase III studies that together involved about 200 evaluable patients.

Based in part on these findings, the Food and Drug Administration issued an approvable letter for conivaptan last December. According to Yamanouchi Pharma America, the company developing the drug, the FDA said that it will license conivaptan for the treatment of hyponatremia if Yamanouchi provides additional safety data and meets certain other conditions. Yamanouchi sponsored the phase III studies.

Currently, no agent has FDA approval for treating hyponatremia, which affects 2%‐3% of all hospitalized patients and is more prevalent among patients with advanced heart failure and in the elderly. Hyponatremia is defined as a serum sodium concentration of less than 136 mEq/L, and is usually managed by restricting fluids.

Conivaptan is an antagonist for the arginine vasopressor receptor. Through this activity, the drug causes aquaresis and reduces vasomotor tone. Patients with heart failure often have abnormally high levels of arginine vasopressin, which promotes water reabsorption and helps produce the edema that often accompanies heart failure. Conivaptan can be administered either orally or intravenously; however, Yamanouchi is only seeking approval to market conivaptan with intravenous administration.

Results from the three studies were presented in posters at the annual scientific sessions of the American Heart Association. One study included 74 men and women at least 18 years old with a serum sodium level of 115‐130 mEq/L who were either hypervolemic or euvolemic. About 43% of the patients had hyponatremia secondary to heart failure, about 20% had idiopathic hyponatremia, and in the remainder it was due to other factors. About 74% of the patients were euvolemic.

Patients were randomized to treatment with 20 mg conivaptan orally b.i.d, 40 mg orally b.i.d, or placebo, and treatment continued for 5 days. Three patients dropped out during the study, one from each treatment group.

During the 5 days of treatment, serum sodium levels increased in the conivaptan group in a dose‐related manner and to levels that were significantly above those reached in the control group, reported Jala K. Ghali, M.D., director of clinical research at Cardiology Centers of Louisiana in Shreveport. The 20‐mg b.i.d dosage boosted sodium levels from a mean of 125 mEq/L at baseline to about 132 mEq/L after 5 days. The 40‐mg b.i.d. dosage raised sodium levels from a mean of 125 mEq/L at baseline to about 133 mEq/L after 5 days. In the placebo group, the starting sodium level averaged 124 mEq/L, which rose to about 127 mEq/L after 5 days.

Conivaptan was effective regardless of whether patients were euvolemic or hypervolemic at baseline, and regardless of the etiologic cause of hyponatremia. Both dosages were well tolerated; the rate of drug‐related adverse events was similar in the three treatment groups, Dr. Ghali reported.

The second study reported at the meeting was very similar in design to the first, except conivaptan was administered intravenously. The study initially treated 84 patients, of whom 66 completed a 4‐day course of treatment. The study enrolled adult men and women with a baseline serum sodium level of 115‐130 mEq/L. Two‐thirds of the patients were euvolemic, and 30% had heart failure as their etiology of hyponatremia. Patients were randomized to treatment with 40 mg/day conivaptan intravenously, 80 mg/day, or placebo.

After 4 days of treatment, serum sodium levels had increased significantly in both treatment groups, compared with the control patients, reported Joseph G. Verbalis, M.D., professor of medicine and chief of the division of endocrinology and metabolism at Georgetown University, Washington. Once again, the increases were dose dependent, and were very similar to those seen with oral dosing. And conivaptan was effective whether patients were euvolemic or hypervolemic, and regardless of the etiology of their hyponatremia.

Both dosages of the intravenous drug were also well tolerated. Although the incidence of drug‐related adverse effects were more than twice as common in patients treated with conivaptan, compared with those who received placebo, the effects were mild to moderate in severity, Dr. Verbalis said. Discontinuations due to adverse effects were similar in all three treatment groups.

The third study closely resembled the first oral‐administration study, but it was run in Europe. It enrolled 89 patients, of whom 72 completed the 5‐day treatment. This study enrolled adult men and women with serum sodium levels of less than 130 mEq/L. About 58% of the patients were euvolemic at baseline, and 30% had heart failure as their cause of hyponatremia. Patients were randomized to receive 20 mg oral conivaptan b.i.d, 40 mg b.i.d., or placebo.

