Heart Failure

NEW ORLEANS — A new-generation heart pump was at least as effective as prior models and was also substantially safer, causing fewer deaths and complications in a study with 133 patients. The new unit is also one-seventh the size of the existing model, and is silent.

These results, in a study that assessed the HeartMate II assist device as a bridge to heart transplant, “give us an encouraging look to the future of the primary indication for this treatment,” as destination therapy for patients who are not eligible for a heart transplant, Dr. Leslie W. Miller said at the annual meeting of the American College of Cardiology. A study of the device as destination therapy that's designed to include 200 patients had enrolled 151 patients by late January 2007.

Despite the limitations of the current results based on the indication studied, “the data are a benchmark and branch point in the field of mechanical support. This represents an amazing accomplishment. It is a device for the future,” said Dr. Miller in a conference call following his report at the meeting. The new results “will significantly impact the use of this technology.”

With the new device, “there's a great future for our patients with severe heart failure,” said Dr. Christopher M. O'Connor, director of the heart failure and transplant program at Duke University, Durham, N.C., at the meeting.

The HeartMate II is made by Thoratec Corp., which markets the HeartMate XVE, the current, standard left ventricular assist device. Dr. Miller is a consultant to and has received honoraria and research support from Thoratec.

HeartMate II produces continuous blood flow, unlike the pulsatile pumps of prior-generation devices. In addition to being substantially smaller, the new pump is about 75% lighter than the XVE model, with a 40% smaller percutaneous lead and just one moving part, which is expected to result in much greater durability. The device should last 5–10 years in most patients, said Dr. Miller, chief of the integrated divisions of cardiology at Georgetown University, Washington.

The device was tested at 26 sites in the United States during March 2005-March 2006. The study was not randomized, and instead compared the new unit to an objective performance criterion based on the historic performance of three prior assist devices. The derived criterion stipulated that at least 75% of patients who received the new device had to survive either to heart transplant or for at least 180 days while remaining transplant eligible.

The enrolled patients were 18–69 years old, and were all listed as status 1A or 1B for a heart transplant. Their average left ventricular ejection fraction was 16%. Because of the device's smaller size, the entry criteria were expanded to include smaller patients; 21% of the patients were women, including seven women with a body surface area of less than 1.5 m2, a size that was previously unable to accommodate an implanted assist device.

During follow-up, 100 patients (75%) either went on to receive a heart transplant (68 patients), survived for more than 180 days while awaiting a transplant (29), or recovered substantially and had the device explanted (3), which meant that the results met the study's primary end point. The overall average duration of device support was 168 days. Among the 29 patients who went longer than 180 days without a transplant, the average time on the device was 360 days, with one patient maintained for 600 days. Among the remaining patients, 25 died within 180 days.

Actuarial 6-month survival for all 133 patients was 75%, and 68% survived for 1 year. Most of the deaths occurred prior to hospital discharge, with only three patients dying during the period 4.5–12 months after their devices were placed. The most common causes of death were sepsis, stroke, and multiorgan failure. The most common adverse events were bleeding (41 patients), infections (37), ventricular arrhythmias (32), and renal failure (18). Five patients had to have their devices replaced, with one death linked to explantation.

While on the device, patients showed dramatic improvements in their heart failure status, their 6-minute walk distance, and their quality of life.

“What's most impressive was the survival rate after 4.5 months,” when only three patients died, said Dr. Miller. In contrast, in the landmark, pivotal trial of the XVE model, the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial, 52% of patients survived for 1 year and 25% survived for 2 years. When deaths immediately after surgery in the new trial are discounted, survival with the HeartMate II model looks to be about 20% better, in absolute terms, compared with the XVE model.

“If we can provide a 20% absolute difference in mortality [with HeartMate II], that would outdistance any medical therapy we have and it would be a tremendous change,” Dr. Miller said during the conference call.

Another notable result was the units' reliability, with only five devices needing removal and only two developing thrombosis. “That's incredible performance,” Dr. Miller said.

The much smaller size of the new model is another important factor. “You need one-seventh of the surgical dissection to create the pocket where the pump goes. That probably accounts for the reduced bleeding, and it's technically easier. My surgeons are looking forward to this.

“I don't honestly see any downside to the data. We saw a safety and efficacy profile that beat anything that's been published. We met the end point with success across the board,” Dr. Miller said.

NEW ORLEANS — A new-generation heart pump was at least as effective as prior models and was also substantially safer, causing fewer deaths and complications in a study with 133 patients. The new unit is also one-seventh the size of the existing model, and is silent.

These results, in a study that assessed the HeartMate II assist device as a bridge to heart transplant, “give us an encouraging look to the future of the primary indication for this treatment,” as destination therapy for patients who are not eligible for a heart transplant, Dr. Leslie W. Miller said at the annual meeting of the American College of Cardiology. A study of the device as destination therapy that's designed to include 200 patients had enrolled 151 patients by late January 2007.

Despite the limitations of the current results based on the indication studied, “the data are a benchmark and branch point in the field of mechanical support. This represents an amazing accomplishment. It is a device for the future,” said Dr. Miller in a conference call following his report at the meeting. The new results “will significantly impact the use of this technology.”

With the new device, “there's a great future for our patients with severe heart failure,” said Dr. Christopher M. O'Connor, director of the heart failure and transplant program at Duke University, Durham, N.C., at the meeting.

The HeartMate II is made by Thoratec Corp., which markets the HeartMate XVE, the current, standard left ventricular assist device. Dr. Miller is a consultant to and has received honoraria and research support from Thoratec.

HeartMate II produces continuous blood flow, unlike the pulsatile pumps of prior-generation devices. In addition to being substantially smaller, the new pump is about 75% lighter than the XVE model, with a 40% smaller percutaneous lead and just one moving part, which is expected to result in much greater durability. The device should last 5–10 years in most patients, said Dr. Miller, chief of the integrated divisions of cardiology at Georgetown University, Washington.

The device was tested at 26 sites in the United States during March 2005-March 2006. The study was not randomized, and instead compared the new unit to an objective performance criterion based on the historic performance of three prior assist devices. The derived criterion stipulated that at least 75% of patients who received the new device had to survive either to heart transplant or for at least 180 days while remaining transplant eligible.

The enrolled patients were 18–69 years old, and were all listed as status 1A or 1B for a heart transplant. Their average left ventricular ejection fraction was 16%. Because of the device's smaller size, the entry criteria were expanded to include smaller patients; 21% of the patients were women, including seven women with a body surface area of less than 1.5 m2, a size that was previously unable to accommodate an implanted assist device.

During follow-up, 100 patients (75%) either went on to receive a heart transplant (68 patients), survived for more than 180 days while awaiting a transplant (29), or recovered substantially and had the device explanted (3), which meant that the results met the study's primary end point. The overall average duration of device support was 168 days. Among the 29 patients who went longer than 180 days without a transplant, the average time on the device was 360 days, with one patient maintained for 600 days. Among the remaining patients, 25 died within 180 days.

Actuarial 6-month survival for all 133 patients was 75%, and 68% survived for 1 year. Most of the deaths occurred prior to hospital discharge, with only three patients dying during the period 4.5–12 months after their devices were placed. The most common causes of death were sepsis, stroke, and multiorgan failure. The most common adverse events were bleeding (41 patients), infections (37), ventricular arrhythmias (32), and renal failure (18). Five patients had to have their devices replaced, with one death linked to explantation.

While on the device, patients showed dramatic improvements in their heart failure status, their 6-minute walk distance, and their quality of life.

“What's most impressive was the survival rate after 4.5 months,” when only three patients died, said Dr. Miller. In contrast, in the landmark, pivotal trial of the XVE model, the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial, 52% of patients survived for 1 year and 25% survived for 2 years. When deaths immediately after surgery in the new trial are discounted, survival with the HeartMate II model looks to be about 20% better, in absolute terms, compared with the XVE model.

“If we can provide a 20% absolute difference in mortality [with HeartMate II], that would outdistance any medical therapy we have and it would be a tremendous change,” Dr. Miller said during the conference call.

Another notable result was the units' reliability, with only five devices needing removal and only two developing thrombosis. “That's incredible performance,” Dr. Miller said.

The much smaller size of the new model is another important factor. “You need one-seventh of the surgical dissection to create the pocket where the pump goes. That probably accounts for the reduced bleeding, and it's technically easier. My surgeons are looking forward to this.

“I don't honestly see any downside to the data. We saw a safety and efficacy profile that beat anything that's been published. We met the end point with success across the board,” Dr. Miller said.

NEW ORLEANS — A new-generation heart pump was at least as effective as prior models and was also substantially safer, causing fewer deaths and complications in a study with 133 patients. The new unit is also one-seventh the size of the existing model, and is silent.

These results, in a study that assessed the HeartMate II assist device as a bridge to heart transplant, “give us an encouraging look to the future of the primary indication for this treatment,” as destination therapy for patients who are not eligible for a heart transplant, Dr. Leslie W. Miller said at the annual meeting of the American College of Cardiology. A study of the device as destination therapy that's designed to include 200 patients had enrolled 151 patients by late January 2007.

Despite the limitations of the current results based on the indication studied, “the data are a benchmark and branch point in the field of mechanical support. This represents an amazing accomplishment. It is a device for the future,” said Dr. Miller in a conference call following his report at the meeting. The new results “will significantly impact the use of this technology.”

With the new device, “there's a great future for our patients with severe heart failure,” said Dr. Christopher M. O'Connor, director of the heart failure and transplant program at Duke University, Durham, N.C., at the meeting.

The HeartMate II is made by Thoratec Corp., which markets the HeartMate XVE, the current, standard left ventricular assist device. Dr. Miller is a consultant to and has received honoraria and research support from Thoratec.

