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Potential new role for FFR
Paris – Fractional flow reserve is under study for a potential major application: guidance on percutaneous coronary intervention (PCI) optimization immediately after stent placement, Roberto Diletti, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
At the end of the procedure, FFR measurement using a novel monorail optical pressure sensor catheter revealed that 43% of the lesions had a suboptimal FFR value of 0.90 or less.
“Just this year, two meta-analyses showed that a cutoff of 0.90 is important to define a group of patients at high risk for major adverse cardiovascular events and revascularization,” noted Dr. Diletti of Erasmus University Medical Center in Rotterdam, the Netherlands.
Using the older, more conservative cutoff of an FFR of 0.85 or less, 20% of the lesions would potentially benefit from further action to optimize the physiologic result, most often in the form of additional expansion of the stent.
“We are used to thinking of FFR as a tool to understand whether a lesion has to be treated or not. Now we can also start thinking about FFR as a tool to guide PCI optimization,” the cardiologist said.
Optimization wasn’t actually performed in this observational registry. That will be the focus of FFR-REACT, a planned randomized trial investigating the clinical impact of intravascular ultrasound (IVUS)-directed FFR optimization of PCI.
In a per-patient analysis, 48% of FFR-SEARCH participants had a poststent FFR of 0.90 or less in one or more treated lesions. Another 22% had a postprocedure FFR of 0.85 or less in at least one treated lesion, while 8.9% had an FFR of 0.80, which is below the threshold for ischemia.
The primary endpoint in the ongoing FFR-SEARCH study is the 2-year composite rate of major adverse cardiovascular events, defined as MI, any revascularization, or all-cause mortality. Only the 30-day MACE rate was available at the time of Dr. Diletti’s presentation in Paris. The rate was 1.5% in patients with a postprocedure FFR greater than 0.90, 2.0% in those with an FFR of 0.86-0.90, 2.6% with an FFR of 0.81-0.85, and 2.8% with a poststent FFR of 0.80 or less. While those early between-group differences weren’t statistically significant, the trend is encouraging, he noted.
Postprocedure FFR measurement took an average of 5 minutes. The procedure was simple and safe, according to Dr. Diletti. There were no complications related to the use of the Navvus MicroCatheter technology. He explained that the device profile is comparable to a 0.022-inch diameter at the lesion site. Wire access to the vessel was maintained throughout. The rapid-exchange monorail microcatheter was inserted over the previously used standard 0.014-inch coronary guidewire. The optical pressure sensor was positioned roughly 20 mm distal to the distal stent edge. Manual pullback with measurements obtained at various locations in the vicinity of the stented lesion was repeated as necessary in order to identify where optimization, if appropriate, should be focused.
Operators were unable to crossover the microcatheter in 3.5% of cases, mostly because of vessel tortuosity or calcification.
Audience members commented that many of the low FFRs after stenting may reflect diffuse coronary disease, which can be corrected only by placing numerous additional stents, creating its own problems. Dr. Diletti offered reassurance on that score. He explained that in an IVUS substudy of FFR-SEARCH, an unstented physiologically important focal lesion or stent underexpansion was identified in 86% of the cases of low FFR.
“That means you can do something about it. In the other 14% of cases, in my opinion, you cannot do a lot because of very diffuse disease distally,” he said.
He reported having no financial conflicts of interest in connection with the study, supported by ACIST Medical Systems. The Navvus MicroCatheter is approved by both the Food and Drug Administration and the European regulatory agency.
Paris – Fractional flow reserve is under study for a potential major application: guidance on percutaneous coronary intervention (PCI) optimization immediately after stent placement, Roberto Diletti, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
At the end of the procedure, FFR measurement using a novel monorail optical pressure sensor catheter revealed that 43% of the lesions had a suboptimal FFR value of 0.90 or less.
“Just this year, two meta-analyses showed that a cutoff of 0.90 is important to define a group of patients at high risk for major adverse cardiovascular events and revascularization,” noted Dr. Diletti of Erasmus University Medical Center in Rotterdam, the Netherlands.
Using the older, more conservative cutoff of an FFR of 0.85 or less, 20% of the lesions would potentially benefit from further action to optimize the physiologic result, most often in the form of additional expansion of the stent.
“We are used to thinking of FFR as a tool to understand whether a lesion has to be treated or not. Now we can also start thinking about FFR as a tool to guide PCI optimization,” the cardiologist said.
Optimization wasn’t actually performed in this observational registry. That will be the focus of FFR-REACT, a planned randomized trial investigating the clinical impact of intravascular ultrasound (IVUS)-directed FFR optimization of PCI.
In a per-patient analysis, 48% of FFR-SEARCH participants had a poststent FFR of 0.90 or less in one or more treated lesions. Another 22% had a postprocedure FFR of 0.85 or less in at least one treated lesion, while 8.9% had an FFR of 0.80, which is below the threshold for ischemia.
The primary endpoint in the ongoing FFR-SEARCH study is the 2-year composite rate of major adverse cardiovascular events, defined as MI, any revascularization, or all-cause mortality. Only the 30-day MACE rate was available at the time of Dr. Diletti’s presentation in Paris. The rate was 1.5% in patients with a postprocedure FFR greater than 0.90, 2.0% in those with an FFR of 0.86-0.90, 2.6% with an FFR of 0.81-0.85, and 2.8% with a poststent FFR of 0.80 or less. While those early between-group differences weren’t statistically significant, the trend is encouraging, he noted.
Postprocedure FFR measurement took an average of 5 minutes. The procedure was simple and safe, according to Dr. Diletti. There were no complications related to the use of the Navvus MicroCatheter technology. He explained that the device profile is comparable to a 0.022-inch diameter at the lesion site. Wire access to the vessel was maintained throughout. The rapid-exchange monorail microcatheter was inserted over the previously used standard 0.014-inch coronary guidewire. The optical pressure sensor was positioned roughly 20 mm distal to the distal stent edge. Manual pullback with measurements obtained at various locations in the vicinity of the stented lesion was repeated as necessary in order to identify where optimization, if appropriate, should be focused.
Operators were unable to crossover the microcatheter in 3.5% of cases, mostly because of vessel tortuosity or calcification.
Audience members commented that many of the low FFRs after stenting may reflect diffuse coronary disease, which can be corrected only by placing numerous additional stents, creating its own problems. Dr. Diletti offered reassurance on that score. He explained that in an IVUS substudy of FFR-SEARCH, an unstented physiologically important focal lesion or stent underexpansion was identified in 86% of the cases of low FFR.
“That means you can do something about it. In the other 14% of cases, in my opinion, you cannot do a lot because of very diffuse disease distally,” he said.
He reported having no financial conflicts of interest in connection with the study, supported by ACIST Medical Systems. The Navvus MicroCatheter is approved by both the Food and Drug Administration and the European regulatory agency.
Paris – Fractional flow reserve is under study for a potential major application: guidance on percutaneous coronary intervention (PCI) optimization immediately after stent placement, Roberto Diletti, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
At the end of the procedure, FFR measurement using a novel monorail optical pressure sensor catheter revealed that 43% of the lesions had a suboptimal FFR value of 0.90 or less.
“Just this year, two meta-analyses showed that a cutoff of 0.90 is important to define a group of patients at high risk for major adverse cardiovascular events and revascularization,” noted Dr. Diletti of Erasmus University Medical Center in Rotterdam, the Netherlands.
Using the older, more conservative cutoff of an FFR of 0.85 or less, 20% of the lesions would potentially benefit from further action to optimize the physiologic result, most often in the form of additional expansion of the stent.
“We are used to thinking of FFR as a tool to understand whether a lesion has to be treated or not. Now we can also start thinking about FFR as a tool to guide PCI optimization,” the cardiologist said.
Optimization wasn’t actually performed in this observational registry. That will be the focus of FFR-REACT, a planned randomized trial investigating the clinical impact of intravascular ultrasound (IVUS)-directed FFR optimization of PCI.
In a per-patient analysis, 48% of FFR-SEARCH participants had a poststent FFR of 0.90 or less in one or more treated lesions. Another 22% had a postprocedure FFR of 0.85 or less in at least one treated lesion, while 8.9% had an FFR of 0.80, which is below the threshold for ischemia.
The primary endpoint in the ongoing FFR-SEARCH study is the 2-year composite rate of major adverse cardiovascular events, defined as MI, any revascularization, or all-cause mortality. Only the 30-day MACE rate was available at the time of Dr. Diletti’s presentation in Paris. The rate was 1.5% in patients with a postprocedure FFR greater than 0.90, 2.0% in those with an FFR of 0.86-0.90, 2.6% with an FFR of 0.81-0.85, and 2.8% with a poststent FFR of 0.80 or less. While those early between-group differences weren’t statistically significant, the trend is encouraging, he noted.
Postprocedure FFR measurement took an average of 5 minutes. The procedure was simple and safe, according to Dr. Diletti. There were no complications related to the use of the Navvus MicroCatheter technology. He explained that the device profile is comparable to a 0.022-inch diameter at the lesion site. Wire access to the vessel was maintained throughout. The rapid-exchange monorail microcatheter was inserted over the previously used standard 0.014-inch coronary guidewire. The optical pressure sensor was positioned roughly 20 mm distal to the distal stent edge. Manual pullback with measurements obtained at various locations in the vicinity of the stented lesion was repeated as necessary in order to identify where optimization, if appropriate, should be focused.
Operators were unable to crossover the microcatheter in 3.5% of cases, mostly because of vessel tortuosity or calcification.
Audience members commented that many of the low FFRs after stenting may reflect diffuse coronary disease, which can be corrected only by placing numerous additional stents, creating its own problems. Dr. Diletti offered reassurance on that score. He explained that in an IVUS substudy of FFR-SEARCH, an unstented physiologically important focal lesion or stent underexpansion was identified in 86% of the cases of low FFR.
“That means you can do something about it. In the other 14% of cases, in my opinion, you cannot do a lot because of very diffuse disease distally,” he said.
He reported having no financial conflicts of interest in connection with the study, supported by ACIST Medical Systems. The Navvus MicroCatheter is approved by both the Food and Drug Administration and the European regulatory agency.
EXPERT ANALYSIS FROM EuroPCR
Youth perfectionism: Too much of a good thing
SAN FRANCISCO – Maladaptive perfectionism contributes to and is a risk factor for many common psychiatric disorders in children and adolescents, panelists said at the annual conference of the Anxiety and Depression Association of America.
“Perfectionism isn’t a disorder, it’s a personality style. Some of the kids who come in don’t meet criteria for any psychiatric disorder, they just have this personality style that really warrants treatment, because it is getting in the way of their living happy and productive lives. But I would say most of the time we see overlap with DSM Axis I disorders,” said Deborah Ledley, PhD, a clinical psychologist at the Children’s and Adult Center for OCD and Anxiety in Plymouth Meeting, Pa.
“Basically, when people present with multiple disorders and underlying perfectionism, it might actually be more effective to target the perfectionism, rather than treating each disorder sequentially,” according to Dr. Ledley. “Do we really need to treat social anxiety and panic disorder, and a subclinical eating disorder, or can we say, ‘This person is a perfectionist – let us treat that and see if we can remit all those disorders.’”
That strategy often has proved successful for Dr. Ledley and her fellow panelist Lynne Siqueland, PhD, who also practices at the center. Both specialize in cognitive-behavioral therapy (CBT). They were quick to note that there are essentially no published studies on CBT for pediatric perfectionism. Nonetheless, they have found CBT to be quite effective in clinical practice, with the caveat that the standard, full-speed-ahead, 12-sessions-and-we’re done manualized approach to CBT as often applied to anxiety disorders, depression, and other CBT-amenable disorders will not work for perfectionistic youths.
Dr. Ledley agreed. “We are not rushing with these patients,” she said. “This is so different from the way we are with an OCD patient, for example. When I have an OCD patient, I have the initial session with the parents, then an assessment session with the kid, then in the next session, I do some psychoeducation, and in the session after that, I’m doing exposures, because I work fast. Working with perfectionist kids is different: I have to earn their trust. I tell them a lot of stories about patients I’ve worked with who are just like them.”
How to spot maladaptive perfectionism
When the therapists meet with the parents for the first time – generally without the kids present – what they hear over and over again is, “My child is wound like a spring.” These are generally children who excel at everything: school, sports, music lessons, and other activities. And they are stressed out.
“These are the kids who are working on their Beethoven at age 8, trying to master the Moonlight Sonata. But the parents say the child is too hard on himself, freaking out over a grade less than 100% on a small quiz,” Dr. Ledley observed.
Sometimes, though, perfectionism backfires even in grade school, and the parents’ concern is not that their child is super accomplished yet not enjoying it, but rather that their kid has great potential and never gets anything done because of procrastination or an inability to hand in work that is less than perfect.
