Conference Coverage

A single 3-hour-long group psychosocial intervention designed specifically for patients in intensive outpatient programs for addiction treatment to prevent future suicide resulted in significantly improved knowledge and attitudes regarding suicide that persisted at 6 months of follow-up in a large multicenter randomized effectiveness study, reported Richard K. Ries, MD.

There is an enormous unmet need for evidence-based strategies for preventing addiction-related suicide, since people with substance use disorders have a 10-fold increased risk of suicide. Based upon these new study findings, the Preventing Addiction Related Suicide (PARS) program can now be considered the first such evidence-based intervention for this extremely high-risk population, Dr. Ries said at the virtual annual meeting of the American Association of Suicidology.

“We’ve shown that suicide prevention in intensive outpatient program addiction groups is feasible, easy to train, and highly rated by counselors, and I’d say it’s very adaptable, easy to go national in almost any addiction treatment program, right out of the box,” said Dr. Ries, professor of psychiatry at the University of Washington, Seattle, and director of outpatient psychiatry as well as the psychiatry addiction division at Harborview Medical Center.

The workbook-based PARS program developed by Dr. Ries and colleagues adapted empirically supported suicide prevention best practices from other settings for use in group-based intensive outpatient addiction treatment, which is the most common form of treatment for chemical dependency in the United States. Dr. Ries recognized the need for a program such as PARS because addiction counselors often feel out of their depth regarding suicide-related issues.

“Nothing had ever really been done before on any scale on suicide prevention in addiction centers,” he explained. “We designed the PARS intervention to be integrated right into the counselors’ workflow. They get trained right in their setting in a one-shot deal that takes 2-3 hours. The training was highly rated by counselors as acceptable and effective in their day-to-day work, not ivory tower-type stuff.”

Once the counselors were trained in PARS, they then trained their alcohol- and drug-addicted patients. Elements of the PARS program include information on suicide risk and protective factors, myths and facts about suicide, action steps to take when warning signs of suicide are observed, and local crisis resources.

The effectiveness study was a randomized, stepped-wedge cluster design intervention that included 905 patients in 15 busy community group–based intensive outpatient addiction treatment programs in Western Washington. Patients were randomized to counselor-delivered PARS or treatment as usual, with follow-up assessments at 2 weeks and 1, 3, and 6 months.

There was no attempt to enrich the study population for suicidality by prescreening potential enrollees, since participation in a drug and alcohol treatment program already places an individual in a high-risk group. For example, 74% of study participants indicated they had thought of suicide at least once in the past year, compared with a background rate of 4% in the U.S. general population. And 29% of study participants reported a lifetime history of one or more suicide attempts, versus roughly 5% in the general population.

Dr. Ries’ coinvestigator, Katherine Anne Comtois, PhD, MPH, presented the study results. The three key outcomes were improvement on structured measures of suicide knowledge, attitudes, and help-seeking behavior. The PARS recipients showed statistically significant improvement compared with baseline on two of the three: they displayed greater knowledge about suicide and its close relationship with addiction, and less stigmatization and other maladaptive attitudes toward suicide. Scores on all three measures remained unchanged over time in the control group.

“Overall, we had small to medium effect sizes, comparable to what you might see in studies measuring antidepressant effect sizes. I think these were meaningful improvements in knowledge and attitudes,” said Dr. Comtois of the University of Washington.

The PARS group showed a small increase in the third endpoint – willingness to seek professional help for themselves, friends, or family if depressed or suicidal, but this didn’t achieve statistical significance. However, Dr. Comtois noted that the study outcomes were assessed per protocol using an intent-to-treat analysis. This likely underestimated the true effectiveness of the PARS intervention, given that 40% of patients randomized to PARS didn’t actually attend the intervention session.

“People with drug and alcohol problems have complicated lives,” she said by way of explanation for the high no-show rate.

The investigators are now performing a per-protocol analysis of the data, restricted to those subjects who actually attended their session. A long-term look at suicide events and outcomes in the study population is planned.

Dr. Ries and Dr. Comtois reported having no financial conflicts regarding the study, which was funded by a multiyear grant from the National Institute on Drug Abuse.

bjancin@mdedge.com

A single 3-hour-long group psychosocial intervention designed specifically for patients in intensive outpatient programs for addiction treatment to prevent future suicide resulted in significantly improved knowledge and attitudes regarding suicide that persisted at 6 months of follow-up in a large multicenter randomized effectiveness study, reported Richard K. Ries, MD.

There is an enormous unmet need for evidence-based strategies for preventing addiction-related suicide, since people with substance use disorders have a 10-fold increased risk of suicide. Based upon these new study findings, the Preventing Addiction Related Suicide (PARS) program can now be considered the first such evidence-based intervention for this extremely high-risk population, Dr. Ries said at the virtual annual meeting of the American Association of Suicidology.

“We’ve shown that suicide prevention in intensive outpatient program addiction groups is feasible, easy to train, and highly rated by counselors, and I’d say it’s very adaptable, easy to go national in almost any addiction treatment program, right out of the box,” said Dr. Ries, professor of psychiatry at the University of Washington, Seattle, and director of outpatient psychiatry as well as the psychiatry addiction division at Harborview Medical Center.

The workbook-based PARS program developed by Dr. Ries and colleagues adapted empirically supported suicide prevention best practices from other settings for use in group-based intensive outpatient addiction treatment, which is the most common form of treatment for chemical dependency in the United States. Dr. Ries recognized the need for a program such as PARS because addiction counselors often feel out of their depth regarding suicide-related issues.

“Nothing had ever really been done before on any scale on suicide prevention in addiction centers,” he explained. “We designed the PARS intervention to be integrated right into the counselors’ workflow. They get trained right in their setting in a one-shot deal that takes 2-3 hours. The training was highly rated by counselors as acceptable and effective in their day-to-day work, not ivory tower-type stuff.”

Once the counselors were trained in PARS, they then trained their alcohol- and drug-addicted patients. Elements of the PARS program include information on suicide risk and protective factors, myths and facts about suicide, action steps to take when warning signs of suicide are observed, and local crisis resources.

The effectiveness study was a randomized, stepped-wedge cluster design intervention that included 905 patients in 15 busy community group–based intensive outpatient addiction treatment programs in Western Washington. Patients were randomized to counselor-delivered PARS or treatment as usual, with follow-up assessments at 2 weeks and 1, 3, and 6 months.

There was no attempt to enrich the study population for suicidality by prescreening potential enrollees, since participation in a drug and alcohol treatment program already places an individual in a high-risk group. For example, 74% of study participants indicated they had thought of suicide at least once in the past year, compared with a background rate of 4% in the U.S. general population. And 29% of study participants reported a lifetime history of one or more suicide attempts, versus roughly 5% in the general population.

Dr. Ries’ coinvestigator, Katherine Anne Comtois, PhD, MPH, presented the study results. The three key outcomes were improvement on structured measures of suicide knowledge, attitudes, and help-seeking behavior. The PARS recipients showed statistically significant improvement compared with baseline on two of the three: they displayed greater knowledge about suicide and its close relationship with addiction, and less stigmatization and other maladaptive attitudes toward suicide. Scores on all three measures remained unchanged over time in the control group.

“Overall, we had small to medium effect sizes, comparable to what you might see in studies measuring antidepressant effect sizes. I think these were meaningful improvements in knowledge and attitudes,” said Dr. Comtois of the University of Washington.

The PARS group showed a small increase in the third endpoint – willingness to seek professional help for themselves, friends, or family if depressed or suicidal, but this didn’t achieve statistical significance. However, Dr. Comtois noted that the study outcomes were assessed per protocol using an intent-to-treat analysis. This likely underestimated the true effectiveness of the PARS intervention, given that 40% of patients randomized to PARS didn’t actually attend the intervention session.

“People with drug and alcohol problems have complicated lives,” she said by way of explanation for the high no-show rate.

The investigators are now performing a per-protocol analysis of the data, restricted to those subjects who actually attended their session. A long-term look at suicide events and outcomes in the study population is planned.

Dr. Ries and Dr. Comtois reported having no financial conflicts regarding the study, which was funded by a multiyear grant from the National Institute on Drug Abuse.

bjancin@mdedge.com

A single 3-hour-long group psychosocial intervention designed specifically for patients in intensive outpatient programs for addiction treatment to prevent future suicide resulted in significantly improved knowledge and attitudes regarding suicide that persisted at 6 months of follow-up in a large multicenter randomized effectiveness study, reported Richard K. Ries, MD.

There is an enormous unmet need for evidence-based strategies for preventing addiction-related suicide, since people with substance use disorders have a 10-fold increased risk of suicide. Based upon these new study findings, the Preventing Addiction Related Suicide (PARS) program can now be considered the first such evidence-based intervention for this extremely high-risk population, Dr. Ries said at the virtual annual meeting of the American Association of Suicidology.

“We’ve shown that suicide prevention in intensive outpatient program addiction groups is feasible, easy to train, and highly rated by counselors, and I’d say it’s very adaptable, easy to go national in almost any addiction treatment program, right out of the box,” said Dr. Ries, professor of psychiatry at the University of Washington, Seattle, and director of outpatient psychiatry as well as the psychiatry addiction division at Harborview Medical Center.

The workbook-based PARS program developed by Dr. Ries and colleagues adapted empirically supported suicide prevention best practices from other settings for use in group-based intensive outpatient addiction treatment, which is the most common form of treatment for chemical dependency in the United States. Dr. Ries recognized the need for a program such as PARS because addiction counselors often feel out of their depth regarding suicide-related issues.

“Nothing had ever really been done before on any scale on suicide prevention in addiction centers,” he explained. “We designed the PARS intervention to be integrated right into the counselors’ workflow. They get trained right in their setting in a one-shot deal that takes 2-3 hours. The training was highly rated by counselors as acceptable and effective in their day-to-day work, not ivory tower-type stuff.”

Once the counselors were trained in PARS, they then trained their alcohol- and drug-addicted patients. Elements of the PARS program include information on suicide risk and protective factors, myths and facts about suicide, action steps to take when warning signs of suicide are observed, and local crisis resources.

The effectiveness study was a randomized, stepped-wedge cluster design intervention that included 905 patients in 15 busy community group–based intensive outpatient addiction treatment programs in Western Washington. Patients were randomized to counselor-delivered PARS or treatment as usual, with follow-up assessments at 2 weeks and 1, 3, and 6 months.

There was no attempt to enrich the study population for suicidality by prescreening potential enrollees, since participation in a drug and alcohol treatment program already places an individual in a high-risk group. For example, 74% of study participants indicated they had thought of suicide at least once in the past year, compared with a background rate of 4% in the U.S. general population. And 29% of study participants reported a lifetime history of one or more suicide attempts, versus roughly 5% in the general population.

Dr. Ries’ coinvestigator, Katherine Anne Comtois, PhD, MPH, presented the study results. The three key outcomes were improvement on structured measures of suicide knowledge, attitudes, and help-seeking behavior. The PARS recipients showed statistically significant improvement compared with baseline on two of the three: they displayed greater knowledge about suicide and its close relationship with addiction, and less stigmatization and other maladaptive attitudes toward suicide. Scores on all three measures remained unchanged over time in the control group.

“Overall, we had small to medium effect sizes, comparable to what you might see in studies measuring antidepressant effect sizes. I think these were meaningful improvements in knowledge and attitudes,” said Dr. Comtois of the University of Washington.

The PARS group showed a small increase in the third endpoint – willingness to seek professional help for themselves, friends, or family if depressed or suicidal, but this didn’t achieve statistical significance. However, Dr. Comtois noted that the study outcomes were assessed per protocol using an intent-to-treat analysis. This likely underestimated the true effectiveness of the PARS intervention, given that 40% of patients randomized to PARS didn’t actually attend the intervention session.

“People with drug and alcohol problems have complicated lives,” she said by way of explanation for the high no-show rate.

The investigators are now performing a per-protocol analysis of the data, restricted to those subjects who actually attended their session. A long-term look at suicide events and outcomes in the study population is planned.

Dr. Ries and Dr. Comtois reported having no financial conflicts regarding the study, which was funded by a multiyear grant from the National Institute on Drug Abuse.

bjancin@mdedge.com

Patients on a tumor necrosis factor inhibitor for their rheumatic disease when they became infected with COVID-19 were markedly less likely to subsequently require hospitalization, according to intriguing early evidence from the COVID-19 Global Rheumatology Alliance Registry.

On the other hand, those registry patients who were on 10 mg of prednisone or more daily when they got infected were more than twice as likely to be hospitalized than were those who were not on corticosteroids, even after controlling for the severity of their rheumatic disease and other potential confounders, Jinoos Yazdany, MD, reported at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

“We saw a signal with moderate to high-dose steroids. I think it’s something we’re going to have to keep an eye out on as more data come in,” said Dr. Yazdany, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital.

The global registry launched on March 24, 2020, and was quickly embraced by rheumatologists from around the world. By May 12, the registry included more than 1,300 patients with a range of rheumatic diseases, all with confirmed COVID-19 infection as a requisite for enrollment; the cases were submitted by more than 300 rheumatologists in 40 countries. The registry is supported by the ACR and European League Against Rheumatism.

Dr. Yazdany, a member of the registry steering committee, described the project’s two main goals: To learn the outcomes of COVID-19–infected patients with various rheumatic diseases and to make inferences regarding the impact of the immunosuppressive and antimalarial medications widely prescribed by rheumatologists.

She presented soon-to-be-published data on the characteristics and disposition of the first 600 patients, 46% of whom were hospitalized and 9% died. A caveat regarding the registry, she noted, is that these are observational data and thus potentially subject to unrecognized confounders. Also, the registry population is skewed toward the sicker end of the COVID-19 disease spectrum because while all participants have confirmed infection, testing for the infection has been notoriously uneven. Many people are infected asymptomatically and thus may not undergo testing even where readily available.
 

Early key findings from registry

The risk factors for more severe infection resulting in hospitalization in patients with rheumatic diseases are by and large the same drivers described in the general population: older age and comorbid conditions including diabetes, hypertension, cardiovascular disease, obesity, chronic kidney disease, and lung disease. Notably, however, patients on the equivalent of 10 mg/day of prednisone or more were at a 105% increased risk for hospitalization, compared with those not on corticosteroids after adjustment for age, comorbid conditions, and rheumatic disease severity.

Patients on a background tumor necrosis factor (TNF) inhibitor had an adjusted 60% reduction in risk of hospitalization. This apparent protective effect against more severe COVID-19 disease is mechanistically plausible: In animal studies, being on a TNF inhibitor has been associated with less severe infection following exposure to influenza virus, Dr. Yazdany observed.

COVID-infected patients on any biologic disease-modifying antirheumatic drug had a 54% decreased risk of hospitalization. However, in this early analysis, the study was sufficiently powered only to specifically assess the impact of TNF inhibitors, since those agents were by far the most commonly used biologics. As the registry grows, it will be possible to analyze the impact of other antirheumatic medications.

Being on hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization.

The only rheumatic disease diagnosis with an odds of hospitalization significantly different from that of RA patients was systemic lupus erythematosus (SLE). Lupus patients were at 80% increased risk of hospitalization. Although this was a statistically significant difference, Dr. Yazdany cautioned against making too much of it because of the strong potential for unmeasured confounding. In particular, lupus patients as a group are known to rate on the lower end of measures of social determinants of health, a status that is an established major risk factor for COVID-19 disease.

“A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” she said.

Being on background NSAIDs at the time of SARS-CoV-2 infection was not associated with increased risk of hospitalization; in fact, NSAID users were 36% less likely to be hospitalized for their COVID-19 disease, although this difference didn’t reach statistical significance.

Dr. Yazdany urged her fellow rheumatologists to enter their cases on the registry website: rheum-covid.org. There they can also join the registry mailing list and receive weekly updates.
 

Other recent insights on COVID-19 in rheumatology

An as-yet unpublished U.K. observational study involving electronic health record data on 17 million people included 885,000 individuals with RA, SLE, or psoriasis. After extensive statistical controlling for the known risk factors for severe COVID-19 infection, including a measure of socioeconomic deprivation, the group with one of these autoimmune diseases had an adjusted, statistically significant 23% increased risk of hospital death because of COVID-19 infection.

“This is the largest study of its kind to date. There’s potential for unmeasured confounding and selection bias here due to who gets tested. We’ll have to see where this study lands, but I think it does suggest there’s a slightly higher mortality risk in COVID-infected patients with rheumatic disease,” according to Dr. Yazdany.

On the other hand, there have been at least eight recently published patient surveys and case series of patients with rheumatic diseases in areas of the world hardest hit by the pandemic, and they paint a consistent picture.

“What we’ve learned from these studies was the infection rate was generally in the ballpark of people in the region. It doesn’t seem like there’s a dramatically higher infection rate in people with rheumatic disease in these surveys. The hospitalized rheumatology patients had many of the familiar comorbidities. This is the first glance at how likely people are to become infected and how they fared, and I think overall the data have been quite reassuring,” she said.

