Heart Failure

DALLAS — An automated system may be able to monitor intracardiac pressures and alert physicians when the pattern suggests impending decompensation, based on a pilot analysis of data collected on 95 acute heart failure events.

The system “continuously scans data and can automatically notify the physician when a patient's pressures change meaningfully,” Dr. Philip B. Adamson said at the annual scientific sessions of the American Heart Association.

The scanning system developed by Dr. Adamson and his associates monitors changes in intracardiac pressures measured by the implanted Chronicle device, which is made by Medtronic Inc. and is under review by the Food and Drug Administration. Dr. Adamson has served as a consultant to Medtronic.

“The key to using this data is to learn the right pressure for each patient,” said Dr. Adamson, director of the Heart Failure Institute at the Oklahoma Heart Hospital in Oklahoma City.

The Chronicle implanted device was tested on 274 patients with advanced heart failure in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial. Intracardiac pressure data collected by the device was used by physicians to guide their management of 134 patients. The collected data were not used in the management of 140 control patients.

Data collected by the device for 56 of the control patients were used in Dr. Adamson's analysis. These 56 patients had a total of 95 episodes of acute decompensation that resulted in either a hospital admission or treatment in an emergency department or urgent-care clinic.

The automated data monitoring focused on the estimated pulmonary-artery diastolic pressure. A rule about changes in this pressure was devised using pressure information gathered before 42 of the 95 events. The pattern was that events usually occurred about 2 weeks after a significant increase in the pulmonary-artery diastolic pressure, said Dr. Adamson. This criterion was able to identify 35 (83%) of the 42 events.

This criterion was then applied on a test basis to the remaining 53 clinical events used in the analysis. A 7-day average of prior pulmonary-artery diastolic pressures was calculated for each patient every day, and this adaptive reference value was applied to each day's new pressure readings.

Small changes in pulmonary-artery pressure over a long period of time, or large changes in pressure over a short period of time were both considered flags of an impending event.

This method identified 43 (81%) of the 53 heart failure events included in the test.

The impending events were flagged an average of 26 days before the events actually occurred.

DALLAS — An automated system may be able to monitor intracardiac pressures and alert physicians when the pattern suggests impending decompensation, based on a pilot analysis of data collected on 95 acute heart failure events.

The system “continuously scans data and can automatically notify the physician when a patient's pressures change meaningfully,” Dr. Philip B. Adamson said at the annual scientific sessions of the American Heart Association.

The scanning system developed by Dr. Adamson and his associates monitors changes in intracardiac pressures measured by the implanted Chronicle device, which is made by Medtronic Inc. and is under review by the Food and Drug Administration. Dr. Adamson has served as a consultant to Medtronic.

“The key to using this data is to learn the right pressure for each patient,” said Dr. Adamson, director of the Heart Failure Institute at the Oklahoma Heart Hospital in Oklahoma City.

The Chronicle implanted device was tested on 274 patients with advanced heart failure in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial. Intracardiac pressure data collected by the device was used by physicians to guide their management of 134 patients. The collected data were not used in the management of 140 control patients.

Data collected by the device for 56 of the control patients were used in Dr. Adamson's analysis. These 56 patients had a total of 95 episodes of acute decompensation that resulted in either a hospital admission or treatment in an emergency department or urgent-care clinic.

The automated data monitoring focused on the estimated pulmonary-artery diastolic pressure. A rule about changes in this pressure was devised using pressure information gathered before 42 of the 95 events. The pattern was that events usually occurred about 2 weeks after a significant increase in the pulmonary-artery diastolic pressure, said Dr. Adamson. This criterion was able to identify 35 (83%) of the 42 events.

This criterion was then applied on a test basis to the remaining 53 clinical events used in the analysis. A 7-day average of prior pulmonary-artery diastolic pressures was calculated for each patient every day, and this adaptive reference value was applied to each day's new pressure readings.

Small changes in pulmonary-artery pressure over a long period of time, or large changes in pressure over a short period of time were both considered flags of an impending event.

This method identified 43 (81%) of the 53 heart failure events included in the test.

The impending events were flagged an average of 26 days before the events actually occurred.

DALLAS — An automated system may be able to monitor intracardiac pressures and alert physicians when the pattern suggests impending decompensation, based on a pilot analysis of data collected on 95 acute heart failure events.

The system “continuously scans data and can automatically notify the physician when a patient's pressures change meaningfully,” Dr. Philip B. Adamson said at the annual scientific sessions of the American Heart Association.

The scanning system developed by Dr. Adamson and his associates monitors changes in intracardiac pressures measured by the implanted Chronicle device, which is made by Medtronic Inc. and is under review by the Food and Drug Administration. Dr. Adamson has served as a consultant to Medtronic.

“The key to using this data is to learn the right pressure for each patient,” said Dr. Adamson, director of the Heart Failure Institute at the Oklahoma Heart Hospital in Oklahoma City.

The Chronicle implanted device was tested on 274 patients with advanced heart failure in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial. Intracardiac pressure data collected by the device was used by physicians to guide their management of 134 patients. The collected data were not used in the management of 140 control patients.

Data collected by the device for 56 of the control patients were used in Dr. Adamson's analysis. These 56 patients had a total of 95 episodes of acute decompensation that resulted in either a hospital admission or treatment in an emergency department or urgent-care clinic.

The automated data monitoring focused on the estimated pulmonary-artery diastolic pressure. A rule about changes in this pressure was devised using pressure information gathered before 42 of the 95 events. The pattern was that events usually occurred about 2 weeks after a significant increase in the pulmonary-artery diastolic pressure, said Dr. Adamson. This criterion was able to identify 35 (83%) of the 42 events.

This criterion was then applied on a test basis to the remaining 53 clinical events used in the analysis. A 7-day average of prior pulmonary-artery diastolic pressures was calculated for each patient every day, and this adaptive reference value was applied to each day's new pressure readings.

Small changes in pulmonary-artery pressure over a long period of time, or large changes in pressure over a short period of time were both considered flags of an impending event.

This method identified 43 (81%) of the 53 heart failure events included in the test.

The impending events were flagged an average of 26 days before the events actually occurred.

DALLAS — Management of heart failure patients with data from an implanted device that continuously monitors hemodynamic pressures led to a 25% reduction in total days spent in the hospital among patients with class III heart failure in a controlled study with more than 200 patients.

“The number of days spent in the hospital for decompensated heart failure is the principal driver of cost for heart failure treatment, and this was significantly decreased,” Dr. William T. Abraham said at the annual scientific sessions of the American Heart Association.

Use of the device in both outpatients and in hospitalized patients with heart failure “may make episodes of decompensation less extreme, and may help get patients out of the hospital more quickly,” said Dr. Abraham, professor and director of the division of cardiovascular medicine at Ohio State University in Columbus.

The finding came from new analyses of data collected in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, which tested the clinical impact of managing patients with intracardiac pressure data collected by the implanted Chronicle device. The device is made by Medtronic, which submitted an application for licensing to the Food and Drug Administration last August that was still pending in January.

The primary end point of the COMPASS-HF was reported last March at the annual meeting of the American College of Cardiology. Although patient management guided by pressure data obtained by the Chronicle device led to a 22% cut in the rate of heart failure-related hospitalizations and emergency department and urgent-care visits, the drop was not statistically significant. However, several secondary analyses also were positive in favor of the device, including a new set of secondary analyses presented by Dr. Abraham, who is a consultant and investigator for Medtronic and has received honoraria from the company for speaking.

He cautioned that the COMPASS-HF study was not designed to provide definitive answers to these secondary analyses, and therefore the findings must be considered exploratory.

In addition, researchers at Medtronic have revised the results presented by Dr. Abraham based on more comprehensive patient follow-up. The revised data showed that use of data from the Chronicle device cut the number of hospitalized days for heart failure by 20% instead of the 25% difference reported by Dr. Abraham. The 20% reduction is what was reported to the FDA, said Dr. David Israeli, director of marketing and business development for Medtronic in Minneapolis.

In the COMPASS-HF study, a total of 274 patients with advanced-stage heart failure underwent surgery to receive the subcutaneously-implanted, hemodynamic monitoring device. The intracardiac pressure information collected by the device was used by physicians to guide the management of 134 patients for 6 months. The pressure information was withheld from the treating physicians in the control group of 140 patients. All patients in the study also received optimal medical care based on clinical findings. The benefits of applying information collected by the Chronicle device were greatest in the 85% of patients who entered the study with New York Heart Association class III disease. Those with class IV disease had much less benefit.

The reduction in hospitalized days using data collected by the implanted device was more marked if the analysis excluded outlier patients with hospitalizations that extended beyond 30 days. With this exclusion, use of the Chronicle data cut the total number of hospitalized days by 42% for all patients in the study, and by 38% in the class III-only patients.

Another secondary analysis examined the impact of using data from the Chronicle device on the rate of prolonged or short hospitalizations for heart failure. Among the class III-only patients, use of Chronicle information was associated with an average rate of 0.19 long hospitalizations (more than 5 days) every 6 months, compared with a rate of 0.31 long hospitalizations every 6 months in the control group, a 40% decrease in favor of the device. Use of the device also was associated with a 0.28 rate of short hospitalizations (5 days or less) every 6 months, compared with a rate of 0.42 short hospitalizations every 6 months in the control group.

Despite the lack of a statistically significant positive result for the primary end point of the COMPASS-HF trial, the researchers who ran the study believe that the results demonstrate the device's efficacy.

“It's a positive study overall,” commented Dr. Robert C. Bourge, lead investigator for the study and professor and director of the division of cardiovascular disease at the University of Alabama, Birmingham.

But other experts are concerned about paying for this intensive approach to patient management.

“The implications are profound regarding the cost of care,” commented Dr. Harlan M. Krumholz, professor of medicine and epidemiology at Yale University, New Haven, Conn. “How should we decide which patients should get this?”

“We're developing models of how to use it,” said Dr. Bourge, who acknowledged that not all physicians would have the expertise or time to review so many pressure measurements for their patients.

Because of this, researchers are working on developing an automated way to review the large number of intracardiac pressure measurements that are made in each patient.

DALLAS — Management of heart failure patients with data from an implanted device that continuously monitors hemodynamic pressures led to a 25% reduction in total days spent in the hospital among patients with class III heart failure in a controlled study with more than 200 patients.

“The number of days spent in the hospital for decompensated heart failure is the principal driver of cost for heart failure treatment, and this was significantly decreased,” Dr. William T. Abraham said at the annual scientific sessions of the American Heart Association.

Use of the device in both outpatients and in hospitalized patients with heart failure “may make episodes of decompensation less extreme, and may help get patients out of the hospital more quickly,” said Dr. Abraham, professor and director of the division of cardiovascular medicine at Ohio State University in Columbus.

The finding came from new analyses of data collected in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, which tested the clinical impact of managing patients with intracardiac pressure data collected by the implanted Chronicle device. The device is made by Medtronic, which submitted an application for licensing to the Food and Drug Administration last August that was still pending in January.

The primary end point of the COMPASS-HF was reported last March at the annual meeting of the American College of Cardiology. Although patient management guided by pressure data obtained by the Chronicle device led to a 22% cut in the rate of heart failure-related hospitalizations and emergency department and urgent-care visits, the drop was not statistically significant. However, several secondary analyses also were positive in favor of the device, including a new set of secondary analyses presented by Dr. Abraham, who is a consultant and investigator for Medtronic and has received honoraria from the company for speaking.

