Heart Failure

Major Finding: One intervention to facilitate the transition from hospitalization to home care cut the 30-day readmission rate by 48%; the other cut the rate by 36%.

Data Source: A prospective pilot study of readmission in 56 heart failure patients participating in a 3-month intervention, and a prospective cohort study of readmission in 257 patients with a variety of disorders who participated in a different, 1-month intervention.

Disclosures: Dr. Stauffer's study was supported by the Baylor Health Care System, Dallas. Ms. Voss's study was funded by the Centers for Medicare & Medicaid Services. Both research groups reported no financial conflicts of interest.

Two interventions to improve the transition from hospital discharge to home care, and to thereby reduce readmissions, were effective in the first attempts to implement them in real-world settings.

Both interventions had been effective in the comparatively controlled conditions of several randomized controlled trials, but until now it wasn't known whether that success would translate into real-world practice.

The first report was a pilot study at a single medical center involving patients with heart failure. The 3-month intervention was a traditional care program in which advanced practice nurses educated patients and families about symptoms and self-management strategies, improved communication patterns with care providers, and marshaled caregiver and community resources to facilitate adherence to treatment and improve quality of life. It included at least eight home visits, beginning within 72 hours of hospital admission, as well as 24-hour phone availability.

A total of 140 Medicare fee-for-service patients with heart failure were eligible, and 56 enrolled in the study.

The 30-day readmission rate was 48% lower after the intervention was implemented than it had been before. No such reduction in readmissions was noted at other medical centers in the same area during the study period, said Dr. Brett D. Stauffer of the Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, and his associates.

Total direct costs were lower for patients who participated in the intervention than for those who did not; however, the cost of the intervention itself was not recovered by the hospital.

In the second report, a Medicare demonstration project following the Care Transitions Intervention (CTI) model was assessed in 257 adults in the Medicare fee-for-service program who were hospitalized for a variety of diagnoses at six Rhode Island medical centers during an 18-month period. The facilities included community hospitals, teaching hospitals, and a tertiary care center, and their size ranged from 129 to 719 beds, said Rachel Voss of Quality Partners of Rhode Island, the Medicare Quality Improvement Organization for Rhode Island, and her associates.

The CTI is a 1-month program designed to help patients on the verge of discharge and their families to manage their health more actively and to communicate more effectively with their providers. Nurses or social workers act as “coaches” who conduct a hospital visit, a home visit within 3 days of discharge, a phone visit within 7-10 days, and a final phone visit within 30 days.

At these visits, the coaches review a booklet in which patients record their health problems, medications, and questions for providers; troubleshoot problems with outpatient care; ensure patients understand the signs and symptoms of any worsening of their condition; and help patients locate other sources of continued support.

Before implementation of the CTI program, the average 30-day readmission rate at the six participating hospitals was 21%. In comparison, the rate was only 12.8% in patients who participated in the intervention.

The primary outcome measure was the difference between the readmission rate among the study participants (12.8%) and a control group of similar patients who did not participate (20%). This represents a 36% reduction in readmissions with intervention, a significant decrease, Ms. Voss and her colleagues said (Arch. Intern. Med. 2011;171:1232-7).

Only 55% of eligible patients who were approached agreed to participate in the intervention, and the attrition rate among those who initially agreed to a home visit was 75%.

View on the News

It is comforting to read about “two successful real-world translations of interventions shown to be effective in reducing hospitalizations in randomized controlled trials.” But other aspects of these real-world successes are sobering, said Dr. Mitchell H. Katz.

Both studies had low participation rates. And in the study by Voss et al, only 14% of the patients who were approached would agree to a home visit. With such a small proportion of patients willing to try such interventions, these programs cannot have a major impact on readmission rates, he noted.

Moreover, they can only reduce health care costs if the savings from the decreased readmissions outweighs the cost of the intervention program. Under the current system that reimburses hospitals 100% for every readmission, this cannot happen.

DR. KATZ is in the Los Angeles County Department of Health Services. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying the two reports (Arch. Intern. Med. 2011;171:1230).

Major Finding: One intervention to facilitate the transition from hospitalization to home care cut the 30-day readmission rate by 48%; the other cut the rate by 36%.

Data Source: A prospective pilot study of readmission in 56 heart failure patients participating in a 3-month intervention, and a prospective cohort study of readmission in 257 patients with a variety of disorders who participated in a different, 1-month intervention.

Disclosures: Dr. Stauffer's study was supported by the Baylor Health Care System, Dallas. Ms. Voss's study was funded by the Centers for Medicare & Medicaid Services. Both research groups reported no financial conflicts of interest.

Two interventions to improve the transition from hospital discharge to home care, and to thereby reduce readmissions, were effective in the first attempts to implement them in real-world settings.

Both interventions had been effective in the comparatively controlled conditions of several randomized controlled trials, but until now it wasn't known whether that success would translate into real-world practice.

The first report was a pilot study at a single medical center involving patients with heart failure. The 3-month intervention was a traditional care program in which advanced practice nurses educated patients and families about symptoms and self-management strategies, improved communication patterns with care providers, and marshaled caregiver and community resources to facilitate adherence to treatment and improve quality of life. It included at least eight home visits, beginning within 72 hours of hospital admission, as well as 24-hour phone availability.

A total of 140 Medicare fee-for-service patients with heart failure were eligible, and 56 enrolled in the study.

The 30-day readmission rate was 48% lower after the intervention was implemented than it had been before. No such reduction in readmissions was noted at other medical centers in the same area during the study period, said Dr. Brett D. Stauffer of the Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, and his associates.

Total direct costs were lower for patients who participated in the intervention than for those who did not; however, the cost of the intervention itself was not recovered by the hospital.

In the second report, a Medicare demonstration project following the Care Transitions Intervention (CTI) model was assessed in 257 adults in the Medicare fee-for-service program who were hospitalized for a variety of diagnoses at six Rhode Island medical centers during an 18-month period. The facilities included community hospitals, teaching hospitals, and a tertiary care center, and their size ranged from 129 to 719 beds, said Rachel Voss of Quality Partners of Rhode Island, the Medicare Quality Improvement Organization for Rhode Island, and her associates.

The CTI is a 1-month program designed to help patients on the verge of discharge and their families to manage their health more actively and to communicate more effectively with their providers. Nurses or social workers act as “coaches” who conduct a hospital visit, a home visit within 3 days of discharge, a phone visit within 7-10 days, and a final phone visit within 30 days.

At these visits, the coaches review a booklet in which patients record their health problems, medications, and questions for providers; troubleshoot problems with outpatient care; ensure patients understand the signs and symptoms of any worsening of their condition; and help patients locate other sources of continued support.

Before implementation of the CTI program, the average 30-day readmission rate at the six participating hospitals was 21%. In comparison, the rate was only 12.8% in patients who participated in the intervention.

The primary outcome measure was the difference between the readmission rate among the study participants (12.8%) and a control group of similar patients who did not participate (20%). This represents a 36% reduction in readmissions with intervention, a significant decrease, Ms. Voss and her colleagues said (Arch. Intern. Med. 2011;171:1232-7).

Only 55% of eligible patients who were approached agreed to participate in the intervention, and the attrition rate among those who initially agreed to a home visit was 75%.

View on the News

It is comforting to read about “two successful real-world translations of interventions shown to be effective in reducing hospitalizations in randomized controlled trials.” But other aspects of these real-world successes are sobering, said Dr. Mitchell H. Katz.

Both studies had low participation rates. And in the study by Voss et al, only 14% of the patients who were approached would agree to a home visit. With such a small proportion of patients willing to try such interventions, these programs cannot have a major impact on readmission rates, he noted.

Moreover, they can only reduce health care costs if the savings from the decreased readmissions outweighs the cost of the intervention program. Under the current system that reimburses hospitals 100% for every readmission, this cannot happen.

DR. KATZ is in the Los Angeles County Department of Health Services. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying the two reports (Arch. Intern. Med. 2011;171:1230).

Major Finding: One intervention to facilitate the transition from hospitalization to home care cut the 30-day readmission rate by 48%; the other cut the rate by 36%.

Data Source: A prospective pilot study of readmission in 56 heart failure patients participating in a 3-month intervention, and a prospective cohort study of readmission in 257 patients with a variety of disorders who participated in a different, 1-month intervention.

Disclosures: Dr. Stauffer's study was supported by the Baylor Health Care System, Dallas. Ms. Voss's study was funded by the Centers for Medicare & Medicaid Services. Both research groups reported no financial conflicts of interest.

Two interventions to improve the transition from hospital discharge to home care, and to thereby reduce readmissions, were effective in the first attempts to implement them in real-world settings.

Both interventions had been effective in the comparatively controlled conditions of several randomized controlled trials, but until now it wasn't known whether that success would translate into real-world practice.

The first report was a pilot study at a single medical center involving patients with heart failure. The 3-month intervention was a traditional care program in which advanced practice nurses educated patients and families about symptoms and self-management strategies, improved communication patterns with care providers, and marshaled caregiver and community resources to facilitate adherence to treatment and improve quality of life. It included at least eight home visits, beginning within 72 hours of hospital admission, as well as 24-hour phone availability.

A total of 140 Medicare fee-for-service patients with heart failure were eligible, and 56 enrolled in the study.

The 30-day readmission rate was 48% lower after the intervention was implemented than it had been before. No such reduction in readmissions was noted at other medical centers in the same area during the study period, said Dr. Brett D. Stauffer of the Institute for Health Care Research and Improvement, Baylor Health Care System, Dallas, and his associates.

Total direct costs were lower for patients who participated in the intervention than for those who did not; however, the cost of the intervention itself was not recovered by the hospital.

In the second report, a Medicare demonstration project following the Care Transitions Intervention (CTI) model was assessed in 257 adults in the Medicare fee-for-service program who were hospitalized for a variety of diagnoses at six Rhode Island medical centers during an 18-month period. The facilities included community hospitals, teaching hospitals, and a tertiary care center, and their size ranged from 129 to 719 beds, said Rachel Voss of Quality Partners of Rhode Island, the Medicare Quality Improvement Organization for Rhode Island, and her associates.

The CTI is a 1-month program designed to help patients on the verge of discharge and their families to manage their health more actively and to communicate more effectively with their providers. Nurses or social workers act as “coaches” who conduct a hospital visit, a home visit within 3 days of discharge, a phone visit within 7-10 days, and a final phone visit within 30 days.

At these visits, the coaches review a booklet in which patients record their health problems, medications, and questions for providers; troubleshoot problems with outpatient care; ensure patients understand the signs and symptoms of any worsening of their condition; and help patients locate other sources of continued support.

Before implementation of the CTI program, the average 30-day readmission rate at the six participating hospitals was 21%. In comparison, the rate was only 12.8% in patients who participated in the intervention.

The primary outcome measure was the difference between the readmission rate among the study participants (12.8%) and a control group of similar patients who did not participate (20%). This represents a 36% reduction in readmissions with intervention, a significant decrease, Ms. Voss and her colleagues said (Arch. Intern. Med. 2011;171:1232-7).

Only 55% of eligible patients who were approached agreed to participate in the intervention, and the attrition rate among those who initially agreed to a home visit was 75%.

View on the News

It is comforting to read about “two successful real-world translations of interventions shown to be effective in reducing hospitalizations in randomized controlled trials.” But other aspects of these real-world successes are sobering, said Dr. Mitchell H. Katz.

Both studies had low participation rates. And in the study by Voss et al, only 14% of the patients who were approached would agree to a home visit. With such a small proportion of patients willing to try such interventions, these programs cannot have a major impact on readmission rates, he noted.

Moreover, they can only reduce health care costs if the savings from the decreased readmissions outweighs the cost of the intervention program. Under the current system that reimburses hospitals 100% for every readmission, this cannot happen.

DR. KATZ is in the Los Angeles County Department of Health Services. He reported no financial conflicts of interest. These remarks were taken from his editorial accompanying the two reports (Arch. Intern. Med. 2011;171:1230).

Major Finding: The incidence of heart failure in type 1 diabetes patients rose as HbA_1c levels did, from 1.42 to 5.20 per 1,000 patient-years in patients with HbA_1c levels of below 6.5% and at least 10.5%, respectively.

Data Source: An analysis of 20,985 type 1 diabetes patients aged at least 18 with no known heart failure in the Swedish national diabetes registry, who were registered during 1998-2003 and followed through 2009.

Disclosures: The study was supported by an unrestricted grant from AstraZeneca, Novo Nordisk Scandinavia, the Swedish Heart and Lung Foundation, and the Swedish Research Council. Dr. Lind has received honoraria from or been a consultant for Bayer, Eli Lilly, Novartis, Novo Nordisk Scandinavia, Medtronic, Pfizer, and Sanofi-Aventis; and has been a member of an advisory board for Novo Nordisk Scandinavia.

SAN DIEGO – Tight control of hemoglobin A_1c levels significantly reduces the risk of heart failure in patients with type 1 diabetes, results from a large, long-term study show.

In fact, patients with very poor glycemic control were four times as likely to experience heart failure, compared with their counterparts with optimal glycemic control.

“Because treatment for heart failure improves survival and quality of life, clinicians should be observant of signs of heart failure in management of patients with type 1 diabetes, starting at an early stage,” lead author Dr. Marcus Lind wrote in the study, which was presented at the meeting and simultaneously published onlinei “Echocardiography might be warranted, especially in the presence of poor glycemic control, long duration of diabetes, or an adverse risk factor profile.”

Dr. Lind of the department of medicine at Uddevalla (Sweden) Hospital and his associates used the Swedish national diabetes registry to identify 20,985 patients aged 18 years or older with type 1 disease who had no known heart failure and who were registered between January 1998 and December 2003. They followed the cohort until hospital admission for heart failure, death, or end of follow-up on Dec. 31, 2009 (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)60471-6]).

The incidence of heart failure was determined by dividing the number of patient-years of follow-up in a particular HbA_1c category, reported as events per 1,000 years of follow-up. The six HbA_1c categories were less than 6.5%, from 6.5% to less than 7.5%, from 7.5% to less than 8.5%, from 8.5% to less than 9.5%, from 9.5% to less than 10.5%, and 10.5% or greater. Cox regression analysis was used to study possible associations between heart failure and patients' characteristics.

The mean age of patients was 39 years, and 45% were female; they had had diabetes for a mean of 14 years, and their mean body mass index was 25 kg/m

After adjustment for age, sex, duration of diabetes, cardiovascular disease risk factors, acute myocardial infarction, and other comorbidities, a Cox regression analysis revealed that patients with an HbA_1c level of 10.5% or higher were four times more likely to develop heart failure than were those who had an HbA_1c level of less than 6.5%.

Other independent predictors of heart failure included age (hazard ratio, 1.64 per 10-year increase); duration of diabetes (HR, 1.34 per 10-year increase); BMI (HR, 1.05 per 1-kg/m

“For many years there have been observations that poor glycemic control is linked to heart attack and cardiovascular mortality,” Dr. Sue Kirkman, senior vice president of medical affairs and community information for the American Diabetes Association, said in an interview at the meeting. “This may be the first time that it's been shown to be linked to heart failure in a type 1 population.”

She called the study “hypothesis generating,” and noted that a long-term randomized trial will be needed to confirm the findings. “It is interesting, because it seems that in type 1 diabetes there may be a stronger link between glucose lowering and cardiac outcomes than in type 2 diabetes,” she said.

View On The News

Tight Control 'Essential'

How tightly should glycemia be controlled in diabetes? The clear message from Dr. Lind's and his colleagues' paper is that tight control of glycemia in type 1 diabetes is essential, especially now that they have shown that such control can prevent heart failure, besides other aspects of cardiovascular disease. In the future, even established type 1 diabetes cardiomyopathy might be rescued by gene-activated prosurvival paths, as shown in a mouse model. Only in developing countries, where tight control is often not feasible, could less-strict control be acceptable for type 1 diabetes.

LIONEL H. OPIE, M.D., is director of the Hatter Cardiovascular Research Institute at the University of Cape Town (South Africa). This was adapted from an accompanying commentary published online (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)6078703]). He reported no conflicts of interest.

Major Finding: The incidence of heart failure in type 1 diabetes patients rose as HbA_1c levels did, from 1.42 to 5.20 per 1,000 patient-years in patients with HbA_1c levels of below 6.5% and at least 10.5%, respectively.

Data Source: An analysis of 20,985 type 1 diabetes patients aged at least 18 with no known heart failure in the Swedish national diabetes registry, who were registered during 1998-2003 and followed through 2009.

Disclosures: The study was supported by an unrestricted grant from AstraZeneca, Novo Nordisk Scandinavia, the Swedish Heart and Lung Foundation, and the Swedish Research Council. Dr. Lind has received honoraria from or been a consultant for Bayer, Eli Lilly, Novartis, Novo Nordisk Scandinavia, Medtronic, Pfizer, and Sanofi-Aventis; and has been a member of an advisory board for Novo Nordisk Scandinavia.