Dr. Yazdany reported serving as a consultant to AstraZeneca and Eli Lilly and receiving research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention.

bjancin@mdedge.com

Patients on a tumor necrosis factor inhibitor for their rheumatic disease when they became infected with COVID-19 were markedly less likely to subsequently require hospitalization, according to intriguing early evidence from the COVID-19 Global Rheumatology Alliance Registry.

On the other hand, those registry patients who were on 10 mg of prednisone or more daily when they got infected were more than twice as likely to be hospitalized than were those who were not on corticosteroids, even after controlling for the severity of their rheumatic disease and other potential confounders, Jinoos Yazdany, MD, reported at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

“We saw a signal with moderate to high-dose steroids. I think it’s something we’re going to have to keep an eye out on as more data come in,” said Dr. Yazdany, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital.

The global registry launched on March 24, 2020, and was quickly embraced by rheumatologists from around the world. By May 12, the registry included more than 1,300 patients with a range of rheumatic diseases, all with confirmed COVID-19 infection as a requisite for enrollment; the cases were submitted by more than 300 rheumatologists in 40 countries. The registry is supported by the ACR and European League Against Rheumatism.

Dr. Yazdany, a member of the registry steering committee, described the project’s two main goals: To learn the outcomes of COVID-19–infected patients with various rheumatic diseases and to make inferences regarding the impact of the immunosuppressive and antimalarial medications widely prescribed by rheumatologists.

She presented soon-to-be-published data on the characteristics and disposition of the first 600 patients, 46% of whom were hospitalized and 9% died. A caveat regarding the registry, she noted, is that these are observational data and thus potentially subject to unrecognized confounders. Also, the registry population is skewed toward the sicker end of the COVID-19 disease spectrum because while all participants have confirmed infection, testing for the infection has been notoriously uneven. Many people are infected asymptomatically and thus may not undergo testing even where readily available.
 

Early key findings from registry

The risk factors for more severe infection resulting in hospitalization in patients with rheumatic diseases are by and large the same drivers described in the general population: older age and comorbid conditions including diabetes, hypertension, cardiovascular disease, obesity, chronic kidney disease, and lung disease. Notably, however, patients on the equivalent of 10 mg/day of prednisone or more were at a 105% increased risk for hospitalization, compared with those not on corticosteroids after adjustment for age, comorbid conditions, and rheumatic disease severity.

Patients on a background tumor necrosis factor (TNF) inhibitor had an adjusted 60% reduction in risk of hospitalization. This apparent protective effect against more severe COVID-19 disease is mechanistically plausible: In animal studies, being on a TNF inhibitor has been associated with less severe infection following exposure to influenza virus, Dr. Yazdany observed.

COVID-infected patients on any biologic disease-modifying antirheumatic drug had a 54% decreased risk of hospitalization. However, in this early analysis, the study was sufficiently powered only to specifically assess the impact of TNF inhibitors, since those agents were by far the most commonly used biologics. As the registry grows, it will be possible to analyze the impact of other antirheumatic medications.

Being on hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization.

The only rheumatic disease diagnosis with an odds of hospitalization significantly different from that of RA patients was systemic lupus erythematosus (SLE). Lupus patients were at 80% increased risk of hospitalization. Although this was a statistically significant difference, Dr. Yazdany cautioned against making too much of it because of the strong potential for unmeasured confounding. In particular, lupus patients as a group are known to rate on the lower end of measures of social determinants of health, a status that is an established major risk factor for COVID-19 disease.

“A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” she said.

Being on background NSAIDs at the time of SARS-CoV-2 infection was not associated with increased risk of hospitalization; in fact, NSAID users were 36% less likely to be hospitalized for their COVID-19 disease, although this difference didn’t reach statistical significance.

Dr. Yazdany urged her fellow rheumatologists to enter their cases on the registry website: rheum-covid.org. There they can also join the registry mailing list and receive weekly updates.
 

Other recent insights on COVID-19 in rheumatology

An as-yet unpublished U.K. observational study involving electronic health record data on 17 million people included 885,000 individuals with RA, SLE, or psoriasis. After extensive statistical controlling for the known risk factors for severe COVID-19 infection, including a measure of socioeconomic deprivation, the group with one of these autoimmune diseases had an adjusted, statistically significant 23% increased risk of hospital death because of COVID-19 infection.

“This is the largest study of its kind to date. There’s potential for unmeasured confounding and selection bias here due to who gets tested. We’ll have to see where this study lands, but I think it does suggest there’s a slightly higher mortality risk in COVID-infected patients with rheumatic disease,” according to Dr. Yazdany.

On the other hand, there have been at least eight recently published patient surveys and case series of patients with rheumatic diseases in areas of the world hardest hit by the pandemic, and they paint a consistent picture.

“What we’ve learned from these studies was the infection rate was generally in the ballpark of people in the region. It doesn’t seem like there’s a dramatically higher infection rate in people with rheumatic disease in these surveys. The hospitalized rheumatology patients had many of the familiar comorbidities. This is the first glance at how likely people are to become infected and how they fared, and I think overall the data have been quite reassuring,” she said.

Dr. Yazdany reported serving as a consultant to AstraZeneca and Eli Lilly and receiving research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention.

bjancin@mdedge.com

Patients on a tumor necrosis factor inhibitor for their rheumatic disease when they became infected with COVID-19 were markedly less likely to subsequently require hospitalization, according to intriguing early evidence from the COVID-19 Global Rheumatology Alliance Registry.

On the other hand, those registry patients who were on 10 mg of prednisone or more daily when they got infected were more than twice as likely to be hospitalized than were those who were not on corticosteroids, even after controlling for the severity of their rheumatic disease and other potential confounders, Jinoos Yazdany, MD, reported at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

“We saw a signal with moderate to high-dose steroids. I think it’s something we’re going to have to keep an eye out on as more data come in,” said Dr. Yazdany, professor of medicine at the University of California, San Francisco, and chief of rheumatology at San Francisco General Hospital.

The global registry launched on March 24, 2020, and was quickly embraced by rheumatologists from around the world. By May 12, the registry included more than 1,300 patients with a range of rheumatic diseases, all with confirmed COVID-19 infection as a requisite for enrollment; the cases were submitted by more than 300 rheumatologists in 40 countries. The registry is supported by the ACR and European League Against Rheumatism.

Dr. Yazdany, a member of the registry steering committee, described the project’s two main goals: To learn the outcomes of COVID-19–infected patients with various rheumatic diseases and to make inferences regarding the impact of the immunosuppressive and antimalarial medications widely prescribed by rheumatologists.

She presented soon-to-be-published data on the characteristics and disposition of the first 600 patients, 46% of whom were hospitalized and 9% died. A caveat regarding the registry, she noted, is that these are observational data and thus potentially subject to unrecognized confounders. Also, the registry population is skewed toward the sicker end of the COVID-19 disease spectrum because while all participants have confirmed infection, testing for the infection has been notoriously uneven. Many people are infected asymptomatically and thus may not undergo testing even where readily available.
 

Early key findings from registry

The risk factors for more severe infection resulting in hospitalization in patients with rheumatic diseases are by and large the same drivers described in the general population: older age and comorbid conditions including diabetes, hypertension, cardiovascular disease, obesity, chronic kidney disease, and lung disease. Notably, however, patients on the equivalent of 10 mg/day of prednisone or more were at a 105% increased risk for hospitalization, compared with those not on corticosteroids after adjustment for age, comorbid conditions, and rheumatic disease severity.

Patients on a background tumor necrosis factor (TNF) inhibitor had an adjusted 60% reduction in risk of hospitalization. This apparent protective effect against more severe COVID-19 disease is mechanistically plausible: In animal studies, being on a TNF inhibitor has been associated with less severe infection following exposure to influenza virus, Dr. Yazdany observed.

COVID-infected patients on any biologic disease-modifying antirheumatic drug had a 54% decreased risk of hospitalization. However, in this early analysis, the study was sufficiently powered only to specifically assess the impact of TNF inhibitors, since those agents were by far the most commonly used biologics. As the registry grows, it will be possible to analyze the impact of other antirheumatic medications.

Being on hydroxychloroquine or other antimalarials at the time of COVID-19 infection had no impact on hospitalization.

The only rheumatic disease diagnosis with an odds of hospitalization significantly different from that of RA patients was systemic lupus erythematosus (SLE). Lupus patients were at 80% increased risk of hospitalization. Although this was a statistically significant difference, Dr. Yazdany cautioned against making too much of it because of the strong potential for unmeasured confounding. In particular, lupus patients as a group are known to rate on the lower end of measures of social determinants of health, a status that is an established major risk factor for COVID-19 disease.

“A strength of the global registry has been that it provides timely data that’s been very helpful for rheumatologists to rapidly dispel misinformation that has been spread about hydroxychloroquine, especially statements about lupus patients not getting COVID-19. We know from these data that’s not true,” she said.

Being on background NSAIDs at the time of SARS-CoV-2 infection was not associated with increased risk of hospitalization; in fact, NSAID users were 36% less likely to be hospitalized for their COVID-19 disease, although this difference didn’t reach statistical significance.

Dr. Yazdany urged her fellow rheumatologists to enter their cases on the registry website: rheum-covid.org. There they can also join the registry mailing list and receive weekly updates.
 

Other recent insights on COVID-19 in rheumatology

An as-yet unpublished U.K. observational study involving electronic health record data on 17 million people included 885,000 individuals with RA, SLE, or psoriasis. After extensive statistical controlling for the known risk factors for severe COVID-19 infection, including a measure of socioeconomic deprivation, the group with one of these autoimmune diseases had an adjusted, statistically significant 23% increased risk of hospital death because of COVID-19 infection.

“This is the largest study of its kind to date. There’s potential for unmeasured confounding and selection bias here due to who gets tested. We’ll have to see where this study lands, but I think it does suggest there’s a slightly higher mortality risk in COVID-infected patients with rheumatic disease,” according to Dr. Yazdany.

On the other hand, there have been at least eight recently published patient surveys and case series of patients with rheumatic diseases in areas of the world hardest hit by the pandemic, and they paint a consistent picture.

“What we’ve learned from these studies was the infection rate was generally in the ballpark of people in the region. It doesn’t seem like there’s a dramatically higher infection rate in people with rheumatic disease in these surveys. The hospitalized rheumatology patients had many of the familiar comorbidities. This is the first glance at how likely people are to become infected and how they fared, and I think overall the data have been quite reassuring,” she said.

Dr. Yazdany reported serving as a consultant to AstraZeneca and Eli Lilly and receiving research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Centers for Disease Control and Prevention.

bjancin@mdedge.com

Children with congenital heart disease exposed to low-dose ionizing radiation from cardiac procedures had a cancer risk more than triple that of pediatric congenital heart disease (CHD) patients without such exposures, according to a large Canadian nested case-control study presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

This cancer risk was dose dependent. It rose stepwise with the number of cardiac procedures involving exposure to low-dose ionizing radiation (LDIR) and the total radiation dose. Moreover, roughly 80% of the cancers were of types known to be associated with radiation exposure in children, reported Elie Ganni, a medical student at McGill University, Montreal, working with MAUDE, the McGill Adult Unit for Congenital Heart Disease.

The MAUDE group previously published the first large, population-based study analyzing the association between LDIR from cardiac procedures and incident cancer in adults with CHD. The study, which included nearly 25,000 adult CHD patients aged 18-64 years with more than 250,000 person-years of follow-up, concluded that individuals with LDIR exposure from six or more cardiac procedures had a 140% greater cancer incidence than those with no or one exposure (Circulation. 2018 Mar 27;137[13]:1334-45).

Because children are considered to be more sensitive to the carcinogenic effects of LDIR than adults, the MAUDE group next did a similar study in a pediatric CHD population included in the Quebec Congenital Heart Disease Database. This nested case-control study included 232 children with CHD who were first diagnosed with cancer at a median age of 3.9 years and 8,160 pediatric CHD controls matched for gender and birth year. About 76% of cancers were diagnosed before age 7, 20% at ages 7-12 years, and the remaining 4% at ages 13-18. Hematologic malignancies accounted for 61% of the pediatric cancers, CNS cancers for another 12.5%, and thyroid cancers 6.6%; all three types of cancer are associated with radiation exposure.

After excluding all cardiac procedures involving LDIR performed within 6 months prior to cancer diagnosis, the risk of developing a pediatric cancer was 230% greater in children with LDIR exposure from cardiac procedures than in CHD patients without such exposure. For every 4 mSv in estimated LDIR exposure from cardiac procedures, the risk of cancer rose by 15.5%. In contrast, in the earlier study in adults with CHD, cancer risk climbed by 10% per 10 mSv. Patients with six or more LDIR cardiac procedures – not at all unusual in contemporary practice – were 2.4 times more likely to have cancer than those with no or one such radiation exposure.

Current ACC guidelines on radiation exposure from cardiac procedures recommend calculating an individual’s lifetime attributable cancer incidence and mortality risks, as well as adhering to the time-honored principle of ensuring that radiation exposure is as low as reasonably achievable without sacrificing quality of care.

“Our findings strongly support these ACC recommendations and moreover suggest that radiation surveillance for patients with congenital heart disease should be considered using radiation badges. Also, cancer surveillance guidelines should be considered for CHD patients exposed to LDIR,” Mr. Ganni said.

These suggestions for creation of patient radiation passports and cancer surveillance guidelines take on greater weight in light of two trends: the increasing life expectancy of children with CHD during the past 3 decades as a result of procedural advances that entail LDIR exposure, mostly for imaging, and the growing number of such procedures performed per patient earlier and earlier in life.

He and the MAUDE group plan to confirm their latest findings in other, larger data sets and hope to identify threshold effects for LDIR for specific cancers, with hematologic malignancies as the top priority.

Mr. Ganni reported having no financial conflicts regarding his study, funded by the Heart and Stroke Foundation of Canada, the Quebec Foundation for Health Research, and the Canadian Institutes for Health Research.

bjancin@mdedge.com

Children with congenital heart disease exposed to low-dose ionizing radiation from cardiac procedures had a cancer risk more than triple that of pediatric congenital heart disease (CHD) patients without such exposures, according to a large Canadian nested case-control study presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

This cancer risk was dose dependent. It rose stepwise with the number of cardiac procedures involving exposure to low-dose ionizing radiation (LDIR) and the total radiation dose. Moreover, roughly 80% of the cancers were of types known to be associated with radiation exposure in children, reported Elie Ganni, a medical student at McGill University, Montreal, working with MAUDE, the McGill Adult Unit for Congenital Heart Disease.

The MAUDE group previously published the first large, population-based study analyzing the association between LDIR from cardiac procedures and incident cancer in adults with CHD. The study, which included nearly 25,000 adult CHD patients aged 18-64 years with more than 250,000 person-years of follow-up, concluded that individuals with LDIR exposure from six or more cardiac procedures had a 140% greater cancer incidence than those with no or one exposure (Circulation. 2018 Mar 27;137[13]:1334-45).

Because children are considered to be more sensitive to the carcinogenic effects of LDIR than adults, the MAUDE group next did a similar study in a pediatric CHD population included in the Quebec Congenital Heart Disease Database. This nested case-control study included 232 children with CHD who were first diagnosed with cancer at a median age of 3.9 years and 8,160 pediatric CHD controls matched for gender and birth year. About 76% of cancers were diagnosed before age 7, 20% at ages 7-12 years, and the remaining 4% at ages 13-18. Hematologic malignancies accounted for 61% of the pediatric cancers, CNS cancers for another 12.5%, and thyroid cancers 6.6%; all three types of cancer are associated with radiation exposure.

After excluding all cardiac procedures involving LDIR performed within 6 months prior to cancer diagnosis, the risk of developing a pediatric cancer was 230% greater in children with LDIR exposure from cardiac procedures than in CHD patients without such exposure. For every 4 mSv in estimated LDIR exposure from cardiac procedures, the risk of cancer rose by 15.5%. In contrast, in the earlier study in adults with CHD, cancer risk climbed by 10% per 10 mSv. Patients with six or more LDIR cardiac procedures – not at all unusual in contemporary practice – were 2.4 times more likely to have cancer than those with no or one such radiation exposure.

Current ACC guidelines on radiation exposure from cardiac procedures recommend calculating an individual’s lifetime attributable cancer incidence and mortality risks, as well as adhering to the time-honored principle of ensuring that radiation exposure is as low as reasonably achievable without sacrificing quality of care.

“Our findings strongly support these ACC recommendations and moreover suggest that radiation surveillance for patients with congenital heart disease should be considered using radiation badges. Also, cancer surveillance guidelines should be considered for CHD patients exposed to LDIR,” Mr. Ganni said.