HeartMate II produces continuous blood flow, unlike the pulsatile pumps of prior-generation devices. In addition to being substantially smaller, the new pump is about 75% lighter than the XVE model, with a 40% smaller percutaneous lead and just one moving part, which is expected to result in much greater durability. The device should last 5–10 years in most patients, said Dr. Miller, chief of the integrated divisions of cardiology at Georgetown University, Washington.

The device was tested at 26 sites in the United States during March 2005-March 2006. The study was not randomized, and instead compared the new unit to an objective performance criterion based on the historic performance of three prior assist devices. The derived criterion stipulated that at least 75% of patients who received the new device had to survive either to heart transplant or for at least 180 days while remaining transplant eligible.

The enrolled patients were 18–69 years old, and were all listed as status 1A or 1B for a heart transplant. Their average left ventricular ejection fraction was 16%. Because of the device's smaller size, the entry criteria were expanded to include smaller patients; 21% of the patients were women, including seven women with a body surface area of less than 1.5 m2, a size that was previously unable to accommodate an implanted assist device.

During follow-up, 100 patients (75%) either went on to receive a heart transplant (68 patients), survived for more than 180 days while awaiting a transplant (29), or recovered substantially and had the device explanted (3), which meant that the results met the study's primary end point. The overall average duration of device support was 168 days. Among the 29 patients who went longer than 180 days without a transplant, the average time on the device was 360 days, with one patient maintained for 600 days. Among the remaining patients, 25 died within 180 days.

Actuarial 6-month survival for all 133 patients was 75%, and 68% survived for 1 year. Most of the deaths occurred prior to hospital discharge, with only three patients dying during the period 4.5–12 months after their devices were placed. The most common causes of death were sepsis, stroke, and multiorgan failure. The most common adverse events were bleeding (41 patients), infections (37), ventricular arrhythmias (32), and renal failure (18). Five patients had to have their devices replaced, with one death linked to explantation.

While on the device, patients showed dramatic improvements in their heart failure status, their 6-minute walk distance, and their quality of life.

“What's most impressive was the survival rate after 4.5 months,” when only three patients died, said Dr. Miller. In contrast, in the landmark, pivotal trial of the XVE model, the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial, 52% of patients survived for 1 year and 25% survived for 2 years. When deaths immediately after surgery in the new trial are discounted, survival with the HeartMate II model looks to be about 20% better, in absolute terms, compared with the XVE model.

“If we can provide a 20% absolute difference in mortality [with HeartMate II], that would outdistance any medical therapy we have and it would be a tremendous change,” Dr. Miller said during the conference call.

Another notable result was the units' reliability, with only five devices needing removal and only two developing thrombosis. “That's incredible performance,” Dr. Miller said.

The much smaller size of the new model is another important factor. “You need one-seventh of the surgical dissection to create the pocket where the pump goes. That probably accounts for the reduced bleeding, and it's technically easier. My surgeons are looking forward to this.

“I don't honestly see any downside to the data. We saw a safety and efficacy profile that beat anything that's been published. We met the end point with success across the board,” Dr. Miller said.

NEW ORLEANS — New results further supported T-wave alternans as a way to identify patients with nonischemic cardiomyopathy who do not need an implantable cardioverter defibrillator.

Findings from a study with 446 patients done in Italy showed that among patients with nonischemic cardiomyopathy and New York Heart Association class II or III heart failure, “patients with a normal TWA [T-wave alternans] test have a very good prognosis and are unlikely to benefit from ICD [implantable cardioverter defibrillator] therapy,” Dr. Gaetano M. De Ferrari said at the annual meeting of the American College of Cardiology.

In contrast, similar patients with an abnormal TWA result had a fourfold increased risk of cardiac death or a life-threatening ventricular arrhythmia during 18–24 months of follow-up, suggesting that these patients are good candidates for an ICD, said Dr. De Ferrari, chief of the cardiac ICU at Hospital San Matteo in Pavia, Italy.

The results from this “methodologically sound, prospective study confirm with high quality what [results from] other studies have shown,” that the predictive value of TWA in patients with nonischemic cardiomyopathy is similar to its predictive value in patients with ischemic cardiomyopathy, said Dr. Theodore Chow, director of electrophysiology research at the Ohio Heart and Vascular Center in Cincinnati. The new findings, in combination with prior results from other studies, “provide a rationale for a careful, prospective evaluation of whether ICD implants are useful in nonischemic patients with normal TWA.”

Until such a trial is done, “I think that most cardiologists will still generally favor placing ICDs based on data from” the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which showed that ICDs significantly cut mortality in all patients with a left ventricular ejection fraction of 35% or less, said Dr. Chow in an interview.

“We need strategies to sort out who gets an ICD. It's not clear why the use of ICDs is so low, but it's hard to picture that it will be solved by having TWA measurement in all patients,” commented Dr. Mariell L. Jessup, professor of medicine and medical director of heart failure and cardiac transplantation at the University of Pennsylvania, Philadelphia.

The T-Wave Alternans in Patients with Heart Failure (ALPHA) study was done at nine centers in Italy, and was funded in part by Boston Scientific, a company that markets an ICD but does not market equipment used for assessing TWA. The equipment used to measure TWA in the ALPHA study was made by Cambridge Heart.

Dr. De Ferrari and his associates screened more than 3,500 patients with heart failure to identify 446 with nonischemic, dilated cardiomyopathy, a left ventricular ejection fraction of 40% or less, New York Heart Association class II or III heart failure, and no other indication for receiving an ICD. TWA testing identified 154 patients with normal readings and 292 patients with an abnormal result.

During follow-up, the incidence of the study's primary end point—cardiac death or development of a life-threatening ventricular arrhythmia—was 10% in the patients with an abnormal TWA and 3% in those with a normal TWA, a statistically significant difference. When adjusted for baseline differences in age, gender, New York Heart Association class, and left ventricular ejection fraction, patients with an abnormal TWA reading at baseline were 3.2-fold more likely to develop the primary end point than were those with a normal TWA result.

“The most important finding” was the negative predictive value of a normal TWA result at baseline, said Dr. De Ferrari. During 18 months of follow-up, 97% of patients with a normal TWA result were free from the primary end point. “Patients with a normal TWA had a very good prognosis and were unlikely to benefit from an ICD,” he said.

Dr. De Ferrari agreed with the opinion voiced by Dr. Chow: The way to prove that TWA can identify patients who do not need an ICD is to randomize patients with a normal TWA result to either receive an ICD or not and then compare the outcomes of patients in these two groups.

'Patients with a normal TWA test have a very good prognosis and are unlikely to benefit from ICD therapy.' DR. DE FERRARI

NEW ORLEANS — New results further supported T-wave alternans as a way to identify patients with nonischemic cardiomyopathy who do not need an implantable cardioverter defibrillator.

Findings from a study with 446 patients done in Italy showed that among patients with nonischemic cardiomyopathy and New York Heart Association class II or III heart failure, “patients with a normal TWA [T-wave alternans] test have a very good prognosis and are unlikely to benefit from ICD [implantable cardioverter defibrillator] therapy,” Dr. Gaetano M. De Ferrari said at the annual meeting of the American College of Cardiology.

In contrast, similar patients with an abnormal TWA result had a fourfold increased risk of cardiac death or a life-threatening ventricular arrhythmia during 18–24 months of follow-up, suggesting that these patients are good candidates for an ICD, said Dr. De Ferrari, chief of the cardiac ICU at Hospital San Matteo in Pavia, Italy.

The results from this “methodologically sound, prospective study confirm with high quality what [results from] other studies have shown,” that the predictive value of TWA in patients with nonischemic cardiomyopathy is similar to its predictive value in patients with ischemic cardiomyopathy, said Dr. Theodore Chow, director of electrophysiology research at the Ohio Heart and Vascular Center in Cincinnati. The new findings, in combination with prior results from other studies, “provide a rationale for a careful, prospective evaluation of whether ICD implants are useful in nonischemic patients with normal TWA.”

Until such a trial is done, “I think that most cardiologists will still generally favor placing ICDs based on data from” the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which showed that ICDs significantly cut mortality in all patients with a left ventricular ejection fraction of 35% or less, said Dr. Chow in an interview.

“We need strategies to sort out who gets an ICD. It's not clear why the use of ICDs is so low, but it's hard to picture that it will be solved by having TWA measurement in all patients,” commented Dr. Mariell L. Jessup, professor of medicine and medical director of heart failure and cardiac transplantation at the University of Pennsylvania, Philadelphia.

The T-Wave Alternans in Patients with Heart Failure (ALPHA) study was done at nine centers in Italy, and was funded in part by Boston Scientific, a company that markets an ICD but does not market equipment used for assessing TWA. The equipment used to measure TWA in the ALPHA study was made by Cambridge Heart.

Dr. De Ferrari and his associates screened more than 3,500 patients with heart failure to identify 446 with nonischemic, dilated cardiomyopathy, a left ventricular ejection fraction of 40% or less, New York Heart Association class II or III heart failure, and no other indication for receiving an ICD. TWA testing identified 154 patients with normal readings and 292 patients with an abnormal result.

During follow-up, the incidence of the study's primary end point—cardiac death or development of a life-threatening ventricular arrhythmia—was 10% in the patients with an abnormal TWA and 3% in those with a normal TWA, a statistically significant difference. When adjusted for baseline differences in age, gender, New York Heart Association class, and left ventricular ejection fraction, patients with an abnormal TWA reading at baseline were 3.2-fold more likely to develop the primary end point than were those with a normal TWA result.

