Heart Failure

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.

NEW ORLEANS – Patients with chronic cardiomyopathy can be successfully weaned from ventricular assist devices, and certain parameters can predict long-term cardiac stability after explantation, according to German investigators.

"Unloading-promoted reversal of heart failure allows for long-term transplant-free outcomes after patients are removed from VADs. However, few patients with chronic cardiomyopathy have been weaned from VADs, and the majority only recently," said principal investigator Dr. Michael Dandel of the German Heart Institute Berlin. "The long-term outcomes of patients, therefore, and the reliability of criteria for making weaning decisions, are not well known."

At his clinic, 91 patients with chronic cardiomyopathy (CCM) as the underlying cause of heart failure were weaned from VADs between 1995 and 2010, including 75 weaned from left ventricular assist devices, 13 weaned from biventricular assist devices, and 3 weaned from right ventricular assist devices. Before VAD implantation, the patients had left ventricular ejection fraction (LVEF) values of 10%-20%.

These patients were evaluated as to the feasibility of weaning and to establish criteria that could predict long-term cardiac stability after VAD removal. "With this information, we can improve future weaning decisions and postweaning patient management," Dr. Dandel said at the annual meeting of the American College of Cardiology.

A total of 47 patients were evaluated. Of these 41 (87.2%) had idiopathic cardiomyopathy, 4 (8.5%) had histologic evidence of chronic myocarditis before VAD implantation, and 2 (4.3%) had chronic ischemic cardiomyopathy with severe left ventricular dilation.

Before VAD insertion, all patients had irreversible end-stage heart failure and required continuous positive inotropic support. No attempts were made to use VADs electively with the aim of myocardial recovery only, he said.

Postweaning results. Cardiac stability lasting at least 15 years was achieved by 2 patients, while 10 patients have been stable at least 10 years and 3 at least 5 years, he reported.

"At 5 years, only five patients, 10.6%, had died due to heart failure recurrence or weaning-related complications. Several patients died of other causes," he said.

Postweaning freedom from heart failure recurrence for all evaluated patients was 74% at 3 years and 66% at 5 years, but these results included nine patients at very high risk for poor outcomes. After 2002, when the investigators tightened their criteria for weaning, freedom from heart failure recurrence reached 100% at 3 years, he noted.

Pre-explantation variables predictive of outcomes. "Echo data obtained during ‘off pump’ trials proved to be reliable for detection of recovery during mechanical unloading," Dr. Dandel said. "In particular, off-pump [left ventricle] size, geometry, and ejection fraction were predictive of outcome after weaning, especially when history of heart failure was also considered."

For cardiac stability lasting at least 5 years, pre-explantation "off pump" LVEF of 50% or more was associated with a positive predictive value of 91.7%, while LVEF of 45% or more had a positive predictive value of 79.1%.

The positive predictive value of LVEF of 45% or more was approximately 90% if additional parameters were considered: pre-explantation left ventricle size and geometry, stability of unloading-induced cardiac improvement before VAD removal, and heart failure duration before VAD implantation.

Time to cardiac recovery seemed important, Dr. Dandel said. "Patients who had recurrences needed more time to show an improvement. They needed twice the duration of VAD support as patients who did not have a recurrence," he said.

"Definite cutoff values for certain parameters – including tissue Doppler-derived LV wall motion velocity – allowed us to formulate weaning criteria with high predictability for postweaning stability," he said.

Risk factors for heart failure recurrence. Dr. Dandel and his colleagues also identified several risk factors that predicted heart failure recurrence during the first 3 years after VAD removal. These factors, and their associated probability for recurrence, were:

• Preweaning off-pump LVEF less than 45% plus history of heart failure longer than 5 years (100%).

• Preweaning LVEF less than 45% (88.9%).

• Preweaning off-pump LVEF less than 50% plus left ventricular internal diastolic diameter greater than 55 mm (90%).

• Pre-explantation LVEF less than 50% and preexisting alteration of greater than 10% best value (87.5%).

• LVEF less than 50% plus relative wall thickness decrease of less than 10% during final off-pump trial (83.3%).

Of these, he emphasized the importance of the final off-pump trial values. "An off-pump ejection fraction less than 45% in patients with a history of heart failure for more than 5 years is an absolute contraindication for VAD removal," he noted. "All such patients in our study had a recurrence of heart failure."

Early instability of ejection fraction and unstable geometry also confer a high probability of recurrence. "A wall thickness increase by more than 10% means the reverse in modeling is not stable enough," he added.

"The notion that we can actually wean patients from VADs is still a fairly new concept, and the European experience is larger than that of the United States. This is still a field that is wide open for determining patient selection and predictors of outcome after VAD removal," session moderator Dr. Gregory A. Ewald, medical director of heart transplantation at Barnes-Jewish Hospital, St. Louis, said in an interview.

"Clearly, the echocardiographic appearance of the heart on and off support is a good predictor," Dr. Ewald said, but he noted that nonechocardiographic factors such as exercise tolerance were not studied. He also noted that the field has moved to continuous-flow pumps rather than pulsatile pumps, which constituted much of the German experience. It remains to be determined if the same parameters are completely applicable to the newer-generation devices.