Dr. Ledley said when she first meets a perfectionist child, she typically sees a kid who looks perfect, has impeccable manners, and is mature beyond their years.
“They’re invested in coming across as successful in every way. They definitely do not let their guard down when you first meet them. But with these kids who look so perfect, we feel that there’s this fragility and fear, and delicacy lurking just below the surface. It’s almost like they’re afraid they’re going to break because they’re so held together,” according to the psychologist.
Once trust has been established and the youth has drawn up a requested list of the pros and cons of their perfectionism, Dr. Siqueland said, she hears a familiar refrain: “No freedom, no fun, no choice, no time for friends, tired all the time, and no sleep. That’s the usual list of the kids.”
The notion that hard-driving parents typically are at fault for pushing their child into perfectionism is a misconception.
“In our practice, I would say it’s self-induced perfectionism in 75% of cases,” according to Dr. Siqueland.
Treatment tips
After spending considerable time establishing rapport with a perfectionist youth, Dr. Ledley and Dr. Siqueland emphasize three key messages:
1. While on the surface your perfectionist strategy makes sense, enabling you to bask in positive feedback from teachers, coaches, friends, and in some cases your parents, it simply can’t be kept up long term.
“To the ones who really want to go to college and med school, I just say, ‘It’s not going to work there. You’ll not survive college. Or maybe college, but certainly not med school. So are you going to fix it now or fix it later? If you want med school as a goal, let’s help you get there,’ ” Dr. Siqueland said.
2. Therapy is not about changing your values.
“They fear that, if they don’t push and sacrifice, they’re going to be average, or even a slacker – and slacker might be worse than average,” Dr. Siqueland continued.
“We tell them it’s OK to have a drive for excellence, to go after your dream, and to take pride in good work well done. These are your values, and that’s great. We are not in the business of turning you into a slacker,” Dr. Ledley added.
3. Perfectionism takes away choices.
Therapy is all about helping you to live your life rather than having anxiety order you around. You can learn to have freedom, fun, choice, and sleep while in most cases doing as well as or better than before on your grades.
For clinicians who are inexperienced in addressing perfectionism in youth, Dr. Ledley and Dr. Siqueland recommended as a useful primer “The Perfectionism Workbook for Teens” (Oakland, Calif.: New Harbinger Publications, 2016).
They reported having no financial conflicts of interest.
SAN FRANCISCO – Maladaptive perfectionism contributes to and is a risk factor for many common psychiatric disorders in children and adolescents, panelists said at the annual conference of the Anxiety and Depression Association of America.
“Perfectionism isn’t a disorder, it’s a personality style. Some of the kids who come in don’t meet criteria for any psychiatric disorder, they just have this personality style that really warrants treatment, because it is getting in the way of their living happy and productive lives. But I would say most of the time we see overlap with DSM Axis I disorders,” said Deborah Ledley, PhD, a clinical psychologist at the Children’s and Adult Center for OCD and Anxiety in Plymouth Meeting, Pa.
“Basically, when people present with multiple disorders and underlying perfectionism, it might actually be more effective to target the perfectionism, rather than treating each disorder sequentially,” according to Dr. Ledley. “Do we really need to treat social anxiety and panic disorder, and a subclinical eating disorder, or can we say, ‘This person is a perfectionist – let us treat that and see if we can remit all those disorders.’”
That strategy often has proved successful for Dr. Ledley and her fellow panelist Lynne Siqueland, PhD, who also practices at the center. Both specialize in cognitive-behavioral therapy (CBT). They were quick to note that there are essentially no published studies on CBT for pediatric perfectionism. Nonetheless, they have found CBT to be quite effective in clinical practice, with the caveat that the standard, full-speed-ahead, 12-sessions-and-we’re done manualized approach to CBT as often applied to anxiety disorders, depression, and other CBT-amenable disorders will not work for perfectionistic youths.
Dr. Ledley agreed. “We are not rushing with these patients,” she said. “This is so different from the way we are with an OCD patient, for example. When I have an OCD patient, I have the initial session with the parents, then an assessment session with the kid, then in the next session, I do some psychoeducation, and in the session after that, I’m doing exposures, because I work fast. Working with perfectionist kids is different: I have to earn their trust. I tell them a lot of stories about patients I’ve worked with who are just like them.”
How to spot maladaptive perfectionism
When the therapists meet with the parents for the first time – generally without the kids present – what they hear over and over again is, “My child is wound like a spring.” These are generally children who excel at everything: school, sports, music lessons, and other activities. And they are stressed out.
“These are the kids who are working on their Beethoven at age 8, trying to master the Moonlight Sonata. But the parents say the child is too hard on himself, freaking out over a grade less than 100% on a small quiz,” Dr. Ledley observed.
Sometimes, though, perfectionism backfires even in grade school, and the parents’ concern is not that their child is super accomplished yet not enjoying it, but rather that their kid has great potential and never gets anything done because of procrastination or an inability to hand in work that is less than perfect.
Dr. Ledley said when she first meets a perfectionist child, she typically sees a kid who looks perfect, has impeccable manners, and is mature beyond their years.
“They’re invested in coming across as successful in every way. They definitely do not let their guard down when you first meet them. But with these kids who look so perfect, we feel that there’s this fragility and fear, and delicacy lurking just below the surface. It’s almost like they’re afraid they’re going to break because they’re so held together,” according to the psychologist.
Once trust has been established and the youth has drawn up a requested list of the pros and cons of their perfectionism, Dr. Siqueland said, she hears a familiar refrain: “No freedom, no fun, no choice, no time for friends, tired all the time, and no sleep. That’s the usual list of the kids.”
The notion that hard-driving parents typically are at fault for pushing their child into perfectionism is a misconception.
“In our practice, I would say it’s self-induced perfectionism in 75% of cases,” according to Dr. Siqueland.
Treatment tips
After spending considerable time establishing rapport with a perfectionist youth, Dr. Ledley and Dr. Siqueland emphasize three key messages:
1. While on the surface your perfectionist strategy makes sense, enabling you to bask in positive feedback from teachers, coaches, friends, and in some cases your parents, it simply can’t be kept up long term.
“To the ones who really want to go to college and med school, I just say, ‘It’s not going to work there. You’ll not survive college. Or maybe college, but certainly not med school. So are you going to fix it now or fix it later? If you want med school as a goal, let’s help you get there,’ ” Dr. Siqueland said.
2. Therapy is not about changing your values.
“They fear that, if they don’t push and sacrifice, they’re going to be average, or even a slacker – and slacker might be worse than average,” Dr. Siqueland continued.
“We tell them it’s OK to have a drive for excellence, to go after your dream, and to take pride in good work well done. These are your values, and that’s great. We are not in the business of turning you into a slacker,” Dr. Ledley added.
3. Perfectionism takes away choices.
Therapy is all about helping you to live your life rather than having anxiety order you around. You can learn to have freedom, fun, choice, and sleep while in most cases doing as well as or better than before on your grades.
For clinicians who are inexperienced in addressing perfectionism in youth, Dr. Ledley and Dr. Siqueland recommended as a useful primer “The Perfectionism Workbook for Teens” (Oakland, Calif.: New Harbinger Publications, 2016).
They reported having no financial conflicts of interest.
SAN FRANCISCO – Maladaptive perfectionism contributes to and is a risk factor for many common psychiatric disorders in children and adolescents, panelists said at the annual conference of the Anxiety and Depression Association of America.
“Perfectionism isn’t a disorder, it’s a personality style. Some of the kids who come in don’t meet criteria for any psychiatric disorder, they just have this personality style that really warrants treatment, because it is getting in the way of their living happy and productive lives. But I would say most of the time we see overlap with DSM Axis I disorders,” said Deborah Ledley, PhD, a clinical psychologist at the Children’s and Adult Center for OCD and Anxiety in Plymouth Meeting, Pa.
“Basically, when people present with multiple disorders and underlying perfectionism, it might actually be more effective to target the perfectionism, rather than treating each disorder sequentially,” according to Dr. Ledley. “Do we really need to treat social anxiety and panic disorder, and a subclinical eating disorder, or can we say, ‘This person is a perfectionist – let us treat that and see if we can remit all those disorders.’”
That strategy often has proved successful for Dr. Ledley and her fellow panelist Lynne Siqueland, PhD, who also practices at the center. Both specialize in cognitive-behavioral therapy (CBT). They were quick to note that there are essentially no published studies on CBT for pediatric perfectionism. Nonetheless, they have found CBT to be quite effective in clinical practice, with the caveat that the standard, full-speed-ahead, 12-sessions-and-we’re done manualized approach to CBT as often applied to anxiety disorders, depression, and other CBT-amenable disorders will not work for perfectionistic youths.
Dr. Ledley agreed. “We are not rushing with these patients,” she said. “This is so different from the way we are with an OCD patient, for example. When I have an OCD patient, I have the initial session with the parents, then an assessment session with the kid, then in the next session, I do some psychoeducation, and in the session after that, I’m doing exposures, because I work fast. Working with perfectionist kids is different: I have to earn their trust. I tell them a lot of stories about patients I’ve worked with who are just like them.”
How to spot maladaptive perfectionism
When the therapists meet with the parents for the first time – generally without the kids present – what they hear over and over again is, “My child is wound like a spring.” These are generally children who excel at everything: school, sports, music lessons, and other activities. And they are stressed out.
“These are the kids who are working on their Beethoven at age 8, trying to master the Moonlight Sonata. But the parents say the child is too hard on himself, freaking out over a grade less than 100% on a small quiz,” Dr. Ledley observed.
Sometimes, though, perfectionism backfires even in grade school, and the parents’ concern is not that their child is super accomplished yet not enjoying it, but rather that their kid has great potential and never gets anything done because of procrastination or an inability to hand in work that is less than perfect.
Dr. Ledley said when she first meets a perfectionist child, she typically sees a kid who looks perfect, has impeccable manners, and is mature beyond their years.
“They’re invested in coming across as successful in every way. They definitely do not let their guard down when you first meet them. But with these kids who look so perfect, we feel that there’s this fragility and fear, and delicacy lurking just below the surface. It’s almost like they’re afraid they’re going to break because they’re so held together,” according to the psychologist.
Once trust has been established and the youth has drawn up a requested list of the pros and cons of their perfectionism, Dr. Siqueland said, she hears a familiar refrain: “No freedom, no fun, no choice, no time for friends, tired all the time, and no sleep. That’s the usual list of the kids.”
The notion that hard-driving parents typically are at fault for pushing their child into perfectionism is a misconception.
“In our practice, I would say it’s self-induced perfectionism in 75% of cases,” according to Dr. Siqueland.
Treatment tips
After spending considerable time establishing rapport with a perfectionist youth, Dr. Ledley and Dr. Siqueland emphasize three key messages:
1. While on the surface your perfectionist strategy makes sense, enabling you to bask in positive feedback from teachers, coaches, friends, and in some cases your parents, it simply can’t be kept up long term.
“To the ones who really want to go to college and med school, I just say, ‘It’s not going to work there. You’ll not survive college. Or maybe college, but certainly not med school. So are you going to fix it now or fix it later? If you want med school as a goal, let’s help you get there,’ ” Dr. Siqueland said.
2. Therapy is not about changing your values.
“They fear that, if they don’t push and sacrifice, they’re going to be average, or even a slacker – and slacker might be worse than average,” Dr. Siqueland continued.
“We tell them it’s OK to have a drive for excellence, to go after your dream, and to take pride in good work well done. These are your values, and that’s great. We are not in the business of turning you into a slacker,” Dr. Ledley added.
3. Perfectionism takes away choices.
Therapy is all about helping you to live your life rather than having anxiety order you around. You can learn to have freedom, fun, choice, and sleep while in most cases doing as well as or better than before on your grades.
For clinicians who are inexperienced in addressing perfectionism in youth, Dr. Ledley and Dr. Siqueland recommended as a useful primer “The Perfectionism Workbook for Teens” (Oakland, Calif.: New Harbinger Publications, 2016).
They reported having no financial conflicts of interest.
EXPERT ANALYSIS FROM THE ANXIETY AND DEPRESSION CONFERENCE 2017
Little treatments show big promise for youth psychiatric problems
SAN FRANCISCO – Very brief, outside-the-box therapeutic interventions are racking up respectable efficacy scores in randomized, controlled trials addressing a variety of common psychiatric problems in youths, Jessica L. Schleider observed at the annual conference of the Anxiety and Depression Association of America.
The impetus for developing very brief interventions – or VBIs, as they are known in psychotherapy research parlance – is mounting recognition that conventional treatment approaches have by and large failed children and adolescents who have mental health problems, explained Ms. Schleider, a doctoral candidate in clinical psychology at Harvard University in Cambridge, Mass.
