International Society for Heart and Lung Transplantation (ISHLT): Annual Meeting

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).

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 – 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.

SAN DIEGO – Transplantation physicians may be increasingly avoiding the use of hearts from donors who have high-risk characteristics, even as demand for transplantable hearts continues to outstrip supply, suggests a retrospective study of more than 42,000 heart transplant recipients.

The percentages of transplanted hearts from donors who have characteristics that are associated with an elevated risk of poor outcomes for the recipient (such as older age or hypertension) initially increased during the recent 2-decade study period. But thereafter, they plateaued or fell – in some cases to levels seen at the start of the period.

There are two possible explanations for the declining use of hearts from high-risk donors, lead investigator Dr. Jose N. Nativi told attendees of the annual meeting of the International Society for Heart and Lung Transplantation.

"One hypothesis is that there is a concern about adverse outcomes" for recipients who would be given these hearts, in the wake of publications describing actual experience with their use, he explained.

"The second hypothesis is that, probably, we have another option to offer these patients, that is, the increasing utilization of left ventricular assist devices," Dr. Nativi said. "So for a patient who is critically ill, instead of offering them a high-risk donor, now we have the luxury in some centers to offer them an alternative, that is, mechanical support."

There have been several key milestones in efforts to make more organs available for transplantation in the United States, according to Dr. Nativi, a fellow in cardiology with the University of Utah and the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City.

The Crystal City Conference in 2001 resulted in a formal recommendation to expand the use of hearts from high-risk donors (Circulation 2002;106:836-41). And the Organ Donation Breakthrough Collaborative in 2003 encouraged increased consent and donation by people with high-risk features (Crit. Care Nurs. Q. 2008;31:190-210).

"These efforts are resulting in the expansion of acceptable donor criteria toward high-risk donors," he said. "But the high-risk donor still remains a matter of controversy."

In the year after the collaborative, there was an increase in the number of all types of organs donated – with the sole exception of hearts. "So we are still struggling to find donors for heart recipients," Dr. Nativi commented.

To assess temporal patterns in the use of hearts from high-risk donors, the investigators analyzed data from the U.S. Scientific Registry of Transplant Recipients, identifying adult patients who underwent single-organ heart transplantation in 1987-2009.

They were divided into three eras by transplantation date: era 1 (1987-1996), when standard donor criteria were used; era 2 (1997-2003), when there was increasing acceptance of the high-risk donor, and reports about the use of organs from such donors increased; and era 3 (2004-2009), after the collaborative was established.

Results were based on 42,023 patients who underwent transplantation during the study period (42% in era 1, 32% in era 2, and 26% in era 3), Dr. Nativi reported.

In multivariate analyses that included more than 40 donor characteristics as well as a transplant center’s patient volume, recipients were more likely to die in the first year post transplantation if their donor was older than 40 years of age (hazard ratio, 1.2), was female (HR, 1.2), had a cerebrovascular cause of death (HR, 1.6), or had a history of hypertension (HR,1.3).

Temporal trends showed a biphasic pattern for three of these high-risk characteristics, with the percentage of hearts having the characteristic increasing significantly between era 1 and era 2, but then decreasing significantly between era 2 and era 3.

For example, the percentage of hearts from donors older than 40 years averaged 21%, 30%, and 28% in eras 1, 2, and 3, respectively. The pattern was similar for hearts from donors who were female (29%, 31%, and 27%) and those having a cerebrovascular cause of death (26%, 29%, and 23%).

The percentage of hearts from donors having hypertension increased from 4% to 11% between eras 1 and 2, and again from 11% to 13% between eras 2 and 3. But in clinical terms, the latter change was really more of a plateau, according to Dr. Nativi.

He acknowledged that factors other than physicians’ decision to avoid the use of hearts from high-risk donors may have contributed to the observed trends. For example, "changes in donor characteristics may have been affected by a potentially changing donor pool," but that possibility is more difficult to study, he said.

Dr. Nativi reported that he had no relevant financial disclosures.

SAN DIEGO – Transplantation physicians may be increasingly avoiding the use of hearts from donors who have high-risk characteristics, even as demand for transplantable hearts continues to outstrip supply, suggests a retrospective study of more than 42,000 heart transplant recipients.

The percentages of transplanted hearts from donors who have characteristics that are associated with an elevated risk of poor outcomes for the recipient (such as older age or hypertension) initially increased during the recent 2-decade study period. But thereafter, they plateaued or fell – in some cases to levels seen at the start of the period.