Dr. Dandel and Dr. Ewald reported having no relevant conflicts of interest.

NEW ORLEANS – Patients with chronic cardiomyopathy can be successfully weaned from ventricular assist devices, and certain parameters can predict long-term cardiac stability after explantation, according to German investigators.

"Unloading-promoted reversal of heart failure allows for long-term transplant-free outcomes after patients are removed from VADs. However, few patients with chronic cardiomyopathy have been weaned from VADs, and the majority only recently," said principal investigator Dr. Michael Dandel of the German Heart Institute Berlin. "The long-term outcomes of patients, therefore, and the reliability of criteria for making weaning decisions, are not well known."

At his clinic, 91 patients with chronic cardiomyopathy (CCM) as the underlying cause of heart failure were weaned from VADs between 1995 and 2010, including 75 weaned from left ventricular assist devices, 13 weaned from biventricular assist devices, and 3 weaned from right ventricular assist devices. Before VAD implantation, the patients had left ventricular ejection fraction (LVEF) values of 10%-20%.

These patients were evaluated as to the feasibility of weaning and to establish criteria that could predict long-term cardiac stability after VAD removal. "With this information, we can improve future weaning decisions and postweaning patient management," Dr. Dandel said at the annual meeting of the American College of Cardiology.

A total of 47 patients were evaluated. Of these 41 (87.2%) had idiopathic cardiomyopathy, 4 (8.5%) had histologic evidence of chronic myocarditis before VAD implantation, and 2 (4.3%) had chronic ischemic cardiomyopathy with severe left ventricular dilation.

Before VAD insertion, all patients had irreversible end-stage heart failure and required continuous positive inotropic support. No attempts were made to use VADs electively with the aim of myocardial recovery only, he said.

Postweaning results. Cardiac stability lasting at least 15 years was achieved by 2 patients, while 10 patients have been stable at least 10 years and 3 at least 5 years, he reported.

"At 5 years, only five patients, 10.6%, had died due to heart failure recurrence or weaning-related complications. Several patients died of other causes," he said.

Postweaning freedom from heart failure recurrence for all evaluated patients was 74% at 3 years and 66% at 5 years, but these results included nine patients at very high risk for poor outcomes. After 2002, when the investigators tightened their criteria for weaning, freedom from heart failure recurrence reached 100% at 3 years, he noted.

Pre-explantation variables predictive of outcomes. "Echo data obtained during ‘off pump’ trials proved to be reliable for detection of recovery during mechanical unloading," Dr. Dandel said. "In particular, off-pump [left ventricle] size, geometry, and ejection fraction were predictive of outcome after weaning, especially when history of heart failure was also considered."

For cardiac stability lasting at least 5 years, pre-explantation "off pump" LVEF of 50% or more was associated with a positive predictive value of 91.7%, while LVEF of 45% or more had a positive predictive value of 79.1%.

The positive predictive value of LVEF of 45% or more was approximately 90% if additional parameters were considered: pre-explantation left ventricle size and geometry, stability of unloading-induced cardiac improvement before VAD removal, and heart failure duration before VAD implantation.

Time to cardiac recovery seemed important, Dr. Dandel said. "Patients who had recurrences needed more time to show an improvement. They needed twice the duration of VAD support as patients who did not have a recurrence," he said.

"Definite cutoff values for certain parameters – including tissue Doppler-derived LV wall motion velocity – allowed us to formulate weaning criteria with high predictability for postweaning stability," he said.

Risk factors for heart failure recurrence. Dr. Dandel and his colleagues also identified several risk factors that predicted heart failure recurrence during the first 3 years after VAD removal. These factors, and their associated probability for recurrence, were:

• Preweaning off-pump LVEF less than 45% plus history of heart failure longer than 5 years (100%).

• Preweaning LVEF less than 45% (88.9%).

• Preweaning off-pump LVEF less than 50% plus left ventricular internal diastolic diameter greater than 55 mm (90%).

• Pre-explantation LVEF less than 50% and preexisting alteration of greater than 10% best value (87.5%).

• LVEF less than 50% plus relative wall thickness decrease of less than 10% during final off-pump trial (83.3%).

Of these, he emphasized the importance of the final off-pump trial values. "An off-pump ejection fraction less than 45% in patients with a history of heart failure for more than 5 years is an absolute contraindication for VAD removal," he noted. "All such patients in our study had a recurrence of heart failure."

Early instability of ejection fraction and unstable geometry also confer a high probability of recurrence. "A wall thickness increase by more than 10% means the reverse in modeling is not stable enough," he added.

"The notion that we can actually wean patients from VADs is still a fairly new concept, and the European experience is larger than that of the United States. This is still a field that is wide open for determining patient selection and predictors of outcome after VAD removal," session moderator Dr. Gregory A. Ewald, medical director of heart transplantation at Barnes-Jewish Hospital, St. Louis, said in an interview.

"Clearly, the echocardiographic appearance of the heart on and off support is a good predictor," Dr. Ewald said, but he noted that nonechocardiographic factors such as exercise tolerance were not studied. He also noted that the field has moved to continuous-flow pumps rather than pulsatile pumps, which constituted much of the German experience. It remains to be determined if the same parameters are completely applicable to the newer-generation devices.