According to data from the Centers for Disease Control and Prevention and the Child Mind Institute, only 20% of American children and adolescents who have significant mental health problems access mental health services. And among those who do, only a minority complete their planned course of treatment.
Reimbursable treatment plans for youth mental health problems typically entail about 16 sessions. Yet national insurance reimbursement data indicate those youths who do access treatment attend on average fewer than four sessions.
“Given that the current model just doesn’t seem to be meeting the needs of kids and families across the country, novel approaches are going to be necessary to really reduce the burden of youth mental illness on a broad scale,” Ms. Schleider asserted.
She characterized VBIs as an example of what is often referred to in TED Talks as “disruptive innovation.” VBIs are intended to extend the reach of youth mental health services by offering interventions that are brief, affordable, accessible, and scalable. It’s a concept that has captured the imagination of officials at the National Institute of Mental Health, which is funding her VBI work and that of others under the institute’s experimental therapeutics initiative.
Ms. Schleider coauthored a recent meta-analysis of 50 randomized, controlled trials of single-session interventions (SSIs) for mental health problems in a collective 10,508 youths. The investigators found that the treatment effect size varied by the target problem. The largest effect size documented – 1.05, which is a strong benefit – was for SSIs targeting eating disorders. The weakest was for the 18 randomized trials addressing substance abuse, with an effect size of a mere 0.08 (J Am Acad Child Adolesc Psychiatry. 2017 Feb;56[2]:107-15).
“The mean effect size across all categories is 0.32, which is decent. It’s in the small-to-medium range,” she noted. “But if you zoom in on the most common types of youth mental health problems – anxiety, conduct, and depression – we see that the overall effect of those single-session programs compares surprisingly well to the full-length treatments that we have, further supporting a possible value as an element of our mental health system.”
For SSIs addressing anxiety, for example, the mean posttreatment effect size was 0.56, compared with 0.61 for conventional multisession programs. For conduct problems, SSIs produced a mean effect size of 0.54, versus 0.46 for full-length treatment programs. And while the effect size of SSIs for depression was small, at 0.18, the same might be said for the 0.28 mean effect size for standard depression therapy programs.
Mean SSI treatment effect sizes were larger for children than for adolescents, at 0.42, compared with 0.19.
Ms. Schleider also presented highlights of a published randomized, double-blind trial of a self-administered computer-guided SSI she and her coauthor have developed. That SSI is designed to briefly teach troubled adolescents a growth personality mindset: that is, the belief that personal traits such as shyness, sadness, and intelligence are malleable through effort and hard work, rather than static and unchangeable.
“Kids with fixed mindsets tend to fare worse than those with growth mindsets,” she said. “They give up prematurely in response to social and academic stress, and they engage in a lot more negative self talk.
The intervention borrows from the achievement motivation theory developed by Carol S. Dweck, Ph.D., professor of psychology at Stanford (Calif.) University and author of the book, “Mindset: the New Psychology of Success.”
The trial randomized 96 subjects aged 12-15 years to a half hour spent on a computer with the growth mindset intervention or a shared feelings control. These were teens with elevated levels of internalizing problems. Eighty-four percent of them met criteria for anxiety by the SCARED CHILD (Screen for Child Anxiety Related Disorders – Child Version) or for depression via the CDI (Children’s Depression Inventory). Subjects were followed up immediately post treatment and again at 3, 6, and 9 months, with 74% of the original group participating in the final follow-up.
The guided growth mindset group showed significant reductions from baseline in CDI and SCARED scores at every follow-up point, while the control group remained unchanged.
“What I see as the bottom line are the 9-month follow-up effects: All effect sizes for youth- and parent-reported outcomes of anxiety and depression are in the small-to-medium range,” Ms. Schleider said. “But this is quite promising, I think, for a 30-minute intervention that kids can complete on their own.”
Also, the mindset intervention strengthened postintervention measures of the adolescents’ perceived control. On a postintervention, laboratory-based, standardized social stress test, the mindset intervention group achieved physiologic recovery more than three times faster than did the controls, as assessed via electrodermal activity.
Ms. Schleider called the study results “promising and exciting.” She is now working with therapists at McLean Hospital, Belmont, Mass., to see whether administering the growth mindset intervention at the start of youth intensive cognitive-behavioral therapy for anxiety results in improved treatment outcomes.
“By teaching kids that change is possible, it might improve their engagement in CBT or reduce their dropout rates,” she noted.
Ms. Schleider is also pilot studying a parent-directed growth mindset intervention to learn whether it improves parents’ attitude toward psychotherapy and seeking services for a troubled child.
Her randomized trial was supported by the National Institute of Mental Health, the American Psychological Association, and the Harvard Center on the Developing Child. She reported having no financial conflicts.
SAN FRANCISCO – Very brief, outside-the-box therapeutic interventions are racking up respectable efficacy scores in randomized, controlled trials addressing a variety of common psychiatric problems in youths, Jessica L. Schleider observed at the annual conference of the Anxiety and Depression Association of America.
The impetus for developing very brief interventions – or VBIs, as they are known in psychotherapy research parlance – is mounting recognition that conventional treatment approaches have by and large failed children and adolescents who have mental health problems, explained Ms. Schleider, a doctoral candidate in clinical psychology at Harvard University in Cambridge, Mass.
According to data from the Centers for Disease Control and Prevention and the Child Mind Institute, only 20% of American children and adolescents who have significant mental health problems access mental health services. And among those who do, only a minority complete their planned course of treatment.
Reimbursable treatment plans for youth mental health problems typically entail about 16 sessions. Yet national insurance reimbursement data indicate those youths who do access treatment attend on average fewer than four sessions.
“Given that the current model just doesn’t seem to be meeting the needs of kids and families across the country, novel approaches are going to be necessary to really reduce the burden of youth mental illness on a broad scale,” Ms. Schleider asserted.
She characterized VBIs as an example of what is often referred to in TED Talks as “disruptive innovation.” VBIs are intended to extend the reach of youth mental health services by offering interventions that are brief, affordable, accessible, and scalable. It’s a concept that has captured the imagination of officials at the National Institute of Mental Health, which is funding her VBI work and that of others under the institute’s experimental therapeutics initiative.
Ms. Schleider coauthored a recent meta-analysis of 50 randomized, controlled trials of single-session interventions (SSIs) for mental health problems in a collective 10,508 youths. The investigators found that the treatment effect size varied by the target problem. The largest effect size documented – 1.05, which is a strong benefit – was for SSIs targeting eating disorders. The weakest was for the 18 randomized trials addressing substance abuse, with an effect size of a mere 0.08 (J Am Acad Child Adolesc Psychiatry. 2017 Feb;56[2]:107-15).
“The mean effect size across all categories is 0.32, which is decent. It’s in the small-to-medium range,” she noted. “But if you zoom in on the most common types of youth mental health problems – anxiety, conduct, and depression – we see that the overall effect of those single-session programs compares surprisingly well to the full-length treatments that we have, further supporting a possible value as an element of our mental health system.”
For SSIs addressing anxiety, for example, the mean posttreatment effect size was 0.56, compared with 0.61 for conventional multisession programs. For conduct problems, SSIs produced a mean effect size of 0.54, versus 0.46 for full-length treatment programs. And while the effect size of SSIs for depression was small, at 0.18, the same might be said for the 0.28 mean effect size for standard depression therapy programs.
Mean SSI treatment effect sizes were larger for children than for adolescents, at 0.42, compared with 0.19.
Ms. Schleider also presented highlights of a published randomized, double-blind trial of a self-administered computer-guided SSI she and her coauthor have developed. That SSI is designed to briefly teach troubled adolescents a growth personality mindset: that is, the belief that personal traits such as shyness, sadness, and intelligence are malleable through effort and hard work, rather than static and unchangeable.
“Kids with fixed mindsets tend to fare worse than those with growth mindsets,” she said. “They give up prematurely in response to social and academic stress, and they engage in a lot more negative self talk.
The intervention borrows from the achievement motivation theory developed by Carol S. Dweck, Ph.D., professor of psychology at Stanford (Calif.) University and author of the book, “Mindset: the New Psychology of Success.”
The trial randomized 96 subjects aged 12-15 years to a half hour spent on a computer with the growth mindset intervention or a shared feelings control. These were teens with elevated levels of internalizing problems. Eighty-four percent of them met criteria for anxiety by the SCARED CHILD (Screen for Child Anxiety Related Disorders – Child Version) or for depression via the CDI (Children’s Depression Inventory). Subjects were followed up immediately post treatment and again at 3, 6, and 9 months, with 74% of the original group participating in the final follow-up.
The guided growth mindset group showed significant reductions from baseline in CDI and SCARED scores at every follow-up point, while the control group remained unchanged.
“What I see as the bottom line are the 9-month follow-up effects: All effect sizes for youth- and parent-reported outcomes of anxiety and depression are in the small-to-medium range,” Ms. Schleider said. “But this is quite promising, I think, for a 30-minute intervention that kids can complete on their own.”
Also, the mindset intervention strengthened postintervention measures of the adolescents’ perceived control. On a postintervention, laboratory-based, standardized social stress test, the mindset intervention group achieved physiologic recovery more than three times faster than did the controls, as assessed via electrodermal activity.
Ms. Schleider called the study results “promising and exciting.” She is now working with therapists at McLean Hospital, Belmont, Mass., to see whether administering the growth mindset intervention at the start of youth intensive cognitive-behavioral therapy for anxiety results in improved treatment outcomes.
“By teaching kids that change is possible, it might improve their engagement in CBT or reduce their dropout rates,” she noted.
Ms. Schleider is also pilot studying a parent-directed growth mindset intervention to learn whether it improves parents’ attitude toward psychotherapy and seeking services for a troubled child.
Her randomized trial was supported by the National Institute of Mental Health, the American Psychological Association, and the Harvard Center on the Developing Child. She reported having no financial conflicts.
SAN FRANCISCO – Very brief, outside-the-box therapeutic interventions are racking up respectable efficacy scores in randomized, controlled trials addressing a variety of common psychiatric problems in youths, Jessica L. Schleider observed at the annual conference of the Anxiety and Depression Association of America.
The impetus for developing very brief interventions – or VBIs, as they are known in psychotherapy research parlance – is mounting recognition that conventional treatment approaches have by and large failed children and adolescents who have mental health problems, explained Ms. Schleider, a doctoral candidate in clinical psychology at Harvard University in Cambridge, Mass.
According to data from the Centers for Disease Control and Prevention and the Child Mind Institute, only 20% of American children and adolescents who have significant mental health problems access mental health services. And among those who do, only a minority complete their planned course of treatment.
Reimbursable treatment plans for youth mental health problems typically entail about 16 sessions. Yet national insurance reimbursement data indicate those youths who do access treatment attend on average fewer than four sessions.
“Given that the current model just doesn’t seem to be meeting the needs of kids and families across the country, novel approaches are going to be necessary to really reduce the burden of youth mental illness on a broad scale,” Ms. Schleider asserted.
She characterized VBIs as an example of what is often referred to in TED Talks as “disruptive innovation.” VBIs are intended to extend the reach of youth mental health services by offering interventions that are brief, affordable, accessible, and scalable. It’s a concept that has captured the imagination of officials at the National Institute of Mental Health, which is funding her VBI work and that of others under the institute’s experimental therapeutics initiative.
Ms. Schleider coauthored a recent meta-analysis of 50 randomized, controlled trials of single-session interventions (SSIs) for mental health problems in a collective 10,508 youths. The investigators found that the treatment effect size varied by the target problem. The largest effect size documented – 1.05, which is a strong benefit – was for SSIs targeting eating disorders. The weakest was for the 18 randomized trials addressing substance abuse, with an effect size of a mere 0.08 (J Am Acad Child Adolesc Psychiatry. 2017 Feb;56[2]:107-15).
“The mean effect size across all categories is 0.32, which is decent. It’s in the small-to-medium range,” she noted. “But if you zoom in on the most common types of youth mental health problems – anxiety, conduct, and depression – we see that the overall effect of those single-session programs compares surprisingly well to the full-length treatments that we have, further supporting a possible value as an element of our mental health system.”
For SSIs addressing anxiety, for example, the mean posttreatment effect size was 0.56, compared with 0.61 for conventional multisession programs. For conduct problems, SSIs produced a mean effect size of 0.54, versus 0.46 for full-length treatment programs. And while the effect size of SSIs for depression was small, at 0.18, the same might be said for the 0.28 mean effect size for standard depression therapy programs.
Mean SSI treatment effect sizes were larger for children than for adolescents, at 0.42, compared with 0.19.