After 5 days of treatment, serum sodium levels were significantly higher in both treatment groups, compared with control patients, said Peter Gross, M.D., professor of medicine and nephrology at the Carl Gustav Carus University Clinic in Dresden, Germany. Sodium levels rose in a dose‐dependent fashion, and the increases were similar to those seen in the two U.S. studies. The effects on sodium levels were similar regardless of volemic status at baseline and hyponatremia etiology. Treatment with conivaptan was well tolerated, with a low rate of drug‐related adverse effects and few discontinuations due to adverse effects.

SAN ANTONIO — Rheumatoid arthritis patients develop heart failure more frequently than the general population, and this increase does not appear to be explained by traditional risk factors, Cynthia Crowson said at the annual meeting of the American College of Rheumatology.

There have been many studies of heart disease in rheumatoid arthritis, but no one has previously looked at heart failure in particular, said Ms. Crowson, a statistician at the Mayo Clinic, Rochester, Minn.

The study followed 575 rheumatoid arthritis patients and 583 control subjects from the time they were 50–60 years of age (mean age 57 years) for 11–15 years, to see how many developed heart failure and what role was played by known cardiovascular risk factors.

Over the course of the study, 165 of the rheumatoid arthritis (RA) patients developed heart failure, as did 115 of the control subjects.

A statistical analysis of the subjects with heart failure—one that took into account each individual's risk factors—indicated that risk factors such as sedentary lifestyle and smoking played less of role in the heart failure of the RA patients than did that of the controls. Instead, the pathogenesis of RA itself may be to blame for the rates of heart failure, Ms. Crowson suggested.

Overall, the analysis indicated that 83% of the heart failure in the control subjects could be attributed to known cardiovascular risk factors and ischemic heart disease. By comparison, 45% of the heart failure in the rheumatoid arthritis patients could be attributed to such factors.

In the control subjects, 64% of the risk of heart failure was attributable to hypertension, but only 18% of the risk was associated with hypertension in the rheumatoid arthritis patients.

A history of ischemic heart disease (myocardial infarction, silent myocardial infarction, angina, or a revascularization procedure) was present in 26% of the control subjects, but only 17% of the risk in the RA patients.

Smoking accounted for 14% of the attributable risk in the control subjects, but only 3% in RA patients.

Body mass index tended to be fairly similar in the two groups; 23% of the RA patients had a BMI greater than 30, compared with 24% of the controls.

Smoking or a history of smoking was more common in the RA patients, but not dramatically so (55% versus 45%).

SAN ANTONIO — Rheumatoid arthritis patients develop heart failure more frequently than the general population, and this increase does not appear to be explained by traditional risk factors, Cynthia Crowson said at the annual meeting of the American College of Rheumatology.

There have been many studies of heart disease in rheumatoid arthritis, but no one has previously looked at heart failure in particular, said Ms. Crowson, a statistician at the Mayo Clinic, Rochester, Minn.

The study followed 575 rheumatoid arthritis patients and 583 control subjects from the time they were 50–60 years of age (mean age 57 years) for 11–15 years, to see how many developed heart failure and what role was played by known cardiovascular risk factors.

Over the course of the study, 165 of the rheumatoid arthritis (RA) patients developed heart failure, as did 115 of the control subjects.

A statistical analysis of the subjects with heart failure—one that took into account each individual's risk factors—indicated that risk factors such as sedentary lifestyle and smoking played less of role in the heart failure of the RA patients than did that of the controls. Instead, the pathogenesis of RA itself may be to blame for the rates of heart failure, Ms. Crowson suggested.

Overall, the analysis indicated that 83% of the heart failure in the control subjects could be attributed to known cardiovascular risk factors and ischemic heart disease. By comparison, 45% of the heart failure in the rheumatoid arthritis patients could be attributed to such factors.

In the control subjects, 64% of the risk of heart failure was attributable to hypertension, but only 18% of the risk was associated with hypertension in the rheumatoid arthritis patients.