These suggestions for creation of patient radiation passports and cancer surveillance guidelines take on greater weight in light of two trends: the increasing life expectancy of children with CHD during the past 3 decades as a result of procedural advances that entail LDIR exposure, mostly for imaging, and the growing number of such procedures performed per patient earlier and earlier in life.

He and the MAUDE group plan to confirm their latest findings in other, larger data sets and hope to identify threshold effects for LDIR for specific cancers, with hematologic malignancies as the top priority.

Mr. Ganni reported having no financial conflicts regarding his study, funded by the Heart and Stroke Foundation of Canada, the Quebec Foundation for Health Research, and the Canadian Institutes for Health Research.

bjancin@mdedge.com

Children with congenital heart disease exposed to low-dose ionizing radiation from cardiac procedures had a cancer risk more than triple that of pediatric congenital heart disease (CHD) patients without such exposures, according to a large Canadian nested case-control study presented at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The meeting was conducted online after its cancellation because of the COVID-19 pandemic.

This cancer risk was dose dependent. It rose stepwise with the number of cardiac procedures involving exposure to low-dose ionizing radiation (LDIR) and the total radiation dose. Moreover, roughly 80% of the cancers were of types known to be associated with radiation exposure in children, reported Elie Ganni, a medical student at McGill University, Montreal, working with MAUDE, the McGill Adult Unit for Congenital Heart Disease.

The MAUDE group previously published the first large, population-based study analyzing the association between LDIR from cardiac procedures and incident cancer in adults with CHD. The study, which included nearly 25,000 adult CHD patients aged 18-64 years with more than 250,000 person-years of follow-up, concluded that individuals with LDIR exposure from six or more cardiac procedures had a 140% greater cancer incidence than those with no or one exposure (Circulation. 2018 Mar 27;137[13]:1334-45).

Because children are considered to be more sensitive to the carcinogenic effects of LDIR than adults, the MAUDE group next did a similar study in a pediatric CHD population included in the Quebec Congenital Heart Disease Database. This nested case-control study included 232 children with CHD who were first diagnosed with cancer at a median age of 3.9 years and 8,160 pediatric CHD controls matched for gender and birth year. About 76% of cancers were diagnosed before age 7, 20% at ages 7-12 years, and the remaining 4% at ages 13-18. Hematologic malignancies accounted for 61% of the pediatric cancers, CNS cancers for another 12.5%, and thyroid cancers 6.6%; all three types of cancer are associated with radiation exposure.

After excluding all cardiac procedures involving LDIR performed within 6 months prior to cancer diagnosis, the risk of developing a pediatric cancer was 230% greater in children with LDIR exposure from cardiac procedures than in CHD patients without such exposure. For every 4 mSv in estimated LDIR exposure from cardiac procedures, the risk of cancer rose by 15.5%. In contrast, in the earlier study in adults with CHD, cancer risk climbed by 10% per 10 mSv. Patients with six or more LDIR cardiac procedures – not at all unusual in contemporary practice – were 2.4 times more likely to have cancer than those with no or one such radiation exposure.

Current ACC guidelines on radiation exposure from cardiac procedures recommend calculating an individual’s lifetime attributable cancer incidence and mortality risks, as well as adhering to the time-honored principle of ensuring that radiation exposure is as low as reasonably achievable without sacrificing quality of care.

“Our findings strongly support these ACC recommendations and moreover suggest that radiation surveillance for patients with congenital heart disease should be considered using radiation badges. Also, cancer surveillance guidelines should be considered for CHD patients exposed to LDIR,” Mr. Ganni said.

These suggestions for creation of patient radiation passports and cancer surveillance guidelines take on greater weight in light of two trends: the increasing life expectancy of children with CHD during the past 3 decades as a result of procedural advances that entail LDIR exposure, mostly for imaging, and the growing number of such procedures performed per patient earlier and earlier in life.

He and the MAUDE group plan to confirm their latest findings in other, larger data sets and hope to identify threshold effects for LDIR for specific cancers, with hematologic malignancies as the top priority.

Mr. Ganni reported having no financial conflicts regarding his study, funded by the Heart and Stroke Foundation of Canada, the Quebec Foundation for Health Research, and the Canadian Institutes for Health Research.

bjancin@mdedge.com

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

mzoler@mdedge.com

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

mzoler@mdedge.com

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

A leadless right-ventricular pacemaker continued to show an edge over conventional transvenous pacemakers by triggering a substantially reduced rate of complications during the 6 months following placement in a review of more than 10,000 Medicare patients treated over 2 years.

The “largest leadless pacemaker cohort to date” showed that in propensity score–matched cohorts, the 3,276 patients who received the Micra leadless transcatheter pacemaker during routine management and were followed for 6 months had a 3.3% rate of total complications, compared with a 9.4% rate among 7,256 patients who received a conventional VVI pacemaker with a transvenous lead, a statistically significant 66% relative risk reduction, Jonathan P. Piccini, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.

The 66% reduced rate of complications – both acutely and with further follow-up – was similar to the complication reductions seen with Micra, compared with historical controls who received transvenous single-chamber pacemakers in both the pivotal study for the device (Heart Rhythm. 2017 May 1;14[3]:702-9) and in a postapproval registry study (Heart Rhythm. 2018 Dec 1;15[12]:1800-7). However, the newly reported advantage came in a population that was notably older and had significantly more comorbidities than in the prior leadless pacemaker studies, said Dr. Piccini, a cardiac electrophysiologist at Duke University, Durham, N.C.

The new Medicare data “tell us that physicians are reaching for these devices [leadless pacemakers] in patients with more comorbidities and a higher risk for complications to give them a [device with] better safety profile,” he said during a press briefing. “At Duke, and I suspect at other centers, when a patients is eligible for a leadless pacemaker that’s the preferred option.”

However, Dr. Piccini cited three examples of the small proportion of patients who are appropriate for the type of pacing the leadless pacemaker supplies but would be better candidates for a device with a transvenous lead: patients who failed treatment with a initial leadless pacemaker and have no suitable alternative subcutaneous spot to place the replacement device in a stable way, those with severe right ventricular enlargement that interferes with optimal placement, and those who don’t currently meet criteria for biventricular pacing but appear likely to switch to that pacing mode in the near term.

The 66% relative reduction in complications was “impressive; I hope this will be a message,” commented Nassir F. Marrouche, MD, a cardiac electrophysiologist and professor of medicine at Tulane University, New Orleans. Importantly, this reduced complication rate occurred in a real-world population that was sicker than any patient group previously studied with the device, he noted as a designated discussant for the report.

But the report’s second designated discussant, Roderick Tung, MD, highlighted some caveats when interpreting the lower complication rate with the leadless device compared with historical controls. He cited the absence of any episodes of pneumothorax among the patients reviewed by Dr. Piccini who received a leadless pacemaker, compared with a 5% rate among the control patients who had received a device with a transvenous lead, a major driver of the overall difference in complication rates. This difference “may not be relevant to operators who use either an axillary extrathoracic vein route for lead placement or a cephalic vein approach,” said Dr. Tung, director of cardiac electrophysiology at the University of Chicago. “There should not be a 5% rate of pneumothorax when implanting a VVI device.” The results reported by Dr. Piccini have the advantages of coming from many patients and from real-world practice, he acknowledged, but interpretation is limited by the lack of a randomized control group and the outsized impact of pneumothorax complications on the safety comparison.

The other major component of the 6-month complication tally was device-related events, which were twice as common in the historical controls who received a transvenous lead at a rate of 3.4%. The sole 6-month event more common among the patients who received a leadless pacemaker was pericarditis, at a rate of 1.3% in the Micra group and 0.5% in the transvenous lead controls, Dr. Piccini reported. The 6-month rate of device revisions was 1.7% with the leadless device and 2.8% with transvenous lead pacemakers, a difference that was not statistically significant. The two treatment arms had virtually identical 6-month mortality rates.

The rate of acute complications during the first 30 days after implant was also virtually the same in the two study arms. Patient who received the leadless device had significantly more puncture-site events, at a rate of 1.2%, and significantly more cardiac effusions or perforations, at a rate of 0.8%. The historical control patients who received devices with transvenous leads had significantly more device-related complications after 30 days, a 2.5% rate.

The 30-day cohorts examined had larger numbers of patients than at 6 months, 5,746 leadless pacemaker recipients and 9,662 matched historical controls who had received a transvenous lead pacemaker. The clinical and demographic profile of the 30-day cohort who received the leadless pacemaker highlighted the sicker nature of these patients compared with earlier studies of the device. They were an average age of 79 years, compared with average ages of 76 years in the two prior Micra studies, and they also had double the prevalence of coronary disease, triple the prevalence of heart failure, more than twice the rate of chronic obstructive pulmonary disease, and almost twice the prevalence of diabetes.

During the period examined in this report from Micra CED (Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers), in 2017-2018, the leadless pacemaker’s initial approved indications were for a circumscribed portion of the overall patient population that needs pacing. Essentially, they were elderly patients with persistent atrial fibrillation who only need ventricular pacing, roughly 15% of the overall cohort of pacing candidates. In January 2020, the FDA added an indication for high-grade atrioventricular block, an expanded population of candidates that roughly tripled the number of potentially appropriate recipients, said Larry A. Chinitz, MD, a cardiac electrophysiologist and a coinvestigator on some of the studies that led to the new indication, in an interview at the time of the revised labeling.

The study was sponsored by Medtronic, which markets the Micra leadless pacemaker. Dr. Piccini has received honoraria from Medtronic and several other companies. Dr. Marrouche has been a consultant to Medtronic as well as to Biosense Webster, Biotronik, Cardiac Design, and Preventice, and has received research funding from Abbott, Biosense Webster, Boston Scientific, and GE Healthcare. Dr. Tung has been a speaker on behalf of Abbott, Boston Scientific, and Biosense Webster. Dr. Chinitz has received fees and fellowship support from Medtronic, and has also received fees from Abbott, Biosense Webster, Biotronik, and Pfizer.

mzoler@mdedge.com

SOURCE: Piccini JP et al. Heart Rhythm 2020, Abstract D-LBCT04-01.

Three investigations that had been scheduled for presentation at the annual meeting of the American Academy of Neurology provide further detail about the efficacy and safety of onasemnogene abeparvovec-xioi in patients with spinal muscular atrophy (SMA). The research was presented online as part of the 2020 AAN Science Highlights.

SMA results from a mutation in SMN1, which encodes the SMN protein necessary for motor function. Deficiency of this protein causes motor neurons to die, resulting in severe muscle weakness. At 2 years of age, untreated patients with SMA type 1 generally die or require permanent ventilation.

The Food and Drug Administration approved onasemnogene abeparvovec-xioi under the brand name Zolgensma in May 2019. The gene-replacement therapy, which is administered once intravenously, delivers a fully functional copy of human SMN1 into the target motor neuron cells. It is indicated as treatment for SMA in infants younger than 2 years of age.
 

Preliminary STR1VE data

Preliminary data from the phase 3 STR1VE study were scheduled to be presented at the meeting. The open-label, single-arm, single-dose study enrolled symptomatic patients with SMA type 1 (SMA1) at multiple US sites. Enrollment was completed in May 2019.

The study included 10 male patients and 12 female patients. Participants’ mean age at dosing was 3.7 months. Of 19 patients who could have reached age 13.6 months at data cutoff, 17 (89.5%) were surviving without permanent ventilation, compared with a 25% survival rate among untreated patients. One of the 19 patients died, and the event was judged to be unrelated to treatment. Another of the 19 reached a respiratory endpoint or withdrew consent.

The population’s mean baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score was 32. This score increased by 6.9, 11.7, and 14.3 points at months 1, 3, and 5, respectively. Half of the 22 infants sat independently for 30 or more seconds, and this milestone was achieved at a mean of 8.2 months after treatment. Five of six (83%) patients age 18 months or older sat independently for 30 or more seconds, which was one of the study’s primary endpoints. As of March 8, 2019, treatment-emergent adverse events of special interest were transient and not associated with any sequelae.

The STR1VE study was sponsored by AveXis, the maker of onasemnogene abeparvovec-xioi. Several of the investigators are employees of AveXis, and others received funding from the company.
 

Long-term follow-up in START

Long-term follow-up data for participants in the phase 1/2a START study also were scheduled to be presented. Patients who completed START were eligible to participate, and the trial’s primary aim was to evaluate the long-term safety of onasemnogene abeparvovec-xioi. Patients are intended to have five annual visits, followed by 10 annual phone calls, and the investigators request local physicians or neurologists to transfer patient records. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include evaluation of the maintenance of developmental milestones.

As of May 31, 2019, 13 patients in two cohorts had been enrolled and had had a baseline visit. For patients in Cohort 2, the mean age and time since dosing were 4.2 years and 3.9 years, respectively. All patients in Cohort 2 were alive and did not require permanent ventilation. Participants did not lose any developmental milestones that they had achieved at the end of START. Two patients were able to walk, and two could stand with assistance during long-term follow-up. This result suggests the durability of the treatment’s effect. No new treatment-related serious adverse events or adverse events of special interest had occurred as of March 8, 2019.

“We know from accumulating experience that treating infants by gene therapy is safe,” said Jerry R. Mendell, MD, the principal investigator and an attending neurologist at Nationwide Children’s Hospital in Columbus, Ohio. “Of the 15 patients we had in our first trial, only four adverse events related to the gene delivery were encountered, and only two of these were considered serious adverse events [i.e., liver enzymes that were 10 times greater than normal laboratory levels]. These laboratory tests occurred without accompanying clinical symptoms or signs. All were suppressed by corticosteroids and related to the liver inflammation. This pattern of safety has been seen in our very large gene therapy experience. No long-term surprises were encountered.”

The START study was sponsored by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
 

Update on the SPR1NT study

Interim safety and efficacy data from the ongoing SPR1NT study, which includes presymptomatic patients, also were scheduled to be presented. The trial “was built on the basic premise that spinal motor neuron degeneration associated with SMN protein deficiency begins in utero, continues to progress rapidly during the first months of life, and is irreversible,” said Kevin Strauss, MD, medical director of the Clinic for Special Children in Strasburg, Pennsylvania. “SPR1NT leveraged the advantages conferred by carrier testing and newborn screening programs for SMA, which allowed the first 22 children enrolled to have a confirmed molecular diagnosis between 1 and 26 days of postnatal life, before the onset of dysphagia, respiratory compromise, or overt weakness.”

In this multicenter, open-label, phase 3 trial, presymptomatic patients age 6 weeks or younger who are expected to develop SMA receive onasemnogene abeparvovec-xioi once and are evaluated during 18 or 24 months. The primary outcomes are sitting for 30 or more seconds for infants with two copies of SMN2 and standing unassisted for infants with three copies of SMN2.

As of December 31, 2019, 29 infants had been treated in the efficacy group at a mean age of 20.6 days among infants with two copies of SMN2 and 28.7 days among infants with three copies of SMN2. All patients are alive, and no patient in SPR1NT required ventilation support at last visit. Among 14 patients with two copies of SMN2, all achieved CHOP INTEND scores of 50 or greater, which exceeds the maximal score observed in untreated patients. Eight have achieved sitting, seven of whom achieved it within the World Health Organization sitting age range of 3.8-9.2 months. The other six patients have not yet passed the WHO developmental window. Among 15 patients with three copies of SMN2, four stood independently and three walked independently, all within the WHO developmental windows of 6.9-16.9 months and 8.2-17.6 months, respectively. The other patients have not yet passed the WHO developmental window. No patient in either cohort required a feeding tube, and most remained within the normal weight range. Treatment-emergent adverse events of special interest were reported in 16 patients. The study is ongoing, and patients continue to meet primary endpoints.

“Comparing functional and motor indices between these two groups [i.e., patients with two copies of SMN2 and those with three copies] should contribute to our understanding of how motor neuron loss during fetal development may impact long-term neurological outcomes over the arc of life and could even form a basis for considering antenatal gene therapy for severe forms of SMA,” said Dr. Strauss.

SPR1NT was funded by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
 

Combination therapy may be a possibility

A benefit of onasemnogene abeparvovec-xioi is that the adeno-associated virus that delivers it does not integrate itself into the genome, said Darryl C. De Vivo, MD, Sidney Carter professor of neurology and professor of pediatrics at Columbia University in New York. “The bad news is that every time the cell divides, the gene therapy goes to one of the two daughter cells, but not to both. ... That means the effectiveness, in theory, would be reduced by 50% with each cell division, possibly affecting the durability of treatment.” The fact that brain and spinal cord neurons are presumed to be fully populated around the time of birth partly mitigates this concern, he added. “There isn’t too much additional cell division going on in neurons after birth at a time when the gene therapy would be administered.”

Furthermore, the cellular distribution of the gene therapy within the nervous system, which is unclear, might affect the therapy’s effect. “These are largely unanswered questions,” said Dr. De Vivo. “The answers to these questions only will come with continued observation of patients who have been treated.”