SAN DIEGO – Tight control of hemoglobin A_1c levels significantly reduces the risk of heart failure in patients with type 1 diabetes, results from a large, long-term study show.

In fact, patients with very poor glycemic control were four times as likely to experience heart failure, compared with their counterparts with optimal glycemic control.

“Because treatment for heart failure improves survival and quality of life, clinicians should be observant of signs of heart failure in management of patients with type 1 diabetes, starting at an early stage,” lead author Dr. Marcus Lind wrote in the study, which was presented at the meeting and simultaneously published onlinei “Echocardiography might be warranted, especially in the presence of poor glycemic control, long duration of diabetes, or an adverse risk factor profile.”

Dr. Lind of the department of medicine at Uddevalla (Sweden) Hospital and his associates used the Swedish national diabetes registry to identify 20,985 patients aged 18 years or older with type 1 disease who had no known heart failure and who were registered between January 1998 and December 2003. They followed the cohort until hospital admission for heart failure, death, or end of follow-up on Dec. 31, 2009 (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)60471-6]).

The incidence of heart failure was determined by dividing the number of patient-years of follow-up in a particular HbA_1c category, reported as events per 1,000 years of follow-up. The six HbA_1c categories were less than 6.5%, from 6.5% to less than 7.5%, from 7.5% to less than 8.5%, from 8.5% to less than 9.5%, from 9.5% to less than 10.5%, and 10.5% or greater. Cox regression analysis was used to study possible associations between heart failure and patients' characteristics.

The mean age of patients was 39 years, and 45% were female; they had had diabetes for a mean of 14 years, and their mean body mass index was 25 kg/m

After adjustment for age, sex, duration of diabetes, cardiovascular disease risk factors, acute myocardial infarction, and other comorbidities, a Cox regression analysis revealed that patients with an HbA_1c level of 10.5% or higher were four times more likely to develop heart failure than were those who had an HbA_1c level of less than 6.5%.

Other independent predictors of heart failure included age (hazard ratio, 1.64 per 10-year increase); duration of diabetes (HR, 1.34 per 10-year increase); BMI (HR, 1.05 per 1-kg/m

“For many years there have been observations that poor glycemic control is linked to heart attack and cardiovascular mortality,” Dr. Sue Kirkman, senior vice president of medical affairs and community information for the American Diabetes Association, said in an interview at the meeting. “This may be the first time that it's been shown to be linked to heart failure in a type 1 population.”

She called the study “hypothesis generating,” and noted that a long-term randomized trial will be needed to confirm the findings. “It is interesting, because it seems that in type 1 diabetes there may be a stronger link between glucose lowering and cardiac outcomes than in type 2 diabetes,” she said.

View On The News

Tight Control 'Essential'

How tightly should glycemia be controlled in diabetes? The clear message from Dr. Lind's and his colleagues' paper is that tight control of glycemia in type 1 diabetes is essential, especially now that they have shown that such control can prevent heart failure, besides other aspects of cardiovascular disease. In the future, even established type 1 diabetes cardiomyopathy might be rescued by gene-activated prosurvival paths, as shown in a mouse model. Only in developing countries, where tight control is often not feasible, could less-strict control be acceptable for type 1 diabetes.

LIONEL H. OPIE, M.D., is director of the Hatter Cardiovascular Research Institute at the University of Cape Town (South Africa). This was adapted from an accompanying commentary published online (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)6078703]). He reported no conflicts of interest.

Major Finding: The incidence of heart failure in type 1 diabetes patients rose as HbA_1c levels did, from 1.42 to 5.20 per 1,000 patient-years in patients with HbA_1c levels of below 6.5% and at least 10.5%, respectively.

Data Source: An analysis of 20,985 type 1 diabetes patients aged at least 18 with no known heart failure in the Swedish national diabetes registry, who were registered during 1998-2003 and followed through 2009.

Disclosures: The study was supported by an unrestricted grant from AstraZeneca, Novo Nordisk Scandinavia, the Swedish Heart and Lung Foundation, and the Swedish Research Council. Dr. Lind has received honoraria from or been a consultant for Bayer, Eli Lilly, Novartis, Novo Nordisk Scandinavia, Medtronic, Pfizer, and Sanofi-Aventis; and has been a member of an advisory board for Novo Nordisk Scandinavia.

SAN DIEGO – Tight control of hemoglobin A_1c levels significantly reduces the risk of heart failure in patients with type 1 diabetes, results from a large, long-term study show.

In fact, patients with very poor glycemic control were four times as likely to experience heart failure, compared with their counterparts with optimal glycemic control.

“Because treatment for heart failure improves survival and quality of life, clinicians should be observant of signs of heart failure in management of patients with type 1 diabetes, starting at an early stage,” lead author Dr. Marcus Lind wrote in the study, which was presented at the meeting and simultaneously published onlinei “Echocardiography might be warranted, especially in the presence of poor glycemic control, long duration of diabetes, or an adverse risk factor profile.”

Dr. Lind of the department of medicine at Uddevalla (Sweden) Hospital and his associates used the Swedish national diabetes registry to identify 20,985 patients aged 18 years or older with type 1 disease who had no known heart failure and who were registered between January 1998 and December 2003. They followed the cohort until hospital admission for heart failure, death, or end of follow-up on Dec. 31, 2009 (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)60471-6]).

The incidence of heart failure was determined by dividing the number of patient-years of follow-up in a particular HbA_1c category, reported as events per 1,000 years of follow-up. The six HbA_1c categories were less than 6.5%, from 6.5% to less than 7.5%, from 7.5% to less than 8.5%, from 8.5% to less than 9.5%, from 9.5% to less than 10.5%, and 10.5% or greater. Cox regression analysis was used to study possible associations between heart failure and patients' characteristics.

The mean age of patients was 39 years, and 45% were female; they had had diabetes for a mean of 14 years, and their mean body mass index was 25 kg/m

After adjustment for age, sex, duration of diabetes, cardiovascular disease risk factors, acute myocardial infarction, and other comorbidities, a Cox regression analysis revealed that patients with an HbA_1c level of 10.5% or higher were four times more likely to develop heart failure than were those who had an HbA_1c level of less than 6.5%.

Other independent predictors of heart failure included age (hazard ratio, 1.64 per 10-year increase); duration of diabetes (HR, 1.34 per 10-year increase); BMI (HR, 1.05 per 1-kg/m

“For many years there have been observations that poor glycemic control is linked to heart attack and cardiovascular mortality,” Dr. Sue Kirkman, senior vice president of medical affairs and community information for the American Diabetes Association, said in an interview at the meeting. “This may be the first time that it's been shown to be linked to heart failure in a type 1 population.”

She called the study “hypothesis generating,” and noted that a long-term randomized trial will be needed to confirm the findings. “It is interesting, because it seems that in type 1 diabetes there may be a stronger link between glucose lowering and cardiac outcomes than in type 2 diabetes,” she said.

View On The News

Tight Control 'Essential'

How tightly should glycemia be controlled in diabetes? The clear message from Dr. Lind's and his colleagues' paper is that tight control of glycemia in type 1 diabetes is essential, especially now that they have shown that such control can prevent heart failure, besides other aspects of cardiovascular disease. In the future, even established type 1 diabetes cardiomyopathy might be rescued by gene-activated prosurvival paths, as shown in a mouse model. Only in developing countries, where tight control is often not feasible, could less-strict control be acceptable for type 1 diabetes.

LIONEL H. OPIE, M.D., is director of the Hatter Cardiovascular Research Institute at the University of Cape Town (South Africa). This was adapted from an accompanying commentary published online (Lancet 2011 June 25 [doi: 10.1016/S0140-6736(11)6078703]). He reported no conflicts of interest.

Steroids Should Be Discontinued as Soon as Possible in All Patients

There is a compelling case for taking all heart transplant recipients off corticosteroids as early as possible, and certainly no later than 3 months after transplantation.

Patients undergoing heart transplantation are in essence trading a disease that will kill them for a disease that is more treatable: immunosuppression. But we physicians can control immunosuppression, which begs the question: Can’t we do better?

We use steroids in more than 80% of our patients. Steroids are our security blanket; they are the drugs that make us feel better. As I was told in training, we sleep better when our patients are on steroids, because we tend to think that they are safe.

But there is no denying that steroids can have life-altering adverse effects for our patients. What if steroids were unnecessary? In fact, they are, but we just haven’t recognized that universally. Steroids are not necessary. This is a not a new idea, as is evident from reports dating back to 1985 (Circulation 1990;82[5 suppl.]:IV318-21).

At least 10 studies have shown the safety of stopping steroids early in heart transplant recipients. Additionally, a recurring finding is that survival is, in fact, better with this practice. You could argue that the patients who are not taken off steroids have a better risk profile, but the weight of evidence does not suggest that this is the case. The following are a few of these studies:

• A case-control study among 420 heart transplant recipients found that steroid withdrawal starting 6 months or more post transplantation was associated with a higher rate of rejection over 7 years, but despite this, survival was better (Am. J. Transplant. 2005;5 [4 Pt. 1]:720-8).

• In a prospective study of 33 heart transplant recipients who were given tacrolimus or sirolimus, all patients were taken off steroids within 6 months (J. Heart Lung Transplant. 2007;26:598-603). There was a single treated rejection and no deaths.

• A retrospective single-institution study of 220 patients found that steroid weaning after heart transplantation was an independent predictor of survival, conferring a significant 40% reduction in the risk of death (Transplant Proc. 2006;38:1501-6).

• In the randomized TICTAC (Tacrolimus in Combination, Tacrolimus Alone Compared) trial, which compared tacrolimus with and without mycophenolate mofetil (MMF), steroids were discontinued in all patients by 8-9 weeks (Circ. Heart Fail. 2011;4:129-37). Over a median follow-up of 3-4 years, none has had to resume steroid maintenance. There was a slight nonsignificant increase in rejection with the monotherapy, but survival – the standard – was identical between groups.

One fear when we began this study was that we would pay the price in allograft vasculopathy if we didn’t provide adequate immunosuppression. Over a 5-year period, however, we have not: The patients on monotherapy and the patients on combination therapy (again, all of them steroid free during follow-up) were indistinguishable in terms of this outcome.

So why do we cling to corticosteroids? What are they doing for us? It’s time to finally admit that they are not necessary. Steroids should be discontinued as rapidly possible among all heart transplant recipients – certainly within 3 months post transplant. We now have good evidence proving the safety and efficacy of this approach.

Dr. Baran is the director of heart failure and transplant research at the Newark (N.J.) Beth Israel Medical Center.

Only Selected Patients Benefit From Early Discontinuation of Steroids

Given current evidence, it is extreme and premature to take all patients off corticosteroids within 3 months of heart transplantation.

Steroids have been used since the beginning of heart transplant therapy, and are still among our most useful drugs for achieving immunosuppression.

We all know about their adverse effects. But they are less common today now that we use lower doses (enabled by combination therapy), and we have other means for preventing some of the adverse effects associated with steroids.

Although other classes of immunosuppressants – such as calcineurin inhibitors, MMF, and mTOR (mammalian target of rapamycin) inhibitors – have become available, it is important to remember that they, too, have adverse effects.

The different classes of immunosuppressants have different mechanisms of action, and this is the theoretical basis of triple-drug therapy. Nonreliance on a single drug also allows us to use smaller doses of each.

Nearly all of the major clinical trials in heart transplantation have used corticosteroids (J. Heart Lung Transplant. 2010;29:914-56). And certainly it is now clear that none of the leading causes of death after heart transplantation in adults (except for infection) seems attributable to these drugs (J. Heart Lung Transplant. 2010;29:1089-103). On the contrary, lack of steroid maintenance therapy has been identified as an independent risk factor for death, conferring a doubling of risk (J. Thorac. Cardiovasc. Surg. 2010;140:161-8).

The TICTAC trial was well done and had some important findings. Unfortunately, it was not a clinical trial of steroid discontinuation because there was no group of patients kept on steroids.

Also, when compared with patients in a similar trial who were given tacrolimus-MMF (Am. J. Transplant. 2006;6:1377-86), patients in the TICTAC trial had higher levels of tacrolimus and serum creatinine. These differences are a little worrisome in terms of long-term outcomes.

At my institution, even later withdrawal of steroids (that is, among patients who were on steroids for at least 4 years without any acute rejection episodes) was associated with a 25% incidence of acute rejection (Transplant Proc. 2007;39:2372-4). In Spain, centers typically stop steroids only in patients who have unacceptable adverse effects and a low immunologic risk for rejection.

Only one trial has directly compared early steroid withdrawal with standard steroid therapy in transplant recipients (Am. J. Transplant. 2008;8:307-16). In that study, in kidney transplant patients who either did not receive any steroids or received them for just the first week, acute rejection occurred both earlier and more often than in the standard therapy group. And there were only modest reductions in adverse events.

In heart transplantation, immunosuppressive therapy is not a one-size-fits-all undertaking. Some patients (for example, those who have preexisting osteoporosis, are elderly, or have diabetes) do benefit from early withdrawal of steroids.

Indeed, guidelines recommend steroid weaning in patients who experience significant adverse effects and have not had a recent acute rejection episode (J. Heart Transplant. 2010;29:914-56). But they also note that although several studies have shown that it is feasible and safe to wean most patients by 6-12 months, and that doing so is desirable to reduce adverse effects, there has not been a randomized trial testing this practice.

It is possible that future well-designed studies will show that the risk of rejection is a reasonable price to pay for avoiding the adverse effects of steroids. These studies must have long-term follow-up and assess the key outcomes of graft and patient survival, rather than just rejection.

In conclusion, there are certainly patients who benefit from early withdrawal of steroids, but current evidence does not support the generalization of this practice.

Dr. Crespo-Leiro is with the heart failure and heart transplant unit at the Hospital Universitario a Coruña (Spain).

Steroids Should Be Discontinued as Soon as Possible in All Patients

There is a compelling case for taking all heart transplant recipients off corticosteroids as early as possible, and certainly no later than 3 months after transplantation.

Patients undergoing heart transplantation are in essence trading a disease that will kill them for a disease that is more treatable: immunosuppression. But we physicians can control immunosuppression, which begs the question: Can’t we do better?

We use steroids in more than 80% of our patients. Steroids are our security blanket; they are the drugs that make us feel better. As I was told in training, we sleep better when our patients are on steroids, because we tend to think that they are safe.

But there is no denying that steroids can have life-altering adverse effects for our patients. What if steroids were unnecessary? In fact, they are, but we just haven’t recognized that universally. Steroids are not necessary. This is a not a new idea, as is evident from reports dating back to 1985 (Circulation 1990;82[5 suppl.]:IV318-21).

At least 10 studies have shown the safety of stopping steroids early in heart transplant recipients. Additionally, a recurring finding is that survival is, in fact, better with this practice. You could argue that the patients who are not taken off steroids have a better risk profile, but the weight of evidence does not suggest that this is the case. The following are a few of these studies:

• A case-control study among 420 heart transplant recipients found that steroid withdrawal starting 6 months or more post transplantation was associated with a higher rate of rejection over 7 years, but despite this, survival was better (Am. J. Transplant. 2005;5 [4 Pt. 1]:720-8).

• In a prospective study of 33 heart transplant recipients who were given tacrolimus or sirolimus, all patients were taken off steroids within 6 months (J. Heart Lung Transplant. 2007;26:598-603). There was a single treated rejection and no deaths.

• A retrospective single-institution study of 220 patients found that steroid weaning after heart transplantation was an independent predictor of survival, conferring a significant 40% reduction in the risk of death (Transplant Proc. 2006;38:1501-6).

• In the randomized TICTAC (Tacrolimus in Combination, Tacrolimus Alone Compared) trial, which compared tacrolimus with and without mycophenolate mofetil (MMF), steroids were discontinued in all patients by 8-9 weeks (Circ. Heart Fail. 2011;4:129-37). Over a median follow-up of 3-4 years, none has had to resume steroid maintenance. There was a slight nonsignificant increase in rejection with the monotherapy, but survival – the standard – was identical between groups.

One fear when we began this study was that we would pay the price in allograft vasculopathy if we didn’t provide adequate immunosuppression. Over a 5-year period, however, we have not: The patients on monotherapy and the patients on combination therapy (again, all of them steroid free during follow-up) were indistinguishable in terms of this outcome.

So why do we cling to corticosteroids? What are they doing for us? It’s time to finally admit that they are not necessary. Steroids should be discontinued as rapidly possible among all heart transplant recipients – certainly within 3 months post transplant. We now have good evidence proving the safety and efficacy of this approach.

Dr. Baran is the director of heart failure and transplant research at the Newark (N.J.) Beth Israel Medical Center.