Ms. Schleider also presented highlights of a published randomized, double-blind trial of a self-administered computer-guided SSI she and her coauthor have developed. That SSI is designed to briefly teach troubled adolescents a growth personality mindset: that is, the belief that personal traits such as shyness, sadness, and intelligence are malleable through effort and hard work, rather than static and unchangeable.
“Kids with fixed mindsets tend to fare worse than those with growth mindsets,” she said. “They give up prematurely in response to social and academic stress, and they engage in a lot more negative self talk.
The intervention borrows from the achievement motivation theory developed by Carol S. Dweck, Ph.D., professor of psychology at Stanford (Calif.) University and author of the book, “Mindset: the New Psychology of Success.”
The trial randomized 96 subjects aged 12-15 years to a half hour spent on a computer with the growth mindset intervention or a shared feelings control. These were teens with elevated levels of internalizing problems. Eighty-four percent of them met criteria for anxiety by the SCARED CHILD (Screen for Child Anxiety Related Disorders – Child Version) or for depression via the CDI (Children’s Depression Inventory). Subjects were followed up immediately post treatment and again at 3, 6, and 9 months, with 74% of the original group participating in the final follow-up.
The guided growth mindset group showed significant reductions from baseline in CDI and SCARED scores at every follow-up point, while the control group remained unchanged.
“What I see as the bottom line are the 9-month follow-up effects: All effect sizes for youth- and parent-reported outcomes of anxiety and depression are in the small-to-medium range,” Ms. Schleider said. “But this is quite promising, I think, for a 30-minute intervention that kids can complete on their own.”
Also, the mindset intervention strengthened postintervention measures of the adolescents’ perceived control. On a postintervention, laboratory-based, standardized social stress test, the mindset intervention group achieved physiologic recovery more than three times faster than did the controls, as assessed via electrodermal activity.
Ms. Schleider called the study results “promising and exciting.” She is now working with therapists at McLean Hospital, Belmont, Mass., to see whether administering the growth mindset intervention at the start of youth intensive cognitive-behavioral therapy for anxiety results in improved treatment outcomes.
“By teaching kids that change is possible, it might improve their engagement in CBT or reduce their dropout rates,” she noted.
Ms. Schleider is also pilot studying a parent-directed growth mindset intervention to learn whether it improves parents’ attitude toward psychotherapy and seeking services for a troubled child.
Her randomized trial was supported by the National Institute of Mental Health, the American Psychological Association, and the Harvard Center on the Developing Child. She reported having no financial conflicts.
EXPERT ANALYSIS FROM THE ANXIETY AND DEPRESSION CONFERENCE 2017
Early neuroimaging essential for Zika-exposed neonates
DENVER – The experience gleaned at ground zero of the Brazilian Zika virus epidemic drives home a clinical imperative: every neonate whose pregnant mother has presumed or confirmed Zika infection needs to undergo prompt neuroimaging, even if head circumference at birth is normal, Vanessa van der Linden, MD, said at the annual meeting of the Teratology Society.
Dr. van der Linden, a pediatric neurologist at the Association for Assistance of Disabled Children in Recife, Brazil, has done pioneering work in characterizing the recently recognized congenital Zika syndrome. She was the lead author of the first report of infants who had laboratory evidence of congenital Zika infection and normal head circumference at birth but who developed poor head growth and microcephaly later in infancy.
Comprehensive multispecialty medical and developmental follow-up documented that 10 of 13 infants had dysphagia, 7 had epilepsy, 3 had chorioretinal abnormalities, all 13 had hypertonia, and 12 had pyramidal and extrapyramidal signs with dystonia (MMWR. 2016 Dec 2;65[47]:1343-8).
In another recent publication, Dr. van der Linden and her coinvestigators described classic congenital Zika syndrome with microcephaly at birth as simply the tip of the Zika virus iceberg. In their retrospective review of 77 infants exposed to Zika in utero, 9 had microcephaly at birth, 7 developed microcephaly postnatally, and 3 didn’t have microcephaly at all. Those with microcephaly at birth showed the traditional neuroimaging findings of congenital Zika syndrome, including reduced brain volume, ventriculomegaly, subcortical calcifications, corpus callosum abnormalities, and an enlarged extra-axial space.
Those who subsequently developed microcephaly later in infancy showed most of the same neuroimaging abnormalities. The three infants who remained normocephalic displayed calcifications in the cortico-subcortical junction, asymmetric frontal polymicrogyria, delayed myelination, and milder ventriculomegaly than in the other two groups (AJNR Am J Neuroradiol. 2017 Jul;38[7]:1427-34).
The rehabilitation center where Dr. van der Linden and her colleagues are currently following roughly 200 children with congenital Zika syndrome is in the state of Pernambuco, which was particularly hard hit by the Zika epidemic.
She reported having no relevant financial disclosures.
DENVER – The experience gleaned at ground zero of the Brazilian Zika virus epidemic drives home a clinical imperative: every neonate whose pregnant mother has presumed or confirmed Zika infection needs to undergo prompt neuroimaging, even if head circumference at birth is normal, Vanessa van der Linden, MD, said at the annual meeting of the Teratology Society.
Dr. van der Linden, a pediatric neurologist at the Association for Assistance of Disabled Children in Recife, Brazil, has done pioneering work in characterizing the recently recognized congenital Zika syndrome. She was the lead author of the first report of infants who had laboratory evidence of congenital Zika infection and normal head circumference at birth but who developed poor head growth and microcephaly later in infancy.
Comprehensive multispecialty medical and developmental follow-up documented that 10 of 13 infants had dysphagia, 7 had epilepsy, 3 had chorioretinal abnormalities, all 13 had hypertonia, and 12 had pyramidal and extrapyramidal signs with dystonia (MMWR. 2016 Dec 2;65[47]:1343-8).
In another recent publication, Dr. van der Linden and her coinvestigators described classic congenital Zika syndrome with microcephaly at birth as simply the tip of the Zika virus iceberg. In their retrospective review of 77 infants exposed to Zika in utero, 9 had microcephaly at birth, 7 developed microcephaly postnatally, and 3 didn’t have microcephaly at all. Those with microcephaly at birth showed the traditional neuroimaging findings of congenital Zika syndrome, including reduced brain volume, ventriculomegaly, subcortical calcifications, corpus callosum abnormalities, and an enlarged extra-axial space.
Those who subsequently developed microcephaly later in infancy showed most of the same neuroimaging abnormalities. The three infants who remained normocephalic displayed calcifications in the cortico-subcortical junction, asymmetric frontal polymicrogyria, delayed myelination, and milder ventriculomegaly than in the other two groups (AJNR Am J Neuroradiol. 2017 Jul;38[7]:1427-34).
The rehabilitation center where Dr. van der Linden and her colleagues are currently following roughly 200 children with congenital Zika syndrome is in the state of Pernambuco, which was particularly hard hit by the Zika epidemic.
She reported having no relevant financial disclosures.
DENVER – The experience gleaned at ground zero of the Brazilian Zika virus epidemic drives home a clinical imperative: every neonate whose pregnant mother has presumed or confirmed Zika infection needs to undergo prompt neuroimaging, even if head circumference at birth is normal, Vanessa van der Linden, MD, said at the annual meeting of the Teratology Society.
Dr. van der Linden, a pediatric neurologist at the Association for Assistance of Disabled Children in Recife, Brazil, has done pioneering work in characterizing the recently recognized congenital Zika syndrome. She was the lead author of the first report of infants who had laboratory evidence of congenital Zika infection and normal head circumference at birth but who developed poor head growth and microcephaly later in infancy.
Comprehensive multispecialty medical and developmental follow-up documented that 10 of 13 infants had dysphagia, 7 had epilepsy, 3 had chorioretinal abnormalities, all 13 had hypertonia, and 12 had pyramidal and extrapyramidal signs with dystonia (MMWR. 2016 Dec 2;65[47]:1343-8).
In another recent publication, Dr. van der Linden and her coinvestigators described classic congenital Zika syndrome with microcephaly at birth as simply the tip of the Zika virus iceberg. In their retrospective review of 77 infants exposed to Zika in utero, 9 had microcephaly at birth, 7 developed microcephaly postnatally, and 3 didn’t have microcephaly at all. Those with microcephaly at birth showed the traditional neuroimaging findings of congenital Zika syndrome, including reduced brain volume, ventriculomegaly, subcortical calcifications, corpus callosum abnormalities, and an enlarged extra-axial space.
Those who subsequently developed microcephaly later in infancy showed most of the same neuroimaging abnormalities. The three infants who remained normocephalic displayed calcifications in the cortico-subcortical junction, asymmetric frontal polymicrogyria, delayed myelination, and milder ventriculomegaly than in the other two groups (AJNR Am J Neuroradiol. 2017 Jul;38[7]:1427-34).
The rehabilitation center where Dr. van der Linden and her colleagues are currently following roughly 200 children with congenital Zika syndrome is in the state of Pernambuco, which was particularly hard hit by the Zika epidemic.
She reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
Antiviral shows early promise for treatment of Zika infection
DENVER – An antiviral drug that is a key player in the recent revolution in the treatment of hepatitis C infection also blocks Zika virus replication both in vitro and in a mouse model, Alysson R. Muotri, PhD, said at the annual meeting of the Teratology Society.
Sofosbuvir is a promising candidate. Not only has it demonstrated efficacy in preclinical work by Dr. Muotri and other groups of investigators, but it is also already a Food and Drug Administration–approved antiviral agent with a relatively reassuring Category B rating for use in pregnancy, meaning no evidence of teratogenicity in animal studies.
Investigators at the Scripps Clinic in La Jolla, Calif., have shown that the replication machinery in the Zika virus genome is closely similar to that of another flavivirus: hepatitis C. Both viruses express an NS2B-NS3 protease essential for generation of functional viral proteins.
“That observation led us to look for drugs that would interact with that replication pocket,” Dr. Muotri said.
The researchers first established in vitro that sofosbuvir can bind to the Zika virus NS2B-NS3 protease interface in an area known as the RNA-directed RNA polymerase domain, both in Zika virus–infected human neural progenitor cells and in cerebral organoids. Next, they demonstrated that sofosbuvir inhibited Zika virus replication in mice in dose-dependent fashion (Antiviral Res. 2017 Jul;143:218-29).
Most recently – and most importantly – the researchers showed that sofosbuvir blocked vertical transmission of Zika virus infection in the mouse model. “It’s neuroprotective for the fetus. There was no PCR [polymerase chain reaction] evidence of Zika virus in the fetal head. Those animals are born normal as far as we can tell,” he said.
The researchers are also engaged in preclinical evaluation of other antiviral agents as potential treatments for Zika infection. Some show even more potent anti-Zika activity than did sofosbuvir. But they have the disadvantage of being nonapproved investigational drugs and hence are far earlier in the developmental pipeline.
Dr. Muotri, whose research is supported by the National Institutes of Health, reported having no relevant financial disclosures.
DENVER – An antiviral drug that is a key player in the recent revolution in the treatment of hepatitis C infection also blocks Zika virus replication both in vitro and in a mouse model, Alysson R. Muotri, PhD, said at the annual meeting of the Teratology Society.
Sofosbuvir is a promising candidate. Not only has it demonstrated efficacy in preclinical work by Dr. Muotri and other groups of investigators, but it is also already a Food and Drug Administration–approved antiviral agent with a relatively reassuring Category B rating for use in pregnancy, meaning no evidence of teratogenicity in animal studies.
Investigators at the Scripps Clinic in La Jolla, Calif., have shown that the replication machinery in the Zika virus genome is closely similar to that of another flavivirus: hepatitis C. Both viruses express an NS2B-NS3 protease essential for generation of functional viral proteins.
“That observation led us to look for drugs that would interact with that replication pocket,” Dr. Muotri said.
The researchers first established in vitro that sofosbuvir can bind to the Zika virus NS2B-NS3 protease interface in an area known as the RNA-directed RNA polymerase domain, both in Zika virus–infected human neural progenitor cells and in cerebral organoids. Next, they demonstrated that sofosbuvir inhibited Zika virus replication in mice in dose-dependent fashion (Antiviral Res. 2017 Jul;143:218-29).
Most recently – and most importantly – the researchers showed that sofosbuvir blocked vertical transmission of Zika virus infection in the mouse model. “It’s neuroprotective for the fetus. There was no PCR [polymerase chain reaction] evidence of Zika virus in the fetal head. Those animals are born normal as far as we can tell,” he said.
The researchers are also engaged in preclinical evaluation of other antiviral agents as potential treatments for Zika infection. Some show even more potent anti-Zika activity than did sofosbuvir. But they have the disadvantage of being nonapproved investigational drugs and hence are far earlier in the developmental pipeline.