A history of ischemic heart disease (myocardial infarction, silent myocardial infarction, angina, or a revascularization procedure) was present in 26% of the control subjects, but only 17% of the risk in the RA patients.

Smoking accounted for 14% of the attributable risk in the control subjects, but only 3% in RA patients.

Body mass index tended to be fairly similar in the two groups; 23% of the RA patients had a BMI greater than 30, compared with 24% of the controls.

Smoking or a history of smoking was more common in the RA patients, but not dramatically so (55% versus 45%).

SAN ANTONIO — Rheumatoid arthritis patients develop heart failure more frequently than the general population, and this increase does not appear to be explained by traditional risk factors, Cynthia Crowson said at the annual meeting of the American College of Rheumatology.

There have been many studies of heart disease in rheumatoid arthritis, but no one has previously looked at heart failure in particular, said Ms. Crowson, a statistician at the Mayo Clinic, Rochester, Minn.

The study followed 575 rheumatoid arthritis patients and 583 control subjects from the time they were 50–60 years of age (mean age 57 years) for 11–15 years, to see how many developed heart failure and what role was played by known cardiovascular risk factors.

Over the course of the study, 165 of the rheumatoid arthritis (RA) patients developed heart failure, as did 115 of the control subjects.

A statistical analysis of the subjects with heart failure—one that took into account each individual's risk factors—indicated that risk factors such as sedentary lifestyle and smoking played less of role in the heart failure of the RA patients than did that of the controls. Instead, the pathogenesis of RA itself may be to blame for the rates of heart failure, Ms. Crowson suggested.

Overall, the analysis indicated that 83% of the heart failure in the control subjects could be attributed to known cardiovascular risk factors and ischemic heart disease. By comparison, 45% of the heart failure in the rheumatoid arthritis patients could be attributed to such factors.

In the control subjects, 64% of the risk of heart failure was attributable to hypertension, but only 18% of the risk was associated with hypertension in the rheumatoid arthritis patients.

A history of ischemic heart disease (myocardial infarction, silent myocardial infarction, angina, or a revascularization procedure) was present in 26% of the control subjects, but only 17% of the risk in the RA patients.

Smoking accounted for 14% of the attributable risk in the control subjects, but only 3% in RA patients.

Body mass index tended to be fairly similar in the two groups; 23% of the RA patients had a BMI greater than 30, compared with 24% of the controls.

Smoking or a history of smoking was more common in the RA patients, but not dramatically so (55% versus 45%).

KEVIN FOLEY, RESEARCH/JULIE KELLER, DESIGN

KEVIN FOLEY, RESEARCH/JULIE KELLER, DESIGN

KEVIN FOLEY, RESEARCH/JULIE KELLER, DESIGN

SAN FRANCISCO — Patients seen in the emergency department for acute decompensated heart failure fared much worse if they had elevated serum troponin, W. Frank Peacock IV, M.D., said in a poster presentation at the annual meeting of the American College of Emergency Physicians.

The results should have a profound impact on controversy about the clinical implications of elevating troponin in patients with heart failure, several speakers said in a session discussing cutting-edge research in emergency medicine at the meeting.

The analysis of data on 67,924 patients in the Acute Decompensated Heart Failure National Registry (ADHERE) showed that 6% had elevated troponin levels, and the rest were considered troponin-negative. Patients with elevated serum troponin were more likely than troponin-negative patients to develop systolic heart failure (61% vs. 51%) or undergo coronary artery bypass grafting (4% vs. 1%), intra-aortic balloon counterpulsation (3% vs. less than 1%), mechanical ventilation (11% vs. 4%), or cardioversion (3% vs. 2%), said Dr. Peacock of the Cleveland Clinic and his associates.

Patients with acute decompensated heart failure and elevated serum troponin also had longer hospitalizations (median 5.1 vs. 4.1 days) and longer ICU stays (a median of 2.9 vs. 2.3 days) and were more likely to die in the hospital (8% vs. 3%), compared with troponin-negative patients.