He cautioned that the COMPASS-HF study was not designed to provide definitive answers to these secondary analyses, and therefore the findings must be considered exploratory.

In addition, researchers at Medtronic have revised the results presented by Dr. Abraham based on more comprehensive patient follow-up. The revised data showed that use of data from the Chronicle device cut the number of hospitalized days for heart failure by 20% instead of the 25% difference reported by Dr. Abraham. The 20% reduction is what was reported to the FDA, said Dr. David Israeli, director of marketing and business development for Medtronic in Minneapolis.

In the COMPASS-HF study, a total of 274 patients with advanced-stage heart failure underwent surgery to receive the subcutaneously-implanted, hemodynamic monitoring device. The intracardiac pressure information collected by the device was used by physicians to guide the management of 134 patients for 6 months. The pressure information was withheld from the treating physicians in the control group of 140 patients. All patients in the study also received optimal medical care based on clinical findings. The benefits of applying information collected by the Chronicle device were greatest in the 85% of patients who entered the study with New York Heart Association class III disease. Those with class IV disease had much less benefit.

The reduction in hospitalized days using data collected by the implanted device was more marked if the analysis excluded outlier patients with hospitalizations that extended beyond 30 days. With this exclusion, use of the Chronicle data cut the total number of hospitalized days by 42% for all patients in the study, and by 38% in the class III-only patients.

Another secondary analysis examined the impact of using data from the Chronicle device on the rate of prolonged or short hospitalizations for heart failure. Among the class III-only patients, use of Chronicle information was associated with an average rate of 0.19 long hospitalizations (more than 5 days) every 6 months, compared with a rate of 0.31 long hospitalizations every 6 months in the control group, a 40% decrease in favor of the device. Use of the device also was associated with a 0.28 rate of short hospitalizations (5 days or less) every 6 months, compared with a rate of 0.42 short hospitalizations every 6 months in the control group.

Despite the lack of a statistically significant positive result for the primary end point of the COMPASS-HF trial, the researchers who ran the study believe that the results demonstrate the device's efficacy.

“It's a positive study overall,” commented Dr. Robert C. Bourge, lead investigator for the study and professor and director of the division of cardiovascular disease at the University of Alabama, Birmingham.

But other experts are concerned about paying for this intensive approach to patient management.

“The implications are profound regarding the cost of care,” commented Dr. Harlan M. Krumholz, professor of medicine and epidemiology at Yale University, New Haven, Conn. “How should we decide which patients should get this?”

“We're developing models of how to use it,” said Dr. Bourge, who acknowledged that not all physicians would have the expertise or time to review so many pressure measurements for their patients.

Because of this, researchers are working on developing an automated way to review the large number of intracardiac pressure measurements that are made in each patient.

DALLAS — Management of heart failure patients with data from an implanted device that continuously monitors hemodynamic pressures led to a 25% reduction in total days spent in the hospital among patients with class III heart failure in a controlled study with more than 200 patients.

“The number of days spent in the hospital for decompensated heart failure is the principal driver of cost for heart failure treatment, and this was significantly decreased,” Dr. William T. Abraham said at the annual scientific sessions of the American Heart Association.

Use of the device in both outpatients and in hospitalized patients with heart failure “may make episodes of decompensation less extreme, and may help get patients out of the hospital more quickly,” said Dr. Abraham, professor and director of the division of cardiovascular medicine at Ohio State University in Columbus.

The finding came from new analyses of data collected in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, which tested the clinical impact of managing patients with intracardiac pressure data collected by the implanted Chronicle device. The device is made by Medtronic, which submitted an application for licensing to the Food and Drug Administration last August that was still pending in January.

The primary end point of the COMPASS-HF was reported last March at the annual meeting of the American College of Cardiology. Although patient management guided by pressure data obtained by the Chronicle device led to a 22% cut in the rate of heart failure-related hospitalizations and emergency department and urgent-care visits, the drop was not statistically significant. However, several secondary analyses also were positive in favor of the device, including a new set of secondary analyses presented by Dr. Abraham, who is a consultant and investigator for Medtronic and has received honoraria from the company for speaking.

He cautioned that the COMPASS-HF study was not designed to provide definitive answers to these secondary analyses, and therefore the findings must be considered exploratory.

In addition, researchers at Medtronic have revised the results presented by Dr. Abraham based on more comprehensive patient follow-up. The revised data showed that use of data from the Chronicle device cut the number of hospitalized days for heart failure by 20% instead of the 25% difference reported by Dr. Abraham. The 20% reduction is what was reported to the FDA, said Dr. David Israeli, director of marketing and business development for Medtronic in Minneapolis.

In the COMPASS-HF study, a total of 274 patients with advanced-stage heart failure underwent surgery to receive the subcutaneously-implanted, hemodynamic monitoring device. The intracardiac pressure information collected by the device was used by physicians to guide the management of 134 patients for 6 months. The pressure information was withheld from the treating physicians in the control group of 140 patients. All patients in the study also received optimal medical care based on clinical findings. The benefits of applying information collected by the Chronicle device were greatest in the 85% of patients who entered the study with New York Heart Association class III disease. Those with class IV disease had much less benefit.

The reduction in hospitalized days using data collected by the implanted device was more marked if the analysis excluded outlier patients with hospitalizations that extended beyond 30 days. With this exclusion, use of the Chronicle data cut the total number of hospitalized days by 42% for all patients in the study, and by 38% in the class III-only patients.

Another secondary analysis examined the impact of using data from the Chronicle device on the rate of prolonged or short hospitalizations for heart failure. Among the class III-only patients, use of Chronicle information was associated with an average rate of 0.19 long hospitalizations (more than 5 days) every 6 months, compared with a rate of 0.31 long hospitalizations every 6 months in the control group, a 40% decrease in favor of the device. Use of the device also was associated with a 0.28 rate of short hospitalizations (5 days or less) every 6 months, compared with a rate of 0.42 short hospitalizations every 6 months in the control group.

Despite the lack of a statistically significant positive result for the primary end point of the COMPASS-HF trial, the researchers who ran the study believe that the results demonstrate the device's efficacy.

“It's a positive study overall,” commented Dr. Robert C. Bourge, lead investigator for the study and professor and director of the division of cardiovascular disease at the University of Alabama, Birmingham.

But other experts are concerned about paying for this intensive approach to patient management.

“The implications are profound regarding the cost of care,” commented Dr. Harlan M. Krumholz, professor of medicine and epidemiology at Yale University, New Haven, Conn. “How should we decide which patients should get this?”

“We're developing models of how to use it,” said Dr. Bourge, who acknowledged that not all physicians would have the expertise or time to review so many pressure measurements for their patients.

Because of this, researchers are working on developing an automated way to review the large number of intracardiac pressure measurements that are made in each patient.

BOCA RATON, FLA. — When it comes to treatment options, palliative care, and decision making for patients with end-stage heart failure, cardiologists, internists, family physicians, and geriatricians are similarly lacking in awareness, according to a national pilot survey.

The American College of Cardiology and the American Heart Association's recommendations for the care of heart failure patients include a call for cardiologists to counsel patients about end-of-life issues.

However, most of the care of heart failure patients is done by noncardiologist physicians, and there is still uncertainty about which physicians should address end-of-life concerns with end-stage heart failure patients.

“The question is, who is going to have 'the talk'?” Dr. Paul J. Hauptman said in an interview.

“More and more patients have heart failure, and more and more patients are going to die from heart failure. What are we going to do with this burgeoning population of patients with heart failure?” asked Dr. Hauptman, professor of medicine, division of cardiology, and director of heart failure/transplantation at St. Louis (Mo.) University.

In an attempt to answer that question, Dr. Hauptman and his associates surveyed cardiologists, family physicians, internists, and geriatricians about the management of patients with end-stage heart failure. The investigators randomly selected physicians from the American Medical Association Master File.

The administration of the 51-question survey is ongoing, with the goal of garnering opinions from 1,450 physicians. Preliminary results from 76 responses were given in a poster presentation at the annual meeting of the Heart Failure Society of America.

The survey indicates a similar lack of awareness about published guidelines for heart failure (44% of cardiologists, 47% of noncardiologists), a similar belief in left-ventricular pacing as a life-extending measure (44% of cardiologists, 41% of noncardiologists), and a similar level of uncertainty about when to refer a patient to hospice care (52% of cardiologists, 53% of noncardiologists).

Almost 85% of the noncardiologists who responded to the survey said they believed that they, and not cardiologists, should initiate end-of-life discussions with their patients. “The noncardiologists really thought they were better [at that] than the cardiologists,” Dr. Hauptman commented.

However, he added, most of the generalists reported that they had never had such a discussion with a patient or a patient's family.

“Cardiologists have an acute-care perspective. We don't really know about what is going on at the end of life,” Dr. Hauptman said. “It's going to take education and discussions at national meetings [to understand that].”

The majority of respondents (91% of cardiologists, 67% of noncardiologists) do not use standard quality of life measurements for patients with end-stage heart failure.

“This would be kind of shocking” if confirmed by the full survey, he said.

Most of the cardiologists who were surveyed (65%) said that they have discussed implantable cardioverter defibrillator deactivation with an end-stage patient or family member, compared with 35% of noncardiologists.

With the increasing prevalence of heart failure, Dr. Hauptman asserted, “more patients are going to show up with a device. Do you turn them off or [do you] not turn them off?”

Dr. Hauptman said that he hoped the final results of the survey would provide even more insight about physicians' attitudes toward end-stage heart failure and that the information will be able to be used to design effective interventions in the future.

BOCA RATON, FLA. — When it comes to treatment options, palliative care, and decision making for patients with end-stage heart failure, cardiologists, internists, family physicians, and geriatricians are similarly lacking in awareness, according to a national pilot survey.

The American College of Cardiology and the American Heart Association's recommendations for the care of heart failure patients include a call for cardiologists to counsel patients about end-of-life issues.

However, most of the care of heart failure patients is done by noncardiologist physicians, and there is still uncertainty about which physicians should address end-of-life concerns with end-stage heart failure patients.

“The question is, who is going to have 'the talk'?” Dr. Paul J. Hauptman said in an interview.

“More and more patients have heart failure, and more and more patients are going to die from heart failure. What are we going to do with this burgeoning population of patients with heart failure?” asked Dr. Hauptman, professor of medicine, division of cardiology, and director of heart failure/transplantation at St. Louis (Mo.) University.

In an attempt to answer that question, Dr. Hauptman and his associates surveyed cardiologists, family physicians, internists, and geriatricians about the management of patients with end-stage heart failure. The investigators randomly selected physicians from the American Medical Association Master File.

The administration of the 51-question survey is ongoing, with the goal of garnering opinions from 1,450 physicians. Preliminary results from 76 responses were given in a poster presentation at the annual meeting of the Heart Failure Society of America.

The survey indicates a similar lack of awareness about published guidelines for heart failure (44% of cardiologists, 47% of noncardiologists), a similar belief in left-ventricular pacing as a life-extending measure (44% of cardiologists, 41% of noncardiologists), and a similar level of uncertainty about when to refer a patient to hospice care (52% of cardiologists, 53% of noncardiologists).