Dr. Dandel and Dr. Ewald reported having no relevant conflicts of interest.

NEW ORLEANS – Patients with chronic cardiomyopathy can be successfully weaned from ventricular assist devices, and certain parameters can predict long-term cardiac stability after explantation, according to German investigators.

"Unloading-promoted reversal of heart failure allows for long-term transplant-free outcomes after patients are removed from VADs. However, few patients with chronic cardiomyopathy have been weaned from VADs, and the majority only recently," said principal investigator Dr. Michael Dandel of the German Heart Institute Berlin. "The long-term outcomes of patients, therefore, and the reliability of criteria for making weaning decisions, are not well known."

At his clinic, 91 patients with chronic cardiomyopathy (CCM) as the underlying cause of heart failure were weaned from VADs between 1995 and 2010, including 75 weaned from left ventricular assist devices, 13 weaned from biventricular assist devices, and 3 weaned from right ventricular assist devices. Before VAD implantation, the patients had left ventricular ejection fraction (LVEF) values of 10%-20%.

These patients were evaluated as to the feasibility of weaning and to establish criteria that could predict long-term cardiac stability after VAD removal. "With this information, we can improve future weaning decisions and postweaning patient management," Dr. Dandel said at the annual meeting of the American College of Cardiology.

A total of 47 patients were evaluated. Of these 41 (87.2%) had idiopathic cardiomyopathy, 4 (8.5%) had histologic evidence of chronic myocarditis before VAD implantation, and 2 (4.3%) had chronic ischemic cardiomyopathy with severe left ventricular dilation.

Before VAD insertion, all patients had irreversible end-stage heart failure and required continuous positive inotropic support. No attempts were made to use VADs electively with the aim of myocardial recovery only, he said.

Postweaning results. Cardiac stability lasting at least 15 years was achieved by 2 patients, while 10 patients have been stable at least 10 years and 3 at least 5 years, he reported.

"At 5 years, only five patients, 10.6%, had died due to heart failure recurrence or weaning-related complications. Several patients died of other causes," he said.

Postweaning freedom from heart failure recurrence for all evaluated patients was 74% at 3 years and 66% at 5 years, but these results included nine patients at very high risk for poor outcomes. After 2002, when the investigators tightened their criteria for weaning, freedom from heart failure recurrence reached 100% at 3 years, he noted.

Pre-explantation variables predictive of outcomes. "Echo data obtained during ‘off pump’ trials proved to be reliable for detection of recovery during mechanical unloading," Dr. Dandel said. "In particular, off-pump [left ventricle] size, geometry, and ejection fraction were predictive of outcome after weaning, especially when history of heart failure was also considered."

For cardiac stability lasting at least 5 years, pre-explantation "off pump" LVEF of 50% or more was associated with a positive predictive value of 91.7%, while LVEF of 45% or more had a positive predictive value of 79.1%.

The positive predictive value of LVEF of 45% or more was approximately 90% if additional parameters were considered: pre-explantation left ventricle size and geometry, stability of unloading-induced cardiac improvement before VAD removal, and heart failure duration before VAD implantation.

Time to cardiac recovery seemed important, Dr. Dandel said. "Patients who had recurrences needed more time to show an improvement. They needed twice the duration of VAD support as patients who did not have a recurrence," he said.

"Definite cutoff values for certain parameters – including tissue Doppler-derived LV wall motion velocity – allowed us to formulate weaning criteria with high predictability for postweaning stability," he said.

Risk factors for heart failure recurrence. Dr. Dandel and his colleagues also identified several risk factors that predicted heart failure recurrence during the first 3 years after VAD removal. These factors, and their associated probability for recurrence, were:

• Preweaning off-pump LVEF less than 45% plus history of heart failure longer than 5 years (100%).

• Preweaning LVEF less than 45% (88.9%).

• Preweaning off-pump LVEF less than 50% plus left ventricular internal diastolic diameter greater than 55 mm (90%).

• Pre-explantation LVEF less than 50% and preexisting alteration of greater than 10% best value (87.5%).

• LVEF less than 50% plus relative wall thickness decrease of less than 10% during final off-pump trial (83.3%).

Of these, he emphasized the importance of the final off-pump trial values. "An off-pump ejection fraction less than 45% in patients with a history of heart failure for more than 5 years is an absolute contraindication for VAD removal," he noted. "All such patients in our study had a recurrence of heart failure."

Early instability of ejection fraction and unstable geometry also confer a high probability of recurrence. "A wall thickness increase by more than 10% means the reverse in modeling is not stable enough," he added.

"The notion that we can actually wean patients from VADs is still a fairly new concept, and the European experience is larger than that of the United States. This is still a field that is wide open for determining patient selection and predictors of outcome after VAD removal," session moderator Dr. Gregory A. Ewald, medical director of heart transplantation at Barnes-Jewish Hospital, St. Louis, said in an interview.

"Clearly, the echocardiographic appearance of the heart on and off support is a good predictor," Dr. Ewald said, but he noted that nonechocardiographic factors such as exercise tolerance were not studied. He also noted that the field has moved to continuous-flow pumps rather than pulsatile pumps, which constituted much of the German experience. It remains to be determined if the same parameters are completely applicable to the newer-generation devices.