Dr. Muotri, whose research is supported by the National Institutes of Health, reported having no relevant financial disclosures.
DENVER – An antiviral drug that is a key player in the recent revolution in the treatment of hepatitis C infection also blocks Zika virus replication both in vitro and in a mouse model, Alysson R. Muotri, PhD, said at the annual meeting of the Teratology Society.
Sofosbuvir is a promising candidate. Not only has it demonstrated efficacy in preclinical work by Dr. Muotri and other groups of investigators, but it is also already a Food and Drug Administration–approved antiviral agent with a relatively reassuring Category B rating for use in pregnancy, meaning no evidence of teratogenicity in animal studies.
Investigators at the Scripps Clinic in La Jolla, Calif., have shown that the replication machinery in the Zika virus genome is closely similar to that of another flavivirus: hepatitis C. Both viruses express an NS2B-NS3 protease essential for generation of functional viral proteins.
“That observation led us to look for drugs that would interact with that replication pocket,” Dr. Muotri said.
The researchers first established in vitro that sofosbuvir can bind to the Zika virus NS2B-NS3 protease interface in an area known as the RNA-directed RNA polymerase domain, both in Zika virus–infected human neural progenitor cells and in cerebral organoids. Next, they demonstrated that sofosbuvir inhibited Zika virus replication in mice in dose-dependent fashion (Antiviral Res. 2017 Jul;143:218-29).
Most recently – and most importantly – the researchers showed that sofosbuvir blocked vertical transmission of Zika virus infection in the mouse model. “It’s neuroprotective for the fetus. There was no PCR [polymerase chain reaction] evidence of Zika virus in the fetal head. Those animals are born normal as far as we can tell,” he said.
The researchers are also engaged in preclinical evaluation of other antiviral agents as potential treatments for Zika infection. Some show even more potent anti-Zika activity than did sofosbuvir. But they have the disadvantage of being nonapproved investigational drugs and hence are far earlier in the developmental pipeline.
Dr. Muotri, whose research is supported by the National Institutes of Health, reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
Preventing Zika in pregnancy: What you need to know
DENVER – Prevention of Zika virus infection in pregnancy is critical, given the lack of an effective treatment or vaccine, but it’s easier said than done.
“The particular mosquito that transmits Zika is really difficult because it tends to be indoors and live under the coffee table in your living room rather than outside. It bites in the day, as well as night, so it’s hard to prevent. Trying to consistently have repellent on [and] wear long-sleeved shirts and long pants, even when you’re indoors, in places that are typically quite warm – it’s challenging,” Margaret Honein, PhD, said at the annual meeting of the Teratology Society.
The CDC’s top Zika prevention advice is that pregnant women should not travel to any area where Zika is a risk. If they absolutely have to go, they should talk to their health care provider first, strictly follow measures to prevent mosquito bites during the trip, take steps to prevent sexual transmission – namely, use a condom – and talk with their health care provider once again upon their return.
It is now clear that Zika can be transmitted sexually. For this reason, even a pregnant woman who doesn’t visit an area with Zika risk, but whose partner has been to such a place, must also practice safe sex using a condom, even if the partner is asymptomatic.
In response to an audience question from a Washington, D.C.–area ob.gyn. who noted that there isn’t a Zika problem in his region, Dr. Honein said that her personal view is that pregnant women living in the vicinity of the nation’s capitol should also follow the CDC recommendations for travelers to, or residents of, areas where Zika is found.
“You have mosquito vectors that can transmit Zika in Washington, D.C., and a lot of other parts of the country,” she said. “There are travelers coming back from areas with risk for Zika all the time. If they get bit by a mosquito, which then bites another person and transmits the infection, there’s a problem. So, for pregnant women in areas that have a mosquito vector that can transmit the virus, I think it’s very wise advice to consistently use mosquito repellent and take the other protective measures. People should be doing everything they can to protect against Zika infection in pregnancy.”
DENVER – Prevention of Zika virus infection in pregnancy is critical, given the lack of an effective treatment or vaccine, but it’s easier said than done.
“The particular mosquito that transmits Zika is really difficult because it tends to be indoors and live under the coffee table in your living room rather than outside. It bites in the day, as well as night, so it’s hard to prevent. Trying to consistently have repellent on [and] wear long-sleeved shirts and long pants, even when you’re indoors, in places that are typically quite warm – it’s challenging,” Margaret Honein, PhD, said at the annual meeting of the Teratology Society.
The CDC’s top Zika prevention advice is that pregnant women should not travel to any area where Zika is a risk. If they absolutely have to go, they should talk to their health care provider first, strictly follow measures to prevent mosquito bites during the trip, take steps to prevent sexual transmission – namely, use a condom – and talk with their health care provider once again upon their return.
It is now clear that Zika can be transmitted sexually. For this reason, even a pregnant woman who doesn’t visit an area with Zika risk, but whose partner has been to such a place, must also practice safe sex using a condom, even if the partner is asymptomatic.
In response to an audience question from a Washington, D.C.–area ob.gyn. who noted that there isn’t a Zika problem in his region, Dr. Honein said that her personal view is that pregnant women living in the vicinity of the nation’s capitol should also follow the CDC recommendations for travelers to, or residents of, areas where Zika is found.
“You have mosquito vectors that can transmit Zika in Washington, D.C., and a lot of other parts of the country,” she said. “There are travelers coming back from areas with risk for Zika all the time. If they get bit by a mosquito, which then bites another person and transmits the infection, there’s a problem. So, for pregnant women in areas that have a mosquito vector that can transmit the virus, I think it’s very wise advice to consistently use mosquito repellent and take the other protective measures. People should be doing everything they can to protect against Zika infection in pregnancy.”
DENVER – Prevention of Zika virus infection in pregnancy is critical, given the lack of an effective treatment or vaccine, but it’s easier said than done.
“The particular mosquito that transmits Zika is really difficult because it tends to be indoors and live under the coffee table in your living room rather than outside. It bites in the day, as well as night, so it’s hard to prevent. Trying to consistently have repellent on [and] wear long-sleeved shirts and long pants, even when you’re indoors, in places that are typically quite warm – it’s challenging,” Margaret Honein, PhD, said at the annual meeting of the Teratology Society.
The CDC’s top Zika prevention advice is that pregnant women should not travel to any area where Zika is a risk. If they absolutely have to go, they should talk to their health care provider first, strictly follow measures to prevent mosquito bites during the trip, take steps to prevent sexual transmission – namely, use a condom – and talk with their health care provider once again upon their return.
It is now clear that Zika can be transmitted sexually. For this reason, even a pregnant woman who doesn’t visit an area with Zika risk, but whose partner has been to such a place, must also practice safe sex using a condom, even if the partner is asymptomatic.
In response to an audience question from a Washington, D.C.–area ob.gyn. who noted that there isn’t a Zika problem in his region, Dr. Honein said that her personal view is that pregnant women living in the vicinity of the nation’s capitol should also follow the CDC recommendations for travelers to, or residents of, areas where Zika is found.
“You have mosquito vectors that can transmit Zika in Washington, D.C., and a lot of other parts of the country,” she said. “There are travelers coming back from areas with risk for Zika all the time. If they get bit by a mosquito, which then bites another person and transmits the infection, there’s a problem. So, for pregnant women in areas that have a mosquito vector that can transmit the virus, I think it’s very wise advice to consistently use mosquito repellent and take the other protective measures. People should be doing everything they can to protect against Zika infection in pregnancy.”
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
Asymptomatic maternal Zika infection doesn’t dampen birth defect risk
DENVER – One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.
This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.
“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”[[{"fid":"199780","view_mode":"medstat_image_flush_right","fields":
She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.
Just how serious is the global threat of Zika virus infection?
On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.
“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?
The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.
The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
When during pregnancy does maternal Zika infection pose the highest risk to the fetus?
Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.
“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
What is the full range of potential health problems Zika infection can cause?
“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”
Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.
Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.
“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”
Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.
“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
How long does Zika virus persist in the body?
The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.
“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.
It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.
“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
Resources
In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).
Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at ZikaMCH@cdc.gov.
bjancin@frontlinemedcom.com
On Twitter @ObGynNews
DENVER – One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.
This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.
“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”[[{"fid":"199780","view_mode":"medstat_image_flush_right","fields":
She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.
Just how serious is the global threat of Zika virus infection?
On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.
“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?
The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.
The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
When during pregnancy does maternal Zika infection pose the highest risk to the fetus?
Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.
“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
What is the full range of potential health problems Zika infection can cause?
“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”
Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.
Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.
“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”
Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.
“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
How long does Zika virus persist in the body?
The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.
“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.
It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.
“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
Resources
In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).
Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at ZikaMCH@cdc.gov.
bjancin@frontlinemedcom.com
On Twitter @ObGynNews
DENVER – One of many daunting challenges posed by the ongoing global Zika virus epidemic stems from the recent realization that the presence or absence of symptoms in women infected in pregnancy has no bearing on whether their babies will have Zika-associated birth defects, Margaret Honein, PhD, observed at the annual meeting of the Teratology Society.
This has profound clinical consequences because roughly 80% of all maternal Zika infections are asymptomatic or feature such mild symptoms that women don’t report them.
“There was, I think, some hope early on that symptoms in the mother would correlate with outcomes, but that has not been the case at all. In the U.S. population, we’ve seen about a 6% Zika-associated birth defects rate in both symptomatic and asymptomatic mothers,” said Dr. Honein, chief of the birth defects branch at the Centers for Disease Control and Prevention in Atlanta. “We have a huge challenge in identifying the women who have asymptomatic infections, yet they’re at the same risk of having an adverse outcome in their baby.”[[{"fid":"199780","view_mode":"medstat_image_flush_right","fields":
She provided conference attendees with the latest information on Zika, including preliminary results from ongoing CDC investigations. Along the way, she tackled many of the questions Zika experts hear most often from clinicians, while emphasizing that much about congenital Zika syndrome remains unknown.
Just how serious is the global threat of Zika virus infection?
On Feb. 8, 2016, the CDC activated a Level 1 emergency response to Zika. To put that into perspective, this is only the fourth time in history the agency has gone to Level 1. The other occasions were for Hurricane Katrina, the H1N1 pandemic flu, and Ebola.
“This is worse than thalidomide,” said Jan M. Friedman, MD, after listening to Dr. Honein and other speakers at the Zika update held during the conference. Dr. Friedman, a medical geneticist at the University of British Columbia, Vancouver, delivered the Robert L. Brent Lecture.
What is the level of risk for fetal/infant birth defects associated with maternal Zika virus infection?
The birth defect risk is somewhere between 5% and 10%, with the true figure probably being on the high end. Reports quoting risks on the lower end are based upon laboratory testing for maternal IgM antibodies, which couldn’t rule out cross reaction with other flaviviruses, including dengue virus, which is common in most of the same locales as Zika. Women who have been infected with dengue but not Zika are not at increased risk for birth defects. Zika is the first mosquito-borne virus to be recognized as teratogenic in humans.
The birth defects seen in conjunction with Zika infection are not unique. They can have many different causes. CDC investigators examined birth defects data from three states during the year before the Zika outbreak in the Western Hemisphere and determined that the background rate of microcephaly, neural tube defects, eye abnormalities, hearing loss, and other Zika-like birth defects was 3 per 1,000 live births. Among women with Zika virus infection in pregnancy, however, the rate is more than 20-fold higher at 50-100 per 1,000, according to Dr. Honein.
When during pregnancy does maternal Zika infection pose the highest risk to the fetus?
Studies published from Colombia and Brazil show the peak risk is when infection occurs during the first trimester or early in the second trimester. That’s consistent with the U.S. registry experience as well. Of note, the median time between development of maternal symptoms and the first notation of fetal microcephaly on ultrasound has been 18 weeks.
“This has important implications for women who’ve been infected. Just because they may have had two consecutive apparently normal monthly fetal ultrasounds doesn’t rule out by any means congenital Zika syndrome because there does appear to be a relatively long time period before these findings appear,” Dr. Honein noted.
What is the full range of potential health problems Zika infection can cause?
“What we’ve seen so far is definitely just the tip of the iceberg,” Dr. Honein cautioned. “It’s very severe, but I think we don’t yet know the full range of disabilities. There’s much more to come here.”
Most of the infants in the U.S. registry are just now reaching 1 year of age. Greater understanding of their neurodevelopment will require follow-up to age 2 or beyond.
Also, the information available to date on Zika-associated birth defects is based largely on scrutiny of infants with microcephaly along with any additional findings, such as chorioretinal scarring.