“The most important finding” was the negative predictive value of a normal TWA result at baseline, said Dr. De Ferrari. During 18 months of follow-up, 97% of patients with a normal TWA result were free from the primary end point. “Patients with a normal TWA had a very good prognosis and were unlikely to benefit from an ICD,” he said.

Dr. De Ferrari agreed with the opinion voiced by Dr. Chow: The way to prove that TWA can identify patients who do not need an ICD is to randomize patients with a normal TWA result to either receive an ICD or not and then compare the outcomes of patients in these two groups.

'Patients with a normal TWA test have a very good prognosis and are unlikely to benefit from ICD therapy.' DR. DE FERRARI

NEW ORLEANS — New results further supported T-wave alternans as a way to identify patients with nonischemic cardiomyopathy who do not need an implantable cardioverter defibrillator.

Findings from a study with 446 patients done in Italy showed that among patients with nonischemic cardiomyopathy and New York Heart Association class II or III heart failure, “patients with a normal TWA [T-wave alternans] test have a very good prognosis and are unlikely to benefit from ICD [implantable cardioverter defibrillator] therapy,” Dr. Gaetano M. De Ferrari said at the annual meeting of the American College of Cardiology.

In contrast, similar patients with an abnormal TWA result had a fourfold increased risk of cardiac death or a life-threatening ventricular arrhythmia during 18–24 months of follow-up, suggesting that these patients are good candidates for an ICD, said Dr. De Ferrari, chief of the cardiac ICU at Hospital San Matteo in Pavia, Italy.

The results from this “methodologically sound, prospective study confirm with high quality what [results from] other studies have shown,” that the predictive value of TWA in patients with nonischemic cardiomyopathy is similar to its predictive value in patients with ischemic cardiomyopathy, said Dr. Theodore Chow, director of electrophysiology research at the Ohio Heart and Vascular Center in Cincinnati. The new findings, in combination with prior results from other studies, “provide a rationale for a careful, prospective evaluation of whether ICD implants are useful in nonischemic patients with normal TWA.”

Until such a trial is done, “I think that most cardiologists will still generally favor placing ICDs based on data from” the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which showed that ICDs significantly cut mortality in all patients with a left ventricular ejection fraction of 35% or less, said Dr. Chow in an interview.

“We need strategies to sort out who gets an ICD. It's not clear why the use of ICDs is so low, but it's hard to picture that it will be solved by having TWA measurement in all patients,” commented Dr. Mariell L. Jessup, professor of medicine and medical director of heart failure and cardiac transplantation at the University of Pennsylvania, Philadelphia.

The T-Wave Alternans in Patients with Heart Failure (ALPHA) study was done at nine centers in Italy, and was funded in part by Boston Scientific, a company that markets an ICD but does not market equipment used for assessing TWA. The equipment used to measure TWA in the ALPHA study was made by Cambridge Heart.

Dr. De Ferrari and his associates screened more than 3,500 patients with heart failure to identify 446 with nonischemic, dilated cardiomyopathy, a left ventricular ejection fraction of 40% or less, New York Heart Association class II or III heart failure, and no other indication for receiving an ICD. TWA testing identified 154 patients with normal readings and 292 patients with an abnormal result.

During follow-up, the incidence of the study's primary end point—cardiac death or development of a life-threatening ventricular arrhythmia—was 10% in the patients with an abnormal TWA and 3% in those with a normal TWA, a statistically significant difference. When adjusted for baseline differences in age, gender, New York Heart Association class, and left ventricular ejection fraction, patients with an abnormal TWA reading at baseline were 3.2-fold more likely to develop the primary end point than were those with a normal TWA result.

“The most important finding” was the negative predictive value of a normal TWA result at baseline, said Dr. De Ferrari. During 18 months of follow-up, 97% of patients with a normal TWA result were free from the primary end point. “Patients with a normal TWA had a very good prognosis and were unlikely to benefit from an ICD,” he said.

Dr. De Ferrari agreed with the opinion voiced by Dr. Chow: The way to prove that TWA can identify patients who do not need an ICD is to randomize patients with a normal TWA result to either receive an ICD or not and then compare the outcomes of patients in these two groups.

'Patients with a normal TWA test have a very good prognosis and are unlikely to benefit from ICD therapy.' DR. DE FERRARI

SEATTLE — One-fourth of 182 women with peripartum cardiomyopathy developed major adverse events, half of which were death or heart transplantation, Dr. Sorel Goland reported in a poster presentation at the annual meeting of the Heart Failure Society of America.

Women with peripartum cardiomyopathy who had very low ejection fractions of 25% or who were not white were most likely to develop major adverse events, 50% of which occurred before the diagnosis of peripartum cardiomyopathy was made, said Dr. Goland of the department of cardiology at Cedars-Sinai Medical Center, Los Angeles, and associates. A diagnostic delay of a week or more raised the risk for death or heart transplant fivefold.

“Early diagnosis and aggressive therapy, including treatment of heart failure, anticoagulation, and sudden death prevention, should improve the outcome of patients,” the investigators stated.

The clinical profile of peripartum cardiomyopathy and risk factors for complications have not been well characterized due to its low incidence. Peripartum cardiomyopathy occurs during pregnancy or the postpartum period for unknown reasons and can cause severe complications.

The retrospective review of 182 patients found that 25% died, had a heart transplantation, developed cardiopulmonary arrest, required temporary circulatory support by an intra-aortic balloon pump or a left ventricular assist device, developed pulmonary edema or thromboembolic complications, or received a pacemaker or implantable cardioverter defibrillator. Of the 46 major adverse events, 36 (78%) occurred within 6 months of the diagnosis of peripartum cardiomyopathy.

Of the 182 patients, 24 (13%) died or underwent heart transplantation; 16 of the 24 deaths or transplants happened within 6 months of diagnosis.

Patients with ejection fractions of 25% or less had quadruple the risk for major adverse events in general and for death or heart transplant, compared with patients with higher ejection fractions. Nonwhites were three times as likely to develop major complications and four times likely to die or need a heart transplant, compared with whites.

ELSEVIER GLOBAL MEDICAL NEWS

SEATTLE — One-fourth of 182 women with peripartum cardiomyopathy developed major adverse events, half of which were death or heart transplantation, Dr. Sorel Goland reported in a poster presentation at the annual meeting of the Heart Failure Society of America.

Women with peripartum cardiomyopathy who had very low ejection fractions of 25% or who were not white were most likely to develop major adverse events, 50% of which occurred before the diagnosis of peripartum cardiomyopathy was made, said Dr. Goland of the department of cardiology at Cedars-Sinai Medical Center, Los Angeles, and associates. A diagnostic delay of a week or more raised the risk for death or heart transplant fivefold.

“Early diagnosis and aggressive therapy, including treatment of heart failure, anticoagulation, and sudden death prevention, should improve the outcome of patients,” the investigators stated.

The clinical profile of peripartum cardiomyopathy and risk factors for complications have not been well characterized due to its low incidence. Peripartum cardiomyopathy occurs during pregnancy or the postpartum period for unknown reasons and can cause severe complications.

The retrospective review of 182 patients found that 25% died, had a heart transplantation, developed cardiopulmonary arrest, required temporary circulatory support by an intra-aortic balloon pump or a left ventricular assist device, developed pulmonary edema or thromboembolic complications, or received a pacemaker or implantable cardioverter defibrillator. Of the 46 major adverse events, 36 (78%) occurred within 6 months of the diagnosis of peripartum cardiomyopathy.

Of the 182 patients, 24 (13%) died or underwent heart transplantation; 16 of the 24 deaths or transplants happened within 6 months of diagnosis.

Patients with ejection fractions of 25% or less had quadruple the risk for major adverse events in general and for death or heart transplant, compared with patients with higher ejection fractions. Nonwhites were three times as likely to develop major complications and four times likely to die or need a heart transplant, compared with whites.

ELSEVIER GLOBAL MEDICAL NEWS

SEATTLE — One-fourth of 182 women with peripartum cardiomyopathy developed major adverse events, half of which were death or heart transplantation, Dr. Sorel Goland reported in a poster presentation at the annual meeting of the Heart Failure Society of America.

Women with peripartum cardiomyopathy who had very low ejection fractions of 25% or who were not white were most likely to develop major adverse events, 50% of which occurred before the diagnosis of peripartum cardiomyopathy was made, said Dr. Goland of the department of cardiology at Cedars-Sinai Medical Center, Los Angeles, and associates. A diagnostic delay of a week or more raised the risk for death or heart transplant fivefold.

“Early diagnosis and aggressive therapy, including treatment of heart failure, anticoagulation, and sudden death prevention, should improve the outcome of patients,” the investigators stated.

The clinical profile of peripartum cardiomyopathy and risk factors for complications have not been well characterized due to its low incidence. Peripartum cardiomyopathy occurs during pregnancy or the postpartum period for unknown reasons and can cause severe complications.

The retrospective review of 182 patients found that 25% died, had a heart transplantation, developed cardiopulmonary arrest, required temporary circulatory support by an intra-aortic balloon pump or a left ventricular assist device, developed pulmonary edema or thromboembolic complications, or received a pacemaker or implantable cardioverter defibrillator. Of the 46 major adverse events, 36 (78%) occurred within 6 months of the diagnosis of peripartum cardiomyopathy.

Of the 182 patients, 24 (13%) died or underwent heart transplantation; 16 of the 24 deaths or transplants happened within 6 months of diagnosis.

Patients with ejection fractions of 25% or less had quadruple the risk for major adverse events in general and for death or heart transplant, compared with patients with higher ejection fractions. Nonwhites were three times as likely to develop major complications and four times likely to die or need a heart transplant, compared with whites.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Maternal peripartum cardiomyopathy, seen in 1 in 3,000 live births, generally carries a good prognosis, Dr. Michael Crawford said at a meeting sponsored by the California chapter of the American College of Cardiology.