Dr. Dandel and Dr. Ewald reported having 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 – 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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

SAN DIEGO – Ventricular assist devices appear to be a "reasonable strategy" for supporting certain patients who have failing cardiac grafts and are waiting for a new heart, concludes a retrospective review of more than 1,500 patients who had a second transplant.

In the group who had retransplantation at least 1 year after their first transplantation, median survival was about 7 years. There was no difference between patients bridged with a ventricular assist device (VAD) and those who did not have bridging with any type of mechanical circulatory support (MCS), according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

But survival was poor for those who were bridged after any interval with extracorporeal membrane oxygenation (ECMO) and for those who underwent retransplantation because they had primary graft failure or a hyperacute rejection, regardless of whether they were mechanically supported.

"The use of ECMO to bridge any patient to retransplantation does not appear judicious, nor does the use of MCS to bridge patients with primary graft failure or hyperacute rejection to retransplantation," said coinvestigator Dr. David L.S. Morales of the departments of surgery and pediatrics at the Texas Children’s Hospital in Houston. "However, the use of VADs to bridge patients to transplant after a year could be a reasonable strategy."

Although MCS is widely accepted for bridging patients to initial heart transplantation, its use for bridging to retransplantation has not been well studied. The investigators therefore took a closer look at this issue, analyzing data from the United Network for Organ Sharing (UNOS) database for 1,535 patients who underwent cardiac retransplantation during 1982-2009.

Results showed that just 8% of the patients were bridged to retransplantation, with a VAD in about two-thirds of cases and ECMO in the other third. The mean age was 41 years in the former and 35 years in the latter, with children (younger than age 18) comprising 15% and 35%, respectively.

The patients bridged to retransplantation were significantly more likely than were their nonbridged counterparts to have primary graft failure or hyperacute rejection (54% vs. 11%) and significantly less likely to have chronic rejection (16% vs. 63%).

And the bridged patients by and large underwent retransplantation early, with 64% in the VAD group and 76% in the ECMO group retransplanted within 3 months of their primary transplantation, compared with just 12% of their nonbridged peers.

"Regardless of MCS, patients retransplanted for primary graft failure or hyperacute rejection do not do well," Dr. Morales commented. Specifically, in patients with these indications for retransplantation, the 1-year mortality rate was 83%, with essentially no difference according to whether they received bridging or the type.

In the entire study population, median overall survival after retransplantation was 6.1 years in nonbridged patients, significantly longer than the 1.5 years in VAD-bridged patients and the 30 days in ECMO-bridged patients.

But when analyses were restricted to patients who underwent retransplantation at least 1 year after primary transplantation, median survival was similar in nonbridged and VAD-bridged patients, at 7.0 and 6.9 years. Compared with those groups, however, survival was significantly shorter – just 6 months – in the ECMO group.

"Patients bridged to retransplant with ECMO have poor outcomes regardless of timing or indication," Dr. Morales concluded of the findings. "And all patients retransplanted for hyperacute rejection or primary graft failure do poorly, regardless of MCS," he said. "However, patients who are bridged with a VAD to retransplant that is done a year post–primary transplant do have similar outcomes as compared to retransplant patients without MCS."

As for study limitations, "it is very important to note that we do not know the number of patients placed on MCS as a bridge to transplant who died while on support," he pointed out.

Despite the more favorable findings for VAD bridging, his pediatric patients needing retransplantation in adolescence often have chronic vasculopathy in their graft, Dr. Morales said. "They are a very, very difficult group to support with mechanical support with LVADs because we have to continue the immunosuppression," and the patients often die from infections as a result.

"It’s one of the reasons I’m interested in the total artificial heart, because the ability to take the heart out completely and stop immunosuppression I think will help bridge those patients," he commented. "The total artificial heart has lasted in patients for quite a long period of time, and I think eventually will start to be used maybe as a bridge to destination, as it was originally intended."

Dr. Morales disclosed having relationships with Berlin Heart Inc., Syncardia Systems Inc., and CircuLite Inc. as an investigator and/or consultant.

SAN DIEGO – Ventricular assist devices appear to be a "reasonable strategy" for supporting certain patients who have failing cardiac grafts and are waiting for a new heart, concludes a retrospective review of more than 1,500 patients who had a second transplant.

In the group who had retransplantation at least 1 year after their first transplantation, median survival was about 7 years. There was no difference between patients bridged with a ventricular assist device (VAD) and those who did not have bridging with any type of mechanical circulatory support (MCS), according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

But survival was poor for those who were bridged after any interval with extracorporeal membrane oxygenation (ECMO) and for those who underwent retransplantation because they had primary graft failure or a hyperacute rejection, regardless of whether they were mechanically supported.

"The use of ECMO to bridge any patient to retransplantation does not appear judicious, nor does the use of MCS to bridge patients with primary graft failure or hyperacute rejection to retransplantation," said coinvestigator Dr. David L.S. Morales of the departments of surgery and pediatrics at the Texas Children’s Hospital in Houston. "However, the use of VADs to bridge patients to transplant after a year could be a reasonable strategy."