Almost 85% of the noncardiologists who responded to the survey said they believed that they, and not cardiologists, should initiate end-of-life discussions with their patients. “The noncardiologists really thought they were better [at that] than the cardiologists,” Dr. Hauptman commented.

However, he added, most of the generalists reported that they had never had such a discussion with a patient or a patient's family.

“Cardiologists have an acute-care perspective. We don't really know about what is going on at the end of life,” Dr. Hauptman said. “It's going to take education and discussions at national meetings [to understand that].”

The majority of respondents (91% of cardiologists, 67% of noncardiologists) do not use standard quality of life measurements for patients with end-stage heart failure.

“This would be kind of shocking” if confirmed by the full survey, he said.

Most of the cardiologists who were surveyed (65%) said that they have discussed implantable cardioverter defibrillator deactivation with an end-stage patient or family member, compared with 35% of noncardiologists.

With the increasing prevalence of heart failure, Dr. Hauptman asserted, “more patients are going to show up with a device. Do you turn them off or [do you] not turn them off?”

Dr. Hauptman said that he hoped the final results of the survey would provide even more insight about physicians' attitudes toward end-stage heart failure and that the information will be able to be used to design effective interventions in the future.

BOCA RATON, FLA. — When it comes to treatment options, palliative care, and decision making for patients with end-stage heart failure, cardiologists, internists, family physicians, and geriatricians are similarly lacking in awareness, according to a national pilot survey.

The American College of Cardiology and the American Heart Association's recommendations for the care of heart failure patients include a call for cardiologists to counsel patients about end-of-life issues.

However, most of the care of heart failure patients is done by noncardiologist physicians, and there is still uncertainty about which physicians should address end-of-life concerns with end-stage heart failure patients.

“The question is, who is going to have 'the talk'?” Dr. Paul J. Hauptman said in an interview.

“More and more patients have heart failure, and more and more patients are going to die from heart failure. What are we going to do with this burgeoning population of patients with heart failure?” asked Dr. Hauptman, professor of medicine, division of cardiology, and director of heart failure/transplantation at St. Louis (Mo.) University.

In an attempt to answer that question, Dr. Hauptman and his associates surveyed cardiologists, family physicians, internists, and geriatricians about the management of patients with end-stage heart failure. The investigators randomly selected physicians from the American Medical Association Master File.

The administration of the 51-question survey is ongoing, with the goal of garnering opinions from 1,450 physicians. Preliminary results from 76 responses were given in a poster presentation at the annual meeting of the Heart Failure Society of America.

The survey indicates a similar lack of awareness about published guidelines for heart failure (44% of cardiologists, 47% of noncardiologists), a similar belief in left-ventricular pacing as a life-extending measure (44% of cardiologists, 41% of noncardiologists), and a similar level of uncertainty about when to refer a patient to hospice care (52% of cardiologists, 53% of noncardiologists).

Almost 85% of the noncardiologists who responded to the survey said they believed that they, and not cardiologists, should initiate end-of-life discussions with their patients. “The noncardiologists really thought they were better [at that] than the cardiologists,” Dr. Hauptman commented.

However, he added, most of the generalists reported that they had never had such a discussion with a patient or a patient's family.

“Cardiologists have an acute-care perspective. We don't really know about what is going on at the end of life,” Dr. Hauptman said. “It's going to take education and discussions at national meetings [to understand that].”

The majority of respondents (91% of cardiologists, 67% of noncardiologists) do not use standard quality of life measurements for patients with end-stage heart failure.

“This would be kind of shocking” if confirmed by the full survey, he said.

Most of the cardiologists who were surveyed (65%) said that they have discussed implantable cardioverter defibrillator deactivation with an end-stage patient or family member, compared with 35% of noncardiologists.

With the increasing prevalence of heart failure, Dr. Hauptman asserted, “more patients are going to show up with a device. Do you turn them off or [do you] not turn them off?”

Dr. Hauptman said that he hoped the final results of the survey would provide even more insight about physicians' attitudes toward end-stage heart failure and that the information will be able to be used to design effective interventions in the future.

DALLAS — The obesity paradox previously described in patients with chronic systolic heart failure has, for the first time, been shown to be strikingly evident in acute heart failure as well, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association.

An analysis of 108,927 hospitalizations recorded in the Acute Decompensated Heart Failure Registry (ADHERE) showed that in-hospital mortality decreased in near-linear fashion with increasing body mass index (BMI) quartile. (See box.)

The same marked reduction in in-hospital mortality that was seen in heavier ADHERE participants who had reduced systolic function was also seen in those with preserved systolic function, added Dr. Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

The paradox lies in the fact that obesity is a well-recognized independent cardiovascular risk factor in the general population, yet in the setting of chronic or acute heart failure, it is somehow protective.

The bottom line is that the paradox in acute heart failure is a real phenomenon. “Given the huge number of hospital episodes we're looking at here, the results are irrefutable,” Dr. Fonarow said.

The obesity paradox has potentially enormous clinical implications for the management of acute decompensated heart failure, a condition that constitutes the primary or secondary diagnosis in an estimated 3 million hospitalizations annually in the United States. The next step in the research is to provide acute nutritional support when normal-weight or underweight patients—those with, say, a BMI below 27 kg/m

“The broad implication is that this represents half of all acute heart failure hospitalizations, and they could potentially be amenable to having their acute mortality rates cut by one-third to one-half if this therapy pans out,” Dr. Fonarow said in an interview.

“We're seriously thinking of doing some pilot studies looking at whether we can improve measures of cardiac function and nutritional status in these patients through acute nutritional support—and if that looks promising, to go forward with an interventional trial,” he said.

Only through such studies will physicians learn whether obesity is causative of reduced mortality in acute heart failure patients or whether it is merely a marker for lower risk. It is worth noting, though, that even after adjustment for known predictors of in-hospital mortality in acute heart failure—including age, gender, blood urea nitrogen, creatinine, blood pressure, and dyspnea at rest—patients in the lowest BMI quartile had a highly significant 46% greater in-hospital mortality than did those in the top quartile, who had a BMI of at least 33.4.

The same held true when patients were grouped by World Health Organization BMI category rather than by quartile. Underweight patients—those with a BMI less than 18.5—had an in-hospital mortality of 6.3%. The rate was 4.6% in normal-weight patients (BMI 18.5–24.9), 3.4% in overweight patients (BMI 25.0–29.9), and 2.4% in obese patients.

The obesity paradox in acute heart failure cannot be explained merely as a reflection of cachectic patients being unable to handle the stress of acute illness. After all, in-hospital mortality was increased even in normal-weight patients, compared with those who were overweight or obese, Dr. Fonarow said.

ADHERE is funded by Scios Inc.

KEVIN FOLEY, RESEARCH

DALLAS — The obesity paradox previously described in patients with chronic systolic heart failure has, for the first time, been shown to be strikingly evident in acute heart failure as well, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association.

An analysis of 108,927 hospitalizations recorded in the Acute Decompensated Heart Failure Registry (ADHERE) showed that in-hospital mortality decreased in near-linear fashion with increasing body mass index (BMI) quartile. (See box.)

The same marked reduction in in-hospital mortality that was seen in heavier ADHERE participants who had reduced systolic function was also seen in those with preserved systolic function, added Dr. Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

The paradox lies in the fact that obesity is a well-recognized independent cardiovascular risk factor in the general population, yet in the setting of chronic or acute heart failure, it is somehow protective.

The bottom line is that the paradox in acute heart failure is a real phenomenon. “Given the huge number of hospital episodes we're looking at here, the results are irrefutable,” Dr. Fonarow said.

The obesity paradox has potentially enormous clinical implications for the management of acute decompensated heart failure, a condition that constitutes the primary or secondary diagnosis in an estimated 3 million hospitalizations annually in the United States. The next step in the research is to provide acute nutritional support when normal-weight or underweight patients—those with, say, a BMI below 27 kg/m

“The broad implication is that this represents half of all acute heart failure hospitalizations, and they could potentially be amenable to having their acute mortality rates cut by one-third to one-half if this therapy pans out,” Dr. Fonarow said in an interview.

“We're seriously thinking of doing some pilot studies looking at whether we can improve measures of cardiac function and nutritional status in these patients through acute nutritional support—and if that looks promising, to go forward with an interventional trial,” he said.

Only through such studies will physicians learn whether obesity is causative of reduced mortality in acute heart failure patients or whether it is merely a marker for lower risk. It is worth noting, though, that even after adjustment for known predictors of in-hospital mortality in acute heart failure—including age, gender, blood urea nitrogen, creatinine, blood pressure, and dyspnea at rest—patients in the lowest BMI quartile had a highly significant 46% greater in-hospital mortality than did those in the top quartile, who had a BMI of at least 33.4.

The same held true when patients were grouped by World Health Organization BMI category rather than by quartile. Underweight patients—those with a BMI less than 18.5—had an in-hospital mortality of 6.3%. The rate was 4.6% in normal-weight patients (BMI 18.5–24.9), 3.4% in overweight patients (BMI 25.0–29.9), and 2.4% in obese patients.

The obesity paradox in acute heart failure cannot be explained merely as a reflection of cachectic patients being unable to handle the stress of acute illness. After all, in-hospital mortality was increased even in normal-weight patients, compared with those who were overweight or obese, Dr. Fonarow said.

ADHERE is funded by Scios Inc.

KEVIN FOLEY, RESEARCH

DALLAS — The obesity paradox previously described in patients with chronic systolic heart failure has, for the first time, been shown to be strikingly evident in acute heart failure as well, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association.

An analysis of 108,927 hospitalizations recorded in the Acute Decompensated Heart Failure Registry (ADHERE) showed that in-hospital mortality decreased in near-linear fashion with increasing body mass index (BMI) quartile. (See box.)

The same marked reduction in in-hospital mortality that was seen in heavier ADHERE participants who had reduced systolic function was also seen in those with preserved systolic function, added Dr. Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

The paradox lies in the fact that obesity is a well-recognized independent cardiovascular risk factor in the general population, yet in the setting of chronic or acute heart failure, it is somehow protective.

The bottom line is that the paradox in acute heart failure is a real phenomenon. “Given the huge number of hospital episodes we're looking at here, the results are irrefutable,” Dr. Fonarow said.

The obesity paradox has potentially enormous clinical implications for the management of acute decompensated heart failure, a condition that constitutes the primary or secondary diagnosis in an estimated 3 million hospitalizations annually in the United States. The next step in the research is to provide acute nutritional support when normal-weight or underweight patients—those with, say, a BMI below 27 kg/m

“The broad implication is that this represents half of all acute heart failure hospitalizations, and they could potentially be amenable to having their acute mortality rates cut by one-third to one-half if this therapy pans out,” Dr. Fonarow said in an interview.

“We're seriously thinking of doing some pilot studies looking at whether we can improve measures of cardiac function and nutritional status in these patients through acute nutritional support—and if that looks promising, to go forward with an interventional trial,” he said.

Only through such studies will physicians learn whether obesity is causative of reduced mortality in acute heart failure patients or whether it is merely a marker for lower risk. It is worth noting, though, that even after adjustment for known predictors of in-hospital mortality in acute heart failure—including age, gender, blood urea nitrogen, creatinine, blood pressure, and dyspnea at rest—patients in the lowest BMI quartile had a highly significant 46% greater in-hospital mortality than did those in the top quartile, who had a BMI of at least 33.4.