Diagnosis of peripartum cardiomyopathy—or of other heart diseases during pregnancy—often is delayed because the symptoms of pregnancy are alike, said Dr. Crawford, professor of medicine at the University of California, San Francisco.

A majority of women with peripartum cardiomyopathy recover after delivery, but 10%–20% require heart transplantation and 1%–2% die, data suggest. The patient's ejection fraction 2 months after diagnosis appears to be the best prognostic factor, he said at the meeting, also sponsored by the university.

Treatment differs for pregnant women compared with nonpregnant patients because some drugs shouldn't be used until after delivery. ACE inhibitors and warfarin are teratogenic, and β-blockers can lead to fetal bradycardia. “You get by with diuretics, digoxin, and hydralazine during pregnancy,” Dr. Crawford said.

In a recent study at a large medical center, ejection fractions improved at least 15% in 62% of women with peripartum cardiomyopathy, remained unchanged in 25%, and declined in 13% (Am. Heart J. 2006;152:509–13).

Ejection fractions returned to normal in 45%. Ten percent of patients required transplantation. No patients died during an average 43-month follow-up. The initial echocardiogram, obtained between 1 month prepartum and 5 months post partum, did not predict which patients required transplantation, nor which had final ejection fractions below or above 50%. “Don't get discouraged with the first echo,” Dr. Crawford said. Echocardiograms 2 months later predicted outcomes in that study.

Patients with ejection fractions below 20% probably are headed for transplant. Those with ejection fractions between 20% and 50% should see some improvement but are unlikely to return to normal. If the 2-month ejection fraction is above 40%, the patient is likely to recover fully (defined as an ejection fraction greater than 50%), he said.

Shortness of breath and decreased exercise capacity—symptoms of cardiomyopathy—also are symptoms of a normal pregnancy. Fatigue, orthopnea, and dizziness or syncope, which might be symptoms of other heart disease, can also be caused by pregnancy.

Electrocardiograms in normal pregnancies often detect sinus tachycardia, and may show nonspecific ST-T changes. As the pregnancy advances, the heart's axis shifts more to the left. Physical findings in normal pregnancies may include jugular venous distention, an enlarged left ventricle apex, right ventricle heave, a palpable pulmonary artery pulse, third heart sounds, systolic ejection murmurs, venous hums, or a mammary souffle noise if you listen over the breast.

The most common peripartum cardiovascular problem is venous thromboembolism, which is the leading cause of death in pregnancy, he added. Consider prophylactic medication in women with risk factors.

Coronary artery disease during pregnancy is more common than one might think, perhaps because more women are having children later in life, he added. Maternal MI occurs in 6 out of 100,000 deliveries, three to four times more common than is expected in age-matched nonpregnant women.

Elevated troponin levels are abnormal in pregnancy, and are a red flag. Thrombolytics can be used without causing a lot of fetal complications. Around 5% of women with peripartum MI die.

SAN FRANCISCO — Maternal peripartum cardiomyopathy, seen in 1 in 3,000 live births, generally carries a good prognosis, Dr. Michael Crawford said at a meeting sponsored by the California chapter of the American College of Cardiology.

Diagnosis of peripartum cardiomyopathy—or of other heart diseases during pregnancy—often is delayed because the symptoms of pregnancy are alike, said Dr. Crawford, professor of medicine at the University of California, San Francisco.

A majority of women with peripartum cardiomyopathy recover after delivery, but 10%–20% require heart transplantation and 1%–2% die, data suggest. The patient's ejection fraction 2 months after diagnosis appears to be the best prognostic factor, he said at the meeting, also sponsored by the university.

Treatment differs for pregnant women compared with nonpregnant patients because some drugs shouldn't be used until after delivery. ACE inhibitors and warfarin are teratogenic, and β-blockers can lead to fetal bradycardia. “You get by with diuretics, digoxin, and hydralazine during pregnancy,” Dr. Crawford said.

In a recent study at a large medical center, ejection fractions improved at least 15% in 62% of women with peripartum cardiomyopathy, remained unchanged in 25%, and declined in 13% (Am. Heart J. 2006;152:509–13).

Ejection fractions returned to normal in 45%. Ten percent of patients required transplantation. No patients died during an average 43-month follow-up. The initial echocardiogram, obtained between 1 month prepartum and 5 months post partum, did not predict which patients required transplantation, nor which had final ejection fractions below or above 50%. “Don't get discouraged with the first echo,” Dr. Crawford said. Echocardiograms 2 months later predicted outcomes in that study.

Patients with ejection fractions below 20% probably are headed for transplant. Those with ejection fractions between 20% and 50% should see some improvement but are unlikely to return to normal. If the 2-month ejection fraction is above 40%, the patient is likely to recover fully (defined as an ejection fraction greater than 50%), he said.

Shortness of breath and decreased exercise capacity—symptoms of cardiomyopathy—also are symptoms of a normal pregnancy. Fatigue, orthopnea, and dizziness or syncope, which might be symptoms of other heart disease, can also be caused by pregnancy.

Electrocardiograms in normal pregnancies often detect sinus tachycardia, and may show nonspecific ST-T changes. As the pregnancy advances, the heart's axis shifts more to the left. Physical findings in normal pregnancies may include jugular venous distention, an enlarged left ventricle apex, right ventricle heave, a palpable pulmonary artery pulse, third heart sounds, systolic ejection murmurs, venous hums, or a mammary souffle noise if you listen over the breast.

The most common peripartum cardiovascular problem is venous thromboembolism, which is the leading cause of death in pregnancy, he added. Consider prophylactic medication in women with risk factors.

Coronary artery disease during pregnancy is more common than one might think, perhaps because more women are having children later in life, he added. Maternal MI occurs in 6 out of 100,000 deliveries, three to four times more common than is expected in age-matched nonpregnant women.

Elevated troponin levels are abnormal in pregnancy, and are a red flag. Thrombolytics can be used without causing a lot of fetal complications. Around 5% of women with peripartum MI die.

SAN FRANCISCO — Maternal peripartum cardiomyopathy, seen in 1 in 3,000 live births, generally carries a good prognosis, Dr. Michael Crawford said at a meeting sponsored by the California chapter of the American College of Cardiology.

Diagnosis of peripartum cardiomyopathy—or of other heart diseases during pregnancy—often is delayed because the symptoms of pregnancy are alike, said Dr. Crawford, professor of medicine at the University of California, San Francisco.

A majority of women with peripartum cardiomyopathy recover after delivery, but 10%–20% require heart transplantation and 1%–2% die, data suggest. The patient's ejection fraction 2 months after diagnosis appears to be the best prognostic factor, he said at the meeting, also sponsored by the university.

Treatment differs for pregnant women compared with nonpregnant patients because some drugs shouldn't be used until after delivery. ACE inhibitors and warfarin are teratogenic, and β-blockers can lead to fetal bradycardia. “You get by with diuretics, digoxin, and hydralazine during pregnancy,” Dr. Crawford said.

In a recent study at a large medical center, ejection fractions improved at least 15% in 62% of women with peripartum cardiomyopathy, remained unchanged in 25%, and declined in 13% (Am. Heart J. 2006;152:509–13).

Ejection fractions returned to normal in 45%. Ten percent of patients required transplantation. No patients died during an average 43-month follow-up. The initial echocardiogram, obtained between 1 month prepartum and 5 months post partum, did not predict which patients required transplantation, nor which had final ejection fractions below or above 50%. “Don't get discouraged with the first echo,” Dr. Crawford said. Echocardiograms 2 months later predicted outcomes in that study.

Patients with ejection fractions below 20% probably are headed for transplant. Those with ejection fractions between 20% and 50% should see some improvement but are unlikely to return to normal. If the 2-month ejection fraction is above 40%, the patient is likely to recover fully (defined as an ejection fraction greater than 50%), he said.

Shortness of breath and decreased exercise capacity—symptoms of cardiomyopathy—also are symptoms of a normal pregnancy. Fatigue, orthopnea, and dizziness or syncope, which might be symptoms of other heart disease, can also be caused by pregnancy.

Electrocardiograms in normal pregnancies often detect sinus tachycardia, and may show nonspecific ST-T changes. As the pregnancy advances, the heart's axis shifts more to the left. Physical findings in normal pregnancies may include jugular venous distention, an enlarged left ventricle apex, right ventricle heave, a palpable pulmonary artery pulse, third heart sounds, systolic ejection murmurs, venous hums, or a mammary souffle noise if you listen over the breast.

The most common peripartum cardiovascular problem is venous thromboembolism, which is the leading cause of death in pregnancy, he added. Consider prophylactic medication in women with risk factors.

Coronary artery disease during pregnancy is more common than one might think, perhaps because more women are having children later in life, he added. Maternal MI occurs in 6 out of 100,000 deliveries, three to four times more common than is expected in age-matched nonpregnant women.

Elevated troponin levels are abnormal in pregnancy, and are a red flag. Thrombolytics can be used without causing a lot of fetal complications. Around 5% of women with peripartum MI die.

ORLANDO — Regularly eating a bowl of whole-grain cereal was linked to a significant drop in the risk for heart failure in a study with more than 20,000 men.

“It's not just breakfast cereal, but the whole-grain concept, including whole-grain bread, pasta, and rice,” Dr. Luc Djoussé said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

Regular consumption of whole-grain cereal probably cuts the risk for heart failure by supplying fiber, nutrients, and phytoestrogens, added Dr. Djoussé, who is a physician and epidemiologist at Harvard University and Brigham and Women's Hospital in Boston. He added that he believes the study to be the first of its kind.