Only Selected Patients Benefit From Early Discontinuation of Steroids

Given current evidence, it is extreme and premature to take all patients off corticosteroids within 3 months of heart transplantation.

Steroids have been used since the beginning of heart transplant therapy, and are still among our most useful drugs for achieving immunosuppression.

We all know about their adverse effects. But they are less common today now that we use lower doses (enabled by combination therapy), and we have other means for preventing some of the adverse effects associated with steroids.

Although other classes of immunosuppressants – such as calcineurin inhibitors, MMF, and mTOR (mammalian target of rapamycin) inhibitors – have become available, it is important to remember that they, too, have adverse effects.

The different classes of immunosuppressants have different mechanisms of action, and this is the theoretical basis of triple-drug therapy. Nonreliance on a single drug also allows us to use smaller doses of each.

Nearly all of the major clinical trials in heart transplantation have used corticosteroids (J. Heart Lung Transplant. 2010;29:914-56). And certainly it is now clear that none of the leading causes of death after heart transplantation in adults (except for infection) seems attributable to these drugs (J. Heart Lung Transplant. 2010;29:1089-103). On the contrary, lack of steroid maintenance therapy has been identified as an independent risk factor for death, conferring a doubling of risk (J. Thorac. Cardiovasc. Surg. 2010;140:161-8).

The TICTAC trial was well done and had some important findings. Unfortunately, it was not a clinical trial of steroid discontinuation because there was no group of patients kept on steroids.

Also, when compared with patients in a similar trial who were given tacrolimus-MMF (Am. J. Transplant. 2006;6:1377-86), patients in the TICTAC trial had higher levels of tacrolimus and serum creatinine. These differences are a little worrisome in terms of long-term outcomes.

At my institution, even later withdrawal of steroids (that is, among patients who were on steroids for at least 4 years without any acute rejection episodes) was associated with a 25% incidence of acute rejection (Transplant Proc. 2007;39:2372-4). In Spain, centers typically stop steroids only in patients who have unacceptable adverse effects and a low immunologic risk for rejection.

Only one trial has directly compared early steroid withdrawal with standard steroid therapy in transplant recipients (Am. J. Transplant. 2008;8:307-16). In that study, in kidney transplant patients who either did not receive any steroids or received them for just the first week, acute rejection occurred both earlier and more often than in the standard therapy group. And there were only modest reductions in adverse events.

In heart transplantation, immunosuppressive therapy is not a one-size-fits-all undertaking. Some patients (for example, those who have preexisting osteoporosis, are elderly, or have diabetes) do benefit from early withdrawal of steroids.

Indeed, guidelines recommend steroid weaning in patients who experience significant adverse effects and have not had a recent acute rejection episode (J. Heart Transplant. 2010;29:914-56). But they also note that although several studies have shown that it is feasible and safe to wean most patients by 6-12 months, and that doing so is desirable to reduce adverse effects, there has not been a randomized trial testing this practice.

It is possible that future well-designed studies will show that the risk of rejection is a reasonable price to pay for avoiding the adverse effects of steroids. These studies must have long-term follow-up and assess the key outcomes of graft and patient survival, rather than just rejection.

In conclusion, there are certainly patients who benefit from early withdrawal of steroids, but current evidence does not support the generalization of this practice.

Dr. Crespo-Leiro is with the heart failure and heart transplant unit at the Hospital Universitario a Coruña (Spain).

Steroids Should Be Discontinued as Soon as Possible in All Patients

There is a compelling case for taking all heart transplant recipients off corticosteroids as early as possible, and certainly no later than 3 months after transplantation.

Patients undergoing heart transplantation are in essence trading a disease that will kill them for a disease that is more treatable: immunosuppression. But we physicians can control immunosuppression, which begs the question: Can’t we do better?

We use steroids in more than 80% of our patients. Steroids are our security blanket; they are the drugs that make us feel better. As I was told in training, we sleep better when our patients are on steroids, because we tend to think that they are safe.

But there is no denying that steroids can have life-altering adverse effects for our patients. What if steroids were unnecessary? In fact, they are, but we just haven’t recognized that universally. Steroids are not necessary. This is a not a new idea, as is evident from reports dating back to 1985 (Circulation 1990;82[5 suppl.]:IV318-21).

At least 10 studies have shown the safety of stopping steroids early in heart transplant recipients. Additionally, a recurring finding is that survival is, in fact, better with this practice. You could argue that the patients who are not taken off steroids have a better risk profile, but the weight of evidence does not suggest that this is the case. The following are a few of these studies:

• A case-control study among 420 heart transplant recipients found that steroid withdrawal starting 6 months or more post transplantation was associated with a higher rate of rejection over 7 years, but despite this, survival was better (Am. J. Transplant. 2005;5 [4 Pt. 1]:720-8).

• In a prospective study of 33 heart transplant recipients who were given tacrolimus or sirolimus, all patients were taken off steroids within 6 months (J. Heart Lung Transplant. 2007;26:598-603). There was a single treated rejection and no deaths.

• A retrospective single-institution study of 220 patients found that steroid weaning after heart transplantation was an independent predictor of survival, conferring a significant 40% reduction in the risk of death (Transplant Proc. 2006;38:1501-6).

• In the randomized TICTAC (Tacrolimus in Combination, Tacrolimus Alone Compared) trial, which compared tacrolimus with and without mycophenolate mofetil (MMF), steroids were discontinued in all patients by 8-9 weeks (Circ. Heart Fail. 2011;4:129-37). Over a median follow-up of 3-4 years, none has had to resume steroid maintenance. There was a slight nonsignificant increase in rejection with the monotherapy, but survival – the standard – was identical between groups.

One fear when we began this study was that we would pay the price in allograft vasculopathy if we didn’t provide adequate immunosuppression. Over a 5-year period, however, we have not: The patients on monotherapy and the patients on combination therapy (again, all of them steroid free during follow-up) were indistinguishable in terms of this outcome.

So why do we cling to corticosteroids? What are they doing for us? It’s time to finally admit that they are not necessary. Steroids should be discontinued as rapidly possible among all heart transplant recipients – certainly within 3 months post transplant. We now have good evidence proving the safety and efficacy of this approach.

Dr. Baran is the director of heart failure and transplant research at the Newark (N.J.) Beth Israel Medical Center.

Only Selected Patients Benefit From Early Discontinuation of Steroids

Given current evidence, it is extreme and premature to take all patients off corticosteroids within 3 months of heart transplantation.

Steroids have been used since the beginning of heart transplant therapy, and are still among our most useful drugs for achieving immunosuppression.

We all know about their adverse effects. But they are less common today now that we use lower doses (enabled by combination therapy), and we have other means for preventing some of the adverse effects associated with steroids.

Although other classes of immunosuppressants – such as calcineurin inhibitors, MMF, and mTOR (mammalian target of rapamycin) inhibitors – have become available, it is important to remember that they, too, have adverse effects.

The different classes of immunosuppressants have different mechanisms of action, and this is the theoretical basis of triple-drug therapy. Nonreliance on a single drug also allows us to use smaller doses of each.

Nearly all of the major clinical trials in heart transplantation have used corticosteroids (J. Heart Lung Transplant. 2010;29:914-56). And certainly it is now clear that none of the leading causes of death after heart transplantation in adults (except for infection) seems attributable to these drugs (J. Heart Lung Transplant. 2010;29:1089-103). On the contrary, lack of steroid maintenance therapy has been identified as an independent risk factor for death, conferring a doubling of risk (J. Thorac. Cardiovasc. Surg. 2010;140:161-8).

The TICTAC trial was well done and had some important findings. Unfortunately, it was not a clinical trial of steroid discontinuation because there was no group of patients kept on steroids.

Also, when compared with patients in a similar trial who were given tacrolimus-MMF (Am. J. Transplant. 2006;6:1377-86), patients in the TICTAC trial had higher levels of tacrolimus and serum creatinine. These differences are a little worrisome in terms of long-term outcomes.

At my institution, even later withdrawal of steroids (that is, among patients who were on steroids for at least 4 years without any acute rejection episodes) was associated with a 25% incidence of acute rejection (Transplant Proc. 2007;39:2372-4). In Spain, centers typically stop steroids only in patients who have unacceptable adverse effects and a low immunologic risk for rejection.

Only one trial has directly compared early steroid withdrawal with standard steroid therapy in transplant recipients (Am. J. Transplant. 2008;8:307-16). In that study, in kidney transplant patients who either did not receive any steroids or received them for just the first week, acute rejection occurred both earlier and more often than in the standard therapy group. And there were only modest reductions in adverse events.

In heart transplantation, immunosuppressive therapy is not a one-size-fits-all undertaking. Some patients (for example, those who have preexisting osteoporosis, are elderly, or have diabetes) do benefit from early withdrawal of steroids.

Indeed, guidelines recommend steroid weaning in patients who experience significant adverse effects and have not had a recent acute rejection episode (J. Heart Transplant. 2010;29:914-56). But they also note that although several studies have shown that it is feasible and safe to wean most patients by 6-12 months, and that doing so is desirable to reduce adverse effects, there has not been a randomized trial testing this practice.

It is possible that future well-designed studies will show that the risk of rejection is a reasonable price to pay for avoiding the adverse effects of steroids. These studies must have long-term follow-up and assess the key outcomes of graft and patient survival, rather than just rejection.

In conclusion, there are certainly patients who benefit from early withdrawal of steroids, but current evidence does not support the generalization of this practice.

Dr. Crespo-Leiro is with the heart failure and heart transplant unit at the Hospital Universitario a Coruña (Spain).

Nesiritide has no effect on 30-day mortality or rehospitalization rates in patients with acute decompensated heart failure, according to results of the ASCEND-HF trial reported in the July 7 issue of the New England Journal of Medicine.

In a large 3-year international clinical trial called by an independent panel "to answer the question of whether nesiritide is effective and safe," the drug also failed to improve self-reported dyspnea at 6 hours or 24 hours. It did not worsen renal function, but it nearly doubled the rates of both symptomatic and asymptomatic hypotension.

"Nesiritide thus cannot be recommended in the broad population of patients with acute decompensated heart failure represented by the study population in this trial," wrote Dr. Christopher M. O’Connor of Duke Clinical Research Institute, Durham, N.C., and his associates in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial.

Nesiritide, a recombinant B-type natriuretic peptide with vasodilatory action, was approved in 2001 for use in patients with acute heart failure, based on separate small studies showing that it reduced pulmonary-capillary wedge pressure and eased dyspnea within 3 hours of administration. Later meta-analyses of these and other small trials, however, indicated that the drug worsened renal function and nearly doubled early mortality.

"In hindsight, nesiritide was approved and swiftly adopted in the United States because of its perceived large benefit in relieving dyspnea and congestion, and then its used markedly decreased because of published meta-analyses reporting a detrimental effect on survival and renal function. Our study showed that neither belief was accurate," Dr. O’Connor and his colleagues noted.

ASCEND-HF involved 7,141 patients treated at 398 medical centers around the world. All the participants received standard therapies including diuretics, morphine, and vasoactive medications. Half also received intravenous nesiritide and half received a placebo for up to 7 days.

The two coprimary end points were change in self-reported dyspnea at 6 and 24 hours and rehospitalization for heart failure or death from any cause within 30 days. There was a slight numerical advantage with nesiritide over placebo for dyspnea (44.5% vs. 42.1%, P = .03), but it did not reach the prespecified level for statistical significance. The rates of the second end point were 9.4% with nesiritide and 10.1% with placebo, another nonsignificant difference.

The two study groups also showed no significant differences in self-reported patient well-being, rehospitalization for cardiovascular causes, death from cardiovascular causes, total days alive and out of the hospital at 1 month, rates of persistent or worsening HF, or death from any cause at 1 month. Rates of renal impairment also were comparable between the two groups, regardless of baseline renal insufficiency, the investigators noted (N. Engl. J. Med. 2011;365:32-43).

Significantly more patients who received nesiritide had an episode of asymptomatic (21.4%) or symptomatic (7.2%) hypotension, compared with patients who received placebo (12.4% and 4.0%, respectively).

"The development of nesiritide poses fundamental questions about the manner in which therapies are developed and assessed. Because nesiritide was not studied in a major outcome trial early in its life cycle, both patients and physicians lacked an appropriate understanding of the proper role of the drug in practice.

"Our findings underscore the fact that systematic overviews with small numbers of events can yield unreliable estimates of the balance of benefits and risks, and interpretation of the data is confounded by these imprecise estimates," Dr. O’Connor and his colleagues wrote.

The results also "highlight the urgent need for rigorously designed trials with adequate power to provide reliable estimates that can replace incomplete or inadequate evidence as a basis for therapeutic decisions," they added. The ASCEND-HF results were presented at the annual scientific sessions of the American Heart Association in November 2010.

ASCEND-HF was sponsored by Scios, a Johnson & Johnson company, which markets nesiritide (Natrecor). The investigators reported ties to numerous industry sources. Dr. O’Connor has received consulting fees from Medtronic, Forest, Amgen, Medpace, Roche, and Actelion. Two of the authors are employees of Johnson & Johnson.

Nesiritide has no effect on 30-day mortality or rehospitalization rates in patients with acute decompensated heart failure, according to results of the ASCEND-HF trial reported in the July 7 issue of the New England Journal of Medicine.

In a large 3-year international clinical trial called by an independent panel "to answer the question of whether nesiritide is effective and safe," the drug also failed to improve self-reported dyspnea at 6 hours or 24 hours. It did not worsen renal function, but it nearly doubled the rates of both symptomatic and asymptomatic hypotension.

"Nesiritide thus cannot be recommended in the broad population of patients with acute decompensated heart failure represented by the study population in this trial," wrote Dr. Christopher M. O’Connor of Duke Clinical Research Institute, Durham, N.C., and his associates in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial.

Nesiritide, a recombinant B-type natriuretic peptide with vasodilatory action, was approved in 2001 for use in patients with acute heart failure, based on separate small studies showing that it reduced pulmonary-capillary wedge pressure and eased dyspnea within 3 hours of administration. Later meta-analyses of these and other small trials, however, indicated that the drug worsened renal function and nearly doubled early mortality.

"In hindsight, nesiritide was approved and swiftly adopted in the United States because of its perceived large benefit in relieving dyspnea and congestion, and then its used markedly decreased because of published meta-analyses reporting a detrimental effect on survival and renal function. Our study showed that neither belief was accurate," Dr. O’Connor and his colleagues noted.

ASCEND-HF involved 7,141 patients treated at 398 medical centers around the world. All the participants received standard therapies including diuretics, morphine, and vasoactive medications. Half also received intravenous nesiritide and half received a placebo for up to 7 days.

The two coprimary end points were change in self-reported dyspnea at 6 and 24 hours and rehospitalization for heart failure or death from any cause within 30 days. There was a slight numerical advantage with nesiritide over placebo for dyspnea (44.5% vs. 42.1%, P = .03), but it did not reach the prespecified level for statistical significance. The rates of the second end point were 9.4% with nesiritide and 10.1% with placebo, another nonsignificant difference.

The two study groups also showed no significant differences in self-reported patient well-being, rehospitalization for cardiovascular causes, death from cardiovascular causes, total days alive and out of the hospital at 1 month, rates of persistent or worsening HF, or death from any cause at 1 month. Rates of renal impairment also were comparable between the two groups, regardless of baseline renal insufficiency, the investigators noted (N. Engl. J. Med. 2011;365:32-43).

Significantly more patients who received nesiritide had an episode of asymptomatic (21.4%) or symptomatic (7.2%) hypotension, compared with patients who received placebo (12.4% and 4.0%, respectively).

"The development of nesiritide poses fundamental questions about the manner in which therapies are developed and assessed. Because nesiritide was not studied in a major outcome trial early in its life cycle, both patients and physicians lacked an appropriate understanding of the proper role of the drug in practice.

"Our findings underscore the fact that systematic overviews with small numbers of events can yield unreliable estimates of the balance of benefits and risks, and interpretation of the data is confounded by these imprecise estimates," Dr. O’Connor and his colleagues wrote.

The results also "highlight the urgent need for rigorously designed trials with adequate power to provide reliable estimates that can replace incomplete or inadequate evidence as a basis for therapeutic decisions," they added. The ASCEND-HF results were presented at the annual scientific sessions of the American Heart Association in November 2010.

ASCEND-HF was sponsored by Scios, a Johnson & Johnson company, which markets nesiritide (Natrecor). The investigators reported ties to numerous industry sources. Dr. O’Connor has received consulting fees from Medtronic, Forest, Amgen, Medpace, Roche, and Actelion. Two of the authors are employees of Johnson & Johnson.

Nesiritide has no effect on 30-day mortality or rehospitalization rates in patients with acute decompensated heart failure, according to results of the ASCEND-HF trial reported in the July 7 issue of the New England Journal of Medicine.