The same held true when patients were grouped by World Health Organization BMI category rather than by quartile. Underweight patients—those with a BMI less than 18.5—had an in-hospital mortality of 6.3%. The rate was 4.6% in normal-weight patients (BMI 18.5–24.9), 3.4% in overweight patients (BMI 25.0–29.9), and 2.4% in obese patients.

The obesity paradox in acute heart failure cannot be explained merely as a reflection of cachectic patients being unable to handle the stress of acute illness. After all, in-hospital mortality was increased even in normal-weight patients, compared with those who were overweight or obese, Dr. Fonarow said.

ADHERE is funded by Scios Inc.

KEVIN FOLEY, RESEARCH

DALLAS — The investigational acute decompensated heart failure drug levosimendan garnered mixed reviews for its less-than-stellar performance in two large, multinational, double-blind, randomized clinical trials presented at the annual scientific sessions of the American Heart Association.

Levosimendan has both inotropic and vasodilator properties. But unlike other positive inotropes, whose action is mediated by increased intracellular calcium, levosimendan enhances cardiac myofilament sensitivity to an unchanged concentration of calcium. The drug also possesses peripheral vasodilator action mediated by an agonist effect on potassium channels.

Dr. Milton Packer reported on 600 patients in the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE II) trial who were hospitalized for acute decompensated heart failure (ADHF) not adequately responsive to intravenous diuretics. They were randomized to a 24-hour infusion of levosimendan or placebo, with intensification of standard background therapies as needed.

The primary end point in REVIVE II was a composite measure of clinical status during the first 5 days of hospitalization. The levosimendan group fared significantly better in this regard than did the controls, even though levosimendan had been stopped after the first 24 hours. Of those in the levosimendan arm, 76% showed moderate or marked improvement in a composite global assessment score, compared with 65% of controls. In the levosimendan arm, 15% required rescue therapy because their condition worsened, compared with 26% in the placebo arm. Levels of brain natriuretic peptide, a surrogate for heart failure severity, were halved in the levosimendan group and stayed low. Patients treated with Levosimendan felt better in as little as 6 hours, and that feeling persisted through 5 days.

But 28 levosimendan-treated patients developed atrial fibrillation and 72 experienced ventricular arrhythmias, compared with 6 and 51, respectively, on placebo. Symptomatic hypotension and headaches were also more common with levosimendan. There were 49 deaths within 90 days with levosimendan and 40 with placebo, said Dr. Packer, professor of medicine and director of the Center for Biostatistics and Clinical Science at the University of Texas Southwestern Medical Center, Dallas.

He stressed that intravenous diuretics—a fast-acting, safe, and relatively inexpensive treatment—will remain the initial intervention for patients who present with ADHF. He estimated, however, that this therapy achieves an adequate response—relief of shortness of breath at rest—in only about half of the 3 million U.S. hospitalizations per year with ADHF as the primary or secondary diagnosis. It's in the other half that he sees levosimendan as potentially playing a major role.

Dr. Alexandre Mebazaa presented the results of the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study, the first large-scale study to examine the survival impact of medications used to treat ADHF. SURVIVE involved 1,327 patients in eight countries who were randomized to levosimendan or dobutamine along with standard background treatments.

In SURVIVE, the primary end point was 6-month all-cause mortality, which was 26% in the levosimendan arm and 28% with dobutamine, a nonsignificant difference. But it was unrealistic to expect a mortality difference so long after a single 24-hour drug infusion, said Dr. Mebazaa, professor and director of the department of anesthesia and critical care medicine at Lariboisière Hospital, Paris.

The results were more impressive closer to the treatment period. At day 5, for example, mortality was 4.4% in the levosimendan group and 6.0% with dobutamine, a 28% reduction in relative risk. As in REVIVE II, there was an increased incidence of atrial fibrillation with levosimendan, he said.

Some audience members were enthused that the levosimendan trials had raised the bar in terms of the rigor with which ADHF drugs are evaluated. All currently available drugs were approved on the basis of hemodynamic gains rather than evidence of the more meaningful end points of improved clinical status or outcomes.

Dr. Gordon F. Tomaselli, vice chairman of the AHA scientific sessions program committee, said in an interview that given the high lethality of ADHF (more than one-quarter of SURVIVE participants died within 6 months) and the very limited current treatment options, levosimendan “probably does have a place in the armamentarium.”

But Dr. Gregg C. Fonarow was skeptical. “It's hard to conceive that with this dosing regimen this would be a treatment that physicians would want to use for their patients. A reduction in symptoms is not going to be acceptable if it comes at a price of substantial increased risk of severe adverse events,” said Dr Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“If you compare the serious adverse events seen in REVIVE II with what was observed in the largest trial with nesiritide, levosimendan comes nowhere close to being as safe as nesiritide,” he said. Nesiritide (Natrecor) has come under fire in the past year after assertions it may worsen renal function and increase mortality.

Dr. Packer is a consultant to Abbott Laboratories and Orion Pharma, which funded REVIVE II and SURVIVE. Dr. Mebazaa is a consultant to Abbott.

Intravenous diuretics will remain the initial intervention for patients who present with ADHF. DR. PACKER

DALLAS — The investigational acute decompensated heart failure drug levosimendan garnered mixed reviews for its less-than-stellar performance in two large, multinational, double-blind, randomized clinical trials presented at the annual scientific sessions of the American Heart Association.

Levosimendan has both inotropic and vasodilator properties. But unlike other positive inotropes, whose action is mediated by increased intracellular calcium, levosimendan enhances cardiac myofilament sensitivity to an unchanged concentration of calcium. The drug also possesses peripheral vasodilator action mediated by an agonist effect on potassium channels.

Dr. Milton Packer reported on 600 patients in the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE II) trial who were hospitalized for acute decompensated heart failure (ADHF) not adequately responsive to intravenous diuretics. They were randomized to a 24-hour infusion of levosimendan or placebo, with intensification of standard background therapies as needed.

The primary end point in REVIVE II was a composite measure of clinical status during the first 5 days of hospitalization. The levosimendan group fared significantly better in this regard than did the controls, even though levosimendan had been stopped after the first 24 hours. Of those in the levosimendan arm, 76% showed moderate or marked improvement in a composite global assessment score, compared with 65% of controls. In the levosimendan arm, 15% required rescue therapy because their condition worsened, compared with 26% in the placebo arm. Levels of brain natriuretic peptide, a surrogate for heart failure severity, were halved in the levosimendan group and stayed low. Patients treated with Levosimendan felt better in as little as 6 hours, and that feeling persisted through 5 days.

But 28 levosimendan-treated patients developed atrial fibrillation and 72 experienced ventricular arrhythmias, compared with 6 and 51, respectively, on placebo. Symptomatic hypotension and headaches were also more common with levosimendan. There were 49 deaths within 90 days with levosimendan and 40 with placebo, said Dr. Packer, professor of medicine and director of the Center for Biostatistics and Clinical Science at the University of Texas Southwestern Medical Center, Dallas.

He stressed that intravenous diuretics—a fast-acting, safe, and relatively inexpensive treatment—will remain the initial intervention for patients who present with ADHF. He estimated, however, that this therapy achieves an adequate response—relief of shortness of breath at rest—in only about half of the 3 million U.S. hospitalizations per year with ADHF as the primary or secondary diagnosis. It's in the other half that he sees levosimendan as potentially playing a major role.

Dr. Alexandre Mebazaa presented the results of the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study, the first large-scale study to examine the survival impact of medications used to treat ADHF. SURVIVE involved 1,327 patients in eight countries who were randomized to levosimendan or dobutamine along with standard background treatments.

In SURVIVE, the primary end point was 6-month all-cause mortality, which was 26% in the levosimendan arm and 28% with dobutamine, a nonsignificant difference. But it was unrealistic to expect a mortality difference so long after a single 24-hour drug infusion, said Dr. Mebazaa, professor and director of the department of anesthesia and critical care medicine at Lariboisière Hospital, Paris.

The results were more impressive closer to the treatment period. At day 5, for example, mortality was 4.4% in the levosimendan group and 6.0% with dobutamine, a 28% reduction in relative risk. As in REVIVE II, there was an increased incidence of atrial fibrillation with levosimendan, he said.

Some audience members were enthused that the levosimendan trials had raised the bar in terms of the rigor with which ADHF drugs are evaluated. All currently available drugs were approved on the basis of hemodynamic gains rather than evidence of the more meaningful end points of improved clinical status or outcomes.

Dr. Gordon F. Tomaselli, vice chairman of the AHA scientific sessions program committee, said in an interview that given the high lethality of ADHF (more than one-quarter of SURVIVE participants died within 6 months) and the very limited current treatment options, levosimendan “probably does have a place in the armamentarium.”

But Dr. Gregg C. Fonarow was skeptical. “It's hard to conceive that with this dosing regimen this would be a treatment that physicians would want to use for their patients. A reduction in symptoms is not going to be acceptable if it comes at a price of substantial increased risk of severe adverse events,” said Dr Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“If you compare the serious adverse events seen in REVIVE II with what was observed in the largest trial with nesiritide, levosimendan comes nowhere close to being as safe as nesiritide,” he said. Nesiritide (Natrecor) has come under fire in the past year after assertions it may worsen renal function and increase mortality.

Dr. Packer is a consultant to Abbott Laboratories and Orion Pharma, which funded REVIVE II and SURVIVE. Dr. Mebazaa is a consultant to Abbott.

Intravenous diuretics will remain the initial intervention for patients who present with ADHF. DR. PACKER

DALLAS — The investigational acute decompensated heart failure drug levosimendan garnered mixed reviews for its less-than-stellar performance in two large, multinational, double-blind, randomized clinical trials presented at the annual scientific sessions of the American Heart Association.

Levosimendan has both inotropic and vasodilator properties. But unlike other positive inotropes, whose action is mediated by increased intracellular calcium, levosimendan enhances cardiac myofilament sensitivity to an unchanged concentration of calcium. The drug also possesses peripheral vasodilator action mediated by an agonist effect on potassium channels.

Dr. Milton Packer reported on 600 patients in the Randomized Multicenter Evaluation of Intravenous Levosimendan Efficacy (REVIVE II) trial who were hospitalized for acute decompensated heart failure (ADHF) not adequately responsive to intravenous diuretics. They were randomized to a 24-hour infusion of levosimendan or placebo, with intensification of standard background therapies as needed.

The primary end point in REVIVE II was a composite measure of clinical status during the first 5 days of hospitalization. The levosimendan group fared significantly better in this regard than did the controls, even though levosimendan had been stopped after the first 24 hours. Of those in the levosimendan arm, 76% showed moderate or marked improvement in a composite global assessment score, compared with 65% of controls. In the levosimendan arm, 15% required rescue therapy because their condition worsened, compared with 26% in the placebo arm. Levels of brain natriuretic peptide, a surrogate for heart failure severity, were halved in the levosimendan group and stayed low. Patients treated with Levosimendan felt better in as little as 6 hours, and that feeling persisted through 5 days.

But 28 levosimendan-treated patients developed atrial fibrillation and 72 experienced ventricular arrhythmias, compared with 6 and 51, respectively, on placebo. Symptomatic hypotension and headaches were also more common with levosimendan. There were 49 deaths within 90 days with levosimendan and 40 with placebo, said Dr. Packer, professor of medicine and director of the Center for Biostatistics and Clinical Science at the University of Texas Southwestern Medical Center, Dallas.