The study used data collected prospectively from 21,410 men who participated in the Physicians' Health Study. Their average age at entry was 54 years (range, 40–86 years). The analysis excluded men with heart failure at the study's start, and those who failed to provide data on their consumption of breakfast cereal. Diet data were collected regularly during up to 24 years of follow-up. Whole-grain breakfast cereal was defined as a formulation that contained at least 25% oats or bran.

Over an average follow-up of 19.6 years, 1,018 men developed heart failure. The risk of heart failure was correlated with the frequency of eating whole-grain breakfast cereal. The men were divided into four categories of consumption: none (33%); one or fewer servings per week but more than none (23%); two to six servings per week (24%); and seven or more servings per week (19%). (The total is less than 100% because of rounding.)

In an analysis that controlled for baseline levels of potential confounders—including age, body mass index, smoking history, alcohol use, multivitamin use, diabetes, hypertension, and valvular heart disease—men who ate seven or more servings of whole-grain cereal a week had about a 30% reduced risk of developing heart failure, compared with men who did not eat whole-grain cereal. Men who ate two to six servings a week had about a 20% reduced risk. Both of these differences were statistically significant. No significant change was seen in men who ate one serving a week or less, and no link was seen between the consumption of refined breakfast cereals and heart failure risk.

The study did not receive any commercial funding.

ORLANDO — Regularly eating a bowl of whole-grain cereal was linked to a significant drop in the risk for heart failure in a study with more than 20,000 men.

“It's not just breakfast cereal, but the whole-grain concept, including whole-grain bread, pasta, and rice,” Dr. Luc Djoussé said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

Regular consumption of whole-grain cereal probably cuts the risk for heart failure by supplying fiber, nutrients, and phytoestrogens, added Dr. Djoussé, who is a physician and epidemiologist at Harvard University and Brigham and Women's Hospital in Boston. He added that he believes the study to be the first of its kind.

The study used data collected prospectively from 21,410 men who participated in the Physicians' Health Study. Their average age at entry was 54 years (range, 40–86 years). The analysis excluded men with heart failure at the study's start, and those who failed to provide data on their consumption of breakfast cereal. Diet data were collected regularly during up to 24 years of follow-up. Whole-grain breakfast cereal was defined as a formulation that contained at least 25% oats or bran.

Over an average follow-up of 19.6 years, 1,018 men developed heart failure. The risk of heart failure was correlated with the frequency of eating whole-grain breakfast cereal. The men were divided into four categories of consumption: none (33%); one or fewer servings per week but more than none (23%); two to six servings per week (24%); and seven or more servings per week (19%). (The total is less than 100% because of rounding.)

In an analysis that controlled for baseline levels of potential confounders—including age, body mass index, smoking history, alcohol use, multivitamin use, diabetes, hypertension, and valvular heart disease—men who ate seven or more servings of whole-grain cereal a week had about a 30% reduced risk of developing heart failure, compared with men who did not eat whole-grain cereal. Men who ate two to six servings a week had about a 20% reduced risk. Both of these differences were statistically significant. No significant change was seen in men who ate one serving a week or less, and no link was seen between the consumption of refined breakfast cereals and heart failure risk.

The study did not receive any commercial funding.

ORLANDO — Regularly eating a bowl of whole-grain cereal was linked to a significant drop in the risk for heart failure in a study with more than 20,000 men.

“It's not just breakfast cereal, but the whole-grain concept, including whole-grain bread, pasta, and rice,” Dr. Luc Djoussé said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

Regular consumption of whole-grain cereal probably cuts the risk for heart failure by supplying fiber, nutrients, and phytoestrogens, added Dr. Djoussé, who is a physician and epidemiologist at Harvard University and Brigham and Women's Hospital in Boston. He added that he believes the study to be the first of its kind.

The study used data collected prospectively from 21,410 men who participated in the Physicians' Health Study. Their average age at entry was 54 years (range, 40–86 years). The analysis excluded men with heart failure at the study's start, and those who failed to provide data on their consumption of breakfast cereal. Diet data were collected regularly during up to 24 years of follow-up. Whole-grain breakfast cereal was defined as a formulation that contained at least 25% oats or bran.

Over an average follow-up of 19.6 years, 1,018 men developed heart failure. The risk of heart failure was correlated with the frequency of eating whole-grain breakfast cereal. The men were divided into four categories of consumption: none (33%); one or fewer servings per week but more than none (23%); two to six servings per week (24%); and seven or more servings per week (19%). (The total is less than 100% because of rounding.)

In an analysis that controlled for baseline levels of potential confounders—including age, body mass index, smoking history, alcohol use, multivitamin use, diabetes, hypertension, and valvular heart disease—men who ate seven or more servings of whole-grain cereal a week had about a 30% reduced risk of developing heart failure, compared with men who did not eat whole-grain cereal. Men who ate two to six servings a week had about a 20% reduced risk. Both of these differences were statistically significant. No significant change was seen in men who ate one serving a week or less, and no link was seen between the consumption of refined breakfast cereals and heart failure risk.

The study did not receive any commercial funding.

CARMEL, CALIF. — B-type natriuretic peptide levels are not effective in detecting clinically relevant heart failure following heart transplantation, results from a study of 130 patients showed.

The finding is important because while the role of B-type natriuretic peptide (BNP) levels in detecting symptomatic heart failure in nontransplanted patients has been well established, its role in patients who have undergone heart transplantation is unclear.

“What we do know is that BNP is elevated right after [heart] transplant,” Meghana Yajnik said during a poster presentation at the Western regional meeting of the American Federation for Medical Research.

“However, several recent studies have said that BNP may have potential as a prognostic marker, in which high levels of BNP for prolonged periods after transplant may portend poorer outcome,” she noted

Ms. Yajnik, who is a second-year undergraduate student at University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 130 consecutive patients who received heart transplants at the university between July 2001 and November 2003. All of the patients had BNP levels assessed at the time of their right heart catheterization and their clinical exams.

The researchers defined heart failure as both the presence of symptoms (including dyspnea, edema, or a documented increase in diuretic dose), and a pulmonary capillary wedge pressure of 15 mm Hg or greater. BNP samples taken during the first 3 months post transplant and those taken in patients with renal insufficiency (defined as a creatinine level of greater than 1.9 mg/dL) were excluded from the analysis. The mean follow-up time was 28 months.

Of the 130 patients, 67 had 124 BNP measurements with a pulmonary capillary wedge pressure of at least 15 mm Hg. Ms. Yajnik reported that the BNP level was at least 150 pg/mL in 42 of the 124 measurements (39%). In 29 patients who had symptomatic heart failure and a pulmonary capillary wedge pressure of at least 15 mm Hg, the BNP level was at least 150 pg/mL in only 19 of the 42 measurements (45%).

“Therefore,” the researchers wrote in their abstract, “a BNP level of 150 pg/mL or greater was found to have a sensitivity of only 45.2%, a specificity of 64.9%, a positive predictive value of 3.7%, and a negative predictive value of 2.4% for the detection of heart failure in heart transplant recipients. In addition, a BNP value of 150 pg/mL or greater within 8 weeks of a clinically significant episode of rejection was noted in only 5 of 10 cases.”

Ms. Yajnik noted that the discrepancy between the use of B-type natriuretic peptide levels for detecting heart failure in the nontransplant and transplant populations requires further study. “Differences in the physiology between nontransplant patients and transplant patients may account for these disparate BNP levels,” she said.

CARMEL, CALIF. — B-type natriuretic peptide levels are not effective in detecting clinically relevant heart failure following heart transplantation, results from a study of 130 patients showed.

The finding is important because while the role of B-type natriuretic peptide (BNP) levels in detecting symptomatic heart failure in nontransplanted patients has been well established, its role in patients who have undergone heart transplantation is unclear.

“What we do know is that BNP is elevated right after [heart] transplant,” Meghana Yajnik said during a poster presentation at the Western regional meeting of the American Federation for Medical Research.

“However, several recent studies have said that BNP may have potential as a prognostic marker, in which high levels of BNP for prolonged periods after transplant may portend poorer outcome,” she noted

Ms. Yajnik, who is a second-year undergraduate student at University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 130 consecutive patients who received heart transplants at the university between July 2001 and November 2003. All of the patients had BNP levels assessed at the time of their right heart catheterization and their clinical exams.

The researchers defined heart failure as both the presence of symptoms (including dyspnea, edema, or a documented increase in diuretic dose), and a pulmonary capillary wedge pressure of 15 mm Hg or greater. BNP samples taken during the first 3 months post transplant and those taken in patients with renal insufficiency (defined as a creatinine level of greater than 1.9 mg/dL) were excluded from the analysis. The mean follow-up time was 28 months.

Of the 130 patients, 67 had 124 BNP measurements with a pulmonary capillary wedge pressure of at least 15 mm Hg. Ms. Yajnik reported that the BNP level was at least 150 pg/mL in 42 of the 124 measurements (39%). In 29 patients who had symptomatic heart failure and a pulmonary capillary wedge pressure of at least 15 mm Hg, the BNP level was at least 150 pg/mL in only 19 of the 42 measurements (45%).

“Therefore,” the researchers wrote in their abstract, “a BNP level of 150 pg/mL or greater was found to have a sensitivity of only 45.2%, a specificity of 64.9%, a positive predictive value of 3.7%, and a negative predictive value of 2.4% for the detection of heart failure in heart transplant recipients. In addition, a BNP value of 150 pg/mL or greater within 8 weeks of a clinically significant episode of rejection was noted in only 5 of 10 cases.”