The study defined elevated serum troponin as a level of at least 1 ng/mL for troponin I or at least 0.1 ng/mL for troponin T. Patients with levels below those cutoffs were considered troponin-negative.

“This [study] is important, because cardiologists everywhere—particularly our heart failure cardiologists—tend to pooh-pooh troponin leaks,” according to Judd E. Hollander, M.D., professor of emergency medicine at the University of Pennsylvania, Philadelphia.

Elevated troponin in heart failure does not necessarily indicate underlying coronary disease, he said. “It's not something that cardiologists can fix in the cath lab—and that's what cardiologists look for. What this doesn't tell us is whether there's something we can fix in the hospital to decrease that mortality” associated with elevated troponin, he added.

Charles V. Pollack Jr., M.D., agreed: Cardiologists “tend to talk about benign troponin leaks. We've got to be careful about that.” Particularly in older patients, elevated troponin has been a marker for sick patients in studies of sepsis, shock, chest pain, or congestive heart failure. “It's a worrisome marker and should be treated as such,” said Dr. Pollack, chair of emergency medicine at the University of Pennsylvania.

Troponin is a structural protein, and elevated levels are produced by cell death, noted Brian J. O'Neil, M.D., of Wayne State University, Detroit. “These are not 'leaks,' ” he said.

In a separate interview, cardiologist Christopher P. Cannon, M.D., agreed that some of his colleagues have been misled by the common use of elevated troponin levels as a marker for acute coronary syndrome. When catheterizations found no arterial blockage in some patients with elevated troponin, the marker gained a reputation for false positives.

“We've learned that there are other things that cause elevations in troponin. We're all learning how to use this in these other patient groups. People are realizing it's a good marker of high-risk patients independent of whether the arteries have blockages or not,” said Dr. Cannon of Brigham and Women's Hospital, Boston.

Previous studies have shown that troponin is a biomarker for myocardial injury. In earlier studies of patients hospitalized for heart failure, troponin elevations have been associated with lower ejection fractions, worse functional status, repeat hospitalizations for heart failure, and death. Studies on the clinical implications of troponin in heart failure are few, however, and have been plagued by methodological problems.

Although speakers at the emergency medicine meeting lauded the current study for the number and breadth of patients in the database, Jerome R. Hoffman, M.D., pointed out one major limitation: possible incorporation bias. Higher rates of procedures and longer hospitalizations may be due to physicians' reactions.

“When somebody tells you a patient has a high troponin level, you might keep them in the hospital or ICU a little longer. It may be a self-fulfilling prophecy” and not necessarily an appropriate step, said Dr. Hoffman of the University of California, Los Angeles.

Cardiologist Sorin J. Brener, M.D., called the study “important and well executed” but agreed with Dr. Hoffman's criticism. A multivariate logistic regression analysis controlling for the differences between patients in the two troponin groups would be necessary to isolate the independent effect of elevated troponin on outcomes, he said in a separate interview. “Elevated troponin levels are indeed a marker of adverse prognosis and cannot be ignored. Unfortunately, more often than not there is no specific intervention tailored to this finding in patients with decompensated heart failure that one would not apply in patients without elevated troponin,” said Dr. Brener, director of the angiography core laboratory at the Cleveland Clinic.

SAN FRANCISCO — Patients seen in the emergency department for acute decompensated heart failure fared much worse if they had elevated serum troponin, W. Frank Peacock IV, M.D., said in a poster presentation at the annual meeting of the American College of Emergency Physicians.

The results should have a profound impact on controversy about the clinical implications of elevating troponin in patients with heart failure, several speakers said in a session discussing cutting-edge research in emergency medicine at the meeting.

The analysis of data on 67,924 patients in the Acute Decompensated Heart Failure National Registry (ADHERE) showed that 6% had elevated troponin levels, and the rest were considered troponin-negative. Patients with elevated serum troponin were more likely than troponin-negative patients to develop systolic heart failure (61% vs. 51%) or undergo coronary artery bypass grafting (4% vs. 1%), intra-aortic balloon counterpulsation (3% vs. less than 1%), mechanical ventilation (11% vs. 4%), or cardioversion (3% vs. 2%), said Dr. Peacock of the Cleveland Clinic and his associates.