He stressed that intravenous diuretics—a fast-acting, safe, and relatively inexpensive treatment—will remain the initial intervention for patients who present with ADHF. He estimated, however, that this therapy achieves an adequate response—relief of shortness of breath at rest—in only about half of the 3 million U.S. hospitalizations per year with ADHF as the primary or secondary diagnosis. It's in the other half that he sees levosimendan as potentially playing a major role.

Dr. Alexandre Mebazaa presented the results of the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support (SURVIVE) study, the first large-scale study to examine the survival impact of medications used to treat ADHF. SURVIVE involved 1,327 patients in eight countries who were randomized to levosimendan or dobutamine along with standard background treatments.

In SURVIVE, the primary end point was 6-month all-cause mortality, which was 26% in the levosimendan arm and 28% with dobutamine, a nonsignificant difference. But it was unrealistic to expect a mortality difference so long after a single 24-hour drug infusion, said Dr. Mebazaa, professor and director of the department of anesthesia and critical care medicine at Lariboisière Hospital, Paris.

The results were more impressive closer to the treatment period. At day 5, for example, mortality was 4.4% in the levosimendan group and 6.0% with dobutamine, a 28% reduction in relative risk. As in REVIVE II, there was an increased incidence of atrial fibrillation with levosimendan, he said.

Some audience members were enthused that the levosimendan trials had raised the bar in terms of the rigor with which ADHF drugs are evaluated. All currently available drugs were approved on the basis of hemodynamic gains rather than evidence of the more meaningful end points of improved clinical status or outcomes.

Dr. Gordon F. Tomaselli, vice chairman of the AHA scientific sessions program committee, said in an interview that given the high lethality of ADHF (more than one-quarter of SURVIVE participants died within 6 months) and the very limited current treatment options, levosimendan “probably does have a place in the armamentarium.”

But Dr. Gregg C. Fonarow was skeptical. “It's hard to conceive that with this dosing regimen this would be a treatment that physicians would want to use for their patients. A reduction in symptoms is not going to be acceptable if it comes at a price of substantial increased risk of severe adverse events,” said Dr Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“If you compare the serious adverse events seen in REVIVE II with what was observed in the largest trial with nesiritide, levosimendan comes nowhere close to being as safe as nesiritide,” he said. Nesiritide (Natrecor) has come under fire in the past year after assertions it may worsen renal function and increase mortality.

Dr. Packer is a consultant to Abbott Laboratories and Orion Pharma, which funded REVIVE II and SURVIVE. Dr. Mebazaa is a consultant to Abbott.

Intravenous diuretics will remain the initial intervention for patients who present with ADHF. DR. PACKER

BOCA RATON, FLA. — Automated home monitoring improved short-term outcomes for patients with heart failure, compared with standard disease management alone, in a multicenter, randomized study, Dr. Andrew R. Weintraub reported at the annual meeting of the Heart Failure Society of America.

Previously, researchers showed the benefit of disease management for heart failure patients, but the studies were nonrandomized, single-center, or assessed nonspecialized teams. Then the prospective, randomized Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) study demonstrated a significant reduction in hospitalizations from heart failure and cardiovascular disease, as well as a shorter length of stay with disease management (Circulation 2004;110:1450–5), said Dr. Weintraub, director of the Coronary Care Unit at the Tufts-New England Medical Center, Boston.

To determine whether the addition of automated home monitoring would further reduce hospitalization and resource use for patients enrolled in the disease management program, Dr. Weintraub and his associates randomized 93 patients to a control group of disease management and another 95 to an intervention group with home monitoring.

The control patients received the same disease management as in the SPAN-CHF study, which included an initial nurse home visit, weekly or biweekly telephone monitoring, and the availability of a nurse manager 24 hours a day via pager. Intervention patients received the same services, but also weighed themselves on an interactive scale, measured their blood pressure, and took their pulse daily using an automated home monitor (Philips Medical Systems, Bothell, Wash.). They also answered health status and compliance questions daily via text messaging (Health Hero Network, Mountain View, Calif.).

The investigators enrolled patients within 2 weeks of discharge after their first episode of heart failure. All had a measurement of left ventricular function within 6 months (mean 30%). They were aged 18–90 years. There was a high incidence of ACE inhibitor, angiotensin receptor blocker, and β-blocker use. Patient demographics were similar. Both groups had a wide range in baseline ejection fractions, said Dr. Weintraub.

“We detected a trend in reduction with intervention of heart failure hospitalized days, cardiac hospitalized days, and all-cause hospitalized days,” he said.

The number of hospitalizations for heart failure more than 90 days in the intervention group was a mean 0.5, compared with 1.8 for the control group (relative risk 0.28). Hospitalizations for all cardiac causes were 0.8 in the intervention group, compared with 2.2 in the control group (RR 0.37). There were no significant differences between groups in all-cause hospitalizations.

There were no differences in hospitalization rates according to gender, age, left ventricular ejection fraction, New York Heart Association classification, or hypertension. However, “our patients with diabetes at baseline were significantly more likely to be hospitalized for heart failure,” Dr. Weintraub added (odds ratio 4.3).

“We documented the 90-day benefit of adding an automated-home-monitoring system to a previously validated telephonic disease management program,” said Dr. Weintraub, who received research support from GlaxoSmithKline Inc., Agilent Technologies/Philips Medical Systems, and the Health Hero Network. “The addition … produced further improvement in the short-term, heart failure-related clinical outcomes in patients recently hospitalized for heart failure.”

An attendee asked whether the benefits were a result of self-management or the increase in nurse-patient interaction. Nurse managers reported spending 15%–20% above the normal standard care time with automated-home-monitoring patients, Dr. Weintraub said. But the benefit was from self- management and “the nurses facilitated that benefit,” he asserted.

BOCA RATON, FLA. — Automated home monitoring improved short-term outcomes for patients with heart failure, compared with standard disease management alone, in a multicenter, randomized study, Dr. Andrew R. Weintraub reported at the annual meeting of the Heart Failure Society of America.

Previously, researchers showed the benefit of disease management for heart failure patients, but the studies were nonrandomized, single-center, or assessed nonspecialized teams. Then the prospective, randomized Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) study demonstrated a significant reduction in hospitalizations from heart failure and cardiovascular disease, as well as a shorter length of stay with disease management (Circulation 2004;110:1450–5), said Dr. Weintraub, director of the Coronary Care Unit at the Tufts-New England Medical Center, Boston.

To determine whether the addition of automated home monitoring would further reduce hospitalization and resource use for patients enrolled in the disease management program, Dr. Weintraub and his associates randomized 93 patients to a control group of disease management and another 95 to an intervention group with home monitoring.

The control patients received the same disease management as in the SPAN-CHF study, which included an initial nurse home visit, weekly or biweekly telephone monitoring, and the availability of a nurse manager 24 hours a day via pager. Intervention patients received the same services, but also weighed themselves on an interactive scale, measured their blood pressure, and took their pulse daily using an automated home monitor (Philips Medical Systems, Bothell, Wash.). They also answered health status and compliance questions daily via text messaging (Health Hero Network, Mountain View, Calif.).

The investigators enrolled patients within 2 weeks of discharge after their first episode of heart failure. All had a measurement of left ventricular function within 6 months (mean 30%). They were aged 18–90 years. There was a high incidence of ACE inhibitor, angiotensin receptor blocker, and β-blocker use. Patient demographics were similar. Both groups had a wide range in baseline ejection fractions, said Dr. Weintraub.

“We detected a trend in reduction with intervention of heart failure hospitalized days, cardiac hospitalized days, and all-cause hospitalized days,” he said.

The number of hospitalizations for heart failure more than 90 days in the intervention group was a mean 0.5, compared with 1.8 for the control group (relative risk 0.28). Hospitalizations for all cardiac causes were 0.8 in the intervention group, compared with 2.2 in the control group (RR 0.37). There were no significant differences between groups in all-cause hospitalizations.

There were no differences in hospitalization rates according to gender, age, left ventricular ejection fraction, New York Heart Association classification, or hypertension. However, “our patients with diabetes at baseline were significantly more likely to be hospitalized for heart failure,” Dr. Weintraub added (odds ratio 4.3).

“We documented the 90-day benefit of adding an automated-home-monitoring system to a previously validated telephonic disease management program,” said Dr. Weintraub, who received research support from GlaxoSmithKline Inc., Agilent Technologies/Philips Medical Systems, and the Health Hero Network. “The addition … produced further improvement in the short-term, heart failure-related clinical outcomes in patients recently hospitalized for heart failure.”

An attendee asked whether the benefits were a result of self-management or the increase in nurse-patient interaction. Nurse managers reported spending 15%–20% above the normal standard care time with automated-home-monitoring patients, Dr. Weintraub said. But the benefit was from self- management and “the nurses facilitated that benefit,” he asserted.

BOCA RATON, FLA. — Automated home monitoring improved short-term outcomes for patients with heart failure, compared with standard disease management alone, in a multicenter, randomized study, Dr. Andrew R. Weintraub reported at the annual meeting of the Heart Failure Society of America.

Previously, researchers showed the benefit of disease management for heart failure patients, but the studies were nonrandomized, single-center, or assessed nonspecialized teams. Then the prospective, randomized Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) study demonstrated a significant reduction in hospitalizations from heart failure and cardiovascular disease, as well as a shorter length of stay with disease management (Circulation 2004;110:1450–5), said Dr. Weintraub, director of the Coronary Care Unit at the Tufts-New England Medical Center, Boston.

To determine whether the addition of automated home monitoring would further reduce hospitalization and resource use for patients enrolled in the disease management program, Dr. Weintraub and his associates randomized 93 patients to a control group of disease management and another 95 to an intervention group with home monitoring.

The control patients received the same disease management as in the SPAN-CHF study, which included an initial nurse home visit, weekly or biweekly telephone monitoring, and the availability of a nurse manager 24 hours a day via pager. Intervention patients received the same services, but also weighed themselves on an interactive scale, measured their blood pressure, and took their pulse daily using an automated home monitor (Philips Medical Systems, Bothell, Wash.). They also answered health status and compliance questions daily via text messaging (Health Hero Network, Mountain View, Calif.).

The investigators enrolled patients within 2 weeks of discharge after their first episode of heart failure. All had a measurement of left ventricular function within 6 months (mean 30%). They were aged 18–90 years. There was a high incidence of ACE inhibitor, angiotensin receptor blocker, and β-blocker use. Patient demographics were similar. Both groups had a wide range in baseline ejection fractions, said Dr. Weintraub.

“We detected a trend in reduction with intervention of heart failure hospitalized days, cardiac hospitalized days, and all-cause hospitalized days,” he said.

The number of hospitalizations for heart failure more than 90 days in the intervention group was a mean 0.5, compared with 1.8 for the control group (relative risk 0.28). Hospitalizations for all cardiac causes were 0.8 in the intervention group, compared with 2.2 in the control group (RR 0.37). There were no significant differences between groups in all-cause hospitalizations.

There were no differences in hospitalization rates according to gender, age, left ventricular ejection fraction, New York Heart Association classification, or hypertension. However, “our patients with diabetes at baseline were significantly more likely to be hospitalized for heart failure,” Dr. Weintraub added (odds ratio 4.3).