Ms. Yajnik noted that the discrepancy between the use of B-type natriuretic peptide levels for detecting heart failure in the nontransplant and transplant populations requires further study. “Differences in the physiology between nontransplant patients and transplant patients may account for these disparate BNP levels,” she said.

CARMEL, CALIF. — B-type natriuretic peptide levels are not effective in detecting clinically relevant heart failure following heart transplantation, results from a study of 130 patients showed.

The finding is important because while the role of B-type natriuretic peptide (BNP) levels in detecting symptomatic heart failure in nontransplanted patients has been well established, its role in patients who have undergone heart transplantation is unclear.

“What we do know is that BNP is elevated right after [heart] transplant,” Meghana Yajnik said during a poster presentation at the Western regional meeting of the American Federation for Medical Research.

“However, several recent studies have said that BNP may have potential as a prognostic marker, in which high levels of BNP for prolonged periods after transplant may portend poorer outcome,” she noted

Ms. Yajnik, who is a second-year undergraduate student at University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 130 consecutive patients who received heart transplants at the university between July 2001 and November 2003. All of the patients had BNP levels assessed at the time of their right heart catheterization and their clinical exams.

The researchers defined heart failure as both the presence of symptoms (including dyspnea, edema, or a documented increase in diuretic dose), and a pulmonary capillary wedge pressure of 15 mm Hg or greater. BNP samples taken during the first 3 months post transplant and those taken in patients with renal insufficiency (defined as a creatinine level of greater than 1.9 mg/dL) were excluded from the analysis. The mean follow-up time was 28 months.

Of the 130 patients, 67 had 124 BNP measurements with a pulmonary capillary wedge pressure of at least 15 mm Hg. Ms. Yajnik reported that the BNP level was at least 150 pg/mL in 42 of the 124 measurements (39%). In 29 patients who had symptomatic heart failure and a pulmonary capillary wedge pressure of at least 15 mm Hg, the BNP level was at least 150 pg/mL in only 19 of the 42 measurements (45%).

“Therefore,” the researchers wrote in their abstract, “a BNP level of 150 pg/mL or greater was found to have a sensitivity of only 45.2%, a specificity of 64.9%, a positive predictive value of 3.7%, and a negative predictive value of 2.4% for the detection of heart failure in heart transplant recipients. In addition, a BNP value of 150 pg/mL or greater within 8 weeks of a clinically significant episode of rejection was noted in only 5 of 10 cases.”

Ms. Yajnik noted that the discrepancy between the use of B-type natriuretic peptide levels for detecting heart failure in the nontransplant and transplant populations requires further study. “Differences in the physiology between nontransplant patients and transplant patients may account for these disparate BNP levels,” she said.

CARMEL, CALIF. — The 5-year survival rate for heart retransplant patients who have severe heart failure symptoms with preserved systolic function is about 67%, results from a single-center study showed.

“These patients have comparable survival to patients retransplanted due to systolic dysfunction and therefore should be considered candidates for retransplantation,” Lakshmi Gokanapudy said at the Western regional meeting of the American Federation for Medical Research.

Ms. Gokanapudy, an undergraduate student at the University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 31 heart transplant patients who underwent retransplantation at the university during 1994–2004. The patients mean age at time of retransplantation was 51 years, and most (75%) were male.

Of the 31 patients, 24 (77%) had severe heart failure symptoms with preserved systolic function, which was defined as having a left ventricular ejection fraction of at least 40%.

Ms. Gokanapudy reported that each of the 24 patients with preserved systolic function had shortness of breath, fatigue, and decreased exercise tolerance. Echocardiography revealed that eight (33%) had left ventricular hypertrophy.

Five of the patients (21%) had no rejection episodes, 19 (79%) had an average of 1.4 rejection episodes, and 20 (83%) developed epicardial cardiac allograft vasculopathy.

The 5-year survival rate among the 24 patients with preserved systolic function was 67%, which was similar to the 5-year survival rate among the 7 retransplanted patients in the study who had severe systolic dysfunction (57%).

CARMEL, CALIF. — The 5-year survival rate for heart retransplant patients who have severe heart failure symptoms with preserved systolic function is about 67%, results from a single-center study showed.

“These patients have comparable survival to patients retransplanted due to systolic dysfunction and therefore should be considered candidates for retransplantation,” Lakshmi Gokanapudy said at the Western regional meeting of the American Federation for Medical Research.

Ms. Gokanapudy, an undergraduate student at the University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 31 heart transplant patients who underwent retransplantation at the university during 1994–2004. The patients mean age at time of retransplantation was 51 years, and most (75%) were male.

Of the 31 patients, 24 (77%) had severe heart failure symptoms with preserved systolic function, which was defined as having a left ventricular ejection fraction of at least 40%.

Ms. Gokanapudy reported that each of the 24 patients with preserved systolic function had shortness of breath, fatigue, and decreased exercise tolerance. Echocardiography revealed that eight (33%) had left ventricular hypertrophy.

Five of the patients (21%) had no rejection episodes, 19 (79%) had an average of 1.4 rejection episodes, and 20 (83%) developed epicardial cardiac allograft vasculopathy.

The 5-year survival rate among the 24 patients with preserved systolic function was 67%, which was similar to the 5-year survival rate among the 7 retransplanted patients in the study who had severe systolic dysfunction (57%).

CARMEL, CALIF. — The 5-year survival rate for heart retransplant patients who have severe heart failure symptoms with preserved systolic function is about 67%, results from a single-center study showed.

“These patients have comparable survival to patients retransplanted due to systolic dysfunction and therefore should be considered candidates for retransplantation,” Lakshmi Gokanapudy said at the Western regional meeting of the American Federation for Medical Research.

Ms. Gokanapudy, an undergraduate student at the University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 31 heart transplant patients who underwent retransplantation at the university during 1994–2004. The patients mean age at time of retransplantation was 51 years, and most (75%) were male.

Of the 31 patients, 24 (77%) had severe heart failure symptoms with preserved systolic function, which was defined as having a left ventricular ejection fraction of at least 40%.

Ms. Gokanapudy reported that each of the 24 patients with preserved systolic function had shortness of breath, fatigue, and decreased exercise tolerance. Echocardiography revealed that eight (33%) had left ventricular hypertrophy.

Five of the patients (21%) had no rejection episodes, 19 (79%) had an average of 1.4 rejection episodes, and 20 (83%) developed epicardial cardiac allograft vasculopathy.

The 5-year survival rate among the 24 patients with preserved systolic function was 67%, which was similar to the 5-year survival rate among the 7 retransplanted patients in the study who had severe systolic dysfunction (57%).

BETHESDA, MD. — More than half of patients in the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) are on two or more medications to treat their disease, said Dr. Michael McGoon, who is chairman of the registry's steering committee.

“One of the revealing outcomes early on … is that already 54% of the 460 patients on any pulmonary arterial hypertension medication are on two or more medications,” said Dr. McGoon, at a meeting on pulmonary hypertension sponsored by the National Institutes of Health.

The REVEAL registry is designed to look at the clinical course and medical management of pulmonary arterial hypertension. Researchers hope to enroll 3,000 patients with PAH, who will be followed for at least 5 years, regardless of their therapy. The registry is intended to capture demographic data and clinical treatment patterns and factors associated with improved clinical outcomes.

As of October 2006, 545 patients had been enrolled. Of these, slightly less than half (46%) had idiopathic PAH. Roughly half (51%) had PAH associated with other diseases. Of those enrolled, 71% also had cardiovascular disease, said Dr. McGoon, who is also director of the pulmonary hypertension clinic at the Mayo Medical School, Rochester, Minn.

The registry is sponsored by CoTherix Inc., which makes Ventavis (iloprost) for the treatment of pulmonary arterial hypertension. Dr. McGoon disclosed that he has financial ties to several pharmaceutical companies, including CoTherix.

BETHESDA, MD. — More than half of patients in the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) are on two or more medications to treat their disease, said Dr. Michael McGoon, who is chairman of the registry's steering committee.

“One of the revealing outcomes early on … is that already 54% of the 460 patients on any pulmonary arterial hypertension medication are on two or more medications,” said Dr. McGoon, at a meeting on pulmonary hypertension sponsored by the National Institutes of Health.

The REVEAL registry is designed to look at the clinical course and medical management of pulmonary arterial hypertension. Researchers hope to enroll 3,000 patients with PAH, who will be followed for at least 5 years, regardless of their therapy. The registry is intended to capture demographic data and clinical treatment patterns and factors associated with improved clinical outcomes.

As of October 2006, 545 patients had been enrolled. Of these, slightly less than half (46%) had idiopathic PAH. Roughly half (51%) had PAH associated with other diseases. Of those enrolled, 71% also had cardiovascular disease, said Dr. McGoon, who is also director of the pulmonary hypertension clinic at the Mayo Medical School, Rochester, Minn.

The registry is sponsored by CoTherix Inc., which makes Ventavis (iloprost) for the treatment of pulmonary arterial hypertension. Dr. McGoon disclosed that he has financial ties to several pharmaceutical companies, including CoTherix.

BETHESDA, MD. — More than half of patients in the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) are on two or more medications to treat their disease, said Dr. Michael McGoon, who is chairman of the registry's steering committee.

“One of the revealing outcomes early on … is that already 54% of the 460 patients on any pulmonary arterial hypertension medication are on two or more medications,” said Dr. McGoon, at a meeting on pulmonary hypertension sponsored by the National Institutes of Health.

The REVEAL registry is designed to look at the clinical course and medical management of pulmonary arterial hypertension. Researchers hope to enroll 3,000 patients with PAH, who will be followed for at least 5 years, regardless of their therapy. The registry is intended to capture demographic data and clinical treatment patterns and factors associated with improved clinical outcomes.