In a large 3-year international clinical trial called by an independent panel "to answer the question of whether nesiritide is effective and safe," the drug also failed to improve self-reported dyspnea at 6 hours or 24 hours. It did not worsen renal function, but it nearly doubled the rates of both symptomatic and asymptomatic hypotension.

"Nesiritide thus cannot be recommended in the broad population of patients with acute decompensated heart failure represented by the study population in this trial," wrote Dr. Christopher M. O’Connor of Duke Clinical Research Institute, Durham, N.C., and his associates in the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial.

Nesiritide, a recombinant B-type natriuretic peptide with vasodilatory action, was approved in 2001 for use in patients with acute heart failure, based on separate small studies showing that it reduced pulmonary-capillary wedge pressure and eased dyspnea within 3 hours of administration. Later meta-analyses of these and other small trials, however, indicated that the drug worsened renal function and nearly doubled early mortality.

"In hindsight, nesiritide was approved and swiftly adopted in the United States because of its perceived large benefit in relieving dyspnea and congestion, and then its used markedly decreased because of published meta-analyses reporting a detrimental effect on survival and renal function. Our study showed that neither belief was accurate," Dr. O’Connor and his colleagues noted.

ASCEND-HF involved 7,141 patients treated at 398 medical centers around the world. All the participants received standard therapies including diuretics, morphine, and vasoactive medications. Half also received intravenous nesiritide and half received a placebo for up to 7 days.

The two coprimary end points were change in self-reported dyspnea at 6 and 24 hours and rehospitalization for heart failure or death from any cause within 30 days. There was a slight numerical advantage with nesiritide over placebo for dyspnea (44.5% vs. 42.1%, P = .03), but it did not reach the prespecified level for statistical significance. The rates of the second end point were 9.4% with nesiritide and 10.1% with placebo, another nonsignificant difference.

The two study groups also showed no significant differences in self-reported patient well-being, rehospitalization for cardiovascular causes, death from cardiovascular causes, total days alive and out of the hospital at 1 month, rates of persistent or worsening HF, or death from any cause at 1 month. Rates of renal impairment also were comparable between the two groups, regardless of baseline renal insufficiency, the investigators noted (N. Engl. J. Med. 2011;365:32-43).

Significantly more patients who received nesiritide had an episode of asymptomatic (21.4%) or symptomatic (7.2%) hypotension, compared with patients who received placebo (12.4% and 4.0%, respectively).

"The development of nesiritide poses fundamental questions about the manner in which therapies are developed and assessed. Because nesiritide was not studied in a major outcome trial early in its life cycle, both patients and physicians lacked an appropriate understanding of the proper role of the drug in practice.

"Our findings underscore the fact that systematic overviews with small numbers of events can yield unreliable estimates of the balance of benefits and risks, and interpretation of the data is confounded by these imprecise estimates," Dr. O’Connor and his colleagues wrote.

The results also "highlight the urgent need for rigorously designed trials with adequate power to provide reliable estimates that can replace incomplete or inadequate evidence as a basis for therapeutic decisions," they added. The ASCEND-HF results were presented at the annual scientific sessions of the American Heart Association in November 2010.

ASCEND-HF was sponsored by Scios, a Johnson & Johnson company, which markets nesiritide (Natrecor). The investigators reported ties to numerous industry sources. Dr. O’Connor has received consulting fees from Medtronic, Forest, Amgen, Medpace, Roche, and Actelion. Two of the authors are employees of Johnson & Johnson.

SAN DIEGO – A new allocation algorithm that is designed to improve regional sharing of donor hearts with sicker patients before they are allocated locally to less-sick patients appears to be having the intended effects, according to a national cohort study.

In the study of nearly 12,000 adult patients who were wait-listed for primary heart transplantation in 2004-2009 in the United States, those who were wait-listed after the new algorithm was implemented were 17% less likely to die on the waiting list or to become too sick for transplantation, Dr. Tajinder P. Singh reported at the meeting.

Moreover, this benefit was achieved without any increase in the rate of in-hospital mortality in transplant recipients, even though they were sicker on average.

“The risk of dying on the heart transplant [waiting list] or becoming too sick for transplant has declined since the change in allocation algorithm in 2006,” said Dr. Singh, a pediatric cardiologist at Children's Hospital Boston. And reassuringly, “the shift in hearts to sicker transplant candidates has not resulted in higher early posttransplant mortality.”

These findings suggest that the new algorithm has been effective “not only from a utilitarian view, which means most benefit for most people, but even from the fairness or justice perspective,” he commented, because the hearts are goint to sicker people.

“The demand for donor hearts continues to exceed their supply,” he said, giving background to the study. “The United Network for Organ Sharing has periodically modified the allocation algorithm in the United States” to improve waiting list outcomes.

The last such modification, implemented in July 2006, expanded the sharing of these scarce organs across a geographic region, making them available first to the sickest patients (those with status 1A or 1B) in a region before allocating them locally to less-sick patients.

The investigators studied all patients aged 18 years or older who were placed on the waiting list for primary heart transplantationbduring July 1004, ane 30, 2009, and who were undergoing transplantation of only a heart.

For comparison, the patients were split according to when they were listed into “era 1” (before the date of implementation of the new algorithm) and “era 2” (after that date). Study results were based on 11,864 patients in total; 38% were listed in era 1 and 62% were listed in era 2.

Patients in the two eras were similar with respect to most sociodemographic and medical factors, except that those in era 2 were more likely to be aged 60 years or older (32% vs. 28%), to receive mechanical support (14% vs. 13%), and to be sicker, as indicated by having a transplantation status of 1A (20% vs. 19%) or 1B (38% vs. 32%), for instance.

Overall, 13% of the patients studied either died or had a worsening of their condition that prevented transplantation while they were on the waiting list, the study's primary end point, Dr. Singh reported.

Before statistical adjustment, patients in era 2 were 14% less likely than those in era 1 to die or worsen while on the wait list (hazard ratio, 0.86). And this benefit was evident in both status 1A patients and status 1B patients individually.

After adjustment for numerous potential confounders, patients in era 2 were 17% less likely to die or worsen while on the wait list (HR, 0.83). This significant benefit was similar in most subgroups, except that by race, it was mainly limited to white patients.

Other risk-reducing factors included having an implantable cardioverter defibrillator (HR, 0.87) and having a continuous-flow left ventricular assist device (HR, 0.56).

Overall, 65% of the patients ultimately underwent transplantation. Compared with those in era 1, era 2 transplant recipients had a significantly shorter median wait time before receiving a heart (55 vs. 63 days) and were more likely to be status 1A at transplantation (48% vs. 37%).

Dr. Singh reported having no conflicts of interest related to the research.

SAN DIEGO – A new allocation algorithm that is designed to improve regional sharing of donor hearts with sicker patients before they are allocated locally to less-sick patients appears to be having the intended effects, according to a national cohort study.

In the study of nearly 12,000 adult patients who were wait-listed for primary heart transplantation in 2004-2009 in the United States, those who were wait-listed after the new algorithm was implemented were 17% less likely to die on the waiting list or to become too sick for transplantation, Dr. Tajinder P. Singh reported at the meeting.

Moreover, this benefit was achieved without any increase in the rate of in-hospital mortality in transplant recipients, even though they were sicker on average.

“The risk of dying on the heart transplant [waiting list] or becoming too sick for transplant has declined since the change in allocation algorithm in 2006,” said Dr. Singh, a pediatric cardiologist at Children's Hospital Boston. And reassuringly, “the shift in hearts to sicker transplant candidates has not resulted in higher early posttransplant mortality.”

These findings suggest that the new algorithm has been effective “not only from a utilitarian view, which means most benefit for most people, but even from the fairness or justice perspective,” he commented, because the hearts are goint to sicker people.

“The demand for donor hearts continues to exceed their supply,” he said, giving background to the study. “The United Network for Organ Sharing has periodically modified the allocation algorithm in the United States” to improve waiting list outcomes.

The last such modification, implemented in July 2006, expanded the sharing of these scarce organs across a geographic region, making them available first to the sickest patients (those with status 1A or 1B) in a region before allocating them locally to less-sick patients.

The investigators studied all patients aged 18 years or older who were placed on the waiting list for primary heart transplantationbduring July 1004, ane 30, 2009, and who were undergoing transplantation of only a heart.

For comparison, the patients were split according to when they were listed into “era 1” (before the date of implementation of the new algorithm) and “era 2” (after that date). Study results were based on 11,864 patients in total; 38% were listed in era 1 and 62% were listed in era 2.

Patients in the two eras were similar with respect to most sociodemographic and medical factors, except that those in era 2 were more likely to be aged 60 years or older (32% vs. 28%), to receive mechanical support (14% vs. 13%), and to be sicker, as indicated by having a transplantation status of 1A (20% vs. 19%) or 1B (38% vs. 32%), for instance.

Overall, 13% of the patients studied either died or had a worsening of their condition that prevented transplantation while they were on the waiting list, the study's primary end point, Dr. Singh reported.

Before statistical adjustment, patients in era 2 were 14% less likely than those in era 1 to die or worsen while on the wait list (hazard ratio, 0.86). And this benefit was evident in both status 1A patients and status 1B patients individually.

After adjustment for numerous potential confounders, patients in era 2 were 17% less likely to die or worsen while on the wait list (HR, 0.83). This significant benefit was similar in most subgroups, except that by race, it was mainly limited to white patients.

Other risk-reducing factors included having an implantable cardioverter defibrillator (HR, 0.87) and having a continuous-flow left ventricular assist device (HR, 0.56).

Overall, 65% of the patients ultimately underwent transplantation. Compared with those in era 1, era 2 transplant recipients had a significantly shorter median wait time before receiving a heart (55 vs. 63 days) and were more likely to be status 1A at transplantation (48% vs. 37%).

Dr. Singh reported having no conflicts of interest related to the research.

SAN DIEGO – A new allocation algorithm that is designed to improve regional sharing of donor hearts with sicker patients before they are allocated locally to less-sick patients appears to be having the intended effects, according to a national cohort study.

In the study of nearly 12,000 adult patients who were wait-listed for primary heart transplantation in 2004-2009 in the United States, those who were wait-listed after the new algorithm was implemented were 17% less likely to die on the waiting list or to become too sick for transplantation, Dr. Tajinder P. Singh reported at the meeting.

Moreover, this benefit was achieved without any increase in the rate of in-hospital mortality in transplant recipients, even though they were sicker on average.

“The risk of dying on the heart transplant [waiting list] or becoming too sick for transplant has declined since the change in allocation algorithm in 2006,” said Dr. Singh, a pediatric cardiologist at Children's Hospital Boston. And reassuringly, “the shift in hearts to sicker transplant candidates has not resulted in higher early posttransplant mortality.”

These findings suggest that the new algorithm has been effective “not only from a utilitarian view, which means most benefit for most people, but even from the fairness or justice perspective,” he commented, because the hearts are goint to sicker people.

“The demand for donor hearts continues to exceed their supply,” he said, giving background to the study. “The United Network for Organ Sharing has periodically modified the allocation algorithm in the United States” to improve waiting list outcomes.

The last such modification, implemented in July 2006, expanded the sharing of these scarce organs across a geographic region, making them available first to the sickest patients (those with status 1A or 1B) in a region before allocating them locally to less-sick patients.

The investigators studied all patients aged 18 years or older who were placed on the waiting list for primary heart transplantationbduring July 1004, ane 30, 2009, and who were undergoing transplantation of only a heart.

For comparison, the patients were split according to when they were listed into “era 1” (before the date of implementation of the new algorithm) and “era 2” (after that date). Study results were based on 11,864 patients in total; 38% were listed in era 1 and 62% were listed in era 2.

Patients in the two eras were similar with respect to most sociodemographic and medical factors, except that those in era 2 were more likely to be aged 60 years or older (32% vs. 28%), to receive mechanical support (14% vs. 13%), and to be sicker, as indicated by having a transplantation status of 1A (20% vs. 19%) or 1B (38% vs. 32%), for instance.

Overall, 13% of the patients studied either died or had a worsening of their condition that prevented transplantation while they were on the waiting list, the study's primary end point, Dr. Singh reported.

Before statistical adjustment, patients in era 2 were 14% less likely than those in era 1 to die or worsen while on the wait list (hazard ratio, 0.86). And this benefit was evident in both status 1A patients and status 1B patients individually.

After adjustment for numerous potential confounders, patients in era 2 were 17% less likely to die or worsen while on the wait list (HR, 0.83). This significant benefit was similar in most subgroups, except that by race, it was mainly limited to white patients.

Other risk-reducing factors included having an implantable cardioverter defibrillator (HR, 0.87) and having a continuous-flow left ventricular assist device (HR, 0.56).

Overall, 65% of the patients ultimately underwent transplantation. Compared with those in era 1, era 2 transplant recipients had a significantly shorter median wait time before receiving a heart (55 vs. 63 days) and were more likely to be status 1A at transplantation (48% vs. 37%).

Dr. Singh reported having no conflicts of interest related to the research.

Major Finding: After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the heart failure clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic.

Data Source: Randomized study of 1,119 heart failure patients treated at 18 Danish centers.

Disclosures: Dr. Schou said that he has received research support from Roche Diagnostics Denmark, Roche Diagnostics International, and Merck Sharp & Dohme.

NEW ORLEANS – General practice physicians who managed stable heart failure patients achieved long-term outcomes that matched the outcomes of patients managed in specialized, outpatient heart failure clinics supervised by cardiologists, in a randomized, Danish study with more than 1,100 patients.

Another facet of the same study showed that repeated, serial measurement of blood levels of N-terminal-proB-type natriuretic peptide (NT-proBNP) in heart failure patients did not improve long-term outcomes compared with no routine measurement of the biomarker, Dr. Morten Schou said at the meeting.

“Clinically stable patients with systolic heart failure on optimal medical therapy did not benefit from long-term follow-up in a heart failure clinic,” said Dr. Schou, a cardiologist at Hillerod University Hospital in Copenhagen.

Heart failure clinics with intensive patient management can aid in stabilizing patients, but they are most suited for newly diagnosed patients who are not yet well controlled on an appropriate maintenance regimen, Dr. Schou said in an interview. “Our study is the first to investigate continuing intensive management once a heart failure patient is stable on an optimized regimen. The long-term benefits of heart failure clinics were never tested before.”

The stabilization regimen used by the investigators involved uptitrating the drugs patients received so that their medical treatment used drugs such as ACE inhibitors, beta-blockers, and aldosterone antagonists at dosages comparable to what has been shown effective in clinical trials. Patients also received comprehensive education about their heart failure and optimal management methods. The stabilization process took from 1 month to 1 year, he said, and slightly more than a quarter of the heart failure patients seen at least once at one of the 18 participating Danish heart failure clinics achieved stability and also met the study's other eligibility criteria.

“The key message is that you need to educate and uptitrate patients, and then they can be followed by a general practitioner [GP],” he said.

The second finding of the study, that multiple, serial measures of blood NT-proBNP did not lead to improved outcomes, should prompt a change in U.S. practice, commented Dr. Prakash C. Deedwania, professor of medicine at the University of California, San Francisco, in Fresno.

In current U.S. practice, “BNP is measured about 10 times on patients in the hospital [for heart failure]. I could never understand it. These results show that it wastes time and money to measure BNP” repeatedly, he said in an interview (see View on the News, below).

The NT-proBNP stratified follow-up in outpatient heart failure clinics (NorthStar) trial enrolled patients with New York Heart Association class I-III systolic heart failure and a left ventricular ejection fraction of 45% or less who also fulfilled the study's prespecified criteria for disease stability. The criteria included completion of a heart failure education course, and daily treatment with an evidence-based dosage of an ACE inhibitor or angiotensin II receptor blocker, beta-blocker, and, when appropriate, an aldosterone antagonist. Participants were also taking a stable diuretic dose and had a stable weight, stable heart failure symptoms, and no crackles on lung auscultation. The study randomized 460 patients to ongoing care by a general practitioner and 659 patients to regular care in a heart failure clinic supervised by a cardiologist.

The heart failure clinic patients underwent further assessment at baseline to identify those with a blood level of NT-proBNP that exceeded 1,000 pg/mL. The 407 patients in this group underwent a second randomization, with 208 patients followed without any subsequent, routine measurement of their NT-proBNP level, and 199 patients who underwent a repeat blood check of NT-proBNP at every follow-up visit to the clinic. The clinic staff received a guide detailing clinical factors to investigate in patients who had a rise in their NT-proBNP level of greater than 30% from one clinic visit to the next. The study followed all patients for a median of 2.5 years.

The average age of the patients randomized to GP or heart failure clinic management was 69 years. A quarter of the patients were women, and all patients had an average ejection fraction of about 31%. Among the subgroup of patients with an elevated blood level of NT-proBNP at baseline, the average age was 73 years, a quarter were women, and their average ejection fraction was 30%.