“We know relatively little about infants with only the other conditions – only hearing loss, for example, or only eye abnormalities,” Dr. Honein said. “While we know there are children who have microcephaly and they have needs, there may be a much larger number of children with lesser impairment, but who still have disabilities that are going to necessitate provision of services. Being prepared for that is very important.”
Reports from multiple countries make it clear that babies exposed to Zika in utero can have a normal-appearing head at birth but then become microcephalic later in their first year. The incidence of this phenomenon hasn’t yet been pinned down.
“We’ve learned in the last year and a-half that microcephaly is a key marker of some of the relevant underlying brain abnormalities, but microcephaly is not where our focus should be,” she said.
How long does Zika virus persist in the body?
The viremia typically lasts for anywhere from a few days up to 2 weeks. However, viral persistence for as long as 107 days has been documented in some pregnant women.
“I hesitate to put a number on it because every new publication has a longer figure,” Dr. Honein said.
It’s not yet known whether viral persistence in a woman infected prior to her pregnancy is associated with adverse fetal outcomes. The central nervous system is clearly a reservoir for persistent virus. Whole blood is now under study as possibly another. Semen poses a major challenge.
“There are case reports of Zika virus RNA being detected in semen for more than 6 months after the timing of infection, but we don’t yet know for how long it can be sexually transmitted. Is there really infectious virus present or just particles of RNA?” she said.
Resources
In partnership with the March of Dimes, the CDC has launched Zika Care Connect, a referral network of roughly 600 specialists in six high-risk states. Their ranks include specialists in maternal-fetal medicine, audiology, radiology, mental health, pediatric neurology, infectious diseases, developmental pediatrics, endocrinology, and pediatric ophthalmology. Another 10 states and at least 600 additional providers will soon be added to the referral network (www.zikacareconnect.org; 1-844-677-0447 toll-free).
Comprehensive, up-to-date Zika information is available to health care providers and the public through the CDC at http://www.cdc.gov/zika, at the Zika Pregnancy Hotline (770-488-7100), and by email at ZikaMCH@cdc.gov.
bjancin@frontlinemedcom.com
On Twitter @ObGynNews
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
CABG with arterial grafts provides excellent outcomes for CTO
PARIS – Eighty-eight percent of chronic total occlusions (CTOs) in a large series of patients undergoing coronary artery bypass graft surgery were successfully bypassed using arterial conduits with durable patency.
“Bypass graft surgery using arterial grafts is an acceptable modality of treatment for patients with CTOs and perhaps can be a benchmark against which PCI [percutaneous coronary intervention] for CTOs should be measured,” Teresa May Kieser, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“We have previously shown in another paper that arterial grafting mitigates the adverse effect of incomplete revascularization,” said Dr. Kieser, a cardiothoracic surgeon at the University of Calgary (Alt.).
In recent years, treatment of CTOs has increasingly drawn the attention of interventional cardiologists. Dr. Kieser presented what she thinks is the first study of coronary artery bypass graft (CABG) surgery for management of CTOs. It included 1,333 consecutive CABG patients with a total of 3,906 bypasses, a whopping 98% of which were arterial grafts, with a mean of 2.9 grafts per patient. Eleven percent of the CABGs were done emergently, 48% urgently, and 41% electively.
The key epidemiologic finding to emerge from the study is that CTOs are quite common in CABG patients. In this series, 47% of CABG patients had a mean of 1.35 chronically occluded coronary arteries.
Of 843 CTOs in three major territories, 88% were able to be bypassed. All of the 246 CTOs in the left anterior descending coronary artery were able to be bypassed, as were 84% of 415 CTOs in the right coronary artery and 85% in the circumflex system.
The CTO group as a whole had significantly greater impairment of left ventricular function. Thirty-seven percent of them had an ejection fraction of 30%-50%, compared with 22% of the non-CTO patients. The 10% prevalence of an left ventricular ejection fraction (LVEF) below 30% in the CTO group was twice that of the non-CTO group. The CTO group was also significantly more likely to undergo incomplete revascularization, by a margin of 21% versus 5.7%.
Operative mortality was 3.7% overall and just 0.55% in the elective CABG patients. In a multivariate logistic regression analysis controlled for surgical urgency, incomplete revascularization, and EuroSCORE risk, operative mortality didn’t differ significantly between the CTO and non-CTO groups.
However, in the presence of CTOs, incomplete revascularization was associated with an 11.6% operative mortality, compared with a 2.8% rate in fully revascularized CTO patients.
A total of 110 patients with bypassed CTOs underwent symptom-driven follow-up coronary angiography at a median of 3.6 years after CABG. Reassuringly, CTO graft patency was noted in 95% of the LAD grafts, 92% of the right coronary artery grafts, and 79% of the circumflex grafts.
Dr. Kieser’s audience of interventional cardiologists was clearly bowled over by her results, not only the high rate of successful surgical bypass of CTOs, but also by her use of arterial grafts 98% of the time.
“This is my personal practice,” she explained. “I just believe in arterial grafting so much. They perform best in CTO arteries because of their lack of competitive flow.”
Session chair Oliver Gämperli, MD, of University Hospital Zurich, commented, “We are very concerned about patency rates, and you showed us fantastic patency rates. This is much better than what we’re used to with saphenous vein grafts. I think we need to talk to our surgeons and try to get them to do more arterial grafts of CTOs.”
It’s worth noting that in the CTO subgroup from the landmark randomized SYNTAX trial, the complete revascularization rate was only about 50% in the PCI group, compared with nearly 65% in the CABG group, he added.
Asked why a cardiac surgeon wouldn’t bypass a CTO, Dr. Kieser rattled off several technical reasons, including a vessel size of less than 1 mm, diffuse disease, extensive scar, or an inaccessible location. But that’s not the whole story, she added. She has heard surgical colleagues say, “The patient doesn’t need that artery, he’s learned to live without it.” That burns her up.
“Patients need every artery in the heart, and the one with a CTO is the best one for an arterial graft because it almost cannot fail, especially to the left anterior descending artery. I think we have to change the mentality of the surgeons to ‘If it can be done, it should be done,’ ” Dr. Kieser said.
She reported having no financial conflicts of interest regarding her study.
PARIS – Eighty-eight percent of chronic total occlusions (CTOs) in a large series of patients undergoing coronary artery bypass graft surgery were successfully bypassed using arterial conduits with durable patency.
“Bypass graft surgery using arterial grafts is an acceptable modality of treatment for patients with CTOs and perhaps can be a benchmark against which PCI [percutaneous coronary intervention] for CTOs should be measured,” Teresa May Kieser, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“We have previously shown in another paper that arterial grafting mitigates the adverse effect of incomplete revascularization,” said Dr. Kieser, a cardiothoracic surgeon at the University of Calgary (Alt.).
In recent years, treatment of CTOs has increasingly drawn the attention of interventional cardiologists. Dr. Kieser presented what she thinks is the first study of coronary artery bypass graft (CABG) surgery for management of CTOs. It included 1,333 consecutive CABG patients with a total of 3,906 bypasses, a whopping 98% of which were arterial grafts, with a mean of 2.9 grafts per patient. Eleven percent of the CABGs were done emergently, 48% urgently, and 41% electively.
The key epidemiologic finding to emerge from the study is that CTOs are quite common in CABG patients. In this series, 47% of CABG patients had a mean of 1.35 chronically occluded coronary arteries.
Of 843 CTOs in three major territories, 88% were able to be bypassed. All of the 246 CTOs in the left anterior descending coronary artery were able to be bypassed, as were 84% of 415 CTOs in the right coronary artery and 85% in the circumflex system.
The CTO group as a whole had significantly greater impairment of left ventricular function. Thirty-seven percent of them had an ejection fraction of 30%-50%, compared with 22% of the non-CTO patients. The 10% prevalence of an left ventricular ejection fraction (LVEF) below 30% in the CTO group was twice that of the non-CTO group. The CTO group was also significantly more likely to undergo incomplete revascularization, by a margin of 21% versus 5.7%.
Operative mortality was 3.7% overall and just 0.55% in the elective CABG patients. In a multivariate logistic regression analysis controlled for surgical urgency, incomplete revascularization, and EuroSCORE risk, operative mortality didn’t differ significantly between the CTO and non-CTO groups.
However, in the presence of CTOs, incomplete revascularization was associated with an 11.6% operative mortality, compared with a 2.8% rate in fully revascularized CTO patients.
A total of 110 patients with bypassed CTOs underwent symptom-driven follow-up coronary angiography at a median of 3.6 years after CABG. Reassuringly, CTO graft patency was noted in 95% of the LAD grafts, 92% of the right coronary artery grafts, and 79% of the circumflex grafts.
Dr. Kieser’s audience of interventional cardiologists was clearly bowled over by her results, not only the high rate of successful surgical bypass of CTOs, but also by her use of arterial grafts 98% of the time.
“This is my personal practice,” she explained. “I just believe in arterial grafting so much. They perform best in CTO arteries because of their lack of competitive flow.”
Session chair Oliver Gämperli, MD, of University Hospital Zurich, commented, “We are very concerned about patency rates, and you showed us fantastic patency rates. This is much better than what we’re used to with saphenous vein grafts. I think we need to talk to our surgeons and try to get them to do more arterial grafts of CTOs.”
It’s worth noting that in the CTO subgroup from the landmark randomized SYNTAX trial, the complete revascularization rate was only about 50% in the PCI group, compared with nearly 65% in the CABG group, he added.
Asked why a cardiac surgeon wouldn’t bypass a CTO, Dr. Kieser rattled off several technical reasons, including a vessel size of less than 1 mm, diffuse disease, extensive scar, or an inaccessible location. But that’s not the whole story, she added. She has heard surgical colleagues say, “The patient doesn’t need that artery, he’s learned to live without it.” That burns her up.
“Patients need every artery in the heart, and the one with a CTO is the best one for an arterial graft because it almost cannot fail, especially to the left anterior descending artery. I think we have to change the mentality of the surgeons to ‘If it can be done, it should be done,’ ” Dr. Kieser said.
She reported having no financial conflicts of interest regarding her study.
PARIS – Eighty-eight percent of chronic total occlusions (CTOs) in a large series of patients undergoing coronary artery bypass graft surgery were successfully bypassed using arterial conduits with durable patency.
“Bypass graft surgery using arterial grafts is an acceptable modality of treatment for patients with CTOs and perhaps can be a benchmark against which PCI [percutaneous coronary intervention] for CTOs should be measured,” Teresa May Kieser, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“We have previously shown in another paper that arterial grafting mitigates the adverse effect of incomplete revascularization,” said Dr. Kieser, a cardiothoracic surgeon at the University of Calgary (Alt.).
In recent years, treatment of CTOs has increasingly drawn the attention of interventional cardiologists. Dr. Kieser presented what she thinks is the first study of coronary artery bypass graft (CABG) surgery for management of CTOs. It included 1,333 consecutive CABG patients with a total of 3,906 bypasses, a whopping 98% of which were arterial grafts, with a mean of 2.9 grafts per patient. Eleven percent of the CABGs were done emergently, 48% urgently, and 41% electively.
The key epidemiologic finding to emerge from the study is that CTOs are quite common in CABG patients. In this series, 47% of CABG patients had a mean of 1.35 chronically occluded coronary arteries.
Of 843 CTOs in three major territories, 88% were able to be bypassed. All of the 246 CTOs in the left anterior descending coronary artery were able to be bypassed, as were 84% of 415 CTOs in the right coronary artery and 85% in the circumflex system.
The CTO group as a whole had significantly greater impairment of left ventricular function. Thirty-seven percent of them had an ejection fraction of 30%-50%, compared with 22% of the non-CTO patients. The 10% prevalence of an left ventricular ejection fraction (LVEF) below 30% in the CTO group was twice that of the non-CTO group. The CTO group was also significantly more likely to undergo incomplete revascularization, by a margin of 21% versus 5.7%.
Operative mortality was 3.7% overall and just 0.55% in the elective CABG patients. In a multivariate logistic regression analysis controlled for surgical urgency, incomplete revascularization, and EuroSCORE risk, operative mortality didn’t differ significantly between the CTO and non-CTO groups.
However, in the presence of CTOs, incomplete revascularization was associated with an 11.6% operative mortality, compared with a 2.8% rate in fully revascularized CTO patients.
A total of 110 patients with bypassed CTOs underwent symptom-driven follow-up coronary angiography at a median of 3.6 years after CABG. Reassuringly, CTO graft patency was noted in 95% of the LAD grafts, 92% of the right coronary artery grafts, and 79% of the circumflex grafts.
Dr. Kieser’s audience of interventional cardiologists was clearly bowled over by her results, not only the high rate of successful surgical bypass of CTOs, but also by her use of arterial grafts 98% of the time.