“We documented the 90-day benefit of adding an automated-home-monitoring system to a previously validated telephonic disease management program,” said Dr. Weintraub, who received research support from GlaxoSmithKline Inc., Agilent Technologies/Philips Medical Systems, and the Health Hero Network. “The addition … produced further improvement in the short-term, heart failure-related clinical outcomes in patients recently hospitalized for heart failure.”

An attendee asked whether the benefits were a result of self-management or the increase in nurse-patient interaction. Nurse managers reported spending 15%–20% above the normal standard care time with automated-home-monitoring patients, Dr. Weintraub said. But the benefit was from self- management and “the nurses facilitated that benefit,” he asserted.

DALLAS — An elevated B-type natriuretic peptide level upon admission for acute decompensated heart failure is an independent predictor of in-hospital mortality, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association. Moreover, B-type natriuretic peptide (BNP) is an equally robust predictor of in-hospital mortality regardless of whether the patient has preserved or reduced left ventricular systolic function, added Dr. Fonarow, professor of cardiovascular medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“These data suggest that the BNP assay should be part of the standard admission assessment of the acute decompensated heart failure patient,” he said.

Dr. Fonarow analyzed the relationship between admission BNP level and in-hospital mortality in 48,629 hospitalizations for acute decompensated heart failure (HF) during 2003–2004 at more than 275 U.S. hospitals participating in the Acute Decompensated Heart Failure National Registry (ADHERE).

He found a near-linear relationship between BNP quartile and in-hospital mortality. (See box.) The relationship was similar in the 52% of patients with a left ventricular ejection fraction of less than 40% and in those with preserved systolic function. The median hospital length of stay rose from 4.0 days in patients in the lowest quartile of BNP to 4.9 days in those in the top quartile, a difference that was highly significant because of the huge number of patients involved in the study. ICU admission was required for 12.8% of patients in BNP quartile 1, compared with 19.6% in quartile 4.

In an earlier study from ADHERE, Dr. Fonarow and coworkers developed and validated a practical bedside tool for mortality risk stratification in patients with acute decompensated heart failure (JAMA 2005;293:572–80).

The strongest in-hospital mortality predictors in this risk stratification method were admission blood urea nitrogen level, systolic blood pressure, and serum creatinine. Other significant predictors included in the bedside assessment tool were age, gender, serum sodium, pulse, and the presence of dyspnea at rest.

After adjustment for all of these other predictive factors, admission BNP quartile remained a highly significant independent predictor of in-hospital mortality. In fact, patients in the highest BNP quartile were 2.2-fold more likely to die during that hospitalization than were those in the lowest quartile, even after adjustment for the other eight predictors.

BNP has previously been shown to facilitate diagnosis of HF and predict long-term mortality risk in patients with chronic heart failure. However, the lab assay's prognostic utility in acute decompensated heart failure had not been studied.

The next step will be to see whether acutely decompensated patients with higher admission BNP levels benefit from a more aggressive monitoring and treatment strategy. If this hypothesis is shown to be sound, then it's possible that treatment regimens will be stratified based upon a patient's admission BNP, said Dr. Fonarow.

ADHERE is funded by Scios Inc.

DALLAS — An elevated B-type natriuretic peptide level upon admission for acute decompensated heart failure is an independent predictor of in-hospital mortality, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association. Moreover, B-type natriuretic peptide (BNP) is an equally robust predictor of in-hospital mortality regardless of whether the patient has preserved or reduced left ventricular systolic function, added Dr. Fonarow, professor of cardiovascular medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“These data suggest that the BNP assay should be part of the standard admission assessment of the acute decompensated heart failure patient,” he said.

Dr. Fonarow analyzed the relationship between admission BNP level and in-hospital mortality in 48,629 hospitalizations for acute decompensated heart failure (HF) during 2003–2004 at more than 275 U.S. hospitals participating in the Acute Decompensated Heart Failure National Registry (ADHERE).

He found a near-linear relationship between BNP quartile and in-hospital mortality. (See box.) The relationship was similar in the 52% of patients with a left ventricular ejection fraction of less than 40% and in those with preserved systolic function. The median hospital length of stay rose from 4.0 days in patients in the lowest quartile of BNP to 4.9 days in those in the top quartile, a difference that was highly significant because of the huge number of patients involved in the study. ICU admission was required for 12.8% of patients in BNP quartile 1, compared with 19.6% in quartile 4.

In an earlier study from ADHERE, Dr. Fonarow and coworkers developed and validated a practical bedside tool for mortality risk stratification in patients with acute decompensated heart failure (JAMA 2005;293:572–80).

The strongest in-hospital mortality predictors in this risk stratification method were admission blood urea nitrogen level, systolic blood pressure, and serum creatinine. Other significant predictors included in the bedside assessment tool were age, gender, serum sodium, pulse, and the presence of dyspnea at rest.

After adjustment for all of these other predictive factors, admission BNP quartile remained a highly significant independent predictor of in-hospital mortality. In fact, patients in the highest BNP quartile were 2.2-fold more likely to die during that hospitalization than were those in the lowest quartile, even after adjustment for the other eight predictors.

BNP has previously been shown to facilitate diagnosis of HF and predict long-term mortality risk in patients with chronic heart failure. However, the lab assay's prognostic utility in acute decompensated heart failure had not been studied.

The next step will be to see whether acutely decompensated patients with higher admission BNP levels benefit from a more aggressive monitoring and treatment strategy. If this hypothesis is shown to be sound, then it's possible that treatment regimens will be stratified based upon a patient's admission BNP, said Dr. Fonarow.

ADHERE is funded by Scios Inc.

DALLAS — An elevated B-type natriuretic peptide level upon admission for acute decompensated heart failure is an independent predictor of in-hospital mortality, Dr. Gregg C. Fonarow reported at the annual scientific sessions of the American Heart Association. Moreover, B-type natriuretic peptide (BNP) is an equally robust predictor of in-hospital mortality regardless of whether the patient has preserved or reduced left ventricular systolic function, added Dr. Fonarow, professor of cardiovascular medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

“These data suggest that the BNP assay should be part of the standard admission assessment of the acute decompensated heart failure patient,” he said.

Dr. Fonarow analyzed the relationship between admission BNP level and in-hospital mortality in 48,629 hospitalizations for acute decompensated heart failure (HF) during 2003–2004 at more than 275 U.S. hospitals participating in the Acute Decompensated Heart Failure National Registry (ADHERE).

He found a near-linear relationship between BNP quartile and in-hospital mortality. (See box.) The relationship was similar in the 52% of patients with a left ventricular ejection fraction of less than 40% and in those with preserved systolic function. The median hospital length of stay rose from 4.0 days in patients in the lowest quartile of BNP to 4.9 days in those in the top quartile, a difference that was highly significant because of the huge number of patients involved in the study. ICU admission was required for 12.8% of patients in BNP quartile 1, compared with 19.6% in quartile 4.

In an earlier study from ADHERE, Dr. Fonarow and coworkers developed and validated a practical bedside tool for mortality risk stratification in patients with acute decompensated heart failure (JAMA 2005;293:572–80).

The strongest in-hospital mortality predictors in this risk stratification method were admission blood urea nitrogen level, systolic blood pressure, and serum creatinine. Other significant predictors included in the bedside assessment tool were age, gender, serum sodium, pulse, and the presence of dyspnea at rest.

After adjustment for all of these other predictive factors, admission BNP quartile remained a highly significant independent predictor of in-hospital mortality. In fact, patients in the highest BNP quartile were 2.2-fold more likely to die during that hospitalization than were those in the lowest quartile, even after adjustment for the other eight predictors.

BNP has previously been shown to facilitate diagnosis of HF and predict long-term mortality risk in patients with chronic heart failure. However, the lab assay's prognostic utility in acute decompensated heart failure had not been studied.

The next step will be to see whether acutely decompensated patients with higher admission BNP levels benefit from a more aggressive monitoring and treatment strategy. If this hypothesis is shown to be sound, then it's possible that treatment regimens will be stratified based upon a patient's admission BNP, said Dr. Fonarow.

ADHERE is funded by Scios Inc.

DALLAS — Intensive treatment with atorvastatin in patients with stable coronary heart disease led to a significant reduction in hospitalization for heart failure in a secondary analysis of results from a study with 10,000 patients.

The results are the best evidence so far that statin treatment confers a heart-failure benefit. The findings also suggest that the benefit is not mediated by a reduction in ischemic coronary events but by another, as-yet unknown, mechanism, Dr. David D. Waters said at the annual scientific sessions of the American Heart Association.

“Randomized, controlled trials of statins in patients with heart failure will likely yield important findings,” reported Dr. Waters, who is chief of the division of cardiology at San Francisco General Hospital.

The heart failure analysis was a prespecified, secondary analysis of the Treating to New Targets (TNT) study, which randomized 10,001 patients with stable coronary disease to daily treatment with 10 mg or 80 mg atorvastatin (Lipitor) and then followed them for a median of 4.9 years.

The primary end point of the study was the combined rate of coronary death, nonfatal myocardial infarction, resuscitated cardiac arrest, and stroke. The 80-mg daily dose of atorvastatin was significantly more effective than the 10-mg daily dose for preventing this end point (N. Engl. J. Med. 2005;352:1425–35).

The study was sponsored by Pfizer, which markets Lipitor. Dr. Waters has been a consultant to and a speaker for Pfizer, and he has also received research grants from the company.

The impact of treatment on heart failure was assessed by the number of hospitalizations for heart failure during the study.

A total of 164 patients (3.3%) on the 10-mg dose were hospitalized for heart failure, compared with 122 patients (2.4%) in the 80-mg group, a 26% relative risk reduction that was statistically significant, Dr. Waters said.

The study excluded those patients with New York Heart Association class IIIb and class IV heart failure, as well as patients who had a left ventricular ejection fraction at baseline of less than 30%. Among those who enrolled, 8% of the patients had heart failure at baseline, but this subgroup accounted for 38% of the hospital admissions for heart failure. Among those who entered the trial without heart failure, the incidence of heart-failure hospitalizations was 1.9%.

In the subgroup with preexisting heart failure, the impact of high-dose atorvastatin was even greater. The hospitalization rate was 17.3% among those who were on 10 mg, compared with 10.6% among those on 80 mg, a “very large” absolute reduction of 6.7%, and a relative risk reduction of 41% that was statistically significant, Dr. Waters said.

In a multivariate analysis, the reduction of low-density lipoprotein (LDL) cholesterol was a significant modifier of risk after adjustment for other clinical and demographic variables. For every 1% drop in the serum level of LDL cholesterol, the risk of hospitalization for heart failure fell by 0.6%.

There was no indication that the drop in heart failure hospitalizations was mediated by an effect of high-dose atorvastatin on the incidence of myocardial infarctions and other ischemic events. During the 3 months prior to their first hospitalization for heart failure, only 15% of the patients had an acute coronary event. That meant that 85% of the hospitalizations for heart failure were not triggered by a coronary event, Dr. Waters noted.

Several other beneficial effects of statins might explain an effect on heart failure, including improved endothelial function, inhibited production of inflammatory cytokines, and direct antifibrotic, antihypertrophic, or antioxidant effects.