Although MCS is widely accepted for bridging patients to initial heart transplantation, its use for bridging to retransplantation has not been well studied. The investigators therefore took a closer look at this issue, analyzing data from the United Network for Organ Sharing (UNOS) database for 1,535 patients who underwent cardiac retransplantation during 1982-2009.

Results showed that just 8% of the patients were bridged to retransplantation, with a VAD in about two-thirds of cases and ECMO in the other third. The mean age was 41 years in the former and 35 years in the latter, with children (younger than age 18) comprising 15% and 35%, respectively.

The patients bridged to retransplantation were significantly more likely than were their nonbridged counterparts to have primary graft failure or hyperacute rejection (54% vs. 11%) and significantly less likely to have chronic rejection (16% vs. 63%).

And the bridged patients by and large underwent retransplantation early, with 64% in the VAD group and 76% in the ECMO group retransplanted within 3 months of their primary transplantation, compared with just 12% of their nonbridged peers.

"Regardless of MCS, patients retransplanted for primary graft failure or hyperacute rejection do not do well," Dr. Morales commented. Specifically, in patients with these indications for retransplantation, the 1-year mortality rate was 83%, with essentially no difference according to whether they received bridging or the type.

In the entire study population, median overall survival after retransplantation was 6.1 years in nonbridged patients, significantly longer than the 1.5 years in VAD-bridged patients and the 30 days in ECMO-bridged patients.

But when analyses were restricted to patients who underwent retransplantation at least 1 year after primary transplantation, median survival was similar in nonbridged and VAD-bridged patients, at 7.0 and 6.9 years. Compared with those groups, however, survival was significantly shorter – just 6 months – in the ECMO group.

"Patients bridged to retransplant with ECMO have poor outcomes regardless of timing or indication," Dr. Morales concluded of the findings. "And all patients retransplanted for hyperacute rejection or primary graft failure do poorly, regardless of MCS," he said. "However, patients who are bridged with a VAD to retransplant that is done a year post–primary transplant do have similar outcomes as compared to retransplant patients without MCS."

As for study limitations, "it is very important to note that we do not know the number of patients placed on MCS as a bridge to transplant who died while on support," he pointed out.

Despite the more favorable findings for VAD bridging, his pediatric patients needing retransplantation in adolescence often have chronic vasculopathy in their graft, Dr. Morales said. "They are a very, very difficult group to support with mechanical support with LVADs because we have to continue the immunosuppression," and the patients often die from infections as a result.

"It’s one of the reasons I’m interested in the total artificial heart, because the ability to take the heart out completely and stop immunosuppression I think will help bridge those patients," he commented. "The total artificial heart has lasted in patients for quite a long period of time, and I think eventually will start to be used maybe as a bridge to destination, as it was originally intended."

Dr. Morales disclosed having relationships with Berlin Heart Inc., Syncardia Systems Inc., and CircuLite Inc. as an investigator and/or consultant.

SAN DIEGO – Ventricular assist devices appear to be a "reasonable strategy" for supporting certain patients who have failing cardiac grafts and are waiting for a new heart, concludes a retrospective review of more than 1,500 patients who had a second transplant.

In the group who had retransplantation at least 1 year after their first transplantation, median survival was about 7 years. There was no difference between patients bridged with a ventricular assist device (VAD) and those who did not have bridging with any type of mechanical circulatory support (MCS), according to results reported at the annual meeting of the International Society for Heart and Lung Transplantation.

But survival was poor for those who were bridged after any interval with extracorporeal membrane oxygenation (ECMO) and for those who underwent retransplantation because they had primary graft failure or a hyperacute rejection, regardless of whether they were mechanically supported.

"The use of ECMO to bridge any patient to retransplantation does not appear judicious, nor does the use of MCS to bridge patients with primary graft failure or hyperacute rejection to retransplantation," said coinvestigator Dr. David L.S. Morales of the departments of surgery and pediatrics at the Texas Children’s Hospital in Houston. "However, the use of VADs to bridge patients to transplant after a year could be a reasonable strategy."

Although MCS is widely accepted for bridging patients to initial heart transplantation, its use for bridging to retransplantation has not been well studied. The investigators therefore took a closer look at this issue, analyzing data from the United Network for Organ Sharing (UNOS) database for 1,535 patients who underwent cardiac retransplantation during 1982-2009.

Results showed that just 8% of the patients were bridged to retransplantation, with a VAD in about two-thirds of cases and ECMO in the other third. The mean age was 41 years in the former and 35 years in the latter, with children (younger than age 18) comprising 15% and 35%, respectively.

The patients bridged to retransplantation were significantly more likely than were their nonbridged counterparts to have primary graft failure or hyperacute rejection (54% vs. 11%) and significantly less likely to have chronic rejection (16% vs. 63%).

And the bridged patients by and large underwent retransplantation early, with 64% in the VAD group and 76% in the ECMO group retransplanted within 3 months of their primary transplantation, compared with just 12% of their nonbridged peers.

"Regardless of MCS, patients retransplanted for primary graft failure or hyperacute rejection do not do well," Dr. Morales commented. Specifically, in patients with these indications for retransplantation, the 1-year mortality rate was 83%, with essentially no difference according to whether they received bridging or the type.