Considering that nusinersen, the antisense oligonucleotide also approved for SMA, targets SMN2, and the gene therapy replaces SMN1, “there may be some wisdom in thinking about combination therapy,” said Dr. De Vivo. “There’s no doubt that these therapeutic agents are effective,” and continued follow-up will clarify their comparative efficacy, he concluded.

egreb@mdedge.com

SOURCES: Day JW, et al. AAN 2020. Abstract S27.001. Mendell JR, et al. AAN 2020. Abstract S27.002. Strauss KA, et al. AAN 2020. Abstract S27.003.

Three investigations that had been scheduled for presentation at the annual meeting of the American Academy of Neurology provide further detail about the efficacy and safety of onasemnogene abeparvovec-xioi in patients with spinal muscular atrophy (SMA). The research was presented online as part of the 2020 AAN Science Highlights.

SMA results from a mutation in SMN1, which encodes the SMN protein necessary for motor function. Deficiency of this protein causes motor neurons to die, resulting in severe muscle weakness. At 2 years of age, untreated patients with SMA type 1 generally die or require permanent ventilation.

The Food and Drug Administration approved onasemnogene abeparvovec-xioi under the brand name Zolgensma in May 2019. The gene-replacement therapy, which is administered once intravenously, delivers a fully functional copy of human SMN1 into the target motor neuron cells. It is indicated as treatment for SMA in infants younger than 2 years of age.
 

Preliminary STR1VE data

Preliminary data from the phase 3 STR1VE study were scheduled to be presented at the meeting. The open-label, single-arm, single-dose study enrolled symptomatic patients with SMA type 1 (SMA1) at multiple US sites. Enrollment was completed in May 2019.

The study included 10 male patients and 12 female patients. Participants’ mean age at dosing was 3.7 months. Of 19 patients who could have reached age 13.6 months at data cutoff, 17 (89.5%) were surviving without permanent ventilation, compared with a 25% survival rate among untreated patients. One of the 19 patients died, and the event was judged to be unrelated to treatment. Another of the 19 reached a respiratory endpoint or withdrew consent.

The population’s mean baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score was 32. This score increased by 6.9, 11.7, and 14.3 points at months 1, 3, and 5, respectively. Half of the 22 infants sat independently for 30 or more seconds, and this milestone was achieved at a mean of 8.2 months after treatment. Five of six (83%) patients age 18 months or older sat independently for 30 or more seconds, which was one of the study’s primary endpoints. As of March 8, 2019, treatment-emergent adverse events of special interest were transient and not associated with any sequelae.

The STR1VE study was sponsored by AveXis, the maker of onasemnogene abeparvovec-xioi. Several of the investigators are employees of AveXis, and others received funding from the company.
 

Long-term follow-up in START

Long-term follow-up data for participants in the phase 1/2a START study also were scheduled to be presented. Patients who completed START were eligible to participate, and the trial’s primary aim was to evaluate the long-term safety of onasemnogene abeparvovec-xioi. Patients are intended to have five annual visits, followed by 10 annual phone calls, and the investigators request local physicians or neurologists to transfer patient records. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include evaluation of the maintenance of developmental milestones.

As of May 31, 2019, 13 patients in two cohorts had been enrolled and had had a baseline visit. For patients in Cohort 2, the mean age and time since dosing were 4.2 years and 3.9 years, respectively. All patients in Cohort 2 were alive and did not require permanent ventilation. Participants did not lose any developmental milestones that they had achieved at the end of START. Two patients were able to walk, and two could stand with assistance during long-term follow-up. This result suggests the durability of the treatment’s effect. No new treatment-related serious adverse events or adverse events of special interest had occurred as of March 8, 2019.

“We know from accumulating experience that treating infants by gene therapy is safe,” said Jerry R. Mendell, MD, the principal investigator and an attending neurologist at Nationwide Children’s Hospital in Columbus, Ohio. “Of the 15 patients we had in our first trial, only four adverse events related to the gene delivery were encountered, and only two of these were considered serious adverse events [i.e., liver enzymes that were 10 times greater than normal laboratory levels]. These laboratory tests occurred without accompanying clinical symptoms or signs. All were suppressed by corticosteroids and related to the liver inflammation. This pattern of safety has been seen in our very large gene therapy experience. No long-term surprises were encountered.”

The START study was sponsored by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
 

Update on the SPR1NT study

Interim safety and efficacy data from the ongoing SPR1NT study, which includes presymptomatic patients, also were scheduled to be presented. The trial “was built on the basic premise that spinal motor neuron degeneration associated with SMN protein deficiency begins in utero, continues to progress rapidly during the first months of life, and is irreversible,” said Kevin Strauss, MD, medical director of the Clinic for Special Children in Strasburg, Pennsylvania. “SPR1NT leveraged the advantages conferred by carrier testing and newborn screening programs for SMA, which allowed the first 22 children enrolled to have a confirmed molecular diagnosis between 1 and 26 days of postnatal life, before the onset of dysphagia, respiratory compromise, or overt weakness.”

In this multicenter, open-label, phase 3 trial, presymptomatic patients age 6 weeks or younger who are expected to develop SMA receive onasemnogene abeparvovec-xioi once and are evaluated during 18 or 24 months. The primary outcomes are sitting for 30 or more seconds for infants with two copies of SMN2 and standing unassisted for infants with three copies of SMN2.

As of December 31, 2019, 29 infants had been treated in the efficacy group at a mean age of 20.6 days among infants with two copies of SMN2 and 28.7 days among infants with three copies of SMN2. All patients are alive, and no patient in SPR1NT required ventilation support at last visit. Among 14 patients with two copies of SMN2, all achieved CHOP INTEND scores of 50 or greater, which exceeds the maximal score observed in untreated patients. Eight have achieved sitting, seven of whom achieved it within the World Health Organization sitting age range of 3.8-9.2 months. The other six patients have not yet passed the WHO developmental window. Among 15 patients with three copies of SMN2, four stood independently and three walked independently, all within the WHO developmental windows of 6.9-16.9 months and 8.2-17.6 months, respectively. The other patients have not yet passed the WHO developmental window. No patient in either cohort required a feeding tube, and most remained within the normal weight range. Treatment-emergent adverse events of special interest were reported in 16 patients. The study is ongoing, and patients continue to meet primary endpoints.

“Comparing functional and motor indices between these two groups [i.e., patients with two copies of SMN2 and those with three copies] should contribute to our understanding of how motor neuron loss during fetal development may impact long-term neurological outcomes over the arc of life and could even form a basis for considering antenatal gene therapy for severe forms of SMA,” said Dr. Strauss.

SPR1NT was funded by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
 

Combination therapy may be a possibility

A benefit of onasemnogene abeparvovec-xioi is that the adeno-associated virus that delivers it does not integrate itself into the genome, said Darryl C. De Vivo, MD, Sidney Carter professor of neurology and professor of pediatrics at Columbia University in New York. “The bad news is that every time the cell divides, the gene therapy goes to one of the two daughter cells, but not to both. ... That means the effectiveness, in theory, would be reduced by 50% with each cell division, possibly affecting the durability of treatment.” The fact that brain and spinal cord neurons are presumed to be fully populated around the time of birth partly mitigates this concern, he added. “There isn’t too much additional cell division going on in neurons after birth at a time when the gene therapy would be administered.”

Furthermore, the cellular distribution of the gene therapy within the nervous system, which is unclear, might affect the therapy’s effect. “These are largely unanswered questions,” said Dr. De Vivo. “The answers to these questions only will come with continued observation of patients who have been treated.”

Considering that nusinersen, the antisense oligonucleotide also approved for SMA, targets SMN2, and the gene therapy replaces SMN1, “there may be some wisdom in thinking about combination therapy,” said Dr. De Vivo. “There’s no doubt that these therapeutic agents are effective,” and continued follow-up will clarify their comparative efficacy, he concluded.

egreb@mdedge.com

SOURCES: Day JW, et al. AAN 2020. Abstract S27.001. Mendell JR, et al. AAN 2020. Abstract S27.002. Strauss KA, et al. AAN 2020. Abstract S27.003.

Three investigations that had been scheduled for presentation at the annual meeting of the American Academy of Neurology provide further detail about the efficacy and safety of onasemnogene abeparvovec-xioi in patients with spinal muscular atrophy (SMA). The research was presented online as part of the 2020 AAN Science Highlights.

SMA results from a mutation in SMN1, which encodes the SMN protein necessary for motor function. Deficiency of this protein causes motor neurons to die, resulting in severe muscle weakness. At 2 years of age, untreated patients with SMA type 1 generally die or require permanent ventilation.

The Food and Drug Administration approved onasemnogene abeparvovec-xioi under the brand name Zolgensma in May 2019. The gene-replacement therapy, which is administered once intravenously, delivers a fully functional copy of human SMN1 into the target motor neuron cells. It is indicated as treatment for SMA in infants younger than 2 years of age.
 

Preliminary STR1VE data

Preliminary data from the phase 3 STR1VE study were scheduled to be presented at the meeting. The open-label, single-arm, single-dose study enrolled symptomatic patients with SMA type 1 (SMA1) at multiple US sites. Enrollment was completed in May 2019.

The study included 10 male patients and 12 female patients. Participants’ mean age at dosing was 3.7 months. Of 19 patients who could have reached age 13.6 months at data cutoff, 17 (89.5%) were surviving without permanent ventilation, compared with a 25% survival rate among untreated patients. One of the 19 patients died, and the event was judged to be unrelated to treatment. Another of the 19 reached a respiratory endpoint or withdrew consent.

The population’s mean baseline Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score was 32. This score increased by 6.9, 11.7, and 14.3 points at months 1, 3, and 5, respectively. Half of the 22 infants sat independently for 30 or more seconds, and this milestone was achieved at a mean of 8.2 months after treatment. Five of six (83%) patients age 18 months or older sat independently for 30 or more seconds, which was one of the study’s primary endpoints. As of March 8, 2019, treatment-emergent adverse events of special interest were transient and not associated with any sequelae.

The STR1VE study was sponsored by AveXis, the maker of onasemnogene abeparvovec-xioi. Several of the investigators are employees of AveXis, and others received funding from the company.
 

Long-term follow-up in START

Long-term follow-up data for participants in the phase 1/2a START study also were scheduled to be presented. Patients who completed START were eligible to participate, and the trial’s primary aim was to evaluate the long-term safety of onasemnogene abeparvovec-xioi. Patients are intended to have five annual visits, followed by 10 annual phone calls, and the investigators request local physicians or neurologists to transfer patient records. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include evaluation of the maintenance of developmental milestones.

As of May 31, 2019, 13 patients in two cohorts had been enrolled and had had a baseline visit. For patients in Cohort 2, the mean age and time since dosing were 4.2 years and 3.9 years, respectively. All patients in Cohort 2 were alive and did not require permanent ventilation. Participants did not lose any developmental milestones that they had achieved at the end of START. Two patients were able to walk, and two could stand with assistance during long-term follow-up. This result suggests the durability of the treatment’s effect. No new treatment-related serious adverse events or adverse events of special interest had occurred as of March 8, 2019.

“We know from accumulating experience that treating infants by gene therapy is safe,” said Jerry R. Mendell, MD, the principal investigator and an attending neurologist at Nationwide Children’s Hospital in Columbus, Ohio. “Of the 15 patients we had in our first trial, only four adverse events related to the gene delivery were encountered, and only two of these were considered serious adverse events [i.e., liver enzymes that were 10 times greater than normal laboratory levels]. These laboratory tests occurred without accompanying clinical symptoms or signs. All were suppressed by corticosteroids and related to the liver inflammation. This pattern of safety has been seen in our very large gene therapy experience. No long-term surprises were encountered.”

The START study was sponsored by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
 

Update on the SPR1NT study

Interim safety and efficacy data from the ongoing SPR1NT study, which includes presymptomatic patients, also were scheduled to be presented. The trial “was built on the basic premise that spinal motor neuron degeneration associated with SMN protein deficiency begins in utero, continues to progress rapidly during the first months of life, and is irreversible,” said Kevin Strauss, MD, medical director of the Clinic for Special Children in Strasburg, Pennsylvania. “SPR1NT leveraged the advantages conferred by carrier testing and newborn screening programs for SMA, which allowed the first 22 children enrolled to have a confirmed molecular diagnosis between 1 and 26 days of postnatal life, before the onset of dysphagia, respiratory compromise, or overt weakness.”

In this multicenter, open-label, phase 3 trial, presymptomatic patients age 6 weeks or younger who are expected to develop SMA receive onasemnogene abeparvovec-xioi once and are evaluated during 18 or 24 months. The primary outcomes are sitting for 30 or more seconds for infants with two copies of SMN2 and standing unassisted for infants with three copies of SMN2.

As of December 31, 2019, 29 infants had been treated in the efficacy group at a mean age of 20.6 days among infants with two copies of SMN2 and 28.7 days among infants with three copies of SMN2. All patients are alive, and no patient in SPR1NT required ventilation support at last visit. Among 14 patients with two copies of SMN2, all achieved CHOP INTEND scores of 50 or greater, which exceeds the maximal score observed in untreated patients. Eight have achieved sitting, seven of whom achieved it within the World Health Organization sitting age range of 3.8-9.2 months. The other six patients have not yet passed the WHO developmental window. Among 15 patients with three copies of SMN2, four stood independently and three walked independently, all within the WHO developmental windows of 6.9-16.9 months and 8.2-17.6 months, respectively. The other patients have not yet passed the WHO developmental window. No patient in either cohort required a feeding tube, and most remained within the normal weight range. Treatment-emergent adverse events of special interest were reported in 16 patients. The study is ongoing, and patients continue to meet primary endpoints.

“Comparing functional and motor indices between these two groups [i.e., patients with two copies of SMN2 and those with three copies] should contribute to our understanding of how motor neuron loss during fetal development may impact long-term neurological outcomes over the arc of life and could even form a basis for considering antenatal gene therapy for severe forms of SMA,” said Dr. Strauss.

SPR1NT was funded by AveXis. Several of the investigators are employees of AveXis, and others received funding from the company.
 

Combination therapy may be a possibility

A benefit of onasemnogene abeparvovec-xioi is that the adeno-associated virus that delivers it does not integrate itself into the genome, said Darryl C. De Vivo, MD, Sidney Carter professor of neurology and professor of pediatrics at Columbia University in New York. “The bad news is that every time the cell divides, the gene therapy goes to one of the two daughter cells, but not to both. ... That means the effectiveness, in theory, would be reduced by 50% with each cell division, possibly affecting the durability of treatment.” The fact that brain and spinal cord neurons are presumed to be fully populated around the time of birth partly mitigates this concern, he added. “There isn’t too much additional cell division going on in neurons after birth at a time when the gene therapy would be administered.”

Furthermore, the cellular distribution of the gene therapy within the nervous system, which is unclear, might affect the therapy’s effect. “These are largely unanswered questions,” said Dr. De Vivo. “The answers to these questions only will come with continued observation of patients who have been treated.”

Considering that nusinersen, the antisense oligonucleotide also approved for SMA, targets SMN2, and the gene therapy replaces SMN1, “there may be some wisdom in thinking about combination therapy,” said Dr. De Vivo. “There’s no doubt that these therapeutic agents are effective,” and continued follow-up will clarify their comparative efficacy, he concluded.

egreb@mdedge.com

SOURCES: Day JW, et al. AAN 2020. Abstract S27.001. Mendell JR, et al. AAN 2020. Abstract S27.002. Strauss KA, et al. AAN 2020. Abstract S27.003.

Certain patterns of frontal lobe glucose hypometabolism may be associated with higher risk for sudden unexpected death in epilepsy (SUDEP) among patients with refractory focal epilepsy, new research suggests.

“The data provide initial evidence that hypometabolism in certain parts of the frontal cortex may be associated with higher SUDEP risk,” said lead author Maysaa M. Basha, MD, associate professor of neurology and director of the Adult Comprehensive Epilepsy Program, Wayne State University/Detroit Medical Center, in Michigan.

If this research is validated, “it potentially can be used to screen patients for higher SUDEP risk,” she said. The idea is to identify those at high risk and then reduce that risk with more aggressive management of seizures or closer monitoring in certain cases, she added.

The research is being presented online as part of the 2020 American Academy of Neurology (AAN) Science Highlights.
 

Hypometabolism

Dr. Basha and colleagues were encouraged to pursue this new line of research after a pilot [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) study revealed frontal lobe hypometabolism among patients who subsequently died.

“We wanted to determine if such a metabolic abnormality is associated with SUDEP risk,” said Dr. Basha. She noted that no PET studies have addressed this question, only MRI studies.

In this new study, researchers aimed to identify specific patterns of objectively detected brain glucose metabolic abnormalities in patients with refractory focal epilepsy who were at risk for SUDEP.