DALLAS — Intensive treatment with atorvastatin in patients with stable coronary heart disease led to a significant reduction in hospitalization for heart failure in a secondary analysis of results from a study with 10,000 patients.

The results are the best evidence so far that statin treatment confers a heart-failure benefit. The findings also suggest that the benefit is not mediated by a reduction in ischemic coronary events but by another, as-yet unknown, mechanism, Dr. David D. Waters said at the annual scientific sessions of the American Heart Association.

“Randomized, controlled trials of statins in patients with heart failure will likely yield important findings,” reported Dr. Waters, who is chief of the division of cardiology at San Francisco General Hospital.

The heart failure analysis was a prespecified, secondary analysis of the Treating to New Targets (TNT) study, which randomized 10,001 patients with stable coronary disease to daily treatment with 10 mg or 80 mg atorvastatin (Lipitor) and then followed them for a median of 4.9 years.

The primary end point of the study was the combined rate of coronary death, nonfatal myocardial infarction, resuscitated cardiac arrest, and stroke. The 80-mg daily dose of atorvastatin was significantly more effective than the 10-mg daily dose for preventing this end point (N. Engl. J. Med. 2005;352:1425–35).

The study was sponsored by Pfizer, which markets Lipitor. Dr. Waters has been a consultant to and a speaker for Pfizer, and he has also received research grants from the company.

The impact of treatment on heart failure was assessed by the number of hospitalizations for heart failure during the study.

A total of 164 patients (3.3%) on the 10-mg dose were hospitalized for heart failure, compared with 122 patients (2.4%) in the 80-mg group, a 26% relative risk reduction that was statistically significant, Dr. Waters said.

The study excluded those patients with New York Heart Association class IIIb and class IV heart failure, as well as patients who had a left ventricular ejection fraction at baseline of less than 30%. Among those who enrolled, 8% of the patients had heart failure at baseline, but this subgroup accounted for 38% of the hospital admissions for heart failure. Among those who entered the trial without heart failure, the incidence of heart-failure hospitalizations was 1.9%.

In the subgroup with preexisting heart failure, the impact of high-dose atorvastatin was even greater. The hospitalization rate was 17.3% among those who were on 10 mg, compared with 10.6% among those on 80 mg, a “very large” absolute reduction of 6.7%, and a relative risk reduction of 41% that was statistically significant, Dr. Waters said.

In a multivariate analysis, the reduction of low-density lipoprotein (LDL) cholesterol was a significant modifier of risk after adjustment for other clinical and demographic variables. For every 1% drop in the serum level of LDL cholesterol, the risk of hospitalization for heart failure fell by 0.6%.

There was no indication that the drop in heart failure hospitalizations was mediated by an effect of high-dose atorvastatin on the incidence of myocardial infarctions and other ischemic events. During the 3 months prior to their first hospitalization for heart failure, only 15% of the patients had an acute coronary event. That meant that 85% of the hospitalizations for heart failure were not triggered by a coronary event, Dr. Waters noted.

Several other beneficial effects of statins might explain an effect on heart failure, including improved endothelial function, inhibited production of inflammatory cytokines, and direct antifibrotic, antihypertrophic, or antioxidant effects.

DALLAS — Intensive treatment with atorvastatin in patients with stable coronary heart disease led to a significant reduction in hospitalization for heart failure in a secondary analysis of results from a study with 10,000 patients.

The results are the best evidence so far that statin treatment confers a heart-failure benefit. The findings also suggest that the benefit is not mediated by a reduction in ischemic coronary events but by another, as-yet unknown, mechanism, Dr. David D. Waters said at the annual scientific sessions of the American Heart Association.

“Randomized, controlled trials of statins in patients with heart failure will likely yield important findings,” reported Dr. Waters, who is chief of the division of cardiology at San Francisco General Hospital.

The heart failure analysis was a prespecified, secondary analysis of the Treating to New Targets (TNT) study, which randomized 10,001 patients with stable coronary disease to daily treatment with 10 mg or 80 mg atorvastatin (Lipitor) and then followed them for a median of 4.9 years.

The primary end point of the study was the combined rate of coronary death, nonfatal myocardial infarction, resuscitated cardiac arrest, and stroke. The 80-mg daily dose of atorvastatin was significantly more effective than the 10-mg daily dose for preventing this end point (N. Engl. J. Med. 2005;352:1425–35).

The study was sponsored by Pfizer, which markets Lipitor. Dr. Waters has been a consultant to and a speaker for Pfizer, and he has also received research grants from the company.

The impact of treatment on heart failure was assessed by the number of hospitalizations for heart failure during the study.

A total of 164 patients (3.3%) on the 10-mg dose were hospitalized for heart failure, compared with 122 patients (2.4%) in the 80-mg group, a 26% relative risk reduction that was statistically significant, Dr. Waters said.

The study excluded those patients with New York Heart Association class IIIb and class IV heart failure, as well as patients who had a left ventricular ejection fraction at baseline of less than 30%. Among those who enrolled, 8% of the patients had heart failure at baseline, but this subgroup accounted for 38% of the hospital admissions for heart failure. Among those who entered the trial without heart failure, the incidence of heart-failure hospitalizations was 1.9%.

In the subgroup with preexisting heart failure, the impact of high-dose atorvastatin was even greater. The hospitalization rate was 17.3% among those who were on 10 mg, compared with 10.6% among those on 80 mg, a “very large” absolute reduction of 6.7%, and a relative risk reduction of 41% that was statistically significant, Dr. Waters said.

In a multivariate analysis, the reduction of low-density lipoprotein (LDL) cholesterol was a significant modifier of risk after adjustment for other clinical and demographic variables. For every 1% drop in the serum level of LDL cholesterol, the risk of hospitalization for heart failure fell by 0.6%.

There was no indication that the drop in heart failure hospitalizations was mediated by an effect of high-dose atorvastatin on the incidence of myocardial infarctions and other ischemic events. During the 3 months prior to their first hospitalization for heart failure, only 15% of the patients had an acute coronary event. That meant that 85% of the hospitalizations for heart failure were not triggered by a coronary event, Dr. Waters noted.

Several other beneficial effects of statins might explain an effect on heart failure, including improved endothelial function, inhibited production of inflammatory cytokines, and direct antifibrotic, antihypertrophic, or antioxidant effects.

STOCKHOLM — A natriuretic peptide was safe and effective for treating patients with acute, decompensated heart failure in a phase II study with a total of 221 patients.

Ularitide, given intravenously, reduced pulmonary capillary wedge pressure, improved dyspnea, and did not worsen renal function when given to patients for 24 hours of continuous infusion, Veselin Mitrovic, M.D., said at the annual congress of the European Society of Cardiology.

A synthetic form of a natriuretic peptide made in human kidneys, ularitide, “was associated with a seemingly greater hemodynamic effect than nesiritide [Natrecor], but this must be validated by a direct comparison,” commented Marco Metra, M.D., a professor of cardiology at the University of Brescia (Italy).

The study enrolled patients with symptomatic decompensated heart failure and a pulmonary capillary wedge pressure (PCWP) of at least 18 mm Hg. They were randomized to treatment with one of three dosages of ularitide or placebo. The drug dosages were 7.5, 15, or 30 ng/kg per minute. The study was done at 19 centers in Germany, Russia, and Serbia.

One primary end point was the change from baseline in PCWP after 6 hours of treatment. All three ularitide dosages resulted in significantly larger declines in PCWP, compared with patients treated with placebo. In the two groups that received the largest ularitide dosages, the average drop in PCWP was about 10 mm Hg, reported Dr. Mitrovic, medical director of the research unit at the Kerckhoff Clinic in Bad Nauheim, Germany.

The second primary end point was patients' self-assessed improvement in dyspnea after 6 hours of treatment. About 45% of the patients who received either of the two highest dosages reported a moderate or marked improvement in their dyspnea, compared with 38% who reported this degree of improvement on the lowest dosage, and 25% with this level of improvement in the placebo group.

Ularitide also produced a dose-related increase in cardiac index and a reduction in systemic vascular resistance.

The drug had no detectable impact on urine output, serum creatinine level, or creatinine clearance. The apparent absence of an effect on kidney function may mean that ularitide acts differently from nesiritide. Evidence from a metaanalysis published earlier this year indicated that a single dose of nesiritide worsens renal function in some patients with acute, decompensated heart failure (Circulation 2005;111:1487–91).

In the new study, treatment with ularitide was associated with fewer serious adverse events and fewer deaths, compared with the placebo group.

The short- and long-term effects of ularitide must be further examined in larger studies that allow assessment of morbidity and mortality events as the primary end points, Dr. Metra said.

The new results did not establish the optimal ularitide dosage, Dr. Mitrovic said. The 30 ng/kg per minute dosage may be best suited for patients with a relatively high systemic blood pressure at baseline, he said. A lower dosage, such as 15 ng/kg per minute, might work best for patients with a lower systemic blood pressure at the start of treatment.

The study was sponsored by Protein Design Labs, which holds worldwide development and marketing rights for ularitide.

STOCKHOLM — A natriuretic peptide was safe and effective for treating patients with acute, decompensated heart failure in a phase II study with a total of 221 patients.

Ularitide, given intravenously, reduced pulmonary capillary wedge pressure, improved dyspnea, and did not worsen renal function when given to patients for 24 hours of continuous infusion, Veselin Mitrovic, M.D., said at the annual congress of the European Society of Cardiology.

A synthetic form of a natriuretic peptide made in human kidneys, ularitide, “was associated with a seemingly greater hemodynamic effect than nesiritide [Natrecor], but this must be validated by a direct comparison,” commented Marco Metra, M.D., a professor of cardiology at the University of Brescia (Italy).

The study enrolled patients with symptomatic decompensated heart failure and a pulmonary capillary wedge pressure (PCWP) of at least 18 mm Hg. They were randomized to treatment with one of three dosages of ularitide or placebo. The drug dosages were 7.5, 15, or 30 ng/kg per minute. The study was done at 19 centers in Germany, Russia, and Serbia.

One primary end point was the change from baseline in PCWP after 6 hours of treatment. All three ularitide dosages resulted in significantly larger declines in PCWP, compared with patients treated with placebo. In the two groups that received the largest ularitide dosages, the average drop in PCWP was about 10 mm Hg, reported Dr. Mitrovic, medical director of the research unit at the Kerckhoff Clinic in Bad Nauheim, Germany.

The second primary end point was patients' self-assessed improvement in dyspnea after 6 hours of treatment. About 45% of the patients who received either of the two highest dosages reported a moderate or marked improvement in their dyspnea, compared with 38% who reported this degree of improvement on the lowest dosage, and 25% with this level of improvement in the placebo group.

Ularitide also produced a dose-related increase in cardiac index and a reduction in systemic vascular resistance.

The drug had no detectable impact on urine output, serum creatinine level, or creatinine clearance. The apparent absence of an effect on kidney function may mean that ularitide acts differently from nesiritide. Evidence from a metaanalysis published earlier this year indicated that a single dose of nesiritide worsens renal function in some patients with acute, decompensated heart failure (Circulation 2005;111:1487–91).

In the new study, treatment with ularitide was associated with fewer serious adverse events and fewer deaths, compared with the placebo group.

The short- and long-term effects of ularitide must be further examined in larger studies that allow assessment of morbidity and mortality events as the primary end points, Dr. Metra said.