The study's primary end point was the combined rate of all-cause death or cardiovascular hospitalization. After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic. In addition, patients managed in heart failure clinics without routine NT-proBNP monitoring had a combined end-point rate similar to those who underwent routine monitoring, Dr. Schou reported. The results showed no statistically significant difference among the study subgroups for any secondary end points assessed.

'You need to educate and uptitrate patients, and then they can be followed by a general practitioner.'

Source DR. SCHOU

View on the News

Findings Point to Lower Costs

The results from this study show that properly treated heart failure patients on an evidence-based regimen can be effectively managed by a primary care physician. That's a very powerful and important message. In the United States, heart failure management has become a big business. But every heart failure patient cannot be managed by a cardiologist because the number of patients is increasing too quickly. In the Danish study, general practitioners got the heart failure patients after they were stabilized, and the GPs were trained in how to adjust the patients' diuretic dosages.

These results do not discount a role for heart failure disease management. Disease management works. It is important to have a specific regimen for monitoring and treating heart failure patients. But the results show that it doesn't matter who does the monitoring and treating as long as they received training in how to do it.

The results also showed that we waste time and money if we measure B-type natriuretic peptide repeatedly in heart failure patients. BNP is good for making an initial diagnosis of heart failure, to distinguish heart failure from other disorders with similar symptoms. But once an initial measure is made and the diagnosis confirmed, more BNP measurements don't add anything further. Many U.S. heart failure patients undergo serial measurements despite the lack of good evidence that this helps. Current guidelines from the Heart Failure Society of America call for only measuring BNP initially in heart failure patients, especially when the initial diagnosis is uncertain based on clinical presentation (J. Card. Fail. 2010;16:e1-e194).

PRAKASH C. DEEDWANIA, M.D., is professor of medicine at the University of California, San Francisco, in Fresno. His comments were made in an interview. He reported having no disclosures.

Major Finding: After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the heart failure clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic.

Data Source: Randomized study of 1,119 heart failure patients treated at 18 Danish centers.

Disclosures: Dr. Schou said that he has received research support from Roche Diagnostics Denmark, Roche Diagnostics International, and Merck Sharp & Dohme.

NEW ORLEANS – General practice physicians who managed stable heart failure patients achieved long-term outcomes that matched the outcomes of patients managed in specialized, outpatient heart failure clinics supervised by cardiologists, in a randomized, Danish study with more than 1,100 patients.

Another facet of the same study showed that repeated, serial measurement of blood levels of N-terminal-proB-type natriuretic peptide (NT-proBNP) in heart failure patients did not improve long-term outcomes compared with no routine measurement of the biomarker, Dr. Morten Schou said at the meeting.

“Clinically stable patients with systolic heart failure on optimal medical therapy did not benefit from long-term follow-up in a heart failure clinic,” said Dr. Schou, a cardiologist at Hillerod University Hospital in Copenhagen.

Heart failure clinics with intensive patient management can aid in stabilizing patients, but they are most suited for newly diagnosed patients who are not yet well controlled on an appropriate maintenance regimen, Dr. Schou said in an interview. “Our study is the first to investigate continuing intensive management once a heart failure patient is stable on an optimized regimen. The long-term benefits of heart failure clinics were never tested before.”

The stabilization regimen used by the investigators involved uptitrating the drugs patients received so that their medical treatment used drugs such as ACE inhibitors, beta-blockers, and aldosterone antagonists at dosages comparable to what has been shown effective in clinical trials. Patients also received comprehensive education about their heart failure and optimal management methods. The stabilization process took from 1 month to 1 year, he said, and slightly more than a quarter of the heart failure patients seen at least once at one of the 18 participating Danish heart failure clinics achieved stability and also met the study's other eligibility criteria.

“The key message is that you need to educate and uptitrate patients, and then they can be followed by a general practitioner [GP],” he said.

The second finding of the study, that multiple, serial measures of blood NT-proBNP did not lead to improved outcomes, should prompt a change in U.S. practice, commented Dr. Prakash C. Deedwania, professor of medicine at the University of California, San Francisco, in Fresno.

In current U.S. practice, “BNP is measured about 10 times on patients in the hospital [for heart failure]. I could never understand it. These results show that it wastes time and money to measure BNP” repeatedly, he said in an interview (see View on the News, below).

The NT-proBNP stratified follow-up in outpatient heart failure clinics (NorthStar) trial enrolled patients with New York Heart Association class I-III systolic heart failure and a left ventricular ejection fraction of 45% or less who also fulfilled the study's prespecified criteria for disease stability. The criteria included completion of a heart failure education course, and daily treatment with an evidence-based dosage of an ACE inhibitor or angiotensin II receptor blocker, beta-blocker, and, when appropriate, an aldosterone antagonist. Participants were also taking a stable diuretic dose and had a stable weight, stable heart failure symptoms, and no crackles on lung auscultation. The study randomized 460 patients to ongoing care by a general practitioner and 659 patients to regular care in a heart failure clinic supervised by a cardiologist.

The heart failure clinic patients underwent further assessment at baseline to identify those with a blood level of NT-proBNP that exceeded 1,000 pg/mL. The 407 patients in this group underwent a second randomization, with 208 patients followed without any subsequent, routine measurement of their NT-proBNP level, and 199 patients who underwent a repeat blood check of NT-proBNP at every follow-up visit to the clinic. The clinic staff received a guide detailing clinical factors to investigate in patients who had a rise in their NT-proBNP level of greater than 30% from one clinic visit to the next. The study followed all patients for a median of 2.5 years.

The average age of the patients randomized to GP or heart failure clinic management was 69 years. A quarter of the patients were women, and all patients had an average ejection fraction of about 31%. Among the subgroup of patients with an elevated blood level of NT-proBNP at baseline, the average age was 73 years, a quarter were women, and their average ejection fraction was 30%.

The study's primary end point was the combined rate of all-cause death or cardiovascular hospitalization. After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic. In addition, patients managed in heart failure clinics without routine NT-proBNP monitoring had a combined end-point rate similar to those who underwent routine monitoring, Dr. Schou reported. The results showed no statistically significant difference among the study subgroups for any secondary end points assessed.

'You need to educate and uptitrate patients, and then they can be followed by a general practitioner.'

Source DR. SCHOU

View on the News

Findings Point to Lower Costs

The results from this study show that properly treated heart failure patients on an evidence-based regimen can be effectively managed by a primary care physician. That's a very powerful and important message. In the United States, heart failure management has become a big business. But every heart failure patient cannot be managed by a cardiologist because the number of patients is increasing too quickly. In the Danish study, general practitioners got the heart failure patients after they were stabilized, and the GPs were trained in how to adjust the patients' diuretic dosages.

These results do not discount a role for heart failure disease management. Disease management works. It is important to have a specific regimen for monitoring and treating heart failure patients. But the results show that it doesn't matter who does the monitoring and treating as long as they received training in how to do it.

The results also showed that we waste time and money if we measure B-type natriuretic peptide repeatedly in heart failure patients. BNP is good for making an initial diagnosis of heart failure, to distinguish heart failure from other disorders with similar symptoms. But once an initial measure is made and the diagnosis confirmed, more BNP measurements don't add anything further. Many U.S. heart failure patients undergo serial measurements despite the lack of good evidence that this helps. Current guidelines from the Heart Failure Society of America call for only measuring BNP initially in heart failure patients, especially when the initial diagnosis is uncertain based on clinical presentation (J. Card. Fail. 2010;16:e1-e194).

PRAKASH C. DEEDWANIA, M.D., is professor of medicine at the University of California, San Francisco, in Fresno. His comments were made in an interview. He reported having no disclosures.

Major Finding: After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the heart failure clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic.

Data Source: Randomized study of 1,119 heart failure patients treated at 18 Danish centers.

Disclosures: Dr. Schou said that he has received research support from Roche Diagnostics Denmark, Roche Diagnostics International, and Merck Sharp & Dohme.

NEW ORLEANS – General practice physicians who managed stable heart failure patients achieved long-term outcomes that matched the outcomes of patients managed in specialized, outpatient heart failure clinics supervised by cardiologists, in a randomized, Danish study with more than 1,100 patients.

Another facet of the same study showed that repeated, serial measurement of blood levels of N-terminal-proB-type natriuretic peptide (NT-proBNP) in heart failure patients did not improve long-term outcomes compared with no routine measurement of the biomarker, Dr. Morten Schou said at the meeting.

“Clinically stable patients with systolic heart failure on optimal medical therapy did not benefit from long-term follow-up in a heart failure clinic,” said Dr. Schou, a cardiologist at Hillerod University Hospital in Copenhagen.

Heart failure clinics with intensive patient management can aid in stabilizing patients, but they are most suited for newly diagnosed patients who are not yet well controlled on an appropriate maintenance regimen, Dr. Schou said in an interview. “Our study is the first to investigate continuing intensive management once a heart failure patient is stable on an optimized regimen. The long-term benefits of heart failure clinics were never tested before.”

The stabilization regimen used by the investigators involved uptitrating the drugs patients received so that their medical treatment used drugs such as ACE inhibitors, beta-blockers, and aldosterone antagonists at dosages comparable to what has been shown effective in clinical trials. Patients also received comprehensive education about their heart failure and optimal management methods. The stabilization process took from 1 month to 1 year, he said, and slightly more than a quarter of the heart failure patients seen at least once at one of the 18 participating Danish heart failure clinics achieved stability and also met the study's other eligibility criteria.

“The key message is that you need to educate and uptitrate patients, and then they can be followed by a general practitioner [GP],” he said.

The second finding of the study, that multiple, serial measures of blood NT-proBNP did not lead to improved outcomes, should prompt a change in U.S. practice, commented Dr. Prakash C. Deedwania, professor of medicine at the University of California, San Francisco, in Fresno.

In current U.S. practice, “BNP is measured about 10 times on patients in the hospital [for heart failure]. I could never understand it. These results show that it wastes time and money to measure BNP” repeatedly, he said in an interview (see View on the News, below).

The NT-proBNP stratified follow-up in outpatient heart failure clinics (NorthStar) trial enrolled patients with New York Heart Association class I-III systolic heart failure and a left ventricular ejection fraction of 45% or less who also fulfilled the study's prespecified criteria for disease stability. The criteria included completion of a heart failure education course, and daily treatment with an evidence-based dosage of an ACE inhibitor or angiotensin II receptor blocker, beta-blocker, and, when appropriate, an aldosterone antagonist. Participants were also taking a stable diuretic dose and had a stable weight, stable heart failure symptoms, and no crackles on lung auscultation. The study randomized 460 patients to ongoing care by a general practitioner and 659 patients to regular care in a heart failure clinic supervised by a cardiologist.

The heart failure clinic patients underwent further assessment at baseline to identify those with a blood level of NT-proBNP that exceeded 1,000 pg/mL. The 407 patients in this group underwent a second randomization, with 208 patients followed without any subsequent, routine measurement of their NT-proBNP level, and 199 patients who underwent a repeat blood check of NT-proBNP at every follow-up visit to the clinic. The clinic staff received a guide detailing clinical factors to investigate in patients who had a rise in their NT-proBNP level of greater than 30% from one clinic visit to the next. The study followed all patients for a median of 2.5 years.

The average age of the patients randomized to GP or heart failure clinic management was 69 years. A quarter of the patients were women, and all patients had an average ejection fraction of about 31%. Among the subgroup of patients with an elevated blood level of NT-proBNP at baseline, the average age was 73 years, a quarter were women, and their average ejection fraction was 30%.

The study's primary end point was the combined rate of all-cause death or cardiovascular hospitalization. After a median of 2.8 years, low-risk patients had 27 deaths and 81 composite events in the GP group vs. 22 deaths and 92 composite events in the clinic group. High-risk patients had 37 deaths and 78 composite events in the GP group and 38 deaths and 85 composite events in the clinic. In addition, patients managed in heart failure clinics without routine NT-proBNP monitoring had a combined end-point rate similar to those who underwent routine monitoring, Dr. Schou reported. The results showed no statistically significant difference among the study subgroups for any secondary end points assessed.

'You need to educate and uptitrate patients, and then they can be followed by a general practitioner.'

Source DR. SCHOU

View on the News

Findings Point to Lower Costs

The results from this study show that properly treated heart failure patients on an evidence-based regimen can be effectively managed by a primary care physician. That's a very powerful and important message. In the United States, heart failure management has become a big business. But every heart failure patient cannot be managed by a cardiologist because the number of patients is increasing too quickly. In the Danish study, general practitioners got the heart failure patients after they were stabilized, and the GPs were trained in how to adjust the patients' diuretic dosages.

These results do not discount a role for heart failure disease management. Disease management works. It is important to have a specific regimen for monitoring and treating heart failure patients. But the results show that it doesn't matter who does the monitoring and treating as long as they received training in how to do it.

The results also showed that we waste time and money if we measure B-type natriuretic peptide repeatedly in heart failure patients. BNP is good for making an initial diagnosis of heart failure, to distinguish heart failure from other disorders with similar symptoms. But once an initial measure is made and the diagnosis confirmed, more BNP measurements don't add anything further. Many U.S. heart failure patients undergo serial measurements despite the lack of good evidence that this helps. Current guidelines from the Heart Failure Society of America call for only measuring BNP initially in heart failure patients, especially when the initial diagnosis is uncertain based on clinical presentation (J. Card. Fail. 2010;16:e1-e194).

PRAKASH C. DEEDWANIA, M.D., is professor of medicine at the University of California, San Francisco, in Fresno. His comments were made in an interview. He reported having no disclosures.

Moderate and severe diastolic dysfunction in patients who have normal systolic function increased all-cause mortality, according to a report in the June 27 issue of the Archives of Internal Medicine.

Such diastolic dysfunction is usually preclinical and often is identified on outpatient echocardiography that was done to assess nonspecific symptoms, ventricular or valvular function, arrhythmia, or ECG abnormalities. Its clinical significance has not been documented until now, said Dr. Carmel M. Halley of the Heart and Vascular Institute at the Cleveland Clinic, and her associates.

"Because the use of echocardiography as a clinical tool in the outpatient setting continues to increase ... our study provides the physician with a prognostic context when diastolic dysfunction is reported, especially because most procedures are requested by noncardiologists," the researchers noted (Arch. Intern. Med. 2011;171:1082-7).

Dr. Halley and her colleagues examined diastolic dysfunction in the absence of systolic dysfunction, because the clinical relevance of the condition has been questioned. Many medical disorders associated with diastolic dysfunction, such as hypertension, coronary artery disease, obesity, and diabetes, are themselves predictors of increased mortality, so it was unclear whether diastolic dysfunction was an independent contributor.

The researchers reviewed the records of consecutive patients who underwent outpatient echocardiography at the Cleveland Clinic and its satellite facilities between 1996 and 2005. They identified 36,261 patients (65,696 echocardiographic tests) who had normal ejection fractions signaling preserved systolic function.

The mean patient age was 58 years, and slightly more than half of the study subjects were women. The subjects were typical of patients usually referred for echocardiography – they frequently had cardiovascular risk factors such as dyslipidemia (35%), hypertension (15%), and diabetes (12%), but usually did not have established CV disease, such as congestive heart failure (4%), peripheral vascular disease (1%), or coronary artery disease (0.6%).

The most frequent indications for ordering the echocardiography were symptom assessment, assessment of ventricular or valvular function, evaluation of suspected or known CAD, and assessment of arrhythmia or ECG abnormalities.

The prevalence of diastolic dysfunction was high, at 65%. The dysfunction was mild in the majority of patients (nearly 60%), moderate in 4.8%, and severe in 0.4%.

During an average follow-up of 6 years, there were 5,789 deaths. Unadjusted all-cause mortality was higher with any degree of diastolic dysfunction than with normal diastolic function: 21% with mild diastolic dysfunction, 24% with moderate diastolic dysfunction, and 39% with severe diastolic dysfunction, compared with 7% in patients who had normal diastolic function.

However, because comorbidities that could confound the analyses were more common among patients with more severe diastolic dysfunction, propensity matching and statistical controlling for comorbidities were performed. Subsequent analysis showed that only moderate and severe diastolic dysfunction raised mortality risk.

Eight-year survival estimates were 78% for patients with normal diastolic function and 72% for mild diastolic dysfunction, compared with 68% for moderate diastolic dysfunction and 58% for severe diastolic dysfunction.

"For the first time, to our knowledge, moderate and severe diastolic dysfunction have been shown to be independent predictors of mortality rate," Dr. Halley and her associates said.

The mechanisms by which diastolic dysfunction raises mortality are not yet known, nor is it known whether therapies targeting such dysfunction can be developed, or whether they would reduce mortality. "However, our results suggest that an increased awareness of the clinical significance of advanced diastolic dysfunction may lead to earlier identification of those patients who are at risk, especially at a preclinical stage," the investigators noted.