The study included 80 patients (45 female patients) aged 16 to 61 years (mean age, 37 years) who underwent FDG-PET as part of their presurgical evaluation for epilepsy surgery. Patients with large brain lesions, such as an infarct or a large tumor, were excluded from the study; such lesions can affect the accuracy of an objective PET analysis, explained Dr. Basha.

The researchers assessed risk for SUDEP using the seven-item SUDEP inventory (SUDEP-7), which was developed as a marker of clinical SUDEP risk. The 0- to 10-point scale is used to evaluate the frequency of tonic-clonic and other seizures, the duration of epilepsy, the use of antiepileptic drugs, and intellectual disability.

The researchers calculated SUDEP-7 inventory scores as closely as possible to FDG-PET assessments. The mean score in the patient population was 3.6.

The investigators divided participants into two subgroups: 22 patients had a SUDEP score of 5 or greater; and 58 had a score of less than 5 (higher scores indicate higher risk for SUDEP).

The researchers compared PET scans of each of these subgroups to PET scans from healthy adults to determine whether they showed common areas of metabolic abnormality. For this, they used an image analytic software program called Statistical Parametric Mapping, which compares group values of metabolic activity measured in small units of the brain (voxels) with statistical methods.

The analysis showed that the higher-risk group displayed a common pattern of hypometabolism in certain brain areas.

“The epilepsy patient subgroup with high SUDEP risk showed areas of decreased metabolism, as compared to the control group, in portions of the frontal cortex,” said Dr. Basha. “The statistically most significant decreases were in the right frontal lobe area—both lateral convexity and medial cortex.”

Dr. Basha added that these group abnormalities were “remarkably similar” to the individual metabolic abnormalities found in the four SUDEP patients in the previous pilot study who underwent PET scanning and who subsequently died.

A similar group analysis showed that the group at low SUDEP risk displayed no common metabolic abnormalities.

MRI findings were normal for 40 patients.

Dr. Basha and colleagues believe that “this is the first PET study assessing the metabolic correlates of SUDEP risk on the group level.”
 

Common feature

Interictal glucose hypometabolism is “common in and around epileptic foci,” noted Dr. Basha. However, this could extend into nonepileptic regions—for example, to remote connected regions where seizures can spread from the primary focus and into subcortical gray matter structures, such the thalamus.

Some of these metabolic abnormalities may indicate subtle, microscopic, structural abnormalities in the affected brain, said Dr. Basha.

Abnormalities that are induced by epilepsy and that result from purely metabolic changes could be partly or fully reversed if seizures are controlled on a long-term basis, she said. “Some metabolic abnormalities can be reversed after better seizure control with antiepileptic drugs, epileptic surgery, or other antiepileptic treatment,” she said.

It’s “quite possible” that the same brain pattern would be evident in children with epilepsy, although her team has not performed the same analysis in a younger pediatric group, said Dr. Basha. She noted that it would be unethical to administer PET scans, which involve radiation, to young, healthy control persons.

It’s too early to recommend that all epilepsy patients undergo FDG-PET scanning to see whether this pattern of brain glucose hypometabolism is present, said Dr. Basha. “But if this is proven to be a good biomarker, the next step would be a prospective study” to see whether this brain marker is a true signal of SUDEP risk.

“I don’t think our single study would do that, but ultimately, that would be the goal,” she added.
 

One more piece of the SUDEP puzzle

Commenting on the study, William Davis Gaillard, MD, president of the American Epilepsy Society and chief of neurology, Children’s National Medical Center, Chevy Chase, Maryland, said this new information provides one more piece of the SUDEP puzzle but doesn’t complete the picture.

The study authors assessed PET scans of a group of patients and found common abnormalities that implicate the right medial frontal cortex. “That’s a pretty reasonable method” of investigation, said Dr. Gaillard.

“The challenge is that they’re looking at people they believe have a risk of SUDEP as opposed to people who died,” said Dr. Gaillard.

But he agreed that the results might signal “a biomarker” that “allows you to identify who’s at high risk, and then you may be able to intervene to save them.”

It’s not clear that people with frontal lobe epilepsy are at greater risk for SUDEP than those with temporal lobe epilepsy, he said.

“What you don’t know is whether this represents people with a seizure focus in that area or this represents a common network implicated in people with diverse forms of focal epilepsy; so you need to do some more work,” he said.

Dr. Gaillard pointed out that other research has implicated regions other than the mesial frontal cortex in SUDEP risk. These regions include the insula, the amygdala, the hippocampus, and the brain stem.

He also noted that the SUDEP-7, which has not been thoroughly validated, is designed for use only in adults.

In his own practice, he asks patients about the frequency of tonic-clonic seizures and whether they occur at night. The number of antiepileptic medications a patient takes reflects the difficulty of controlling seizures and may not be “an independent variable for risk,” said Dr. Gaillard.

“It’s clear one needs a better assessment and better idea of who is at risk,” he said.

The researchers have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Basha A et al. AAN 2020. Abstract P5.001.

Certain patterns of frontal lobe glucose hypometabolism may be associated with higher risk for sudden unexpected death in epilepsy (SUDEP) among patients with refractory focal epilepsy, new research suggests.

“The data provide initial evidence that hypometabolism in certain parts of the frontal cortex may be associated with higher SUDEP risk,” said lead author Maysaa M. Basha, MD, associate professor of neurology and director of the Adult Comprehensive Epilepsy Program, Wayne State University/Detroit Medical Center, in Michigan.

If this research is validated, “it potentially can be used to screen patients for higher SUDEP risk,” she said. The idea is to identify those at high risk and then reduce that risk with more aggressive management of seizures or closer monitoring in certain cases, she added.

The research is being presented online as part of the 2020 American Academy of Neurology (AAN) Science Highlights.
 

Hypometabolism

Dr. Basha and colleagues were encouraged to pursue this new line of research after a pilot [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) study revealed frontal lobe hypometabolism among patients who subsequently died.

“We wanted to determine if such a metabolic abnormality is associated with SUDEP risk,” said Dr. Basha. She noted that no PET studies have addressed this question, only MRI studies.

In this new study, researchers aimed to identify specific patterns of objectively detected brain glucose metabolic abnormalities in patients with refractory focal epilepsy who were at risk for SUDEP.

The study included 80 patients (45 female patients) aged 16 to 61 years (mean age, 37 years) who underwent FDG-PET as part of their presurgical evaluation for epilepsy surgery. Patients with large brain lesions, such as an infarct or a large tumor, were excluded from the study; such lesions can affect the accuracy of an objective PET analysis, explained Dr. Basha.

The researchers assessed risk for SUDEP using the seven-item SUDEP inventory (SUDEP-7), which was developed as a marker of clinical SUDEP risk. The 0- to 10-point scale is used to evaluate the frequency of tonic-clonic and other seizures, the duration of epilepsy, the use of antiepileptic drugs, and intellectual disability.

The researchers calculated SUDEP-7 inventory scores as closely as possible to FDG-PET assessments. The mean score in the patient population was 3.6.

The investigators divided participants into two subgroups: 22 patients had a SUDEP score of 5 or greater; and 58 had a score of less than 5 (higher scores indicate higher risk for SUDEP).

The researchers compared PET scans of each of these subgroups to PET scans from healthy adults to determine whether they showed common areas of metabolic abnormality. For this, they used an image analytic software program called Statistical Parametric Mapping, which compares group values of metabolic activity measured in small units of the brain (voxels) with statistical methods.

The analysis showed that the higher-risk group displayed a common pattern of hypometabolism in certain brain areas.

“The epilepsy patient subgroup with high SUDEP risk showed areas of decreased metabolism, as compared to the control group, in portions of the frontal cortex,” said Dr. Basha. “The statistically most significant decreases were in the right frontal lobe area—both lateral convexity and medial cortex.”

Dr. Basha added that these group abnormalities were “remarkably similar” to the individual metabolic abnormalities found in the four SUDEP patients in the previous pilot study who underwent PET scanning and who subsequently died.

A similar group analysis showed that the group at low SUDEP risk displayed no common metabolic abnormalities.

MRI findings were normal for 40 patients.

Dr. Basha and colleagues believe that “this is the first PET study assessing the metabolic correlates of SUDEP risk on the group level.”
 

Common feature

Interictal glucose hypometabolism is “common in and around epileptic foci,” noted Dr. Basha. However, this could extend into nonepileptic regions—for example, to remote connected regions where seizures can spread from the primary focus and into subcortical gray matter structures, such the thalamus.

Some of these metabolic abnormalities may indicate subtle, microscopic, structural abnormalities in the affected brain, said Dr. Basha.

Abnormalities that are induced by epilepsy and that result from purely metabolic changes could be partly or fully reversed if seizures are controlled on a long-term basis, she said. “Some metabolic abnormalities can be reversed after better seizure control with antiepileptic drugs, epileptic surgery, or other antiepileptic treatment,” she said.

It’s “quite possible” that the same brain pattern would be evident in children with epilepsy, although her team has not performed the same analysis in a younger pediatric group, said Dr. Basha. She noted that it would be unethical to administer PET scans, which involve radiation, to young, healthy control persons.

It’s too early to recommend that all epilepsy patients undergo FDG-PET scanning to see whether this pattern of brain glucose hypometabolism is present, said Dr. Basha. “But if this is proven to be a good biomarker, the next step would be a prospective study” to see whether this brain marker is a true signal of SUDEP risk.

“I don’t think our single study would do that, but ultimately, that would be the goal,” she added.
 

One more piece of the SUDEP puzzle

Commenting on the study, William Davis Gaillard, MD, president of the American Epilepsy Society and chief of neurology, Children’s National Medical Center, Chevy Chase, Maryland, said this new information provides one more piece of the SUDEP puzzle but doesn’t complete the picture.

The study authors assessed PET scans of a group of patients and found common abnormalities that implicate the right medial frontal cortex. “That’s a pretty reasonable method” of investigation, said Dr. Gaillard.

“The challenge is that they’re looking at people they believe have a risk of SUDEP as opposed to people who died,” said Dr. Gaillard.

But he agreed that the results might signal “a biomarker” that “allows you to identify who’s at high risk, and then you may be able to intervene to save them.”

It’s not clear that people with frontal lobe epilepsy are at greater risk for SUDEP than those with temporal lobe epilepsy, he said.

“What you don’t know is whether this represents people with a seizure focus in that area or this represents a common network implicated in people with diverse forms of focal epilepsy; so you need to do some more work,” he said.

Dr. Gaillard pointed out that other research has implicated regions other than the mesial frontal cortex in SUDEP risk. These regions include the insula, the amygdala, the hippocampus, and the brain stem.

He also noted that the SUDEP-7, which has not been thoroughly validated, is designed for use only in adults.

In his own practice, he asks patients about the frequency of tonic-clonic seizures and whether they occur at night. The number of antiepileptic medications a patient takes reflects the difficulty of controlling seizures and may not be “an independent variable for risk,” said Dr. Gaillard.

“It’s clear one needs a better assessment and better idea of who is at risk,” he said.

The researchers have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Basha A et al. AAN 2020. Abstract P5.001.

Certain patterns of frontal lobe glucose hypometabolism may be associated with higher risk for sudden unexpected death in epilepsy (SUDEP) among patients with refractory focal epilepsy, new research suggests.

“The data provide initial evidence that hypometabolism in certain parts of the frontal cortex may be associated with higher SUDEP risk,” said lead author Maysaa M. Basha, MD, associate professor of neurology and director of the Adult Comprehensive Epilepsy Program, Wayne State University/Detroit Medical Center, in Michigan.

If this research is validated, “it potentially can be used to screen patients for higher SUDEP risk,” she said. The idea is to identify those at high risk and then reduce that risk with more aggressive management of seizures or closer monitoring in certain cases, she added.

The research is being presented online as part of the 2020 American Academy of Neurology (AAN) Science Highlights.
 

Hypometabolism

Dr. Basha and colleagues were encouraged to pursue this new line of research after a pilot [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET) study revealed frontal lobe hypometabolism among patients who subsequently died.

“We wanted to determine if such a metabolic abnormality is associated with SUDEP risk,” said Dr. Basha. She noted that no PET studies have addressed this question, only MRI studies.

In this new study, researchers aimed to identify specific patterns of objectively detected brain glucose metabolic abnormalities in patients with refractory focal epilepsy who were at risk for SUDEP.

The study included 80 patients (45 female patients) aged 16 to 61 years (mean age, 37 years) who underwent FDG-PET as part of their presurgical evaluation for epilepsy surgery. Patients with large brain lesions, such as an infarct or a large tumor, were excluded from the study; such lesions can affect the accuracy of an objective PET analysis, explained Dr. Basha.

The researchers assessed risk for SUDEP using the seven-item SUDEP inventory (SUDEP-7), which was developed as a marker of clinical SUDEP risk. The 0- to 10-point scale is used to evaluate the frequency of tonic-clonic and other seizures, the duration of epilepsy, the use of antiepileptic drugs, and intellectual disability.

The researchers calculated SUDEP-7 inventory scores as closely as possible to FDG-PET assessments. The mean score in the patient population was 3.6.

The investigators divided participants into two subgroups: 22 patients had a SUDEP score of 5 or greater; and 58 had a score of less than 5 (higher scores indicate higher risk for SUDEP).

The researchers compared PET scans of each of these subgroups to PET scans from healthy adults to determine whether they showed common areas of metabolic abnormality. For this, they used an image analytic software program called Statistical Parametric Mapping, which compares group values of metabolic activity measured in small units of the brain (voxels) with statistical methods.

The analysis showed that the higher-risk group displayed a common pattern of hypometabolism in certain brain areas.

“The epilepsy patient subgroup with high SUDEP risk showed areas of decreased metabolism, as compared to the control group, in portions of the frontal cortex,” said Dr. Basha. “The statistically most significant decreases were in the right frontal lobe area—both lateral convexity and medial cortex.”

Dr. Basha added that these group abnormalities were “remarkably similar” to the individual metabolic abnormalities found in the four SUDEP patients in the previous pilot study who underwent PET scanning and who subsequently died.

A similar group analysis showed that the group at low SUDEP risk displayed no common metabolic abnormalities.

MRI findings were normal for 40 patients.

Dr. Basha and colleagues believe that “this is the first PET study assessing the metabolic correlates of SUDEP risk on the group level.”
 

Common feature

Interictal glucose hypometabolism is “common in and around epileptic foci,” noted Dr. Basha. However, this could extend into nonepileptic regions—for example, to remote connected regions where seizures can spread from the primary focus and into subcortical gray matter structures, such the thalamus.

Some of these metabolic abnormalities may indicate subtle, microscopic, structural abnormalities in the affected brain, said Dr. Basha.

Abnormalities that are induced by epilepsy and that result from purely metabolic changes could be partly or fully reversed if seizures are controlled on a long-term basis, she said. “Some metabolic abnormalities can be reversed after better seizure control with antiepileptic drugs, epileptic surgery, or other antiepileptic treatment,” she said.

It’s “quite possible” that the same brain pattern would be evident in children with epilepsy, although her team has not performed the same analysis in a younger pediatric group, said Dr. Basha. She noted that it would be unethical to administer PET scans, which involve radiation, to young, healthy control persons.

It’s too early to recommend that all epilepsy patients undergo FDG-PET scanning to see whether this pattern of brain glucose hypometabolism is present, said Dr. Basha. “But if this is proven to be a good biomarker, the next step would be a prospective study” to see whether this brain marker is a true signal of SUDEP risk.

“I don’t think our single study would do that, but ultimately, that would be the goal,” she added.
 

One more piece of the SUDEP puzzle

Commenting on the study, William Davis Gaillard, MD, president of the American Epilepsy Society and chief of neurology, Children’s National Medical Center, Chevy Chase, Maryland, said this new information provides one more piece of the SUDEP puzzle but doesn’t complete the picture.

The study authors assessed PET scans of a group of patients and found common abnormalities that implicate the right medial frontal cortex. “That’s a pretty reasonable method” of investigation, said Dr. Gaillard.

“The challenge is that they’re looking at people they believe have a risk of SUDEP as opposed to people who died,” said Dr. Gaillard.

But he agreed that the results might signal “a biomarker” that “allows you to identify who’s at high risk, and then you may be able to intervene to save them.”

It’s not clear that people with frontal lobe epilepsy are at greater risk for SUDEP than those with temporal lobe epilepsy, he said.

“What you don’t know is whether this represents people with a seizure focus in that area or this represents a common network implicated in people with diverse forms of focal epilepsy; so you need to do some more work,” he said.

Dr. Gaillard pointed out that other research has implicated regions other than the mesial frontal cortex in SUDEP risk. These regions include the insula, the amygdala, the hippocampus, and the brain stem.

He also noted that the SUDEP-7, which has not been thoroughly validated, is designed for use only in adults.

In his own practice, he asks patients about the frequency of tonic-clonic seizures and whether they occur at night. The number of antiepileptic medications a patient takes reflects the difficulty of controlling seizures and may not be “an independent variable for risk,” said Dr. Gaillard.