The new results did not establish the optimal ularitide dosage, Dr. Mitrovic said. The 30 ng/kg per minute dosage may be best suited for patients with a relatively high systemic blood pressure at baseline, he said. A lower dosage, such as 15 ng/kg per minute, might work best for patients with a lower systemic blood pressure at the start of treatment.

The study was sponsored by Protein Design Labs, which holds worldwide development and marketing rights for ularitide.

STOCKHOLM — A natriuretic peptide was safe and effective for treating patients with acute, decompensated heart failure in a phase II study with a total of 221 patients.

Ularitide, given intravenously, reduced pulmonary capillary wedge pressure, improved dyspnea, and did not worsen renal function when given to patients for 24 hours of continuous infusion, Veselin Mitrovic, M.D., said at the annual congress of the European Society of Cardiology.

A synthetic form of a natriuretic peptide made in human kidneys, ularitide, “was associated with a seemingly greater hemodynamic effect than nesiritide [Natrecor], but this must be validated by a direct comparison,” commented Marco Metra, M.D., a professor of cardiology at the University of Brescia (Italy).

The study enrolled patients with symptomatic decompensated heart failure and a pulmonary capillary wedge pressure (PCWP) of at least 18 mm Hg. They were randomized to treatment with one of three dosages of ularitide or placebo. The drug dosages were 7.5, 15, or 30 ng/kg per minute. The study was done at 19 centers in Germany, Russia, and Serbia.

One primary end point was the change from baseline in PCWP after 6 hours of treatment. All three ularitide dosages resulted in significantly larger declines in PCWP, compared with patients treated with placebo. In the two groups that received the largest ularitide dosages, the average drop in PCWP was about 10 mm Hg, reported Dr. Mitrovic, medical director of the research unit at the Kerckhoff Clinic in Bad Nauheim, Germany.

The second primary end point was patients' self-assessed improvement in dyspnea after 6 hours of treatment. About 45% of the patients who received either of the two highest dosages reported a moderate or marked improvement in their dyspnea, compared with 38% who reported this degree of improvement on the lowest dosage, and 25% with this level of improvement in the placebo group.

Ularitide also produced a dose-related increase in cardiac index and a reduction in systemic vascular resistance.

The drug had no detectable impact on urine output, serum creatinine level, or creatinine clearance. The apparent absence of an effect on kidney function may mean that ularitide acts differently from nesiritide. Evidence from a metaanalysis published earlier this year indicated that a single dose of nesiritide worsens renal function in some patients with acute, decompensated heart failure (Circulation 2005;111:1487–91).

In the new study, treatment with ularitide was associated with fewer serious adverse events and fewer deaths, compared with the placebo group.

The short- and long-term effects of ularitide must be further examined in larger studies that allow assessment of morbidity and mortality events as the primary end points, Dr. Metra said.

The new results did not establish the optimal ularitide dosage, Dr. Mitrovic said. The 30 ng/kg per minute dosage may be best suited for patients with a relatively high systemic blood pressure at baseline, he said. A lower dosage, such as 15 ng/kg per minute, might work best for patients with a lower systemic blood pressure at the start of treatment.

The study was sponsored by Protein Design Labs, which holds worldwide development and marketing rights for ularitide.

BOCA RATON, FLA. — The brain natriuretic peptide, nesiritide, which is used to treat acute heart failure symptoms, did not facilitate diuresis or protect renal function in a small study of stable hospitalized patients.

Many clinicians believe nesiritide (Natrecor, Scios Inc.) facilitates furosemide diuresis and prevents renal dysfunction, Margaret M. Redfield, M.D., said in an interview. However, a recent metaanalysis indicated that the agent might actually increase the risk of renal dysfunction (Circulation 2005;111:1487–91).

To sort it out, Dr. Redfield and her associates studied 65 patients who were hospitalized for decompensated heart failure and who were treated with a standard dose of nesiritide for relief of their heart failure symptoms. They were randomized to nesiritide as a 2-mcg/kg bolus at admission and a 0.01-mcg/kg per minute infusion at 48 hours (34 patients) or to standard therapy (31 patients).

The participants also received 40-mg b.i.d. intravenous furosemide if they had mild renal dysfunction at baseline, defined as a creatinine clearance of 40–60 mL/min. They received 80-mg b.i.d. intravenous furosemide if they had moderate renal dysfunction, or a creatinine clearance of 20–39 mL/min.

“We looked at nesiritide in the broader heart failure population where you don't need an acute effect,” said Dr. Redfield, professor of medicine, Mayo Clinic College of Medicine, Rochester, Minn.

Approximately one-quarter of heart failure patients experience renal dysfunction during hospitalization, and the researchers sought to determine if nesiritide is protective, Dr. Redfield said during a poster session at the annual meeting of the Heart Failure Society of America.

A secondary objective was to determine if the agent could obviate the need for furosemide diuresis in some patients.

Mean baseline creatinine was 1.8 mg/dL in the nesiritide group and 1.7 mg/dL in the standard therapy group; by 48 hours, the mean changes were increases of 0.12 mg/dL and 0.07 mg/dL, respectively. Mean baseline brain natriuretic peptide level was 640 pg/mL for the nesiritide group and 538 pg/mL for the standard therapy group; by 48 hours, the mean changes were a 474 pg/mL increase in the nesiritide group and a 59 pg/mL decrease in the control group. Total furosemide use was 272 mg in the nesiritide group and 255 mg in the standard treatment group at 48 hours.

“Nesiritide causes no harm, but has no significant benefit,” Dr. Redfield said. “Nesiritide did not enhance the response to furosemide. We hypothesized that nesiritide should have a beneficial effect on renal function—we didn't see that either.”

Systolic blood pressure was lower in the nesiritide group at 24 hours, but not significantly different between groups by 48 hours.

“The standard dose was designed for hemodynamic effects,” Dr. Redfield commented. “The next step is to look at a lower dose, which might provide renal protection.”

BOCA RATON, FLA. — The brain natriuretic peptide, nesiritide, which is used to treat acute heart failure symptoms, did not facilitate diuresis or protect renal function in a small study of stable hospitalized patients.

Many clinicians believe nesiritide (Natrecor, Scios Inc.) facilitates furosemide diuresis and prevents renal dysfunction, Margaret M. Redfield, M.D., said in an interview. However, a recent metaanalysis indicated that the agent might actually increase the risk of renal dysfunction (Circulation 2005;111:1487–91).

To sort it out, Dr. Redfield and her associates studied 65 patients who were hospitalized for decompensated heart failure and who were treated with a standard dose of nesiritide for relief of their heart failure symptoms. They were randomized to nesiritide as a 2-mcg/kg bolus at admission and a 0.01-mcg/kg per minute infusion at 48 hours (34 patients) or to standard therapy (31 patients).

The participants also received 40-mg b.i.d. intravenous furosemide if they had mild renal dysfunction at baseline, defined as a creatinine clearance of 40–60 mL/min. They received 80-mg b.i.d. intravenous furosemide if they had moderate renal dysfunction, or a creatinine clearance of 20–39 mL/min.

“We looked at nesiritide in the broader heart failure population where you don't need an acute effect,” said Dr. Redfield, professor of medicine, Mayo Clinic College of Medicine, Rochester, Minn.

Approximately one-quarter of heart failure patients experience renal dysfunction during hospitalization, and the researchers sought to determine if nesiritide is protective, Dr. Redfield said during a poster session at the annual meeting of the Heart Failure Society of America.

A secondary objective was to determine if the agent could obviate the need for furosemide diuresis in some patients.

Mean baseline creatinine was 1.8 mg/dL in the nesiritide group and 1.7 mg/dL in the standard therapy group; by 48 hours, the mean changes were increases of 0.12 mg/dL and 0.07 mg/dL, respectively. Mean baseline brain natriuretic peptide level was 640 pg/mL for the nesiritide group and 538 pg/mL for the standard therapy group; by 48 hours, the mean changes were a 474 pg/mL increase in the nesiritide group and a 59 pg/mL decrease in the control group. Total furosemide use was 272 mg in the nesiritide group and 255 mg in the standard treatment group at 48 hours.

“Nesiritide causes no harm, but has no significant benefit,” Dr. Redfield said. “Nesiritide did not enhance the response to furosemide. We hypothesized that nesiritide should have a beneficial effect on renal function—we didn't see that either.”

Systolic blood pressure was lower in the nesiritide group at 24 hours, but not significantly different between groups by 48 hours.

“The standard dose was designed for hemodynamic effects,” Dr. Redfield commented. “The next step is to look at a lower dose, which might provide renal protection.”

BOCA RATON, FLA. — The brain natriuretic peptide, nesiritide, which is used to treat acute heart failure symptoms, did not facilitate diuresis or protect renal function in a small study of stable hospitalized patients.

Many clinicians believe nesiritide (Natrecor, Scios Inc.) facilitates furosemide diuresis and prevents renal dysfunction, Margaret M. Redfield, M.D., said in an interview. However, a recent metaanalysis indicated that the agent might actually increase the risk of renal dysfunction (Circulation 2005;111:1487–91).

To sort it out, Dr. Redfield and her associates studied 65 patients who were hospitalized for decompensated heart failure and who were treated with a standard dose of nesiritide for relief of their heart failure symptoms. They were randomized to nesiritide as a 2-mcg/kg bolus at admission and a 0.01-mcg/kg per minute infusion at 48 hours (34 patients) or to standard therapy (31 patients).

The participants also received 40-mg b.i.d. intravenous furosemide if they had mild renal dysfunction at baseline, defined as a creatinine clearance of 40–60 mL/min. They received 80-mg b.i.d. intravenous furosemide if they had moderate renal dysfunction, or a creatinine clearance of 20–39 mL/min.

“We looked at nesiritide in the broader heart failure population where you don't need an acute effect,” said Dr. Redfield, professor of medicine, Mayo Clinic College of Medicine, Rochester, Minn.

Approximately one-quarter of heart failure patients experience renal dysfunction during hospitalization, and the researchers sought to determine if nesiritide is protective, Dr. Redfield said during a poster session at the annual meeting of the Heart Failure Society of America.

A secondary objective was to determine if the agent could obviate the need for furosemide diuresis in some patients.

Mean baseline creatinine was 1.8 mg/dL in the nesiritide group and 1.7 mg/dL in the standard therapy group; by 48 hours, the mean changes were increases of 0.12 mg/dL and 0.07 mg/dL, respectively. Mean baseline brain natriuretic peptide level was 640 pg/mL for the nesiritide group and 538 pg/mL for the standard therapy group; by 48 hours, the mean changes were a 474 pg/mL increase in the nesiritide group and a 59 pg/mL decrease in the control group. Total furosemide use was 272 mg in the nesiritide group and 255 mg in the standard treatment group at 48 hours.

“Nesiritide causes no harm, but has no significant benefit,” Dr. Redfield said. “Nesiritide did not enhance the response to furosemide. We hypothesized that nesiritide should have a beneficial effect on renal function—we didn't see that either.”

Systolic blood pressure was lower in the nesiritide group at 24 hours, but not significantly different between groups by 48 hours.

“The standard dose was designed for hemodynamic effects,” Dr. Redfield commented. “The next step is to look at a lower dose, which might provide renal protection.”