In the entire study population, median overall survival after retransplantation was 6.1 years in nonbridged patients, significantly longer than the 1.5 years in VAD-bridged patients and the 30 days in ECMO-bridged patients.

But when analyses were restricted to patients who underwent retransplantation at least 1 year after primary transplantation, median survival was similar in nonbridged and VAD-bridged patients, at 7.0 and 6.9 years. Compared with those groups, however, survival was significantly shorter – just 6 months – in the ECMO group.

"Patients bridged to retransplant with ECMO have poor outcomes regardless of timing or indication," Dr. Morales concluded of the findings. "And all patients retransplanted for hyperacute rejection or primary graft failure do poorly, regardless of MCS," he said. "However, patients who are bridged with a VAD to retransplant that is done a year post–primary transplant do have similar outcomes as compared to retransplant patients without MCS."

As for study limitations, "it is very important to note that we do not know the number of patients placed on MCS as a bridge to transplant who died while on support," he pointed out.

Despite the more favorable findings for VAD bridging, his pediatric patients needing retransplantation in adolescence often have chronic vasculopathy in their graft, Dr. Morales said. "They are a very, very difficult group to support with mechanical support with LVADs because we have to continue the immunosuppression," and the patients often die from infections as a result.

"It’s one of the reasons I’m interested in the total artificial heart, because the ability to take the heart out completely and stop immunosuppression I think will help bridge those patients," he commented. "The total artificial heart has lasted in patients for quite a long period of time, and I think eventually will start to be used maybe as a bridge to destination, as it was originally intended."

Dr. Morales disclosed having relationships with Berlin Heart Inc., Syncardia Systems Inc., and CircuLite Inc. as an investigator and/or consultant.

Major Finding: For the primary end point of echocardiographic response, defined as a greater than 15% change in left ventricular end systolic volume from baseline to 6-month follow-up, the speckle-tracking echocardiography group had a 70% response and the standard placement group had a 55% response (P = .031).

Data Source: A single-blinded, randomized, controlled trial of 220 patients recruited from three different hospitals in the United Kingdom. Participants were in sinus rhythm, had NYHA class III/IV heart failure, left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 milliseconds.

Disclosures: Dr. Khan said he had no relevant financial disclosures.

NEW ORLEANS – Using speckle-tracking echocardiography to guide pacemaker lead placement improved the outcomes of cardiac resynchronization therapy for patients with severe heart failure in the TARGET trial.

When speckle-tracking echocardiography (STE) was used to identify target sites for pacemaker lead placement for individual patients, leads were more likely to be placed at concordant sites. The result was improved echocardiographic response at 6 months – defined as a greater than 15% change in left ventricular end systolic volume (LVESV) from baseline to 6-month follow-up. The STE group had a 70% response as compared with a 55% response in the group with conventional lead placement without echocardiography guidance (P = .031), said Dr. Fakhar Z. Khan of Cambridge (England) University, who reported the results of the TARGET (Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy in Patients with Heart Failure) trial at the meeting.

Lower rates were also seen with STE for the combined end point of all-cause mortality and heart failure hospitalization. The difference was primarily driven by fewer heart failure hospitalizations. Looking at mortality alone at a mean follow-up of 400 days, the investigators found the two groups did not significantly differ.

“This is a well-designed, well-conducted study with impressive differences in clinical outcomes,” said Dr. Byron Kwock Lee, who is with the University of California, San Francisco, and chaired the session where the TARGET results were presented. “Other studies have shown echocardiographic outcomes but have had difficulty showing clinical differences.”

“I am impressed that the modest echocardiographic changes translated to dramatic clinical effects,” commented Dr. Michael Crawford, also of the University of California, San Francisco, and a panelist at the presentation of the study results.

Up to 40% of patients fail to gain significant clinical benefit from cardiac resynchronization therapy, Dr. Khan noted. The position of the left ventricular lead has emerged as an important determinant of response, with better results achieved when pacing at the latest site of contraction and lesser responses noted when pacing areas of scar.

Speckle-tracking radial strain imaging correlates with delayed enhanced cardiac MRI for determination of scar, Dr. Khan said. In patients undergoing cardiac resynchronization therapy, less than 10% amplitude of radial strain at the left ventricular pacing site has a high negative predictive value (91%) for response.

Using STE, “we found that concordant lead placement, baseline dyssynchrony, and pacing away from areas of scar are strongly related to improved outcomes,” he said.

The single-blinded, randomized, controlled trial enrolled 220 patients recruited from three different hospitals in the United Kingdom. Participants were in sinus rhythm, had severe heart failure (New York heart Association class III/IV), left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 msec. Patients were randomized in a 1:1 ratio to receive either standard lead placement without the benefit of echocardiographic guidance or targeted lead placement using STE to position the lead at the latest site of contraction and away from areas of scar. Following implantation, all devices were optimized using echocardiography.

Concordant lead placement was achieved in 61% of the STE group vs. 45% of control group. Placement was adjacent in 25% of the STE group and 28% of the control group, and was remote in 10% and 24%, respectively.

At baseline, both groups were comparable in demographic and disease characteristics. Mean age was about 70 years, about 86% were male, about 94% had NYHA class III heart failure, and 56% had underlying ischemic cardiomyopathy.