“It’s clear one needs a better assessment and better idea of who is at risk,” he said.

The researchers have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

SOURCE: Basha A et al. AAN 2020. Abstract P5.001.

A novel telemedicine approach to remotely guide ST-segment elevation myocardial infarction treatment in four Latin American countries screened more than 780,000 patients and resulted in a mortality rate of 5.2%, results from a 1-year, prospective, observational study showed.

“We have created a modality where the care of acute MI can be remotely guided,” lead investigator Sameer Mehta, MD, MBA, said during a press briefing at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “This flattens the disparity between the developed and the developing countries, particularly in the poorer parts of Africa, the Middle East, and Southeast Asia.”

Dr. Mehta, chairman of the Lumen Foundation in Miami, and colleagues developed a “hub and spoke” platform to expand STEMI access to more than 100 million people in Brazil, Colombia, Mexico, and Argentina. For the effort, known as the Latin America Telemedicine Infarct Network (LATIN), “spokes” consisted of small clinics and primary health care centers in remote locations, while the “hubs” were medical centers that provided percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) surgery. There were 313 spokes, 47 hubs, and more than 2,000 health care professionals who participated in the endeavor, including about 600 physicians.

The study, which is the largest of its kind, implemented a 3T strategy: telemedicine, triage, and transport, “which was the hardest part,” Dr. Mehta said. “In some cases, the spokes were located up to 300 miles away from the hubs. Up to 11% of these spokes in the remote areas did not even have a physician. Some had nurses who were triaging the patients.”

Patients who presented at spoke sites were enrolled into LATIN and data were collected through a form that included patient demographics, previous medical history, and an ECG. This information was sent through an app to one of three telemedicine diagnosis centers with 24/7 access to a cardiologist: one in Colombia, one in Brazil, one in Argentina. Once STEMI was identified by ECG, the STEMI protocol was activated, sending alerts to both designated hub and spoke sites and triggering ambulance dispatch. At the spoke sites, thrombolysis, a pharmaco-invasive strategy, or a primary PCI was performed, depending on case and treatment availability. Patients with successful thrombolysis were stabilized for up to 24 hours before transferral to a hub. Patients for whom reperfusion failed were transferred immediately to a hub for rescue PCI.

Dr. Mehta reported findings from 780,234 telemedicine encounters that occurred in the LATIN network in 2018. Telemedicine experts diagnosed 8,395 patients (1%) with STEMI, of which 3,872 (46%) were urgently treated at 47 hubs. A total of 3,015 (78%) were reperfused with PCI. Time-to-telemedicine diagnosis averaged 3.5 minutes. “It used to take us 11 minutes of time to make a diagnosis by telemedicine,” Dr. Mehta said. “By the time we were done with the trial, the time to diagnosis was brought down to 3.5 minutes.” Average door-to-balloon time was 48 minutes and the STEMI mortality was 5.2%. This represents a 55% reduction in STEMI mortality from when LATIN began as a pilot project in 2013, Dr. Mehta said.

Hypertension was the most prevalent underlying disease (59%), followed by smoking (30%) and diabetes (29%), and the male to female STEMI diagnosis ratio was 1.71. The chief reason for nontreatment was coverage denial from insurance carriers (71%). “Getting payers onboard is extremely difficult, because being located here in Miami, is it very hard for me to convince them about the importance of supporting these people,” Dr. Mehta said. “However, as time has passed [and with] coverage of LATIN by the media, the program has become better known. We have been able to work mainly through the health secretaries [in these four countries], but is difficult from there onward.”

LATIN investigators faced other hurdles, which were unique in each of the four countries. “In Colombia, we were facing all sorts of geographical challenges; Brazil was challenging because of its size of the country and [difficulty establishing relationships with] some of the inner-city hospitals,” he said. “Mexico and Argentina were unique from the telemedicine point of view.” The fact that the care of LATIN patients was navigated from one of three telemedicine diagnosis centers “demonstrates the ability of telemedicine,” he said. “If I am able to guide a patient in Mexico from Bogotá, Colombia, it should be easy to guide a patient from Miami who’s presenting in Zambia.”

Dealing with the lack of ambulance services in Brazil, Colombia, Mexico, and Argentina has also been a hitch to the effort. “There is either a complete lack of ambulances or there is no central ambulance system,” he said. “In one of the earlier cities where we started the program in Colombia, 84% of patients used to self-transport. At the moment, 79% are being transported by ambulance. So, the halo effect of how LATIN has helped MI management has been impressive.”

Despite the lack of a comparator study as robust as LATIN, the program was estimated to reach between $39.6 million and $119 million USD total savings during the study period. This includes the cost of tele-emergency encounters, avoided transfers, and the cost of transportation. The investigators project that by the year 2026, 5 million patients could be triaged by this telemedicine pathway, saving $249 million. “As we are getting excited about the developments and the possibilities of telemedicine in the COVID-19 era, I think the work of LATIN becomes all the more relevant,” Dr. Mehta said during his main presentation.

During the press briefing, Timothy D. Henry, MD, praised the success of LATIN in reaching an underserved population. “The majority of these patients 10 years ago were not being treated with any reperfusion therapy at all,” said Dr. Henry, medical director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati. “With rapid diagnosis and the process of putting [LATIN] in place, that has increased to the point where 78% are now getting primary PCI. That is remarkable.”

dbrunk@mdedge.com

A novel telemedicine approach to remotely guide ST-segment elevation myocardial infarction treatment in four Latin American countries screened more than 780,000 patients and resulted in a mortality rate of 5.2%, results from a 1-year, prospective, observational study showed.

“We have created a modality where the care of acute MI can be remotely guided,” lead investigator Sameer Mehta, MD, MBA, said during a press briefing at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “This flattens the disparity between the developed and the developing countries, particularly in the poorer parts of Africa, the Middle East, and Southeast Asia.”

Dr. Mehta, chairman of the Lumen Foundation in Miami, and colleagues developed a “hub and spoke” platform to expand STEMI access to more than 100 million people in Brazil, Colombia, Mexico, and Argentina. For the effort, known as the Latin America Telemedicine Infarct Network (LATIN), “spokes” consisted of small clinics and primary health care centers in remote locations, while the “hubs” were medical centers that provided percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) surgery. There were 313 spokes, 47 hubs, and more than 2,000 health care professionals who participated in the endeavor, including about 600 physicians.

The study, which is the largest of its kind, implemented a 3T strategy: telemedicine, triage, and transport, “which was the hardest part,” Dr. Mehta said. “In some cases, the spokes were located up to 300 miles away from the hubs. Up to 11% of these spokes in the remote areas did not even have a physician. Some had nurses who were triaging the patients.”

Patients who presented at spoke sites were enrolled into LATIN and data were collected through a form that included patient demographics, previous medical history, and an ECG. This information was sent through an app to one of three telemedicine diagnosis centers with 24/7 access to a cardiologist: one in Colombia, one in Brazil, one in Argentina. Once STEMI was identified by ECG, the STEMI protocol was activated, sending alerts to both designated hub and spoke sites and triggering ambulance dispatch. At the spoke sites, thrombolysis, a pharmaco-invasive strategy, or a primary PCI was performed, depending on case and treatment availability. Patients with successful thrombolysis were stabilized for up to 24 hours before transferral to a hub. Patients for whom reperfusion failed were transferred immediately to a hub for rescue PCI.

Dr. Mehta reported findings from 780,234 telemedicine encounters that occurred in the LATIN network in 2018. Telemedicine experts diagnosed 8,395 patients (1%) with STEMI, of which 3,872 (46%) were urgently treated at 47 hubs. A total of 3,015 (78%) were reperfused with PCI. Time-to-telemedicine diagnosis averaged 3.5 minutes. “It used to take us 11 minutes of time to make a diagnosis by telemedicine,” Dr. Mehta said. “By the time we were done with the trial, the time to diagnosis was brought down to 3.5 minutes.” Average door-to-balloon time was 48 minutes and the STEMI mortality was 5.2%. This represents a 55% reduction in STEMI mortality from when LATIN began as a pilot project in 2013, Dr. Mehta said.

Hypertension was the most prevalent underlying disease (59%), followed by smoking (30%) and diabetes (29%), and the male to female STEMI diagnosis ratio was 1.71. The chief reason for nontreatment was coverage denial from insurance carriers (71%). “Getting payers onboard is extremely difficult, because being located here in Miami, is it very hard for me to convince them about the importance of supporting these people,” Dr. Mehta said. “However, as time has passed [and with] coverage of LATIN by the media, the program has become better known. We have been able to work mainly through the health secretaries [in these four countries], but is difficult from there onward.”

LATIN investigators faced other hurdles, which were unique in each of the four countries. “In Colombia, we were facing all sorts of geographical challenges; Brazil was challenging because of its size of the country and [difficulty establishing relationships with] some of the inner-city hospitals,” he said. “Mexico and Argentina were unique from the telemedicine point of view.” The fact that the care of LATIN patients was navigated from one of three telemedicine diagnosis centers “demonstrates the ability of telemedicine,” he said. “If I am able to guide a patient in Mexico from Bogotá, Colombia, it should be easy to guide a patient from Miami who’s presenting in Zambia.”

Dealing with the lack of ambulance services in Brazil, Colombia, Mexico, and Argentina has also been a hitch to the effort. “There is either a complete lack of ambulances or there is no central ambulance system,” he said. “In one of the earlier cities where we started the program in Colombia, 84% of patients used to self-transport. At the moment, 79% are being transported by ambulance. So, the halo effect of how LATIN has helped MI management has been impressive.”

Despite the lack of a comparator study as robust as LATIN, the program was estimated to reach between $39.6 million and $119 million USD total savings during the study period. This includes the cost of tele-emergency encounters, avoided transfers, and the cost of transportation. The investigators project that by the year 2026, 5 million patients could be triaged by this telemedicine pathway, saving $249 million. “As we are getting excited about the developments and the possibilities of telemedicine in the COVID-19 era, I think the work of LATIN becomes all the more relevant,” Dr. Mehta said during his main presentation.

During the press briefing, Timothy D. Henry, MD, praised the success of LATIN in reaching an underserved population. “The majority of these patients 10 years ago were not being treated with any reperfusion therapy at all,” said Dr. Henry, medical director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati. “With rapid diagnosis and the process of putting [LATIN] in place, that has increased to the point where 78% are now getting primary PCI. That is remarkable.”

dbrunk@mdedge.com

A novel telemedicine approach to remotely guide ST-segment elevation myocardial infarction treatment in four Latin American countries screened more than 780,000 patients and resulted in a mortality rate of 5.2%, results from a 1-year, prospective, observational study showed.

“We have created a modality where the care of acute MI can be remotely guided,” lead investigator Sameer Mehta, MD, MBA, said during a press briefing at the Society for Cardiovascular Angiography & Interventions virtual annual scientific sessions. “This flattens the disparity between the developed and the developing countries, particularly in the poorer parts of Africa, the Middle East, and Southeast Asia.”

Dr. Mehta, chairman of the Lumen Foundation in Miami, and colleagues developed a “hub and spoke” platform to expand STEMI access to more than 100 million people in Brazil, Colombia, Mexico, and Argentina. For the effort, known as the Latin America Telemedicine Infarct Network (LATIN), “spokes” consisted of small clinics and primary health care centers in remote locations, while the “hubs” were medical centers that provided percutaneous coronary intervention (PCI) and/or coronary artery bypass graft (CABG) surgery. There were 313 spokes, 47 hubs, and more than 2,000 health care professionals who participated in the endeavor, including about 600 physicians.

The study, which is the largest of its kind, implemented a 3T strategy: telemedicine, triage, and transport, “which was the hardest part,” Dr. Mehta said. “In some cases, the spokes were located up to 300 miles away from the hubs. Up to 11% of these spokes in the remote areas did not even have a physician. Some had nurses who were triaging the patients.”

Patients who presented at spoke sites were enrolled into LATIN and data were collected through a form that included patient demographics, previous medical history, and an ECG. This information was sent through an app to one of three telemedicine diagnosis centers with 24/7 access to a cardiologist: one in Colombia, one in Brazil, one in Argentina. Once STEMI was identified by ECG, the STEMI protocol was activated, sending alerts to both designated hub and spoke sites and triggering ambulance dispatch. At the spoke sites, thrombolysis, a pharmaco-invasive strategy, or a primary PCI was performed, depending on case and treatment availability. Patients with successful thrombolysis were stabilized for up to 24 hours before transferral to a hub. Patients for whom reperfusion failed were transferred immediately to a hub for rescue PCI.

Dr. Mehta reported findings from 780,234 telemedicine encounters that occurred in the LATIN network in 2018. Telemedicine experts diagnosed 8,395 patients (1%) with STEMI, of which 3,872 (46%) were urgently treated at 47 hubs. A total of 3,015 (78%) were reperfused with PCI. Time-to-telemedicine diagnosis averaged 3.5 minutes. “It used to take us 11 minutes of time to make a diagnosis by telemedicine,” Dr. Mehta said. “By the time we were done with the trial, the time to diagnosis was brought down to 3.5 minutes.” Average door-to-balloon time was 48 minutes and the STEMI mortality was 5.2%. This represents a 55% reduction in STEMI mortality from when LATIN began as a pilot project in 2013, Dr. Mehta said.

Hypertension was the most prevalent underlying disease (59%), followed by smoking (30%) and diabetes (29%), and the male to female STEMI diagnosis ratio was 1.71. The chief reason for nontreatment was coverage denial from insurance carriers (71%). “Getting payers onboard is extremely difficult, because being located here in Miami, is it very hard for me to convince them about the importance of supporting these people,” Dr. Mehta said. “However, as time has passed [and with] coverage of LATIN by the media, the program has become better known. We have been able to work mainly through the health secretaries [in these four countries], but is difficult from there onward.”

LATIN investigators faced other hurdles, which were unique in each of the four countries. “In Colombia, we were facing all sorts of geographical challenges; Brazil was challenging because of its size of the country and [difficulty establishing relationships with] some of the inner-city hospitals,” he said. “Mexico and Argentina were unique from the telemedicine point of view.” The fact that the care of LATIN patients was navigated from one of three telemedicine diagnosis centers “demonstrates the ability of telemedicine,” he said. “If I am able to guide a patient in Mexico from Bogotá, Colombia, it should be easy to guide a patient from Miami who’s presenting in Zambia.”

Dealing with the lack of ambulance services in Brazil, Colombia, Mexico, and Argentina has also been a hitch to the effort. “There is either a complete lack of ambulances or there is no central ambulance system,” he said. “In one of the earlier cities where we started the program in Colombia, 84% of patients used to self-transport. At the moment, 79% are being transported by ambulance. So, the halo effect of how LATIN has helped MI management has been impressive.”

Despite the lack of a comparator study as robust as LATIN, the program was estimated to reach between $39.6 million and $119 million USD total savings during the study period. This includes the cost of tele-emergency encounters, avoided transfers, and the cost of transportation. The investigators project that by the year 2026, 5 million patients could be triaged by this telemedicine pathway, saving $249 million. “As we are getting excited about the developments and the possibilities of telemedicine in the COVID-19 era, I think the work of LATIN becomes all the more relevant,” Dr. Mehta said during his main presentation.

During the press briefing, Timothy D. Henry, MD, praised the success of LATIN in reaching an underserved population. “The majority of these patients 10 years ago were not being treated with any reperfusion therapy at all,” said Dr. Henry, medical director of The Carl and Edyth Lindner Center for Research and Education at The Christ Hospital in Cincinnati. “With rapid diagnosis and the process of putting [LATIN] in place, that has increased to the point where 78% are now getting primary PCI. That is remarkable.”

dbrunk@mdedge.com

Bariatric surgery is a safe and effective means for obese patients with advanced heart failure supported by a left ventricular assist device to qualify for heart transplantation, Praneet Wander, MD, reported in an abstract released as part of the annual Digestive Disease Week^®.

She presented a systematic review and meta-analysis of nine retrospective or cross-sectional cohort studies totaling 86 patients with a left ventricular assist device (LVAD) and advanced heart failure who had a mean body mass index (BMI) of 44.8 kg/m² when they underwent bariatric surgery at an average age of 44 years and 33.2 kg/m² at follow-up a mean of 14.3 months later.

Of the 86 patients, 50 (58%) were able to drop their BMI below 35, a requirement for inclusion on the heart transplant waiting list, noted Dr. Wander, a gastroenterology fellow at Hofstra University, Hempstead, N.Y., and North Shore LIJ Hospital in Manhasset, N.Y.

“A lot of bariatric surgeons don’t feel comfortable operating on patients who have a low ejection fraction,” she explained in an interview. “This study should encourage bariatric surgeons to do procedures even in patients with advanced heart failure so they can meet the BMI requirement for heart transplantation.”