“This is my personal practice,” she explained. “I just believe in arterial grafting so much. They perform best in CTO arteries because of their lack of competitive flow.”
Session chair Oliver Gämperli, MD, of University Hospital Zurich, commented, “We are very concerned about patency rates, and you showed us fantastic patency rates. This is much better than what we’re used to with saphenous vein grafts. I think we need to talk to our surgeons and try to get them to do more arterial grafts of CTOs.”
It’s worth noting that in the CTO subgroup from the landmark randomized SYNTAX trial, the complete revascularization rate was only about 50% in the PCI group, compared with nearly 65% in the CABG group, he added.
Asked why a cardiac surgeon wouldn’t bypass a CTO, Dr. Kieser rattled off several technical reasons, including a vessel size of less than 1 mm, diffuse disease, extensive scar, or an inaccessible location. But that’s not the whole story, she added. She has heard surgical colleagues say, “The patient doesn’t need that artery, he’s learned to live without it.” That burns her up.
“Patients need every artery in the heart, and the one with a CTO is the best one for an arterial graft because it almost cannot fail, especially to the left anterior descending artery. I think we have to change the mentality of the surgeons to ‘If it can be done, it should be done,’ ” Dr. Kieser said.
She reported having no financial conflicts of interest regarding her study.
AT EUROPCR
Key clinical point:
Major finding: Chronic total occlusions were present in 47% of 1,333 consecutive CABG patients, and 88% of the CTOs were successfully bypassed using arterial conduits.
Data source: A retrospective observational study of 1,333 consecutive CABG patients, 47% of whom had one or more chronic total occlusions.
Disclosures: The study presenter reported having no financial conflicts.
Evolute transcatheter valve, now FDA approved for intermediate-risk patients, impresses in real-world practice
PARIS – The Evolut R transcatheter aortic valve demonstrated excellent 30-day results in a real-world, mixed surgical risk population in the large Evolut R FORWARD study.
In this 1,038-patient observational study conducted at 53 sites in 20 countries, the Evolut R valve showed excellent forward hemodynamics and low 30-day rates of all-cause mortality and stroke that were unaffected by utilization of the device’s repositioning feature, Eberhard Grube, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
The importance of the FORWARD study, Dr. Grube observed, is that it illustrates the clinical outcomes obtained in a large population drawn from routine clinical practice. Unlike in a randomized trial such as SURTAVI, the participating sites in the Evolut R Forward study weren’t all high-volume enrollment centers, and operators had widely varying degrees of experience with the valve.
Also, SURTAVI utilized the first generation of the self-expanding CoreValve, which lacked the repositioning feature introduced in the second-generation Evolut R. The FORWARD study is the first rigorous evaluation of Evolut R with centrally adjudicated outcomes.
The mean Society of Thoracic Surgeons predicted risk of mortality score in participants was 5.5%, and 47% had a low-risk score of less than 4%. However, the patients had a mean age of 82 years, one-third were deemed frail, 30% had diabetes, and 26% had chronic lung disease.
The primary study endpoint was 30-day all-cause mortality. The rate was 1.9%, compared with a predicted 5.5% rate based on STS score, for an impressive observed-to-expected ratio of 0.35.
Hemodynamically, the effective orifice area improved from 0.8 cm2 at baseline to 1.9 cm2 at 30 days, while the mean aortic valve gradient plunged from 41.7 to 8.5 mm Hg.
At baseline only 1.5% of patients were New York Heart Association functional class I and 26.5% were class II. At 30 days, 44.7% were class I and 43.4% were class II. The prevalence of NYHA class III status decreased from 63.8% to 11.3%.
There was no or only trace paravalvular leak at discharge in 67.2% of patients as adjudicated in a core laboratory, mild leak in 30.9%, moderate in 1.9%, and severe leak in just 0.1%.
The 30-day total stroke rate was 2.8%, including a 1.8% rate of disabling stroke. Major vascular complications occurred in 6.5% of patients, valve embolization in 0.7%, and life-threatening or disabling bleeding in 3.3%. There were no cases of coronary obstruction or annular rupture.
New pacemaker implantation was required within 30 days in 17.5% of patients. Three-quarters of the pacemakers were placed because of third-degree atrioventricular block.
The new valve ended up in proper anatomic position in 98.9% of patients.
The repositioning feature was utilized in 26% of participants. It had no impact on the rate of pacemaker implantation, mortality, stroke, or other safety endpoints.
“I think the ability to reposition this valve, which is a safety feature, is an important feature, particularly for centers that don’t have so much experience. If the valve is considered to be too high or too low, or you see, for example, a higher degree of paravalvular leak, you have the chance to correct that by using this feature. So it’s an important feature for the operator. It helps to get an optimal result. And the most important thing is there was no price in terms of safety that we paid for repositioning,” said Dr. Grube, professor of cardiology and head of the Center for Innovative Intervention in Cardiology at the University of Bonn in Siegberg, Germany.
Session cochair Alain Cribier, MD, famed for having performed the world’s first TAVR procedure, pronounced the FORWARD results “very impressive.”
“Less than 2% mortality, around a 2% disabling stroke rate, and the data on paravalvular leak are excellent as well. It’s very nice to see that what was a limited data set earlier, with a smaller number of patients, has now been replicated in 1,000 patients. So I think now we can confidently talk about the clinical outcomes – and they are excellent,” declared Dr. Cribier, professor of medicine at the University of Rouen (France) and chief of cardiology at Charles Nicolle Hospital.
The FORWARD study was sponsored by Medtronic. Dr. Grube reported serving as a consultant to that company as well as to Boston Scientific, Abbott, and Millipede Medical.
PARIS – The Evolut R transcatheter aortic valve demonstrated excellent 30-day results in a real-world, mixed surgical risk population in the large Evolut R FORWARD study.
In this 1,038-patient observational study conducted at 53 sites in 20 countries, the Evolut R valve showed excellent forward hemodynamics and low 30-day rates of all-cause mortality and stroke that were unaffected by utilization of the device’s repositioning feature, Eberhard Grube, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
The importance of the FORWARD study, Dr. Grube observed, is that it illustrates the clinical outcomes obtained in a large population drawn from routine clinical practice. Unlike in a randomized trial such as SURTAVI, the participating sites in the Evolut R Forward study weren’t all high-volume enrollment centers, and operators had widely varying degrees of experience with the valve.
Also, SURTAVI utilized the first generation of the self-expanding CoreValve, which lacked the repositioning feature introduced in the second-generation Evolut R. The FORWARD study is the first rigorous evaluation of Evolut R with centrally adjudicated outcomes.
The mean Society of Thoracic Surgeons predicted risk of mortality score in participants was 5.5%, and 47% had a low-risk score of less than 4%. However, the patients had a mean age of 82 years, one-third were deemed frail, 30% had diabetes, and 26% had chronic lung disease.
The primary study endpoint was 30-day all-cause mortality. The rate was 1.9%, compared with a predicted 5.5% rate based on STS score, for an impressive observed-to-expected ratio of 0.35.
Hemodynamically, the effective orifice area improved from 0.8 cm2 at baseline to 1.9 cm2 at 30 days, while the mean aortic valve gradient plunged from 41.7 to 8.5 mm Hg.
At baseline only 1.5% of patients were New York Heart Association functional class I and 26.5% were class II. At 30 days, 44.7% were class I and 43.4% were class II. The prevalence of NYHA class III status decreased from 63.8% to 11.3%.
There was no or only trace paravalvular leak at discharge in 67.2% of patients as adjudicated in a core laboratory, mild leak in 30.9%, moderate in 1.9%, and severe leak in just 0.1%.
The 30-day total stroke rate was 2.8%, including a 1.8% rate of disabling stroke. Major vascular complications occurred in 6.5% of patients, valve embolization in 0.7%, and life-threatening or disabling bleeding in 3.3%. There were no cases of coronary obstruction or annular rupture.
New pacemaker implantation was required within 30 days in 17.5% of patients. Three-quarters of the pacemakers were placed because of third-degree atrioventricular block.
The new valve ended up in proper anatomic position in 98.9% of patients.
The repositioning feature was utilized in 26% of participants. It had no impact on the rate of pacemaker implantation, mortality, stroke, or other safety endpoints.
“I think the ability to reposition this valve, which is a safety feature, is an important feature, particularly for centers that don’t have so much experience. If the valve is considered to be too high or too low, or you see, for example, a higher degree of paravalvular leak, you have the chance to correct that by using this feature. So it’s an important feature for the operator. It helps to get an optimal result. And the most important thing is there was no price in terms of safety that we paid for repositioning,” said Dr. Grube, professor of cardiology and head of the Center for Innovative Intervention in Cardiology at the University of Bonn in Siegberg, Germany.
Session cochair Alain Cribier, MD, famed for having performed the world’s first TAVR procedure, pronounced the FORWARD results “very impressive.”
“Less than 2% mortality, around a 2% disabling stroke rate, and the data on paravalvular leak are excellent as well. It’s very nice to see that what was a limited data set earlier, with a smaller number of patients, has now been replicated in 1,000 patients. So I think now we can confidently talk about the clinical outcomes – and they are excellent,” declared Dr. Cribier, professor of medicine at the University of Rouen (France) and chief of cardiology at Charles Nicolle Hospital.
The FORWARD study was sponsored by Medtronic. Dr. Grube reported serving as a consultant to that company as well as to Boston Scientific, Abbott, and Millipede Medical.
PARIS – The Evolut R transcatheter aortic valve demonstrated excellent 30-day results in a real-world, mixed surgical risk population in the large Evolut R FORWARD study.
In this 1,038-patient observational study conducted at 53 sites in 20 countries, the Evolut R valve showed excellent forward hemodynamics and low 30-day rates of all-cause mortality and stroke that were unaffected by utilization of the device’s repositioning feature, Eberhard Grube, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
The importance of the FORWARD study, Dr. Grube observed, is that it illustrates the clinical outcomes obtained in a large population drawn from routine clinical practice. Unlike in a randomized trial such as SURTAVI, the participating sites in the Evolut R Forward study weren’t all high-volume enrollment centers, and operators had widely varying degrees of experience with the valve.
Also, SURTAVI utilized the first generation of the self-expanding CoreValve, which lacked the repositioning feature introduced in the second-generation Evolut R. The FORWARD study is the first rigorous evaluation of Evolut R with centrally adjudicated outcomes.
The mean Society of Thoracic Surgeons predicted risk of mortality score in participants was 5.5%, and 47% had a low-risk score of less than 4%. However, the patients had a mean age of 82 years, one-third were deemed frail, 30% had diabetes, and 26% had chronic lung disease.
The primary study endpoint was 30-day all-cause mortality. The rate was 1.9%, compared with a predicted 5.5% rate based on STS score, for an impressive observed-to-expected ratio of 0.35.
Hemodynamically, the effective orifice area improved from 0.8 cm2 at baseline to 1.9 cm2 at 30 days, while the mean aortic valve gradient plunged from 41.7 to 8.5 mm Hg.
At baseline only 1.5% of patients were New York Heart Association functional class I and 26.5% were class II. At 30 days, 44.7% were class I and 43.4% were class II. The prevalence of NYHA class III status decreased from 63.8% to 11.3%.
There was no or only trace paravalvular leak at discharge in 67.2% of patients as adjudicated in a core laboratory, mild leak in 30.9%, moderate in 1.9%, and severe leak in just 0.1%.
The 30-day total stroke rate was 2.8%, including a 1.8% rate of disabling stroke. Major vascular complications occurred in 6.5% of patients, valve embolization in 0.7%, and life-threatening or disabling bleeding in 3.3%. There were no cases of coronary obstruction or annular rupture.
New pacemaker implantation was required within 30 days in 17.5% of patients. Three-quarters of the pacemakers were placed because of third-degree atrioventricular block.
The new valve ended up in proper anatomic position in 98.9% of patients.
The repositioning feature was utilized in 26% of participants. It had no impact on the rate of pacemaker implantation, mortality, stroke, or other safety endpoints.
“I think the ability to reposition this valve, which is a safety feature, is an important feature, particularly for centers that don’t have so much experience. If the valve is considered to be too high or too low, or you see, for example, a higher degree of paravalvular leak, you have the chance to correct that by using this feature. So it’s an important feature for the operator. It helps to get an optimal result. And the most important thing is there was no price in terms of safety that we paid for repositioning,” said Dr. Grube, professor of cardiology and head of the Center for Innovative Intervention in Cardiology at the University of Bonn in Siegberg, Germany.
Session cochair Alain Cribier, MD, famed for having performed the world’s first TAVR procedure, pronounced the FORWARD results “very impressive.”