There are two possible explanations for the declining use of hearts from high-risk donors, lead investigator Dr. Jose N. Nativi told attendees of the annual meeting of the International Society for Heart and Lung Transplantation.

"One hypothesis is that there is a concern about adverse outcomes" for recipients who would be given these hearts, in the wake of publications describing actual experience with their use, he explained.

"The second hypothesis is that, probably, we have another option to offer these patients, that is, the increasing utilization of left ventricular assist devices," Dr. Nativi said. "So for a patient who is critically ill, instead of offering them a high-risk donor, now we have the luxury in some centers to offer them an alternative, that is, mechanical support."

There have been several key milestones in efforts to make more organs available for transplantation in the United States, according to Dr. Nativi, a fellow in cardiology with the University of Utah and the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City.

The Crystal City Conference in 2001 resulted in a formal recommendation to expand the use of hearts from high-risk donors (Circulation 2002;106:836-41). And the Organ Donation Breakthrough Collaborative in 2003 encouraged increased consent and donation by people with high-risk features (Crit. Care Nurs. Q. 2008;31:190-210).

"These efforts are resulting in the expansion of acceptable donor criteria toward high-risk donors," he said. "But the high-risk donor still remains a matter of controversy."

In the year after the collaborative, there was an increase in the number of all types of organs donated – with the sole exception of hearts. "So we are still struggling to find donors for heart recipients," Dr. Nativi commented.

To assess temporal patterns in the use of hearts from high-risk donors, the investigators analyzed data from the U.S. Scientific Registry of Transplant Recipients, identifying adult patients who underwent single-organ heart transplantation in 1987-2009.

They were divided into three eras by transplantation date: era 1 (1987-1996), when standard donor criteria were used; era 2 (1997-2003), when there was increasing acceptance of the high-risk donor, and reports about the use of organs from such donors increased; and era 3 (2004-2009), after the collaborative was established.

Results were based on 42,023 patients who underwent transplantation during the study period (42% in era 1, 32% in era 2, and 26% in era 3), Dr. Nativi reported.

In multivariate analyses that included more than 40 donor characteristics as well as a transplant center’s patient volume, recipients were more likely to die in the first year post transplantation if their donor was older than 40 years of age (hazard ratio, 1.2), was female (HR, 1.2), had a cerebrovascular cause of death (HR, 1.6), or had a history of hypertension (HR,1.3).

Temporal trends showed a biphasic pattern for three of these high-risk characteristics, with the percentage of hearts having the characteristic increasing significantly between era 1 and era 2, but then decreasing significantly between era 2 and era 3.

For example, the percentage of hearts from donors older than 40 years averaged 21%, 30%, and 28% in eras 1, 2, and 3, respectively. The pattern was similar for hearts from donors who were female (29%, 31%, and 27%) and those having a cerebrovascular cause of death (26%, 29%, and 23%).

The percentage of hearts from donors having hypertension increased from 4% to 11% between eras 1 and 2, and again from 11% to 13% between eras 2 and 3. But in clinical terms, the latter change was really more of a plateau, according to Dr. Nativi.

He acknowledged that factors other than physicians’ decision to avoid the use of hearts from high-risk donors may have contributed to the observed trends. For example, "changes in donor characteristics may have been affected by a potentially changing donor pool," but that possibility is more difficult to study, he said.

Dr. Nativi reported that he had no relevant financial disclosures.

SAN DIEGO – Transplantation physicians may be increasingly avoiding the use of hearts from donors who have high-risk characteristics, even as demand for transplantable hearts continues to outstrip supply, suggests a retrospective study of more than 42,000 heart transplant recipients.

The percentages of transplanted hearts from donors who have characteristics that are associated with an elevated risk of poor outcomes for the recipient (such as older age or hypertension) initially increased during the recent 2-decade study period. But thereafter, they plateaued or fell – in some cases to levels seen at the start of the period.

There are two possible explanations for the declining use of hearts from high-risk donors, lead investigator Dr. Jose N. Nativi told attendees of the annual meeting of the International Society for Heart and Lung Transplantation.

"One hypothesis is that there is a concern about adverse outcomes" for recipients who would be given these hearts, in the wake of publications describing actual experience with their use, he explained.

"The second hypothesis is that, probably, we have another option to offer these patients, that is, the increasing utilization of left ventricular assist devices," Dr. Nativi said. "So for a patient who is critically ill, instead of offering them a high-risk donor, now we have the luxury in some centers to offer them an alternative, that is, mechanical support."