Even if patients don’t actually undergo heart transplantation because of the perpetual donor organ shortage or inability to meet non–BMI-related eligibility criteria, they gain other major benefits from bariatric surgery: Their blood pressure goes down, their diabetes improves, and they become better able to engage in physical activity, she added.

Of the 86 patients in the meta-analysis, 84 underwent laparoscopic sleeve gastrectomy. That’s the preferred bariatric operation in patients with advanced heart failure at the Mayo Clinic as well, according to Andres J. Acosta, MD, PhD, a gastroenterologist at the medical center in Rochester, Minn.

There’s less weight loss achieved than with an open Roux-en-Y gastric bypass, but it’s a simpler operation in these high-risk patients, who typically have multiple comorbid conditions, he explained.

He predicted that Dr. Wander’s study will indeed influence bariatric surgeons at tertiary medical centers around the country to become more willing to consider weight-loss surgery in patients with advanced heart failure, while those in community practice will likely continue to be most comfortable operating on more stable patients with minimal comorbidities aside from their obesity.

“Data such as [these] will be reassuring to bariatric surgery programs such as ours, where we’re able to say: ‘Yes, there are risks, but these patients will benefit in the long term if we assume those risks,’ ” Dr. Acosta said.

He’s confident that, in the near future, the preferred form of bariatric surgery in patients with advanced heart failure will be a minimally invasive procedure performed endoscopically by gastroenterologists. He and his Mayo Clinic colleagues have already established a track record of success with endoscopic sleeve gastrectomy in patients with advanced kidney, liver, or lung disease in order to make them eligible for transplantation, as well as for the ancillary benefits provided by massive weight loss.

“There’s a little less weight loss than with laparoscopic sleeve gastrectomy, but it’s a significantly less risky operation. Shorter operative time, shorter hospital length of stay, less risk of infections and leaks,” he said in an interview. “We haven’t done it yet in heart disease, but I think based on this study this should be the next step at Mayo.”

Radha Gopalan, MD, director of heart failure and transplantation at Banner–University Medical Center in Phoenix, pronounced Dr. Wander’s meta-analysis “a positive study that’s very supportive of what we’re doing at our center.

“At a busy heart transplant center like ours, we are comfortable managing these patients, so the bariatric surgeons are reassured that the heart failure team is behind them. The risk of the procedure is mitigated by the availability of the multidisciplinary team to get the patient with obesity and heart failure through the surgery,” he explained.

Dr. Gopalan heads a novel bariatric heart failure program at Banner. While Dr. Wander’s meta-analysis focused on bariatric surgery in heart failure patients on LVAD circulatory support, Dr. Gopalan and colleagues are moving the intervention upstream. Roughly roughly 80% of patients in his bariatric heart failure program who meet criteria for LVAD implantation are now offered bariatric surgery before an LVAD is put in.

“I am moving away from putting the LVAD in first and then doing bariatric surgery. We have gotten comfortable taking these patients for bariatric surgery with inotropic support before going to the LVAD, which has the potential to even eliminate the requirement for an LVAD. Some patients get so much better that they become transplant ineligible,” Dr. Gopalan said.

Dr. Wander reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Wander P. DDW 2020 Abstract, #Mo2010.

Bariatric surgery is a safe and effective means for obese patients with advanced heart failure supported by a left ventricular assist device to qualify for heart transplantation, Praneet Wander, MD, reported in an abstract released as part of the annual Digestive Disease Week^®.

She presented a systematic review and meta-analysis of nine retrospective or cross-sectional cohort studies totaling 86 patients with a left ventricular assist device (LVAD) and advanced heart failure who had a mean body mass index (BMI) of 44.8 kg/m² when they underwent bariatric surgery at an average age of 44 years and 33.2 kg/m² at follow-up a mean of 14.3 months later.

Of the 86 patients, 50 (58%) were able to drop their BMI below 35, a requirement for inclusion on the heart transplant waiting list, noted Dr. Wander, a gastroenterology fellow at Hofstra University, Hempstead, N.Y., and North Shore LIJ Hospital in Manhasset, N.Y.

“A lot of bariatric surgeons don’t feel comfortable operating on patients who have a low ejection fraction,” she explained in an interview. “This study should encourage bariatric surgeons to do procedures even in patients with advanced heart failure so they can meet the BMI requirement for heart transplantation.”

Even if patients don’t actually undergo heart transplantation because of the perpetual donor organ shortage or inability to meet non–BMI-related eligibility criteria, they gain other major benefits from bariatric surgery: Their blood pressure goes down, their diabetes improves, and they become better able to engage in physical activity, she added.

Of the 86 patients in the meta-analysis, 84 underwent laparoscopic sleeve gastrectomy. That’s the preferred bariatric operation in patients with advanced heart failure at the Mayo Clinic as well, according to Andres J. Acosta, MD, PhD, a gastroenterologist at the medical center in Rochester, Minn.

There’s less weight loss achieved than with an open Roux-en-Y gastric bypass, but it’s a simpler operation in these high-risk patients, who typically have multiple comorbid conditions, he explained.

He predicted that Dr. Wander’s study will indeed influence bariatric surgeons at tertiary medical centers around the country to become more willing to consider weight-loss surgery in patients with advanced heart failure, while those in community practice will likely continue to be most comfortable operating on more stable patients with minimal comorbidities aside from their obesity.

“Data such as [these] will be reassuring to bariatric surgery programs such as ours, where we’re able to say: ‘Yes, there are risks, but these patients will benefit in the long term if we assume those risks,’ ” Dr. Acosta said.

He’s confident that, in the near future, the preferred form of bariatric surgery in patients with advanced heart failure will be a minimally invasive procedure performed endoscopically by gastroenterologists. He and his Mayo Clinic colleagues have already established a track record of success with endoscopic sleeve gastrectomy in patients with advanced kidney, liver, or lung disease in order to make them eligible for transplantation, as well as for the ancillary benefits provided by massive weight loss.

“There’s a little less weight loss than with laparoscopic sleeve gastrectomy, but it’s a significantly less risky operation. Shorter operative time, shorter hospital length of stay, less risk of infections and leaks,” he said in an interview. “We haven’t done it yet in heart disease, but I think based on this study this should be the next step at Mayo.”

Radha Gopalan, MD, director of heart failure and transplantation at Banner–University Medical Center in Phoenix, pronounced Dr. Wander’s meta-analysis “a positive study that’s very supportive of what we’re doing at our center.

“At a busy heart transplant center like ours, we are comfortable managing these patients, so the bariatric surgeons are reassured that the heart failure team is behind them. The risk of the procedure is mitigated by the availability of the multidisciplinary team to get the patient with obesity and heart failure through the surgery,” he explained.

Dr. Gopalan heads a novel bariatric heart failure program at Banner. While Dr. Wander’s meta-analysis focused on bariatric surgery in heart failure patients on LVAD circulatory support, Dr. Gopalan and colleagues are moving the intervention upstream. Roughly roughly 80% of patients in his bariatric heart failure program who meet criteria for LVAD implantation are now offered bariatric surgery before an LVAD is put in.

“I am moving away from putting the LVAD in first and then doing bariatric surgery. We have gotten comfortable taking these patients for bariatric surgery with inotropic support before going to the LVAD, which has the potential to even eliminate the requirement for an LVAD. Some patients get so much better that they become transplant ineligible,” Dr. Gopalan said.

Dr. Wander reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Wander P. DDW 2020 Abstract, #Mo2010.

Bariatric surgery is a safe and effective means for obese patients with advanced heart failure supported by a left ventricular assist device to qualify for heart transplantation, Praneet Wander, MD, reported in an abstract released as part of the annual Digestive Disease Week^®.

She presented a systematic review and meta-analysis of nine retrospective or cross-sectional cohort studies totaling 86 patients with a left ventricular assist device (LVAD) and advanced heart failure who had a mean body mass index (BMI) of 44.8 kg/m² when they underwent bariatric surgery at an average age of 44 years and 33.2 kg/m² at follow-up a mean of 14.3 months later.

Of the 86 patients, 50 (58%) were able to drop their BMI below 35, a requirement for inclusion on the heart transplant waiting list, noted Dr. Wander, a gastroenterology fellow at Hofstra University, Hempstead, N.Y., and North Shore LIJ Hospital in Manhasset, N.Y.

“A lot of bariatric surgeons don’t feel comfortable operating on patients who have a low ejection fraction,” she explained in an interview. “This study should encourage bariatric surgeons to do procedures even in patients with advanced heart failure so they can meet the BMI requirement for heart transplantation.”

Even if patients don’t actually undergo heart transplantation because of the perpetual donor organ shortage or inability to meet non–BMI-related eligibility criteria, they gain other major benefits from bariatric surgery: Their blood pressure goes down, their diabetes improves, and they become better able to engage in physical activity, she added.

Of the 86 patients in the meta-analysis, 84 underwent laparoscopic sleeve gastrectomy. That’s the preferred bariatric operation in patients with advanced heart failure at the Mayo Clinic as well, according to Andres J. Acosta, MD, PhD, a gastroenterologist at the medical center in Rochester, Minn.

There’s less weight loss achieved than with an open Roux-en-Y gastric bypass, but it’s a simpler operation in these high-risk patients, who typically have multiple comorbid conditions, he explained.

He predicted that Dr. Wander’s study will indeed influence bariatric surgeons at tertiary medical centers around the country to become more willing to consider weight-loss surgery in patients with advanced heart failure, while those in community practice will likely continue to be most comfortable operating on more stable patients with minimal comorbidities aside from their obesity.

“Data such as [these] will be reassuring to bariatric surgery programs such as ours, where we’re able to say: ‘Yes, there are risks, but these patients will benefit in the long term if we assume those risks,’ ” Dr. Acosta said.

He’s confident that, in the near future, the preferred form of bariatric surgery in patients with advanced heart failure will be a minimally invasive procedure performed endoscopically by gastroenterologists. He and his Mayo Clinic colleagues have already established a track record of success with endoscopic sleeve gastrectomy in patients with advanced kidney, liver, or lung disease in order to make them eligible for transplantation, as well as for the ancillary benefits provided by massive weight loss.

“There’s a little less weight loss than with laparoscopic sleeve gastrectomy, but it’s a significantly less risky operation. Shorter operative time, shorter hospital length of stay, less risk of infections and leaks,” he said in an interview. “We haven’t done it yet in heart disease, but I think based on this study this should be the next step at Mayo.”

Radha Gopalan, MD, director of heart failure and transplantation at Banner–University Medical Center in Phoenix, pronounced Dr. Wander’s meta-analysis “a positive study that’s very supportive of what we’re doing at our center.

“At a busy heart transplant center like ours, we are comfortable managing these patients, so the bariatric surgeons are reassured that the heart failure team is behind them. The risk of the procedure is mitigated by the availability of the multidisciplinary team to get the patient with obesity and heart failure through the surgery,” he explained.

Dr. Gopalan heads a novel bariatric heart failure program at Banner. While Dr. Wander’s meta-analysis focused on bariatric surgery in heart failure patients on LVAD circulatory support, Dr. Gopalan and colleagues are moving the intervention upstream. Roughly roughly 80% of patients in his bariatric heart failure program who meet criteria for LVAD implantation are now offered bariatric surgery before an LVAD is put in.

“I am moving away from putting the LVAD in first and then doing bariatric surgery. We have gotten comfortable taking these patients for bariatric surgery with inotropic support before going to the LVAD, which has the potential to even eliminate the requirement for an LVAD. Some patients get so much better that they become transplant ineligible,” Dr. Gopalan said.

Dr. Wander reported having no financial conflicts regarding her study, conducted free of commercial support.

bjancin@mdedge.com

SOURCE: Wander P. DDW 2020 Abstract, #Mo2010.

Quitting smoking prior to a lung cancer diagnosis is associated with a survival benefit, even among patients who recently stopped smoking, according to results of a pooled analysis.

Brett Mulcahy/ThinkStock

The overall survival advantage was significant regardless of how long ago patients had last smoked, including among those who quit within 2 years prior to their diagnosis.

These findings create a “teachable moment” for health care providers in scenarios when patients might be more receptive to a stop-smoking message, according to investigator Aline F. Fares, MD, a clinical research fellow at Princess Margaret Cancer Centre in Toronto.

“Our study can be summarized to patients as, ‘it’s never too late to quit,’ ” Dr. Fares said.

She presented results from this study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online May 29-31. The virtual education program will be available Aug. 8-10.
 

Results

Dr. Fares presented data on 35,481 patients with a diagnosis of lung cancer who had been enrolled in 17 studies conducted by the International Lung Cancer Consortium. (Data in the presentation were updated from the abstract.)

At diagnosis, 47.5% of the patients were current smokers, 30% were former smokers, and 22.5% were never smokers.

The risk of death from any cause was cut by 20% among former smokers who quit more than 5 years before their lung cancer diagnosis (P < .001). Patients who quit smoking 2-5 years before diagnosis had a 16% reduction in the risk of death, while those who quit within 2 years of diagnosis had a 12% reduced risk (P < .001 for both comparisons).

The overall survival advantage was evident in this pooled analysis regardless of patient sex, disease stage, histology, or amount of smoking as measured in pack-years, according to Dr. Fares. That said, the overall survival advantage appeared to be even greater among heavier smokers (i.e., greater than 30 pack-years) as compared with lighter smokers.

Lung cancer–specific survival was improved by 15% for patients who quit smoking more than 5 years prior to their diagnosis. For those who had quit more recently, there was a nonsignificant trend toward improvement in this outcome.

Overall survival was higher in never smokers in comparison with current smokers, a finding that was expected based on previous studies, according to Dr. Fares.
 

Implications

These findings could be important to share with individuals who are current smokers at the time of lung cancer screening, according to Maher A. Karam-Hage, MD, medical director of the tobacco treatment program at the University of Texas MD Anderson Cancer Center, Houston.

“The power of this data is that it shows quitting makes a difference, and that it can be more impactful the longer you quit before you get diagnosed,” Dr. Karam-Hage said in an interview.

Negative lung cancer screening results sometimes give individuals the false impression that they are “one of the lucky ones” who won’t get lung cancer and don’t have to quit smoking, according to Dr. Karam-Hage, who is studying the comparative effectiveness of different smoking cessation strategies.

“Now, as part of shared decision making, we can provide people with specific numbers before the scan that [suggest] no matter what the scan comes out with, the earlier they quit, the better off they will be,” he said.

In her presentation, Dr. Fares said that lung cancer screening may be an “interesting time” to address smoking cessation, particularly among patients with a heavier smoking history.

“After a lifetime of smoking, patients often feel it’s too late to quit smoking and that the damage has already been done,” she added.

The International Lung Cancer Consortium studies had multiple supporters. Dr. Fares reported having no disclosures related to the research. One researcher reported relationships with AbbVie, AstraZeneca, MedImmune, Bayer, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche Canada, and Takeda. Dr. Karam-Hage reported having no relevant disclosures.

SOURCE: Fares AF et al. ASCO 2020, Abstract 1512.

This article was updated 5/15/20.

Quitting smoking prior to a lung cancer diagnosis is associated with a survival benefit, even among patients who recently stopped smoking, according to results of a pooled analysis.

Brett Mulcahy/ThinkStock

The overall survival advantage was significant regardless of how long ago patients had last smoked, including among those who quit within 2 years prior to their diagnosis.

These findings create a “teachable moment” for health care providers in scenarios when patients might be more receptive to a stop-smoking message, according to investigator Aline F. Fares, MD, a clinical research fellow at Princess Margaret Cancer Centre in Toronto.

“Our study can be summarized to patients as, ‘it’s never too late to quit,’ ” Dr. Fares said.

She presented results from this study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online May 29-31. The virtual education program will be available Aug. 8-10.
 

Results

Dr. Fares presented data on 35,481 patients with a diagnosis of lung cancer who had been enrolled in 17 studies conducted by the International Lung Cancer Consortium. (Data in the presentation were updated from the abstract.)

At diagnosis, 47.5% of the patients were current smokers, 30% were former smokers, and 22.5% were never smokers.

The risk of death from any cause was cut by 20% among former smokers who quit more than 5 years before their lung cancer diagnosis (P < .001). Patients who quit smoking 2-5 years before diagnosis had a 16% reduction in the risk of death, while those who quit within 2 years of diagnosis had a 12% reduced risk (P < .001 for both comparisons).

The overall survival advantage was evident in this pooled analysis regardless of patient sex, disease stage, histology, or amount of smoking as measured in pack-years, according to Dr. Fares. That said, the overall survival advantage appeared to be even greater among heavier smokers (i.e., greater than 30 pack-years) as compared with lighter smokers.

Lung cancer–specific survival was improved by 15% for patients who quit smoking more than 5 years prior to their diagnosis. For those who had quit more recently, there was a nonsignificant trend toward improvement in this outcome.

Overall survival was higher in never smokers in comparison with current smokers, a finding that was expected based on previous studies, according to Dr. Fares.
 