“Less than 2% mortality, around a 2% disabling stroke rate, and the data on paravalvular leak are excellent as well. It’s very nice to see that what was a limited data set earlier, with a smaller number of patients, has now been replicated in 1,000 patients. So I think now we can confidently talk about the clinical outcomes – and they are excellent,” declared Dr. Cribier, professor of medicine at the University of Rouen (France) and chief of cardiology at Charles Nicolle Hospital.
The FORWARD study was sponsored by Medtronic. Dr. Grube reported serving as a consultant to that company as well as to Boston Scientific, Abbott, and Millipede Medical.
AT EUROPCR
Key clinical point:
Major finding: Thirty-day all-cause mortality was 1.9% with a 2.8% stroke rate in a large, real-world study of TAVR with the repositionable self-expanding Evolut R transcatheter aortic valve.
Data source: The Evolut R FORWARD study of 1,038 recipients of the Evolut R transcatheter aortic valve at 53 sites in 20 countries.
Disclosures: The FORWARD study was sponsored by Medtronic. The presenter reported serving as a consultant to that company as well as to Boston Scientific, Abbott, and Millipede Medical.
Watchman device for AF patients ineligible for oral anticoagulation gains support from 1-year registry outcomes
PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.
Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA2DS2-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.
However, the ESC guidelines were largely based on randomized trials of the Watchman versus oral anticoagulation, including PREVAIL and PROTECT-AF, showing noninferiority. The safety and efficacy of the device in warfarin-ineligible patients was less well studied at the time the guidelines were formulated. And in fact, such patients are excluded from the Food and Drug Administration’s approved indication, which is specifically for patients judged “suitable for warfarin.”
“This gap is now filled by EWOLUTION. This is a registry that’s as good as it gets. We have all the things in place that you need these days to be able to rely on the outcome data,” according to the cardiologist.
EWOLUTION is a prospective, multicenter, all-comers registry. The EWOLUTION population of AF patients on DAPT was high risk: 89% had a CHA2DS2-VASc score of 3 or more, 31% were at least 80 years old, the mean HAS-BLED score was 2.4, and oral anticoagulation was contraindicated in 84% of participants.
Eighty-seven percent of subjects underwent follow-up transesophageal echocardiography. The imaging study showed the Watchman effectively sealed the left atrial appendage in 99.2% of patients as defined by no leak greater than 5 mm. The echo exam also showed the presence of thrombus on the device at follow-up in 4% of patients, although only 1 of the 22 patients with device thrombus experienced a stroke.
“We can conclude two things from this which are in line with earlier studies. First, the rate of thrombus on the device is equal to the rate reported in the randomized controlled trials, which was also 4%, even if the patients were on warfarin for the first 45 days. And second, these thrombi are not related to stroke,” Dr. Bergmann said.
At the 1-year mark, 71% of patients had switched to a single antiplatelet agent, while 17% remained on DAPT, mainly because of comorbid coronary disease for which DAPT is indicated. Seven percent of patients were on no antithrombotic medications. The remaining 5% were transiently on warfarin or a novel oral anticoagulant.
The 1-year cumulative rate of ischemic stroke or TIA was 1.8%, with no instances of systemic embolism. Of note, there were no hemorrhagic strokes. And of the 11 cases of ischemic stroke, none were fatal and only one was disabling.
“This is a sign that comes also from the PREVAIL trial, that if you have a stroke while on left atrial appendage–closure therapy, most of the time it’s not disabling. It’s much less severe on the modified Rankin Scale than if you’re on oral anticoagulation,” said Dr. Bergmann.
The 1.4% rate of ischemic stroke at 1 year in Watchman recipients represents an 81% reduction in risk compared with the expected 7.5% rate in patients with similar CHA2DS2-VASc scores not on oral anticoagulation. This level of stroke risk reduction is similar to that seen in the pivotal ARISTOTLE trial of apixaban (Eliquis) in a high-risk AF population (Lancet. 2012 Nov 17;380[9855]:1749-58).
Major bleeding occurred in 2.5% of patients. The rate of fatal bleeding was 0.5%. To put that in perspective, the 2.5% major bleeding rate was 52% lower than would be expected based upon similar HAS-BLED scores in patients on warfarin. Still, 2.5% is unacceptably high.
“The major serious adverse event is not pericardial effusion or late device embolization, it’s major bleeding occurring during the time the patient is on DAPT, mostly within the first 3 months. So I think we have to do something about this,” he said.
One possibility worthy of formal study is 3 months of periprocedural NOAC monotherapy. “Maybe even low-dose therapy, like 75 mg of dabigatran [Pradaxa] twice daily. We have an antidote that works nicely [idarucizumab, Praxbind] so I think maybe this is the way to go,” Dr. Bergmann observed.
The ongoing EWOLUTION registry is sponsored by Boston Scientific. Dr. Bergmann is a consultant to that company as well as Bayer AG, Daiichi Sankyo, Eli Lilly, and St. Jude Medical.
PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.
Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA2DS2-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.
However, the ESC guidelines were largely based on randomized trials of the Watchman versus oral anticoagulation, including PREVAIL and PROTECT-AF, showing noninferiority. The safety and efficacy of the device in warfarin-ineligible patients was less well studied at the time the guidelines were formulated. And in fact, such patients are excluded from the Food and Drug Administration’s approved indication, which is specifically for patients judged “suitable for warfarin.”
“This gap is now filled by EWOLUTION. This is a registry that’s as good as it gets. We have all the things in place that you need these days to be able to rely on the outcome data,” according to the cardiologist.
EWOLUTION is a prospective, multicenter, all-comers registry. The EWOLUTION population of AF patients on DAPT was high risk: 89% had a CHA2DS2-VASc score of 3 or more, 31% were at least 80 years old, the mean HAS-BLED score was 2.4, and oral anticoagulation was contraindicated in 84% of participants.
Eighty-seven percent of subjects underwent follow-up transesophageal echocardiography. The imaging study showed the Watchman effectively sealed the left atrial appendage in 99.2% of patients as defined by no leak greater than 5 mm. The echo exam also showed the presence of thrombus on the device at follow-up in 4% of patients, although only 1 of the 22 patients with device thrombus experienced a stroke.
“We can conclude two things from this which are in line with earlier studies. First, the rate of thrombus on the device is equal to the rate reported in the randomized controlled trials, which was also 4%, even if the patients were on warfarin for the first 45 days. And second, these thrombi are not related to stroke,” Dr. Bergmann said.
At the 1-year mark, 71% of patients had switched to a single antiplatelet agent, while 17% remained on DAPT, mainly because of comorbid coronary disease for which DAPT is indicated. Seven percent of patients were on no antithrombotic medications. The remaining 5% were transiently on warfarin or a novel oral anticoagulant.
The 1-year cumulative rate of ischemic stroke or TIA was 1.8%, with no instances of systemic embolism. Of note, there were no hemorrhagic strokes. And of the 11 cases of ischemic stroke, none were fatal and only one was disabling.
“This is a sign that comes also from the PREVAIL trial, that if you have a stroke while on left atrial appendage–closure therapy, most of the time it’s not disabling. It’s much less severe on the modified Rankin Scale than if you’re on oral anticoagulation,” said Dr. Bergmann.
The 1.4% rate of ischemic stroke at 1 year in Watchman recipients represents an 81% reduction in risk compared with the expected 7.5% rate in patients with similar CHA2DS2-VASc scores not on oral anticoagulation. This level of stroke risk reduction is similar to that seen in the pivotal ARISTOTLE trial of apixaban (Eliquis) in a high-risk AF population (Lancet. 2012 Nov 17;380[9855]:1749-58).
Major bleeding occurred in 2.5% of patients. The rate of fatal bleeding was 0.5%. To put that in perspective, the 2.5% major bleeding rate was 52% lower than would be expected based upon similar HAS-BLED scores in patients on warfarin. Still, 2.5% is unacceptably high.
“The major serious adverse event is not pericardial effusion or late device embolization, it’s major bleeding occurring during the time the patient is on DAPT, mostly within the first 3 months. So I think we have to do something about this,” he said.
One possibility worthy of formal study is 3 months of periprocedural NOAC monotherapy. “Maybe even low-dose therapy, like 75 mg of dabigatran [Pradaxa] twice daily. We have an antidote that works nicely [idarucizumab, Praxbind] so I think maybe this is the way to go,” Dr. Bergmann observed.
The ongoing EWOLUTION registry is sponsored by Boston Scientific. Dr. Bergmann is a consultant to that company as well as Bayer AG, Daiichi Sankyo, Eli Lilly, and St. Jude Medical.
PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.
Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA2DS2-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.
However, the ESC guidelines were largely based on randomized trials of the Watchman versus oral anticoagulation, including PREVAIL and PROTECT-AF, showing noninferiority. The safety and efficacy of the device in warfarin-ineligible patients was less well studied at the time the guidelines were formulated. And in fact, such patients are excluded from the Food and Drug Administration’s approved indication, which is specifically for patients judged “suitable for warfarin.”
“This gap is now filled by EWOLUTION. This is a registry that’s as good as it gets. We have all the things in place that you need these days to be able to rely on the outcome data,” according to the cardiologist.
EWOLUTION is a prospective, multicenter, all-comers registry. The EWOLUTION population of AF patients on DAPT was high risk: 89% had a CHA2DS2-VASc score of 3 or more, 31% were at least 80 years old, the mean HAS-BLED score was 2.4, and oral anticoagulation was contraindicated in 84% of participants.
Eighty-seven percent of subjects underwent follow-up transesophageal echocardiography. The imaging study showed the Watchman effectively sealed the left atrial appendage in 99.2% of patients as defined by no leak greater than 5 mm. The echo exam also showed the presence of thrombus on the device at follow-up in 4% of patients, although only 1 of the 22 patients with device thrombus experienced a stroke.
“We can conclude two things from this which are in line with earlier studies. First, the rate of thrombus on the device is equal to the rate reported in the randomized controlled trials, which was also 4%, even if the patients were on warfarin for the first 45 days. And second, these thrombi are not related to stroke,” Dr. Bergmann said.
At the 1-year mark, 71% of patients had switched to a single antiplatelet agent, while 17% remained on DAPT, mainly because of comorbid coronary disease for which DAPT is indicated. Seven percent of patients were on no antithrombotic medications. The remaining 5% were transiently on warfarin or a novel oral anticoagulant.
The 1-year cumulative rate of ischemic stroke or TIA was 1.8%, with no instances of systemic embolism. Of note, there were no hemorrhagic strokes. And of the 11 cases of ischemic stroke, none were fatal and only one was disabling.
“This is a sign that comes also from the PREVAIL trial, that if you have a stroke while on left atrial appendage–closure therapy, most of the time it’s not disabling. It’s much less severe on the modified Rankin Scale than if you’re on oral anticoagulation,” said Dr. Bergmann.
The 1.4% rate of ischemic stroke at 1 year in Watchman recipients represents an 81% reduction in risk compared with the expected 7.5% rate in patients with similar CHA2DS2-VASc scores not on oral anticoagulation. This level of stroke risk reduction is similar to that seen in the pivotal ARISTOTLE trial of apixaban (Eliquis) in a high-risk AF population (Lancet. 2012 Nov 17;380[9855]:1749-58).
Major bleeding occurred in 2.5% of patients. The rate of fatal bleeding was 0.5%. To put that in perspective, the 2.5% major bleeding rate was 52% lower than would be expected based upon similar HAS-BLED scores in patients on warfarin. Still, 2.5% is unacceptably high.
“The major serious adverse event is not pericardial effusion or late device embolization, it’s major bleeding occurring during the time the patient is on DAPT, mostly within the first 3 months. So I think we have to do something about this,” he said.
One possibility worthy of formal study is 3 months of periprocedural NOAC monotherapy. “Maybe even low-dose therapy, like 75 mg of dabigatran [Pradaxa] twice daily. We have an antidote that works nicely [idarucizumab, Praxbind] so I think maybe this is the way to go,” Dr. Bergmann observed.
The ongoing EWOLUTION registry is sponsored by Boston Scientific. Dr. Bergmann is a consultant to that company as well as Bayer AG, Daiichi Sankyo, Eli Lilly, and St. Jude Medical.
AT EUROPCR
Key clinical point:
Major finding: Patients with AF at high stroke risk and ineligible for oral anticoagulation experienced an 81% reduction in their expected risk of ischemic stroke during their first year of LAA closure with the Watchman device backed by limited-duration dual-antiplatelet therapy
Data source: A prospective, multicenter, single-arm registry that includes 605 patients with AF who underwent left atrial appendage closure with the WATCHMAN device supported by limited-duration dual-antiplatelet therapy.
Disclosures: The ongoing EWOLUTION registry is sponsored by Boston Scientific. The presenter is a consultant to that company and several others.