Both groups had a 14% rate of implant-related complications. Procedural length of time was similar for both groups.

In addition to the primary end point improvements in echocardiographic response at 6-month follow-up, the STE group also had significantly improved clinical end points, compared with the standard placement group. Statistically significant differences from baseline to follow-up for the STE group vs. the standard placement group included improvement in heart failure class, 6-mile walk test results, and quality of life scores.

Patients in the study will continue to have ongoing follow-up.

“STE software can be applied to any existing echocardiographic image at no additional risk to the patient,” Dr. Khan said.

“STE makes targeting of the lead feasible at any facility that performs echocardiography and has the software available to analyze their images, so it is widely accessible at smaller centers and nonacademic hospitals where more and more pacemakers are being implanted. That being said, it requires training and experience.”

Major Finding: For the primary end point of echocardiographic response, defined as a greater than 15% change in left ventricular end systolic volume from baseline to 6-month follow-up, the speckle-tracking echocardiography group had a 70% response and the standard placement group had a 55% response (P = .031).

Data Source: A single-blinded, randomized, controlled trial of 220 patients recruited from three different hospitals in the United Kingdom. Participants were in sinus rhythm, had NYHA class III/IV heart failure, left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 milliseconds.

Disclosures: Dr. Khan said he had no relevant financial disclosures.

NEW ORLEANS – Using speckle-tracking echocardiography to guide pacemaker lead placement improved the outcomes of cardiac resynchronization therapy for patients with severe heart failure in the TARGET trial.

When speckle-tracking echocardiography (STE) was used to identify target sites for pacemaker lead placement for individual patients, leads were more likely to be placed at concordant sites. The result was improved echocardiographic response at 6 months – defined as a greater than 15% change in left ventricular end systolic volume (LVESV) from baseline to 6-month follow-up. The STE group had a 70% response as compared with a 55% response in the group with conventional lead placement without echocardiography guidance (P = .031), said Dr. Fakhar Z. Khan of Cambridge (England) University, who reported the results of the TARGET (Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy in Patients with Heart Failure) trial at the meeting.

Lower rates were also seen with STE for the combined end point of all-cause mortality and heart failure hospitalization. The difference was primarily driven by fewer heart failure hospitalizations. Looking at mortality alone at a mean follow-up of 400 days, the investigators found the two groups did not significantly differ.

“This is a well-designed, well-conducted study with impressive differences in clinical outcomes,” said Dr. Byron Kwock Lee, who is with the University of California, San Francisco, and chaired the session where the TARGET results were presented. “Other studies have shown echocardiographic outcomes but have had difficulty showing clinical differences.”

“I am impressed that the modest echocardiographic changes translated to dramatic clinical effects,” commented Dr. Michael Crawford, also of the University of California, San Francisco, and a panelist at the presentation of the study results.

Up to 40% of patients fail to gain significant clinical benefit from cardiac resynchronization therapy, Dr. Khan noted. The position of the left ventricular lead has emerged as an important determinant of response, with better results achieved when pacing at the latest site of contraction and lesser responses noted when pacing areas of scar.

Speckle-tracking radial strain imaging correlates with delayed enhanced cardiac MRI for determination of scar, Dr. Khan said. In patients undergoing cardiac resynchronization therapy, less than 10% amplitude of radial strain at the left ventricular pacing site has a high negative predictive value (91%) for response.

Using STE, “we found that concordant lead placement, baseline dyssynchrony, and pacing away from areas of scar are strongly related to improved outcomes,” he said.

The single-blinded, randomized, controlled trial enrolled 220 patients recruited from three different hospitals in the United Kingdom. Participants were in sinus rhythm, had severe heart failure (New York heart Association class III/IV), left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 msec. Patients were randomized in a 1:1 ratio to receive either standard lead placement without the benefit of echocardiographic guidance or targeted lead placement using STE to position the lead at the latest site of contraction and away from areas of scar. Following implantation, all devices were optimized using echocardiography.

Concordant lead placement was achieved in 61% of the STE group vs. 45% of control group. Placement was adjacent in 25% of the STE group and 28% of the control group, and was remote in 10% and 24%, respectively.

At baseline, both groups were comparable in demographic and disease characteristics. Mean age was about 70 years, about 86% were male, about 94% had NYHA class III heart failure, and 56% had underlying ischemic cardiomyopathy.

Both groups had a 14% rate of implant-related complications. Procedural length of time was similar for both groups.

In addition to the primary end point improvements in echocardiographic response at 6-month follow-up, the STE group also had significantly improved clinical end points, compared with the standard placement group. Statistically significant differences from baseline to follow-up for the STE group vs. the standard placement group included improvement in heart failure class, 6-mile walk test results, and quality of life scores.

Patients in the study will continue to have ongoing follow-up.

“STE software can be applied to any existing echocardiographic image at no additional risk to the patient,” Dr. Khan said.

“STE makes targeting of the lead feasible at any facility that performs echocardiography and has the software available to analyze their images, so it is widely accessible at smaller centers and nonacademic hospitals where more and more pacemakers are being implanted. That being said, it requires training and experience.”