They added that this study was limited in that it was retrospective and involved only a single institution.

This new study provides "an important piece of the puzzle," shedding light on the continuum from mild and asymptomatic to severe and symptomatic diastolic dysfunction, said Dr. Ileana L. Piña in remarks taken from her invited commentary that accompanied Dr. Halley’s report (Arch. Intern. Med. 2011;171:1088-9).

The findings that diastolic dysfunction is so common – affecting 65% of this study cohort – and that physicians must be alert to the prognostic value of more severe dysfunction are "novel and important for physicians."

In the future, it will be critical to elucidate the missing link between diagnosis of diastolic dysfunction on echocardiography and the later presentation of older patients, particularly older women, with acute decompensated heart failure in which systolic function is preserved, Dr. Piña of the departments of epidemiology and biostatistics at Case Western Reserve University, Cleveland, added.

One of Dr. Halley’s associates reported ties to GE Healthcare, Philips Healthcare, and Siemens AG. Dr. Piña reported no financial disclosures.

Moderate and severe diastolic dysfunction in patients who have normal systolic function increased all-cause mortality, according to a report in the June 27 issue of the Archives of Internal Medicine.

Such diastolic dysfunction is usually preclinical and often is identified on outpatient echocardiography that was done to assess nonspecific symptoms, ventricular or valvular function, arrhythmia, or ECG abnormalities. Its clinical significance has not been documented until now, said Dr. Carmel M. Halley of the Heart and Vascular Institute at the Cleveland Clinic, and her associates.

"Because the use of echocardiography as a clinical tool in the outpatient setting continues to increase ... our study provides the physician with a prognostic context when diastolic dysfunction is reported, especially because most procedures are requested by noncardiologists," the researchers noted (Arch. Intern. Med. 2011;171:1082-7).

Dr. Halley and her colleagues examined diastolic dysfunction in the absence of systolic dysfunction, because the clinical relevance of the condition has been questioned. Many medical disorders associated with diastolic dysfunction, such as hypertension, coronary artery disease, obesity, and diabetes, are themselves predictors of increased mortality, so it was unclear whether diastolic dysfunction was an independent contributor.

The researchers reviewed the records of consecutive patients who underwent outpatient echocardiography at the Cleveland Clinic and its satellite facilities between 1996 and 2005. They identified 36,261 patients (65,696 echocardiographic tests) who had normal ejection fractions signaling preserved systolic function.

The mean patient age was 58 years, and slightly more than half of the study subjects were women. The subjects were typical of patients usually referred for echocardiography – they frequently had cardiovascular risk factors such as dyslipidemia (35%), hypertension (15%), and diabetes (12%), but usually did not have established CV disease, such as congestive heart failure (4%), peripheral vascular disease (1%), or coronary artery disease (0.6%).

The most frequent indications for ordering the echocardiography were symptom assessment, assessment of ventricular or valvular function, evaluation of suspected or known CAD, and assessment of arrhythmia or ECG abnormalities.

The prevalence of diastolic dysfunction was high, at 65%. The dysfunction was mild in the majority of patients (nearly 60%), moderate in 4.8%, and severe in 0.4%.

During an average follow-up of 6 years, there were 5,789 deaths. Unadjusted all-cause mortality was higher with any degree of diastolic dysfunction than with normal diastolic function: 21% with mild diastolic dysfunction, 24% with moderate diastolic dysfunction, and 39% with severe diastolic dysfunction, compared with 7% in patients who had normal diastolic function.

However, because comorbidities that could confound the analyses were more common among patients with more severe diastolic dysfunction, propensity matching and statistical controlling for comorbidities were performed. Subsequent analysis showed that only moderate and severe diastolic dysfunction raised mortality risk.

Eight-year survival estimates were 78% for patients with normal diastolic function and 72% for mild diastolic dysfunction, compared with 68% for moderate diastolic dysfunction and 58% for severe diastolic dysfunction.

"For the first time, to our knowledge, moderate and severe diastolic dysfunction have been shown to be independent predictors of mortality rate," Dr. Halley and her associates said.

The mechanisms by which diastolic dysfunction raises mortality are not yet known, nor is it known whether therapies targeting such dysfunction can be developed, or whether they would reduce mortality. "However, our results suggest that an increased awareness of the clinical significance of advanced diastolic dysfunction may lead to earlier identification of those patients who are at risk, especially at a preclinical stage," the investigators noted.

They added that this study was limited in that it was retrospective and involved only a single institution.

This new study provides "an important piece of the puzzle," shedding light on the continuum from mild and asymptomatic to severe and symptomatic diastolic dysfunction, said Dr. Ileana L. Piña in remarks taken from her invited commentary that accompanied Dr. Halley’s report (Arch. Intern. Med. 2011;171:1088-9).

The findings that diastolic dysfunction is so common – affecting 65% of this study cohort – and that physicians must be alert to the prognostic value of more severe dysfunction are "novel and important for physicians."

In the future, it will be critical to elucidate the missing link between diagnosis of diastolic dysfunction on echocardiography and the later presentation of older patients, particularly older women, with acute decompensated heart failure in which systolic function is preserved, Dr. Piña of the departments of epidemiology and biostatistics at Case Western Reserve University, Cleveland, added.

One of Dr. Halley’s associates reported ties to GE Healthcare, Philips Healthcare, and Siemens AG. Dr. Piña reported no financial disclosures.

Moderate and severe diastolic dysfunction in patients who have normal systolic function increased all-cause mortality, according to a report in the June 27 issue of the Archives of Internal Medicine.

Such diastolic dysfunction is usually preclinical and often is identified on outpatient echocardiography that was done to assess nonspecific symptoms, ventricular or valvular function, arrhythmia, or ECG abnormalities. Its clinical significance has not been documented until now, said Dr. Carmel M. Halley of the Heart and Vascular Institute at the Cleveland Clinic, and her associates.

"Because the use of echocardiography as a clinical tool in the outpatient setting continues to increase ... our study provides the physician with a prognostic context when diastolic dysfunction is reported, especially because most procedures are requested by noncardiologists," the researchers noted (Arch. Intern. Med. 2011;171:1082-7).

Dr. Halley and her colleagues examined diastolic dysfunction in the absence of systolic dysfunction, because the clinical relevance of the condition has been questioned. Many medical disorders associated with diastolic dysfunction, such as hypertension, coronary artery disease, obesity, and diabetes, are themselves predictors of increased mortality, so it was unclear whether diastolic dysfunction was an independent contributor.

The researchers reviewed the records of consecutive patients who underwent outpatient echocardiography at the Cleveland Clinic and its satellite facilities between 1996 and 2005. They identified 36,261 patients (65,696 echocardiographic tests) who had normal ejection fractions signaling preserved systolic function.

The mean patient age was 58 years, and slightly more than half of the study subjects were women. The subjects were typical of patients usually referred for echocardiography – they frequently had cardiovascular risk factors such as dyslipidemia (35%), hypertension (15%), and diabetes (12%), but usually did not have established CV disease, such as congestive heart failure (4%), peripheral vascular disease (1%), or coronary artery disease (0.6%).

The most frequent indications for ordering the echocardiography were symptom assessment, assessment of ventricular or valvular function, evaluation of suspected or known CAD, and assessment of arrhythmia or ECG abnormalities.

The prevalence of diastolic dysfunction was high, at 65%. The dysfunction was mild in the majority of patients (nearly 60%), moderate in 4.8%, and severe in 0.4%.

During an average follow-up of 6 years, there were 5,789 deaths. Unadjusted all-cause mortality was higher with any degree of diastolic dysfunction than with normal diastolic function: 21% with mild diastolic dysfunction, 24% with moderate diastolic dysfunction, and 39% with severe diastolic dysfunction, compared with 7% in patients who had normal diastolic function.

However, because comorbidities that could confound the analyses were more common among patients with more severe diastolic dysfunction, propensity matching and statistical controlling for comorbidities were performed. Subsequent analysis showed that only moderate and severe diastolic dysfunction raised mortality risk.

Eight-year survival estimates were 78% for patients with normal diastolic function and 72% for mild diastolic dysfunction, compared with 68% for moderate diastolic dysfunction and 58% for severe diastolic dysfunction.

"For the first time, to our knowledge, moderate and severe diastolic dysfunction have been shown to be independent predictors of mortality rate," Dr. Halley and her associates said.

The mechanisms by which diastolic dysfunction raises mortality are not yet known, nor is it known whether therapies targeting such dysfunction can be developed, or whether they would reduce mortality. "However, our results suggest that an increased awareness of the clinical significance of advanced diastolic dysfunction may lead to earlier identification of those patients who are at risk, especially at a preclinical stage," the investigators noted.

They added that this study was limited in that it was retrospective and involved only a single institution.

This new study provides "an important piece of the puzzle," shedding light on the continuum from mild and asymptomatic to severe and symptomatic diastolic dysfunction, said Dr. Ileana L. Piña in remarks taken from her invited commentary that accompanied Dr. Halley’s report (Arch. Intern. Med. 2011;171:1088-9).

The findings that diastolic dysfunction is so common – affecting 65% of this study cohort – and that physicians must be alert to the prognostic value of more severe dysfunction are "novel and important for physicians."

In the future, it will be critical to elucidate the missing link between diagnosis of diastolic dysfunction on echocardiography and the later presentation of older patients, particularly older women, with acute decompensated heart failure in which systolic function is preserved, Dr. Piña of the departments of epidemiology and biostatistics at Case Western Reserve University, Cleveland, added.

One of Dr. Halley’s associates reported ties to GE Healthcare, Philips Healthcare, and Siemens AG. Dr. Piña reported no financial disclosures.

SAN DIEGO – Heart transplant recipients who develop circulating antibodies to human tissues in the first year post transplantation are at heightened risk for poor outcomes and may therefore need closer monitoring, suggests a prospective observational study.

One in seven of the patients studied developed circulating antibodies that specifically targeted human leukocyte antigens on donor tissue, and one in three developed nonspecific antibodies, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Relative to their counterparts who did not develop any antibodies, patients who developed either type were more likely to experience both antibody-mediated and cellular rejection. In addition, those developing the donor-specific type were more likely to experience cardiac allograft vasculopathy and to die.

"Patients with donor-specific antibodies or nonspecific antibodies may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes," commented lead investigator Dr. Jignesh Patel, co–medical director of the heart transplant program at the Cedars-Sinai Heart Institute in Los Angeles. "Further studies are needed to determine the optimum therapy for these patients."

He acknowledged that the issue is complicated, because some patients with donor-specific antibodies (DSA) never experienced rejection, yet others with nonspecific antibodies did. These outcomes suggest that the nature of the antibodies is key. As a result, it is tricky to manage patients who develop antibodies but don’t have any symptoms of rejection.

At his institution, Dr. Patel said, clinicians don’t step up the number of biopsies performed to monitor for rejection in heart transplant recipients who develop antibodies unless they become symptomatic. However, they are cautious about long-term management of immunosuppression. "We will think twice about weaning them off prednisone," he noted. "More likely, we are kind of tending to switch them to a proliferation signaling inhibitor earlier when we see donor-specific antibodies."

Dr. Patel and his coinvestigators studied 144 patients who underwent heart transplantation in 2003-2010 and had serial antibody monitoring by solid-phase assays at baseline (the time of transplantation) and at 1, 3, 6, 9, and 12 months, at minimum.

"More recently introduced methods using solid-phase matrices coated with HLA antigens have demonstrated the ability to detect and identify HLA antibodies with high sensitivity and accuracy," he said.

Because the study period preceded the guidelines that recommended antibody monitoring, these patients were being followed more closely than usual out of concern that they were at heightened risk for antibody development, he said.

On average, the patients had seven antibody measurements during their first year post transplantation.

Study results showed that in the first year after transplantation, 14% of patients developed DSA and 32% developed non–donor-specific antibodies (non-DSA), while the rest did not develop any.

The mean age (approximately 53 years) was similar across groups. Relative to those who did not develop any antibodies, patients who developed non-DSA were more likely to be female (54% vs. 22%). Also, ischemic time was shorter for patients who developed DSA (183 minutes) or non-DSA (195 minutes) than for their counterparts who did not develop any antibodies (230 minutes).

The three groups of patients were generally similar with respect to immunosuppressive therapy at baseline, including receipt of calcineurin inhibitors and antiproliferative agents.

But the group developing DSA was significantly less likely than the group not developing antibodies to be weaned off prednisone (7% vs. 46%), and both the DSA and non-DSA groups were more likely than their counterparts with no antibodies to have received induction therapy (45% and 39% vs. 15%).

The 1-year rate of freedom from antibody-mediated rejection was poorer for patients who developed DSA (65%) or non-DSA (76%), compared with their peers who developed no antibodies (94%). The findings were similar with respect to rates of freedom from acute cellular rejection (80% and 87% vs. 99%, respectively).

The temporal patterns did differ somewhat according to type of rejection, according to Dr. Patel.

"With regard to cellular rejection, it appeared that a lot of events in the patients who developed donor-specific antibodies occurred toward the end of the first year, in comparison to the patients who developed antibody-mediated rejection, where most of the events tended to occur early" post transplant, he observed.

Relative to their counterparts who did not develop antibodies, the patients who developed DSA also had significantly poorer 3-year rates of survival (65% vs. 85%) and freedom from cardiac allograft vasculopathy, which was defined as the development of vascular stenosis exceeding 30% (70% vs. 88%).

Dr. Patel reported that he had no conflicts of interest related to the study.

SAN DIEGO – Heart transplant recipients who develop circulating antibodies to human tissues in the first year post transplantation are at heightened risk for poor outcomes and may therefore need closer monitoring, suggests a prospective observational study.

One in seven of the patients studied developed circulating antibodies that specifically targeted human leukocyte antigens on donor tissue, and one in three developed nonspecific antibodies, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Relative to their counterparts who did not develop any antibodies, patients who developed either type were more likely to experience both antibody-mediated and cellular rejection. In addition, those developing the donor-specific type were more likely to experience cardiac allograft vasculopathy and to die.

"Patients with donor-specific antibodies or nonspecific antibodies may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes," commented lead investigator Dr. Jignesh Patel, co–medical director of the heart transplant program at the Cedars-Sinai Heart Institute in Los Angeles. "Further studies are needed to determine the optimum therapy for these patients."

He acknowledged that the issue is complicated, because some patients with donor-specific antibodies (DSA) never experienced rejection, yet others with nonspecific antibodies did. These outcomes suggest that the nature of the antibodies is key. As a result, it is tricky to manage patients who develop antibodies but don’t have any symptoms of rejection.

At his institution, Dr. Patel said, clinicians don’t step up the number of biopsies performed to monitor for rejection in heart transplant recipients who develop antibodies unless they become symptomatic. However, they are cautious about long-term management of immunosuppression. "We will think twice about weaning them off prednisone," he noted. "More likely, we are kind of tending to switch them to a proliferation signaling inhibitor earlier when we see donor-specific antibodies."

Dr. Patel and his coinvestigators studied 144 patients who underwent heart transplantation in 2003-2010 and had serial antibody monitoring by solid-phase assays at baseline (the time of transplantation) and at 1, 3, 6, 9, and 12 months, at minimum.

"More recently introduced methods using solid-phase matrices coated with HLA antigens have demonstrated the ability to detect and identify HLA antibodies with high sensitivity and accuracy," he said.

Because the study period preceded the guidelines that recommended antibody monitoring, these patients were being followed more closely than usual out of concern that they were at heightened risk for antibody development, he said.

On average, the patients had seven antibody measurements during their first year post transplantation.

Study results showed that in the first year after transplantation, 14% of patients developed DSA and 32% developed non–donor-specific antibodies (non-DSA), while the rest did not develop any.

The mean age (approximately 53 years) was similar across groups. Relative to those who did not develop any antibodies, patients who developed non-DSA were more likely to be female (54% vs. 22%). Also, ischemic time was shorter for patients who developed DSA (183 minutes) or non-DSA (195 minutes) than for their counterparts who did not develop any antibodies (230 minutes).

The three groups of patients were generally similar with respect to immunosuppressive therapy at baseline, including receipt of calcineurin inhibitors and antiproliferative agents.

But the group developing DSA was significantly less likely than the group not developing antibodies to be weaned off prednisone (7% vs. 46%), and both the DSA and non-DSA groups were more likely than their counterparts with no antibodies to have received induction therapy (45% and 39% vs. 15%).

The 1-year rate of freedom from antibody-mediated rejection was poorer for patients who developed DSA (65%) or non-DSA (76%), compared with their peers who developed no antibodies (94%). The findings were similar with respect to rates of freedom from acute cellular rejection (80% and 87% vs. 99%, respectively).

The temporal patterns did differ somewhat according to type of rejection, according to Dr. Patel.