There have been several key milestones in efforts to make more organs available for transplantation in the United States, according to Dr. Nativi, a fellow in cardiology with the University of Utah and the UTAH (Utah Transplantation Affiliated Hospitals) Cardiac Transplant Program in Salt Lake City.

The Crystal City Conference in 2001 resulted in a formal recommendation to expand the use of hearts from high-risk donors (Circulation 2002;106:836-41). And the Organ Donation Breakthrough Collaborative in 2003 encouraged increased consent and donation by people with high-risk features (Crit. Care Nurs. Q. 2008;31:190-210).

"These efforts are resulting in the expansion of acceptable donor criteria toward high-risk donors," he said. "But the high-risk donor still remains a matter of controversy."

In the year after the collaborative, there was an increase in the number of all types of organs donated – with the sole exception of hearts. "So we are still struggling to find donors for heart recipients," Dr. Nativi commented.

To assess temporal patterns in the use of hearts from high-risk donors, the investigators analyzed data from the U.S. Scientific Registry of Transplant Recipients, identifying adult patients who underwent single-organ heart transplantation in 1987-2009.

They were divided into three eras by transplantation date: era 1 (1987-1996), when standard donor criteria were used; era 2 (1997-2003), when there was increasing acceptance of the high-risk donor, and reports about the use of organs from such donors increased; and era 3 (2004-2009), after the collaborative was established.

Results were based on 42,023 patients who underwent transplantation during the study period (42% in era 1, 32% in era 2, and 26% in era 3), Dr. Nativi reported.

In multivariate analyses that included more than 40 donor characteristics as well as a transplant center’s patient volume, recipients were more likely to die in the first year post transplantation if their donor was older than 40 years of age (hazard ratio, 1.2), was female (HR, 1.2), had a cerebrovascular cause of death (HR, 1.6), or had a history of hypertension (HR,1.3).

Temporal trends showed a biphasic pattern for three of these high-risk characteristics, with the percentage of hearts having the characteristic increasing significantly between era 1 and era 2, but then decreasing significantly between era 2 and era 3.

For example, the percentage of hearts from donors older than 40 years averaged 21%, 30%, and 28% in eras 1, 2, and 3, respectively. The pattern was similar for hearts from donors who were female (29%, 31%, and 27%) and those having a cerebrovascular cause of death (26%, 29%, and 23%).

The percentage of hearts from donors having hypertension increased from 4% to 11% between eras 1 and 2, and again from 11% to 13% between eras 2 and 3. But in clinical terms, the latter change was really more of a plateau, according to Dr. Nativi.

He acknowledged that factors other than physicians’ decision to avoid the use of hearts from high-risk donors may have contributed to the observed trends. For example, "changes in donor characteristics may have been affected by a potentially changing donor pool," but that possibility is more difficult to study, he said.

Dr. Nativi reported that he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

SAN DIEGO – Heart transplant recipients in their 70s have outcomes that are generally similar to those of their counterparts in their 60s, new data show.

In a retrospective study of 18,534 wait-listed older adults, the rates of posttransplantation complications in septuagenarians were much the same as those in sexagenarians, except that the former were in fact less likely to experience rejection.

And on average, the septuagenarians lived roughly 8 years after getting their new heart, which is not much shorter than the 9.8 years seen in sexagenarians, according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

"Selected septuagenarians – and I underscore the word selected – with advanced heart failure derive great benefit from heart transplantation," said lead investigator Dr. Daniel Goldstein. "This is not every 70-year-old [who is] going to walk into your office."

The findings raise the thorny ethical issue of expanding age limits on eligibility for heart transplantation, as organs are scarce and every heart given to an older adult is one that is not given to a young person, he noted.

One approach would be to limit transplantation to those septuagenarians who have the best risk profile. Another would be to use an alternative list, as first tested by the University of California, Los Angeles, whereby older recipients are given hearts that are typically rejected by transplant centers.

"I don’t see being able to do this without having an alternative list situation. UCLA is the perfect model," asserted Dr. Goldstein, a cardiothoracic surgeon at the Montefiore Einstein Center for Heart and Vascular Care at Montefiore Medical Center in the Bronx, N.Y. "It would be hard to get an 18-year-old donor and give the heart to a 70-year-old, but if you take in a heart that nobody else wants, I think it’s a little more palatable."