As of October 2006, 545 patients had been enrolled. Of these, slightly less than half (46%) had idiopathic PAH. Roughly half (51%) had PAH associated with other diseases. Of those enrolled, 71% also had cardiovascular disease, said Dr. McGoon, who is also director of the pulmonary hypertension clinic at the Mayo Medical School, Rochester, Minn.

The registry is sponsored by CoTherix Inc., which makes Ventavis (iloprost) for the treatment of pulmonary arterial hypertension. Dr. McGoon disclosed that he has financial ties to several pharmaceutical companies, including CoTherix.

SAN FRANCISCO — A majority of patients presenting to emergency departments with pulmonary edema have diastolic heart failure, also known as heart failure with preserved ejection fraction, Dr. William Grossman said.

A recent analysis of data from more than 100,000 hospitalizations in the Acute Decompensated Heart Failure Registry (ADHERE) showed that 51% of patients with heart failure had preserved ejection fractions, and 49% had depressed ejection fractions, also called systolic heart failure (J. Am. Coll. Cardiol. 2006;47:76–84). In-hospital mortality rates were 3% with diastolic heart failure and 4% with systolic heart failure, he said at a meeting sponsored by the California chapter of the American College of Cardiology.

That finding may surprise many people who attribute death from heart failure mainly to systolic dysfunction, said Dr. Grossman, chief of cardiology at the University of California, San Francisco. Many patients have both types of heart failure.

Compared with the systolic heart failure group, patients who had diastolic heart failure were more likely to be women and less likely to have a prior MI or to be taking ACE inhibitors or angiotensin receptor blockers (ARBs).

In a separate recent study, investigators from the Mayo Clinic, Rochester, Minn., followed 556 patients with heart failure in the community for 6 months. The mortality rate was 16% both in the 55% of patients with diastolic heart failure and in the rest of the cohort, who had systolic heart failure, Dr. Grossman noted.

“The prognosis is really not much better than for classic systolic heart failure,” he said at the meeting, also sponsored by the university.

In the Mayo Clinic study, diastolic dysfunction and the patient's ejection fraction independently predicted elevation of brain natriuretic peptide (BNP).

“When patients come to the emergency ward with acute shortness of breath, many of us look to the BNP to tell us, is this pneumonia? Is this asthma? Is this hypertension? BNP is elevated in heart failure whether it's systolic or diastolic,” an important fact to recognize, he said.

If diastolic heart failure is so widespread, what's causing it? It's not all caused by amyloidosis, and is unlikely to be due to untreated hypertension in so many cases, Dr. Grossman believes.

German investigators performed cardiac biopsies and other tests on 70 patients hospitalized with diastolic heart failure and found that 84% were infected with parvovirus B19. Presence of the virus was strongly associated with coronary endothelial dysfunction (Circulation 2005;111:879–86).

“I'm not saying this is what's going on in our emergency wards, but it's certainly something that I would never have thought to look for. We should pay attention. There may be increased information about this in the future,” Dr. Grossman commented.

There are few data from randomized trials to guide treatment of diastolic heart failure. Dr. Grossman approaches management much as he would for patients with systolic heart failure.

SAN FRANCISCO — A majority of patients presenting to emergency departments with pulmonary edema have diastolic heart failure, also known as heart failure with preserved ejection fraction, Dr. William Grossman said.

A recent analysis of data from more than 100,000 hospitalizations in the Acute Decompensated Heart Failure Registry (ADHERE) showed that 51% of patients with heart failure had preserved ejection fractions, and 49% had depressed ejection fractions, also called systolic heart failure (J. Am. Coll. Cardiol. 2006;47:76–84). In-hospital mortality rates were 3% with diastolic heart failure and 4% with systolic heart failure, he said at a meeting sponsored by the California chapter of the American College of Cardiology.

That finding may surprise many people who attribute death from heart failure mainly to systolic dysfunction, said Dr. Grossman, chief of cardiology at the University of California, San Francisco. Many patients have both types of heart failure.

Compared with the systolic heart failure group, patients who had diastolic heart failure were more likely to be women and less likely to have a prior MI or to be taking ACE inhibitors or angiotensin receptor blockers (ARBs).

In a separate recent study, investigators from the Mayo Clinic, Rochester, Minn., followed 556 patients with heart failure in the community for 6 months. The mortality rate was 16% both in the 55% of patients with diastolic heart failure and in the rest of the cohort, who had systolic heart failure, Dr. Grossman noted.

“The prognosis is really not much better than for classic systolic heart failure,” he said at the meeting, also sponsored by the university.

In the Mayo Clinic study, diastolic dysfunction and the patient's ejection fraction independently predicted elevation of brain natriuretic peptide (BNP).

“When patients come to the emergency ward with acute shortness of breath, many of us look to the BNP to tell us, is this pneumonia? Is this asthma? Is this hypertension? BNP is elevated in heart failure whether it's systolic or diastolic,” an important fact to recognize, he said.

If diastolic heart failure is so widespread, what's causing it? It's not all caused by amyloidosis, and is unlikely to be due to untreated hypertension in so many cases, Dr. Grossman believes.

German investigators performed cardiac biopsies and other tests on 70 patients hospitalized with diastolic heart failure and found that 84% were infected with parvovirus B19. Presence of the virus was strongly associated with coronary endothelial dysfunction (Circulation 2005;111:879–86).

“I'm not saying this is what's going on in our emergency wards, but it's certainly something that I would never have thought to look for. We should pay attention. There may be increased information about this in the future,” Dr. Grossman commented.

There are few data from randomized trials to guide treatment of diastolic heart failure. Dr. Grossman approaches management much as he would for patients with systolic heart failure.

SAN FRANCISCO — A majority of patients presenting to emergency departments with pulmonary edema have diastolic heart failure, also known as heart failure with preserved ejection fraction, Dr. William Grossman said.

A recent analysis of data from more than 100,000 hospitalizations in the Acute Decompensated Heart Failure Registry (ADHERE) showed that 51% of patients with heart failure had preserved ejection fractions, and 49% had depressed ejection fractions, also called systolic heart failure (J. Am. Coll. Cardiol. 2006;47:76–84). In-hospital mortality rates were 3% with diastolic heart failure and 4% with systolic heart failure, he said at a meeting sponsored by the California chapter of the American College of Cardiology.

That finding may surprise many people who attribute death from heart failure mainly to systolic dysfunction, said Dr. Grossman, chief of cardiology at the University of California, San Francisco. Many patients have both types of heart failure.

Compared with the systolic heart failure group, patients who had diastolic heart failure were more likely to be women and less likely to have a prior MI or to be taking ACE inhibitors or angiotensin receptor blockers (ARBs).

In a separate recent study, investigators from the Mayo Clinic, Rochester, Minn., followed 556 patients with heart failure in the community for 6 months. The mortality rate was 16% both in the 55% of patients with diastolic heart failure and in the rest of the cohort, who had systolic heart failure, Dr. Grossman noted.

“The prognosis is really not much better than for classic systolic heart failure,” he said at the meeting, also sponsored by the university.

In the Mayo Clinic study, diastolic dysfunction and the patient's ejection fraction independently predicted elevation of brain natriuretic peptide (BNP).

“When patients come to the emergency ward with acute shortness of breath, many of us look to the BNP to tell us, is this pneumonia? Is this asthma? Is this hypertension? BNP is elevated in heart failure whether it's systolic or diastolic,” an important fact to recognize, he said.

If diastolic heart failure is so widespread, what's causing it? It's not all caused by amyloidosis, and is unlikely to be due to untreated hypertension in so many cases, Dr. Grossman believes.

German investigators performed cardiac biopsies and other tests on 70 patients hospitalized with diastolic heart failure and found that 84% were infected with parvovirus B19. Presence of the virus was strongly associated with coronary endothelial dysfunction (Circulation 2005;111:879–86).

“I'm not saying this is what's going on in our emergency wards, but it's certainly something that I would never have thought to look for. We should pay attention. There may be increased information about this in the future,” Dr. Grossman commented.

There are few data from randomized trials to guide treatment of diastolic heart failure. Dr. Grossman approaches management much as he would for patients with systolic heart failure.

SALT LAKE CITY — The investigational endothelin receptor antagonist ambrisentan appears to provide a more favorable risk/benefit ratio than current therapies do for pulmonary artery hypertension, Dr. Lewis J. Rubin said at the annual meeting of the American College of Chest Physicians.

Results of the phase III randomized double-blind ARIES-I trial demonstrate that ambrisentan has good efficacy as once-daily oral therapy. What sets it apart from other effective endothelin receptor antagonists is that it displayed no liver toxicity in ARIES-I. Indeed, the incidence of liver function test abnormalities in the trial was zero, noted Dr. Rubin, professor of medicine at the University of California, San Diego.

Ambrisentan is a high-affinity propanoic acid-class endothelin receptor type A-selective agent with no interactions with warfarin or sildenafil. Its dosing is 10–100 times less than with bosentan—the endothelin receptor antagonist now on the market—and sitaxsentan, now under FDA review. Bosentan and sitaxsentan are oral twice-daily sulfonamide-class agents, and both are associated with dose-dependent increases in liver function abnormalities that can force treatment discontinuation.

ARIES-I involved 202 patients with pulmonary artery hypertension (PAH) who were randomized to 12 weeks of double-blind placebo or once-daily ambrisentan at 5 or 10 mg. Roughly two-thirds had idiopathic PAH. Most others had PAH associated with connective tissue disease. Most subjects had moderate disease; 58% of patients were WHO class III, while 32% of patients were class II. The mean baseline 6-minute walk distance was 341 m, indicative of moderate impairment.