Major Finding: For the primary end point of echocardiographic response, defined as a greater than 15% change in left ventricular end systolic volume from baseline to 6-month follow-up, the speckle-tracking echocardiography group had a 70% response and the standard placement group had a 55% response (P = .031).

Data Source: A single-blinded, randomized, controlled trial of 220 patients recruited from three different hospitals in the United Kingdom. Participants were in sinus rhythm, had NYHA class III/IV heart failure, left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 milliseconds.

Disclosures: Dr. Khan said he had no relevant financial disclosures.

NEW ORLEANS – Using speckle-tracking echocardiography to guide pacemaker lead placement improved the outcomes of cardiac resynchronization therapy for patients with severe heart failure in the TARGET trial.

When speckle-tracking echocardiography (STE) was used to identify target sites for pacemaker lead placement for individual patients, leads were more likely to be placed at concordant sites. The result was improved echocardiographic response at 6 months – defined as a greater than 15% change in left ventricular end systolic volume (LVESV) from baseline to 6-month follow-up. The STE group had a 70% response as compared with a 55% response in the group with conventional lead placement without echocardiography guidance (P = .031), said Dr. Fakhar Z. Khan of Cambridge (England) University, who reported the results of the TARGET (Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy in Patients with Heart Failure) trial at the meeting.

Lower rates were also seen with STE for the combined end point of all-cause mortality and heart failure hospitalization. The difference was primarily driven by fewer heart failure hospitalizations. Looking at mortality alone at a mean follow-up of 400 days, the investigators found the two groups did not significantly differ.

“This is a well-designed, well-conducted study with impressive differences in clinical outcomes,” said Dr. Byron Kwock Lee, who is with the University of California, San Francisco, and chaired the session where the TARGET results were presented. “Other studies have shown echocardiographic outcomes but have had difficulty showing clinical differences.”

“I am impressed that the modest echocardiographic changes translated to dramatic clinical effects,” commented Dr. Michael Crawford, also of the University of California, San Francisco, and a panelist at the presentation of the study results.

Up to 40% of patients fail to gain significant clinical benefit from cardiac resynchronization therapy, Dr. Khan noted. The position of the left ventricular lead has emerged as an important determinant of response, with better results achieved when pacing at the latest site of contraction and lesser responses noted when pacing areas of scar.

Speckle-tracking radial strain imaging correlates with delayed enhanced cardiac MRI for determination of scar, Dr. Khan said. In patients undergoing cardiac resynchronization therapy, less than 10% amplitude of radial strain at the left ventricular pacing site has a high negative predictive value (91%) for response.

Using STE, “we found that concordant lead placement, baseline dyssynchrony, and pacing away from areas of scar are strongly related to improved outcomes,” he said.

The single-blinded, randomized, controlled trial enrolled 220 patients recruited from three different hospitals in the United Kingdom. Participants were in sinus rhythm, had severe heart failure (New York heart Association class III/IV), left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 msec. Patients were randomized in a 1:1 ratio to receive either standard lead placement without the benefit of echocardiographic guidance or targeted lead placement using STE to position the lead at the latest site of contraction and away from areas of scar. Following implantation, all devices were optimized using echocardiography.

Concordant lead placement was achieved in 61% of the STE group vs. 45% of control group. Placement was adjacent in 25% of the STE group and 28% of the control group, and was remote in 10% and 24%, respectively.

At baseline, both groups were comparable in demographic and disease characteristics. Mean age was about 70 years, about 86% were male, about 94% had NYHA class III heart failure, and 56% had underlying ischemic cardiomyopathy.

Both groups had a 14% rate of implant-related complications. Procedural length of time was similar for both groups.

In addition to the primary end point improvements in echocardiographic response at 6-month follow-up, the STE group also had significantly improved clinical end points, compared with the standard placement group. Statistically significant differences from baseline to follow-up for the STE group vs. the standard placement group included improvement in heart failure class, 6-mile walk test results, and quality of life scores.

Patients in the study will continue to have ongoing follow-up.

“STE software can be applied to any existing echocardiographic image at no additional risk to the patient,” Dr. Khan said.

“STE makes targeting of the lead feasible at any facility that performs echocardiography and has the software available to analyze their images, so it is widely accessible at smaller centers and nonacademic hospitals where more and more pacemakers are being implanted. That being said, it requires training and experience.”

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, in a study presented at the meeting.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

“We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new … is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH,” Dr. Arshad Jahangir said at the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass, mass index, and posterior wall thickness, indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, and renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116 g/m

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

To see a video interview with Dr. Jahangir, scan this QR code or visit www.youtube.com/watch?v=qvm1sSQ9LdM&NR=1

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, in a study presented at the meeting.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

“We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new … is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH,” Dr. Arshad Jahangir said at the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass, mass index, and posterior wall thickness, indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, and renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116 g/m

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

To see a video interview with Dr. Jahangir, scan this QR code or visit www.youtube.com/watch?v=qvm1sSQ9LdM&NR=1

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, in a study presented at the meeting.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

“We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new … is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH,” Dr. Arshad Jahangir said at the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass, mass index, and posterior wall thickness, indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, and renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116 g/m

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

To see a video interview with Dr. Jahangir, scan this QR code or visit www.youtube.com/watch?v=qvm1sSQ9LdM&NR=1