With the aging of the population and the epidemic of heart failure among older adults, this dilemma is likely to intensify, he noted.

Centers generally use an age cutoff of 65 years for cardiac transplantation eligibility. But an informal survey of centers in the New York City and New Jersey areas suggests that "there is great variability in who we think is too old for transplantation," he said. "It’s clear that more centers are doing away with chronological age criteria."

In the study, the investigators analyzed data from the UNOS (United Network for Organ Sharing) database for the years 1987-2010, first looking at trends among 18,534 adults aged 60 years or older put on the waiting list for a primary, single-organ heart transplantation.

Results showed that "in the current era, septuagenarians are being transplanted more frequently, without a doubt," Dr. Goldstein reported. The number undergoing transplantation increased almost every year, and their median age was 71 years.

For age-group comparisons, the investigators restricted analyses to the years 1998-2010, a period when the data became robust and contemporary medical and surgical practices were in use, he explained.

Relative to the 5,807 sexagenarians who underwent transplantation during this period, the 332 septuagenarians who did were generally similar in terms of a wide range of comorbidities and risk factors, with a few exceptions.

Patients in the older group were more likely to be male and nondiabetic and, in terms of acuity, were less likely to be on a ventricular assist device and more likely to have the lower status 2 priority at transplantation.

With respect to recipient-donor matching, the septuagenarians were more likely to have a donor who was not an identical ABO match and who died from intracranial hemorrhage. Also, their donors were older.

In findings that Dr. Goldstein called "quite eye opening," there were no differences between septuagenarians and sexagenarians in most posttransplantation complications (rejection during hospitalization, stroke, length of hospital stay, and receipt of a pacemaker) or in cause of death. The former were less likely to be treated for graft rejection in the first year (19% vs. 32%).

In a multivariate analysis, an age of 70 years or older was a significant risk factor for death (hazard ratio, 1.29). And relative to sexagenarians, septuagenarians had both shorter unadjusted median survival (8.5 vs. 9.8 years) and predicted median adjusted survival (8.15 vs. 9.83 years), although most of the difference between groups appeared to result from a difference in the first year.

"I was rather surprised" by the 8-year value for the septuagenarians. "That’s a very important number," commented Dr. Goldstein. "While survival is comparatively reduced, it still exceeds by a lot what we currently see with mechanical support therapy."

In a final analysis that was restricted to patients who survived the first year post transplantation, patients aged 70 years or older no longer had an increased risk of death, compared with their counterparts aged 60-69 years.

Dr. Goldstein said he had no relevant financial disclosures.

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, researchers reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Moreover, this benefit was achieved without any increase in the rate of in-hospital mortality among 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 [in the United States] since the change in allocation algorithm in 2006," said lead investigator Dr. Tajinder P. 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. "By granting the hearts to sicker people, you are taking care of that point of view, too."

An attendee asked whether patterns might differ at the local or regional level vs. the national level, given that some centers in the New York City area, for example, feel they have been hurt by the new algorithm. Dr. Singh replied that because of small patient numbers and regional variations, it was not possible to get a reliable picture at those levels.

"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 goal of such a change was to lower national [waiting list] mortality without a concurrent increase in posttransplant mortality, and that consideration is more than theoretical because sicker patients will be at higher risk of dying post transplant," he explained. "The early outcome trends after the allocation change have been supportive, but regional analyses have questioned the merits of the new allocation."

The investigators studied all patients aged 18 years or older who were placed on the waiting list for primary heart transplantation between July 1, 2004, and June 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 their counterparts in era 1 to die or worsen while on the wait list (hazard ratio, 0.86; P = .005). And this benefit was evident among 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; P = .001). The 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 their counterparts in era 1, era 2 transplant recipients had a shorter median wait time before receiving a heart (55 vs. 63 days; P less than .001) and were more likely to be status 1A at transplantation (48% vs. 37%; P less than .001).

The donor ischemic time was longer for recipients in era 2 (3.3 vs. 3.2 hours; P = .02), but the small difference was probably not clinically important, according to Dr. Singh.

The lack of a greater difference in ischemic time – despite the sharing of organs over larger geographic areas in the latter era – was not surprising, he said. "The way it occurred, it went from local to within 500 miles, say. It may be broader regional sharing, but it’s not long distance to get to [the heart] and bring the heart in to the surgery."