Implications

These findings could be important to share with individuals who are current smokers at the time of lung cancer screening, according to Maher A. Karam-Hage, MD, medical director of the tobacco treatment program at the University of Texas MD Anderson Cancer Center, Houston.

“The power of this data is that it shows quitting makes a difference, and that it can be more impactful the longer you quit before you get diagnosed,” Dr. Karam-Hage said in an interview.

Negative lung cancer screening results sometimes give individuals the false impression that they are “one of the lucky ones” who won’t get lung cancer and don’t have to quit smoking, according to Dr. Karam-Hage, who is studying the comparative effectiveness of different smoking cessation strategies.

“Now, as part of shared decision making, we can provide people with specific numbers before the scan that [suggest] no matter what the scan comes out with, the earlier they quit, the better off they will be,” he said.

In her presentation, Dr. Fares said that lung cancer screening may be an “interesting time” to address smoking cessation, particularly among patients with a heavier smoking history.

“After a lifetime of smoking, patients often feel it’s too late to quit smoking and that the damage has already been done,” she added.

The International Lung Cancer Consortium studies had multiple supporters. Dr. Fares reported having no disclosures related to the research. One researcher reported relationships with AbbVie, AstraZeneca, MedImmune, Bayer, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche Canada, and Takeda. Dr. Karam-Hage reported having no relevant disclosures.

SOURCE: Fares AF et al. ASCO 2020, Abstract 1512.

This article was updated 5/15/20.

Quitting smoking prior to a lung cancer diagnosis is associated with a survival benefit, even among patients who recently stopped smoking, according to results of a pooled analysis.

Brett Mulcahy/ThinkStock

The overall survival advantage was significant regardless of how long ago patients had last smoked, including among those who quit within 2 years prior to their diagnosis.

These findings create a “teachable moment” for health care providers in scenarios when patients might be more receptive to a stop-smoking message, according to investigator Aline F. Fares, MD, a clinical research fellow at Princess Margaret Cancer Centre in Toronto.

“Our study can be summarized to patients as, ‘it’s never too late to quit,’ ” Dr. Fares said.

She presented results from this study at the American Society of Clinical Oncology virtual scientific program during a press briefing in advance of the meeting. This year, ASCO’s annual meeting is split into two parts. The virtual scientific program will be presented online May 29-31. The virtual education program will be available Aug. 8-10.
 

Results

Dr. Fares presented data on 35,481 patients with a diagnosis of lung cancer who had been enrolled in 17 studies conducted by the International Lung Cancer Consortium. (Data in the presentation were updated from the abstract.)

At diagnosis, 47.5% of the patients were current smokers, 30% were former smokers, and 22.5% were never smokers.

The risk of death from any cause was cut by 20% among former smokers who quit more than 5 years before their lung cancer diagnosis (P < .001). Patients who quit smoking 2-5 years before diagnosis had a 16% reduction in the risk of death, while those who quit within 2 years of diagnosis had a 12% reduced risk (P < .001 for both comparisons).

The overall survival advantage was evident in this pooled analysis regardless of patient sex, disease stage, histology, or amount of smoking as measured in pack-years, according to Dr. Fares. That said, the overall survival advantage appeared to be even greater among heavier smokers (i.e., greater than 30 pack-years) as compared with lighter smokers.

Lung cancer–specific survival was improved by 15% for patients who quit smoking more than 5 years prior to their diagnosis. For those who had quit more recently, there was a nonsignificant trend toward improvement in this outcome.

Overall survival was higher in never smokers in comparison with current smokers, a finding that was expected based on previous studies, according to Dr. Fares.
 

Implications

These findings could be important to share with individuals who are current smokers at the time of lung cancer screening, according to Maher A. Karam-Hage, MD, medical director of the tobacco treatment program at the University of Texas MD Anderson Cancer Center, Houston.

“The power of this data is that it shows quitting makes a difference, and that it can be more impactful the longer you quit before you get diagnosed,” Dr. Karam-Hage said in an interview.

Negative lung cancer screening results sometimes give individuals the false impression that they are “one of the lucky ones” who won’t get lung cancer and don’t have to quit smoking, according to Dr. Karam-Hage, who is studying the comparative effectiveness of different smoking cessation strategies.

“Now, as part of shared decision making, we can provide people with specific numbers before the scan that [suggest] no matter what the scan comes out with, the earlier they quit, the better off they will be,” he said.

In her presentation, Dr. Fares said that lung cancer screening may be an “interesting time” to address smoking cessation, particularly among patients with a heavier smoking history.

“After a lifetime of smoking, patients often feel it’s too late to quit smoking and that the damage has already been done,” she added.

The International Lung Cancer Consortium studies had multiple supporters. Dr. Fares reported having no disclosures related to the research. One researcher reported relationships with AbbVie, AstraZeneca, MedImmune, Bayer, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche Canada, and Takeda. Dr. Karam-Hage reported having no relevant disclosures.

SOURCE: Fares AF et al. ASCO 2020, Abstract 1512.

This article was updated 5/15/20.

A polygenic risk score based on analysis of 29 discrete genetic variants linked with abdominal aortic aneurysms appeared better than the current criteria that clinicians use to identify people to screen for this disorder, potentially paving the way for more efficient use of screening resources.

Ryuji Suzuki

Future screening guidelines for abdominal aortic aneurysms (AAA) “should consider including individuals with high polygenic risk for screening ultrasonography,” Derek Klarin, MD, said at the virtual Vascular Discovery Scientific Sessions 2020, organized by the American Heart Association.

The data he reported showed that when researchers applied the polygenic risk score (PRS) to men aged older than 50 years in three independent validation cohorts of people with primarily European ancestry, those with scores in the top 5 percentile within each cohort had a collective AAA prevalence rate of 8.6% (95% CI 7.3%-9.8%).

This 8.6% pick-up rate using the PRS to help identify screening candidates for this male demographic subgroup compared favorably with previously reported prevalence rates of AAA detected by ultrasonography (defined as aneurysms of at least 3.0 cm in diameter) in men aged 65 years or older with a history of ever smoking. Last year, the U.S. Preventive Services Task Force issued an updated recommendation to perform a one-time ultrasound screening of 65- to 75-year-old men who ever smoked and cited five reported screening studies that found prevalence rates in these people of 3.3%-7.6% (JAMA. 2019 Dec 10;322[22]:2211-8). An earlier review of the topic by the task force cited an average estimated prevalence of 6%-7% in men at least 65 years old and with a smoking history (Ann Intern Med. 2014 Aug 19;161[4]: 281-90).

“You can use [the PRS] with other risk factors to increase the yield of identifying those at high risk,” Dr. Klarin said during a discussion of his report. He noted the possibility of using it to identify people at-risk early on, at birth, “prior to other risk factors being present,” as well as using the PRS as an add-on to known risk factors when assessing adults. He stressed that validations he has run so far still leave the PRS a step away from routine use, although it is “quite close,” said Dr. Klarin, a vascular surgeon at the University of Florida in Gainesville.

For use in routine practice, the PRS needs “further validation,” including further assessment of its performance in other age groups, in a wider range of ethnic groups, and in women, said Chris Semsarian, MBBS, professor of medicine at the University of Sydney and head of the Molecular Cardiology Program at its Centenary Institute. However, Dr. Semsarian also said that he saw great promise for the potential of the PRS, and its development so far had been solid.

“The study was meticulously undertaken, with a large number of AAA cases and controls. Both the derivation and validation are robust. There is great potential to use such a genetic risk score in the clinical setting, along with other risk factors such as smoking, high blood pressure, and lipid levels. The PRS adds another piece in the puzzle of risk of AAA by adding in genetic or inherited risk. An additional 1%-2% in pick-up rate would still lead to many thousands more AAA detected and lives saved. The PRS doesn’t replace environmental factors that contribute to AAA risk but adds a genetic component” when estimating a person’s overall risk and the appropriateness of screening ultrasound, Dr. Semsarian said in an interview.

The derivation analysis that Dr. Klarin and associates ran used data from the Million Veteran Program that included 7,642 people with AAA and matched them with more than 172,000 controls from the same database. This generated three alternative PRSs that involved testing for 29, 301, or 3,699 different mutations or polymorphisms that discriminated cases from controls. They compared these three scoring formulas in 1,000 AAA cases and 7,700 matched controls from the Mayo Clinic’s patient database, which showed that the 29-item PRS performed best, boosting identification of cases with a statistically significant odds ratio of 1.26.

They then ran the 29-item PRS in four additional large data banks, three that included mostly people of European ancestry and one that included mostly people with an African heritage. In the three data banks with people of mostly European background, the 29-item PRS performed even better than it did using the Mayo Clinic data, but this PRS was less informative in people with African ancestry. The analyses also suggested that the PRS identified elevated AAA risk independently of information on a family history of AAA, Dr. Klarin said.

The study had no commercial funding. Dr. Klarin has been a consultant to Regeneron.

mzoler@mdedge.com

SOURCE: Klarin D et al. Vascular Discovery 2020, abstract 170.

A polygenic risk score based on analysis of 29 discrete genetic variants linked with abdominal aortic aneurysms appeared better than the current criteria that clinicians use to identify people to screen for this disorder, potentially paving the way for more efficient use of screening resources.

Ryuji Suzuki

Future screening guidelines for abdominal aortic aneurysms (AAA) “should consider including individuals with high polygenic risk for screening ultrasonography,” Derek Klarin, MD, said at the virtual Vascular Discovery Scientific Sessions 2020, organized by the American Heart Association.

The data he reported showed that when researchers applied the polygenic risk score (PRS) to men aged older than 50 years in three independent validation cohorts of people with primarily European ancestry, those with scores in the top 5 percentile within each cohort had a collective AAA prevalence rate of 8.6% (95% CI 7.3%-9.8%).

This 8.6% pick-up rate using the PRS to help identify screening candidates for this male demographic subgroup compared favorably with previously reported prevalence rates of AAA detected by ultrasonography (defined as aneurysms of at least 3.0 cm in diameter) in men aged 65 years or older with a history of ever smoking. Last year, the U.S. Preventive Services Task Force issued an updated recommendation to perform a one-time ultrasound screening of 65- to 75-year-old men who ever smoked and cited five reported screening studies that found prevalence rates in these people of 3.3%-7.6% (JAMA. 2019 Dec 10;322[22]:2211-8). An earlier review of the topic by the task force cited an average estimated prevalence of 6%-7% in men at least 65 years old and with a smoking history (Ann Intern Med. 2014 Aug 19;161[4]: 281-90).

“You can use [the PRS] with other risk factors to increase the yield of identifying those at high risk,” Dr. Klarin said during a discussion of his report. He noted the possibility of using it to identify people at-risk early on, at birth, “prior to other risk factors being present,” as well as using the PRS as an add-on to known risk factors when assessing adults. He stressed that validations he has run so far still leave the PRS a step away from routine use, although it is “quite close,” said Dr. Klarin, a vascular surgeon at the University of Florida in Gainesville.

For use in routine practice, the PRS needs “further validation,” including further assessment of its performance in other age groups, in a wider range of ethnic groups, and in women, said Chris Semsarian, MBBS, professor of medicine at the University of Sydney and head of the Molecular Cardiology Program at its Centenary Institute. However, Dr. Semsarian also said that he saw great promise for the potential of the PRS, and its development so far had been solid.

“The study was meticulously undertaken, with a large number of AAA cases and controls. Both the derivation and validation are robust. There is great potential to use such a genetic risk score in the clinical setting, along with other risk factors such as smoking, high blood pressure, and lipid levels. The PRS adds another piece in the puzzle of risk of AAA by adding in genetic or inherited risk. An additional 1%-2% in pick-up rate would still lead to many thousands more AAA detected and lives saved. The PRS doesn’t replace environmental factors that contribute to AAA risk but adds a genetic component” when estimating a person’s overall risk and the appropriateness of screening ultrasound, Dr. Semsarian said in an interview.

The derivation analysis that Dr. Klarin and associates ran used data from the Million Veteran Program that included 7,642 people with AAA and matched them with more than 172,000 controls from the same database. This generated three alternative PRSs that involved testing for 29, 301, or 3,699 different mutations or polymorphisms that discriminated cases from controls. They compared these three scoring formulas in 1,000 AAA cases and 7,700 matched controls from the Mayo Clinic’s patient database, which showed that the 29-item PRS performed best, boosting identification of cases with a statistically significant odds ratio of 1.26.

They then ran the 29-item PRS in four additional large data banks, three that included mostly people of European ancestry and one that included mostly people with an African heritage. In the three data banks with people of mostly European background, the 29-item PRS performed even better than it did using the Mayo Clinic data, but this PRS was less informative in people with African ancestry. The analyses also suggested that the PRS identified elevated AAA risk independently of information on a family history of AAA, Dr. Klarin said.

The study had no commercial funding. Dr. Klarin has been a consultant to Regeneron.

mzoler@mdedge.com

SOURCE: Klarin D et al. Vascular Discovery 2020, abstract 170.

A polygenic risk score based on analysis of 29 discrete genetic variants linked with abdominal aortic aneurysms appeared better than the current criteria that clinicians use to identify people to screen for this disorder, potentially paving the way for more efficient use of screening resources.

Ryuji Suzuki

Future screening guidelines for abdominal aortic aneurysms (AAA) “should consider including individuals with high polygenic risk for screening ultrasonography,” Derek Klarin, MD, said at the virtual Vascular Discovery Scientific Sessions 2020, organized by the American Heart Association.

The data he reported showed that when researchers applied the polygenic risk score (PRS) to men aged older than 50 years in three independent validation cohorts of people with primarily European ancestry, those with scores in the top 5 percentile within each cohort had a collective AAA prevalence rate of 8.6% (95% CI 7.3%-9.8%).

This 8.6% pick-up rate using the PRS to help identify screening candidates for this male demographic subgroup compared favorably with previously reported prevalence rates of AAA detected by ultrasonography (defined as aneurysms of at least 3.0 cm in diameter) in men aged 65 years or older with a history of ever smoking. Last year, the U.S. Preventive Services Task Force issued an updated recommendation to perform a one-time ultrasound screening of 65- to 75-year-old men who ever smoked and cited five reported screening studies that found prevalence rates in these people of 3.3%-7.6% (JAMA. 2019 Dec 10;322[22]:2211-8). An earlier review of the topic by the task force cited an average estimated prevalence of 6%-7% in men at least 65 years old and with a smoking history (Ann Intern Med. 2014 Aug 19;161[4]: 281-90).

“You can use [the PRS] with other risk factors to increase the yield of identifying those at high risk,” Dr. Klarin said during a discussion of his report. He noted the possibility of using it to identify people at-risk early on, at birth, “prior to other risk factors being present,” as well as using the PRS as an add-on to known risk factors when assessing adults. He stressed that validations he has run so far still leave the PRS a step away from routine use, although it is “quite close,” said Dr. Klarin, a vascular surgeon at the University of Florida in Gainesville.

For use in routine practice, the PRS needs “further validation,” including further assessment of its performance in other age groups, in a wider range of ethnic groups, and in women, said Chris Semsarian, MBBS, professor of medicine at the University of Sydney and head of the Molecular Cardiology Program at its Centenary Institute. However, Dr. Semsarian also said that he saw great promise for the potential of the PRS, and its development so far had been solid.

“The study was meticulously undertaken, with a large number of AAA cases and controls. Both the derivation and validation are robust. There is great potential to use such a genetic risk score in the clinical setting, along with other risk factors such as smoking, high blood pressure, and lipid levels. The PRS adds another piece in the puzzle of risk of AAA by adding in genetic or inherited risk. An additional 1%-2% in pick-up rate would still lead to many thousands more AAA detected and lives saved. The PRS doesn’t replace environmental factors that contribute to AAA risk but adds a genetic component” when estimating a person’s overall risk and the appropriateness of screening ultrasound, Dr. Semsarian said in an interview.

The derivation analysis that Dr. Klarin and associates ran used data from the Million Veteran Program that included 7,642 people with AAA and matched them with more than 172,000 controls from the same database. This generated three alternative PRSs that involved testing for 29, 301, or 3,699 different mutations or polymorphisms that discriminated cases from controls. They compared these three scoring formulas in 1,000 AAA cases and 7,700 matched controls from the Mayo Clinic’s patient database, which showed that the 29-item PRS performed best, boosting identification of cases with a statistically significant odds ratio of 1.26.

They then ran the 29-item PRS in four additional large data banks, three that included mostly people of European ancestry and one that included mostly people with an African heritage. In the three data banks with people of mostly European background, the 29-item PRS performed even better than it did using the Mayo Clinic data, but this PRS was less informative in people with African ancestry. The analyses also suggested that the PRS identified elevated AAA risk independently of information on a family history of AAA, Dr. Klarin said.

The study had no commercial funding. Dr. Klarin has been a consultant to Regeneron.

mzoler@mdedge.com

SOURCE: Klarin D et al. Vascular Discovery 2020, abstract 170.