The primary study end point was change in 6-minute walk distance over 12 weeks. It increased by 43.6 m with 10 mg/day of ambrisentan and 22.8 m with 5 mg, and it decreased by 7.8 m on placebo, suggesting a possible dose-response effect.

ARIES-I broke new ground as the first trial in PAH to use change in plasma brain natriuretic peptide (BNP) as a secondary end point. BNP is a marker of right heart stress. It reflects severity of PAH and is predictive of long-term outcome. BNP dropped by a mean of 62.5 and 149.3 pg/mL in patients on 5 and 10 mg/day of ambrisentan, respectively, while climbing 11.8 pg/mL with placebo.

In terms of other secondary end points, the Borg dyspnea index showed significant improvement in ambrisentan-treated patients. They were also only half as likely to experience clinical worsening during the study period. The ambrisentan arms showed nonsignificant trends for improvement in WHO functional class and on the Short Form-36 physical function scale.

Ambrisentan's chief side effects were peripheral edema, occurring in more than one-quarter of patients, and nasal congestion, in 9%. The edema is an endothelin receptor antagonist-class effect. It is typically mild and readily managed with low-dose diuretics without need for dose adjustment of the anti-PAH drug, Dr. Rubin said.

With a mean extended follow-up of 1.4 years and a maximum of 2.8 years, the incidence of confirmed liver function test abnormalities in ambrisentan-treated ARIES-I participants was 0.5%. That's less than the 3% incidence noted in the placebo arm during the 12-week double-blind treatment period.

Several audience members who have used ambrisentan said it's their impression there is a dose-response effect, although that hasn't been proven. Dr. Rubin agreed.

“I don't think that 10 mg is clearly superior to 7.5 mg, but my sense is that 5–7.5 mg is better than 2.5 mg. My guess is there's a potential advantage to having a range of doses with this drug, so you can start on the low side with the ability to increase,” he said.

Dr. Rubin is a consultant to Myogen Inc., which sponsored ARIES-I and was recently acquired by Gilead Sciences Inc. Giliad filed a new drug application with FDA in December, according to a statement. GlaxoSmithKline will market ambrisentan outside the United States.

Unlike other effective endothelin receptor antagonists, ambrisentan displayed no liver toxicity. DR. RUBIN

SALT LAKE CITY — The investigational endothelin receptor antagonist ambrisentan appears to provide a more favorable risk/benefit ratio than current therapies do for pulmonary artery hypertension, Dr. Lewis J. Rubin said at the annual meeting of the American College of Chest Physicians.

Results of the phase III randomized double-blind ARIES-I trial demonstrate that ambrisentan has good efficacy as once-daily oral therapy. What sets it apart from other effective endothelin receptor antagonists is that it displayed no liver toxicity in ARIES-I. Indeed, the incidence of liver function test abnormalities in the trial was zero, noted Dr. Rubin, professor of medicine at the University of California, San Diego.

Ambrisentan is a high-affinity propanoic acid-class endothelin receptor type A-selective agent with no interactions with warfarin or sildenafil. Its dosing is 10–100 times less than with bosentan—the endothelin receptor antagonist now on the market—and sitaxsentan, now under FDA review. Bosentan and sitaxsentan are oral twice-daily sulfonamide-class agents, and both are associated with dose-dependent increases in liver function abnormalities that can force treatment discontinuation.

ARIES-I involved 202 patients with pulmonary artery hypertension (PAH) who were randomized to 12 weeks of double-blind placebo or once-daily ambrisentan at 5 or 10 mg. Roughly two-thirds had idiopathic PAH. Most others had PAH associated with connective tissue disease. Most subjects had moderate disease; 58% of patients were WHO class III, while 32% of patients were class II. The mean baseline 6-minute walk distance was 341 m, indicative of moderate impairment.

The primary study end point was change in 6-minute walk distance over 12 weeks. It increased by 43.6 m with 10 mg/day of ambrisentan and 22.8 m with 5 mg, and it decreased by 7.8 m on placebo, suggesting a possible dose-response effect.

ARIES-I broke new ground as the first trial in PAH to use change in plasma brain natriuretic peptide (BNP) as a secondary end point. BNP is a marker of right heart stress. It reflects severity of PAH and is predictive of long-term outcome. BNP dropped by a mean of 62.5 and 149.3 pg/mL in patients on 5 and 10 mg/day of ambrisentan, respectively, while climbing 11.8 pg/mL with placebo.

In terms of other secondary end points, the Borg dyspnea index showed significant improvement in ambrisentan-treated patients. They were also only half as likely to experience clinical worsening during the study period. The ambrisentan arms showed nonsignificant trends for improvement in WHO functional class and on the Short Form-36 physical function scale.

Ambrisentan's chief side effects were peripheral edema, occurring in more than one-quarter of patients, and nasal congestion, in 9%. The edema is an endothelin receptor antagonist-class effect. It is typically mild and readily managed with low-dose diuretics without need for dose adjustment of the anti-PAH drug, Dr. Rubin said.

With a mean extended follow-up of 1.4 years and a maximum of 2.8 years, the incidence of confirmed liver function test abnormalities in ambrisentan-treated ARIES-I participants was 0.5%. That's less than the 3% incidence noted in the placebo arm during the 12-week double-blind treatment period.

Several audience members who have used ambrisentan said it's their impression there is a dose-response effect, although that hasn't been proven. Dr. Rubin agreed.

“I don't think that 10 mg is clearly superior to 7.5 mg, but my sense is that 5–7.5 mg is better than 2.5 mg. My guess is there's a potential advantage to having a range of doses with this drug, so you can start on the low side with the ability to increase,” he said.

Dr. Rubin is a consultant to Myogen Inc., which sponsored ARIES-I and was recently acquired by Gilead Sciences Inc. Giliad filed a new drug application with FDA in December, according to a statement. GlaxoSmithKline will market ambrisentan outside the United States.

Unlike other effective endothelin receptor antagonists, ambrisentan displayed no liver toxicity. DR. RUBIN

SALT LAKE CITY — The investigational endothelin receptor antagonist ambrisentan appears to provide a more favorable risk/benefit ratio than current therapies do for pulmonary artery hypertension, Dr. Lewis J. Rubin said at the annual meeting of the American College of Chest Physicians.

Results of the phase III randomized double-blind ARIES-I trial demonstrate that ambrisentan has good efficacy as once-daily oral therapy. What sets it apart from other effective endothelin receptor antagonists is that it displayed no liver toxicity in ARIES-I. Indeed, the incidence of liver function test abnormalities in the trial was zero, noted Dr. Rubin, professor of medicine at the University of California, San Diego.

Ambrisentan is a high-affinity propanoic acid-class endothelin receptor type A-selective agent with no interactions with warfarin or sildenafil. Its dosing is 10–100 times less than with bosentan—the endothelin receptor antagonist now on the market—and sitaxsentan, now under FDA review. Bosentan and sitaxsentan are oral twice-daily sulfonamide-class agents, and both are associated with dose-dependent increases in liver function abnormalities that can force treatment discontinuation.

ARIES-I involved 202 patients with pulmonary artery hypertension (PAH) who were randomized to 12 weeks of double-blind placebo or once-daily ambrisentan at 5 or 10 mg. Roughly two-thirds had idiopathic PAH. Most others had PAH associated with connective tissue disease. Most subjects had moderate disease; 58% of patients were WHO class III, while 32% of patients were class II. The mean baseline 6-minute walk distance was 341 m, indicative of moderate impairment.

The primary study end point was change in 6-minute walk distance over 12 weeks. It increased by 43.6 m with 10 mg/day of ambrisentan and 22.8 m with 5 mg, and it decreased by 7.8 m on placebo, suggesting a possible dose-response effect.

ARIES-I broke new ground as the first trial in PAH to use change in plasma brain natriuretic peptide (BNP) as a secondary end point. BNP is a marker of right heart stress. It reflects severity of PAH and is predictive of long-term outcome. BNP dropped by a mean of 62.5 and 149.3 pg/mL in patients on 5 and 10 mg/day of ambrisentan, respectively, while climbing 11.8 pg/mL with placebo.

In terms of other secondary end points, the Borg dyspnea index showed significant improvement in ambrisentan-treated patients. They were also only half as likely to experience clinical worsening during the study period. The ambrisentan arms showed nonsignificant trends for improvement in WHO functional class and on the Short Form-36 physical function scale.

Ambrisentan's chief side effects were peripheral edema, occurring in more than one-quarter of patients, and nasal congestion, in 9%. The edema is an endothelin receptor antagonist-class effect. It is typically mild and readily managed with low-dose diuretics without need for dose adjustment of the anti-PAH drug, Dr. Rubin said.

With a mean extended follow-up of 1.4 years and a maximum of 2.8 years, the incidence of confirmed liver function test abnormalities in ambrisentan-treated ARIES-I participants was 0.5%. That's less than the 3% incidence noted in the placebo arm during the 12-week double-blind treatment period.

Several audience members who have used ambrisentan said it's their impression there is a dose-response effect, although that hasn't been proven. Dr. Rubin agreed.

“I don't think that 10 mg is clearly superior to 7.5 mg, but my sense is that 5–7.5 mg is better than 2.5 mg. My guess is there's a potential advantage to having a range of doses with this drug, so you can start on the low side with the ability to increase,” he said.

Dr. Rubin is a consultant to Myogen Inc., which sponsored ARIES-I and was recently acquired by Gilead Sciences Inc. Giliad filed a new drug application with FDA in December, according to a statement. GlaxoSmithKline will market ambrisentan outside the United States.

Unlike other effective endothelin receptor antagonists, ambrisentan displayed no liver toxicity. DR. RUBIN