There was no rise in the rate of in-hospital mortality post transplantation with implementation of the new algorithm. In fact, "interestingly, in-hospital mortality was lower rather than higher [in era 2], even though sicker patients were getting transplanted," Dr. Singh commented, with a rate of 5.3% in era 2, compared with 6.3% in era 1.

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, researchers reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Moreover, this benefit was achieved without any increase in the rate of in-hospital mortality among 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 [in the United States] since the change in allocation algorithm in 2006," said lead investigator Dr. Tajinder P. 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. "By granting the hearts to sicker people, you are taking care of that point of view, too."

An attendee asked whether patterns might differ at the local or regional level vs. the national level, given that some centers in the New York City area, for example, feel they have been hurt by the new algorithm. Dr. Singh replied that because of small patient numbers and regional variations, it was not possible to get a reliable picture at those levels.

"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 goal of such a change was to lower national [waiting list] mortality without a concurrent increase in posttransplant mortality, and that consideration is more than theoretical because sicker patients will be at higher risk of dying post transplant," he explained. "The early outcome trends after the allocation change have been supportive, but regional analyses have questioned the merits of the new allocation."

The investigators studied all patients aged 18 years or older who were placed on the waiting list for primary heart transplantation between July 1, 2004, and June 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 their counterparts in era 1 to die or worsen while on the wait list (hazard ratio, 0.86; P = .005). And this benefit was evident among 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; P = .001). The 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 their counterparts in era 1, era 2 transplant recipients had a shorter median wait time before receiving a heart (55 vs. 63 days; P less than .001) and were more likely to be status 1A at transplantation (48% vs. 37%; P less than .001).

The donor ischemic time was longer for recipients in era 2 (3.3 vs. 3.2 hours; P = .02), but the small difference was probably not clinically important, according to Dr. Singh.

The lack of a greater difference in ischemic time – despite the sharing of organs over larger geographic areas in the latter era – was not surprising, he said. "The way it occurred, it went from local to within 500 miles, say. It may be broader regional sharing, but it’s not long distance to get to [the heart] and bring the heart in to the surgery."

There was no rise in the rate of in-hospital mortality post transplantation with implementation of the new algorithm. In fact, "interestingly, in-hospital mortality was lower rather than higher [in era 2], even though sicker patients were getting transplanted," Dr. Singh commented, with a rate of 5.3% in era 2, compared with 6.3% in era 1.

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, researchers reported at the annual meeting of the International Society for Heart and Lung Transplantation.

Moreover, this benefit was achieved without any increase in the rate of in-hospital mortality among 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 [in the United States] since the change in allocation algorithm in 2006," said lead investigator Dr. Tajinder P. 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. "By granting the hearts to sicker people, you are taking care of that point of view, too."

An attendee asked whether patterns might differ at the local or regional level vs. the national level, given that some centers in the New York City area, for example, feel they have been hurt by the new algorithm. Dr. Singh replied that because of small patient numbers and regional variations, it was not possible to get a reliable picture at those levels.

"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 goal of such a change was to lower national [waiting list] mortality without a concurrent increase in posttransplant mortality, and that consideration is more than theoretical because sicker patients will be at higher risk of dying post transplant," he explained. "The early outcome trends after the allocation change have been supportive, but regional analyses have questioned the merits of the new allocation."

The investigators studied all patients aged 18 years or older who were placed on the waiting list for primary heart transplantation between July 1, 2004, and June 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 their counterparts in era 1 to die or worsen while on the wait list (hazard ratio, 0.86; P = .005). And this benefit was evident among 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; P = .001). The 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 their counterparts in era 1, era 2 transplant recipients had a shorter median wait time before receiving a heart (55 vs. 63 days; P less than .001) and were more likely to be status 1A at transplantation (48% vs. 37%; P less than .001).

The donor ischemic time was longer for recipients in era 2 (3.3 vs. 3.2 hours; P = .02), but the small difference was probably not clinically important, according to Dr. Singh.

The lack of a greater difference in ischemic time – despite the sharing of organs over larger geographic areas in the latter era – was not surprising, he said. "The way it occurred, it went from local to within 500 miles, say. It may be broader regional sharing, but it’s not long distance to get to [the heart] and bring the heart in to the surgery."

There was no rise in the rate of in-hospital mortality post transplantation with implementation of the new algorithm. In fact, "interestingly, in-hospital mortality was lower rather than higher [in era 2], even though sicker patients were getting transplanted," Dr. Singh commented, with a rate of 5.3% in era 2, compared with 6.3% in era 1.

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