Patients with acute decompensated heart failure and elevated serum troponin also had longer hospitalizations (median 5.1 vs. 4.1 days) and longer ICU stays (a median of 2.9 vs. 2.3 days) and were more likely to die in the hospital (8% vs. 3%), compared with troponin-negative patients.

The study defined elevated serum troponin as a level of at least 1 ng/mL for troponin I or at least 0.1 ng/mL for troponin T. Patients with levels below those cutoffs were considered troponin-negative.

“This [study] is important, because cardiologists everywhere—particularly our heart failure cardiologists—tend to pooh-pooh troponin leaks,” according to Judd E. Hollander, M.D., professor of emergency medicine at the University of Pennsylvania, Philadelphia.

Elevated troponin in heart failure does not necessarily indicate underlying coronary disease, he said. “It's not something that cardiologists can fix in the cath lab—and that's what cardiologists look for. What this doesn't tell us is whether there's something we can fix in the hospital to decrease that mortality” associated with elevated troponin, he added.

Charles V. Pollack Jr., M.D., agreed: Cardiologists “tend to talk about benign troponin leaks. We've got to be careful about that.” Particularly in older patients, elevated troponin has been a marker for sick patients in studies of sepsis, shock, chest pain, or congestive heart failure. “It's a worrisome marker and should be treated as such,” said Dr. Pollack, chair of emergency medicine at the University of Pennsylvania.

Troponin is a structural protein, and elevated levels are produced by cell death, noted Brian J. O'Neil, M.D., of Wayne State University, Detroit. “These are not 'leaks,' ” he said.

In a separate interview, cardiologist Christopher P. Cannon, M.D., agreed that some of his colleagues have been misled by the common use of elevated troponin levels as a marker for acute coronary syndrome. When catheterizations found no arterial blockage in some patients with elevated troponin, the marker gained a reputation for false positives.

“We've learned that there are other things that cause elevations in troponin. We're all learning how to use this in these other patient groups. People are realizing it's a good marker of high-risk patients independent of whether the arteries have blockages or not,” said Dr. Cannon of Brigham and Women's Hospital, Boston.

Previous studies have shown that troponin is a biomarker for myocardial injury. In earlier studies of patients hospitalized for heart failure, troponin elevations have been associated with lower ejection fractions, worse functional status, repeat hospitalizations for heart failure, and death. Studies on the clinical implications of troponin in heart failure are few, however, and have been plagued by methodological problems.

Although speakers at the emergency medicine meeting lauded the current study for the number and breadth of patients in the database, Jerome R. Hoffman, M.D., pointed out one major limitation: possible incorporation bias. Higher rates of procedures and longer hospitalizations may be due to physicians' reactions.

“When somebody tells you a patient has a high troponin level, you might keep them in the hospital or ICU a little longer. It may be a self-fulfilling prophecy” and not necessarily an appropriate step, said Dr. Hoffman of the University of California, Los Angeles.

Cardiologist Sorin J. Brener, M.D., called the study “important and well executed” but agreed with Dr. Hoffman's criticism. A multivariate logistic regression analysis controlling for the differences between patients in the two troponin groups would be necessary to isolate the independent effect of elevated troponin on outcomes, he said in a separate interview. “Elevated troponin levels are indeed a marker of adverse prognosis and cannot be ignored. Unfortunately, more often than not there is no specific intervention tailored to this finding in patients with decompensated heart failure that one would not apply in patients without elevated troponin,” said Dr. Brener, director of the angiography core laboratory at the Cleveland Clinic.

SAN FRANCISCO — Patients seen in the emergency department for acute decompensated heart failure fared much worse if they had elevated serum troponin, W. Frank Peacock IV, M.D., said in a poster presentation at the annual meeting of the American College of Emergency Physicians.

The results should have a profound impact on controversy about the clinical implications of elevating troponin in patients with heart failure, several speakers said in a session discussing cutting-edge research in emergency medicine at the meeting.