"With regard to cellular rejection, it appeared that a lot of events in the patients who developed donor-specific antibodies occurred toward the end of the first year, in comparison to the patients who developed antibody-mediated rejection, where most of the events tended to occur early" post transplant, he observed.

Relative to their counterparts who did not develop antibodies, the patients who developed DSA also had significantly poorer 3-year rates of survival (65% vs. 85%) and freedom from cardiac allograft vasculopathy, which was defined as the development of vascular stenosis exceeding 30% (70% vs. 88%).

Dr. Patel reported that he had no conflicts of interest related to the study.

SAN DIEGO – Heart transplant recipients who develop circulating antibodies to human tissues in the first year post transplantation are at heightened risk for poor outcomes and may therefore need closer monitoring, suggests a prospective observational study.

One in seven of the patients studied developed circulating antibodies that specifically targeted human leukocyte antigens on donor tissue, and one in three developed nonspecific antibodies, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Relative to their counterparts who did not develop any antibodies, patients who developed either type were more likely to experience both antibody-mediated and cellular rejection. In addition, those developing the donor-specific type were more likely to experience cardiac allograft vasculopathy and to die.

"Patients with donor-specific antibodies or nonspecific antibodies may require more intensive monitoring and augmented immunosuppression to improve their long-term outcomes," commented lead investigator Dr. Jignesh Patel, co–medical director of the heart transplant program at the Cedars-Sinai Heart Institute in Los Angeles. "Further studies are needed to determine the optimum therapy for these patients."

He acknowledged that the issue is complicated, because some patients with donor-specific antibodies (DSA) never experienced rejection, yet others with nonspecific antibodies did. These outcomes suggest that the nature of the antibodies is key. As a result, it is tricky to manage patients who develop antibodies but don’t have any symptoms of rejection.

At his institution, Dr. Patel said, clinicians don’t step up the number of biopsies performed to monitor for rejection in heart transplant recipients who develop antibodies unless they become symptomatic. However, they are cautious about long-term management of immunosuppression. "We will think twice about weaning them off prednisone," he noted. "More likely, we are kind of tending to switch them to a proliferation signaling inhibitor earlier when we see donor-specific antibodies."

Dr. Patel and his coinvestigators studied 144 patients who underwent heart transplantation in 2003-2010 and had serial antibody monitoring by solid-phase assays at baseline (the time of transplantation) and at 1, 3, 6, 9, and 12 months, at minimum.

"More recently introduced methods using solid-phase matrices coated with HLA antigens have demonstrated the ability to detect and identify HLA antibodies with high sensitivity and accuracy," he said.

Because the study period preceded the guidelines that recommended antibody monitoring, these patients were being followed more closely than usual out of concern that they were at heightened risk for antibody development, he said.

On average, the patients had seven antibody measurements during their first year post transplantation.

Study results showed that in the first year after transplantation, 14% of patients developed DSA and 32% developed non–donor-specific antibodies (non-DSA), while the rest did not develop any.

The mean age (approximately 53 years) was similar across groups. Relative to those who did not develop any antibodies, patients who developed non-DSA were more likely to be female (54% vs. 22%). Also, ischemic time was shorter for patients who developed DSA (183 minutes) or non-DSA (195 minutes) than for their counterparts who did not develop any antibodies (230 minutes).

The three groups of patients were generally similar with respect to immunosuppressive therapy at baseline, including receipt of calcineurin inhibitors and antiproliferative agents.

But the group developing DSA was significantly less likely than the group not developing antibodies to be weaned off prednisone (7% vs. 46%), and both the DSA and non-DSA groups were more likely than their counterparts with no antibodies to have received induction therapy (45% and 39% vs. 15%).

The 1-year rate of freedom from antibody-mediated rejection was poorer for patients who developed DSA (65%) or non-DSA (76%), compared with their peers who developed no antibodies (94%). The findings were similar with respect to rates of freedom from acute cellular rejection (80% and 87% vs. 99%, respectively).

The temporal patterns did differ somewhat according to type of rejection, according to Dr. Patel.

"With regard to cellular rejection, it appeared that a lot of events in the patients who developed donor-specific antibodies occurred toward the end of the first year, in comparison to the patients who developed antibody-mediated rejection, where most of the events tended to occur early" post transplant, he observed.

Relative to their counterparts who did not develop antibodies, the patients who developed DSA also had significantly poorer 3-year rates of survival (65% vs. 85%) and freedom from cardiac allograft vasculopathy, which was defined as the development of vascular stenosis exceeding 30% (70% vs. 88%).

Dr. Patel reported that he had no conflicts of interest related to the study.

SAN DIEGO – For men undergoing heart transplantation, the sex of their donor may mean the difference between life and death, according to a pair of large retrospective cohort studies

The studies, which were reported at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), each analyzed data from more than 60,000 recipients over periods spanning several decades.

Their conclusion: Men were more likely to die if they received a heart from a female donor vs. a male donor, with the elevation in risk largely resulting from excess deaths in the first year. Overall mortality was 13% higher for these men after potential confounders were taken into account.

In contrast, women undergoing heart transplantation had a similar risk of death regardless of whether their donor was male or female.

A possible explanation for the higher risk of death in men with female donors, according to Dr. Ingo Kaczmarek, a cardiac surgeon at the Transplantation Center Munich of Ludwig-Maximilians University of Munich and the lead investigator of one of the studies, is that women’s hearts are smaller than men’s, even given the same body height and weight (J. Am. Coll. Cardiol. 2002;39:1055-60).

Additionally, medication nonadherence may play a part. "In our population ... I can tell you that females take their medication and males don’t," he said. "And that might be a big confounder that you can’t measure."

Although her study took donor characteristics into account, it is still possible that the smaller size of female hearts played a role, agreed Dr. Kiran K. Khush, lead investigator of the other study. "But I think there are probably also some immunological processes involved and sex differences that we don’t completely understand," she added.

This new information helps explain why some patients fare better than others after heart transplantation, but it would not necessarily alter her practice, said Dr. Khush, a cardiologist and instructor in cardiovascular medicine at Stanford (Calif.) University.

"I would worry about it clinically, but I’m not sure that would preclude me from accepting a female graft for a male recipient, because – as we all know – when you have a very sick recipient who is in imminent danger of dying, you just want to have a heart for that patient," she commented.

However, she added, perhaps given a situation wherein several highest-priority patients on the waiting list were otherwise similar, sex matching might be something to consider.

Dr. Khush and her colleagues analyzed data from the ISHLT database, the largest repository of heart transplant outcomes, for the years 1990-2008, restricting analyses to 60,584 adult recipients having at least 2 years of follow-up post transplantation.

"The ISHLT database pulls data from a lot of different transplant centers worldwide," she noted, including ones in North America, Europe, Australia, and New Zealand, among others. "So this really represents a truly international experience."

Fully 79% of the heart transplant recipients were men. On average, the men were 52 years old and the women were 49 years old at the time of transplantation.

Men’s odds of acute rejection within 2 years of transplantation were higher if their donor was female vs. male before adjustment for more than a dozen potential confounders (odds ratio, 1.22), although not afterward. Women’s odds of this outcome did not differ by the sex of their donor.

The donor’s sex did not affect the likelihood of cardiac allograft vasculopathy for either group before adjustment. But afterward, men actually had a lower risk of this outcome if their donor was female (OR, 0.77).

Here, Dr. Khush sounded a note of caution about the variability in assessing and defining vasculopathy across centers. "Some use angiography, some use IVUS [intravascular ultrasound], maybe some use clinical suspicion," she explained, and disease extent is often not documented. "So I think this is a really hard end point to interpret because the definition is so vague."

But there is no gray area when it comes to defining death, she noted, and results showed that men were more likely to die after transplantation if their donor was female vs. male, both before statistical adjustment (hazard ratio, 1.18) and afterward (HR, 1.13). The donor’s sex had no influence on this outcome among women.

Temporal patterns, assessed with follow-up out to 20 years, suggested that the poorer survival of men who were given a female heart was largely because of increased mortality in the first year post transplantation.

Men also had a higher risk of graft failure resulting in death or retransplantation (after censoring for death from other causes) if their donor was female (HR, 1.17).

A study caveat was that the numbers of patients were limited for several of the outcomes because of missing data, acknowledged Dr. Khush. "It is very difficult to account for center-specific differences – for example, differences in patient populations and management practices," she further noted. And unknown confounders could have influenced the findings.

Dr. Kaczmarek and his coinvestigators similarly analyzed data from the ISHLT database, but for a wider range of years (1980-2009). Their analyses were based on 67,833 heart transplant recipients.

Overall, 80% were men. On average, the men were 53 years old and the women were 51 years old. One-quarter of men received a female donor heart, and slightly fewer than one-half of women received a male donor heart.

The 15-year survival rate was best for women who were given a female heart and worst for men who were given a female heart. "The curves divide in the first year," Dr. Kaczmarek pointed out. "In the long run, they seem to be parallel, but women with female hearts do a bit better."

The 1-year rate of survival ranged from a low of 78% among men who were given a female heart to a high of 84% among men who were given a male heart. "This [latter] effect lasts for a few years, and then the better combination is female donor, female recipient," he said.

When patients who died in the first year post transplantation were excluded, the survival curves diverged gradually over time, but still arrived at the same final pattern, with long-term survival best for women who were given a female heart and worst for men who were given a female heart.

"We have seen that acute rejection contributes to that effect," Dr. Kaczmarek commented. "Acute rejection [rates] are a bit higher in male recipients who receive female donor hearts."

Results were similar when the investigators focused just on the subgroup of patients from their own institution in Munich.

"I want to carefully conclude that the combination of male recipient, female donor carries a higher risk for early mortality, whereas other gender constellations yield similar outcomes," said Dr. Kaczmarek.

"In the long-term follow-up, female recipients reveal superior results, especially the combination of female recipient and female donor," he concluded.

Dr. Khush reported having no conflicts of interest related to the research. Dr. Kaczmarek reported receiving travel or research grants from Novartis, Astellas, Roche, Orion Pharma, and Berlin Heart.

SAN DIEGO – For men undergoing heart transplantation, the sex of their donor may mean the difference between life and death, according to a pair of large retrospective cohort studies

The studies, which were reported at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), each analyzed data from more than 60,000 recipients over periods spanning several decades.

Their conclusion: Men were more likely to die if they received a heart from a female donor vs. a male donor, with the elevation in risk largely resulting from excess deaths in the first year. Overall mortality was 13% higher for these men after potential confounders were taken into account.

In contrast, women undergoing heart transplantation had a similar risk of death regardless of whether their donor was male or female.

A possible explanation for the higher risk of death in men with female donors, according to Dr. Ingo Kaczmarek, a cardiac surgeon at the Transplantation Center Munich of Ludwig-Maximilians University of Munich and the lead investigator of one of the studies, is that women’s hearts are smaller than men’s, even given the same body height and weight (J. Am. Coll. Cardiol. 2002;39:1055-60).

Additionally, medication nonadherence may play a part. "In our population ... I can tell you that females take their medication and males don’t," he said. "And that might be a big confounder that you can’t measure."

Although her study took donor characteristics into account, it is still possible that the smaller size of female hearts played a role, agreed Dr. Kiran K. Khush, lead investigator of the other study. "But I think there are probably also some immunological processes involved and sex differences that we don’t completely understand," she added.

This new information helps explain why some patients fare better than others after heart transplantation, but it would not necessarily alter her practice, said Dr. Khush, a cardiologist and instructor in cardiovascular medicine at Stanford (Calif.) University.

"I would worry about it clinically, but I’m not sure that would preclude me from accepting a female graft for a male recipient, because – as we all know – when you have a very sick recipient who is in imminent danger of dying, you just want to have a heart for that patient," she commented.

However, she added, perhaps given a situation wherein several highest-priority patients on the waiting list were otherwise similar, sex matching might be something to consider.

Dr. Khush and her colleagues analyzed data from the ISHLT database, the largest repository of heart transplant outcomes, for the years 1990-2008, restricting analyses to 60,584 adult recipients having at least 2 years of follow-up post transplantation.

"The ISHLT database pulls data from a lot of different transplant centers worldwide," she noted, including ones in North America, Europe, Australia, and New Zealand, among others. "So this really represents a truly international experience."

Fully 79% of the heart transplant recipients were men. On average, the men were 52 years old and the women were 49 years old at the time of transplantation.

Men’s odds of acute rejection within 2 years of transplantation were higher if their donor was female vs. male before adjustment for more than a dozen potential confounders (odds ratio, 1.22), although not afterward. Women’s odds of this outcome did not differ by the sex of their donor.

The donor’s sex did not affect the likelihood of cardiac allograft vasculopathy for either group before adjustment. But afterward, men actually had a lower risk of this outcome if their donor was female (OR, 0.77).

Here, Dr. Khush sounded a note of caution about the variability in assessing and defining vasculopathy across centers. "Some use angiography, some use IVUS [intravascular ultrasound], maybe some use clinical suspicion," she explained, and disease extent is often not documented. "So I think this is a really hard end point to interpret because the definition is so vague."

But there is no gray area when it comes to defining death, she noted, and results showed that men were more likely to die after transplantation if their donor was female vs. male, both before statistical adjustment (hazard ratio, 1.18) and afterward (HR, 1.13). The donor’s sex had no influence on this outcome among women.

Temporal patterns, assessed with follow-up out to 20 years, suggested that the poorer survival of men who were given a female heart was largely because of increased mortality in the first year post transplantation.

Men also had a higher risk of graft failure resulting in death or retransplantation (after censoring for death from other causes) if their donor was female (HR, 1.17).

A study caveat was that the numbers of patients were limited for several of the outcomes because of missing data, acknowledged Dr. Khush. "It is very difficult to account for center-specific differences – for example, differences in patient populations and management practices," she further noted. And unknown confounders could have influenced the findings.

Dr. Kaczmarek and his coinvestigators similarly analyzed data from the ISHLT database, but for a wider range of years (1980-2009). Their analyses were based on 67,833 heart transplant recipients.

Overall, 80% were men. On average, the men were 53 years old and the women were 51 years old. One-quarter of men received a female donor heart, and slightly fewer than one-half of women received a male donor heart.

The 15-year survival rate was best for women who were given a female heart and worst for men who were given a female heart. "The curves divide in the first year," Dr. Kaczmarek pointed out. "In the long run, they seem to be parallel, but women with female hearts do a bit better."

The 1-year rate of survival ranged from a low of 78% among men who were given a female heart to a high of 84% among men who were given a male heart. "This [latter] effect lasts for a few years, and then the better combination is female donor, female recipient," he said.

When patients who died in the first year post transplantation were excluded, the survival curves diverged gradually over time, but still arrived at the same final pattern, with long-term survival best for women who were given a female heart and worst for men who were given a female heart.

"We have seen that acute rejection contributes to that effect," Dr. Kaczmarek commented. "Acute rejection [rates] are a bit higher in male recipients who receive female donor hearts."

Results were similar when the investigators focused just on the subgroup of patients from their own institution in Munich.

"I want to carefully conclude that the combination of male recipient, female donor carries a higher risk for early mortality, whereas other gender constellations yield similar outcomes," said Dr. Kaczmarek.

"In the long-term follow-up, female recipients reveal superior results, especially the combination of female recipient and female donor," he concluded.

Dr. Khush reported having no conflicts of interest related to the research. Dr. Kaczmarek reported receiving travel or research grants from Novartis, Astellas, Roche, Orion Pharma, and Berlin Heart.

SAN DIEGO – For men undergoing heart transplantation, the sex of their donor may mean the difference between life and death, according to a pair of large retrospective cohort studies

The studies, which were reported at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), each analyzed data from more than 60,000 recipients over periods spanning several decades.

Their conclusion: Men were more likely to die if they received a heart from a female donor vs. a male donor, with the elevation in risk largely resulting from excess deaths in the first year. Overall mortality was 13% higher for these men after potential confounders were taken into account.

In contrast, women undergoing heart transplantation had a similar risk of death regardless of whether their donor was male or female.

A possible explanation for the higher risk of death in men with female donors, according to Dr. Ingo Kaczmarek, a cardiac surgeon at the Transplantation Center Munich of Ludwig-Maximilians University of Munich and the lead investigator of one of the studies, is that women’s hearts are smaller than men’s, even given the same body height and weight (J. Am. Coll. Cardiol. 2002;39:1055-60).

Additionally, medication nonadherence may play a part. "In our population ... I can tell you that females take their medication and males don’t," he said. "And that might be a big confounder that you can’t measure."

Although her study took donor characteristics into account, it is still possible that the smaller size of female hearts played a role, agreed Dr. Kiran K. Khush, lead investigator of the other study. "But I think there are probably also some immunological processes involved and sex differences that we don’t completely understand," she added.