The analysis of data on 67,924 patients in the Acute Decompensated Heart Failure National Registry (ADHERE) showed that 6% had elevated troponin levels, and the rest were considered troponin-negative. Patients with elevated serum troponin were more likely than troponin-negative patients to develop systolic heart failure (61% vs. 51%) or undergo coronary artery bypass grafting (4% vs. 1%), intra-aortic balloon counterpulsation (3% vs. less than 1%), mechanical ventilation (11% vs. 4%), or cardioversion (3% vs. 2%), said Dr. Peacock of the Cleveland Clinic and his associates.

Patients with acute decompensated heart failure and elevated serum troponin also had longer hospitalizations (median 5.1 vs. 4.1 days) and longer ICU stays (a median of 2.9 vs. 2.3 days) and were more likely to die in the hospital (8% vs. 3%), compared with troponin-negative patients.

The study defined elevated serum troponin as a level of at least 1 ng/mL for troponin I or at least 0.1 ng/mL for troponin T. Patients with levels below those cutoffs were considered troponin-negative.

“This [study] is important, because cardiologists everywhere—particularly our heart failure cardiologists—tend to pooh-pooh troponin leaks,” according to Judd E. Hollander, M.D., professor of emergency medicine at the University of Pennsylvania, Philadelphia.

Elevated troponin in heart failure does not necessarily indicate underlying coronary disease, he said. “It's not something that cardiologists can fix in the cath lab—and that's what cardiologists look for. What this doesn't tell us is whether there's something we can fix in the hospital to decrease that mortality” associated with elevated troponin, he added.

Charles V. Pollack Jr., M.D., agreed: Cardiologists “tend to talk about benign troponin leaks. We've got to be careful about that.” Particularly in older patients, elevated troponin has been a marker for sick patients in studies of sepsis, shock, chest pain, or congestive heart failure. “It's a worrisome marker and should be treated as such,” said Dr. Pollack, chair of emergency medicine at the University of Pennsylvania.

Troponin is a structural protein, and elevated levels are produced by cell death, noted Brian J. O'Neil, M.D., of Wayne State University, Detroit. “These are not 'leaks,' ” he said.

In a separate interview, cardiologist Christopher P. Cannon, M.D., agreed that some of his colleagues have been misled by the common use of elevated troponin levels as a marker for acute coronary syndrome. When catheterizations found no arterial blockage in some patients with elevated troponin, the marker gained a reputation for false positives.

“We've learned that there are other things that cause elevations in troponin. We're all learning how to use this in these other patient groups. People are realizing it's a good marker of high-risk patients independent of whether the arteries have blockages or not,” said Dr. Cannon of Brigham and Women's Hospital, Boston.

Previous studies have shown that troponin is a biomarker for myocardial injury. In earlier studies of patients hospitalized for heart failure, troponin elevations have been associated with lower ejection fractions, worse functional status, repeat hospitalizations for heart failure, and death. Studies on the clinical implications of troponin in heart failure are few, however, and have been plagued by methodological problems.

Although speakers at the emergency medicine meeting lauded the current study for the number and breadth of patients in the database, Jerome R. Hoffman, M.D., pointed out one major limitation: possible incorporation bias. Higher rates of procedures and longer hospitalizations may be due to physicians' reactions.

“When somebody tells you a patient has a high troponin level, you might keep them in the hospital or ICU a little longer. It may be a self-fulfilling prophecy” and not necessarily an appropriate step, said Dr. Hoffman of the University of California, Los Angeles.

Cardiologist Sorin J. Brener, M.D., called the study “important and well executed” but agreed with Dr. Hoffman's criticism. A multivariate logistic regression analysis controlling for the differences between patients in the two troponin groups would be necessary to isolate the independent effect of elevated troponin on outcomes, he said in a separate interview. “Elevated troponin levels are indeed a marker of adverse prognosis and cannot be ignored. Unfortunately, more often than not there is no specific intervention tailored to this finding in patients with decompensated heart failure that one would not apply in patients without elevated troponin,” said Dr. Brener, director of the angiography core laboratory at the Cleveland Clinic.