This new information helps explain why some patients fare better than others after heart transplantation, but it would not necessarily alter her practice, said Dr. Khush, a cardiologist and instructor in cardiovascular medicine at Stanford (Calif.) University.

"I would worry about it clinically, but I’m not sure that would preclude me from accepting a female graft for a male recipient, because – as we all know – when you have a very sick recipient who is in imminent danger of dying, you just want to have a heart for that patient," she commented.

However, she added, perhaps given a situation wherein several highest-priority patients on the waiting list were otherwise similar, sex matching might be something to consider.

Dr. Khush and her colleagues analyzed data from the ISHLT database, the largest repository of heart transplant outcomes, for the years 1990-2008, restricting analyses to 60,584 adult recipients having at least 2 years of follow-up post transplantation.

"The ISHLT database pulls data from a lot of different transplant centers worldwide," she noted, including ones in North America, Europe, Australia, and New Zealand, among others. "So this really represents a truly international experience."

Fully 79% of the heart transplant recipients were men. On average, the men were 52 years old and the women were 49 years old at the time of transplantation.

Men’s odds of acute rejection within 2 years of transplantation were higher if their donor was female vs. male before adjustment for more than a dozen potential confounders (odds ratio, 1.22), although not afterward. Women’s odds of this outcome did not differ by the sex of their donor.

The donor’s sex did not affect the likelihood of cardiac allograft vasculopathy for either group before adjustment. But afterward, men actually had a lower risk of this outcome if their donor was female (OR, 0.77).

Here, Dr. Khush sounded a note of caution about the variability in assessing and defining vasculopathy across centers. "Some use angiography, some use IVUS [intravascular ultrasound], maybe some use clinical suspicion," she explained, and disease extent is often not documented. "So I think this is a really hard end point to interpret because the definition is so vague."

But there is no gray area when it comes to defining death, she noted, and results showed that men were more likely to die after transplantation if their donor was female vs. male, both before statistical adjustment (hazard ratio, 1.18) and afterward (HR, 1.13). The donor’s sex had no influence on this outcome among women.

Temporal patterns, assessed with follow-up out to 20 years, suggested that the poorer survival of men who were given a female heart was largely because of increased mortality in the first year post transplantation.

Men also had a higher risk of graft failure resulting in death or retransplantation (after censoring for death from other causes) if their donor was female (HR, 1.17).

A study caveat was that the numbers of patients were limited for several of the outcomes because of missing data, acknowledged Dr. Khush. "It is very difficult to account for center-specific differences – for example, differences in patient populations and management practices," she further noted. And unknown confounders could have influenced the findings.

Dr. Kaczmarek and his coinvestigators similarly analyzed data from the ISHLT database, but for a wider range of years (1980-2009). Their analyses were based on 67,833 heart transplant recipients.

Overall, 80% were men. On average, the men were 53 years old and the women were 51 years old. One-quarter of men received a female donor heart, and slightly fewer than one-half of women received a male donor heart.

The 15-year survival rate was best for women who were given a female heart and worst for men who were given a female heart. "The curves divide in the first year," Dr. Kaczmarek pointed out. "In the long run, they seem to be parallel, but women with female hearts do a bit better."

The 1-year rate of survival ranged from a low of 78% among men who were given a female heart to a high of 84% among men who were given a male heart. "This [latter] effect lasts for a few years, and then the better combination is female donor, female recipient," he said.

When patients who died in the first year post transplantation were excluded, the survival curves diverged gradually over time, but still arrived at the same final pattern, with long-term survival best for women who were given a female heart and worst for men who were given a female heart.

"We have seen that acute rejection contributes to that effect," Dr. Kaczmarek commented. "Acute rejection [rates] are a bit higher in male recipients who receive female donor hearts."

Results were similar when the investigators focused just on the subgroup of patients from their own institution in Munich.

"I want to carefully conclude that the combination of male recipient, female donor carries a higher risk for early mortality, whereas other gender constellations yield similar outcomes," said Dr. Kaczmarek.

"In the long-term follow-up, female recipients reveal superior results, especially the combination of female recipient and female donor," he concluded.

Dr. Khush reported having no conflicts of interest related to the research. Dr. Kaczmarek reported receiving travel or research grants from Novartis, Astellas, Roche, Orion Pharma, and Berlin Heart.

SAN DIEGO – Cardiac transplant recipients who are given hearts from donors with left ventricular hypertrophy are not at increased risk of death, Dr. Omar Wever Pinzon reported at the annual meeting of the International Society for Heart and Lung Transplantation.

In a retrospective nationwide study of more than 2,500 adults who underwent cardiac transplantation during a recent 4-year period, nearly half of the donor hearts had LVH, although it was mild in most cases.

Recipients who had been given hearts with LVH did not have poorer survival overall than did their counterparts who had been given hearts without this high-risk characteristic. But getting a heart with LVH did reduce survival if, in addition, the donor was older than 55 years or the graft had a longer ischemic time.

"Overall survival of recipients of donor hearts with LVH is similar to those without LVH, which indicates that the current donor selection and allocation algorithms successfully mitigate the risk that donor LVH could pose to recipient survival," Dr. Pinzon said. However, "the combination of donor LVH with certain other high-risk characteristics can result in excess mortality."

Because few donor hearts had moderate or severe LVH, "I think we have to be very cautious" when using those hearts, he added. "But I would say [hearts having an interventricular septum and posterior wall thickness] up to 1.3 cm may be safe in the absence of other high-risk characteristics."

The scarcity of donor hearts – coupled with growing knowledge about the impact of various donor characteristics on recipient outcomes – has led to strategies to make more hearts available for transplantation, according to Dr. Pinzon.

"Thanks to these strategies, patients with left ventricular hypertrophy, considered a high-risk characteristic, are more likely now to become donors," he commented. However, some studies have raised concerns that such hearts are more susceptible to ischemic graft injury, which could translate into poorer outcomes for the recipients.

Using data from the United Network for Organ Sharing and the Organ Procurement and Transplantation Network, the investigators studied 2,626 adult patients who underwent a first, single-organ heart transplantation in 2006-2010.

On the basis of the thickness of the interventricular septum and posterior wall, donor hearts were classified as having no LVH (less than 1.1 cm) or LVH that was mild (1.1-1.3 cm), moderate (1.4-1.6 cm), or severe (1.7 cm or greater).

Study results showed that the transplant recipients were 52 years old on average, and 78% were men. The donors were 33 years old on average, and 72% were men.

Fully 44% of the donor hearts had some degree of LVH, reported Dr. Pinzon, who is a heart failure/transplant fellow with the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City. The LVH was mild in most cases (38%) but occasionally moderate (5%) or severe (1%).

Relative to their peers who had been given donor hearts without LVH, recipients who had been given donor hearts with LVH had a higher body mass index and a higher ratio of donor-to-recipient BMI, had been on the waiting list for a shorter time, and were marginally more likely to have a graft ischemic time exceeding 4 hours.

During a follow-up period of 3.3 years post transplantation, 13% of the recipients died or – rarely – underwent retransplantation.

In univariate and multivariate analyses, neither recipients of donor hearts with mild LVH nor recipients of donor hearts with moderate or severe LVH were more likely to die than their counterparts whose donor hearts did not have any LVH, Dr. Pinzon reported.

However, recipients’ risk of death increased with the age of their donor (hazard ratio, 1.01) and with their own serum creatinine level (HR, 1.31) and mean pulmonary artery pressure (HR, 1.01).

Also, they were more likely to die if their donor had used tobacco (HR, 1.32), or if they themselves were older than 55 years of age (HR, 1.30) or had been on extracorporeal membrane oxygenation support (HR, 6.0).

Further analyses revealed an interaction between donor heart LVH and donor age. Among recipients whose donor was older than 55 years, those getting a heart with any LVH had roughly six times the risk of death (P = .01). But there was no such association among recipients whose donors were younger.

There was also an interaction between donor heart LVH and graft ischemic time. Among recipients whose graft had an ischemic time of 4 hours or longer, those receiving a heart with moderate or severe LVH had twice the risk of death (P = .04). There was no such association among recipients whose graft ischemic time was shorter.

The presence of LVH in a donor heart does not adversely affect the survival of transplant recipients, concluded Dr. Pinzon.

But "organ selection and allocation is not a random process," and transplantation involving hearts with moderate or severe LVH was rare. "This indicates that these patients were carefully selected, which can bias our results," he cautioned; therefore, the safety of using such hearts remains uncertain.

Dr. Pinzon reported that he had no relevant conflicts of interest.

SAN DIEGO – Cardiac transplant recipients who are given hearts from donors with left ventricular hypertrophy are not at increased risk of death, Dr. Omar Wever Pinzon reported at the annual meeting of the International Society for Heart and Lung Transplantation.

In a retrospective nationwide study of more than 2,500 adults who underwent cardiac transplantation during a recent 4-year period, nearly half of the donor hearts had LVH, although it was mild in most cases.

Recipients who had been given hearts with LVH did not have poorer survival overall than did their counterparts who had been given hearts without this high-risk characteristic. But getting a heart with LVH did reduce survival if, in addition, the donor was older than 55 years or the graft had a longer ischemic time.

"Overall survival of recipients of donor hearts with LVH is similar to those without LVH, which indicates that the current donor selection and allocation algorithms successfully mitigate the risk that donor LVH could pose to recipient survival," Dr. Pinzon said. However, "the combination of donor LVH with certain other high-risk characteristics can result in excess mortality."

Because few donor hearts had moderate or severe LVH, "I think we have to be very cautious" when using those hearts, he added. "But I would say [hearts having an interventricular septum and posterior wall thickness] up to 1.3 cm may be safe in the absence of other high-risk characteristics."

The scarcity of donor hearts – coupled with growing knowledge about the impact of various donor characteristics on recipient outcomes – has led to strategies to make more hearts available for transplantation, according to Dr. Pinzon.

"Thanks to these strategies, patients with left ventricular hypertrophy, considered a high-risk characteristic, are more likely now to become donors," he commented. However, some studies have raised concerns that such hearts are more susceptible to ischemic graft injury, which could translate into poorer outcomes for the recipients.

Using data from the United Network for Organ Sharing and the Organ Procurement and Transplantation Network, the investigators studied 2,626 adult patients who underwent a first, single-organ heart transplantation in 2006-2010.

On the basis of the thickness of the interventricular septum and posterior wall, donor hearts were classified as having no LVH (less than 1.1 cm) or LVH that was mild (1.1-1.3 cm), moderate (1.4-1.6 cm), or severe (1.7 cm or greater).

Study results showed that the transplant recipients were 52 years old on average, and 78% were men. The donors were 33 years old on average, and 72% were men.

Fully 44% of the donor hearts had some degree of LVH, reported Dr. Pinzon, who is a heart failure/transplant fellow with the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City. The LVH was mild in most cases (38%) but occasionally moderate (5%) or severe (1%).

Relative to their peers who had been given donor hearts without LVH, recipients who had been given donor hearts with LVH had a higher body mass index and a higher ratio of donor-to-recipient BMI, had been on the waiting list for a shorter time, and were marginally more likely to have a graft ischemic time exceeding 4 hours.

During a follow-up period of 3.3 years post transplantation, 13% of the recipients died or – rarely – underwent retransplantation.

In univariate and multivariate analyses, neither recipients of donor hearts with mild LVH nor recipients of donor hearts with moderate or severe LVH were more likely to die than their counterparts whose donor hearts did not have any LVH, Dr. Pinzon reported.

However, recipients’ risk of death increased with the age of their donor (hazard ratio, 1.01) and with their own serum creatinine level (HR, 1.31) and mean pulmonary artery pressure (HR, 1.01).

Also, they were more likely to die if their donor had used tobacco (HR, 1.32), or if they themselves were older than 55 years of age (HR, 1.30) or had been on extracorporeal membrane oxygenation support (HR, 6.0).

Further analyses revealed an interaction between donor heart LVH and donor age. Among recipients whose donor was older than 55 years, those getting a heart with any LVH had roughly six times the risk of death (P = .01). But there was no such association among recipients whose donors were younger.

There was also an interaction between donor heart LVH and graft ischemic time. Among recipients whose graft had an ischemic time of 4 hours or longer, those receiving a heart with moderate or severe LVH had twice the risk of death (P = .04). There was no such association among recipients whose graft ischemic time was shorter.

The presence of LVH in a donor heart does not adversely affect the survival of transplant recipients, concluded Dr. Pinzon.

But "organ selection and allocation is not a random process," and transplantation involving hearts with moderate or severe LVH was rare. "This indicates that these patients were carefully selected, which can bias our results," he cautioned; therefore, the safety of using such hearts remains uncertain.

Dr. Pinzon reported that he had no relevant conflicts of interest.

SAN DIEGO – Cardiac transplant recipients who are given hearts from donors with left ventricular hypertrophy are not at increased risk of death, Dr. Omar Wever Pinzon reported at the annual meeting of the International Society for Heart and Lung Transplantation.

In a retrospective nationwide study of more than 2,500 adults who underwent cardiac transplantation during a recent 4-year period, nearly half of the donor hearts had LVH, although it was mild in most cases.

Recipients who had been given hearts with LVH did not have poorer survival overall than did their counterparts who had been given hearts without this high-risk characteristic. But getting a heart with LVH did reduce survival if, in addition, the donor was older than 55 years or the graft had a longer ischemic time.

"Overall survival of recipients of donor hearts with LVH is similar to those without LVH, which indicates that the current donor selection and allocation algorithms successfully mitigate the risk that donor LVH could pose to recipient survival," Dr. Pinzon said. However, "the combination of donor LVH with certain other high-risk characteristics can result in excess mortality."

Because few donor hearts had moderate or severe LVH, "I think we have to be very cautious" when using those hearts, he added. "But I would say [hearts having an interventricular septum and posterior wall thickness] up to 1.3 cm may be safe in the absence of other high-risk characteristics."

The scarcity of donor hearts – coupled with growing knowledge about the impact of various donor characteristics on recipient outcomes – has led to strategies to make more hearts available for transplantation, according to Dr. Pinzon.

"Thanks to these strategies, patients with left ventricular hypertrophy, considered a high-risk characteristic, are more likely now to become donors," he commented. However, some studies have raised concerns that such hearts are more susceptible to ischemic graft injury, which could translate into poorer outcomes for the recipients.

Using data from the United Network for Organ Sharing and the Organ Procurement and Transplantation Network, the investigators studied 2,626 adult patients who underwent a first, single-organ heart transplantation in 2006-2010.

On the basis of the thickness of the interventricular septum and posterior wall, donor hearts were classified as having no LVH (less than 1.1 cm) or LVH that was mild (1.1-1.3 cm), moderate (1.4-1.6 cm), or severe (1.7 cm or greater).

Study results showed that the transplant recipients were 52 years old on average, and 78% were men. The donors were 33 years old on average, and 72% were men.

Fully 44% of the donor hearts had some degree of LVH, reported Dr. Pinzon, who is a heart failure/transplant fellow with the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City. The LVH was mild in most cases (38%) but occasionally moderate (5%) or severe (1%).

Relative to their peers who had been given donor hearts without LVH, recipients who had been given donor hearts with LVH had a higher body mass index and a higher ratio of donor-to-recipient BMI, had been on the waiting list for a shorter time, and were marginally more likely to have a graft ischemic time exceeding 4 hours.

During a follow-up period of 3.3 years post transplantation, 13% of the recipients died or – rarely – underwent retransplantation.

In univariate and multivariate analyses, neither recipients of donor hearts with mild LVH nor recipients of donor hearts with moderate or severe LVH were more likely to die than their counterparts whose donor hearts did not have any LVH, Dr. Pinzon reported.

However, recipients’ risk of death increased with the age of their donor (hazard ratio, 1.01) and with their own serum creatinine level (HR, 1.31) and mean pulmonary artery pressure (HR, 1.01).

Also, they were more likely to die if their donor had used tobacco (HR, 1.32), or if they themselves were older than 55 years of age (HR, 1.30) or had been on extracorporeal membrane oxygenation support (HR, 6.0).

Further analyses revealed an interaction between donor heart LVH and donor age. Among recipients whose donor was older than 55 years, those getting a heart with any LVH had roughly six times the risk of death (P = .01). But there was no such association among recipients whose donors were younger.

There was also an interaction between donor heart LVH and graft ischemic time. Among recipients whose graft had an ischemic time of 4 hours or longer, those receiving a heart with moderate or severe LVH had twice the risk of death (P = .04). There was no such association among recipients whose graft ischemic time was shorter.

The presence of LVH in a donor heart does not adversely affect the survival of transplant recipients, concluded Dr. Pinzon.

But "organ selection and allocation is not a random process," and transplantation involving hearts with moderate or severe LVH was rare. "This indicates that these patients were carefully selected, which can bias our results," he cautioned; therefore, the safety of using such hearts remains uncertain.

Dr. Pinzon reported that he had no relevant conflicts of interest.